*** START OF THE PROJECT GUTENBERG EBOOK 69874 ***

[Illustration: GOUTY ARTHRITIS.

Note large tuberous swellings on knuckle and metacarpo-phalangeal joints
due to uratic deposits.]




                                   GOUT

                                    BY
                  LLEWELLYN JONES LLEWELLYN, M.B. Lond.

      GOVERNOR AND SENIOR PHYSICIAN, ROYAL MINERAL WATER HOSPITAL,
          BATH; FELLOW OF ROYAL SOCIETY OF MEDICINE; AUTHOR OF
       “ARTHRITIS DEFORMANS”; CO-AUTHOR OF “FIBROSITIS”; CO-AUTHOR
      OF “MALINGERING, OR THE SIMULATION OF DISEASE”; CO-AUTHOR OF
     “PENSIONS AND THE PRINCIPLES OF THEIR EVALUATION”; CONTRIBUTOR
     TO LATHAM AND ENGLISH’S “SYSTEM OF TREATMENT,” ALSO TO “OXFORD
        ENCYCLOPÆDIA OF TREATMENT” AND TO “STUDENT’S TEXT-BOOK OF
                                SURGERY.”

                            WITH A SECTION ON
                       OCULAR DISEASE IN THE GOUTY

                                    BY
                              W. M. BEAUMONT

            CONSULTING OPHTHALMIC SURGEON TO THE SOUTH-WESTERN
         REGION OF THE MINISTRY OF PENSIONS; AUTHOR OF “INJURIES
       OF THE EYES OF THE UNEMPLOYED, PROBLEMS IN PROGNOSIS,” ETC.

                                ST. LOUIS
                           C. V. MOSBY COMPANY
                                   1921

                       _Printed in Great Britain._




                                Dedicated
                                    TO
                                 MY WIFE




PREFACE


“A knowledge of the real nature of gout ... is, in my opinion, at the
very foundation of all sound pathology,” wrote Todd many years since;
and the passing years have but invested his reflection with deeper
significance and something of prophetic insight. For who can doubt that
he who would elucidate the pathological groundwork of gout must be at
once a clinical physician, a bio-chemist, a bacteriologist, a morbid
anatomist? and well may we ask, Who is sufficient for all this?

How vivid the light thrown upon the problems of clinical medicine by the
bio-chemists! The story of the fate of protein and purin substances in
the animal body, at one time a medley of guesses and gaps, is gradually
evolving into one of relative certitude and completeness. Revolutionary,
in truth, the change, and many a cherished shibboleth has been ruthlessly
cast aside! With admiration not unmingled with awe we see them laying
well and truly the foundations upon which in the ultimate scientific
medicine must inevitably rest.

Of these the very corner-stones are _chemical physiology_ and _chemical
pathology_, the rapid evolution of which is profoundly altering our
conceptions of health and disease. Those vital processes of the organism
that but yesterday we saw “as through a glass, darkly,” are now in great
part illumined, and the distortions wrought in them by disease made more
manifest.

How pregnant, too, with warning their findings! Processes that to
our untutored minds seem simple are revealed as infinitely complex.
Through what a maze must we thread our way if we would disentangle the
intricacies of metabolism! Intricate enough, forsooth, in health, but how
much more so in disease! For, as Sir Archibald Garrod eloquently phrases
it, “it is becoming evident that special paths of metabolism exist, not
only for proteins, fats, and carbohydrates as such, but that even the
individual primary fractions of the protein molecule follow their several
katabolic paths, and are dealt with in successive stages by series of
enzymes until the final products of katabolism are formed. Any of these
paths may be locked while others remain open.”

It is with chastening reflections such as these that we may best approach
our study of gout, that riddle of the ages upon which so many physicians
from time immemorial have expended their dialectic skill. But, vast
though the increase in our knowledge of the chemical structure of uric
acid and its allies, uncertainty still dogs our steps, and, doubtful of
the pathway to solution of the pathological mystery of gout, we must
perforce approach the problem in a more strictly catholic attitude.

_Uric acid_ has apparently failed us as the _causa causans_. Neither this
substance nor its precursors can be held responsible for the fever, local
inflammation and constitutional disturbances in gout, being, as they are,
practically _non-toxic_. Albeit, though I hold this view, I do not for
one moment suggest that _uric acid_ has nothing whatever to do with gout.
The fact that _tophi_, its pathognomonic stigmata, are compounded of
_biurate of soda_, would _per se_ stamp such an attitude as untenable. On
the other hand, _uric acid_ must be viewed at its proper perspective as a
_concomitant_ or _sequel_ of _gouty inflammation_, the essential cause of
which must be sought elsewhere.

“The old order changeth, giving place to new,” and happily with the
advent of _bacteriology_ our views, or rather our hazards, as to the
nature of joint diseases underwent profound modification. But, strange
to say, though quick to apprehend the significance of infection, its
causal relation to other joint disorders, we still seem unaccountably
loth to discard our timeworn conception of “gouty” arthritis as of purely
_metabolic_ origin. This to my mind is the more remarkable in that the
onset, clinical phenomena, and course of acute gout, and no less the life
history of the disorder as a whole, are emphatically indicative of the
intrusion of an _infective element_ in its genesis.

The extreme frequency with which _infective foci_ are met with in the
victims of gout, the frequency, too, with which exacerbations of the
disorder are presaged by _acute glandular affections_ of undeniably
_infective_ source, is by no means adequately realised. For our
forefathers gout began, and, forsooth, often ended, in the “stomach,” or
it was the “liver” that was impeached. But the portal to the alimentary
canal was for them only a cavity, the contained structures of which,
albeit, to their mind often betrayed evidences of a “gouty diathesis.”
They distinguished “gouty” teeth, “gouty” tonsillitis, “gouty”
pharyngitis, even “gouty” parotitis; but all these they classed as tokens
or sequelæ of gout, not possible causes or _excitants_ thereof.

Now as to the true significance of these acute glandular affections
held by clinicians of repute to be of “gouty” origin. What of “gouty”
tonsillitis, pharyngitis, parotitis? Still more, what of our deductions
regarding the relationship of these same when met with in association
with _non-gouty_ forms of arthritis? Do we not hold them each and all as
evidences of _infection_? and, we may well ask, why not in gout?

The marvel then is that even to-day many still hold that the tonsillitis,
pharyngitis, even the gingivitis, like the subsequent articular lesions,
are one and all attributable to the underlying _gout_. We certainly
should not do so in the case of any arthritis other than “gouty,” and to
my mind the time is ripe for a change of attitude.

The “gouty” throats, like the “gouty” teeth, should be regarded not as
symptomatic of gout, but _etiologically_ related thereto. We should cease
to talk of “gouty” throats, teeth, etc., should renounce the prefix,
for there is nothing _specific_ of _gout_ either in the tonsillar,
pharyngeal, or dental lesions. We should instead view these various local
disorders in their true perspective as _foci_ of _infection, causally_
related to the subsequent and _secondary_ “gouty” arthritis.

Similarly, when we come to analyse the component elements of an acute
paroxysm of gout, how strongly indicative of the intrusion of an
_infective_ element the following features: the onset, temperature curve,
character of local articular changes of the disorder, the presence of
_leucocytosis_, with secondary anæmia and enlargement of the lymphatic
glands! Again, how suggestive the occasional complication of acute
gout by _lymphangitis_ and _phlebitis_! Of like significance, too, the
paroxysmal nature and periodicity of the disorder, and the compatibility
of the morbid anatomical changes and the cytological content of the
aspirated joint fluid with their genesis by _infection_.

As to correlation of the metabolic phenomena of gout with the postulated
infective element, I would suggest that, although abnormalities of
metabolism form an integral part of gout, they are of themselves
inadequate to achieve its efflorescence. As we shall see when we come to
consider those elemental manifestations of gout, _i.e._, uratic deposits,
or _tophi_, neither the purely physical nor the purely chemical theory
of their origin will suffice, nor, for that matter, can any solution of
their formation be gleaned from even a blend of the twain. In short, such
hypotheses are too _mechanical_.

The intrusion of some other factor, “something vital, something
biological,” seems essential for the elucidation of _uratosis_,
_i.e._, uratic deposition. For this, _not uricæmia_, is the specific
characteristic phenomenon of gout. If we cannot explain uratosis on
physical or chemical grounds, then how much less, in view of the
_non-toxicity_ of _uric acid_, can we on this basis account for the
_inflammatory_ phenomena of the disorder!

Now _inflammatory reaction_ is, I hold, an invariable _antecedent_ in all
gouty processes, whether of _articular_ or _ab-articular_ site. Granted
that inflammatory reaction is a necessary prelude, the specificity
of gout is attested by the fact that the same is followed by local
deposition of urates. But while this sequential uratic deposition invests
all forms of “gouty” inflammation with a specific character unshared by
any other disease, it follows that the cause of the said inflammation
must, if possible, be ascertained.

Now, as I believe, “gouty” subjects are _ab initio_ victimised by innate
tissue peculiarities, doubtless reflected in corresponding obliquities of
tissue function and metamorphosis, and through their medium the general
resistance of the body to invasion by _infections_ is lowered; in other
words, under the influence of these morbific agencies the latent morbid
potentialities of the gouty become overt and manifest. For in the gouty,
as Walker Hall observes, “a slight injury or indiscretion of diet, an
overloaded intestine, or increased toxicity of the intestinal flora, may
be followed by a disturbance of the general nuclein metabolism and a
local reaction in certain tissues.”

Enough has been said to disclose the dominant trend of this work, and
although there are many aspects of the subject in regard to which I hold
somewhat iconoclastic views, yet exigencies of space forbid me even to
allude to them in this foreword. I hasten therefore to discharge the
pleasing duty of acknowledging my great indebtedness to the acumen and
discrimination which has been brought to bear on this subject by a long
succession of eminent physicians, in proof of which I need only adduce
the names of those giants of the past the illustrious Sydenham, Sir
Thomas Watson, Sir Charles Scudamore, Jonathan Hutchinson, not to mention
Trousseau, Charcot, Lecorche, and Rendu. But I should fail in my duty did
I not in a special sense express my deep indebtedness to the classic and
epoch-making work of Sir Alfred Garrod. For the rest, too, I have derived
much enlightenment from Sir Dyce Duckworth’s treatise and the various
works on the subject by Luff, Lindsay, and others.

From the bio-chemical aspect I owe much to the researches of Walker Hall,
and to those of our American _confrères_ Folin, Denis, Benedict, Pratt,
McLeod, Walker Jones, Gideon Wells, etc.

Reverting to my own colleagues at the Royal Mineral Water Hospital,
Bath, I would tender my deep thanks to the Honorary Physicians, Drs.
Waterhouse, Thomson, Lindsay, and King Martyn, for the uniformly generous
manner in which they afforded me opportunities for studying cases under
their care.

To Dr. Munro, our senior pathologist, I am especially beholden for
invaluable, nay indispensable, help in the matter of blood examinations,
the cytological study of joint fluids, and the microscopic verifications
of tophi. To Dr. MacKay also my cordial thanks are due for the
skiagraphs contained in this work.

For the section dealing with the ocular disorders met with in the gouty
my most sincere thanks are due to Mr. W. M. Beaumont, of Bath, whose
singularly wide experience in this sphere renders him unusually equipped
to deal with this highly controversial aspect of gout. To Drs. Cave and
Gordon, of Bath, also I am indebted for many valuable suggestions kindly
afforded me while writing this volume. To my brother Dr. Bassett Jones I
am under deep obligation for unwearying assistance in our joint endeavour
to ascertain the exact relationship of gout to lumbago, sciatica, and
other types of fibrositis.

For the preparation of the index of this work I would proffer my grateful
thanks to Mr. Charles Hewitt and to Miss Donnan and Miss Crosse for
having undertaken the arduous task of typing the manuscript thereof.

Lastly, I would express my thanks to my publisher, Mr. Heinemann, for
much consideration and many courtesies.

                                                                LL. J. LL.

31, UPPER BROOK STREET, W. 1.




TABLE OF CONTENTS


                                CHAPTER I

                       HISTORICAL AND INTRODUCTORY

  The Antiquity of Gout. Prevalence of Gout in the Anglo-Saxon
  Period. Views of the Humoralist. The Aphorisms of Hippocrates.
  Introduction of the Word Gout. Early Views as to the Nature of
  Tophi. The “Honour of the Gout.” That Gout confers Immunity
  from other Disorders. Growing Infrequency and Attenuation of
  Gout                                                        _pp._    1-13

                               CHAPTER II

                          THE PEDIGREE OF GOUT

  Tardy Dissociation of Chronic Gout. Identification of Muscular
  Rheumatism. Differentiation of Chronic Gout from Arthritis
  Deformans. Cleavage of Arthritis Deformans into Two Types.
  Elimination of the Infective Arthritides                    _pp._   14-20

                               CHAPTER III

                    EARLIER THEORIES OF PATHOGENESIS

  Garrod’s Theory. Antagonistic Views. Histogenous Theories.
  Antecedent Structural Changes. Hepatic Inadequacy.
  Hyperpyræmia. Nervous Theories. Growing Scepticism as to
  Garrod’s Pathogeny of Gout                                  _pp._   21-34

                               CHAPTER IV

        DEFINITION, CLASSIFICATION, ETIOLOGY, AND MORBID ANATOMY

  Definition. Classification. Suggested Classification
  of Articular Gout. Etiology and Morbid Anatomy. Bodily
  Conformation and Individual Temperament. Locality, Race,
  Climate. Food, Drink, Occupation. Lead Poisoning. Mental and
  Physical Over-exertion. Summary. Morbid Anatomy             _pp._   35-58

                                CHAPTER V

                  PATHOLOGY OF GOUT-PROTEIN METABOLISM

  Revelations of the Bio-chemist. The Formation of Urea. Fate
  of the Amino-acids. Seat of Formation of Urea. Amino-acids
  in Relation to Gout. The Glycocoll Theory of Gout. Urea
  Excretion in Gout. Creatine and Creatinine. Inborn Errors
  of Metabolism                                               _pp._   59-70

                               CHAPTER VI

                           NUCLEIN METABOLISM

  The Isolation of Nucleic Acid. Researches on Spermatozoa. The
  Discovery of Purins. Uric Acid a Derivative of Nucleic Acid.
  The Chemistry of Uric Acid and the Purin Bodies. Chemical
  Constitution. Properties of Uric Acid. Uric Acid in the Blood.
  Gudzent and Schade’s Theories. Organic Combinations. Complexity
  of the Problem                                              _pp._   71-82

                               CHAPTER VII

                          SOURCES OF URIC ACID

  Exogenous Purins. Exogenous Uric Acid Excretion. Fate of the
  Unexcreted Purins. Endogenous Purins. Source of Endogenous
  Purins. Proteins and their Derivatives. Amino-acids and
  Dicarboxylic Amino-acids. Endogenous Uric Acid Excretion.
  Factors influencing Endogenous Uric Acid Excretion.
  Physiological Conditions. Pathological States. Ingestion of
  Certain Drugs. Synthetic Formation of Uric Acid             _pp._   83-97

                              CHAPTER VIII

                 FORMATION AND DESTRUCTION OF URIC ACID

  Distribution of the Enzymes. Stages in Disruption of Nucleic
  Acid. Destruction of Uric Acid                              _pp._  98-106

                               CHAPTER IX

                      URIC ACID IN RELATION TO GOUT

  Uric Acid Excretion in Gout. Uric Acid Variations in Acute
  Gout. Uric Acid Variations in Chronic Gout. Retarded Exogenous
  Uric Acid Output. Lowered Endogenous Uric Acid Output. Other
  Anomalies in Excretion in Gout. Purin Metabolism in other
  Disorders. Purin Metabolism in Chronic Alcoholism and
  Plumbism                                                    _pp._ 107-116

                                CHAPTER X

                        THE RENAL THEORY OF GOUT

  Anomalies in Uric Acid Excretion in Gout. Uricæmia in
  Nephritis. The Relationship, if any, between the Amounts of
  Uric Acid and of Urea, and Total Non-protein Nitrogen in Human
  Blood. Uricæmia not necessarily due to Renal Defect. Uricæmia
  not Peculiar to Nephritis. Uricæmia does not necessarily
  Portend Gout. To what may be ascribed the Deficient
  Eliminating Capacity of the Kidney for Uric Acid. Uratic
  Deposits in Nephritis. Differentiation of Uratic Deposits in
  Gout and Nephritis. Clinical Associations of Gout and Granular
  Kidney                                                      _pp._ 117-132

                               CHAPTER XI

                            URICÆMIA IN GOUT

  Folin and Denis’s Method. Uric Acid a Normal Constituent of
  Blood. Effect of Exogenous Purins. Uric Acid Content of Blood
  in Gout. Hyperuricæmia in Non-gouty Arthritis. Variations
  in Uric Acid Content of Blood independently of Diet. What
  Relationship, if any, Exists between the Uric Acid Content of
  the Blood and Attacks of Gout. Discussion of the Foregoing
  Data. The Significance of Uricæmia. Sources of Fallacy in Uric
  Acid Estimation. Disabilities of Modern Tests. Need for further
  Investigations                                              _pp._ 133-148

                               CHAPTER XII

                      URATOSIS IN RELATION TO GOUT

  Constitution of Tophi. Mode of Formation. Localisation of
  Uratic Deposits. The Causation of Tophi. Solubilities of Uric
  Acid. Tophi in Relation to Uricæmia. Tissue Affinities for Uric
  Acid. Retention Capacity of Tissues for Uric Acid. Clinical
  Evolution of Tophi. The Cause of the Inflammatory Phenomena.
  Non-toxicity of Uric Acid. Are the Precursors of Uric Acid
  Toxic?                                                      _pp._ 149-170

                              CHAPTER XIII

                    THE RISE OF THE INFECTIVE THEORY

  Boerhaave’s Forecast of the Infective Theory. Ringrose Gore on
  Infective Origin. Leucocytosis in Acute Gouty Polyarthritis.
  Chalmers Watson’s Researches on Gout in a Fowl. Trautner’s
  Suggestion of a Specific Infection                          _pp._ 171-176

                               CHAPTER XIV

                          GOUT AS AN INFECTION

  Local Foci of Infection: Dental, Nasal, Pharyngeal, etc.
  Gastro-intestinal Disorders. Variation in Free HCL. Intestinal
  Disorders. Infection or Sub—infection                       _pp._ 177-187

                               CHAPTER XV

                   GOUT AS AN INFECTION (_continued_)

  Analysis of the Acute Paroxysm. The Evolution and Life History
  of Gout. Analogies between Gout and the Specific Infective
  Arthritides. Correlation of the Metabolic Phenomena of Gout
  with the Postulated Infective Element                       _pp._ 188-199

                               CHAPTER XVI

                            CLINICAL ACCOUNT

  Acute Localised Gout. Prodromal Symptoms. Dyspepsia.
  Premonitory Symptoms of Tophus Formation. Premonitory Articular
  Pains. The Acute Paroxysm. Detailed Consideration of Phenomena.
  Mode of Onset. Localisation. Nature of Pain. General Phenomena.
  Pyrexia. Changes in the Blood. Uric Acid Excretion. Local
  Phenomena. Tophus Formation                                 _pp._ 200-213

                              CHAPTER XVII

                     CLINICAL ACCOUNT (_continued_)

  Acute Gouty Polyarthritis. Mode of Invasion. Distribution of
  Lesions. Local Characters. Constitutional Symptoms. Changes in
  the Blood. Leucocytosis. Collateral Phenomena of Gout. Lumbago,
  Sciatica, etc. Incidence of Gouty Stigmata in Various Types of
  Fibrositis                                                  _pp._ 214-224

                              CHAPTER XVIII

                     CLINICAL ACCOUNT (_continued_)

  Chronic Articular Gout. The Joint Deformities of Chronic Gout.
  Tophi: Their Evolution and Distribution. Other Sites of Tophi.
  Affinities between Gout and other Diseases. Gout in Relation to
  Glycosuria. Gout in Relation to Phlebitis. Cutaneous Disorders.
  Gout and Nephritis. Prognosis in Gout                       _pp._ 225-246

                               CHAPTER XIX

                   ETIOLOGICAL AND CLINICAL DIAGNOSIS.

  Articular Gout. Etiological Diagnosis. Clinical Diagnosis.
  Introductory Remarks. The Diagnostic Status of Tophi. Tophi
  in Relation to Arthritis. Frequency of Tophi in True Gouty
  Arthritis Underestimated. Difficulty of Detecting Tophi     _pp._ 247-257

                               CHAPTER XX

                    CLINICAL DIAGNOSIS (_continued_)

  Acute Articular Gout. Localised Variety. Differential
  Diagnosis. Infections. Acute Gonococcal Arthritis. Traumatic
  Lesions. Acute Osteoarthritis. Static Foot Deformities. Hallux
  Valgus with Inflamed Bunion. Hallux Rigidus. Metatarsalgia.
  Gout in the Instep. Gonococcal Arthritis. Tuberculosis and
  Syphilitic Disease of the Tarsal Joints or the Related Joints.
  Pes Planus. Gout in the Heel. Referred Pain. Local Sources
  of Fallacy. Post-calcaneal Bursitis. Synovitis of the Tendo
  Achillis. Gout in the Sole. Plantar Neuralgia. Erythromelalgia.
  Anomalous Sites for Initial Outbreaks                       _pp._ 258-267

                               CHAPTER XXI

                    CLINICAL DIAGNOSIS (_continued_)

  Acute Gouty Polyarthritis. Differential Diagnosis. Acute
  Articular Rheumatism. Acute Gonococcal Arthritis. Etiology.
  Onset. General Symptoms. Distribution of Lesions. Local
  Characters. Associated Phenomena. Secondary Syphilitic
  Arthritis. Acute Rheumatoid or Atrophic Arthritis. Age and
  Sex. Onset. General Symptoms. Distribution of Lesions. Local
  Characters. Associated Phenomena. Infective Arthritis of
  Undifferentiated Type                                       _pp._ 268-274

                              CHAPTER XXII

                    CLINICAL DIAGNOSIS (_continued_)

  Chronic Articular Gout. Chronic Monarticular Gout. Monarticular
  Gout in Large Articulation a Rarity. Chronic Gout of
  Oligo-articular Distribution. Its Confusion with Chronic
  Villous Synovitis. Villous Synovitis Static and Non-gouty in
  Origin. Clinical Symptoms of Villous Synovitis. Bilateral
  Hydrarthrosis. Peri-synovial and Peri-bursal Gummata. Chronic
  Gout of Polyarticular Distribution. Differential Diagnosis.
  Osteoarthritis. Local Characters of Joint Swellings. Rheumatoid
  Arthritis. Local Characters of Joint Swellings. Nerve
  Arthropathies. Hæmophilic Arthritis                         _pp._ 275-285

                              CHAPTER XXIII

                    CLINICAL DIAGNOSIS (_continued_)

  Skiagraphy. Significance of Local Areas of Rarefaction. The
  Radiographic Types of Gouty Arthritis. Differential Diagnosis.
  Infective Arthritis. Hypertrophic or Osteoarthritis. Rheumatoid
  or Atrophic Arthritis                                       _pp._ 286-292

                              CHAPTER XXIV

                             IRREGULAR GOUT

  Historical Account. Murchison’s Views. Retrocedent Gout. Gout
  in the Stomach. Cardiac and Cerebral Forms. Other Irregular
  Manifestations. Conclusions. Infantile Gout                 _pp._ 293-307

                               CHAPTER XXV

                       OCULAR DISEASE IN THE GOUTY

  Evidence of Gout in the Eye. Deposition of Urates. Gouty
  Diathesis. Significance and Location of Tophi. Relative
  Incidence of Iritis. Metastasis. Arthritic Iritis. Gouty Iritis
  not a Clinical Entity. Ocular Symptoms in Hyperuricæmia.
  False Gout. Retinal Hæmorrhage. Neuro-retinitis. Glaucoma.
  Conclusions                                                 _pp._ 308-326

                              CHAPTER XXVI

                            TREATMENT OF GOUT

  Radical Treatment of Local Foci of Infection or Toxic
  Absorption. Diet in Acute and Chronic Gout. The Fallacy of
  Fixed Dietaries. Thorough Physical Examination a necessary
  Prelude to Dieting. Need for Collaboration of Clinician and
  Bio-chemist                                                 _pp._ 327-341

                              CHAPTER XXVII

                     TREATMENT OF GOUT (_continued_)

  Regulation of Diet in the Gouty. The Individual Foodstuffs,
  Proteins, Carbohydrates, Fats, Vegetables, Fruits, Condiments.
  Special Dietaries. Amylaceous Dyspepsia. Hyperchlorhydria   _pp._ 342-371

                             CHAPTER XXVIII

             MEDICINAL AND OTHER MODES OF THERAPY—ACUTE GOUT

  Initial Purgation. Colchicum in Acute Gout. Method of
  Administration. Preparations and Dosage. Colchicine, Salicylate
  of Colchicine. Atophan. Alternative Remedies in Acute Gout.
  Salicylates. Alkalies. Quinine. Thyminic Acid. Anodynes in
  Acute Gout. Local Measures. Analgesics. Liniments, etc.
  Ionisation. Massage. Surgical Methods                       _pp._ 372-388

                              CHAPTER XXIX

                  MEDICINAL AND OTHER MODES OF THERAPY
                  (_continued_)—INTER-PAROXYSMAL PERIOD

  Prophylactic Measures. Treatment of Atonic Dyspepsia.
  Hyperacidity due to Organic Acids. Treatment of
  Hypochlorhydria. Alkalies, Atophan, and Colchicum as
  Prophylactics                                               _pp._ 389-396

                               CHAPTER XXX

       MEDICINAL AND OTHER MODES OF THERAPY (_continued_)—CHRONIC
             ARTICULAR GOUT AND ASSOCIATED MORBID CONDITIONS

  Alkalies. Contrasts between Salts of Sodium and Potash.
  Differential Indications for their Usage. Alternatives.
  Salicylates. Benzoates. Hexamine. Iodides. Iodine. Albumen
  Compounds. Collosol Preparations of Iodine. Guaiacum. Local
  Measures in Chronic Articular Gout. Treatment of Tophi.
  Ionisation. Surgical Measures. Treatment of Associated
  Morbid Conditions. Fibrositis. Lumbago. Sciatica. Acute
  Brachial Fibrositis. Local Massage. Oxaluria. Glycosuria.
  Hyperchlorhydria. Gouty Phlebitis. Gouty Eczema. Gouty
  Nephritis                                                   _pp._ 397-417

                              CHAPTER XXXI

                  CLIMATO-THERAPY, HYDRO-THERAPY, ETC.

  Climate. Choice of Residence. Clothing. Exercise. Massage.
  General Hydro-therapy. Importance of thorough Physical
  Examination. Individual Reactive Peculiarities. Prophylactic
  Measures. Contra-indications and Untoward Complications.
  Methods of Application of General Hydro-therapy. Immersion
  Baths. Aix and Vichy Massage. Vapour Baths. Indications for
  Sub-thermal Baths. Local Hydro-therapy. Varieties of Douche.
  Treatment by Hyperæmia                                      _pp._ 418-430

                              CHAPTER XXXII

                    MINERAL SPRINGS AND CHOICE OF SPA

  Difficulties of Definition and Classification. Radio-activity.
  General Principles of Spa Treatment. Physiological Action
  of Radium Emanation. Activation of Body Ferments. Influence
  of Uric Acid Metabolism. Increased Excretion of Uric Acid.
  Subjective Phenomena of Gout in Relation to Blood Content and
  Excretion of Uric Acid. Therapeutic Action and Application.
  Alimentary Disorders. Glycosuria. Raised Blood Pressure. Choice
  of Spa. The Spare and the Obese. Waters Suitable for Various
  Types of Dyspepsia. Bickel’s Experiments. Mineral Waters in
  Associated Morbid Conditions. Glycosuria. Oxaluria. Phlebitis.
  Respiratory Disorders. Fibrositis. Gouty Eczema. Uric Acid
  Gravel. Arterio-sclerosis. Chronic Nephritis. Concluding
  Remarks on Spa Treatment                                    _pp._ 431-465

  INDEX                                                       _pp._ 457-469





CHAPTER I

HISTORICAL AND INTRODUCTORY


THE ANTIQUITY OF GOUT

“Teeth, bones, and hair,” quoth the Sage of Norwich, “give the most
lasting defiance to corruption,” and were it not that “Time which
antiquates antiquities and hath an art to make dust of all things hath
yet spared these minor monuments,” it might perhaps have been inferred
that gout was the primordial arthritic disease that afflicted mankind.

That it was the first articular affection to achieve clinical
individuality may be allowed, but, from the aspect of antiquity, gout
is relatively modern—the appanage of civilisation. True, Hippocrates,
discoursing in the famous Asclepion at Cos, enunciated his aphorisms on
gout some 300 years before the Christian Era, the dawn of which moreover
found Cicero in his discussions at Tusculum lamenting its excruciating
tortures “doloribus podagræ cruciari” and the peculiar burning character
of its pains “cum arderet podagræ doloribus.”

But what of that? For did not Flinders Petrie in the hoary tombs of Gurob
(dating back to the 28th Dynasty 1300 B.C.) find in mouldering skeletons
of bygone civilisations unequivocal evidence of _osteoarthritis_.[1] But
despite these sure though silent witnesses of the prevalence of this
disorder among the ancient people of Egypt, yet in contrast with gout, no
hint transpires in the writings of Greek or Roman physicians, nor those
of much later date, that the condition was recognised _clinically_, as a
joint disorder, distinct from others of the same category.

Small call to marvel thereat, for how much more arresting the clinical
_facies_ of gout, with its classic insignia—tumor, robor, calor, et
dolor—than of osteoarthritis, its etiolate tokens indicative rather of
infirmity than of disease. Apart from this, it may well be that the
early Egyptians owed their relative immunity from gout, and alike their
proneness to osteoarthritis, to living hard laborious days, unenervated
by that luxury and sloth, which in the first century A.D. drew upon the
ancient Romans the caustic reproofs of Pliny and Seneca. For the old
philosophers lamented the growing prevalence of the disorder, almost
unknown in the early, more virile days of the Empire, rightly seeing in
it but another harbinger of impending decadence, clearly attributable as
it was to riotous living and debauchery.

Indeed, we have it on the authority of Galen that “In the time of
Hippocrates there were only a few who suffered from podagra, such was the
moderation in living, but in our own times, when sensuality has touched
the highest conceivable point, the number of patients with the gout has
grown to an extent that cannot be estimated.”

Nothing, in truth, seems more clearly established than this, that gout
is the Nemesis that overtakes those addicted to luxurious habits and
dietetic excesses. On the testimony of eminent travellers we are assured
that amongst aborigines the disease is unknown. The indigenous native
tribes of India are immune, but not so the immigrant flesh-loving
Parsees. Strange to relate, Anglo-Indians of gouty habit, while resident
in the Orient, seem exempt, some say, owing to cutaneous activity, but
more probably because _quâ_ Rendu “these are countries in which we cannot
survive unless we are frugal.”

Nations too, like individuals, when fallen on hard times, lose their
gout. Thus the Arabs, at the zenith of their mediæval Empire, were prone
thereto, but in these latter days are almost exempt from its ravages.
But, on the other hand, if we are to believe Professor Cantani, in no
other disorder are the “sins of the fathers visited upon the children”
with such pertinacity, claiming as he does that its marked incidence in
Southern Italians is a direct heritage from the ancient Greeks and Romans.


PREVALENCE OF GOUT IN THE ANGLO-SAXON PERIOD

Reverting to our own country, what evidences as to its antiquity are
forthcoming? This much may at any rate be affirmed, that according to
Mason Good “Gout is one of the maladies which seem to have been common in
England in its earliest ages of barbarism. It is frequently noticed by
the Anglo-Saxon historian, and the name assigned to it is Fot-adl.”

Cockayne, in his “Leechdoms Wortcumming and Starcraft,” of early England,
has it that the word “addle” appears to have been a synonym for ailment,
thus “Shingles was hight circle addle.” That gout should have flourished
so among our Anglo-Saxon forbears is perhaps a matter for regret but not
for astonishment, when we recall their coarse Gargantuan feasts, washed
down with doughty draughts of ale, “sack and the well spic’d hippocras.”

Gout, we see then, even in our own land, is full ancient, and the word,
as Bradley as shown, may be traced in the English tongue right through
the literature of the various periods.[2] This not only in the brochures
of physicians, but also as in the days of Lucian in the works of
historians, and the satires of poets, which indeed abound with allusions
to the disease.


VIEWS OF THE HUMORALISTS

The Greek physicians, quite familiar as they were with the overt
manifestations of gout, did not, as far as its nosology was concerned,
commit themselves to any appellation that might imply their adherence
to any theory as to its causation. They contented themselves with a
mere _topographical_ designation, terming the affection, _podagra_,
_chirargra_, etc., according as foot or hand was the seat of the
disorder, while for polyarticular types the generic term _arthritis_ was
invoked.

Nevertheless the old Greek physicians had their views as to its
pathology. Thus the source of the peccant humours resided for them in the
_brain_, which they had invested with all the functions of an absorbent
and secreting gland. This hypothesis in time was displaced by the true
humoral theory, according to which the bodily fluids, those found in the
alimentary canal, the blood stream, and the glandular organs, were the
primordial agents of disease. No need, albeit, for gibes on our part, for
how true much of their conception of the genesis of disease even to-day.
Indeed, what else than a fusion of the foregoing views? the modern theory
of Sir Dyce Duckworth, who would ascribe gout to the combined influence
of _neural_ and _humoral_ factors. And now to consider briefly the
individual views of the fathers of medicine.


THE APHORISMS OF HIPPOCRATES

In the eyes of the pioneer priest-physician, the disorder was
attributable to a retention of humours, and many of his dicta have stood
the corroding test of time. He noted, like Sydenham, its tendency to
periodicity, its liability to recur at spring and fall. Also that eunuchs
are immune and youths also, _ante usum veneris_, while in females its
incidence is usually delayed until after the menopause.

The curability of the disease in its earlier stages was affirmed, but
that after the deposit of chalk in the joints it proved rebellious to
treatment, which for him resided in purgation and the local application
of cooling agents.

In the first and second centuries Celsus, Galen, and Aretæus the
Cappadocian recounted their views as to its nature and therapy, while the
Augustan poet in his Pontic epistles, like Hippocrates, laments that his
gouty swellings defy the art of medicine.

    “Tollere nodosam nescit medicina podogram.”

             _Ovid_, _Ep. ex Pont._, I, 3, 23.

To Celsus, venesection at the onset of an attack seemed both curative and
prophylactic. Corpulence of habit a state to be avoided, and conformably
he prescribed frugality of fare and adequate exercise. Galen (130-200),
more venturesome than his contemporaries, voiced his belief that tophi
were compact of phlegm, blood, or bile, singly or in combination. For
the rest, he enjoined bleeding and purgation and local applications,
contravening, by the bye, Hippocrates’ claim as to the immunity of
eunuchs in that in his (Galen’s) day their sloth and intemperance were
such as readily begat the disorder.

About this period Lucian of Saramosta enumerated the various anti-gout
nostrums vaunted as specifics in his day. Though in his comic poems, the
Trago-podagra and Ocypus he rightly holds up to scorn the charlatanism
rampant at the time, still it is quite clear that he possessed no mean
knowledge of the clinical vagaries of gout and was quite alive to the
mischief of too meddlesome treatment thereof.

Said the hero of the Trago-podagra:

                “Irritantibus me
    Soleo occupere multo iracundior
    His vero qui cogitant nihil adversum mihi
    Benignam adhibeo mentem, facilisque fio.”

Again, Seneca, in a jeremiad on the decadent habits of Roman ladies of
the patrician order, observes: “The nature of women is not altered but
their manner of living, for while they rival the men in every kind of
licentiousness, they equal them too in their very bodily disorders. Why
need we then be surprised at seeing so many of the female sex afflicted
with gout.” That the old philosopher’s misgivings were but too well
founded is obvious when we recall that so widespread were the ravages of
gout among the Romans in the third century that Diocletian, by an edict,
exempted from the public burdens those severely crippled thereby, in
sooth a blatant illustration of political pandering to national vice.

But to return to the researches of physicians, those of Aretæus seem
to have been the most enlightened of his time. A succinct account of
the mode of invasion of gout and its centripetal spread in later stages
to the larger joints is followed by enumeration of the exciting causes
of outbreaks. Anent these, he quaintly notes the reluctance which the
victims display to assigning the malady to its true cause—their own
excesses—preferring to attribute it to a new shoe, a long walk, or an
injury. Noting that men are more liable than women, he tells us, too,
that between the gouty attacks the subject has even carried off the palm
in the Olympic games. The white hellebore, to his mind, at any rate in
early attacks, was the remedy _par excellence_. But, for the true nature
of the disease, he, with humility and piety, avows that its secret origin
is known only to the gods.

Not so his successor Cælius Aurelianus, who affirmed it to be not
only hereditary but due to indigestion, over-drinking, debauchery,
and exposure. Under their maleficent influence morbid humours were
generated which sooner or later found a vent in one or other foot, with
a predilection for tendons and ligaments; these structures he averred
being the locus morbi. An abstemious dietary with exercise was his sheet
anchor in therapy, with local scarification in preference to cupping and
leeching, but violent purging and emetics he decried, and drugs to him
made little appeal.

More ambitious than his predecessors, Alexander of Tralles, in the
sixth century, held that there were many varieties of gout, some due
to intra-articular effusions of blood, reminding us of Rieken’s view
(1829) that hæmophilia is an anomalous variant of gout. Other cases,
Alexander averred, were the outcome of extravasation of bile or other
peccant fluids between tendons and ligaments. Abstinence, especially
from wine and blood-forming foods, was enjoined and a plentiful use of
drastic purgatives, elaterium, etc., with local sinapisms and blisters.
For the absorption of chalk stones he commended unguents containing oil,
turpentine, ammoniacum, dragon’s blood, and litharge.

Aetius, a contemporary, is noteworthy in that during the intervals of
attacks he highly eulogised the use of friction while, like Alexander
of Tralles, he seems to have been much impressed with the virtues
of colchicum, of which he says, “Hermodactylon confestim minuit
dolores.” Planchon, in 1855, in his treatise, “De hermodactes au point
de vue botanique et pharmaceutique,” claims to have proved that the
hermodactylon of the ancients was _Colchicum variegatum_, of similar
properties to the _Colchicum autumnale_.

Paulus Ægineta, like most of his _confrères_, regarded gout and
rheumatism as the same disorder, differing only in their location. He
subscribed whole heartedly to the prevailing humoral theory, but inclined
to think the site of the discharged humours was influenced by weakness or
injury of the parts. He noted, too, that mental states, sorrow, anxiety,
etc., might act as determining causes.

Nor will any historical _résumé_ rest complete without a reference to the
numerous works of the Arabian physicians—Avicenna, Rhazes, Serapion, and
Haly Abbas—who one or other all maintained gout to be hereditary, rare in
women and due to peccant humours, developed in the train of depletions,
debaucheries, and the like.


INTRODUCTION OF THE WORD “GOUT”

In the thirteenth century the Greek terms “podagra,” “chirargra,” etc.,
were to a large extent abandoned, and following Radulfe’s lead gave way
to the use of the generic term “gout,” derived from the Latin “gutta.”
Its adoption was doubtless traceable to the prevailing humoral views
of the origin of the disorder, as due to some morbid matter exuding by
“drops” into the joint cavities. Indeed, according to Johnson, the word
“gut” was used as a synonym for “drop” by Scottish physicians even in his
day.

In any case, the term found little difficulty in installing itself among
all nations, taking in French the form “goutte,” in German “gicht,” in
Spanish “gota,” etc. Trousseau thought it “an admirable name, because in
whatever sense it may have been originally employed by those by whom it
was invented, it is not now given to anything else than that to which
it is applied.” In contrast therewith, that trenchant critic Pye-Smith
complained of the laxity with which the Germans invoked the word “gicht.”
He says it is popularly credited with all the pains which are called
“rheumatics” in England. “Sometimes ‘gicht’ is nothing but bad corns and
is rarely true gout.” Albeit, Pye-Smith did not, as we shall see later,
hold even his English _confrères_ in this respect void of offence.

From these remote times onwards through the Middle Ages to the present
day, an almost continuous series of historical records testify that not
only has gout always been with us, but that its clinical characters
throughout the ages have remained unaltered, conforming ever to the
primitive type. During the seventeenth and eighteenth centuries many
physicians, both British and continental, ventilated their views as to
the nature of gout, all swearing allegiance to the old humoral pathology,
notably Sydenham, Boerhaave, Van Swieten, Hoffmann, Cadogan, etc.

The English Hippocrates, as Trousseau christened the illustrious
Sydenham, displayed his catholic outlook by the pregnant words: “No very
limited theory and no one particular hypothesis can be found applicable
to explain the whole nature of gout.” A live-long martyr himself thereto,
he brought all the strength of his dominating intellect to bear upon its
elucidation. As to its causation, he held it to be due to a “morbific
matter,” the outcome of imperfect “coctions” in the _primæ viæ_ and in
the secondary assimilating organs. He refrained from speculating as to
the constitution of the _materia peccans_, but as Trousseau observes, “he
made his _morbi seminium_ play the part which modern chemistry attributes
to the products it has discovered. Take it all in all,” he says, “the
theory of the great English physician is much more medical than the
theories of modern chemists.”


EARLY VIEWS AS TO THE NATURE OF TOPHI

    “Et tophus scaber, et nigris exesa chelydris Creta.”

                                    _Georg._, ii., 214.

The word “tophus” or “tofus,” the Greek τοφος, seems to have been applied
to rough crumbling rock, the disintegrated volcanic tufa. As to its
constitution it is clear from the above quotation that Virgil evidently
associated it with chalk, a shrewder guess than the fanciful hypothesis
of Galen, though the views of Paracelsus (1493-1541) enunciated some
centuries subsequently, were even more grotesque, a “mucous essence,” a
“Tartarus” burning “like hell fire.”

Nevertheless, our contempt need be chastened when we recollect that, up
to the latter half of the eighteenth century, equally weird assumptions
found acceptance. By some “various excrementitial humours,” by others
“checked and decomposing sweat” were deemed the basis of tophi.

A mucilaginous extract, derived from the solid and liquid intake,
appealed to some as an explanation of their formation, while to others,
tophi were compounds of subtle and penetrating salts.

But the later view, doubtless the reflex of _etiological_ hypotheses,
was that tophi were of _tartareous_ nature, closely similar to that
encrusting the interior of wine casks. Hoffmann declared that the
_materies morbi_ actually was a salt of tartar circulating in the blood.
His investigations of tophi and also of the stools, saliva, and urine of
gouty subjects, convinced him that the peccant matter was tartar of wine.

Hoffmann’s views, however, were laughed to scorn by M. Coste as being
obviously absurd, inasmuch as gout was not uncommon amongst those who
had never partaken of wine, _ergo_, never of tartar. How infinitely
more physicianly the inference of Sydenham, who, like some of the older
humoralists held the tophus to be “undigested gouty matter thrown out
around the joints in a liquid form and afterwards becoming hardened.”

So it went on until, alchemy being displaced by chemistry, uric acid was
in 1775 discovered by Scheele, and in 1787 Wollaston established its
existence in tophi, and to the further elaboration of our knowledge of
this substance we shall allude later. Here we would only observe that
Wollaston’s researches marked the coming substitution of the humoral and
solidist theories by a chemical hypothesis as to the etiology of gout.


THE “HONOUR OF THE GOUT”

The absurd delusion, not wholly dissipated even to-day, that to have the
gout, “Morbus Dominorum,” was highly creditable, a mark of good breeding,
was firmly ingrained in our forefathers. We all recall the story of the
old Scottish gentlewoman who would never allow that any but people of
family could have _bonâ fide_ gout. Let but the _roturier_ aspire to this
privilege, and she scouted the very idea—“Na, na, it is only my father
and Lord Gallowa’ that have the regular gout.” As to the origin of this
mistaken ambition, it most probably was the outcome of the fact that it
was peculiarly an appanage of the great, the wealthy, and alas! those of
intellectual distinction!

Statesmen, warriors, literary men and poets loom large amongst its
victims. Lord Burleigh suffered greatly therefrom, and good Queen Bess
on that account always bid him sit in her presence, and was wont to say,
“My Lord, we make much of you, not for your bad legs, but for your good
head!” With more humour, Horace Walpole complained, “If either my father
or mother had had it I should not dislike it so much! I am herald enough
to approve it, if descended genealogically, but it is an absolute upstart
in me, and what is more provoking, I had trusted in my great abstinence
for keeping it from me, but thus it is!”[3]

Of warriors, Lord Howe, Marshal Saxe, Wallenstein, and Condé were among
its victims; while of literary men and poets thus afflicted may be
mentioned Milton, Dryden, Congreve, Linnæus, Newton, and Fielding. Of
physicians, the great Harvey was a martyr to gout, and was wont to treat
it after the following heroic fashion. Sitting, in the coldest weather,
with bare legs on the leads of Cockaine House, he would immerse them in
a pail of water until he nearly collapsed from cold. Mrs. Hunter, wife
of John Hunter, in a letter to Edward Jenner about her distinguished
husband, dated Bath, September 18th, 1785, laments that “He has been
tormented with the flying gout since last March!” In short, the disorder,
with a notable frequency, figures in the life history of some of the
ablest men in all ages, hence the complacency with which lesser men,
often without good reason, affect to have the gout.

“But nothing,” as Sir Thomas Watson says, “can show more strongly the
power of fashion than this desire to be thought to possess, not only
the tone and manners of the higher orders of society, not their follies
merely and pleasant vices, but their very pains and aches, their bodily
imperfections and infirmities. All this is more than sufficiently
ludicrous and lamentable, but so it is. Even the philosophic Sydenham
consoled himself under the sufferings of the gout with the reflection
that it destroys more rich men than poor, more wise men than fools.”

    “At vero (quod mihi aliisque licet, tam fortunæ quam Ingenii
    dotibus mediocriter instructis, hoc morbo laborantibus solatio
    esse possit) ita vixerunt atque ita tandem mortem obierunt
    magni Reges, Dynastæ, exercituum classiumque Duces, Philosophi,
    aliique his similes haud pauci.

    “Verbo dicam, articularis hicce morbus (quod vix de quovis alio
    adfirmaveris) divites plures interemit quam pauperes, plures
    sapientes quam fatuos.”

The Scotch at one time regarded gout as fit and meet punishment for the
luxurious living of the English. But, as was pointed out, the cogency of
the moral was somewhat spoilt by the fact that the disorder was found
to exist even among the poor and temperate Faroe Islanders. In truth,
although “the taint may be hereditary, it may be generated by a low diet
and abstinence carried to extremes.”


THAT GOUT CONFERS IMMUNITY FROM OTHER DISORDERS

The fallacy that longevity and freedom from other maladies was ensured
by gout was prevalent among our forefathers. In satire of this, one
Philander Misaurus issued a brochure entitled “The Honour of the Gout,”
and purporting to be writ, “Right in the Heat of a violent Paroxysm; and
now publish’d for the common Good” (1735). “Bless us,” says he, “that any
man should wish to be rid of the Gout; for want of which he may become
obnoxious to fevers and headache, be blinded in his understanding, loose
the best of his Health and the Security of his Life”; and forthwith in
his zeal for the common good gives us the following invocation:—

    “Blessed Gout, most desirable Gout, Sovereign Antidote
    Of murdering Maladies; powerful corrector of Intemperance;
    Deign to visit me with thy purging Fires, and throw off the
    Tophous Injury which I may have suffer’d by Wine and Wit,
    Too hard for the Virtue of a Devotee upon a Holy Festival.
    But fail not thy humble Supplicant, who needs thy
    Friendly Help, to keep his tottering Tenement in
    Order: Fail him not, every Vernal and Autumnal
    Æquinox.”

He quaintly suggests that Paracelsus, if he would ensure men against
death, had but to inoculate them with gout. Gout, indeed, was held to
be a jealous disorder, intolerant of usurpation by any other disease,
recalling the remark of Posthumus to his gaolers:—

                            “Yet am I better
    Than one that’s sick o’ the Gout: since he had rather
    Groan so in perpetuity, than be cur’d
    By the sure physician, death: who is the key
    To unbar these locks.”

                                               _Cymbeline._

Still the fallacy that gout was salutary died hard, and although it seems
incredible, yet, Archbishop Sheldon is said not only to have longed for
gout but actually to have offered £1,000 to any one who would procure him
this blessing; for he regarded gout as “the only remedy for the distress
in his head.” How ingrained the notion may be gathered from the fact that
in the early part of the last century, M. Coste in his “Traité Pratique
de la Goutte,” observed: “A popular error, which I wish to expose in a
few words, is this prejudice, which has already lasted more than two
thousand years, and which has reached even the thrones of princes,
where the disease commonly shows itself, viz., that gout prolongs life
(_que la goutte prolonge la vie_). This error,” says he, “has taken the
surest method of introducing itself, by making flattering promises, by
persuading its victims that there is a singular advantage in having gout,
and that the malady drives away all other evils, and that it ensures long
life to those whom it attacks.”

In like refrain, our own countryman Heberden deplores that people “are
neither ashamed nor afraid of it; but solace themselves with the hope
that they shall one day have the gout; or, if they have already suffered
it, impute all their other ails, not to having had too much of that
disease, but to wanting more. The gout, far from being blamed as the
cause, is looked up to as the expected deliverer from these evils.” Such
deluded views being prevalent, it is hardly a matter for surprise that
misguided persons deliberately courted a “fit of the gout” by resorting
to excess and intemperance.

But alas, while the initial visitations of gout, after their passing, may
leave behind them a renewed sense of well-being, it is no less certain
that, when once installed, the intervals of respite grow shorter and
shorter. Crippledom grows apace, the general health breaks and untimely
senescence overtakes the worn-out victim, and, as Heberden puts it, “that
gout causes premature death, when all the comforts of life ...

    ‘Multæ formæ infortunatorum,
    Meditatio pœnæ, et consuetudo,
    Podagros miseros consolentur.’

                        _Lucian._

are destroyed, and the physical powers either insensibly undermined or
suddenly crushed by an attack of paralysis or apoplexy, should hardly be
reckoned among the misfortunes attending the disease.”

But for our encouragement it may be observed that not always does gout
carry with it such a terrible Nemesis. “Gout is the disease of those
who _will_ have it,” said a wise physician, and though the inbred gouty
tendency may be so strong as to cast defiance at abstinence, yet it is
by no means always so. A man may inherit gout, but he need not foster
it by self-indulgence. Much less need he, as so often happens, acquire
it by depraved habits of life. In no disease do sobriety and virtuous
living ensure so great a reward. As Sir Thomas Watson long since said
to those inheriting this unwelcome legacy: “Let the son of a rich and
gouty nobleman change places with the son of a farm servant, and earn his
temperate meal by the daily sweat of his brow, and the chance of his
being visited with gout will be very small.”

    “O fortunatos nimium, sua si bona norint
    Agricolas!”

                          _Georg._, ii., 458.


GROWING INFREQUENCY AND ATTENUATION OF GOUT

So accurate and graphic were the clinical pictures of gout depicted by
the ancient physicians that there is no doubt the gout of to-day conforms
to the primitive type as met with among the Greeks and Romans. This
certainly as regards the _arthritic_ phenomena of the disease; for in
those remote ages little or no account seems to have been taken of its
_irregular_ or _ab-articular_ manifestations. While disregard of the
latter group renders more credible their claims as to the widespread
prevalence of the affection, nevertheless, I think there can be no doubt
that the frequency of _gout_ amongst the ancient Greeks and Romans was
probably over-estimated.

Can it be questioned that a large percentage of the cases of gout in
those bygone times consisted of undifferentiated _infective_ forms of
_arthritis_. _Syphilis_ and _gonorrhœa_ must have existed then as now,
and their _specific_ forms of _arthritis_, how easily confused with “rich
man’s gout!” Surely too, they, like ourselves, must have suffered with
states of _oral sepsis_, _pyorrhœa alveolaris_, etc., not to speak of
_infective disorders_, with their correlated _arthritides_. In short, the
_differentiation_ of arthritic disorders was then hardly in its infancy,
and it is in light of this disability that we must appraise their clearly
extravagant assertions as to the widespread ravages of gout in their day.

But passing to more recent times, there is little doubt that the
classical type of _podagra_ is very much rarer to-day than, say, in the
time of Sydenham. Indeed, it may be said to be becoming progressively
infrequent. Thus, writing in 1890, Sir Dyce Duckworth tells us that some
twenty-six years prior to that date, Sir George Burrows informed him
that “he then saw fewer cases of acute gout than he was accustomed to
see in his earlier practice.” It may be recalled, too, that Sir Charles
Scudamore, in retrospect of his own experience, of still earlier date,
was led to much the same conclusion. Moreover, not only is the disorder
less frequent, but its virulence seems to have suffered attenuation, and
this to a marked degree.

Again, Ewart, writing in 1896, observed that “goutiness” is becoming
relatively more common than declared gout. This, he thought, by reason
of the increasing attenuation in transmission of the “gouty” taint.
In this, as well as the more mitigated character of the arthritic
manifestations, he saw hope of “an ultimate extinction of the bias in
‘gouty’ families.” For, as he rightly says, side by side with “the
tendency to a reproduction of morbid parental peculiarities, there is a
yet stronger tendency in Nature to reproduce the healthy type of the race
in each successive generation.”

But while there is a general consensus of opinion as to the growing
rarity of acute regular gout, on the other hand, many, as if loth to part
with the disorder, claim that _pari passu_ with the decline of regular
types the incidence of _irregular_ manifestations grew proportionately.

In my experience the incidence of _regular_ gout has appreciably
diminished during the past twenty years. Moreover, such examples as
one has met with incline much more in character to the _asthenic_ than
to the sthenic variety of _podagra_. But, in contrast to many, I have
observed no increase in the _irregular_ manifestations of gout. On the
contrary, a steady diminution in the nebulous content of this category,
but to this vexed subject we shall recur in a subsequent chapter dealing
with the propriety or not of retaining this ill-defined term in medical
nomenclature.

My conclusion, then, is that not only is arthritic gout becoming
less prevalent, but that the type of the disease also has suffered
attenuation. Probably this dual change is the outcome of many factors,
not the least of these an increase in national sobriety. For as Sir
Alfred Garrod long since observed, “There is no truth in medicine better
established than the fact that the use of fermented liquors is the most
powerful of all the predisposing causes of gout; nay, so powerful, that
it may be a question whether gout would ever have been known to mankind
had such beverages not being indulged in.

    “Αυσιμελου Βάκχου, και λυσιμελους Αφοδίτης,
    Γένναται θυχατηρ, λυσιμελὴς, Ποδὰγρα.”




CHAPTER II

THE PEDIGREE OF GOUT


Under the vague term “articulorum passio” or “arthritis” the physicians
of antiquity handed down to posterity the clinical description of a
disease in the varied symptomatology of which we may descry at one time
the features of gout and anon those of rheumatism. But centuries had to
elapse before gout became differentiated from rheumatism. For there is no
doubt that not only the Greek and Roman physicians, but those also of the
Græco-Arabian school, confounded these two disorders, or more accurately
failed to differentiate rheumatism.

So it is that Charcot, reviewing the antiquity of gout, while he
pays a graceful tribute to the ancient physicians for their masterly
disquisitions thereon, at the same time deplored their silence on the
subject of articular rheumatism.

This absence of allusion thereto is the more remarkable in that the term
“rheumatism” or “rheumes” dates from a very remote period. Both words,
in truth, were indifferently enlisted to denote all those diseases
deemed attributable to the defluxion of some acrid humour upon one or
other part of the body. Used by the ancients more in accordance with its
etymological sense, the term “rheumes” or “rheumatism,” finds a place
even in the writings of Pliny and Ovid. But our modern conception of
the disorder differs widely from “the flux of humours” which the Greeks
named rheumatism, or “the sharpe and eager flux of fleam” which for them
characterised an attack of the “rheumes.”

The early English authors, too, invoked the word as a general term
descriptive of various forms of disease. Sir Thomas Elyot, in his
“Castel of Health,” so scoffed at by the faculty in his day, inculcates
abstemiousness in those afflicted with the “rheumes,” and in “Julius
Caesar,” Brutus is warned by Portia not to tempt “the rheumy unpurged
ayre of night,” a clear indication that the term was used as a synonym
for fluxions, humours and catarrhs of all sorts. But as to the malign
_articular_ forms of the affection, never a word; and this almost
inexplicable silence led Sydenham, Haecker and Leupoldt to surmise that
articular rheumatism was a modern disease unknown amongst the ancients.


ISOLATION OF ACUTE ARTICULAR RHEUMATISM FROM GOUT

Hallowed by tradition, this erroneous conception of the identity of gout
and rheumatism endured until 1642, when Baillon, in his treatise “De
Rheumatismo et Pleuritide,” effected a cleavage, at any rate between the
acute varieties of these two diseases.

Dissociating the term “rheumatism” from its primitive interpretation,
Baillon restricted its usage to that particular group of symptoms we now
call _acute articular rheumatism_. In the same century Sydenham, in his
“Classical Observations,” materially clarified the existing clinical
confusion, defining with his customary lucidity the essential differences
between the two disorders.


TARDY DISSOCIATION OF CHRONIC GOUT FROM CHRONIC RHEUMATISM

Bearing in mind the centuries that elapsed before the _acute_ articular
forms of gout and rheumatism were dissociated, one ceases to marvel that
the task, incomparably more difficult, of discriminating between the
_chronic_ forms of these diseases is even now barely accomplished.

“Rheumatissimus agnatus podagræ” said our forefathers, the axiom
postulating not the actual identity of the two affections, but a near
relationship, and in this non-committal phrase we may, I think, descry
the birth of that modern term “_L’arthritisme_,” so beloved of the French
physicians. Even as late as the beginning of the nineteenth century
Chomel at the Saltpetrière taught his pupils that gout and rheumatism
were but clinical variants of an underlying “arthritic diathesis,” his
successor Pidoux being still more insistent that the two disorders sprang
from one common root. Even Charcot and Trousseau, convinced as they were
of the essential distinctness of the two disorders, nevertheless admitted
that at the bedside their _chronic_ manifestations were with difficulty
dissociated, the former pointing to the terms “rhumatisme goutteux” and
“rheumatic gout” as tacit acknowledgments of our impotence.

Nor did this view that _gout_ and alike _rheumatism_ are the outcome of a
_basic arthritic diathesis_ fail of doughty supporters in this country.
Thus Hutchinson, in his “Pedigree of Disease,” observes “gout is but
rarely of pure breed, and often a complication of rheumatism. It so often
mixes itself up with rheumatism, and the two, in hereditary transmission,
become so intimately united, that it is a matter of considerable
difficulty to ascertain how far rheumatism pure can go ... when this
complication exists. It shows its power, we may suspect, by inducing a
permanent modification of tissue, and it is to this modification that
the peculiarities in the processes (transitory rheumatic pains in joints,
fasciæ, and muscles, chronic crippling arthritis, destructive arthritis
with eburnation, lumbago, sciatica) are due. Hence the impossibility
under many conditions of discriminating between gout and rheumatism.”

Laycock also subscribed to Charcot’s view, and Sir Dyce Duckworth
confesses that the conception of “a basic diathetic habit of body
called _arthritic_ has well commended itself to my mind,” while as to
the clinical commingling of the two disorders Sir Charles Scudamore
spoke with no uncertain voice. That an individual may in youth suffer
from _acute articular rheumatism_, and later in life develop _gout_, is
undeniable, as also the reverse, that a gouty subject may be harassed by
manifestations of chronic rheumatism or _fibrositis_. But this mutual
trenching of the one upon the clinical territory of the other must not be
allowed to impair our views as to the essential distinctness of _gout_
and _rheumatism_. It is undeniable that the difficulty of differentiating
between the _chronic_ forms of these two disorders is great, for not even
the revelations of _skiagraphy_, in the absence of a clinical history,
will suffice to effect a discrimination. But to a further consideration
of this vexed matter we refer the reader to the coming chapters on
Diagnosis.


IDENTIFICATION OF MUSCULAR RHEUMATISM

But to resume our thread, one great step forward we owe to Cullen, who
not only differentiated _acute_ from _chronic_ articular rheumatism, but
also clearly portrayed the clinical distinctness from both of _muscular_
rheumatism. In so doing, he materially assisted in the differentiation
of these same disorders from _gout_. But at the same time, owing to his
immoderate advocacy of “chill” as the one great cause of _rheumatism_
in all its forms, he undoubtedly retarded progress. For immediately
there arose a cloud of witnesses who claimed a “rheumatic kinship” for a
myriad _visceral_ disorders, the victims of which had suffered exposure.
Thus throughout the seventeenth and eighteenth centuries many of the
conditions now assigned to _irregular gout_ were affiliated instead to
_rheumatism_.


DIFFERENTIATION OF CHRONIC GOUT FROM ARTHRITIS DEFORMANS

Apart from Cullen’s contribution the eighteenth century was unmarked by
any further advance in differentiating the mass of heterogenous joint
affections, indifferently classed as gout and rheumatism. The physicians
of this period, indeed, appear not only to have done little themselves,
but had omitted to utilise the useful indications furnished by their
predecessors.

Thus how much more swiftly would the clinical distinctness of chronic
articular gout from _rheumatoid arthritis_ have been realised had
Sydenham’s dicta in the seventeenth century regarding this intricate
problem been duly appreciated. Up to his time, the clinical descriptions
of rheumatoid arthritis appeared now under gout, now under rheumatism.
As for Sydenham himself, he placed the disorder, nosologically speaking,
under _chronic rheumatism_, of which he believed it to be an _apyretic_
variety. But the importance of his researches resides in this—he pointed
out that it differed essentially from _gout_, but that, in resemblance
thereof, it might endure throughout life, its course diversified by
remissions and exacerbations. Also he tells us that its excruciating
pains, even when of prolonged standing, sometimes cease spontaneously,
noting also that the joints are, so to speak, turned over, and that there
are nodosities, especially on the inside of the fingers.

Nevertheless, if we except Musgrave’s work (1703), “Arthritis ex
Chlorosi,” which included some undoubted examples of _rheumatoid_ or
atrophic arthritis, no note was taken of Sydenham’s contention until
a century afterwards. True, John Hunter in 1759 described the morbid
anatomy of _osteoarthritis_ or the hypertrophic forms of arthritis
deformans, but not until 1868 was the true significance of Sydenham’s
work appreciated, a most generous tribute being then accorded him by the
great French physician Trousseau.

In 1800 Landre Beauvais published his clinical description of
_rheumatoid_ arthritis under the title “goutte asthenique primitif.” That
Beauvais, as Sir Archibald Garrod contends, included under this title
some cases of true _gout_ is beyond doubt. But the words “Doit admettre
une nouvelle espèce de goutte,” go far to justify Charcot in his claim
that Beauvais, despite the title of his brochure, fully realised that the
disease differed from gout.

A few years later (1804-1816), Heberden, in his Commentaries, insisted
on the essential distinctness of rheumatoid arthritis from gout. Thus he
wrote, “The disease called chronical rheumatism, which often passes under
the general name of rheumatism and is sometimes supposed to be _gout_, is
in reality a very different distemper from the genuine gout, and from the
acute rheumatism, and ought to be carefully distinguished from both.” As
to its salient features he noted its afebrile nature, the lack of redness
in the skin over the affected joints, the relative absence of pain,
and that it displayed no special tendency to begin in the feet. It was
further marked by a protracted course involving severe crippling, while
the peculiar nodosities on the fingers are still associated with his name.

In 1805 Haygarth published his classical essay, “A Clinical History
of the Nodosity of the Joints,” the opening sentence of which shows
that, comparably with his successors, he lamented the laxity with which
the term “rheumatism” was invoked and applied “to a great variety of
disorders which beside pain, have but few symptoms that connect them
together.” A purist in nosology, he equally deplored the term “rheumatick
gout” as tending to perpetuate its confusion with gout and rheumatism,
and suggested the term “Nodosities,” in the hope that “as a distinct
genus it will become a more direct object of medical attention.”

Alas, even as late as 1868 Trousseau deplored the retention of the term
“rheumatic gout” by Garrod and Fuller and his own countryman Trastour.
But, in common justice to Garrod, it must be allowed that in the third
edition of his work he definitely applied the term _rheumatoid_ arthritis
to the disorder in question. Nor can we refrain from recording Fuller’s
words that “the natural history of _rheumatic gout_ accords but little
with that of _acute rheumatism_, and is equally inconsistent with that of
true gout.”


CLEAVAGE OF ARTHRITIS DEFORMANS INTO TWO TYPES

In reviewing the researches of the foregoing writers it will be clearly
seen that though they did yeoman service in differentiating broadly
_gout_ from the disorders grouped under _Arthritis Deformans_, there is
little doubt that not for many years afterwards was their distinctiveness
sufficiently realised. This may be in large part attributed to the fact
that they still awaited the next great process of fission as applied to
chronic joint disorders.

I allude in the first place to Charcot’s momentous discovery of the
_nerve arthropathies_, and secondly, to the cleavage of arthritis
deformans into the _rheumatoid_ or _atrophic_, and the _osteoarthritic_
or _hypertrophic_ varieties.

It is to Vidal that we are indebted for the first clinical description
of the _atrophic_ type. Charcot in his lectures refers to it as the
“Atrophic form of Vidal,” noting that in this variety “induration of the
skin, a sort of scleroderma develops, the cutaneous covering is cold,
pale, smooth, polished, and will not wrinkle, adding also that in such
cases atrophy of the bones and muscles accompanies the wasting of the
soft tissues.”

Notwithstanding this, Charcot, to our mind, unquestionably refers to
the category of _chronic articular gout_ certain of these examples of
Vidal’s _atrophic_ type of _arthritis deformans_. The reasons he adduces
for their _gouty_ nature are, to say the least of it, both conflicting
and unconvincing. On the one hand, he admits that they are clinically
indistinguishable from Vidal’s type, in respect of their pronounced
_atrophic_ changes; on the other, he postulates them as _gouty_ even
though the _uratic deposits_ “either do not exist at all, or only mere
traces of them, or when only the articular cartilages are invaded by the
urate of soda.” It must be conceded that _chronic articular gout_ and
_rheumatoid_ or _atrophic arthritis_ are totally distinct affections.

Now as to the _hypertrophic_ variety, or osteoarthritis, which, of the
twain, more closely resembles gout, and whose confusion therewith is far
from infrequent even at the present time. Sir Dyce Duckworth, while he
recognises with Charcot a _tophaceous_ form of chronic articular gout,
postulates the existence of another type, _arthritis deformans uratica_.
Unlike Charcot, however, he seems only to have included under this term
instances of the osteoarthritic or _hypertrophic_ variety. But like
Charcot, his claim that this particular variety is of _gouty_ nature
seems to rest on equally frail foundations, as witness his statement that
they “may be complicated with visible or invisible tophaceous deposits!”

That osteoarthritis and gout may coexist in the same individual is
certain, and equally sure is it that uratic deposits may supervene in
joints the seat of osteoarthritis. But it is now, I think, generally
conceded that, despite these coincidences, _gouty arthritis_ and
_osteoarthritis_ are wholly distinct disorders, of wholly different
origin.

At this period of our historical _résumé_ we see that by the withdrawal
of these three great groups—_rheumatism_, the _nerve arthropathies_ and
_arthritis deformans_—the domain of gout has, through these several
allotments, undergone substantial shrinkage.


ELIMINATION OF THE INFECTIVE ARTHRITIDES

Yet again was the territory of gout destined to undergo further
restriction, and this largely owing to the rise of the science of
_bacteriology_. For in light of recent improvements in _diagnostic_
methods, who can escape the conviction that under the term “gout” had
been wrongfully included many forms of arthritis, now known to be due to
_specific infections_. What, for example, of Hippocrates’ aphorism that
gout was unknown in youths—_ante usum veneris_—who can doubt that some of
his reputed cases of gout were examples of _gonococcal_ or _syphilitic_
arthritis?

What, too, of all the other infective arthritides—_influenzal_,
_pneumoccocal_, _scarlatinal_, _typhoidal_, _meningococcal_—to mention
only those actually affiliated to some specific organism. For gout, be
it noted, confers no exemption from other arthritic diseases, but how in
time past were such to be differentiated therefrom?

Again, gouty subjects, as has been recently emphasised, are notoriously
prone to _pyorrhœa alveolaris_, and how difficult, given the supervention
of an _arthritis_ in such to define the causal agent—_gout_ or _sepsis_,
which? Small wonder then, that the clinical content of gout, not only to
ancient, but also to latter day physicians, loomed large, swollen as it
undoubtedly was by the inclusion of infective arthritides, not to mention
those of _traumatic_ or _static_ origin.

That more of these alien joint disorders—_les pseudo-rheumatismes
infectieux_, as M. Bouchard terms them, were relegated to the “rheumatic”
than to the “gouty” category, may perhaps be allowed, but still gout
was undoubtedly allotted its full share and to boot. Moreover, if to
“rheumatism” was wrongly affiliated the lion’s share of the _infective
arthritides_, on the other hand to “gout” accrued a host of unrelated
_visceral_ disorders, not to mention affections of the _nervous_ and
_vascular_ structures, etc.

In endeavouring to summarise the results of our brief retrospect, the
somewhat chastening fact emerges, viz., that the isolation of articular
gout has been achieved not so much by an increase in our knowledge as
to what _is_ gout, but through our growing perception of what is _not_
gout. For of the _causa causans_ of gout we are still as ignorant as
in the days of Sydenham. But, in contrast, our enlightenment as to the
clinical and pathological features of other forms of arthritis has
steadily progressed. In this way, shorn of many alien joint disorders,
gouty arthritis has slowly but surely asserted itself as a specific joint
affection, distinct both from rheumatism and arthritis deformans.

In the course of our sketch, too, we have traced the evolution of the
modern opinion that at least two separate conditions, “rheumatoid
arthritis” and “osteoarthritis,” are comprised under arthritis deformans.
This most tardily arrived at differentiation has done more than any other
to clarify our conceptions as to what constitutes true “gouty arthritis.”

If to this be added the further differentiation, not only of the _nerve
arthropathies_, but also of the _infective arthridites_—both specific and
undifferentiated forms—it will be seen that the term “gouty arthritis,”
once the most comprehensive perhaps in all medical nomenclature, has now
been brought within, at any rate, reasonable distance of more or less
exact definition.




CHAPTER III

EARLIER THEORIES OF PATHOGENESIS


The fanciful views of the humoralists as to the etiology of gout
exercised almost undisputed sway up to the latter half of the eighteenth
century. At that time the great Scottish physician, Cullen, took up arms
against a doctrine which appeared to him unjustifiable in conception and
baneful in practice. He inclined to the solidists rather than to the
humoralists, claiming that gout was the outcome of a peculiar bodily
conformation, and more especially of an affection of the nervous system.
While he categorically denied that any _materia peccans_ was the cause of
gout, he yet admitted that in prolonged cases a peculiar matter appeared
in gouty patients. But, in view of latter day revelations, Cullen, with
singular prescience, maintained that the said matter was the _effect_ and
not the cause of gout.

Albeit, notwithstanding the almost universal deference accorded to
Cullen, his theory, promulgated in 1874, though previously adumbrated
by Stahl and afterwards reinforced by Henle, secured but few adherents.
The source of this was not far to seek. For ever since the discovery of
uric acid by Scheele in 1776, and its detection in tophi by Wollaston, an
increasing body of opinion inclined to the view, that in some obscure way
the life history of gout was bound up with that of _uric acid_.

Still, despite able advocacy in this country by Sir Henry Holland,
Wollaston, and others, not to mention Continental authorities, such as
Cruveilhier, it was felt that scientific proof of the truth of their
contention was still lacking. But not for long were they left in doubt.
For, in 1848, Sir Alfred Garrod’s momentous and epoch-making discovery
of the presence of _uric acid_ in the _blood_ of the victims of _gout_
allayed all doubts, and seemed then and for long after an all-sufficient
explanation of the protean manifestations of the disease.

This distinguished physician enunciated his views in a series of
propositions which embodied the result of his researches and incidentally
laid the foundations of the _uric acid_ theory.


GARROD’S THEORY

This great physician held that, in true gout, uric acid in the form of
urate of soda was, both prior to and during an attack, invariably present
in the _blood in abnormal quantities_, and was moreover essential to its
production; but with this reservation, that occasionally for a short time
uric acid might be present in the circulating fluid without exciting
inflammatory symptoms. This comparably with what obtains in _lead
poisoning_, and on this account therefore he did not claim that the mere
presence of uric acid therein would explain the occurrence of the gouty
paroxysm.

He further averred that gouty inflammation is _always_ accompanied by a
_deposition_ of _urate of soda_, crystalline and interstitial, in the
inflamed part. Also that “the deposited urate of soda may be looked upon
as the _cause_ and not the effect of the gouty inflammation. Moreover,
that the said inflammation tends to destruction of the urate of soda not
only in the blood of the inflamed part, but also in the system generally.”

In addition, Garrod postulated implication of the _kidneys_, probably
in the early, and certainly in the chronic stages of gout; and that the
renal affection, though possibly only _functional_ at first, subsequently
became _organic_, with alterations in the urinary secretions.

As to the anomalous symptoms met with in gouty subjects, and alike those
premonitory of a paroxysm, he ascribed them to the impure state of the
blood, and due principally to the presence therein of urate of soda. Of
causes predisposing to gout, if we except those attaching to individual
peculiarities, they are either such as will lead to increased formation
of uric acid or to retention of the same in the blood.

On the other hand, the determining causes of a gouty fit are those which
induce a _less alkaline condition of the blood_, or which greatly augment
for the time the formation of uric acid or such as temporarily check the
eliminating powers of the kidneys. Lastly, his final axiom was that—in
_no disease but true gout is there a deposition of uric acid_.

No tribute to Garrod’s masterly achievement could err on the side of
generosity. A truly scientific physician, he built on the rock of sound
clinical and pathological observations. For measured restraint, he stands
out in pleasing contrast to those who, lacking his clinical acumen and
sound judgment, brought not grist to the mill, but vain imaginings based
on Garrod’s hard-won facts. His researches in truth constitute a landmark
in the history of the pathology of gout, with their substitution of
facts for pure hypotheses. True, though it was that, for half a century
before, there was a growing suspicion that lithic (_uric_) acid was the
malign factor in the induction of gout, still it was not till Garrod’s
discovery of _uric acid_ in the _blood_ and _tissues_ of the “gouty,”
that any definite step towards the elucidation of the problem presented
by gout was attained.


ANTAGONISTIC VIEWS

One aspect of Garrod’s theory that much exercised the minds of his
contemporaries was that for him _uric acid_ was the alpha and omega of
the disease, and as Ewart remarks, “If we are not over-anxious as to the
stability of this mid-air foundation, everything is evolved smoothly from
it on the lines of the theory.” Fortunately, however, for the progress of
the art of medicine, men _were_ over-anxious as to the why and wherefore
of that accumulation of uric acid in the blood which Garrod held to be a
necessary antecedent of gout. He himself, as we know, attributed it to a
_functional renal defect_ which may be inherited or acquired. To others,
however, this assumption of renal inadequacy was not wholly satisfying,
hence the origin of the many widely differing hypotheses from time to
time advanced as to the pathogeny of the disorder.

Broadly speaking, the various conceptions proffered as to the causation
of gout fall into one or other of the following categories. The primary
alteration in gout is variously assumed to be:—

(1) In the blood or tissues, the so-called histogenous theories.

(2) In the bodily structures, either inborn or induced.

(3) In hepatic inadequacy.

(4) In hyperpyræmia.

(5) In the nervous system.


HISTOGENOUS THEORIES

In his classic work, “On Urine” (1860), Parkes expressed his scepticism
as to the valency of Garrod’s assumption of a _primary renal inadequacy_.
In shrewd forecast of latter day views he was of opinion that both uric
and phosphoric acids existed in some untoward combination in the _blood_
or _organs_, and that this same impeded its excretion. As he says, “If
this be the case, the deficient elimination is, as it were, only a
consequence of more important antecedent aberrations in metamorphosis of
which impeded excretion is a natural sequence. What these are, however,
is quite unknown; but an unnatural formation of uric acid, either from
food or tissues, may possibly be part of them.”

In 1866 Barclay lodged another objection to Garrod’s hypothesis, viz.,
that the baneful influence of uric acid was _exercised passively and
physically_. Not only did he regard it as “far too mechanical,” but he
also strongly dissented from his axiom that gouty inflammation was
invariably attended by _uratic deposits_. Thus he asks, “Must we of
necessity find urate of soda in the stomach and the bronchi before we can
admit gouty gastritis, or gouty bronchitis?” Seemingly he believed in the
existence of these two clinical entities, and inasmuch as urate of soda
had not been detected _in situ_ in these disorders, he felt justified
in denying that “true gouty inflammation is always associated with,
or caused by, the deposit.” Moreover, this conclusion, he considered,
derived colour from the fact that, “though the deposit and the
inflammation were associated together in the joints, the urate of soda
was seen in other parts without any evidence of its exciting inflammation
there.”

His own view was that the _primary change lay in the blood corpuscles_,
this being induced by the serial ingress of “gout producing elements”
into the blood stream. As to the retention of uric acid, he deemed it not
the cause, but merely a _symptom_, a consequence of gout. Thus he says,
“The good living and the stimulants do not simply cause an excess of uric
acid to form, but they end by causing some more permanent change, and
probably one affecting the blood globules, which reacts on the kidney,
putting a stop to the excretion of uric acid, and causing its retention
in the serum, where, passing in the round of the circulation, it is very
apt to become deposited as urate of soda.” Moreover, his observations of
the effect of colchicum in checking a gouty paroxysm, seem to indicate,
“that there is a disease to which the name ‘gout’ is applied, distinct
from the excess of uric acid in the blood serum which attends its
progress.”

The imaginative insight of Barclay is very remarkable. If we substitute
the _white_ for the red corpuscles we see how closely his views accord
with those prevalent at the present time, when so important a _rôle_ in
the genesis of gout is attributed to the _leucocytes_. Moreover, as Ewart
observed, the views of Barclay and Parkes approximate in principle to
those afterwards propounded by Ord and Ebstein, that the bodily tissues
“take an active share in determining the deposition of uric acid.”

It is, however, but fair to note that, long prior (1854) to Barclay,
Gairdner held that “the disappearance of urea and uric acid in the urine
and their accumulation in the blood” was but _symptomatic_ and not
causative of gout, coupling with it the suggestion that there was some
antecedent _nerve_ influence at work.

Laycock, too, it may be noted, considered Garrod’s theory inadequate,
adding that “Gout is characterised not by urates in the blood but by the
genesis of uric acid _in the tissues_, and its action thereon, and is
especially characterised by _peculiar changes in the innervation of the
individual_.”


ANTECEDENT STRUCTURAL CHANGES

In 1872 Ord took up the novel standpoint that there was an inborn
tendency in the fibroid tissues of gouty subjects to undergo a special
type of _degeneration_, which same might be inherited or acquired. Also
that this innate peculiarity was attended by excessive formation of
urate of soda in these tissues, and which subsequently gaining entry
therefrom into the blood, was deposited promiscuously in the body with a
predilection for relatively non-vascular structures, viz., _cartilages_.

As to the _local_ inflammations typical of gout, Ord’s attitude was
somewhat ambiguous. Thus he maintains, “The local inflammations do not
necessarily depend upon the deposit of urate and the deposit is not a
consequence of inflammation; at the same time, it is probable that excess
of urate in the blood produces irritation of tissues.” Neither did he
believe that the local inflammatory reactions were of necessity in every
instance _specific_, viz., due invariably to mechanical irritation by
_uratic deposits_, but that they might be initiated by injuries, exposure
to cold, etc. Lastly, as to the migration of the disorder from place to
place, he believed that for its explanation direct or reflex _nervous_
agencies had to be invoked, for he held the opinion that the local gouty
“degeneration and inflammation tend to infect the rest of the system
through the blood, and to set up similar actions elsewhere through reflex
nervous influence.”

We see, therefore, that for Ord gout, as Ewart observes, was “a
mode of decay” or a “disease of degenerations.” “The local tissue
degeneracies supply a basis for the uratic deposits and the general
degenerative changes multiply the sites exposed to an infiltration from
the contaminated blood; whilst reflex mechanisms step in as additional
determining agents.”[4]

Reminiscent of Ord’s view is the hypothesis associated with the name
of Ebstein. As the outcome of experimental study he arrived at the
conclusion that the primary factor in the causation of gout was a
disturbance of tissue nutrition culminating in death or _necrosis_ of
the damaged textures. The initial nutritional derangement was ascribed
by him to the irritant effect of soluble _neutral sodium urate_. This
necrotising agent, following the development of “free acid” during the
process of necrosis, was transmuted into the acid urate. Subsequently
this same was deposited in crystalline form in the necrosed area. He held
these areas of necrosis quite as typical of gout as the uratic deposits,
and postulated their combinations to be necessary for the production of
a true gouty focus, claiming that he had detected such foci in cartilage,
tendons, kidneys, and connective tissue.

Experimentally, Ebstein endeavoured to induce a gouty condition in
fowls by ligaturing both _ureters_, thus thrusting upon the circulation
the dammed-up uratic secretion. In other instances he administered
to the same animals subcutaneous injections of neutral _chromate_ of
_potassium_, attributing to this substance the power of inhibiting the
excretion of uric acid _viâ_ the kidneys through its action on the renal
parenchyma. Subsequently, after death he noted the incidence of _uratic
deposits_ in joints, muscles, tendon sheaths, and liver, the same being
more copious in those animals subjected to chromate injections.

His conclusions were: (1) That necrosing and necrotic processes are
developed in various organs as a result of some irritant. (2) That uratic
deposits occur in the necrosed area resembling those met with in gouty
subjects. (3) That an inflammatory reaction with small cell infiltration
ensues in the vicinity of such necrotic areas.

But, in regard to these experimental investigations, they are obviously
incomparable to the morbid processes that presumably occur in gout in
man. Moreover, as shrewdly pointed out by Levison, experimental ligation
of both ureters would certainly engender _uræmia_ rather than anything
approximating to gout.

Again, his experiments with urates and uric acid, by which he claims to
have demonstrated their action as chemical irritants capable of inducing
necroses in tissues, have proved fallacious. This, for the very cogent
reasons pointed out by Luff, which run as follows: “Not only is there
no proof that the neutral sodium urate upon which he depends for the
starting of the gouty changes, ever exists in the human body, but, on the
other hand, very strong evidence to show that it never can exist in the
human body.”... “The neutral sodium urate is an extremely caustic and
unstable compound, and is decomposed in the presence of carbonates, so
that it is impossible for it to exist in the blood. The first factor upon
which Ebstein relied for his theory for the causation of gout therefore
disappears.”

Again, Ebstein’s fundamental proposition that in gout uric acid was
produced in many tissues not normally concerned in its production, was
ruled out by Horbaczewski’s establishing the fact that in health uric
acid is a by-product of the metabolism of almost all tissues. Lastly,
the strong _toxic_ properties accredited by him to solutions of the
urates was disproved by Pfeiffer’s experiments. This observer showed that
urates, in such degrees of concentration as may exist in the human body,
are incapable, when injected into the tissues, of inducing _necrosis_.

In summarising the doctrines of Ord and Ebstein, it may be observed that
if the latter’s contentions have been disproved, Ord’s claim that the
tissues of gouty subjects exhibit a specific tendency to _degeneration_
has also as yet not been substantiated. Albeit, we must not forget that
in 1883 Ralfe subscribed to Ord’s views as to the tendency to _textural
degenerations_ in gouty subjects, either through heredity or acquirement.
For this observer, however, the basal factor in the production of the
disease was a diminished _alkalinity of the blood_, due to a surcharging
of it with acid and acid salts. Disagreeing with Garrod’s assumption
that _deficient renal elimination_ was the prime cause of the retention
of uric acid, he was of opinion that “the first step in the process lies
in the failure of the _tissues_ to reduce the acid, as it occurs in
health.”... “In the large glands or where the current of the circulation
is free, the uric acid is carried into the blood and gradually reduced to
urea; in tissues outside the current of the circulation, the insoluble
uric acid is not so readily carried off, and so on the slightest
disturbance is deposited, as is the case in cartilages of the joint, the
ear, etc.” As to the determining cause of the gouty attack, he invokes
the agency of the _nervous_ system to explain its incidence, for he held
it probable that the primitive failure of the tissues to reduce uric
acid eventually led to derangement of some special nerve centre, which
disturbance occasioned the gouty outbreak, with resultant “accumulation
of uric acid in the blood and deposition of urate of soda in the tissues.”

In 1895 Berkart propounded a mode of genesis which may be regarded as
a variant of Ord’s theory. The severity of the symptoms of acute gout
were such as he deemed incompatible with their production as a result of
simple mechanical irritation by crystals of biurate of soda. Uric acid,
he held, must be afforded a humbler _rôle_ than that of a proximate
cause. It was, for him, but an _epi-phenomenon_, the accompaniment of a
_panarthritis_, the origin of which was as follows:—

While not postulating the identity of rheumatoid arthritis in gout, he
yet held that both disorders originated in some obscure form of _atrophy_
of the bone substance, and that the degenerative change also overtook the
cartilages and fibrous tissues of the joints. Subsequently, there ensued
a _necrosis_ in the tissues in and around the joint. The degeneration
and subsequent necrosis, he held, were the outcome of a profound “vice
of nutrition.” The pain, inflammatory reaction, œdema, and cuticular
desquamation were the direct result, he thought, of the necrosis. The
excess of uric acid in the blood he referred to _leucocytosis_, and in
part to disintegration of the tissues.


HEPATIC INADEQUACY

That some obscure connection obtained between gout and hepatic disorder
has been for long an axiom in high favour, with both clinicians and
pathologists. This hypothesis found its chief exponents in Murchison and
subsequently Latham, and to discussion of their individual views we now
proceed. The first named authority held gout to be either merely a result
or a variety of what he termed _lithæmia_. In other words, gout was the
outcome of a depraved condition of the blood, due to faulty digestion and
functional disturbance of the liver.

Now the conditions that lead to functional derangement of the liver are
in the main such as favour the development of gout. Nevertheless, such
hepatic disturbances do not inevitably culminate in outbreaks of gout,
at any rate of classical type; but, unquestionably, such may eventuate
in symptoms currently recognised as distinctive of _incomplete_ gout,
_e.g._, headache, palpitation, cramps, dizziness, sleeplessness, etc.
Moreover, if the faulty habits leading to such hepatic derangement be
persisted in, they are but too likely to induce outbreaks of frank gout.
“Articular gout,” said Murchison, “is so to speak a local accident which,
though sometimes determined by an injury, yet may occur at any time in
persons in whom the normal process by which albuminous matter becomes
disintegrated in the liver into urea is persistently deranged.” Following
such hepatic disturbance, the secretion of bile decreased with resultant
abnormal metabolism of proteins, and in this way was produced an
_accumulation of uric acid_. This, moreover, according to Murchison, was,
especially in the later stages of gout, reinforced by the concurrence
of _renal inadequacy_, which he also postulated as a factor in the
production of the disorder.

The tendency to lithæmia Murchison held to be _hereditary_, and in this
was supported by Goodhart, who, discussing its occurrence in young
children, was strongly of the opinion that it was due not to dietetic
irregularities but to a “constitutional tendency on the part of the
individual”; a conclusion, as he thought, strongly supported by the fact
that it is more commonly met with in the children or descendants of the
“gouty.”

But we have to recollect, as Duckworth observes, that lithæmia, “even
when persistent and not due to accidental causes, is not by itself gout.”
Moreover, gout is not the only morbid condition in which urates are in
excess in the blood, for such obtains, _e.g._, in _leukæmia_, pneumonia,
anæmia, Bright’s disease, etc. Also, underlying Murchison’s theory is the
further unwarrantable assumption, viz., that the “gouty” diathesis is
identical with the “uric acid” diathesis.

Now, as we hope to show later, whatever be the proximate cause of gout
it is at any rate _not uric acid_. The fact, too, that higher degrees of
_lithæmia_ are to be met with in conditions, not even remotely connected
with gout, renders it impossible to accept the view that the excess of
urates in the blood is responsible for all the varied symptoms accredited
by Murchison and his followers to lithæmia. For the same reason, it is
difficult to uphold the hypothesis that “the tendency to lithæmia in
early life may be an early expression of the ‘gouty’ diathesis.”

In short, excess of uric acid in the blood or lithæmia is not
pathognomonic of gout, much less of “potential” gout. But further
discussion of this assumed relationship of lithæmia to gout may well
be postponed until, in the light of recent blood analyses, we come to
consider more narrowly the contention at one time widely held, that
lithæmia is an _irregular_ manifestation of gout.

If we are compelled to adopt a more judicial attitude in regard to
lithæmia, what of the similar assumptions as to the relationship of
_lithuria_ or _lithiasis_ to gout? Now lithuria, like lithæmia, was and
probably still is by some held to be an inherited “gouty” proclivity.
Sufferers in youth from lithiasis were deemed likely to develop gout
in later years. Not only was lithiasis observed to precede but also to
be a concomitant or sequel to gout. Nevertheless, although uric acid,
gravel and calculi, sometimes arise in those of “gouty” diathesis, these
instances are but isolated, so rare indeed as to entitle them to be
regarded as mere coincidences. Moreover, when we recall the fact that
the formation of calculi takes place in the urinary passages, _i.e._,
_outside_ the economy, it renders even more improbable the hypothesis
that the two morbid phenomena are diverse expressions of the “gouty”
diathesis.

As a matter of fact, the large bulk of “gouty” subjects are immune from
gravel. Conversely, only a negligible percentage of the victims of
gravel develop gout. The geographical distribution of the two disorders
is wholly distinct one from the other. The Indian native is a martyr to
stone, but notably exempt from gout. Coming nearer home, we find stone
relatively common in Scotland, but gout rare. Plowright’s researches,
too, revealed no correspondence between the incidence of gout and the
prevalence of stone in the several counties of England. In some counties
in which the mortality from gout was high that from stone was low, and
Norfolk, the one most prolific of stone in England, enjoys comparative
immunity from gout.

Reverting now to Latham’s views as to the _hepatic_ origin of gout, we
find them very similar to those formulated by Murchison. He held that
the defective transmutation of glycocine into urea was responsible for
the occurrence of uric acid in the urine. These chemical irregularities
were attributed by him to functional disturbance or partial suspension of
the normal hepatic metabolism. This, again, was referred back by him to
some obscure change in the central system, viz., that part of the medulla
oblongata from which the vagus takes origin.


HYPERPYRÆMIA

Excess of carbonaceous materials in the blood was considered by Hare to
be an essential, though by no means the sole factor in the genesis of
gout. This same “hyperpyræmia,” as he terms it, was also, he believed,
responsible for migraine, asthma, epilepsy, and other paroxysmal
neuroses. For the alternation of attacks of acute articular gout with
paroxysms of migraine, asthma, and epilepsy, seemed to him to indicate a
kindred origin. The same inference, also, he deemed might be drawn from
the well-ascertained fact that the temporary or even permanent cessation
of long standing asthma, migraine, and epilepsy, might exactly coincide
with the onset of acute gout.

These alternations and substitutions seem to suggest that the preceding
alterations in metabolism are similar in nature, finding expression
indifferently in gout, asthma, epilepsy, etc. Carbon foods, he
considered, are much more likely to accumulate in the blood than the
nitrogenous. Ingestion of the latter is swiftly reflected in increased
elimination of nitrogenous excreta. On the other hand, following the
intake of carbonaceous foodstuffs, no such rapid and proportionate
increase in the excretion of carbonic acid ensues. In other words, the
capacity of the organism to deal with or katabolise in response to the
absorption of excess of carbon foods, is strictly limited. Muscular
exercise and exposure to cold, factors which but slightly influence
protein katabolism, are largely responsible for adequate carbon
katabolism. Accordingly, given deficient exercise, excess of carbonaceous
food and a warm temperature, an accumulation of the carbon content of the
blood is favoured.

Hare considered that present day habits of warm clothing, warm rooms
combined with excessive intake of starch and sugar, are precisely the
favourable conditions for producing a state of hyperpyræmia. Increased
fat formation would of course tend to diminish such a tendency to carbon
accumulation, but this capacity in many subjects is conspicuously
lacking, and may already have attained its limit.

Hare contended also that excessive intake of starch and sugar by
inducing a state of “glycogenic distension” of the liver, might through
compression of the intra-hepatic portal capillaries, lead to congestion
of the retro-hepatic portal venous system, and sequentially of the
gastric and intestinal mucosa. Through consequent inhibition of digestion
and absorption, a condition of hyperpyræmia is induced. This, under
varying conditions, may eventuate in acute gout, the coincident pyrexia
of which is curative of the underlying hyperpyræmic state, and of all
those hyperpyræmic manifestations (irregular or suppressed gout) which so
often are the harbingers of an on-coming articular outbreak.


NERVOUS THEORIES

It may be noted _en passant_ that the influence of the nervous system was
frequently invoked directly or indirectly in many of the theories already
discussed. Stahl, it will be recalled, was the pioneer in this direction,
and later Cullen and Henle propounded the view that “the origin of the
affection was probably to be found in the central nervous system.”
Gairdner, too, by implication, as also Laycock, postulated a neural
origin for at any rate some of, the phenomena of gout.

But it was reserved for Edward Liveing (1873) explicitly to advocate the
nervous origin of the disease, his reflections on the paroxysmal nature
of the attacks, its tendency to periodicity leading him to suspect its
kinship with other neuroses.

Those inclining towards the neural conception were later strengthened in
their convictions by Charcot’s momentous identification of the nervous
origin of certain arthropathies. Accordingly, in 1880, we find Sir Dyce
Duckworth advocating the view that gout was “a primary neurosis,” “a
functional disorder of a definite tract of the nervous system.”

The gouty neurosis, Duckworth contended, may “be acquired, intensified,
and transmitted; also that it may be modified variously and commingled
with other neuroses; that it may suffer metamorphic transformations,
or be altogether repressed.” Arguing by analogy, Duckworth saw in the
paroxysmal attacks, the tendency to periodicity and alternation in the
manifestations, evidence of an alliance between gout and the various
neuroses.

He further postulated that “this diathetic neurosis determined a disorder
of nutrition and led to the perverted relations of uric acid and sodium
salts in the economy.” He also held that the localisation of attacks, and
the determination of urate of soda to the affected part was also due, in
all probability to nervous influence. And the temporary renal incapacity
for excretion of uric acid was also attributed by him to the same nerve
inhibition.

We see, therefore, from the above, that Duckworth was well justified in
describing his view as a combine of the humoral and neural hypotheses.
His pathological differentiation between primary or inherited gout
and secondary or acquired gout is as follows: In the _primary_ type
“the toxæmia is dependent on the gouty neurosis ... and is therefore a
secondary manifestation.”

In _secondary_ or _acquired_ gout, “the toxæmia is directly induced
by such habits as overload the digestive and excretory organs, and
consequently prevents complete secondary disposal of nutritional elements
of food; that if, together with such toxæmia, distinctly depressing and
exhausting agencies, affecting the nervous system, come into operation,
the special neurotic manifestations of the gouty diathesis will occur,
and be impressed more or less deeply upon the individual and his
offspring.” It is generally conceded that Duckworth’s theory as to the
genesis of gout is pre-eminently catholic in conception, because, as
Ewart rightly remarks, “it represents the most complete theory published
in this country on the general pathology of gout,” and because “the able
advocacy of its propounder has given it the support of arguments derived
from pathological analogy and from clinical influence which will demand
careful examination and searching criticism before they can be either
disproved or adopted.”

Albeit, it must be frankly admitted that Duckworth’s perception of gout
as a _tropho-neurosis_ of central nervous origin has never gained wide
acceptance; this no doubt largely because it was insusceptible of proof.
In an endeavour to remove this reproach. Sir Willoughby Wade promulgated
the view that the causal change in gout was partly in the central nervous
system, partly in the _peripheral_ nerves of the inflamed limb. In other
words, he regarded gouty arthritis as the outcome of a local _neuritis_,
this latter being set up in the first instance by the faulty blood state,
viz., uricæmia. On the other hand, the central nerve centres might
occasion or aggravate the general gouty tendency through their influence
over “recognised seats of metabolic activity.” Also the same might,
through the medium of the vaso-motor nerves, determine the incidence of
local attacks. It will be seen that Wade’s theory is but a variant of
that propounded by Duckworth, viz., neuro-humoral.


GROWING SCEPTICISM AS TO GARROD’S PATHOGENY OF GOUT

It will be recalled that as far back as 1889 Duckworth displayed
disquietude as to the adequacy of the purely chemical or purely physical
view of the pathogeny of gout, as sufficing for an explanation of all its
varied phenomena. Thus he writes: “It is incumbent, I believe, to invoke
not only a chemical and physical basis for gouty disease, but to include
also, in a comprehensive view, the marked determining influence of the
_nervous_ factor in the problem.”

Whether we agree or not with Duckworth’s view of gout “as a diathetic
neurosis, due to a central neurotic taint, and originating from prolonged
toxæmia,” it does, I think, mark the dawn of a reaction from the uric
acid theory of its causation. Still, this latter conception continued
to dominate the field until seriously called in question by the results
of Magnus Levy’s researches. His revelations were, in truth, almost
revolutionary, and doubts now accumulated as to the propriety of the
terms “uric acid diathesis,” “uric acid intoxications,” “lithæmia,” etc.,
so long credited as being responsible for not only nearly all the minor
ailments flesh is heir to, but especially those relating to joints and
muscles, all alike attributable to the presence of excess of uric acid or
urates in the blood.

To hasten the process of disillusionment there came from the side
of the physiologists the announcement, almost unanimous, that _uric
acid_, though in minimal amounts, is a normal constituent of the blood,
organs, and tissues. Thoroughly purged now of their obsession as to the
pathological potency of _uric acid_, there awoke a spirit of inquiring
scepticism. On all sides it was felt that the whole problem must be
looked at afresh, untrammelled by previous conceptions, no matter how
high the sanction. How else, indeed, could the chaff be winnowed from the
grain, the illusions born of inaccurate observations be replaced by the
substantial form of truth?

Still, it would be ungracious to withhold our due meed of admiration
for the masterly manner in which the views of the earlier physicians
as to the causation of gout were elaborated, the shrewd and often
prophetic inferences, well buttressed by arguments based on clinical
and pathological analogies; these the more wonderful when we recall the
meagreness of the positive material at their disposal, and that little,
alas! how often ambiguous!

In light of latter day views, too, we may well admire the swiftness
with which the inadequacy of Garrod’s theory to explain all the protean
phenomena of gout was realised. Like Duckworth, they rightly apprehended
gout to be “something beyond the resultant effects of aberrant relations
of uric acid; that it consists in something more than a perversion of
animal chemistry; that it is not to be explained as a mere outcome of
gastric or hepatic distemper; and that it is not the appanage only of the
middle-aged or elderly high liver, and intemperate drinker, because, as
is well known, it affects also sometimes in early life the high thinker
and the laborious bread-winner.”

That the _uric acid theory_ should more than any other have found
ready acceptance, is not so much to be wondered at. The one solitary
pathological fact that emerged out of the mist of hypotheses was that
established by Garrod, viz., the _excess of uric acid in the blood_. It
survived and still survives the corroding test of time. Surely such must
be the _fons et origo mali_, and how obtrusive _the uratic deposits_, so
ready to hand, objective affirmations of the truth of their contention.

This apparent simplicity how delusive! yet not wholly unprofitable. For
if in these latter days our knowledge of the life-history of _uric acid_
and _purin bodies_ in the organism has evolved from “a state of chaos and
guesswork to one of system and scientific accuracy,” the seeds thereof
were sown by these hardy pioneers, their, to us crude, researches in the
dark regions of bio-chemistry.

Here it would appear opportune to outline our plan of procedure in
approaching this abstruse subject—_gout_. In the coming chapter we shall
attempt to define and classify the various types of the disorder before
passing on to discuss its _etiology_ and _morbid anatomy_.

Now all will agree that the more recent revelations of _chemical
physiology_ and _chemical pathology_ have an intimate bearing on the
problem to be considered. We shall therefore, before proceeding to the
more purely _clinical_ aspects of the disease, deal with the modern
conceptions of _protein_ and _purin metabolism_, more especially the
latter. Subsequently our scrutiny will be narrowed to consideration of
the _chemical_ structure of _uric acid_, its solubility, sources, mode of
formation and destruction. In possession of these facts the relationship
of uric acid to gout will be dealt with, in regard to respectively _uric
acid excretion_, _uricæmia_, and _uratosis_.

The inadequacy of the uric acid theory of the causation of gout will
then be discussed and the possible intrusion of an _infective_ element
in its genesis advocated. This accomplished, we shall proceed to the
section dealing with the clinical aspects of the disorder, its _regular_
and so-called _irregular_ manifestations. Thence we shall proceed to the
diagnosis of gout, while the terminal chapter will be devoted to that
all-important subject—the prophylaxis and treatment of the affection.




CHAPTER IV

DEFINITION, CLASSIFICATION, ETIOLOGY, AND MORBID ANATOMY


DEFINITION AND CLASSIFICATION

Said Locke long since, “There are some words which will not be defined,”
and surely of these is gout; for reflection upon the proffered
definitions thereof is apt to leave one with the depressing impression
that the disorder is both “incomprehensible and infinite.”

But have we not by unjustifiable and unwarrantable assumptions
deliberately complicated the issue, in recklessly relegating to the
_gouty_ category a myriad affections of the intimate nature of which
we are as ignorant as we are of gout? Doubtless, this is in part the
outcome of a too slavish adherence to tradition, an undue reverence
for authority. In all deference, our forefathers were somewhat too
hasty in their speculations as to the causation of gout. Dominated by
the prevalent philosophy of their days, they strove to interpret the
phenomena of gout through its lights, endeavouring to reduce the study
of its pathology to philosophical order when the very elements of
philosophical order were lacking.

The same is reflected in the earlier, and to a lesser extent in the
latter day definitions or _descriptions_, as some of them more aptly may
be designated, notably that put forward by Sir Charles Scudamore.

    “A constitutional disease, producing an external local
    inflammation of a specific kind; the susceptibility to it often
    depending on hereditary bodily conformation and constitution,
    but with great frequency wholly acquired; almost never
    occurring before the age of puberty, not frequently under the
    age of five-and-twenty, and most commonly between the ages of
    twenty-five and forty; affecting chiefly the male sex, and
    particularly persons of capacious chest and plethoric habit;
    in the first attack invading usually one foot only, and most
    frequently at the first joint of the great toe; but in its
    returns, affecting both feet or other situations, as the hands,
    knees, and elbows; and not only in the articular structure,
    but also in the other textures belonging to the moving powers,
    different parts being affected together or in succession;
    often accompanied with sympathetic inflammatory fever, which
    is usually marked by nocturnal exacerbations and morning
    remissions; much disposed to return at periodical intervals,
    and for the most part preceded by some premonitory symptoms.”

    In extenuation of this prolixity, Scudamore observed that, “In
    an attempt to mark the general characters of gout, I feel the
    necessity of entering into a description rather in detail,
    instead of confining myself to a brief definition, because the
    disease is too complex in its nature to be distinguishable with
    certainty by a few signs alone.”

    Trousseau, in his lectures on gout, refrains, perhaps wisely,
    from attempting any definitions of the disorder, resting
    content with the reflection that, “The production in excess
    of uric acid is a pathological phenomenon, inherent, like
    all others, in the disease, and, like all the others, it is
    dominated by a specific cause, which we know only by its
    effects, and which we term the _gouty diathesis_.”

    Sir William Roberts defines gout “as a constitutional disorder
    characterised by paroxysmal attacks of inflammation of the
    joints, associated with the formation of chalk-like concretions
    in and about the joints.”

    Sir William Osler regards gout as “a nutritional disorder,
    one factor of which is an excessive formation of uric acid,
    characterised clinically by attacks of acute arthritis, by the
    gradual deposition of urate of soda in and about the joints,
    and by the occurrence of irregular constitutional symptoms.”

For myself, I would proffer the following definition, which, of course,
the reader must accept provisionally, viz., pending the perusal of
subsequent chapters, dealing with the pathology and clinical features of
gout, and the inferences drawn therefrom as to the nature of the disease.

_Definition._—Gout is an hereditary disorder, the _intrinsic_ element of
which is an inborn instability of nuclein metabolism which may remain
latent, but under the influence of _extrinsic_ factors, _infections_,
becomes manifest, as betokened by local inflammatory tissue reactions in
joints or elsewhere the specific character of which is attested by the
associated _uratic deposition_.


CLASSIFICATION

At the present time, under the most liberal interpretation, the word
“gout” comprises the following conditions, viz., acute and chronic
articular gout, and the so-called ab-articular forms. But it is clear
that not only the latter or _irregular_ manifestations, but even the
former or _regular_ varieties of the disorder seem destined to undergo
considerable pruning.

As to the classical podagra—_acute_ articular gout—no question can
arise as to the propriety of its retention in this category. But as to
the _chronic_ articular types we are on less certain ground, and to
discussion of this vexed question we now proceed.

Let us take, for example, Sir Dyce Duckworth’s classification of the
_arthritic_ types of gout. He distinguishes the following forms:—

    (1) Acute articular gout.
    (2) Chronic articular gout

the latter (2) further subdivided into—

    (_a_) the “tophaceous” variety.
    (_b_) the “deforming” variety.

Of these twain the “tophaceous” form need not detain us, and why? Simply
and solely this—the _uratic deposits_ stamp the seal of specificity on
the disorder. In short, the presence of _tophi_ places the “gouty” origin
of the arthritis beyond the pale of cavil.

Now, if we accept, as we must, the fact that _uratic deposition is the
solitary unequivocal clinical criterion of gout_, we are not, I contend,
justified in classing any _chronic_ arthritis as “gouty,” the victim of
which does not exhibit _tophi_ of articular or ab-articular site, either
clinically demonstrable or deducible from skiagraphic revelations.

Nevertheless, be it noted _tophi_ do but bespeak the “gouty diathesis,”
not necessarily the “_gouty_” nature of an associated arthritis. For
clearly tophi, of _ab-articular_ location, may coexist with an arthritis
of _gonococcal_ or other origin. But given uratic deposits, either in
the joint proper or its related structures, all reasonable doubts as to
the true “gouty” nature of the arthritis are disposed of. On the other
hand, in _the absence of tophi_, the diagnosis of an arthritis as “gouty”
is _presumptive_, not absolute. This even in acute classical outbreaks
in the _big toe_, viz., pending the finding or subsequent eruption of
_tophi_.

In saying this, I do not for one moment depreciate the diagnostic value
of the clue afforded by location of the initial outbreak of the disorder,
in the vast majority of instances, in the _big toe_. It is an invaluable,
but not an _infallible_ clue; for, unfortunately, acute arthritic
diseases other than gout may elect to announce themselves in the great
toe.

Moreover, there is nothing _specific_ in the external characters of
acute “gouty” inflammation, nothing in the objective changes which would
stamp them on sight as “gouty,” save only their _location in the great
toe_; nothing distinctive about the angry blush, œdema, and engorged
veins, all of which may be met with in _infective_ arthritis. There
may be, as Garrod with good reason affirms, a local _intra-articular_
deposit of urate of soda, but this lies beyond our ken, presumptive but
undemonstrable.

Let but the _initial_ outbreak of gout occur elsewhere than at the _big
toe_, say, _e.g._, in the _wrist_, _hand_, _ankle_, or _knee_, and we
are at once, diagnostically speaking, _en l’air_. In this _impasse_ how
impotent are we, and how painfully we realise that our diagnosis of
acute gout is largely _topographical_, not _etiological_! Not, strictly
speaking, etiologically diagnosable pending the eruption and detection
of _tophi_. In short, location _per se_ in the big toe is strongly
suggestive but not _diagnostic_ of “gout.” (_Vide_ Chapters on Diagnosis.)

If this be done in the green, what then shall be done in the dry?
In other words, if so precarious our diagnostic foothold in _acute_,
how much more so in _chronic_ articular gout! for in the latter
even _topography_ may wholly fail us, what then our diagnostic
criterion?—_tophi_ and _tophi_ alone—aye, and demonstrable at that.

Yet both Charcot and Duckworth would have us recognise not only a
tophaceous but a _non-tophaceous_ variety of chronic articular gout, for
that is what it amounts to. They apparently feel justified in labelling a
chronic arthritis as “gouty” even though _tophi_ “may not exist” or “be
invisible”! _Deformity_, say they, is its hall-mark, not _tophi_, and its
character forsooth, they add, is not only _not peculiar to gout_, but
clinically indistinguishable from the similar defacements met with in
_arthritis deformans_. Nor is Duckworth alone in his contention, for both
Ewart and Luff also recognise what they term “chronic deforming gout.”

_Tophi_, I contend, notwithstanding, are essential for the diagnosis of
gout. In their absence, the designation of an arthritis as “gouty” is
unjustifiable. Either tophi are, or tophi are not the sole pathognomonic
feature of gout. If the latter, then gout ceases to exist as a clinically
recognisable entity.

Holding tophi indispensable for the diagnosis of gout, I maintain that
Charcot and Duckworth’s plea for the recognition of a chronic type of
articular gout, apart from the _tophaceous_ variety, is untenable.
Fraught, moreover, with risk, as I am satisfied that their so-called,
“deforming” type is largely made up of the _atrophic_ and _hypertrophic_
forms of arthritis deformans.


SUGGESTED CLASSIFICATION OF ARTICULAR GOUT

For myself, as to the classification of the articular types of gout, I
would divide them into:

    (1) Acute articular gout.
    (2) Chronic articular gout.

Under the first group I would place not only the acute _localised_ type,
but also those acute varieties of _polyarticular_ distribution. As to the
second category, I would exclude therefrom, for the reasons cited, the
so-called “_deforming_” varieties of chronic articular gout, recognising
only the so-called _tophaceous_ form. But I would place a different
interpretation on this term in opposition to that generally accepted;
for, by most writers the word _tophaceous_ is apparently limited in its
application to examples which, so to speak, exhibit _tophi_ of phenomenal
size or number. Scudamore was the chief offender in this respect. As a
consequence, he found tophi in only 10 per cent. of his cases of gout.
Accordingly, he went so far as to postulate for such victims as did
present this peculiarity an _idiosyncratic_ tendency to chalk-stones!
In other words, he would seem to suggest that there is a gout within
gout, that one displays _chalk-stones_, the other _not_. By inference,
Duckworth and his followers, by differentiating _tophaceous_ gout,
tacitly concur, and so “confusion twice confounded” results.

This usage of the term “tophaceous” is unjustifiable and misleading.
The significance of tophi is _qualitative_ not _quantitative_. One
tophus bespeaks the “gouty diathesis” as surely as a myriad concretions.
Solitary though it be, the same, given elimination of all other sources
of arthritis, will suffice to establish the “gouty” nature of an
associated joint disorder. It is in this more catholic sense that I would
translate the term “_tophaceous_ gout.” The conclusion, then, to my mind,
is obvious—there is but one form of articular gout, and one only, viz.,
an arthritis, the victim of which exhibits _uratic deposits in situ or
elsewhere in his body_. On this and on no other grounds can a chronic
arthritis, with any show of certitude, be certified as truly “uratic” or
“gouty.”

This rigid attitude may not commend itself to some, but I feel convinced
that, only by holding on grimly to the tophus, shall we steer a safe
course through all the pitfalls that beset the diagnosis of the chronic
arthritides. Only in this way, too, can we preserve for ourselves a
clear conception of _gouty arthritis_ as a specific disorder, the
which otherwise loses its identity, submerged in a medley of joint
diseases. Prior to the differentiation of gout, on the one hand, from
_rheumatism_ and _arthritis deformans_, and on the other from the _nerve
arthropathies_ and the _infective arthritides_, such laxity might be
condonable, but not, we think, in the present stage of our knowledge.

In drawing to a close my remarks on the classifications of articular
gout, it will be noted that I have made no reference to that variety
known as _retrocedent_ gout, but to this I shall allude at a more
favourable juncture, viz., in the chapter devoted to the clinical
account of articular gout. Conformably, too, it will, I think, be more
convenient, to defer any criticisms of the term “irregular gout” to
the chapter I purpose devoting to consideration of the varied clinical
content of the same.


ETIOLOGY AND MORBID ANATOMY

To the antiquity of gout and no less its distinctive clinical _facies_,
when of classic type, we owe not a little. Its salient phenomena have
endured unchanged from the time of Hippocrates onward through the ages.
So it is that, even allowing for the enhanced powers of discrimination
of latter days, we are in no doubt that the gout of the ancients is the
gout of to-day. How signal the advantage thus accruing, when we come to
consider the conditions which engender or tend to engender the disease!
For, _quâ_ its broad etiological factors, we find ourselves in accord
with the physicians of old, our experience a confirmation of their
old-time findings.

Our forefathers, like ourselves, realised the innate complexity of the
problem, that in the development of the disorder both _heredity_ and
_environment_ played a _rôle_. In other words, that in the genesis of
gout not only _intrinsic_ but _extrinsic_ agencies were concerned. Of the
intrinsic influences the most important are age, sex, heredity, bodily
conformation, and individual peculiarities.

_Age._—Gout is slow in evolution, tardy of appearance, confined in the
main to the middle and declining years of life. Said Sir Thomas Browne,
“Leprosie awakes not sometimes before forty, the gout and stone often
later.” Experience but confirms the dictum, for, as Cullen long since
observed, it rarely declares itself under the age of five-and-thirty.
This relative immunity of youth is not the least striking feature of the
disorder; whence the Hippocratic aphorism, “Puer non laborat podagra,
ante veneris usum.” Both Sydenham and Heberden were also doubtful of its
occurrence before the age of puberty. Gairdner, however, records the
incidence of fits of gout even in _infants_ at the breast! and in one
death therefrom. Garrod, too, met with two cases of classical type in
_girls_, both of them under _ten_ years of age. But Scudamore states that
he never witnessed more than one example of a first attack before twenty,
or any after sixty-six.

For myself, I have never seen a case under thirty-five years of age,
and am sceptical as to the occurrence of _infantile_ gout of _regular_
type, believing with Scudamore that “the commonly asserted cases which
represent the existence of the gout in very early youth are really
examples of _rheumatism_.” Nor am I less but more inclined to cavil at
the claims of Comby and others, as to the frequency in _children_ of
_irregular_ manifestations. As Osler dryly observes, “The tendency in
some families is to call every affection gouty. Even infantile complaints
such as scald-head, naso-pharyngeal vegetations, and enuresis, are often
regarded, without sufficient grounds, I believe, as evidences of the
family ailment.”

To sum up, the majority of cases of gout ensue between thirty-five and
fifty years of age. But, given a strong _hereditary_ taint, it may break
out in _youths_ and _young adults_, or haply even in _children_. But
such, in my experience, are phenomenally rare. Indeed, it may be said of
gout that only exceptionally is it met with at either extreme of life;
though Garrod records several examples in which the initial attack was
postponed until nigh eighty years of age; while in one instance, a lady
experienced her first classical attack of podagra in her ninety-first
year.

_Sex._—In the matter of liability to gout the sexes stand in marked
contrast, the disorder being infinitely more common in males. Out of
eighty cases submitted to the French Academy, seventy-eight were men
and only two women; but according to other authorities, this is an
under-estimate. Thus in James Lindsay’s series of cases of gout, 84·7 per
cent. were males, 15·3 per cent. females, percentages which he notes “are
in accordance with the observations of other writers.” J. Lambert, out of
125 examples of gout, noted that 102 were men, _i.e._, 81·6 per cent.,
twenty-three women, _i.e._, 18·4 per cent.

From my own experience, the figures submitted to the French Academy
probably represent the ratio of incidence in males as opposed to females.
This certainly, if _regular_, in opposition to “irregular,” types of gout
be the criterion; for it must be admitted that regular gout does occur
in women, though exceptionally rare either prior or subsequent to the
climacteric.

As to the current opinion that the _regular_ manifestations of gout
in women are of _asthenic_ as opposed to sthenic character, this has,
I think, often proved a source of fallacy. At any rate, in many of
these cases the assumed _gouty_ inflammation resolves itself into one
of inflamed _bunion_. Again, in but too many instances, women, showing
_Heberden’s nodes_, are held to have gout or “rheumatic gout.” The latter
term, as Pye-Smith observed, “is a bad name for _osteoarthritis_,” to
which category Heberden’s nodes belong.

Judged by the one unequivocal diagnostic criterion, _i.e._, _tophi_,
gout in women is extremely rare. If to this be added the further fact,
viz., the rarity in their sex of classical attacks in the _great toe_,
we see clearly that the diagnosis of gout in women is often a matter of
_assumption_ rather than of certitude.

Moreover, having regard to the fact that the diagnosis of gout in women
is frequently based on so-called “masked and irregular manifestations,”
I must admit that, to my mind, statistics, purporting to indicate the
percentage incidence of gout in women and men, are not very convincing.

As to the why and wherefore of the relative immunity of _women_ it may be
due to the fact that their habits and mode of life are less calculated
to evoke the disorder. There is also the further possibility that the
_catamenial_ discharges to a certain extent are protective against gout,
for most authorities support Hippocrates’ aphorism, “Mulier podagra non
laborat nisi ipsi menstrua defecerint.”

_Heredity._—By the ancient physicians gout was held to be hereditary,
and even to-day most will agree that “From father to son its seeds are
transmitted, and bear fruit in exact proportion to the degree in which
circumstances prove favourable to their growth.” Cullen, indeed, went
further and held it _purely hereditary_; but, on the other hand, the
belief, that it is often _acquired_ is widely countenanced.

That gout is an _hereditary_ disease is, I think, beyond question,
and certainly, of all _arthritic_ disorders, gout furnishes by far
the greater number of instances in which _parents_ and _children_ are
victimised by the same articular affection. Scudamore in 522 cases found
that 332 could trace their disease to the father, mother, grandfather,
grandmother, or aunt. But in the remaining 190 no evidence of the
existence of gout in their forbears could be elicited. Out of eighty
examples submitted to the French Academy an hereditary predisposition
was established in thirty-four, and in the residue it appeared to have
been _acquired_. Garrod found that 50 per cent. of his hospital examples
of gout were hereditary, and of his private patients nearly 75 per
cent. came of gouty stock. Again, Sir William Roberts found that “fully
three-fourths of the cases of gout occurring among the easy classes, can
be traced back distinctly to a gouty ancestry.” Luff’s estimate is even
higher, inasmuch as analysis of a series of 300 examples disclosed a
“definite family history of gout in 81·3 per cent.”

Nevertheless, Garrod’s experience, he tells us, convinced him that “in
this country gout is frequently _acquired_ even at a moderately early
age, for in many most inveterate cases not the least hereditary influence
could be discovered.” For myself, I find it difficult to appreciate
the attitude of those who, like this observer, postulate _innate_ or
_static_ morbid proclivities on the part of the “gouty,” and in the same
breath, as it were, are equally insistent that it may be “acquired” _de
novo_. Now, in the taking of family histories _positive_ evidence is
more valuable than negative. Surely, therefore, in the light of Garrod’s
and Luff’s findings, it is obvious that _heredity_ plays not merely an
important, but an _essential_ and _indispensable rôle_ in the genesis of
gout. To my mind, accordingly, the balance of evidence is more in favour
of the same ancestral taint, though apparently undiscoverable, being
present in the remaining 20 or 25 per cent., than that the disease in
their instance was wholly and newly _acquired_.

Personally, I therefore question whether the alleged acquisition _de
novo_ of gout is not _apparent_ rather than real. My own opinion is
that the _innate predisposition_ thereto is _always inherited_, and the
predisposing factors, that we presume may originate gout, are in reality
merely _excitants_ or _determining_ agents. In other words, the remote,
the primary or essential cause of gout, is an _inborn_ morbid tissue
potentiality, and in the absence of this intrinsic warp the various
contributory or exciting causes are impotent to evoke the disorder.

Apart from _statistical_ proof of heredity, how else, save on the basis
of an _organic predisposition_ to the disease, can we explain the fact
that of a large number of individuals, of slothful habit, and given to
alcoholic and dietetic excesses, not one may get _gout_; while others
who lead literally “a godly, sober, and righteous life,” become martyrs
thereto. How escape then the conviction that in gout “breed is stronger
than pasture”? for, apart from gluttony and indolence, gout is much more
prone to arise in persons in whose pedigree it can be traced than in
others.

It is not gout, but the _predisposition_ thereto, that is inherited.
This proclivity, moreover, may descend to the children of those who,
in their own persons, have never suffered from the disease. In Luff’s
series it was so in 27 per cent. of the cases, _i.e._, the disease was
transmitted from grandparents to grandchildren without the fathers
or mothers suffering from “active gout.” In other words, the morbid
potentiality may lie _latent_ until _evoked_. Thus, the _females_ of
“gouty” families, infinitely more often than not, escape overt gout, but
hand on nevertheless their inborn liability thereto to their offspring.
Looked at in this light, I see no difficulty in accepting the fact that
gout may skip a generation. The son of a gouty parent, happily warned by
the excesses of his father, may remain immune, while in turn his son,
forgetful of his evil heritage, may bring it again to fruition.

The more one reflects on the essential cause of gout, the more inevitable
seems the conclusion that gouty individuals, as Walker-Hall contends,
“possess some inborn defect or alteration of nuclein metabolism.” And
the vague phrases “constitutional” or “nutritional,” as applied by older
writers to the disorder, are only explicable on the basis of _inherited
structural peculiarities_, with their correlated perversions of tissue
function.

That such constitute the pathological groundwork of gout, is, I think,
further indicated by the fact that _“gouty” inflammation_, in virtue
of its associated _uratic deposition_, is _sui generis_. No tissues,
other than the _gouty_, react in this _specific_ fashion. Does not this
seem to indicate that the _inborn tissue peculiarities_ dictate, so to
speak, the _character_ of the pathological reaction; this indifferently,
whatever the nature of the so-called _predisposing_ causes which, if our
assumption be correct, are merely _provocative_ of gout, in other words,
do but evoke or make _manifest_ what is already latent.

To sum up, on statistical, and more cogently, general clinical and
pathological grounds, my own conclusions are that—

    (1) Gout is always an hereditary disease.

    (2) The factors currently regarded as predisposing agencies are
    in reality merely _determining_ agents, not the cause of gout,
    but the _occasion of its appearance_.

    (3) In the absence of an hereditary taint, these same are
    powerless to evoke the _specific_ manifestations of true
    _“gouty” inflammation_ as estimated by associated _uratic
    deposition_.

_Bodily Conformation and Individual Temperament._—Of the hereditary
character of gout no doubt remains, but as to the influence of physical
build and temperament no such certainty prevails. Said Cullen, “Gout
attacks especially men of robust and large bodies, men of large heads, of
full and corpulent habit, and men whose skins are covered with a thicker
_rete mucosum_, which gives a coarser surface.” Doubtless, in its more
sthenic form, gout affects persons like Falstaff, of sanguine temperament
and corpulent habit. But its milder or more asthenic manifestations occur
often in men like Cassius, of lean and nervous type.[5]

Of objective stigmata, I know of none, save _tophi_, that can be truly
regarded as pathognomonic of the outward semblance of the “gouty.” The
skin of the face may be coarse, unctuous, and studded with ramifying
venules. Such appearances, though not always, betray the tippler. Indeed,
such stigmata as these are only of value as indicating the habits of the
individual, favourable or not, to the development of gout.

Again, it has become a tradition with us that gout produces
characteristic _teeth_. The mere fact that they are “ground down” so
as to display the dentine in section is held as evidence of a “gouty”
diathesis, or of lithæmia. The teeth of the gouty, it is true, often
appear long and square-topped; but the gouty, no more than others, are
immune from early _recession of the gums_. Again, we must recollect that
there are several causes which may lead to the teeth being worn down more
quickly than normally. Thus the _formation of the jaw_ may be such that
the upper and lower incisors meet edge to edge instead of overlapping.
This so-called “edge to edge bite” subjects the incisors to marked
attrition. Also we must recall that these effects may be aggravated by
the nature of the diet. All of us are familiar with the fact that in old
horses the teeth are ground down to the gums. The same also is observed
in races condemned to live on coarsely prepared flour and hard vegetable
food.

In conclusion, having regard to the marked frequency with which disorders
leading to early recession of the gums are met with in the “gouty,” and
the ease with which the early attrition of the teeth is explicable on
tangible mechanical reasons, I am inclined to refer such changes to their
combined agency, rather than to the nebulous “gouty” diathesis.

Again, despite Duckworth’s assertion that “the gouty throat is like no
other,” I am convinced that it presents no specific appearances. Nor
have I been able to satisfy myself that striated and fluted nails of,
it is usually affirmed, exceptionally brittle nature, are distinctive
of gout any more than the premature whitening of the hair so frequently
accredited to the subjects of this diathesis.

One point, however, I would emphasise is, the frequency with which
potentially gouty persons suffer from local _syncopes_ and _asphyxias_ of
the hands. They are precisely similar to those met with in _rheumatoid_
or _atrophic arthritis_, certain cases of which, as we shall see later,
have another affinity with gout, viz., _retardation in the output of
exogenous purin_.

_Locality, Race, Climate, etc._—As to the geographical distribution of
gout, the salient fact would appear to be the almost complete restriction
of the disorder to the _temperate_ zone. Among the natives of Africa
gout, according to Livingstone, is unknown. Neither apparently is it
to be met with in Turkey, China, Japan, Peru, and the Brazils. The
indigenous peoples of India, and the East Indian Archipelago, also seem
exempt, though the immunity does not extend to Europeans resident in
these tropical climes.

It is significant that Duckworth, inquiring of practitioners from foreign
parts as to their experience of gout, found that little or none was
forthcoming “save where Europeans have formed part of the community.”
This statement, to my mind, does but add cogency to my contention that
gout is always _hereditary_.

If we restrict our purview to the British Isles and the Continent, we
find that as a nation we have achieved the unenviable distinction of
being _facile princeps_ in point of the liability to and incidence of
gout. The bulk of examples, too, are met with in England, the disorder
being much less frequent in Scotland and Ireland. Moreover, in the two
latter countries, the disorder is practically restricted to the upper
classes. By contrast, in England it has extended to the lower orders
also, in respect of which peculiarity we stand unique as compared with
all other countries.

Reverting to the Continent, gout appears to be more common in France
than in Germany, Austria, and Italy. Indeed, it is said to be endemic
in Normandy, Burgundy, and the Rhone Valleys. In Holland, according to
Duckworth, there is practically no gout, and the same is true of Russia,
save in Petrograd and the Baltic Provinces.

In Belgium, also, gout is not common, and in Greece it is much less
prevalent than in France or England.

In regard to the incidence of gout, its greater prevalence in _temperate_
as opposed to tropical climes, and the disparities between different
countries, it would be unsafe to assume that the variations are the
outcome solely of _climate_. Thus the immunity of, _e.g._, strict
Mohammedans is attributable in part to their sobriety and the less highly
nitrogenous character of their food. But, if seduced into the ways of the
“infidel,” their exemption, it is said, ceases. Europeans, of “gouty”
heritage, may, if temperate, escape gout when resident in the tropics,
otherwise they fall victims thereto just as surely as at home.

Gout, indeed, is more a matter of _morals_ than climate. In the palmy
days of the Roman Empire, when luxury and indolence were rampant, gout
flourished, but declined following the installation of a republican form
of government. In like fashion and for similar reasons, the inhabitants
of modern Greece suffer infinitely less from the ravages of gout than of
yore. In short, the climate of Italy and Greece has presumably endured
unchanged, but the “habits” of their peoples have altered.

Formerly it was held that the incidence of gout in any country or
district varied according as to whether the population drank wine and
malt liquors, or distilled spirits. Where the taste for the latter
predominated, the disease was relatively rare, whence the comparative
immunity of Scotland, Russia, Poland, and Denmark. But what of the rarity
of gout in the wine-producing country Spain? Nor for that matter have I
ever seen it claimed that gout was especially prevalent in Portugal, the
home of “port,” that _bête noir_ of the “gouty.” In truth, dogmatism is
here out of place, for though overeating and overdrinking are undeniably
important factors in eliciting gout, they are not the _sole_ factors.

In reviewing the statements made as to the geographical distribution and
the race incidence of gout it is but too manifest that they are largely
provisional; indeed, such information as we do possess as to its relative
frequency in various countries, must be taken _cum grano salis_. Thus,
who can doubt that the various affirmations must have been very largely
influenced by the “personal equation,” that what one authority would
define as gout would by another be deemed inadmissible to this category.
Moreover, many of the original statements were made at a time when the
differentiation of arthritic disorders, as we now know it, was but in its
infancy. For obvious reasons, therefore, no researches in this sphere can
ever be satisfactory, until the opinion of the profession at home and
abroad be crystallised into some definite pronouncement, some precise
definition, of the exact criteria by which the diagnosis of gout stands
or falls.

In justification of these strictures, may I cite some opinions as to
the frequency of gout in the United States. In 1890, Sir Dyce Duckworth
affirmed that in America gout was “practically unknown.” But a few
years later, we find Sir William Osier convinced that gout was often
_unrecognised_ in the United States. More pertinent still, only twenty
years after Duckworth’s affirmation, Luff quoted the statistics of the
Johns Hopkins Hospital, Baltimore, from which it appeared that during a
period of fourteen years 0·26 per cent. of the total admissions thereto
were examples of gout. This he contrasts with the number of cases of gout
admitted to St. Bartholomew’s Hospital, London, during a similar period.
_Mirabile dictu_, the percentage was only 0·37, but a third more than
that of the Johns Hopkins Hospital!

Yet again, J. H. Pratt, of Boston, writing in 1916, observes “the
greatest confusion exists in the minds of many practitioners in America
to-day regarding this disease (gout) and its diagnosis. In some parts
of the country the diagnosis is frequently made in conditions that are
not gout; in other sections there seems to be a skepticism in the minds
of many practitioners regarding the existence of such a disease. In
New England I have found that chronic gout, even when tophi occur, is
often mistaken for rheumatism or arthritis deformans. Some physicians
of large experience assert that they see gout frequently. Enquiry has
shown that they mistake typical cases of arthritis deformans for gout,
and the swellings about the joints and even Heberden’s nodes for ‘gouty’
deposits.”

Can it for one moment be denied that even to ourselves, living in
England, the so-called “home of gout,” these trenchant criticisms are
but too applicable. So long, then, as such confusion exists as to what
does and what does not constitute gout, how can we, with any show of
scientific precision, presume to discuss, much less lay down, dogmatic
statements as to the geographical distribution and the race incidence of
gout?

_Food, Drink, and Occupation._—Gout, it has been well said, is the
“Nemesis of high living,” for, unquestionably _overeating_ is most
fertile in evoking any latent tendency thereto. Attempts to throw all the
blame on particular foodstuffs, _e.g._, red meats, etc., on the ground
that these highly nitrogenous substances engender excessive formation of
uric acid, have failed of their object. Even the much-maligned “purin
bodies” have of late been largely absolved of blame, and the virtues
of a “purin-free” diet, _e.g._, milk, are probably referable to the
_intestinal asepsis_ that such a regimen promotes.

My experience, like that of others, is, that it is not the quality, but
the _quantity_ of the food that is responsible. Moreover, I believe that
the _toxicity_ of the blood plasma thus produced exerts its evil effects
_indirectly_, viz., by lowering the _vis resistantiæ_ of the individual
to _microbic_ invasion. Nor have I any doubt that it is this same but too
common tendency to gluttony on the part of the “gouty” which is in part
responsible for the _cardio-vascular_, _hepatic_, and renal changes so
frequently associated with gout in its later stages.

Reverting to _alcohol_, there are many who regard it as _par excellence_
the predisposing cause of gout, and some even question whether gout would
have evolved had alcohol been unknown to mankind. But the interesting
point is, that _all_ forms of alcohol are not equally pernicious in
this respect, and the difference in their potency in this direction is
apparently little or at all referable to their _percentage content of
alcohol_. Port, madeira, sherry, burgundy, strong ales, and stout are far
more provocative of gout than distilled spirits. In England, where gout
is prevalent, malt liquors are the common drink, whereas in Scotland,
where the predilection is for whisky, the disorder is much more rare,
and the same applies to Ireland. In the Burgundian province of France
gout is common, but exceptional in the Rhenish district of Germany, where
hock is largely consumed. The why and the wherefore of these vagaries is
not as yet explicable; but of those forms of alcohol, most conducive to
gout, neither their _acidity_, _sugar content_, etc., can be impeached as
imparting to the alcohol its predisposing influence in this direction.
Incidentally, to those who advocate the primary _renal_ origin of gout,
one would propound the question, why is it that _distilled spirits_ are
less provocative of gout than wines, seeing these particular liquors are
so fruitful of _granular kidney_?

Again, if alcohol be such a potent factor in gout, why is it so rarely
met with in habitual drunkards, and how account for the comparative
rarity in gouty subjects of _hepatic cirrhosis_, or for that matter of
other disorders of alcoholic origin? Beset by these eccentricities of
behaviour, Sir William Roberts was tempted to regard gout as “rather an
incident of the legitimate dietetic use of alcoholic beverages.”

The relationship of _alcohol_ to gout is as erratic as it is to _atrophic
cirrhosis_. Thus an individual may drink hard through life, and escape
cirrhosis; another luckless wight, though he be quite temperate, yet
falls a prey thereto; still another, who may never have tasted alcohol,
acquires cirrhosis; lastly, cirrhosis is occasionally met with in the
lower animals, into whose diet alcohol does not enter.

In like fashion, an habitually intemperate man may pass through life
without incurring gout. Another, handicapped by his heritage, though he
be strictly abstemious, yet falls a prey thereto. Even a total abstainer,
when coming of gouty stock, may develop gout, haply through overeating.

To my mind, the only supposition deducible from these facts is that some
individuals are born with a tendency to gout, and that this tendency
may never assert itself as actual disease; that in others the dormant
proclivity, under the influence of alcohol, forthwith becomes manifest;
lastly, in some again, so nicely poised is the equilibrium of their
_nuclein_ metabolism, that the most venial alcoholic indulgence suffices
to evoke an outbreak.

I incline, therefore, to the view that alcohol _per se_ is not a cause
of gout; in other words, alcohol will not, in the absence of a _gouty
heredity_, produce gout. On the other hand, given an innate proclivity
thereto, alcohol, especially certain forms of it, will almost infallibly
evoke the disease; this often though the subject be conspicuously
moderate in its use.

That alcohol will produce the disorder even more swiftly and surely if
reinforced by _overeating_ also, cannot, I think, be gainsaid. As to the
_modus operandi_ of alcohol in inducing gout, I believe that it acts
_indirectly_, viz., by slowly sapping the protective mechanisms of the
body, and so paving the way to _infections_.

Much stress has been laid on the fact that certain _occupations_ conduce
to gout; but, if we exclude _plumbers_, _painters_, or other workers
in _lead_, no other callings in life can be held to entail a specific
predisposition to its development, save in so far as they promote
_overeating_, _overdrinking_, and _inactivity_.

It is well established that workers in _lead_ are specially prone to
develop gout. I take pride in noting that two of my predecessors at the
Royal Mineral Water Hospital, Bath, William Falconer (1772) and Caleb
Hillier Parry (1807), drew attention to the frequent occurrence of gout
in those exposed to the action of _lead_; nevertheless the major part
of our knowledge of lead as a predisposing cause of gout we owe to Sir
Alfred Garrod (1854). This authority noted that at least one out of
every four gouty patients that had come under his care at King’s College
Hospital had at some time in their lives been the subjects of _plumbism_,
and for the most part were plumbers or painters. Out of 136 undoubted
examples of gout, Sir Dyce Duckworth noted that of these twenty-five
males showed signs of lead poisoning, and were either plumbers, painters,
compositors, or workers in lead mills. My colleague, James Lindsay, out
of a total of 482 instances of males afflicted with gout, found that 108,
or 22·4 per cent., were workers in lead.

In light of these findings the question naturally arose as to whether
lead impregnation _per se_ could produce gout. It was then elicited
that the association of lead with gout was noticeably less frequent in
Scotland and in the North of England than in London. On this interesting
point Dr. T. Oliver observes, “We do not see in the north that intimate
relationship between gout and saturnine poisoning. Workmen from the south
develop it in the North of England. The natives of the north, though
equally exposed, seldom become gouty even when the kidneys are affected.”
Again, Osler tells us that in America lead-gout is comparatively rare,
though chronic lead poisoning is frequently met with in that country
in association with arterio-sclerosis and contracted kidneys. Again,
Frerichs, out of 163 cases of plumbism in the Berlin Hospital, found not
a single case of true gout.

Some remarkable instances illustrating the influence even of medicinal
doses of lead in determining outbreaks of gout are on record. In a
man aged 25-30, suffering from chronic diarrhœa, Sir Lauder Brunton
prescribed lead and opium pills. In less than ten days he returned with
gout in one of his joints, though he had never previously suffered from
an attack. My colleague, Dr. Munro, tells me of an even more striking
case. A lady under his care had used a hair wash, for many years, with
apparently no ill effects. She recommended a friend of hers to try the
same lotion, and within a few days she developed acute arthritic gout,
though she had never previously experienced the disorder. Analysing the
preparation, Dr. Munro found the clue in the contained lead.

As to proffered explanations of lead-gout some have sought it in the
production by this poison of _arterio-sclerosis_ and _chronic nephritis_.
But this is scarcely satisfying when we contrast the frequency of chronic
plumbism and associated arterio-sclerosis and contracted kidneys with the
relative rarity of lead gout.

The balance of evidence would appear to be in favour of the view that
lead _per se_ cannot produce gout. For the incidence of lead-gout is
scarcely appreciable, save in a population amongst whom from other causes
gout is prevalent. In short, lead in the absence of an hereditary bias,
is impotent to evoke gout.

As to its _modus operandi_, I think it exerts its effect through
derangement of the intestinal secretions, and so favours the migration
inwards into the system of pathogenic _bacteria_.

As for occupations other than those concerned with lead, it is certainly
notorious that gout is extremely frequent in those that are rich in
opportunities for overeating, overdrinking, and sluggish habits. This
point has never been more clearly illustrated than by James Lindsay,
whose analysis I take the liberty of transcribing.

Thus, out of 482 males the victims of gout, eighty-one were cabmen,
coachmen, grooms, stablemen, and bus drivers; fifty-one were draymen,
publicans, barmen, cellarmen, potmen, innkeepers, maltsters, coopers,
storekeepers, brewers’ travellers, and brewers’ labourers; twenty-five
butlers, men servants, ship’s stewards, and hotel servants; while
forty-five were labourers, and of the residue, although all kinds of
trades and occupations were represented, yet no other class reached ten
in number.

Of these various stations and occupations, it cannot be held that, in
themselves, these callings necessarily contain the “seeds of the gout.”
The banefulness resides in the _associated habits of living_; for but
too frequently repletion, intemperance, and indolence go hand in hand
with these vocations. In other words, dietetic excesses, overloaded
intestines, and too much alcohol, what more likely to impair the
digestive functions, to increase the toxicity of the intestinal flora,
and in turn to upset the equilibrium of general nuclein metabolism, with
its associated specific local reaction in certain tissues?

_Mental and Physical Over-exertion, etc._—Sydenham said of gout that it
destroys “more wise men than fools,” and in a letter to Dr. Short, he
complains, “I send you a short tract upon Gout and Dropsy instead of
the thicker volume, which in my own mind I had determined on, viz., a
history of such chronic diseases as my practice has most especially met
with. By applying my mind, however, to its utmost, and by bringing all my
powers of thought on the subject, I brought on a fit of gout, such as I
had never before suffered from; so that the fact itself warned me to lay
aside, even against my own will, such lucubrations, and to take care of
myself; well satisfied with having, in some measure, dealt with these two
diseases. Whenever I returned to my studies, gout returned to me.”

It is doubtful if, in the absence of an _hereditary_ proclivity,
intellectual strain would promote the development of gout. On the other
hand, there is, I think, no doubt that immoderate mental exertion will
indirectly precipitate an outbreak. I can well understand that the
illustrious Sydenham, absorbed in his life study, forgot to take a
normal amount of exercise. Perhaps, like the renowned Jenner, he would
have said, “I never walk at all except from my house into my carriage.
I hate walking, and if I could, I would get my servants to carry me to
bed.” Nevertheless, I doubt not that Sydenham’s intellectual efforts
necessarily entailed sedentary habits, which brought in their wake
digestive and intestinal derangements, whence his occasional gouty
outbreaks.

Gout, indeed, has taken its full toll of the “Intellectuals.” Thus
Scudamore tells us that “The late Mr. Pitt and his father had gout at
a very early period of life. The father was never a votary of Bacchus,
and neither of Venus (as we are told), but both were _ardent students_.”
Probably, in many instances, however, the evils of immoderate study are
reinforced by more reprehensible excesses. The ancients insisted on
sexual debauchery as favouring outbreaks of gout. Whence the Latin verse:

    “Ut Venus enervat vires, sic copia vini,
    Et tentat gressus, debilitatque pedes.”

Doubtless, in some instances of this supposed origin, a _gonococcal_
arthritis was confused with gout. Doubtless sexual neurasthenia with
diatetic excess favours the onset of gout. In the same way grief,
anxiety, and other depressing emotions are provocative of gout in that
they impair the digestive functions, lead to hepatic torpor, and sluggish
bowels.


SUMMARY

In conclusion, we have now dealt with those factors currently regarded
as _predisposing_ causes of gout. Personally, as I have before said, the
differentiation of the foregoing from the so-called _exciting_ causes of
gout is purely arbitrary. Thus even those who countenance such division
are forced to admit that many of the predisposing causes will, “if at any
time suddenly increased,” immediately excite a fit of gout.

In other words, the difference is _quantitative_ rather than qualitative.
Thus, a moderate drinker, if perchance he exceed his usual limits,
pays the penalty by an outbreak. Another habitually addicted to the
fleshpots eclipses himself, and a similar retribution is exacted. Or, he
exposes himself to a chill, with subsequent gastro-intestinal or hepatic
functional derangement. Yet again, the cessation of wonted exercise, and
more often the taking of it when unaccustomed, may determine the onset of
a paroxysm.

But far more arresting are the numerous and well authenticated instances
in which local _trauma_ not only determines an outbreak but also its
locality. How frequently, too, have blows, strains, sprains, _fractures_,
_dislocations_, or other trivial or severe injuries, been the signal
for an attack. Now, as we hope to show later, _local foci of infection_
are extremely _common_ in the _gouty_. Such are especially frequent in
the _teeth_, _tonsils_, _naso-pharynx_, etc. Is it not then extremely
probable that organisms may, _viâ_ the _blood-stream_, find their way
to a _joint_, the resistance of whose tissues has been lowered by a
_trauma_, however slight its degree? This I apprehend to be the true
explanation of the undoubted intimate connection between traumatisms and
arthritic outbreaks of gout.

Of similar significance, too, the numerous instances on record in
which acute attacks of gout have followed acute _tonsillitis_, acute
_pharyngitis_, acute _parotitis_, etc. How frequently, also, competent
observers, such as Garrod, noted that _boils_ and _carbuncles_ frequently
appeared to be excitant of acute attacks. But to this important point,
the intrusion of an _infective_ element in the genesis of gout, we shall
return in a later chapter entitled “Gout as an Infection.” It will
suffice here if we record our belief that—

    (1) Heredity is the sole _predisposing_ factor in gout.

    (2) That the differentiation between the usually cited
    predisposing and exciting causes is unwarrantable.

    (3) That both alike are merely _determinants_.

    (4) That their influence as such in exciting outbreaks is
    exerted through the medium of _infection_, this achieved either
    directly or indirectly.


MORBID ANATOMY

It has been truthfully affirmed that we know more of the _results_ or
products of gout, and less of its _essential_ nature, than of almost any
other disease. Thus the post-mortem history of the disorder is concerned
almost exclusively with more or less graphic accounts of the _uratic
deposits_, their sites of predilection, and the changes that they induce.
Hence it is that the morbid anatomy of gout relates for the most part to
its _regular_ or _articular_ manifestations, for it is in and around the
joint structures that the deposits for the main part occur.

As to the assumed localisations of the disease in the _internal_ organs,
there is no _anatomical_ evidence that they are due to an invasion of
the “gouty” inflammation. Not even the _renal_ changes, despite the
attestation, as it were, of the gouty process by _uratic deposits_ in the
_papillæ_, can be held as distinctive of gout. Norman Moore found them
present in only twelve out of eighty cases. As Osler said, “The presence
of uratic concretions at the apices of the pyramids is not a positive
indication of gout. They are not infrequent in this country [U.S.], in
which gout is rare.... It is not possible to say in a given case that
the condition has been due to gout unless marked evidence of the disease
co-exists.”

If, then, nothing distinctive can be claimed of the _renal_, how much
less can we construe as “gouty” the anatomical alterations that may
or may not be met with in other organs in this disorder. In short, it
may be said of the _renal_ as well as the other _visceral_ lesions, so
often met with in association with gout, that they are met with even
more frequently in its absence, and most certainly fail to attest their
“gouty” nature by the appearances which they present.

The only morbid structural changes, therefore, that can legitimately be
defined as _specific_ of gout relate to its _regular_ or _articular_
lesions. As to the _anatomical_ alterations in the articulations, their
specificity depends essentially on the _uratic deposits_, rather than
upon the associated inflammatory and degenerative processes.

Given death during an _acute_ paroxysm, examination reveals the
usual tokens of inflammation, hyperæmia, effusion, and swelling of
the ligamentous tissues. The synovial lining is injected and spongy,
while the exuded fluid is thick, scanty and turbid, containing
polymorphonuclear leucocytes as well as _crystalline deposits_. Charged
therewith, not only is the synovia thick, but of a milky appearance.
Examined microscopically, it is found to contain the acicular crystals
of _sodium biurate_. The synovia has occasionally been found covered
with blood, but no _pus_ formation has ever been known to occur in
uncomplicated acute gouty arthritis. The reaction of the synovial fluid
is generally neutral or alkaline, but exceptionally Garrod found it acid.

Uratic deposit has a predilection for _cartilage_, and in some instances
is strictly confined thereto; but in the more _chronic_ forms it
permeates all the component elements of the articulation. In the synovial
membrane and fringes deposition takes place in the subepithelial and
subserous layers. It invades also the ligaments, the tendons, and even
the periarticular fibrous tissues become impregnated with biurate.
Moreover, like the synovial sheaths of the tendons, the neighbouring
bursæ are specially prone to deposits, which again encroaching upon the
subcutaneous connective tissues, infiltrate the skin itself, forming
chalk stones or tophi.

Inspected after death, the articular cartilages are seemingly overlaid
with a white mortar or chalk-like material, _i.e._, sodium biurate. Their
surfaces, however, though defaced by stains, streaks, or dull patches,
nevertheless, at any rate at first, retain their pristine smoothness.
This because closer scrutiny reveals that the deposit is not in reality
_upon_ the surface of the cartilage, but is located _interstitially_ in
its substance.

Microscopic examination of a vertical section, taken at the site of the
deposit, shows clearly that it is composed of felted masses of acicular
crystals. Lying in the matrix of the cartilage, they are more densely
packed just below its free surface. The crystals do not penetrate further
than one-third or one-half of the depth of the cartilage. Becoming more
and more sparse towards the deeper layers, those near the bone are
entirely free from deposit. This clearly indicates that the uratic matter
originated from the synovial fluid bathing the articular ends and was
precipitated therefrom.

As to the primary site of the deposition, it usually takes place at the
centre of the articular cartilage. Opinions differ as to whether the
cartilage cells are foci of deposition. Garrod thought so, but Duckworth
found no relationship between it and any histological elements, while
others locate it in the matrix.

While, as before stated, the cartilage at first retains its smoothness,
later it becomes pitted in patches. Ultimately the cartilage, through
atrophic changes and erosions, may disappear, the joint cavity becomes
filled with a plaster-like material, and the joint structures undergo
more or less disorganisation. _Pari passu_ with the central atrophy
of the cartilage, hypertrophic outgrowths form at its free margin.
In late stages the bones, too, undergo changes; their outer layers
become more dense through proliferative osteitis, while their spongy
tissue becomes rarefied, and the cells of the marrow fatty. Duckworth
held that uratic deposits might occur _primarily_ in the bone without
any similar implication of the related cartilage. On the other hand,
Garrod dissented, claiming that when the bone was involved, it was only
_secondarily_ to uratic deposition in the cartilage, of which indeed it
was but an extension.

In reviewing the foregoing findings, it must be admitted that morbid
anatomy fails to shed light on the _essential_ cause of gout. This, at
any rate, is true of the older studies with which, up to the present,
we have been engaged. Still, as Berkart’s more recent researches show,
our knowledge of even the _morbid anatomy_ of gout is as yet but in its
infancy.

_Histological_ examination of the _articular ends_ adjacent to gouty
joints reveals the presence of certain _cystic_ changes in the
_diaphyses_. Thereupon Berkart propounded an hypothesis, explanatory of
the acute phenomena of a paroxysm of gout. His view was that these cysts
in the bone, at first minute, gradually enlarge. Ultimately, through
concomitant thinning of the surface bone, there comes a day when the cyst
bursts into the joint, its content voided into the cavity thereof.

An interesting point noted by Berkart was that in many cases of “acute”
gout the articular cartilage was found apparently normal and devoid of
_uratic deposits_, and this although the attack had been sufficiently
severe. This would appear to contravene Garrod’s dictum that “gouty
inflammation is invariably attended with deposition of urate of soda.”
The same inference was drawn from a case of Sir Dyce Duckworth’s. The
subject had had two attacks of gout in the right great toe joint. Yet
at the autopsy neither toe joint contained a speck of uratic deposit.
Nevertheless, this does not prove that uratic deposition had not ensued
during the gouty attacks. All it can be held to prove is, that such
deposits are not always permanent, and that, under certain conditions,
they may undergo resolution. That this is so is almost certain, seeing
that tophi in the ear have been seen to come and go, and equally
certainly, after an acute attack, tophi in the neighbourhood of a joint
may lessen even though fresh ones form coincidently at another site.

Albeit, the importance of Berkart’s hypothesis and histological findings
resides in the fact that they suggest strongly that a pathological
process, more vital and biological than the mechanical uric acid theory,
is at the root of the clinical phenomena of a gouty paroxysm. It does
not put out of court Garrod’s assumption that uric acid is an invariable
_accompaniment_ of acute gouty inflammation, but it militates strongly
against his contention that uric acid deposition is the _cause_ of acute
gouty inflammation. It indicates the reverse, viz., that the uratic
deposition is the _consequence_ of a more vital underlying morbid process.

Let us revert now more in detail to Berkart’s findings. The bones
adjacent to gouty joints were fully prepared for microscopic examination.
Investigation of the first metatarsals, and in some instances of the
phalanges also, revealed the presence of _cystoid degeneration_. Its
starting point is in the _epiphyses_. Thence it extends to the articular
cartilage, through which it bores at one or more points. The contents
of the cyst then find their way into the joint through the fistulous
openings in the cartilage, with a resultant acute “perforative synovitis.”

The cysts, at first minute, may be either single or multiple. Small
in size, they are easily concealed by the fat marrow, unless the bone
is properly prepared for microscopic examination. The isolated cysts
eventually coalesce, and so lead to considerable excavation.

As to the contents of the cysts little is known, as, save through
accidents or surgical operations, they are rarely available for
examination. When of relatively recent origin they apparently consist
of a coagulable substance which later on become serous or hæmorrhagic.
So long as the fistulæ thus formed in the cartilage remain pervious, a
direct way into the articular cavity is provided, and through this, if
of sufficient calibre, the necrotic matter periodically gains entry into
the joint, with ensuing periodic outbreaks of acute synovitis. In other
instances in which the cysts are located in proximity to, or within, the
diaphysis they may fail to extend to the cartilage, and no perforation
ensues. In this event, through accumulation of its contents, the cyst
enlarges, and the bone is gradually expanded through pressure.

Berkart holds that the histological changes in the affected epiphyses
indicate that the cystoid degeneration is the outcome of an _anomaly_ of
the _vascular_ and _osseous_ structures. The degenerative area contains
an abundance of dilated and thin-walled veins, evidence of a condition
of chronic congestion. In consequence thereof, the trabeculæ undergo
decalcification, and the adjacent fat marrow becomes fibrous. The areas
of fibrosis thus formed, owing to thrombosis of the related veins, become
softened and transmuted into cysts.

Now, as we all know, some persons, after indulging in wine, almost
immediately experience sharp twinges in the small bones of their hands
or feet. Garrod attached diagnostic importance to such swift response
as a sign of gout. These pains he attributed to uric acid deposition.
In contrast, Berkart attributes the twinges to atony and consequent
over-distension of the related vessels, which lack the normal support
afforded by the osseous trabeculæ.

As far as we are aware, these findings of Berkart’s are as yet
unconfirmed. Nevertheless they provide us with a much more probable
explanation of the phenomena of acute gout than the older _uric
acid theory_, which, not to mention the many other obstacles to its
acceptance, has always laboured under the aspersion of being too
“mechanical” in conception.

Moreover, his studies clearly indicate that not only the intra-articular
surfaces but the adjacent _bone-ends_ and _marrow_ must, as the somewhat
rare opportunities present themselves, be exhaustively investigated.
For myself, I cannot believe that so passive an agent as an “anomaly of
the vascular and osseous systems” is the _fons et origo mali_ in gout.
Some more vital element must, I feel convinced, intrude, and I incline
to think an _infection_. Berkart himself brings forth evidence in favour
of this contention, inasmuch as he noted the frequent co-existence of
_lymphangitis_, so pronounced that the whole of the affected leg became
the seat of a _leuco-phlegmatic œdema_.




CHAPTER V

PATHOLOGY OF GOUT—PROTEIN METABOLISM


Not only is the proximate cause of gout unknown, but the essential nature
of the disease is still shrouded in obscurity; for the obliquity in trend
of protein metabolism, manifested though it be by striking phenomena, is
clearly only the outcome of some, as yet undetermined, derangement in the
mechanism of _intermediary_ metabolic or bio-chemical change.

This is, of course, but to restate the problem we are confronted with.
Wholly to solve the enigma would postulate ability on our part to trace
ingested foodstuffs through all their vicissitudes from the moment of
entry into the blood or lymph-stream till flung out as effete matter
through the various avenues of excretion; but, unhappily, we know the
story only in part, its beginning and end, but not what lies between.

We know much of the complex changes that take place in food prior to
absorption, and of the _modus operandi_ of the latter not a little.
Comparably, too, we can gauge the quality and quantity of end-products,
the chemical outcasts, as they escape in the urine, sweat or breath, and
largely how achieved; but of the intermediate steps between absorption
and excretion we catch but a glimpse here and there. The sequestered path
by which the inanimate molecules of food uprise to Life, and anon go down
to decay and death, are still hidden.

In other words, little do we know of the relationship of _labile_, or
food-protein, to _tissue_ protein. True, the coarse fact of abnormal
protein loss in _renal_ disease may be revealed in the urine, as
likewise the waste of albumoses in _myeloma_, etc., and the incidence
of amino-acids in disease of the _liver_. Similarly, the appearance
of _cystin_ or of _alkapton_ in the urine bespeaks flaws in protein
metabolism, failures in the normal disruption of amino-acids. All these
are of the grosser anomalies of protein metabolism, but more subtle those
of gout!

Complex, in truth, the problem here presented, than which none more
subtle exists in the realm of bio-chemistry. True, _quantitative_
variations in the content of the urine as to _urea_, _uric acid_, etc.,
undoubtedly bear a direct relation to _protein_ metabolism, but they give
us little, if any, substantial clue as to the particular metabolic warp
responsible. We see this particularly in regard to uric acid, so long
accredited with an essential _rôle_ in gout.

Thus we cannot, on the basis of the _variations_ in its _excretion_ only,
presume to diagnose “gout.” This because even more extensive variations
occur in _healthy_ persons. On the other hand, attacks of gout never
occur when urates are absent from the _blood_. To reduce the amount of
these urates is clearly then of importance, and obviously to this end a
knowledge of their source is essential. We have an analogy to hand in
diabetes, in which the somewhat similar problem relating to _glycosuria_
has been partially solved.


REVELATIONS OF THE BIO-CHEMIST

But before proceeding to the more strictly biological aspect of the
relationship of uric acid to gout, we must, as in the study of any other
problem of metabolism, place ourselves in possession of the main facts
relating to the chemistry of _protein_, and more particularly of _purin_
or _nuclein_ metabolism; for it was just this same lack of even the most
rudimentary facts, especially regarding the chemistry of uric acid,
that vitiated the conclusions arrived at by the earlier workers in this
sphere. Disabilities of technique of necessity rendered inaccurate the
results obtained by these pioneers in research, while the significance of
the facts they laboriously gleaned was likewise misinterpreted.

But with the advent of highly trained organic chemists, well skilled
in the investigation of bio-chemical problems, a basis of accurate
chemical facts was established. The story of the fate of protein and
purin substances in the animal body, at one time a medley of guesses and
gaps, was brought to one of relative certitude and completeness. The
change involved has proved in truth revolutionary, and many the cherished
shibboleth that has been ruthlessly cast aside.

How vivid the light thrown upon the problems of clinical medicine by the
bio-chemists! With admiration not unmingled with awe we see them laying
well and truly the foundations upon which in the ultimate scientific
medicine must inevitably rest. Of these the very corner stones are
_chemical physiology and chemical pathology_, the rapid evolution
of which is profoundly altering our conceptions of health and alike
disease. Those vital processes of the organism that but yesterday we saw
“as through a glass darkly,” are now in great part illumined, and the
distortions wrought in them by disease made more manifest.

How pregnant, too, with warning their findings! Processes that, to our
untutored minds, seemed simple are revealed as infinitely complex.
Through what a labyrinth must we thread our way if we would unravel the
intricacies of metabolism! Intricate enough, forsooth, in health, but how
much more so in disease!—for as Sir Archibald Garrod eloquently phrases
it, “It is becoming evident that special paths of metabolism exist, not
only for proteins, fats and carbohydrates as such, but that even the
individual primary fractions of the protein molecule follow their several
catabolic paths, and are dealt with in successive stages by series of
enzymes until the final products of catabolism are formed. Any of these
paths may be blocked, while others remain open.”

It is with chastening reflections such as these that we may best approach
our study of gout, that Riddle of the Ages, upon the elucidation of which
so many physicians from time immemorial have expended their dialectic
skill. Would that we could affirm that the bio-chemists of to-day had
found the “Open Sesame!” But, alas, it is not so! The chamber is still
sealed.

Vast though the increase in our knowledge of the chemical structure of
uric acid and its allies, uncertainty still dogs our steps. Doubtful of
the pathway to solution of the pathological mystery of gout, we must
perforce approach the problem in a more strictly catholic attitude. _Uric
acid_ has apparently failed us as the _causa causans_. We can, therefore,
no longer restrict our enquiry to _purin_, but must take cognisance
of _protein_ metabolism as a whole, for some, perhaps not unnaturally
despairing of the _uric acid_ hypothesis, are turning therefrom to
other end-products of metabolism, _e.g._, _creatinine_. In keeping
with this altered outlook, it will not be out of place if we, at this
juncture, allude, though in brief, to the later revelations as to protein
metabolism, before we pass on to more detailed consideration of those
relating to the _purin_ bodies.


PROTEIN METABOLISM

No longer can we, like the older physiologists, envisage _protein_
as being absorbed as such from the alimentary canal and forthwith
incorporated with the body tissue, for the researches of Fischer have
revealed that the complex _protein_ molecule must previously undergo
complete disruption into the _a-amino-acids_, its ultimate “building
stones,” this through the hydrolytic action of the digestive enzymes
of the alimentary tract. The fact that Fischer[6] was able to maintain
nitrogen equilibrium in animals fed with completely digested protein
mixtures is, of course, direct evidence in favour of his contention,
viz., that proteins undergo disruption into amino-acids.


THE FORMATION OF UREA

The question as to whether urea, the end-product of general nitrogenous
catabolism, was derived from the _amino-acids_, brought in the portal
blood to the liver, was for long a vexed one. This because the earlier
attempts to detect amino-acids in the _portal blood_, during the
digestion of copious amounts of protein, proved futile. On the other
hand, the same workers found that free _ammonia_ was present in greater
amounts in the portal vein than in the systemic circulation.

This, to their mind, seemed to indicate that the amino-acids, during
their passage through the intestinal mucous membrane, underwent
_deaminisation_. According to this view the _ammonia_, thus split off
from the amino-acids, was the precursor of _urea_.

But the claim that more free ammonia was present in the portal vein than
in the systemic circulation was disproved by Folin and Denis. Invoking
more delicate methods of hæmo-analysis, they found that the amount
of ammonia and urea in the portal blood was not increased during the
absorption of amino-acids from the lumen of the intestine. Moreover, they
found that the ammonia present was of minimal amount, produced in the
main by putrefactive bacteria. Lastly, they discovered that _amino-acids_
were actually present in the _portal blood_.


FATE OF THE AMINO-ACIDS

In the gastro-intestinal tract the complex food proteins, under the
hydrolytic action of enzymes, break down into a variety of substances,
all of which belong to the group of a-amino-acids. These same absorbed
from thence into the blood are transported to the various organs and
tissues. Arrived thither the amino-acids are subjected to a process of
sifting. Thus some are invoked for the reconstruction of broken down
proteins, _i.e._, are re-synthesised into the body’s own characteristic
tissues.

The surplus amino-acids, viz., those not required for purposes of cell
repair, undergo deaminisation. Two residues then result, one represented
by ammonia, and the other by the remaining relics of the amino-acid
molecule. The former is excreted as _urea_ and the latter is oxidised to
produce energy.

But there is yet another source of amino-acids, viz., the disintegration
of tissue protein. To this end almost all bodily tissues possess
intracellular enzymes capable of converting their proteins into the same
simple products from which they took origin.

Comparably with those of exogenous origin, these amino-acids of
_endogenous_ formation undergo a like deaminisation; in other words, the
bulk of their carbon, oxygen, and hydrogen is oxidised to form CO₂ and
water, the residue combining with nitrogen to form _urea_, etc.

The main end-product, then, of protein metabolism is _urea_, with traces
of its forerunner _ammonia_. But there are also other waste nitrogenous
metabolites. Thus, of the various amino-acids that become built up into
tissue protein, some subsequently break down into products not belonging
to the amino-acid category, viz., _creatine_ and _creatinine_. Some of
the amino-acids, too, are excreted unchanged in the urine. Lastly, to
these must be added those closely related substances, the _purin_ bodies,
the end-products of _nuclein_ as opposed to general protein metabolism,
of which latter _urea_ is the terminal product. To sum up, in a man on
ordinary diet about 90 per cent. of his total nitrogen is excreted as
urea, about 3 per cent. as ammonia, the residue of the nitrogen appearing
in the form of other nitrogenous metabolites.


SEAT OF FORMATION OF UREA

The _liver_, it is generally held, is the main centre wherein urea is
produced from the amino-acids; but not exclusively so, for it has been
definitely established that, _even after removal of the entire liver in
animals_, its production may not cease.

Moreover, some researches of Otto Folin and W. Denis into _urea
formation_ seem to indicate that the older views call for revision.
Experimenting on cats, they injected them with _alanine_ and _glycocoll
nitrogen_ and other amino-acids as well as Witte’s _peptone_. They
were able to prove definitely that, at the end of an hour or more, the
formation of _urea_ from the absorbed amino-acids was unmistakably
demonstrable. Also they noted that interesting fact, that the “_urea
nitrogen_ obtained from the _hepatic blood_ is not larger than the urea
in the blood obtained at about the same time from the _iliac artery_.”
This they claim indicates that “_the liver has not brought about any
demonstrable specialised deaminisation_.”

The experimental data forthcoming in their researches, while they prove
that the absorption of _amino-acids_ is very swiftly followed by the
formation of urea, does not afford any definite evidence as to the _site_
of urea formation; but, as they rightly contend, we have no satisfactory
proof that _deaminisation_ and _urea formation_ is _localised_.
Consequently “we are not justified in assuming that the process is a
specialised process in the sense of being confined to some particular
organ.”

Indeed, they bring forward evidence that the process of urea formation,
far from being localised to any particular organ, _i.e._, the liver, is
almost ubiquitous.

Thus, experimenting with the injection of _alanine_, they noted that
prior to the same the muscle content of _non-protein nitrogen_ and _urea
nitrogen_ was respectively 194 and 26 mg.; but 180 minutes after the
injection the non-protein content in muscle had risen to 232 and that of
urea nitrogen to 41 mg. Working with _glycocoll_, the non-protein and
urea nitrogen in muscle before injection of the same was 248 and 42 mg.
respectively, while 240 minutes after injection the figures were 304 and
54 mg.

The significance of these figures is more striking when contrasted with
the fact that in the same subjects the urea nitrogen content of the
_hepatic_ blood did not exceed that obtained almost simultaneously from
the _iliac_ artery. The deduction made by Folin and Denis is that—

(1) “_The urea-forming process is one characteristic of all the tissues,
and by far the greatest amount of the urea is, therefore, probably formed
in the muscles._”

(2) “_The negative results, so far as any localised urea formation is
concerned, is almost satisfactory proof that there is none, for if
there were one central focus from which all or nearly all of the urea
originated we could scarcely fail to find it._”


AMINO-ACIDS IN RELATION TO GOUT

The vista opened up by these advances in physiology suggested
investigations into the _amino-acids_, their association with the output
of _uric acid_ in _gouty_ patients. No less than eighteen different
amino-acids enter into the constitution of protein, but of these the most
interesting from our point of view is _glycocoll_ or amino-acetic-acid.
Now, glycocoll plays a great _rôle_ in the organism as a _detoxicating_
agent, rendering innocuous, _e.g._, benzoic and cholic acids by
transmuting them into _hippuric_ and _glycocholic_ acids. In short, the
body always has glycocoll at its disposal for coupling or combination
purposes.

Now it appears likely that glycocoll can be split off from all the
amino-acids, a probability reinforced by the results of the researches
of Embden and Reese and Lipstein, these observers having shown that
amino-acids are present in all urines to about 1 per cent. of the total
nitrogen output.

Ignatowski, working with the urine of _gouty_ patients, found
_amino-acids_ present in large amounts; not that it was peculiar to
such subjects, for he found it in other diseases, but only traces were
detectable in the urine of _healthy_ individuals. Again, Walker Hall,
investigating urines drawn from the subjects of gout, the victims of
other diseases, as well as healthy and diseased children, determined
the presence of _glycocoll_ in about 70 per cent. of the cases. His
researches, to his mind, confirmed the conclusion that “normally a
certain amount of glycocoll escapes through or is eliminated by the renal
filter.”

Burger and Schweriner, from their researches on gouty subjects, have
confirmed Walker Hall’s findings as to the excretion in excess of
amino-acids, especially _glycocoll_. Lastly, Almagia has in gouty urines
detected the presence of _glyoxylic_ acid. What its significance may be
is uncertain, but it is at least interesting to note that, as MacLeod
suggests, the synthetic formation within the body of glycocoll may very
probably result from the interaction of ammonia and glyoxylic acid.


THE GLYCOCOLL THEORY OF GOUT

Excessive meat feeding in dogs, according to Kochmann, induces
degenerative changes in the liver and kidneys. Similar tissue
alterations were noted by Walker Hall in rabbits, after injection with
_hypoxanthine_, while the same was observed by Kionka in mice. These
findings suggest that, although _anatomical lesions_ are not apparent in
the _livers_ of “gouty” men, it is at least probable that _functional_
damage results from the overeating of meat.

Now, if glycocoll be added to a solution of (neutral) dialkali-urate,
it expedites the appearance of the (acid) mono-alkali-urate, a reaction
more noticeable with the sodium salt. _Urea_, in contrast to glycocoll,
markedly inhibits the formation of the acid salt. But if _glycocoll_
be added to a solution of the (neutral) dialkali-urate and urea, the
latter parts to some extent with its powers in this respect, and the
mono-alkali-urate is deposited.

It is reasonable, then, to suppose that if, as testified by Ignatowski
and Walker Hall, glycocoll is present in gouty _urine_, it is also
present in the _tissue fluids_ of the gouty individual, and so the
_precipitation_ of _uric acid_ is favoured. Glycocoll, normally, is
almost entirely transmuted into _urea_ by the urea-forming ferment of the
liver.

Impressed by these considerations, Kionka advances the hypothesis that
gout is due to:

    (1) Functional changes in the liver, a depressed urea-ferment
    action.

    (2) A deficient uric acid excretion by the kidney, possibly due
    to the changed uric acid combinations in the blood.

    (3) These pathological conditions may be “hereditary” or
    “acquired,” from overeating, alcohol, lead, etc.

In other words, given deficient action of the urea ferment in the liver,
then more glycocoll will be present in the blood-stream, and the uric
acid may be thrown out of solution.[7]

For it is possible, as Kionka suggests, that normally uric acid, on its
way to urea, may pass through a _glycocoll_ stage. Now, in the gouty
individual the glycocoll may not be entirely transformed to _urea_, and
its excess in the _tissue fluids_ may lead to _uric acid deposits_.
Perhaps, as Walker Hall observes, “since hepatic deficiency is generally
admitted in the gouty, diminished destruction of uric acid and glycocoll
may go hand in hand.”

In healthy _cartilage_ glycocoll is undemonstrable. But, according to
Kionka, if bruised or damaged, a considerable amount thereof is formed.
Now, when blood, rich in uric acid, circulates through injured cartilage,
the presence of glycocoll favours precipitation of the urates, a possible
explanation of the formation of _tophi_. Unfortunately for the valency of
this theory, Aberhalden and Schittenhelm show that the methods employed
by Frey, to isolate glycocoll from cartilage, were such as yield errors
which would quite account for the amount obtained by this worker. They,
therefore, deny the presence of glycocoll in damaged cartilages. But, in
conclusion, Kionka’s plea for a primary _hepatic functional disability_
derives colour from the fact that the drugs which have gained most
approval in the treatment of gout are those which increase the quantity
of bile without augmenting the amount of bile acids; and the which are
excreted in combination with _glycocoll_, for instance, salicyclic acid
combines with glycocoll, and is excreted as salicyluric acid, and benzoic
acid, which combines with glycocoll to form hippuric acid. Albeit, we
must not overlook the fact that the presence of glycocoll is not peculiar
to _gouty_ urine, but, as shown by Walker Hall and Embden, is met with in
other disorders. The glycocoll hypothesis as to the origin of gout is,
though attractive, therefore still unproven.


UREA EXCRETION IN GOUT

According to Tilden Brown, the rhythm of urea excretion constitutes a
warning as to the approach of gout. A very lowered elimination thereof he
holds to be an excellent and pathognomonic symptom. The excretion of urea
may at times run so low as to lead to a suspicion of _renal_ disease. He
considers that this sign may find a place in the prophylaxis of gout,
a signal for the initiation of treatment with the object of lessening
the severity of symptoms (viz., extent of toxic action as manifested by
destruction of proteid, etc.).

This point was advanced by Brown (1905) during a discussion at the
Harvard Medical Society, but as far as we know it has not been confirmed.
Presumably it rested upon the assumed existence of a normal ratio of
uric acid elimination to that of urea with the corollary that every
deviation therefrom was due to a pathological cause. Haig held this view,
which was, however, disproved by Herringham, Groves and Luff. The latter
authority estimated the daily eliminations of uric acid and urea in a
healthy adult man on a mixed diet for a period of fifty days, and clearly
showed that no constant ratio exists in a given individual between the
excretion of uric acid and urea.

Also, it is obvious that, before attaching any valency to Tilden Brown’s
dictum, it is essential that it be established that the cases were
instances of pure gout, unaccompanied by _nephritis_. Moreover, modern
workers tend more and more to rely not on analyses of the urine but
of the _blood_, especially in the unravelling of so-called metabolic
disorders. Also, it may be added, that their findings in this sphere
indicate no harmony between the urea and the uric acid content of the
blood. Thus, Otto Folin observes, “One most interesting fact which we
constantly meet with in blood analysis is that there is no correspondence
between uric acid and the total non-protein nitrogen in the blood. In
gout or lead poisoning, or leukæmia, the blood is uniformly rich in
uric acid, yet the total non-protein nitrogen or _urea_ nitrogen may be
normal.”


CREATINE AND CREATININE

As before pointed out, it has been suggested that these substances may
be in some obscure way related to the genesis of _gout_. To this end a
great amount of research has been expended on the metabolism of creatine
and creatinine. But although, as far as I am aware, the revelations
hitherto forthcoming have disclosed no link between these substances and
the development of gout, still, by reason of the potentialities possibly
resident therein, a brief digression is permissible.

The exact origin of creatine and creatinine is still obscure. All we know
is that they are, in the main, the outcome of chemical processes in the
tissues, viz., products of _endogenous_ metabolism. Also of the creatine
and creatinine present in food a moiety may appear as creatine in the
urine.

_Creatinine_ occurs in the urine of adults, and is practically
independent of the protein intake. The amount excreted varies with the
size, and not with the weight of the body. In other words, it varies
with the _volume_ or _mass_ of the _voluntary muscles_, which structures
have the highest content of creatinine and creatine. MacLeod, discussing
this relationship, tells us that, “in the muscular atrophies creatine
excretion is distinctly below normal.” It must, he adds, be the “mass
of the muscles rather than their activities that is the determining
factor, for the creatine excretion does not become increased by
muscular exercises.” Otto Folin, discussing the clinical application
of pathological chemistry, observes, “Nothing definite is as yet known
concerning the creatinine output in abnormal metabolism, except that in
fevers and other diseases there is an increase, sometimes a very large
increase.” But this much we do know that creatine, after ingestion, is
almost quantitatively excreted in the urine. _Creatine_, in considerable
amount, is a normal constituent of children’s urine, but in normal adults
hardly a trace occurs, though in some diseases it is met with even in
their case. In boys it gradually dwindles and disappears at about seven
years of age. On the contrary, in girls creatine is excreted until
puberty. Subsequently, its presence in the urine is intermittent, its
incidence confined to the menstrual cycles, the period of pregnancy, and
for some days after parturition.

From our point of view, the most interesting of the above revelations is
the fact that the largest percentage amount of creatine and creatinine is
located in the _muscular tissues_. On this point we cannot do better than
quote the following words of Otto Folin:—

“It is to be noted that we are as yet entirely ignorant of the origin and
significance of the creatine which is so abundant in muscles, and it is
scarcely to be doubted that fundamentally important metabolism problems
somehow are connected with the muscle creatine and urinary creatinine,
but these are as yet problems of normal metabolism, and it is too early
to say whether, or in what way, light may be thrown on clinical problems
by studies of these products. The fact that the muscles of mammals,
including man, contain 0·3-0·4 per cent. of creatine, and only traces of
the chief nitrogenous waste product urea, constitutes to my mind strong
presumptive evidence that creatine serves some important function, and it
is quite conceivable that metabolism diseases of one kind or another may
be associated with this curious substance, but investigations rather than
hypotheses are needed in the study of such obscure problems.”


INBORN ERRORS OF METABOLISM

Apart from its intrinsic fascination, the tracing out of analogies,
clinical or pathological, between diseases apparently diverse has often
proved a fruitful source of enlightenment, for the natural history of
disease is such that one disorder trenches upon the clinical territory of
another, symptoms overlap and similarity if not community of origin is
revealed.

Few will gainsay that gouty individuals are the victims of some inborn
defect or eccentricity of metabolism, and instinctively the thought
arises, are there no other disorders of like character? Immediately
we bethink ourselves of alkaptonuria, cystinuria and pentosuria. Sir
Archibald Garrod, as we know, classed these disorders as “chemical
malformation” of hereditary origin. In other words, all are the outcome
of an abnormality in intermediary metabolism.

In alkaptonuria the metabolic warp concerns the _aromatic_ groups, in
cystinuria the sulphur-containing radicles of the _protein_ molecule.
On the other hand, in pentosuria the origin of the endogenous pentose
is variously ascribed to the _nucleo-protein_ of the cell nuclei or to
galactose. Lastly, in gout it is in the metabolism of _nucleo-protein_,
or rather of the _nucleic acids_ of the cell nuclei that the flaw resides.

We see, therefore, that Langdon Brown, discussing gout, is well justified
in observing that, “We may look upon a person who is readily poisoned by
purins in the same light as the person who has cystinuria, alkaptonuria,
or pentosuria, _i.e._, they all lack a link in the chain of protein
katabolism, so that intermediate products appear in the urine instead of
the usual end-products.” In other words, they all display a pathological
kinship, viz., in that they are all due to inborn errors of metabolism.

Certain broad clinical resemblances also obtain. All members of the
group, including gout, display _hereditary_ tendencies. All occur much
more often in _males_ than in females. They all alike tend to persist
through life. Lastly, their distinctive chemical products, including uric
acid, are all apparently of _low toxicity_.

But when we pass to the realm of their symptomatology, resemblance, if it
does not cease, becomes relatively obscured. Cystinuria and pentosuria
appear to be “harmless anomalies,” and the same is true of alkaptonuria.
The cystinuric, albeit, does suffer with _urinary_ concretions, and we
may recall that some authorities hold that gout and uric acid _calculi_
are not unrelated. As to alkaptonuria, it has this attenuated link
with gout that in its later stages the victims thereof tend to develop
a degenerative type of _arthritis_, while the frequently associated
pigmentary change, _ochronosis_, has a predilection for deposition in the
cartilages of the ears and _joints_.

But how colourless the clinical features of alkaptonuria, etc., as
contrasted with the vivid arresting phenomena of gout! how remote the
latter disorder from these “harmless anomalies”!

Apart from this general distinction, before gout could with justice be
relegated to the same category of disorders, it would be necessary to
prove that uric acid was an _intermediary_ and not a terminal product of
metabolism. All modern research, however, tends to indicate that uric
acid is an _end-product_, and, moreover, that there are no _uricolytic_
ferments within the body whereby its destruction can be accomplished. The
term “chemical malformation,” therefore, though strictly applicable to
alkaptonuria, cystinuria, etc., is inapplicable to gout. In other words,
though, for example, the _homogentisic acid_ met with in alkaptonuria is
a “chemical malformation,” _uric acid_ cannot be regarded as such. We
see, therefore, that though gout may, superficially regarded, appear to
have kinship with alkaptonuria and its congeners, yet in reality there is
a profound and essential difference between it and this fascinating group
of disorders.




CHAPTER VI

NUCLEIN METABOLISM


No hard and fast line can be drawn between the metabolism of protein
and that of nuclein. For though, morphologically speaking, the _nuclei_
of cells are sharply differentiated from the circumambient _cytoplasm_,
and exhibit equally distinct staining reactions, yet, _chemically_, the
differences between them are _quantitative_ rather than qualitative.

But while, as far as chemical changes are concerned, nuclein metabolism
is comparable with that of protein, nevertheless the former in respect of
its “energy” and its bearing upon growth and production, is infinitely
more vital, incomparably more active; for it is in _nuclear_ changes that
we may best discern evidence of the initiation of _oxidation_ processes
and other varieties of enzymatic activity. Moreover, as Walker Hall
points out, “the presence of masked iron phosphorus and certain forms of
fat in the cell nucleus strengthens this view, and thus we are led to
recognise the important part played by the nucleus in the life of the
cell, and to appreciate the influence of nuclein heredity in cellular
exchanges.”

So much by way of prelude, but the story of the growth of our knowledge
of _nuclein_ as opposed to protein is so fascinating as to be worthy of a
slight digression.


THE ISOLATION OF NUCLEIC ACID

Functionally regarded, the _nucleus_ is the essential element of the
cell. Embedded within the cytoplasm, its isolation therefrom, and this in
quantities sufficient for analysis, may well have dismayed the earlier
workers. But the resources of Friedrich Miescher were equal thereto.
Treating surgical bandages soaked with pus with a dilute solution of
sodium sulphate, he extracted the heavy pus cells. These, then, by
careful decantation, were easily disengaged. The pus cells, still intact,
were then subjected to the digestive action of artificial gastric juice.
The protoplasm was thus dissolved, but not the more resistant _nuclei_,
which remained as an insoluble grey powder. In this manner cell nuclei,
_free from protoplasm_, became available for chemical analysis. Treating
the insoluble nuclei thus obtained with dilute sodium carbonate, a
solution was formed. Acetic acid added thereto produced a flocculent
precipitate which was found to contain phosphorus, and responded to
protein colour tests. This substance Miescher christened by the name
of _nuclein_. Subsequent observers prepared nuclein from the nuclei of
_yeast_ cells and the _red blood corpuscles_ of birds. All nucleins are
insoluble acids which form soluble salts with sodium. But while they
respond to protein colour reactions they differ from _protein_ in that
they contain _phosphorus_ and _resist the solvent action of artificial
gastric juice_.

Migrating some ten years afterwards (1897) from Tubingen to Basle,
Miescher entered upon his celebrated researches into the habits of the
Rhine salmon. He found the belief had long been current that the fish,
during their passage from the sea up the Rhine to their spawning haunts,
never partook of food. That this belief was well founded he was able
to prove; for, saving isolated and easily explicable exceptions, he
noted that their alimentary canal was devoid of food _débris_, while
their digestive juices were as a rule inert. One startling change he
noted, that while, on the one hand, their _muscular_ tissue profoundly
wasted during their migration, their _organs of reproduction_ enlarged
enormously, the inevitable conclusion being that eggs and spermatozoa had
been created from muscle protein.


RESEARCHES ON SPERMATOZOA

Struck by the opportunities for scientific investigation during the
spawning season, Miescher determined to resume his work upon _nuclein_.
Spermatic fluid or _lachsmilch_, being readily obtainable in great
quantities, he had to hand a mass of material admirably adapted for
chemical examination of the cell _nucleus_. The conclusion that the
_heads_ of the spermatozoa might be regarded as a _metamorphosed nucleus_
seemed obvious, and the opportunity too good to be lost.

On examination he found the “sperm heads” protein-free, made up almost
entirely of a single chemical entity, a salt of an organic base rich
in nitrogen and an organic acid containing phosphorus. The former was
_protamine_, the latter _nucleic acid_.

The presence of this salt protamine nucleate led to the conclusion that
nuclein was merely a salt of protein and nucleic acid.


THE DISCOVERY OF PURINS

Miescher, who had already isolated nuclein and nucleic acid, came nigh to
one other equally important discovery. Heating a specimen of protamine
with nitric acid, he noted that a yellow spot formed which turned to
bright red when moistened with alkali.

Alive to the import of the reaction, Miescher requested Piccard to
examine salmon sperm for _purin_ bases. Extracting the same with
hydrochloric acid, Piccard found _guanine_, and what he thought was
_hypoxanthine_, but which was in truth _adenine_.

Another distinguished worker in this sphere, Kossel, noted that,
subjected to the action of hydrolytic agents, nucleins always yield
_purin derivatives_; also that the same were derived, not from the
_protein_ of the nuclein, but from the _nucleic acid_. Thus it
was to Kossel that we are indebted for the discovery of the purin
bases, hypoxanthine, xanthine, guanine, and lastly adenine. It was,
indeed, through his brilliant achievements that _nucleic acid_ became
recognisable as a definite entity, distinguishable from proteins and
other body elements, this latter differentiation by token of the _purin
bases_ which are contained in nucleic acid.

Moreover, it led to the dissipation of the old belief that _uric acid_
was an intermediate product of _protein_ metabolism, for the revelation
of purin bases as decomposition products of _nucleic acid_ carried with
it the inference that uric acid also had chemical affinities therewith.
The chemical structure of the purin bases and that of uric acid
betrayed a common likeness, and, therefore, a presumptive physiological
connection; in other words, that a chemical _nexus_ obtained between the
cell nucleus or _nucleic acid_ and uric acid.

The physiological derivation of uric acid from nucleic acid did not long
lack experimental proof. In 1886 Minkowski found that, given extirpation
of their livers, the urine of birds contained ammonium lactate, evidently
a substitute for the uric acid normally present, notwithstanding the
uric acid never entirely disappeared from the urine. This indicated the
derivation of uric acid from two sources:—

    (1) Conversion in the liver of ammonium lactate into uric acid.
    (2) Some other, though unknown, process of formation.

To clear up the obscurity regarding the latter, V. Mach, after
extirpating the livers of geese, injected them subcutaneously with
hypoxanthine, finding that the same was converted into uric acid, which
was excreted in the urine. In this way the capacity of the organism to
elaborate uric acid from a purin precursor was demonstrated.


URIC ACID A DERIVATIVE OF NUCLEIC ACID

Despite V. Mach’s revelation, the origin of uric acid from nucleic acid
was still to seek. In the year following (1889) Horbaczewski traced it to
this source, and in the following manner. Mixed with water, the pulp of
the calf’s spleen was put to digest at 50° until putrefaction began. The
fluid was then sterilised with a solution of lead acetate, and arterial
blood being added it was kept at 50°, a current of air meanwhile being
passed slowly through the mixture. Subsequently the fluid was found to
contain _uric acid_; but the experiment being repeated, without the
passage of air, _xanthine and hypoxanthine_ and not uric acid resulted.

While Horbaczewski’s experimental findings were amply confirmed, some
of his deductions therefrom were subsequently proved faulty. (Thus, he
thought putrefaction an essential factor; also he believed that the
formation of uric acid ensued _before_ the purin groups were disengaged
from the nucleic acid, and definitely affirmed that the uric acid was not
produced by the oxidation of _free_ xanthine or hypoxanthine.)

But, nevertheless, this pioneer established that in both _man_ and
rabbits _uric acid_ was derived from _nucleic acid_. Also, having
observed that when after starvation the food intake was resumed, a
_leucocytosis_ occurred, he announced his belief in the following theory.
Thus, he noted that _leukæmics_, whose blood showed a high leucocyte
count, excreted an unusually large amount of uric acid; consequently,
he came to the conclusion that _uric acid_ was formed from _defunct
leucocytes_. Also that nuclein-rich food, when ingested, contributed to
the formation of uric acid only in so far as it induced leucocytosis.
Hence the origin of the increased uric acid excretion which occurs when
feeding is resumed after starvation.

This increased excretion of uric acid after the ingestion of food rich in
_nucleic acid_ has been amply confirmed; but all the earlier attempts to
achieve an increased excretion by the ingestion of _free_ purin bases,
as opposed to the _combined_ purin bases, existing as such in _nucleic
acid_, failed, although tried repeatedly.

So much for the various stages by which our knowledge of the purin
derivatives of nucleic acid has been gradually acquired, for though
_purin bases_ had, from early times, been known to exist in _animal_
tissues, their presence there could not be rationally accounted for prior
to the discovery of _nucleic acid_.

It still remains for us to deal in detail with the further developments
of our knowledge which concern the _disruption of nucleic acid in the
body_ and the process by which _uric acid_ is derived therefrom.

But before proceeding to consider in detail the complex series or
_enzymatic_ transformation that this entails, it will, I think, be wiser
to deal first with the _chemistry_ of uric acid, its _solubilities_, and
its _sources_, whether exogenous, endogenous or synthetic.


THE CHEMISTRY OF URIC ACID AND THE PURIN BODIES

Much of the vague philosophy of disease in past times may fairly be
attributed to the complexity and mystery of action inherent in living
matter. The subjects of physics, chemistry and biology, in their wider
acceptation, were unevolved, and scientific pathology, the offspring of
this ancestry, was yet unborn. How much we owe to physics, chemistry, and
biology, those handmaids of medicine, is inestimable! But something at
least of our debt thereto will be revealed in the following pages.

Of the purins in human urine, the most important is _uric acid_, and
far behind comes xanthine, while traces of hypoxanthine, guanine, and
adenine are also detectable. Some years ago the current view was that the
metabolism of any _protein_ gave rise to _uric acid_. This assumption has
now proved to be erroneous, for it is known that only certain foodstuffs
lead to an increase in the uric acid excretion; in other words, on a
diet rich in _purin_ the output thereof is considerably higher than
on a purin-free diet, this being due to the large amount of _nuclein_
and purin bases in flesh foods, especially those containing glandular
substances. Under ordinary conditions the excretion of uric acid ranges
from 0·3-1·2 gm. per diem, or 0·02-0·10 per cent. The oscillations in
output vary with the state of health, diet, and personal idiosyncrasy.


CHEMICAL CONSTITUTION

The empirical formula of the uric acid molecule, C₅H₄N₄O₃, has for long
been known, but it was reserved for Emil Fischer to reveal the chemical
structure thereof. Through his labours we now know that uric acid is one
of a group of substances which owe their kinship to their possession in
common of the heterocyclic ring termed by Fischer the “purin nucleus”
(1898).

The intimate relations of the purins of bio-chemical interest to
the purin nucleus, and alike to each other, will be rendered more
intelligible by examination of their structural formulæ as hereafter
given. All, as will be seen, are derivatives of a synthetically formed
body _purin_ which, though unimportant in itself, is yet interesting in
that it is the basic substance from which the following take origin:—

  Purin          C₅H₄N₄
  Hypoxanthine   C₅H₄N₄O      Monoxy-purin   }
  Adenine        C₅H₃N₄NH₂    Amino-purin    }
  Xanthine       C₅H₄N₄O₂     Dioxy-purin    } Purin Bases.
  Guanine        C₅H₃N₄ONH₂   Aminooxy-purin }
  Uric acid      C₅H₄N₄O₃     Trioxy-purin   }

It now devolves upon us to note the arrangement of the atoms in the purin
nucleus. To each atom is affixed a number indicating the exact location
of the various atoms and groups attached to the said nucleus. The manner
in which the various purin bodies are built up around the _purin nucleus_
C₅N₄ will become apparent from a study of the following structural
formulæ culled from Wells’ “Chemical Pathology”:—


STRUCTURAL FORMULÆ

    N (1)—C (6)                              N CH
    C (2)—C (5)—N (7)                       HC C NH
                                     C (8)            CH
    N (3)—C (4)—N (9)                        N C—N

    Purin nucleus.                           Purin.

To describe the individual _derivatives of purin_ we have to indicate
to which particular atom of the _purin nucleus_ the combining groups
are attached. Thus, for example, _adenine_ in structure is classed as a
6-amino-purin, and accordingly has the following formula:

         N==C—NH₂
          |  |
         HC  C—NH
          ‖  ‖  \
          ‖  ‖   CH
          ‖  ‖  /
          N—C—N

         Adenine
      (6-amino-purin).


Other important bodies built up round the purin nucleus C₅N₄, variously
designated as xanthine, alloxuric and nuclein bodies:—

         HN—C==O                   HN—C==O
          |  |                       |  |
    H₂NC  C—NH                O==C  C—NH
          ‖  ‖  \                    |  ‖  \
          ‖  ‖   CH                  |  ‖   CH
          ‖  ‖  //                   |  ‖  //
         N—C—N                      HN—C—N

          Guanine                    Xanthine
     (2-amino-6-oxypurin).        (2-6-dioxypurin).

         HN—C==O                   HN—C==O
          |  |                       |  |
         HC  C—NH                   O==C C—NH
          ‖  ‖  \                    |  ‖    \
          ‖  ‖   CH                  |  ‖    C==O
          ‖  ‖  //                   |  ‖    /
         N—C—N                      HN—C—NH

          Hypoxanthine                Uric acid
         (6-oxypurin).           (2-6-8-trioxypurin).


     H₃C—N—C==O                HN==C==O
          |  |                       |  |
          |  |    CH₃                |  |     CH₃
          |  |   /                   |  |    /
       O==C  C—N                 O==C  C—N
          |  ‖    \                  |  ‖    \
          |  ‖     CH                |  ‖     CH
          |  ‖    //                 |  ‖     /
        H₃C—N—C—N                  H₃C—N—C—N

        Caffeine                   Theobromine
    (1-3-7-trimethyl,             (3-7-dimethyl,
     1-2-6-dioxypurin).            2-6-dioxypurin).

It will be seen that the _purin bases_ stand in very close chemical
relationship to _uric acid_ in that the latter also is marked by
the possession of a group called the _purin nucleus_; indeed, the
relationship of uric acid to the purin bases is more intimate than to
_urea_ (CON₂H₄), close though this latter be as may be seen from the
study of its constitutional formula. (For uric acid may be regarded as
composed of two urea radicles, linked by a tricarbon chain. By oxidation
and hydrolysis, two molecules of urea may be obtained from one of uric
acid, and conversely uric acid is produced by the condensation of urea
with hydroxy acids).

The first product of the _oxidation_ of purin is _hypoxanthine_, long
recognised as a constituent of meat extracts. _Adenine_, the amino
derivative of hypoxanthine, is met with in combination with other
substances in _nuclear_ material. The second oxidation product of
purin is _xanthine_, and its amino derivative _guanine_, both of which
are found in the same substances as hypoxanthine and adenine. Further
oxidation of purin gives rise to _uric acid_. We have to recognise,
also, that in addition to the purins of animal origin there are some
also derived from _vegetables_, viz., the _methyl_ purins, caffeine,
theobromine, and theine.

Now, as will be seen later, certain compounds, containing nitrogen and
phosphorus, constitute the chief, if not the exclusive, source of _uric
acid_. These substances, long known as _nucleins_ or _nucleo-proteins_,
exist in the animal tissues, and in special abundance in those
largely made up of cell nuclei, viz., thymus, lymph-glands, etc. The
important and, indeed, the distinguishing component of the nucleins or
nucleo-proteins is _nucleic acid_. This, in that through the action of
ferments, it is from the nucleic acids that _uric acid_ and the _purin
bases_ are derived.

But, apart from this, we have to recollect that nucleic acids yield
constituents other than purin bases, viz., the _pyrimidine bases_,
phosphoric acid, and a carbohydrate group. From a study of the structural
formulæ of the pyrimidine bases it will be seen that they are closely
related to the purin bases, lacking, however, one of the _urea_ radicles.
Moreover, it is believed that, though included in the makeup of nucleic
acid, they are not derived from purin but are _primary_ products.


            { NH—CO              { N==C—NH₂          { NH—CO
    Thymine { CO C CH₃  Cytocine { CO  CH     Uracil { CO  CH
            { NH—CH              { NH—CH             { NH—CH

To sum up, the characteristic constituents of _nucleic acid_ are the
purin bases (adenine, guanine, hypoxanthine, and xanthine), pyrimidine
bases (uracil, cytosine, thymine), phosphoric acid and a carbohydrate
group.

We have now discussed the _chemical structure_ of uric acid and its
relationship to the _purin bases_; but before proceeding to consider
the various sources from which uric acid is derived, it will I think be
convenient to consider (1) the physical properties of uric acid and (2)
the condition in which it circulates in the blood.


PROPERTIES OF URIC ACID

When pure, uric acid is white in colour and crystallises in rhombic form.
In contrast to _urea_ it is very insoluble, but much less so in _blood
serum_ than in distilled water, viz., ⅟₄₀₀₀₀ of water as opposed to ⅟₁₀₀₀
parts of plasma. It yields with alkalies two series of salts, viz., the
biurate or mono-basic, and the so-called neutral or bi-basic urate, the
latter of which is much more soluble. In water the mono-basic urate
forms a colloidal solution from which the crystalline salt gradually
precipitates.

The greater solubility of uric acid in blood plasma was, by Garrod and
Haig, attributed to the _alkalinity_ of the plasma. But it must be
recalled that the earlier workers in this sphere judged of the alkalinity
of the plasma by its reaction to _litmus_, a crude procedure as compared
with the use of _phenol-phthalein_, and Frankel’s _electro-potential_
measurements. Working with these as criteria, it has been shown that
blood is normally _alkaline_ in only a _minority_ of cases, and indeed,
according to Flack and Hill, the plasma is in reality _neutral_.

In the _urine_ uric acid and the urates are held in solution by the
neutral _phosphates_. This because the decomposition of the urates into
uric acid by the acid salts of the urine is inhibited by the di-sodium
phosphate present therein. Its maintenance in solution is possibly also
reinforced through the influence of other constituents in the urine,
notably, the urinary pigments and sodium chloride.


URIC ACID IN THE BLOOD

As to the form in which uric acid circulates in the blood, Sir William
Roberts believed that when dissolved in blood serum it was transformed
into the relatively soluble sodium _quadriurate_. This authority held
that in gout, either through deficient excretion or over-production, the
quadriurate accumulates in the blood. Circulating therein, in a medium
rich in sodium carbonate, it takes up an additional atom of the base, and
is transmuted into the _biurate_, which is less soluble and less easily
excreted by the kidneys; consequently, the biurate is hoarded up in the
blood, at first in gelatinous, and later in an almost crystalline form,
when its precipitation is imminent or actually ensues. This, moreover,
was apt to occur at sites where the circulation was poor, the temperature
low, and more particularly in regions in which the plasma contained a
relatively high percentage of sodium chloride, _e.g._, synovial sheaths.

But, unfortunately for the valency of this otherwise plausible theory,
it was proved by Tunnicliffe, Rosenheim, and others, that _quadriurates_
do not exist as definite chemical compounds; in short, it is generally
conceded that their existence should no longer be accepted.


GUDZENT AND SCHADE’S THEORIES

Gudzent was of opinion that uric acid can only exist in the blood as
the _mono-sodium-urate_, of which there are two isomeric varieties, the
easily soluble unstable _lactam_, and the stable relatively insoluble
_lactim_ urate. It is the former, or lactam, variety that accumulates
in the blood in gout and, according to Gudzent, it is the transmutation
thereof into the lactim modification that determines the precipitation of
urates in the tissues. The lactim urate is soluble only to the extent of
8·3 mg. per 100 cc. serum, whereas the lactam form is soluble up to 18 mg.

Others, like Bechhold, maintain that the urates are present in the blood
in a _colloidal_ form, impossible of excretion by the kidneys. Thus
Schade contends that, in the presence of alkalies (hydrates), uric acid
or its salts may pass into a state in which it is far more soluble than
usual. Moreover, on its path to crystallisation from this over-saturated
solution, it passes through a _colloid_ stage in which it is relatively
stable. The maintenance of this colloid stage and consequently the
retardation of precipitation is promoted by certain substances, _i.e._,
glycerine, urea, serum, albumen, nucleic acid, etc. But hitherto the
therapeutic possibilities suggested have not been invoked.


ORGANIC COMBINATIONS

It will be recalled that purin bodies cannot be detected in the _blood_
in health, though their administration by the mouth results in an
increase in the excreta. Minkowski, to account for this, suggested
that the purins in the blood were circulating in a combination which
prevented them from giving the usual reactions, typical of their presence
therein. We have an analogy in the masking of arsenic and iron in the
cacodyl compounds and the ferrocyanide ion.[8]

The explanation proffered by Minkowski was elaborated by Von Noorden.
His view was that lying at the disposal of the normal organism are a
certain number of organic substances. These latter can combine with uric
acid and render it soluble. It is then in this form passed through the
blood in the kidneys, which eliminate from it the uric acid. Now, in
gout these organic substances are deficient or wanting, and the result
is that the uric acid is passed into the blood in the form of _urates_,
the elimination of which only proceeds with difficulty; in other words,
the purins normally circulate in _organic_ combination and abnormally as
_salts_ of _sodium_.

It is worthy of note that, from a solution containing albuminous
substances, Burian and Walker Hall found that while it was easy to remove
the bulk of the purins, a certain percentage always remained which it was
difficult to extract.

The view that uric acid is probably carried in the blood in combination
with some other organic body and not, as was formerly supposed, with
sodium salts, rapidly gained adherents, but the nature of the organic
complex is still not accurately known. Many believe that at least
a moiety of the uric acid circulates in combination with _nucleic_
(thyminic) _acid_, but no such compound has yet been isolated from
the blood. Nevertheless, as MacLeod suggests, this theory, were it
proved correct, would account for the fact that some purins at least
are katabolised in the body when they are given in a combined state,
as _thyminic acid_, but are excreted unchanged when ingested in a free
state. Thus, certain purins, _e.g._, _adenine_, when given freely,
cause inflammation and calculous deposits in the kidneys of dogs which,
however, does not ensue when they are fed with thymic acid.

But Walker Hall, discussing the good results obtained by Schmoll and
Fenner from the administration of thyminic acid, states that his
experiments do not indicate that the improvement is at all associated
with any change in the _uric acid_ excretion.

To sum up, it is obvious, from the mere variety of the hypotheses
advanced, that we are still much in the dark as to the actual form in
which uric acid circulates in the blood. While on the one hand the
quadriurate theory appears no longer tenable,[9] on the other the nature
of the suggested uric acid organic complex is still unknown.

Nay, more, Walker Hall, writing in 1913-14, states “there are many who
consider that the _sodium mono-urate_ is the only possible compound;”
while Wells, in his “Chemical Pathology” (1918), claims that the best
evidence points to uric acid existing in the blood “in a _free_ state and
not combined, as was at one time urged by several students of gout.”


COMPLEXITY OF THE PROBLEM

How complex, indeed, the task of the bio-chemist may be gathered from
some reflections of Walker Hall. He reminds us that the oxidation and
deaminisation of the nuclein derivatives, nucleins, nucleotides and
nucleosides, is never complete. For _purin bases_ and _pyrimidin_ bases
run side by side in the blood-stream together with uric acid. Also, that
the unstable but soluble biurate is constantly changing into a less
soluble type, viz., from one isomer to another. Moreover, since the red
blood corpuscles abound in potassium, urates of _potassium_ must also
occur, and to these may be added, too, ammonium and calcium compounds in
small quantities.

But more striking is his inference that the occurrence of _isomeric
forms_ of _uric acid_ suggests that _isomers_ of _purins_ and
_pyrimidins_ also may occur. For the purin ring or pyrimidin nucleus,
with their numerous receptors for the linking up of other substances,
offer wide potentialities in the direction of isomerism.[10] Some of
these, he hazards, may be born of one type of cell nucleus, some of
another, while it is not inherently improbable that, “In response to
abnormal stimuli or excessive demand, other isomers may be formed.”

Now, though uric acid and the urates can be extracted from the blood,
it does not, as he remarks, necessarily follow that they circulate as
such _in vivo_; for, despite modern achievements, “the best of the
existing methods for the determination of uric acid in the blood are
nearly barbarous in their crudity and intensity.” The various procedures
available for such estimates fall short of distinction between the
several tautomeric forms of uric acid, much less do they furnish
any information as to the associations or combinations of purins or
pyrimidins with other substances.

For himself, recognising the generally more complex nature of biological
processes, he considers that “the circulation of the purins as sodium
mono-urate and its simple extraction by kidney cells, seems almost too
simple to be true.”

As to the _solubilities_ of uric acid and urates in gouty blood he points
out that the suspension capability of the blood-stream for uric acid much
transcends the highest amount of uric acid as yet found in the gouty
subject. Accordingly, to him, therefore, it seems that “neither chemical
nor physico-chemical processes suffice to explain the problem. There must
be something more, something vital, biological.”

Having ascertained as far as possible the measure of our knowledge in
regard to the foregoing points, we shall, in the succeeding chapter,
proceed to discuss the _sources_ of _uric acid_, whether of intrinsic or
extrinsic origin.




CHAPTER VII

SOURCES OF URIC ACID


Uric acid, like the “purin bodies” (xanthine, hypoxanthine, guanine,
and adenine), is derived from _nucleins_, _i.e._, from the breaking
down of tissues rich in cells. The end-product of purin or nuclein
katabolism _uric acid_ represents but a further stage in the oxidation
of the _purin_ bodies. To the serial enzymatic transformations that mark
its derivation from _nucleic acid_ we shall allude later, but at this
juncture we are concerned not with the _mode_ of _formation_ of uric
acid, but with the sources thereof.

In this sphere we are greatly indebted to the pioneer researches of
Burian and Schur. These observers noted that on a diet rich in _nucleins_
(sweetbreads, liver, kidneys) the total daily excretion of uric acid was
considerably higher than on a milk or purin-free diet. This difference
in response to varying dietaries, in respect of the excretion of uric
acid, led Burian and Schur to the conclusion that the purins excreted
must be partly of _exogenous_ and partly of _endogenous_ origin; in other
words, the exogenous purins are derived from the nucleins ingested in the
food, whereas the endogenous are the outcome of the breaking down of the
cellular tissue of the organism itself.

Here it may be noted that all the ingested purins are not excreted in the
urine as uric acid, for some pass away as _purins_. Moreover, the amount
excreted will vary with the kind of purin ingested, and also with the
_species_ of the animal that consumes it. Thus, in man “only one half of
the hypoxanthine administered as such appears as uric acid in the urine,
and but one fourth of the purin in nuclein when that is fed. In the
dog, compared with man, about ten times as much purin disappears in its
passage through the organism; in the rabbit, about three times” (Flack
and Hill).[11]

In amount about 0·4-0·7 gramme of uric acid is excreted in _human_ urine
daily, and the purin bodies, hypoxanthine, xanthine, and adenine, in
small quantities.

Beyond exogenous and endogenous purins there is yet one other possible
source of uric acid, viz., its _synthetic formation_ within the organism.
This supposition took origin in Horbaczewski’s discovery that in the
laboratory he was able to produce uric acid by the interaction of _urea_
and _glycocine_, a finding afterwards confirmed by Latham. The theory
was then advanced that a similar synthesis might be effected by the
_kidneys_; but it was found that glycocine and urea, even when given in
excess to mammals, caused no change in the uric acid excretion.

So much by way of preface to our detailed discussion _seriatim_ of the
various sources of uric acid, and to which we now pass on.


EXOGENOUS PURINS

The foodstuffs that cause an increase in purin excretion are divisible
into three groups:—

    (_a_) Amino-purins.
    (_b_) Oxy-purins.
    (_c_) Methyl-purins.

_Amino-purins._—In man the taking of food rich in nucleated cells and
therefore in nucleo-protein and nucleins, increases the quantity of
uric acid in the urine. Thymus gland, pig’s pancreas, and herring roe,
containing the characteristic conjugated proteins of nuclei, or Liebig’s
meat extract, rich in purin bases, when ingested, lead to a distinct
increase in purin excretion.

The researches of Kossel and Horbaczewski showed that such augmentation
was mainly due to the production of uric acid from the _nuclein_
substances of the food; in other words, it was due to the katabolism of
_nuclein_, the cleavage products of which comprise _adenine_ derived
from thymus, and _guanine_ from the pancreas, both of these bodies
being amino-purins. According to Burian and Schur, of the amino-purins
ingested, a fourth is excreted as purin.

_Oxy-purins._—To this group belong xanthine and hypoxanthine. These
substances occur in muscle, and in great abundance in meat extract, and
Minkowski noted that the ingestion of xanthine bases markedly augmented
the amount of uric acid excreted. In man, given ingestion of hypoxanthine
as such, only one half thereof appears as uric acid in the urine. It may
here be mentioned that not all the purin bases ingested exist bound up in
the nuclein substances. An appreciable amount is present in the tissues
in a _free_ state, _e.g._, hypoxanthine in the muscles; consequently,
a moiety of the intake of purin bodies, especially in the animal
constituents of the food, is to hand ready formed, and does not require
the disruption of _nucleic acid_ for its liberation.

_Methyl-purins._—The nuclei of _vegetable_ cells also contain
nucleo-protein, and, therefore, can add their quota to the purin intake.
The most important are _caffeine_, _theobromine_, and _theophyllin_, the
active principles of tea, coffee, and cocoa. It may here be recalled that
of the purins administered in food, not all are excreted as uric acid,
but some as _purins_. Now it is doubtful whether the _methyl-purins_ lead
to the formation of _uric acid_ in the organism, or whether they are
excreted as purin bases in the urine. According to Stewart, a fractional
part of the _purin bases_ in the urine is composed of heteroxanthine,
1-methyl-xanthine, and paraxanthine derived from the active principles of
coffee, tea, and cocoa when consumed as beverages. As stated by Burian
and Schur, one third of the methyl-purins ingested is excreted as purin.

From the foregoing data it will be obvious that the _exogenous_ urinary
purins are derived from _nuclein_ and certain _free xanthine bases_, and
that the influence of other nitrogenous foodstuffs in this direction is
practically negligible.


EXOGENOUS URIC ACID EXCRETION

As to the amount of exogenous purins that, when administered orally,
can be recovered from the urine, it would appear that a certain rough
parallelism obtains between the purin content of the food and that of the
urine. The amount of the exogenous urinary purin differs for different
forms of food, a variation well illustrated by the following table,
giving the results of Burian and Schur’s researches.

  ---------------+-------------------+----------------
                 | Total percentage  | Percentage of
      Diet.      |    of purin       |   exogenous
                 |substances in diet.| urinary purin.
  ---------------+-------------------+----------------
  Beef           |        0·06       |      0·030
  Coffee         |        0·20       |      0·075
  Calf’s liver   |        0·12       |      0·060
  Calf’s spleen  |        0·16       |      0·080
  Calf’s thymus  |        0·40       |      0·100
  ---------------+-------------------+----------------

Walker Hall, experimenting with various purin-containing foods, found
that (1) with chicken 54·4 per cent., (2) with plaice 58·7 per cent., (3)
with beef 47·4 per cent., (4) with haricot beans 55 per cent. of the food
purin appears in the urine as exogenous purin. These findings of Walker
Hall’s, like Burian’s and Schur’s, reveal that, roughly speaking, 50 per
cent. of the purin content in food is excreted in the urine.[12]

These figures must be taken as a broad average relating only to healthy
individuals upon diets capable of perfect assimilation.

More recently, Mendel and Lyman found that about 60 per cent. of injected
hypoxanthine, 50 per cent. of xanthine, 19-30 per cent. of guanosine,
and 30-37 per cent. of adenine were excreted in the form of _uric acid_.
While this is true of free purins, on the other hand, when _bound_
purins, _i.e._, nucleins are administered, only a small proportion
thereof appears as uric acid in the urine. But before proceeding to
canvass the fate of the missing purin, it will, we think, be helpful
if we interpolate here a table (Taylor and Rose), illustrative of the
variations in uric acid excretion that attend a _purin_ as opposed to a
_purin-free_ diet.

The subject of the experiment was, for three days, fed on a purin-free
diet of milk, eggs, starch and sugar. At the end of this period a
portion of the total nitrogen (3 grams) was administered in the form of
_sweetbreads_, thymus gland, etc., with a high percentage content (0·482)
of purin nitrogen. During the succeeding four days still more (6 grams)
of the total nitrogen was replaced by sweetbread nitrogen. Subsequently
the person was placed on the original purin-free diet.

  ---------------+-------------+--------------+-------------+--------------
                 |First period.|Second period.|Third period.|Fourth period.
                 | Purin-free  |              |             |  Purin-free
                 |    diet.    |              |             |    diet.
  ---------------+-------------+--------------+-------------+--------------
  Total urinary N|     8·9     |      8·7     |     9·1     |     8·8
  Urea N and NH₂ |     7·3     |      7·1     |     7·1     |     7·05
  Creatine       |     0·58    |      0·55    |     0·56    |     0·47
  Purin N (total)|     0·11    |      0·17    |     0·26    |     0·10
  Uric acid N    |     0·09    |      0·14    |     0·24    |     0·07
  Remainder N    |     0·91    |      0·88    |     0·18    |     1·18
  ---------------+-------------+--------------+-------------+--------------

From a study of the table it will be noted that, following the
introduction of sweetbreads rich in _nucleins_, the uric acid content of
the urine markedly increased, to sink again when a purin-free diet was
substituted. But it will be seen also, as MacLeod points out, that “the
increase of uric acid accounted for less than half of the purin nitrogen
ingested. This appeared as uric acid, the excretion of purin bases being
practically unchanged.” In other words, a moiety of the bound purins,
_i.e._, nucleins ingested, appears as uric acid in the urine.


FATE OF THE UNEXCRETED PURIN

As to what becomes of that portion of the ingested purin that, so to
speak, disappears in the body, is largely a matter of speculation. As
MacCallum states, “the liberation of guanine and adenine is well in the
line of uric acid formation,” but “the fate of the pyrimidin groups,
thymine and cytosine, is still uncertain.” According to this observer,
Levene has hitherto been unable to find an enzyme which will decompose
the _nucleoside_ in which they occur, and that since they cannot form
uric acid, they are possibly excreted as _urea_ or in other forms. He
adds that only 50 per cent. of the nucleic acid nitrogen can be counted
on for the production of _uric acid_, viz., that in the guanine and
adenine groups.

MacLeod, discussing this same point, suggests that some of the
unrecovered purin may undergo decomposition in the intestine, but why so
much should, after absorption of the blood, disappear is, as he remarks,
difficult of explanation; for while _uricase_, which can decompose uric
acid, exists in the tissues of the lower animals, no such ferment is
found in man, and uric acid is excreted as such. According to MacLeod,
too, “the destroyed purins cannot be shown to influence any of the other
well-known nitrogenous metabolites of the urine.”

Lastly, Stewart, discussing the ultimate destiny of the absorbed
products of _nucleic acid_ digestion, suggests that, when undergoing
further cleavages, “they may be in part utilised for the synthesis
of nucleo-proteins, replacing those destroyed in the process of cell
metabolism;” or, that it is “possible that they may be wholly disrupted
into their components, and these again re-synthesised.”... “Finally, and
this fate is probably not long delayed in the case of the surplus of
purin compounds contained in ordinary dietaries, both the purins of the
food and the purins arising from the waste of the tissues, are for the
most part converted into uric acid and excreted in the urine.”

Also, it should be recollected that the purin bases normally found in
human _fæces_ are in part of _exogenous_ origin, and are increased in
amount after the ingestion of meat extract or thymus.


ENDOGENOUS PURINS

Even if we entirely eliminate all purin substances, by restricting the
diet to _purin-free_ foodstuffs (bread, milk, cheese, eggs and butter),
purin in the form of _uric acid_ is still excreted in the urine.

To this moiety the term _endogenous_ purin is applied; for the continued
excretion of purin on such a diet is explicable only on the view that
they are derived from the waste of the tissues, the daily “wear and
tear” of cells. In other words, it is the outcome of the katabolism of
the _nucleo-protein_ of the body tissues.


SOURCE OF ENDOGENOUS PURINS

_Is the nuclear destruction of localised or generalised distribution?_

Mares (and subsequently many other observers), having noted that,
following the ingestion of _purin-free_ protein food, a marked increase
in endogenous uric acid excretion ensued, suggested that the said
augmentation was the outcome of the “wear and tear” entailed upon the
nuclear material of the _secretory glands of the gastro-intestinal
tract_, following such intake.

The effects yielded on uric acid excretion by those antithetic drugs,
atropine and pilocarpine, certainly seem to lend colour to Mares’
hypothesis.

Following the injection of _atropine_, the rise in uric acid output, that
normally follows the ingestion of protein, was inhibited. But in sequence
to _pilocarpine_, an _excitant_ and not like _atropine_, a depressor of
secretory activity, a marked increase in uric acid excretion followed.
The contrast in response was naturally translated as striking evidence
of the important _rôle_ played by the _digestive glands_ on uric acid
excretion; in other words, it was held that the major portion of the
endogenous uric acid was the reflex of such intensified glandular action.

In opposition, however, Burian, as the outcome of his experimental
studies, maintained that a _fractional_ portion only of the endogenous
uric acid could be derived from the _nucleo-protein of the body cells_.
This, inasmuch as it would entail a far too extensive katabolism of
nuclear substance. Accordingly he propounded the view that the endogenous
uric acid in the main was derived from the _hypoxanthine_ of the
_inosinic_ acid present in _muscular_ tissue. In this connection it may
be noted that, on a diet approximating to Voit’s standard, 0·5 gram of
purin is excreted daily. This, it is calculated, is equivalent to nearly
100 grams of thymus or allied tissue, which probably far exceeds the
amount that could be gleaned from cellular katabolism.


PROTEINS AND THEIR DERIVATIVES

A comparison of the influence of _proteins_ as contrasted with that of
their digested products, the _amino-acids_, it was thought, might furnish
a clue as to the extent of which the alleged activity of the _digestive
glands_ was responsible for the increased uric acid output that followed
the intake of non-purin protein food.

Such was the supposition entertained by H. B. Lewis, M. S. Dunn, and E.
A. Doisy. Alive, moreover, to the deficiency of the older procedure in
use for the determination of small amounts of uric acid, Lewis and his
collaborators invoked the more accurate colorimetric method of Folin and
Denis (as modified by Benedict and Hitchcock).

The experiments were conducted with great care, and with as complete
control as possible of the variable factors concerned. The investigators
realised that, if any significance was to be attached to fluctuations
in uric acid excretion following the intake of proteins and their
derivatives, it was essential that accurate information be obtained as to
the extent of the _variations_ to be expected _normally_ in the subjects
when _fasting_. “Controls,” therefore, in which no food was consumed
throughout the experiments, were instituted at frequent intervals so as
to make sure that the level of endogenous uric acid metabolism was not
altered by the long-continued _purin-free_ diet.[13]

Passing now to the results obtained, it was noted that, after the intake
of three types of _purin-free_ protein food (egg white, cottage cheese,
and glidine), there ensued _a rise in uric acid output_, reaching
its maximum during the third or fourth hour after their intake. No
quantitative differences in the uric acid output after ingestion of these
three types of protein were observed; in short, the findings did but
confirm what had been repeatedly demonstrated, viz., that the _excretion
of the endogenous uric acid is increased by purin-free protein food_.


AMINO-ACIDS AND DICARBOXYLIC AMINO-ACIDS

But the further interesting fact emerged, viz., that _glycocoll_ and
_alanine_, end-products of protein digestion, also _augmented_ uric acid
excretion; moreover, this even more swiftly than _proteins_, the maximum
being reached within two hours after their intake.

In addition, like results followed the ingestion of the _dicarboxylic_
amino-acids (glutaminic and aspartic acids), the increase in endogenous
uric acid excretion being even more pronounced than with glycocoll or
alanine.

Now, it must be recalled that the _amino-acids_ represent the
_end-products_ of protein digestion. Accordingly, Lewis and his
co-workers argue that “since no digestive processes are required for
the utilisation of amino-acids, it can hardly be considered that the
_rises in endogenous uric acid_ observed following the ingestion of four
different amino-acids can be attributed to the _work of the digestive
glands_.” The effect, they held, is more probably attributable to “a
direct stimulation of the body cells by amino-acids or their katabolism
products, a stimulation of nuclear metabolism,” for it is known that
amino-acids disappear very swiftly from the _blood-stream_ to be stored
up temporarily in the _tissues_.

The question that now confronted the observers was whether the
stimulation of nuclear metabolism was an _inherent_ property of
amino-acids. If so, “_substituted_ amino-acids might be expected to exert
a similar influence.” But, if on the contrary, it was due not to the
amino-acids as such but “either to the cellular work of their katabolism
or to the intermediary products of their breakdown, a substituted
amino-acid which does not follow the normal path of amino-acid catabolism
would in all probability be devoid of the power of stimulation.”

To this end, they selected _sarcosine_ or _methyl-glycocoll_ to elucidate
the point at issue; this, inasmuch as it has been found to pass through
the organism for the most part unchanged. The result justified their
inference, for _no_ perceptible influence on uric acid excretion was
noted. Hence, on the basis of this experiment, they inferred that the
stimulation of uric acid metabolism was not an _inherent_ property of
_amino-acids_; in other words, that if an amino-acid when ingested does
not undergo disruptive katabolism, it is without effect on uric acid
excretion.

Now _deaminisation_ is the first stage in the katabolism of
_amino-acids_, yielding as products _ammonia_ and _a-ketonic_ or _hydroxy
acids_. The ammonia thus formed normally undergoes conversion into _urea_
and is excreted as such. In order to ascertain whether the _ammonia_
stimulated uric acid excretion, _ammonium chloride_ was administered,
but no rise in the uric acid output above the normal level ensued.
Also, the ingestion of _urea_ seemed to entail no appreciable increase
in the uric acid elimination; in other words, these katabolic products
of the _nitrogenous_ moiety of the amino-acids are without effect.
As to the _non-nitrogenous_ intermediary products of the katabolism
of amino-acids, _i.e._, the _a-ketonic_ or _hydroxy acids_, it was
impossible to investigate the influence of these on the endogenous uric
acid elimination.[14]

Lusk also has brought forward evidence that in the presence of
amino-acids cellular activities are intensified markedly. According to
Taylor and Rose, too, not only _nuclear katabolism_, but also _nuclear
anabolism_, may be accelerated by the presence of large amounts of
amino-acids.

Lewis and his collaborators consider that the results of their researches
militate against Mares’ hypothesis, viz., that the origin of the
increased amounts of endogenous uric acid that follow the intake of
purin-free protein stuffs is referable to _intensified activity of the
digestive glands_.

_They hold that “it can be accounted for equally well as the result of
a general stimulation of all cellular metabolism by the products of
digestion of proteins the amino-acids.”_

The recorded increases in endogenous urinary purin are, they consider,
far too great to be the outcome of the stimulation of so small a
proportion of the cells of the body as those of the digestive tract. On
the other hand, they do not deem it necessary to assume that the whole
of the endogenous uric acid is the outcome of _nuclear_ disruption,
concurring with Burian’s view, that a moiety thereof may be derived from
the _hypoxanthine_ of _muscular_ tissue.


ENDOGENOUS URIC ACID EXCRETION

The researches of Leathes and his collaborators permit the deduction that
endogenous uric acid excretion bears a definite relation to the activity
of cellular processes. Given unchanged physiological conditions, _e.g._,
muscular exercise, the amount of the endogenous uric acid excreted is,
for the same individual, fairly _constant_, and this _irrespective of
diet_; but it is not the same for _different_ individuals, even those of
identical body weight.

According to MacLeod, the endogenous excretion in an adult man fluctuates
between 0·12 and 0·20 per cent. purin nitrogen. The average daily
endogenous uric acid output of a normal adult, as stated by Walker Hall,
is about 0·5 gram, while that of a gouty individual is 0·45 gram.

Now Burian and Schur’s original contention was that, in a given
individual on a _purin-free_ diet, the endogenous purin output was
_constant_, and this despite _marked_ variations in the amount of the
purin-free food digested.

Recent researches, however, of Folin and of Hopkins and Hope, indicate
that this dictum must be modified to this extent, viz., that although it
is true that the endogenous excretion continues remarkably constant, with
_moderate_ variations in the amount of purin-free food, it is not so in
the presence of _marked_ variations.

The subject (Hopkins and Hope), after a fast of six hours, was given a
meal of bread and potatoes, and at every subsequent hour estimates were
made of the amount of _urea_ and _uric acid_ excreted in the urine.

  ------------------+--------------+--------------+--------------
                    |              |  Uric acid.  |   Amount of
        Time.       | Urea. Grams. |  Milligrams. |  urine. C.C.
  ------------------+--------------+--------------+--------------
       10-11        |      1·07    |       26     |      175
       11-12        |      1·13    |       27     |      118
       12-1 p.m.    |      1·07    |       24     |      164
        1-2 (meal). |      0·64    |       21     |       60
        2-3         |      1·12    |       22     |       43
        3-4         |      1·16    |       38     |       41
        4-5         |      0·84    |       40     |       53
        5-6         |      1·16    |       56     |       59
        6-7         |      1·20    |       39     |       56
        7-8         |      1·37    |       30     |       95
        8-9         |      1·47    |       33     |      183
        9-10        |      1·33    |       24     |      155
       10-11        |      1·33    |       23     |      180
  ------------------+--------------+--------------+--------------

It is clear from the results obtained that a very definite increase of
endogenous purin excretion ensued, and that the said increase occurred
sooner as regards _uric acid_ than urea. This bears out what Mares
demonstrated many years ago, viz., that the greatest increase in uric
acid excretion occurs in a few hours after a meal, whereas the increase
in the case of urea comes more tardily, not reaching its maximum until
some hours after.

Horbaczewski referred such increase in uric acid excretion to a digestive
_leucocytosis_; in other words, that the uric acid was the outcome of
destruction of the leucocytes, and consequent formation of purin from the
released nucleic acid. Unfortunately for this theory, the period of most
marked augmentation in uric acid excretion ensues when the leucocytes are
most in evidence in the blood-stream, not _after_ they have disappeared,
as would be the case if uric acid was derived from the purin product of
the nucleic acid liberated by leucocytic destruction. We have a parallel
instance in the case of _pneumonia_, in which it has been shown that
the elimination of uric acid and other purins is at its acme when the
leucocytes are most abundant; in other words, the highest uric acid
output coincides with the period of most marked leucocytosis, whereas
during the post-critical stage, viz., when leucocytes are being destroyed
in great numbers, the output of uric acid is very markedly lowered.
Discussing Horbaczewski’s theory in light of the above criticisms,
MacLeod suggests, “that the facts appear to indicate that the purin
substance is a metabolic product of the living leucocytes,” and not, so
to speak, the chemical outcast of their disruption and death.

Lastly, Walker Hall, discussing endogenous uric acid excretion,
emphasises the necessity of discriminating between the _uric acid_
output and the _total purin_ output. He reminds us that the actual cell
nucleins belong chiefly to the group of amino-purins, _i.e._, guanine
and adenine, and that the oxypurines, xanthine and hypoxanthine, are
intermediate products on their way to excretion, another and more
advanced intermediate product being uric acid. Now, only a proportion of
these intermediary products appears in the urine, this commonly cited to
be approximately 50 per cent.

But this, as Walker Hall states, must be taken only as a very broad
estimate, for in the same individual the output varies with the number of
conditions, not as yet fully determined. But the point most emphasised
by him is, that though “the _uric acid_ output varies considerably, the
_total purin_ output does not show similar variations; for when the
uric acid excretion wanes that of the purin bases usually rises. As a
consequence, the total purin output is more constant, less influenced by
circumstances, than the output of _uric acid_.”

This being so, we shall now pass on to consider other conditions
influencing endogenous uric acid excretion.


FACTORS INFLUENCING ENDOGENOUS URIC ACID EXCRETION

The output of endogenous uric acid excretion is influenced by (1)
Physiological conditions, (2) Pathological states, and (3) The ingestion
of certain drugs.


PHYSIOLOGICAL CONDITIONS

It is now recognised that the purin bases of the body exist not only in
the bound form (nucleic acid), but also _free_, especially in _muscular_
tissue. Also, that from such free purin bases uric acid can be readily
formed as from those liberated by the disruption of nucleic acid. Thus,
_inosinic_ acid, a nucleotid first isolated from meat extract, yields
phosphoric acid and the purin base, _hypoxanthine_. In possession of
these facts, we shall be better able to appreciate the significance of
the researches of Burian and others.

(_a_) _Muscular Exercise._—According to Burian a large increase in the
excretion of uric acid was found to follow _muscular exercise_. The same
observer also noted the presence of _hypoxanthine_ in defibrinated
blood after its perfusion through the hind legs of a dog whose muscles
had been thrown into tetanus. Moreover, subsequent to contraction, the
muscles themselves contained an increased amount of oxypurine. From these
findings Burian concluded that hypoxanthine was a product of _muscular
action_, and that this substance or its precursor, _inosinic acid_, was
an important source of _endogenous uric acid_. The uric acid thus formed
by oxidation was then partly destroyed in the liver and partly excreted
by the kidneys. But Burian noted also during activity of the muscles
that a certain amount of the _purin bases_ failed of oxidation, and
consequently a larger amount of the same, as compared with uric acid,
passed into the circulation.

Kennaway, discussing the effect of _muscular exercise_ on the excretion
of endogenous purins, noted that during unaccustomed exercise the _uric
acid output_ of the kidneys diminished, but that of the purin bases is
relatively augmented, but, on the whole, he found that the total purin
output (bases plus uric acid) was not very much increased.

Leathes and others, investigating the effects on uric acid excretion of
strenuous exercise, established the occurrence of a distinct increase.
Given that the same kind of exercise is practised on the day following,
the said increase is much less marked. If, however, some different
form of muscular activity is undertaken, another increase in uric acid
follows. It would appear, therefore, that, despite conflicting evidence,
the balance of opinion favours the view that muscular activity does lead
to increase in endogenous uric acid excretion.

(_b_) _Periodic Variations._—Leathes noted _diurnal_ and _nocturnal_
variations in the excretion of endogenous uric acid, the maximum
occurring within the early waking hours, and sinking to a minimum towards
the evening. His experiments, he held, indicated a variation in the
actual formation of endogenous uric acid at different periods of the day.
Rockwood also found that an increase occurred during the daytime, and
Pfeil, that there was a morning rise in the amount of uric acid passed.
The fact that doubt still obtains as to whether muscular exercise has any
effect on endogenous uric acid excretion, renders explanation of this
diurnal variation difficult. This especially as there are no fluctuations
in the urinary functions that could in any way account for it.


PATHOLOGICAL STATES

Endogenous uric acid is increased under certain pathological conditions.
Leathes’ recent work confirmed the view that there is an increased
production of nitrogenous waste in _fevers_. After taking a large dose
of anti-typhoid serum his temperature rose to 103° F. Experimenting
on himself, he found his output of urea, uric acid, and creatinine
all increased, but of all three _uric acid_ showed the most marked
alteration. The question now arises as to whether such is due to
increased production or diminished destruction. Some further experiments
conducted by Leathes on himself may serve to elucidate this point.
Subjecting himself for a prolonged period to cold baths, a similar
increase in his _uric acid_ output ensued. This would appear to indicate
that, through increased loss of heat, the bodily processes of combustion
were augmented to maintain the body temperature, with, as a consequence,
increased uric acid excretion.

In _leukæmia_ protein-destroying forces are at work, and the urine
contains large quantities of _uric acid_. The same is attributed to the
formation and destruction of enormous numbers of _leucocytes_, but the
urinary findings in this respect have been extremely variable. While
increased uric acid elimination has been vouched for by many authors,
some have noted increase in the _purin bases_, sometimes with, and
sometimes without increase in the uric acid; while others again have even
noted a decrease in uric acid and _phosphoric acid_ excretion.

Apart from these contradictory findings, it would appear, according to
Magnus-Levy, that in _acute_ leukæmias the relation between the number
of leucocytes and the uric acid output is most variable. Lastly, the
different types of leukæmia present differences in regard of their uric
acid output, the increase in the _myelogenous_ variety being much more
marked than in the _lymphatic_ form.

Wells, discussing these conflicting data, considers that they are but
the reflex of the “known fluctuations in the course of the pathological
processes of leukæmia; the number of leucocytes, the size of the
lymphatic organs, and the general condition of the patient all vary
greatly from time to time, often with remarkable rapidity and the
excretion of products of metabolic activity must vary likewise.”
Continuing, he observes that the enormous increase in the amount of
lymphoid tissue in the body and blood must give rise to a greatly
augmented _nuclein katabolism_, with sequential appearance of _uric
acid_, _purin bases_, and _phosphoric acid_ in the urine. This he holds
to be well demonstrated by the increased elimination of uric acid and
purin bases, together with a general increase in the nitrogen output such
as has been frequently noted in sequence to the therapeutic use of X-rays
in leukæmia, this attributable to the increased autolysis known to be
induced by X-rays.

As to this question of the relationship of _leucocytosis_ to _uric acid
excretion_, it must be borne in mind that the number of leucocytes and
the excretion of uric acid do not always vary directly. Parallel studies
of the blood and urine have shown that _leucocytosis does not invariably
accompany increased uric acid excretion_. Indeed, Hutchison and MacLeod
have recorded cases of _leucopenia_ without any reduction in the amount
of uric acid eliminated.

Also, we have to recall that on a _purin-free_ diet the amount of
endogenous uric acid is more than can come from _nuclein_ destruction
in the body. As suggested by Burian, some may be derived from the
_hypoxanthine_ in muscular tissue. In short, while nuclein disintegration
is the outstanding source of endogenous purin, yet, for the reason cited,
it cannot be regarded as the sole source, for the exact origin of all the
endogenous purin is not as yet established.

In conclusion, it would appear that some _drugs_ influence more or less
markedly the excretion of endogenous uric acid, notably, atophan; but
discussion of these will, we think, be best postponed to the section
dealing with the medicinal treatment of gout. Meanwhile we shall proceed
to consider the vexed question of the formation within the organism of
uric acid by synthesis.


SYNTHETIC FORMATION OF URIC ACID

Birds eliminate most of their nitrogen in the form of uric acid, and,
undoubtedly, in their instance synthetic formation of uric acid in the
liver takes place on a large scale. Thus, when blood containing ammonium
lactate is perfused through the liver of the goose, an increase in the
uric acid content of the blood occurs. Also the ingestion of lactic,
pyruvic and other organic acids leads to augmented output of uric acid;
in short, it is generally agreed that in birds _synthesis_ is the chief
mode of formation of uric acid, homologous with the formation of _urea_
in the liver of mammals.

If this be true of birds, on the other hand, _splitting_ and _oxidation_
of _nucleins_ is in _mammals_ the most important source of uric acid,
but there is evidence that it cannot all be accounted for in this way.
As before remarked, the old belief that purin excretion remains almost
constant on a _purin-free_ diet, despite great variations in the amount
of the ingests, is not strictly true. Thus, using swifter and more
reliable methods for the estimation of nitrogenous metabolites, Folin
noted, on an absolutely purin-free diet, that an increase in purin
excretion ensued, given _marked_ variations in the intake of food. Again,
the Dalmatian dog, as we have seen, excretes uric acid in his urine.
S. R. Benedict was therefore able to demonstrate that a very distinct
increase in his uric acid output ensued in sequence to increase in the
amount of his _non-purin_ food; moreover, that even when such non-purin
foods were continued for a year, “the total amount of uric acid excreted
was at least ten times greater than could have come from the traces
unavoidably included in the food” (MacLeod).

Also Ascoli and Izar, experimenting with dog livers, noted on incubation
thereof and passage through the same of oxygen that the uric acid
disappeared; but on the substitution of carbon dioxide an accumulation
thereof ensued. Wells, however, was unable to confirm this re-synthesis
of uric acid by dog livers, and Spiers also failed to corroborate their
findings.

On the other hand, there is evidence pointing to the fact that a certain
small percentage of synthetic formation does take place in the organism.
Thus certain chemical substances, and these not purin, do cause an
appreciable though slight increase in the purin excretion of mammals,
and a very marked augmentation of the same in birds, viz., _lactic_,
_tartronic_ and _B-oxybutyric acids_.

But, as MacLeod, discussing these experimental and clinical findings,
observes, there are to hand even more direct proofs that _purin
synthesis_ occurs in mammals. Thus, as McCallum has pointed out, we
cannot escape the admission that young mammals are able to synthetise
the purins essential for their growth, and this from food containing no
purin, _e.g._, milk. Again, prior to incubation, a hen’s egg contains
practically no nucleic acid, whereas after development its content in
the same increases by great strides. The eggs of insects, too, with the
progress of development, amass purin very rapidly.

Again, Miescher noted long since that salmon, on leaving the sea
to ascend rivers for the object of spawning, have at that time
well-developed muscles; but on arriving at the upper reaches, marked
muscular wasting ensues, while the testes undergo enormous enlargement.
MacLeod, reflecting on these observations, argues that, “as the fish
takes no food during the migration, there must be conversion of the
protein of the muscles into the cellular tissue of the sexual glands,
and _nucleic acid_ must be produced.” MacLeod’s conclusion is that
“Purin synthesis undoubtedly occurs in the mammalian body, but it is
difficult to recognise in metabolism investigation, because it is a
slow continuous process ... whether or not changes in the activity of
purin synthesis occur in conditions of disease, is a question which
awaits investigation.” Lastly, the opinion of most authorities is that,
while they concede the possibility of synthetic formation, the amount
of uric acid produced in this manner is negligible, and that by far the
most important mode of formation in mammals is by the _splitting_ and
_oxidation_ of _nucleins_; in other words, that uric acid in the main
is derived from the _amino-purins_ by _deaminisation_ and subsequent
oxidation, and from the _oxy-purins_ directly by oxidation.




CHAPTER VIII

FORMATION AND DESTRUCTION OF URIC ACID


The chemical structure and sources of uric acid having been dealt with,
we are now in a position to resume our narrative, and to take up the
thread at the point when Horbaczewski revealed the derivation of uric
acid from nucleic acid. It now devolves upon us to scrutinise more
narrowly the process by which the formation of _uric acid_ from _nucleic
acid_ is achieved. Incidentally, it will not be unprofitable to note, if
only briefly, the steps by which the necessary expansion of our chemical
and physiological knowledge of nucleic acids has been acquired.

As may be imagined, the primary difficulty was to prepare nucleic acids
of such purity as admitted of their elementary chemical analysis. The
necessary researches were to a large extent confined to two types of
nucleic acid, one derived from _yeast_, and the other from the _thymus
gland_; in other words, to representatives of the only two nucleic acids
in nature, one derived from the nuclei of _animal_ cells, the other from
the nuclei of _vegetable_ cells.

A feature common to nucleic acids of animal and vegetable origin is
that, on hydrolysis with boiling mineral acid, they yield two purin
derivatives, _guanine_ and _adenine_, and a pyrimidin derivative,
_cytosine_. From thence as regards their remaining constituent elements
they display distinctions. Thus animal nucleic acids yield _thymine_, and
contain a _hexose_ group in their molecule. On the other hand, vegetable
nucleic acids give forth _uracil_ and possess a _hexose_ group.

To sum up, _nucleic_ acid is a chemical complex, made up of phosphoric
acid with purin bases, pyrimidin bases and carbohydrate radicles.
Moreover, nucleic acids, whatever their source, show a striking
similarity in structure, containing always two amino-purins (adenine
and guanine), two pyrimidines (either cytosine and uracil, or cytosine
and thymine), and a carbohydrate. Now, while _purin bases_ are always
present, yet, in respect of their _carbohydrate_ group, nucleic acids
display variations; this, according as they are of animal or vegetable
origin. If the former, the carbohydrate group is a _hexose_ (contains six
carbon atoms) with _thymine_. If the latter, it contains _pentose_ (five
carbon atoms) with _uracil_.

The constancy in the content of the various nucleic acids is such that
Levene and Jacobs have felt justified in putting forward the following
provisional formula as to the constitution of a _nucleic acid_ of animal
origin.

[Illustration: STRUCTURAL FORMULA OF NUCLEIC ACID]


DISTRIBUTION OF THE ENZYMES

The enzymes responsible for the disruption of the _nucleic acid_ complex
are not to be found in all the body tissues. Moreover, the distribution
of the enzymes in the various organs and tissues varies in different
species of animals. Of the various organs the _liver_, _spleen_,
_thymus_, and _pancreas_ more particularly contain enzymes in abundance.
As to their varied location in different animals, it may be noted that
the enzyme responsible for the oxidation of _xanthine_ into _uric acid_,
viz., _xanthine-oxidase_, is found in man only in the liver. In other
animals, also, it is of localised distribution, being as a rule only
found in the liver or in the liver and kidney. The dog, however, appears
to be an exception, _xanthine-oxidase_ being found in a variety of its
tissues.

_Adenase_, the deaminising enzyme, is not to be found in any organs
in man. Neither does it exist in any of the tissues of the rat.
Consequently, if _adenine_ be injected subcutaneously in rats, it
undergoes oxidation, without abstraction of its amino group.

On the other hand, _guanase_, also a deaminising enzyme, is in man to be
detected in the _kidney_, _lung_, and _liver_, but not in the pancreas or
spleen. In the pig, however, guanase is lacking, and its absence no doubt
explains why deposits of guanine may occur in the muscles constituting
the so-called _guanine gout_ met with in swine. It is worthy of note also
that in pigs’ urine the content of purin bases exceeds that of uric acid.

To sum up, in man the enzyme, _xanthine-oxidase_, which forms uric acid
from xanthine, is located chiefly or exclusively in the _liver_. This,
of course, represents the _final_ stage of purin metabolism, but the
antecedent chemical processes involved in the disruption of nucleic acids
are initiated by the action of enzymes in the _intestinal juices_ and
_wall_, and to a consideration _seriatim_ of these changes we now proceed.


STAGES IN DISRUPTION OF NUCLEIC ACID

As might be expected from the complex structure of the nucleic acid
molecule, a number of ferments are concerned in its disruption. The
gastric and pancreatic juices contain not a trace of any enzymes. Thus,
when _nucleo-protein_ is subjected to the gastric juice a moiety of
protein is readily split off and hydrolysed to peptone and other products
of proteolysis.

But the nuclein element remains unacted upon until it comes under the
action of the pancreatic juice. Hydrolysis then ensues, and the ingested
nuclein is broken down into nucleic acid and protein. The _nucleic acid_
remains unaffected by the pancreatic juice, but, coming in contact with
the _succus entericus_, it undergoes partial decomposition through the
action of a ferment called nuclease or _nucleic_-acidase. Under its
disruptive effect the nucleic acids or _poly-nucleotides_ are further
split up into groups known as _nucleotides_. The two _pyrimidine_
nucleotides split off and undergo no further change. But, through the
action of another ferment, _nucleotidase_, the _purin_ nucleotides are
further decomposed to yield _nucleosides_ (substances of the glucoside
class made up of a combination of a purin base with a carbohydrate group
of the nucleic acid with which also phosphoric acid is linked).

No further stage in hydrolysis of nucleic acid occurs in the intestine,
but the _nucleosides_ are again in turn split up after reaching the
tissues, particularly in the _spleen_, _liver_, and _thymus_. This,
under the action of specific enzymes, _nucleosidases_, which succeed in
breaking the nucleosides down into the so-called “building stones” of
the _nucleic acid molecule_, phosphoric acid group, carbohydrate group,
pyrimidine and purin bases, especially adenine and guanine. The adenine
and guanine thus formed are, by the action of the ferments _adenase_
and _guanase_, converted and, by the removal of their amino group,
transformed, adenine into hypoxanthine, and guanine into xanthine, thus:—

    C₅H₅N₅ + H₂O = C₅H₄N₄O + NH₃;   C₅H₅N₅O + H₂O = C₅H₄N₄O₂ + NH₃
    Adenine.      Hypoxanthine.       Guanine.        Xanthine.

By the action of oxidases also present in the tissues hypoxanthine is
changed into xanthine and xanthine into uric acid (trioxy-purine), this
by a specific ferment xanthine oxidase.

    C₅H₄N₄O       O—C₅H₅N₄O₂;   C₅H₅N₄O₂ O    C₅H₄N₄O₃
    Hypoxanthine.   Xanthine.   Xanthine.    Uric acid.

[Illustration: SCHEME ILLUSTRATING THE PROBABLE STAGES IN THE PASSAGE OF
PURIN THROUGH THE BODY (WALKER HALL)]

It will be seen that the disintegration of nucleic acid involves many
stages, and its complexity is such that we make no apology for drawing
upon the masterly monograph of Walter Jones for further elucidation
of this intricate question. In relating the history of nucleic acid
in the animal body Jones has found it convenient to introduce certain
terms wherewith to designate the various elements of the _nucleic
acid molecule_. Thus, the molecule in its entirety is termed a
_tetra-nucleotide_. The cleavage of this complex is initiated by the
action of two specific enzymes. Through their agency the tetra-nucleotide
is first cloven into two _di-nucleotides_, which immediately divide up
into four _mono-nucleotides_. These ferments are:—

(1) _Phospho-nuclease_ (which splits off the phosphoric acid radicle,
leaving a nucleoside, guanosine or adenosine).


    H₂PO₄—C₅H₈O₃—C₅H₄N₅O + H₂O----->H₃PO₄ + C₅H₉O₄—C₅H₄N₅O
          Guanylic acid.    Phospho-nuclease.      Guanosine.

(2) _Purin-nuclease_ (which splits off the purin radicle, viz., separates
out both phosphoric acid and carbohydrate groups, leaving free purin
bases).


    H₂PO₄—C₅H₈O₃—C₅H₄N₅O + H₂O----->H₂PO₄—C₅H₉O₄ + C₅H₅N₅O
          Guanylic acid.   Purin-nuclease.          Guanine.

Now, in sequence to either of the foregoing cleavages by the phospho- or
purin-nucleases another set of enzymes come into the field. Under their
_deaminising_ effect the amino group is abstracted, with the formation
of either free _oxy-purins_ or oxy-purins still bound in glucoside-like
combination with sugar.

If the oxy-purins are free, the following is the reaction:—


    C₅H₅N₅O + H₂O------>C₅H₄N₄O₂ + NH₃
    Guanine.   Guanase.  Xanthine.

Should, however, the guanine glucoside be present:—


    C₅H₉O₄—C₅H₄N₅O + H₂O------>C₅H₉O₄—C₅H₃N₄O₂ + NH₃
    Guanosine.   Guanosine-deaminase.   Xanthosine.

In the latter instance a hydrolysing enzyme, _xanthosine-hydrolase_, by
its action, splits off xanthine. We see, therefore, that by either route
the end-product is the same. Following a like series of changes, the
adenine radicle is transmuted into hypoxanthine. This either directly by
the action of adenase:—


      C₅H₅N₅ + H₂O------>C₅H₄N₄O + NH₃
    Adenine.   Adenase.  Hypoxanthine.

or indirectly through the agency of adenosine-deaminase, the
hypoxanthine-glucoside (inosine) is formed, and subsequently the
hypoxanthine is split off.

Xanthine and hypoxanthine are, therefore, now to hand, and given the
presence of oxygen, their oxidation to _uric acid_ ensues:—


    C₅H₄N₄O + O---------------------> C₅H₄N₄O₂
       Hypoxanthine.    Hypoxanthine-oxidase.       Xanthine.

    C₅H₄N₄O₂ + O----------------->C₅H₄N₄O₃
           Xanthine.        Xanthine-oxidase.      Uric acid.

Now, in man and the anthropoid apes, _uric acid_ is the end-product of
_purin_ catabolism. In contrast therewith in most mammals only a minimal
amount of the exogenous or endogenous purins escapes in the urine as uric
acid. Most of it undergoes further oxidation into _allantoin_,[15] this
change taking place in most mammals chiefly in the _liver_. According to
Schittenhelm, if nucleic acid be given to dogs, pigs or rabbits, from
93-95 per cent. thereof appears in the urine as allantoin, and only 3-6
per cent. as uric acid, and 1-2 per cent. as purin bases.

[Illustration: DISRUPTION OF NUCLEIC ACID MOLECULE (AMBERG AND JONES).]

In man, as in most mammals, uric acid is formed chiefly in the _liver_
from purins, and in the preceding table Amberg and Walter Jones
schematically represent the various steps by which disruption of the
nucleic acid molecule is attained, and uric acid formed.


DESTRUCTION OF URIC ACID

_Uricolysis_, or the destruction of uric acid, is, in most mammals,
achieved through the agency of the oxidising enzyme _uricase_, which
oxidises uric acid to _allantoin_. Consequently, in their instance,
purin bases, ingested as such or set free in the tissues, appear in the
urine, not as uric acid, but in the form of _allantoin_. On the other
hand, both in man and in the anthropoid apes, this particular enzyme
uricase is absent. In accordance therewith, only a trace of allantoin is
to be found in the urine of man and the higher apes, while in the lower
animals, _e.g._, dogs, pigs, and rabbits, a large proportion of the purin
excretion assumes this form.

Now, the absence of _uricase_, in _man_, is held to be proved by the
fact established by Wiechowski and others, viz., that uric acid, if
_injected subcutaneously_, may be almost wholly recovered in the urine,
and moreover, unchanged. On the other hand, the total excretion of uric
acid and the other purin bodies by no means tallies exactly with the
amount of the uric acid ingested as purin bases in the food and that
produced from the tissues; in other words, it has been found that,
when given by the mouth, _nucleic acid_ or _purins_ are by no means
_quantitatively_ excreted in the urine, even though not only _uric acid_,
but also _allantoin_ and the _purin bases_, are included within the
estimate. According to most experiments, a considerable proportion of the
purin-nitrogen intake, about 50 per cent., is excreted as _urea_.

The question then arises as to what becomes of that moiety of the _food
purins_ which fails to appear in the urine as _uric acid_. Now the amount
of allantoin that appears in the urine is negligible. Moreover, Ackroyd,
having shown that the organism cannot destroy allantoin, it is possible
that the minimal amounts excreted thereof in the urine are all derived
from the food.

Accordingly, if, as experimental feeding with _purins_ or _nucleic acid_
appears to indicate, purins are destroyed in the body they “pass through
some other route than allantoin, and possibly, that part of the purin
which is destroyed does not pass through the stage of uric acid.” Such is
Wells’ opinion, and he reminds us that _in vitro_ the destruction of uric
acid can be attained by other routes than through allantoin. Thus, it can
be broken down into glycocoll, ammonia, and CO₂, or by another method of
disintegration it furnishes first alloxan (C₄H₂N₂O₄), then parabanic acid
(C₃H₂N₂O₃), which in turn yields oxalic acid and urea.

But while it is probable that there is more than one way in which uric
acid can be decomposed in the body, nevertheless there is, according to
Wells, no evidence that either of the alternative routes above suggested
is ever affected in the animal body. In this _impasse_ Siven suggests the
further possibility, viz., that the moiety of the food-purins which fail
of recovery from the urine undergo partial destruction in the intestine
by _bacteria_.

Stewart, however, in his “Physiology,” discussing _uricolysis_, maintains
that a considerable destruction of uric acid and other purin bodies
goes on in the body and mainly in the _liver_. He reminds us that when
uric acid is heated in a sealed tube with strong hydrochloric acid, it
breaks down into glycin, carbon-dioxide and ammonia, and he maintains
that “there are grounds for believing that a similar decomposition takes
place in the body, and that the products are then transformed into urea
in the _liver_”; this, through the agency of a special ferment called the
_uricolytic enzyme_.

Also, Flack and Hill, discussing the metabolism of _nuclein_, hold that
some of the uric acid thus formed may be transmuted into urea by an
uricolytic ferment present in the _liver_, muscles, and _kidneys_. This
same agent they consider “probably destroys a considerable amount of the
uric acid formed in the body. Indeed, uric acid, even when given in the
food, owing to the presence of this enzyme, causes no increase in the
uric acid output of the body.”

On the other hand, Wells, discussing the destruction of uric acid,
observes that repeated investigations show “that the tissues of man have
no power whatever to destroy uric acid _in vitro_; the earlier reports of
positive uricolysis undoubtedly being erroneous.” His final conclusion,
after weighing all available evidence, is that it is highly probable that
in man “most of the purin absorbed from the food, and practically all
the purin from cell metabolism, is converted into uric acid and excreted
as such.” MacLeod, however, reflecting on the fact that uric acid is not
destroyed when extracts of the organs are incubated at body temperature
with uric acid or its precursors, bids us bear in mind that, “although
the uric acid is thus shown not to be destroyed _in vitro_, it may
nevertheless be destroyed in the living animal.”

We see, therefore, that the question, Whether uric acid can undergo
destruction in the human body? is still a matter of dispute, and must,
pending further investigation, remain _sub judice_. Still, despite the
conflict of evidence, clinicians have felt justified in assuming that one
of the factors in the genesis of gout may be an entire _absence_ or a
_diminution_ in the amount or activity of this _uricolytic ferment_.

But the awkward fact remains that all researches up to date have failed
to establish the presence in the human body of any enzyme which can
decompose uric acid. Should, therefore, future investigators place beyond
the reach of cavil the claim that no _uric-acid-destroying enzyme exists
in the body_, it would seem that, _ipso facto_, man, through lack of this
capacity for rapid oxidation of uric acid, is, by this same disability,
rendered a potential victim of _uric acid retention_ and _deposition_.

Elucidation of this vexed point seems more probable in view of the
striking discovery recently made by R. Benedict, viz., that in one
particular breed of dog, the Dalmatian, _uricase_ is wholly absent. In
respect of this _lack of a uric-acid-destroying ferment_, the Dalmatian
breed of dog has a _purin_ metabolism apparently identical with that of
man.[16] Thus, if fed on a purin-free diet, he passes large quantities of
uric acid, and if the latter be injected subcutaneously, elimination in
quantity as such ensues; this, in striking contrast to what obtains in
all other animals in whom, as before noted, uric acid is mostly oxidised
to _allantoin_ before excretion. Now, as MacLeod observes, investigation
into the metabolism of nucleic acid has, in man, been hampered greatly,
in that the absence of uricase from his tissues, prior to Benedict’s
discovery, rendered experimental researches on the lower animals
valueless. But, in light of the above revelation later by R. Benedict, it
may reasonably be hoped that in the near future our knowledge as to the
location and nature of the intermediary chemical processes occurring in
the metabolism of nucleic acids may be materially clarified.




CHAPTER IX

URIC ACID IN RELATION TO GOUT


It will be recalled that at the close of our chapter on Pathogenesis we
referred to the growing scepticism of Garrod’s views as to the pathogeny
of gout. Still, if we except Edward Liveing’s pertinent observation that
_uricæmia_ was not peculiar to gout, naught, save alternative hypotheses,
unsupported by pathological data, was advanced. Consequently, Garrod’s
facts never being seriously called in question, his position remained
unassailable, until, in the year 1898, his original observations as to
the lowered alkalinity of the blood in acute gout, and the increased uric
acid content thereof during the same, were definitely contradicted by
Magnus Levy.

Working with more modern and more reliable methods of technique, this
observer, in a series of seventeen cases of acute gout, found no evidence
of any lessening in alkalinity of the blood or of any augmentation of its
uric acid content as compared with the inter-paroxysmal period.

Again, as to Garrod’s claim that there was a diminished excretion of uric
acid during the attack, this also, while supported by Minkowski, was
called in question by Pfeiffer, Levy, and Badt, who found the reverse to
be the case, _i.e._, a notable increase in the excretion of uric acid
during the paroxysm.

These results were again in 1900 confirmed by Chalmers Watson. An
exhaustive study of a series of cases of _acute gouty polyarthritis_
convinced him that:—

    (1) The alkalinity of the blood is not diminished during the
    attack.

    (2) The excretion of uric acid is not lessened during the
    paroxysm, but the reverse; there is, therefore, no ground for
    the supposition that there is a temporary diminution in the
    capacity of the kidneys to excrete uric acid.

    (3) The amount of the uric acid in the blood is not greater
    during the attack than in the intervening period, and if these
    points be accepted, we must start _de novo_ in search of the
    cause of the acute paroxysm.

The iconoclastic revelations of the foregoing researches may well form a
preface to our discussion of gout from the triple aspect of:—

    (1) Uric acid excretion.
    (2) Uricæmia.
    (3) Uratosis.


URIC ACID EXCRETION IN GOUT

The earlier investigations as to the behaviour of uric acid in the
organism were necessarily restricted to the noting of any variations in
the uric acid output in the urine. That the findings and, alike, the
deductions proved bewilderingly contradictory is not to be marvelled
at when we recall the many factors that govern the amount of uric acid
excreted in the urine.

How fallacious, it now transpires, were the assumptions based upon the
mere uric acid output in the urine, and how little understood even to-day
the many conditions that determine its variations.[17] But, fortunately,
we can now to some extent control and review our urinary findings in
light of the uric acid content of the _blood_. But we anticipate, and
meanwhile let us confine our discussion to the variations in uric acid
excretion that occur in _gout_, and this as revealed by more modern
students of the disease. This will be more conveniently dealt with if
we consider first the oscillations in uric acid output in relation to
_acute_ attacks of the disorder, and subsequently the same as met with in
its more _chronic_ manifestations.


URIC ACID VARIATIONS IN ACUTE GOUT

Generally speaking, there appears to be a consensus of opinion on the
following points:—

    (1) That in the _intervals_ between _acute_ attacks of gout the
    elimination of uric acid lies within the normal limits, but that

    (2) For one or two days _prior_ to an acute attack an
    appreciable _decline_ in the output of uric acid occurs. This,
    however, is not so marked as the subsequent

    (3) _Increased_ output of uric acid _during_ the acute attack.
    According to Magnus Levy the increase may reach from 0·3-0·5
    gram, daily, and more, and may sometimes last for a week or
    even two.

    (4) Following attack a tardy decline in uric acid output to
    former level.

To sum up, during an attack of _acute_ gout the uric acid output stands
at a relatively low level between the paroxysms. But one or two days
before the oncoming attack a _diminution_ in uric acid output ensues.
In contrast with the outbreak of the attack, the uric acid excretion
_increases_ markedly, this enduring for a week or more, when the output
again _declines_. The augmented output _during_ the paroxysm is more
constant than the diminished excretion antecedent thereto. Now, while it
may be taken that the foregoing variations in _uric acid output_, prior,
during, and subsequent to, acute attacks, obtain as a general rule,
such behaviour is not invariable; for, unfortunately, as Wells reminds
us, instances are met with in which “the uric acid excretion shows no
variation from that of normal persons.”


URIC ACID VARIATIONS IN CHRONIC GOUT

It must never be forgotten that the _elimination of uric acid_ displays
wide _variations_, this even when the subject under investigation is on
a _constant_ diet. Consequently, as Folin has pointed out, “even in the
case of gout, which is distinctly associated with uric acid, it is an
extremely difficult matter to prove by means of urine analyses that the
uric acid elimination is not entirely normal.” And he adds, “If it had
not been for the fact that uric acid, because of its insolubility, is so
easily found in the joints, it would unquestionably have been a very long
time before any definite relationship between uric acid and gout could
have been established.”

None can gainsay the truth of these reflections, for, when placed on
a fixed diet, the uric acid output in the victims of _chronic gout_
differs but little from that of _normal_ individuals on a similar regime;
save in this respect, that, following the intake of _purin-containing_
substances, the period of augmented uric acid excretion that ensues is
_prolonged_ as compared with the normal.


RETARDED EXOGENOUS URIC ACID OUTPUT

In 1901 Vogt showed that in gout the excretion of exogenous purins was
not only delayed but diminished. Giving simultaneously to a _gouty_
subject and a _healthy_ individual a diet rich in purins, he found that,
in the former, _retention_ and _delayed excretion_ of _purins_ ensued.
Vogt’s findings were confirmed by Reach, Soetbeer, Pollak, Mallory, and
others.

Brugsch and Schittenhelm also observed that, following the intake of
purin-containing substances, the exogenous uric acid excretion was
_retarded_ and _reduced_; in other words, the percentage of exogenous
nitrogen excreted as uric acid nitrogen is less than in normal
individuals, although the increased elimination extends over a longer
period of time.

On the other hand, Walker Hall finds that, though there is _retardation_,
there is _no diminution_ in the output in gouty subjects. Thus he states:
“When an adult takes a meal consisting of half a pound of beef and a
quarter of a pound of sweetbread, containing about 0·620 gram purins, the
moiety which usually occurs in the urine, say 0·300 gram, is not fully
excreted until 6-10 hours have elapsed. When a similar meal is taken by
a gouty individual the full 0·300 gram is eliminated, but the rate of
output is delayed, some 48-72 hours being necessary.”

The same observer states that, given _intravenous_ injection of acid
into a _normal_ man, its elimination is spread over several days, and
the total amount injected fails to appear in the urine. But if the
injection be administered during a course of _atophan_, then the uric
acid excretion is completed within twenty-four hours, and the whole
amount injected can be recovered from the urine. Now if in a _gouty_
subject the same method of procedure be adopted, the sequence of events
is precisely similar, and like results have been reported, following the
administration of _sodium salicylate_ to vegetarians of five or more
years’ standing. To sum up, the above findings would appear to indicate
that:—

    (1) A gouty subject can excrete exogenous purins as adequately
    as a normal man, but he takes longer to do so.

    (2) If the extra purins be taken during a course of atophan,
    even this departure from normal is obliterated, _i.e._, the
    customary delay in excretion is obviated.[18]

But, unfortunately for the diagnostic valency of this symptom in gout,
viz., _retarded exogenous purin output_, it has not been found to be
_invariable_. Thus Magnus Levy has shown that, in some instances of gout,
the elimination of exogenous purin is neither reduced nor protracted.
Pratt, too, has confirmed this observer’s findings, while, as we shall
see later, this authority, also McClure, Mallory, and others, have placed
on record the still more disconcerting fact, viz., that a diminished and
retarded output of exogenous purin is _not peculiar to gout_.

The inference then would appear to be that:—

    (1) Reduction and retardation of the excretion of exogenous
    purin, though common in gout, is not invariable.

    (2) The same is not peculiar to gout, but occurs in other
    disorders.

    (3) Its diagnostic valency, as a characteristic feature of
    gout, is correspondingly depreciated.


LOWERED ENDOGENOUS URIC ACID OUTPUT

As a rule, gouty subjects, on a _purin-free_ diet, excrete less
endogenous uric acid than _normal_ persons. Thus, according to Walker
Hall, the average daily endogenous urinary uric acid output of a _normal_
adult is about 0·5 gramme, while that of a gouty subject is about 0·45
gramme. Brugsch and Schittenhelm hold that in about 80 per cent. of cases
the average endogenous excretion is lower than normal.[19]

According to these same observers, “the maximum fluctuation during
attack-free periods was at first believed to be less than in the normal
cases; more recent examinations, however, have shown that in the
same case of gout there may be _periods of high, and periods of low,
endogenous uric acid excretion_.” These variations, they hold, are not to
be accounted for by either mild or severe attacks of gout, for they occur
in the _attack-free_ period.

Again Laird, investigating the elimination of endogenous uric acid in a
case of _chronic_ gout, noted that the output thereof was _sub-normal_,
and, as Brugsch and Schittenhelm observed, the same presented marked
_variations_. The leucocyte counts he found normal, but the phosphorus
output and the acidity were sub-normal. Bloch again, while he agrees
that endogenous purin excretion is usually below the average in _gouty_
subjects, found that the output thereof is at its minimum before an acute
attack of gout.

The foregoing observations would suggest that the _retention_ or delayed
excretion of uric acid applies both to _exogenous_ and _endogenous_
purins. But, when we come to analyse the foregoing findings as to
the variations in uric acid output, both in acute and chronic gout,
one feels inclined to agree with O. Folin, “that the clinically
useful contributions obtained by _urine analysis_ have not been very
numerous.” Thus we cannot, on the basis of the _variations_ in _uric
acid excretion_, presume to diagnose gout; in other words, if we take
_urine analysis_ alone, it is extremely difficult to prove that the uric
acid elimination in gout is really and truly abnormal. Our uncertainty,
moreover, is the more pronounced when we realise that in some cases
of _rheumatoid arthritis_, etc., there is a disturbance of _purin_
metabolism which in some of its features is reminiscent of that obtaining
in typical gout. But, before proceeding to discuss this interesting
resemblance, it will, we think, be convenient here to recall that the
obliquities in metabolism found in gout are not wholly restricted to
_uric acid_.


OTHER ANOMALIES IN EXCRETION IN GOUT

As Levene and Kristeller have shown, side by side with the delayed
excretion of ingested purins, there occurs also a tardy elimination
of the other nitrogenous products of protein food. Vogt observed that
fluctuations in nitrogen retention and nitrogen loss are quite typical
of gouty subjects. As to the why and wherefore, however, of this
variability, it remains a mystery. Nor do we know the form in which the
nitrogen is retained, though Vogt maintains that the uneliminated moiety
takes the form of purin bodies. According to Brugsch, it is during the
acute attacks of gout that the nitrogen loss reaches its zenith, and he
suggests that the nitrogen retention in the inter-paroxysmal periods is
in part compensatory. On the other hand, the gain in weight that ensues
is not adequate to account for the sum total of the nitrogen retention;
while, as before observed, in gout there occurs, not only retarded
elimination of exogenous purins, but also of other nitrogenous products
of protein food. Yet, according to Heffter, the ratio of _purin bases_ to
uric acid is unaltered in the urine of gouty subjects.

Again, all _nucleins_ contain a _phosphoric_ acid group, and
Futcher found that the curve of the uric acid output ran in a
striking parallel with that of phosphoric acid. But the attempts of
subsequent investigators to show that the two end-products of nuclein
disintegration—uric acid and phosphoric acid—go hand-in-hand prove
contradictory. Hence Wells, in regard to phosphoric elimination, observes
that, “it seems probable that it shows no characteristic alterations
in gout.” Lastly, we will recall to the reader that in the chapter on
protein metabolism it was pointed out that the _amino-acids_, especially
_glycocoll_, are found in excess in “gouty” urines.

In conclusion, it must, we fear, be admitted that the results of
_urinary analyses_ have proved insufficient of themselves to unravel the
intricacies of metabolism in gout, and, after a brief digression, we
shall proceed to ascertain whether, on the other hand, chemical analysis
of the _blood_ by modern methods can in any way shed further light on
this obscure problem.


PURIN METABOLISM IN OTHER DISORDERS

Working at the Research Hospital for the Study of Special Diseases at
Cambridge, Strangeways (1910) commented on the striking resemblance that
obtained between certain cases of so-called _rheumatoid arthritis_ and
gout, as evidenced by X-ray findings and section of the joints. Their
similitude in these respects suggested that the nature of the apparent
kinship of the two disorders might be elucidated by a study of _purin
metabolism_ in instances of rheumatoid arthritis.

To this end Ackroyd studied the purin metabolism in eleven persons, the
victims of rheumatoid arthritis. His conclusion was that there was no
important variation from the normal. To quote his own words, he states
that “it may be (1) completely normal, or (2) while normal as regards
endogenous excretion, the period of increased uric acid excretion which
follows the administration of hypoxanthine may be prolonged for more than
four days. It is more likely that this effect is individual, than that it
is characteristic of any particular form of the disease, excepting those
cases in which the prolongation is accompanied by active manifestation of
the disease.”

W. J. Mallory, critically analysing Ackroyd’s cases, points out that he
used only _hypoxanthine_ in his studies; also that, while _hypoxanthine_
has this advantage, that it is of definite and known chemical
composition, furnishing a known quantity of basic nitrogen, it labours
under this drawback: “It is by simple oxidation converted into uric acid,
and probably calls into action only a limited part of the ferment system
concerned in the formation of uric acid.” As a consequence, therefore,
the amount of information on metabolism that can be gleaned through its
usage is more restricted than if _nucleinic acid_ were invoked in its
place; for this substance, on the other hand, calls into action all the
various enzymes concerned in the disruption of nuclein or nucleic acid.

Alive to these advantages, Mallory, in addition to hypoxanthine, used
_nucleinic acid_ in his investigations of purin metabolism in a series of
eight “undoubted cases of so-called rheumatoid arthritis.” The value of
the inclusion of nucleinic acid is revealed by the fact that some of the
cases, when given exogenous purin in the form of _hypoxanthine_, showed
no deviation from the normal. On the other hand, when given _nucleinic
acid_, a prolongation of the period of increased uric acid excretion
ensued; this even though the total amount of basic nitrogen in nucleinic
acid is less than in hypoxanthine. Thus 4 grams of nucleinic acid have
0·2632 gram of basic nitrogen, while 0·75 gram hypoxanthine has 0·309
gram of basic nitrogen.

Apart from his own series of cases, Mallory analysed those of other
observers, and his conclusions are as follows: “Of nineteen cases of
rheumatoid arthritis in which the purin metabolism has been studied
by three different observers, nine cases, or 47·3 per cent., show a
marked variation from the normal in their reaction to purin-containing
substances while they are on a purin-free diet.

“In these cases the period of increased uric acid excretion which
follows the administration of purin-containing substances is much
_prolonged_. Following the administration of purin-containing substances,
a considerable number of cases suffer from attacks of _sub-acute
arthritis_, accompanied in some cases by an increased uric acid
excretion.”

It will be seen that in virtue of:—

    (1) The prolongation of the period of exogenous uric acid
    excretion, and

    (2) Increased uric acid excretion during attacks of sub-acute
    arthritis,

certain cases of _rheumatoid arthritis_ manifest a certain resemblance to
gout, though, as Mallory remarks, “other features characteristic of that
disease are lacking.”

It may be observed that the attacks of _sub-acute arthritis_ that ensued
in rheumatoid subjects followed the administration of _hypoxanthine_,
as shown in Ackroyd’s series. That this reaction to exogenous purin
is suggestive of a relationship between rheumatoid arthritis and gout
derives colour from the fact that it has been repeatedly induced in
_gouty_ subjects by the same means. Thus, Brugsch and Mallory (1910),
after giving 0·5 gram of hypoxanthine to a gouty patient, noted a typical
outbreak of gout. Again, Brugsch and Schittenhelm, in the same year,
reported attacks of arthritis following the administration of _nucleinic_
acid to gouty subjects.

Another feature worthy of note is that, in the cases of _rheumatoid
arthritis_ investigated by Ackroyd and Mallory, the percentage of
exogenous purin nitrogen excreted as uric acid nitrogen largely exceeds
that observed in any case of _gout_ available for comparison by these
authors.

Mallory’s final conclusions were that “there seemed to be sufficient
data to show that, in certain cases of so-called rheumatoid arthritis,
the purin metabolism is not normal. Whether these cases are real gout,
or only resemble that disease in certain features, must be determined by
further studies.”


PURIN METABOLISM IN CHRONIC ALCOHOLISM AND PLUMBISM

Quoting from Mallory’s contribution, we note that Pollak investigated the
purin metabolism in a series of cases of _chronic alcoholism_. In five
of the examples a marked derangement of _purin metabolism_ was noted and
manifested, “partly in retention, and partly in delayed excretion, or a
combination of the two.” Having observed these variations in cases of
what he considered were _non-gouty_ alcoholics, Pollak felt justified in
attaching but limited diagnostic import to the results of the examination
of uric acid metabolism in gout, this though he realises the importance
of alcoholic excess as a cause of disturbed purin metabolism.

Mallory’s observations, too, on uric acid excretion in gout complicated
by _lead poisoning_ are highly interesting. In two cases of this
nature he noted that the percentage of uric acid nitrogen excreted
was relatively small—in this respect in full accord with previous
observations of Brugsch and Schittenhelm on a gouty patient with a
history of plumbism, with this reservation, that in the latter observers’
example there were indications of early _renal_ disease, while in
Mallory’s two cases such was absent, the urine being normal, and likewise
the blood pressure.

Again, Pollak in a case of _lead gout_ noted an extremely _low endogenous
average_, viz., a daily average endogenous excretion of 0·06 gram uric
acid in a period of five days. Eschemburg, quoted by Pollak, has recorded
an instance of gout with plumbism in which the excretion fell as low as
0·02-0·04 grams. It may be noted that Pollak’s was the victim also of
incipient _renal_ disease.

Reverting to Mallory’s conclusions, this observer’s studies of examples
of _gout_ with _lead poisoning_ seem to indicate that “these cases differ
from normal persons to a greater degree than do other cases of gout.” It
may, he thinks, be affirmed that the subjects of gout and plumbism, as a
rule, show “some or all of the following characteristics in a much more
marked degree than do cases unassociated with lead”:—

    (1) Slight fluctuation in the endogenous excretion.

    (2) Low endogenous average.

    (3) Small percentage of exogenous purin nitrogen excreted as
    uric acid nitrogen.

To sum up, then, we see that poisons, other than those responsible for
gout, may engender obliquities of general metabolism, with disturbances
of purin assimilation and output, viz., lead, alcohol, and the _causa
causans_ of rheumatoid arthritis. Also, in respect of lead poisoning and
alcoholism, further affinities with gout are discernible in that, like
the latter disorder, they tend in their later stages to be associated
with arterio-sclerosis and renal inadequacy.


INFANTILE GOUT

Apart from the fact that gouty arthritis may occur in young children,
Comby and other observers have noted that children born of _gouty_
parents display a tendency to inflammatory changes in the cutaneous
tissues and also in the mucous membranes.

These proclivities are difficult of explanation, but some further
observations by Czerny, Paltauf, Escherich, and Pfaunder are also
worthy of note. Under the headings of “exudative diathesis” or
“neuro-lymphatismus” they have described a symptom complex marked
by lymphatism with asthma, occasional vomiting, defective nervous
equilibrium, and eosinophilia. These varied phenomena also are common in
the descendants of _gouty_, diabetic, and arthritic subjects.

The clue to the true nature of these phenomena may possibly reside in
the fact noted and emphasised by Uffenheimer, viz., that these children
exhibit a _purin metabolism_ identical with that met with in _gouty_
patients.

From the foregoing consideration it is clear that further observations
are called for in the sphere of purin metabolism, and it is, perhaps, not
too much to hope that extended investigations of the uric acid content of
the _blood_ may clarify and illumine the conflicting results obtained by
urine analysis.

As before stated, we had intended in the next chapter dealing with
the question of “Uricæmia in Gout,” but on second thoughts it appears
desirable to us to interpolate a chapter devoted to discussion of the
primary _renal_ origin of gout; for we take it that, with the phenomena
of _uric acid excretion_ in _gout_ fresh in our minds, it will be more
easy at this juncture to attempt solution of this very intricate problem.
This achieved, we shall resume our thread and pass to the consideration
of uricæmia and subsequently uratosis in gout.




CHAPTER X

THE RENAL THEORY OF GOUT


This time-worn hypothesis as to the pathogeny of gout has, perhaps,
provoked more controversy than any other etiological problem in the
sphere of clinical medicine. Nor, unfortunately, despite the endless
laborious research expended upon its solution, the dialectic skill
exercised in attempts at its elucidation, can we claim even to-day that
its complexities have been wholly unravelled. But, perhaps it will be
wiser to postpone decision, pending detailed analysis of the several
grounds upon which the theory of the primary renal origin of gout rests.

Broadly speaking, the arguments adduced tend to concern themselves with
or rather to arise out of certain apparent _abnormalities_ in _uric acid
excretion_, currently held distinctive of gout, certain resemblances also
suggestive of a hidden _nexus_ between _gout_ and _renal_ disorders,
viz.:—

(1) _Anomalies in uric acid excretion in gout._

(2) _Uricæmia, a condition common to gout and nephritis._

(3) _Uratosis, a feature also common to both disorders._

(4) _Occasional co-existence of gout and nephritis._


ANOMALIES IN URIC ACID EXCRETION IN GOUT

As to the variations in _purin_ excretion that occur in _gout_, it must
be admitted that, notwithstanding the magnitude of the researches, no
very striking departures from normal have emerged. Such as have been
elicited occur in relation to (_a_) the acute paroxysm, (_b_) the
excretion of exogenous purin.

_The Acute Paroxysm._—Garrod, it will be recalled, claimed that during
an _acute_ attack of gout the excretion of uric acid was diminished, and
that coincidently therewith the uric acid blood content rose. But these
findings in the _blood_ and _urine_, which constituted the basis of his
hypothesis that gout was due to _renal inadequacy_, have, as previously
noted, been categorically disproved.

Turning to the more modern findings upon which such refutation of
Garrod’s view was achieved, one point emerges that appears to favour
the assumption of _renal block_. It is that, _one or two days prior to
an acute attack_, an appreciable _decline_ in the output of uric acid
occurs.

But this, be it noted, is neither so marked nor so constant as the
subsequent _increase_; in short, at the zenith of an acute attack, _an
augmented output of uric acid_ ensues. At the very time when presumably
the alleged functional renal impediment would be most pronounced, the
impermeability of the organs for uric acid accentuated! Surely such
behaviour seems scarcely compatible with the supposition that there is
even a temporary diminution in the capacity of the kidney to excrete
uric acid. Does it not in truth constitute strong proof of the reverse?
Moreover, the said vagaries that herald the oncoming and that chequer the
course of the paroxysm are not _invariable_, an obvious _caveat_ against
hasty _etiological_ inferences therefrom. Any tendency thereto should
also be curbed by the reflection that, viewing the character of the uric
acid excretion in gout as a whole, the variations therein are not more
extensive than in _healthy_ individuals, and assuredly, _on the mere
basis of the fluctuations in uric acid excretion_, no diagnosis of gout
is possible.

_Retarded Purin Elimination._—The mainstay in argument, however, as
advanced by more modern advocates of the renal theory of gout, is that a
_retarded output of exogenous purin_ is typical of this disorder; but,
here, again, there is no room for dogmatism. Thus Walker Hall reminds
us that “the quantity of purins present in the food does not overstep
the solubility of urates in the blood-stream, for once the material
is metabolised and ready for removal the amount of blood, so far as
solubility goes, places the whole amount of purins within the reach of
the renal cells in less than twenty-five minutes.” We see, therefore, as
far as _rapidity of transport_ to the kidneys is concerned, there is no
delay in presentation of the opportunity for the excretion of exogenous
purin. While the alleged tardiness of output is attributed to defective
action of the _kidneys_, it is at least equally possible that the delay,
as Walker Hall states, “may be due to a defective or idiosyncratic
nuclear metabolism, which results in the formation of isomeric purins or
incomplete purin combination, and which makes greater demands upon the
selective activities of the renal cells;” for it must be recollected that
as yet we are ignorant as to the exact form in which uric acid circulates
in the blood-stream, whether as _sodium mono-urate_ or in _organic_
combination.

Moreover, experimental _injections of uric acid_ into the _tissues_ or
_veins_ show no impairment in the elimination capacity of the kidneys for
uric acid. Thus, Wells cites evidence that “the kidney in gout shows no
lack of ability to excrete uric acid injected into the tissues.”

Again, given _intravenous_ injection of uric acid into a _normal_
man, its excretion occupies several days, and it fails to appear
_quantitatively_ in the urine. But if administered during a course
of _atophan_, then the _whole_ amount injected is excreted within
twenty-four hours. If the same procedure be followed in a _gouty_
individual, precisely the same results are obtained; in other words, both
normal and gouty kidneys react in identical fashion to atophan. Given
an inherent functional defect, _quâ_ uric acid excretion, in the _gouty
kidney_, one would scarcely expect a wholly _normal_ reaction thereto.
Surely some disparity would be disclosed, some aberration in response as
compared with _normal_ renal organs.

Again, while McLester and others claim that atophan exerts “a selective
stimulating influence on uric acid excretion,” it is quite possible that
its _rôle_ may be otherwise explained. May it not influence the actual
_formation_ of uric acid, or, failing this, the _form_ in which it is
presented to the kidneys for excretion? Nicolaier and Dohrn, indeed,
believe that _atophan_ influences in some way purin metabolism within
the _muscles_ and so leads to _increased formation and excretion of uric
acid_. At any rate, whatever be the explanation of the action of atophan,
the fact that _healthy_ and _gouty_ kidneys react _alike_ thereto cannot
be interpreted as proof of defective capacity for uric acid elimination
in gouty subjects, indeed the reverse.

Moreover, in all our attempts to saddle the kidneys with the
responsibility for the delay in exogenous purin excretion, we are for
ever hampered in that we know not whether the alleged renal impairment
is _primary_ or _secondary_ to the gout. That the kidneys are frequently
functionally inefficient in the _later_ stages of gout may be conceded.
But what of the _initial_ phases of the disorder? Some talk very glibly
of subjects who are, they say, “potentially gouty.” But has the rate
of disposal of ingested purins been investigated in persons suffering
from so-called “goutiness,” or, perhaps more pertinently, in those
individuals, not uncommon, who, while exhibiting _auricular tophi_, have
yet experienced no frank attack of gout?

In this connection we may note that McClure has recently emphasised
the fact that the _kidneys_, in the _later_ stages of gout, are often
_functionally_ deficient, and that, accordingly, the faulty elimination
of exogenous uric acid by gouty persons may be simply the result of such
_functional renal depression_; in other words, not due to gout, but to
the _secondary_ or _associated renal deficiency_. Hence, having regard to
the frequency with which renal inefficiency is met with in gout of any
standing, he is inclined to discount the value of studies of _exogenous
uric acid elimination_ as an aid to the diagnosis of gout. Consequently,
he holds that before the diagnostic status of retarded purin
elimination, as a symptom of gout, can be established, an investigation
of the output of uric acid in the different types of _nephritis_ is
essential.

From the foregoing it will be seen that we stand in urgent need of
further studies of _early_ or _oncoming_ gout and of _early nephritis_
before we can with certitude impeach the _kidneys_ as responsible for
the delay in exogenous purin output. Meanwhile, too, we must be careful
not to overlook the further disconcerting fact, previously adverted to,
that the retardation and diminution of exogenous purin output is not
_invariable_ in gout. Nor, for that matter, is it _peculiar_ to gout,
considerations both of which, if confirmed, will still further discount
the _diagnostic_ significance of this phenomenon.


URICÆMIA IN NEPHRITIS

Von Jaksch and Klemperer noted long since that in chronic interstitial
nephritis urates are always present in the _blood_. Now, according to
Folin and Denis, human blood contains 1·5-2·5 mg. of uric acid per 100
c.c.; but if the eliminating powers of the _kidney_ be deficient, the
uric acid content thereof rises, sometimes to as high as from 15-20 mg.
per 100 c.c.

But more interesting still the fact noted by Fine, viz., that even in
_early_ interstitial nephritis the same feature is well marked, _i.e._,
the blood may contain 4-8 mg. of uric acid per 100 c.c. Indeed, according
to this authority, increase in the _uric acid_ content of the blood is
the first signal of impaired renal efficiency. This, be it noted, without
any coincident proportional increase in the blood content of _urea_ or
_creatinine_. The sequence would appear to indicate that the damaged
organ encounters greater difficulty in excreting _uric acid_ than these
other metabolites.

But, _pari passu_ with the advance of the renal disease, retention of
_urea_ is superadded, and still later _creatinine_. So constant, indeed,
the sequence that, by determining the percentage amount of these three
_metabolites in the blood_, the measure of the renal mischief may be
gauged.

But of striking significance is the further point established by Myers
and Fine, viz., that the blood content, in respect of _uric acid_,
_urea_, and _creatinine_, in _early nephritis_, is an almost exact
replica of that met with in typical cases of _gout_. The same is well
illustrated in the following table, in which the blood content, in
respect of these three metabolites, in cases of gout and early and late
nephritis is contrasted. The percentage of the retained metabolites in
relation to the severity of the case is gauged by the blood pressure
findings.


URIC ACID, UREA N, AND CREATININE OF BLOOD IN GOUT AND EARLY AND LATE
NEPHRITIS

  ===========================+=====+===========+===========+=========
                             |Uric |  Urea N.  |Creatinine.|Systolic
           Diagnosis.        |acid.|Mg. to 100 |           |  blood
                             |     |c.c. blood.|           |pressure.
  ---------------------------+-----+-----------+-----------+---------
  Typical cases of gout.     | 9·5 |     13    |    1·1    |   230
                             | 8·4 |     12    |    2·2    |   164
                             | 7·2 |     17    |    2·4    |   200
                             | 6·8 |     14    |    1·7    |
  ---------------------------+-----+-----------+-----------+---------
  Typical early interstitial | 9·5 |     25    |    2·5    |   185
  nephritis.                 | 8·0 |     37    |    2·7    |   150
                             | 5·0 |     37    |    3·9    |   130
                             | 7·1 |     16    |    2·0    |
                             | 6·6 |     24    |    3·3    |   185
                             | 6·3 |     18    |    2·1    |
                             | 8·7 |     20    |    3·6    |   100
                             | 7·0 |     33    |    2·6    |   117
                             | 6·3 |     31    |    2·1    |
                             | 6·3 |     23    |    2·4    |   150
  ---------------------------+-----+-----------+-----------+---------
  Chronic diffuse and        | 8·0 |     80    |    4·8    |   240
  chronic interstitial       | 4·9 |     17    |    2·9    |   170
  nephritis.                 | 8·3 |     72    |    3·2    |   238
                             | 5·3 |     21    |    1·9    |   145
                             | 9·5 |     44    |    3·5    |   210
                             | 2·5 |     19    |    1·9    |   120
                             | 7·7 |     67    |    3·1    |
                             | 6·7 |     17    |    1·6    |   165
                             | 8·3 |     39    |    2·9    |
                             | 6·5 |     24    |    3·0    |   200
  ---------------------------+-----+-----------+-----------+---------
  Typical fatal chronic      |22·4 |    236    |   16·7    |   210
  interstitial nephritis.    |15·0 |    240    |   20·5    |   225
                             |14·3 |    263    |   22·2    |   220
                             |13·0 |     90    |   11·1    |   265
                             | 8·7 |    144    |   11·0    |   225
  ---------------------------+-----+-----------+-----------+---------

  (Myers and Fine: “Arch. Int. Med.,” 1916.)

The salient feature of the table is, however, the fact that in _early
interstitial nephritis_ the retention of _uric acid_ precedes that of
_urea_ or _creatinine_.

Its importance resides in the reflection that it lends support to those
who contend that _renal change_, leading to failure of excretion of uric
acid, _is the primary cause of gout_; in other words, it gives colour to
Magnus Levy’s contention that the phenomena of gout are referable to “a
deficient and restricted secretory power of the kidney.” The existence
of such a selective excretory incapacity, _i.e._, for _uric acid_, does
not, he considers, predicate a genuine nephritis. He maintains that such
disability on the part of the kidney for uric acid excretion may exist
without _morphological_ change; in other words, he thinks it conceivable
that a _single_ function of the kidney can become almost exclusively
insufficient, though later real damage to the organ and a nephritis
frequently follow.

Reflecting on the above theory, it is obvious that, if carried to its
logical conclusion, it would appear to postulate that gout is nothing
more than a form of _renal disorder_, marked simply by _functional
inability to excrete uric acid_. The postulate is no mean one, for,
as Sir Archibald Garrod says, “If the fault is in the kidneys alone,
gout must be removed once and for all from the category of metabolic
disorders, and placed among the sequelæ of renal inadequacy, at least in
so far as the uric acid phenomena of the disease are concerned.”

Furthermore, Levy’s hypothesis involves the assumption that the excreting
functions of the kidney for _uric acid and urea_ are separate and
independent of each other, and to discussion of this we now pass on.


THE RELATIONSHIP, IF ANY, BETWEEN THE AMOUNTS OF URIC ACID AND OF UREA,
AND TOTAL NON-PROTEIN NITROGEN IN HUMAN BLOOD

Taking samples of human blood from (1) _unselected insane_ subjects and
(2) _chronic nephritics_, Folin and Denis determined the amounts therein
of urea, total non-protein nitrogen, and uric acid. The figures obtained
showed that “there is apparently no relationship between the amount of
uric acid and the amount of urea or total non-protein in nitrogen, in
human blood.”

That such a discrepancy should obtain is doubtless of profound though as
yet imperfectly grasped significance. These authorities rightly assume
that, since the kidney is practically the sole avenue for nitrogenous
waste excretion, it follows that the _urea_ and _total non-protein
nitrogen_ of the _blood_ must in the main be inversely proportional to
the general efficiency of the _renal_ organs. Then, obviously, the same
law, too, should, in lack of some other plausible explanation, govern the
excretion of _uric acid_ also. But, as the above generalisation portends,
it is apparently not so.

Fortunately, Folin and Denis prosecuted their study still further,
taking in examples of _gout_ (with and without clinically recognisable
_nephritis_), also instances of _leukæmia_ and _lead poisoning_.

The blood, again, in these disorders betrayed the same peculiarity,
viz., that while containing an excess of uric acid, it did not contain
correspondingly large amounts of urea or other waste nitrogen; in other
words, the findings in the blood in gout were in full accord with the
above generalisation, _i.e._, _the apparent lack of any relationship
between the amount of uric acid and that of urea or total non-protein
nitrogen in the blood_.

Now in _leukæmia_ the cause of the _uricæmia_ is _over-production_ of
uric acid, but in this instance the same is correlated with an increased
_elimination_ of uric acid by the kidneys.

Turning to lead poisoning, the medicinal administration of lead acetate
results in a great _diminution_ of uric acid excretion, a response
consistent with the view that lead inhibits the excretory power of the
kidney for _uric acid_, the change, at first functional, becoming later
organic; for it is held that the _uricæmia_, associated with plumbism,
proves that the action of the lead is not due to inhibition of the
formation of uric acid.

Lastly, as to gout, opinion still wavers as to whether or not the
excretion of uric acid in this disorder is appreciably _lowered_. On
the other hand, it is significant that the reverse is never claimed,
viz., that in gout the uric acid output is _abnormally raised_. Now, as
we saw in _leukæmia_, the _high uric acid blood content_ is accompanied
by a correspondingly _high uric acid output_; but, on the contrary, in
gout, despite the _accumulation of uric acid in the blood_, there is _no
parallel increase in its elimination_.

Reflecting on the above considerations, Folin and Denis claim that
“the mere fact that the uric acid may accumulate in the blood of the
gouty without being accompanied by an increased elimination constitutes
definite proof that the gouty kidney is damaged with reference to its
ability to eliminate uric acid.”

In all deference, we doubt the legitimacy of the inference, if only for
the very excellent reason that, to quote Von Noorden’s words, even to-day
“it remains uncertain whether the retention of urate arises because the
outlet is blocked, or because the uric acid is held fast by chemical
affinities.”

Apart from this, there are several objections to Folin and Denis’
assumption.


URICÆMIA NOT NECESSARILY DUE TO RENAL DEFECT

Thus Pratt, in some examples of his cases of gout, found that there was
no apparent diminution or delay in the output of exogenous purin in
the urine. On the other hand, he observes that “our study of the blood
shows that _a marked increase in retention of uric acid in the blood_
may result from the ingestion of purin bases even when _no evidence of
retention is found on examination of the urine_.” This would appear to
indicate that the uricæmia, sequential to exogenous purin intake, ensues
independently of and apparently despite the absence of any delay or
diminution in uric acid elimination.

Again, Walker Hall, discussing the metabolism of exogenous purins,
reminds us that a gouty subject excretes an excess thereof as completely
as a normal individual, with only this difference, that he takes a longer
time to do so; but even this disability is removed by a simultaneous
intake of atophan. His comment is that “the gouty kidney, therefore, is
not poisoned beyond compensating for and responding to an extra load.”
“Perhaps,” he says, “the situation may be summed up in the observation
that _the uricæmia of the gouty is maintained in spite of a fair renal
elimination_.”


URICÆMIA NOT PECULIAR TO NEPHRITIS

Again, a grave obstacle to the acceptance of Folin and Denis’ inference
is that uricæmia, though incidental to nephritis, is not peculiar thereto.

Thus Roy Upham and Higley noted its presence in 85·6 per cent. of their
cases of _nephritis_; but, on the other hand, they found that no less
than 40 per cent. of another series of clinical cases, not _suffering
from nephritis_, also showed uricæmia.

This would appear to indicate that, while uricæmia is an exceedingly
common symptom of early chronic interstitial nephritis, it is by no means
_specific_ for that disorder; in other words, its diagnostic valency as a
symptom of _nephritis_ is distinctly limited.

_Reverting_ now to _gout_, what evidence is there that the uricæmia
therein is due to defective eliminatory capacity on the part of the
kidney for uric acid? Certainly there is no proof that the kidney, at
any rate in the _initial_ stages of gout, suffers from this particular
functional disability. Indeed, the fact that, at the very acme of an
acute attack, the output of uric acid is not only not diminished, but
actually _increased_, constitutes strong proof of the reverse.

Again, as modern investigations show, the variations in the uric acid
content of the _blood_, _re_ the incidence or intensity of attacks, are
most _erratic_. Far from its being essential that uricæmia be present,
acute attacks may occur with even a _sub-normal_ uric acid blood content;
in short, the variations are so erratic as to seem quite out of keeping
with the assumption that the uricæmia in gout is primarily of _renal_
origin.

If it were so, one would expect no such vagaries in the uric acid content
of the blood. One would rather, given the existence _ab initio_ of a
_renal functional defect_, look for not only a permanent _uricæmia_,
but further, from time to time, augmentations and diminutions thereof,
synchronising with the rise and wane of gouty paroxysms; in other words,
that in gout the clinical course and crises of the disorder would be
linked up with harmonious variations in the degrees of uricæmia.


URICÆMIA DOES NOT NECESSARILY PORTEND GOUT

If it were so, why does not every case of nephritis develop gout?
The researches of Myers and Fine have shown that _uric acid_ is the
nitrogenous metabolite that first _accumulates_ in the _blood_ in _early_
interstitial nephritis. Only in its _later_ stages do urea and other
waste nitrogenous products undergo like retention therein.

Now let us review these findings, _re_ nephritis, in light of another
statement by Folin and Denis, which runs as follows:—

“In pure gout, unaccompanied by any abnormal urea retention in the blood,
the kidney is damaged (so far as we yet know) only with its function of
removing down to the normal level the uric acid of the blood.”

Is it not clear, then, that in the _early_ stages of _nephritis_, viz.,
prior to retention of urea and other waste nitrogen, we have precisely
that isolated functional renal disability, _i.e._, _inability to excrete
uric acid_, that we postulate to be in operation in the _initial_ stages
of _gout_?

Yet, notwithstanding this similitude in the blood content of the two
disorders, cases of nephritis do not necessarily develop gout. Indeed, as
a matter of fact, examples of nephritis, of all grades and intensities,
may run to their full end without manifesting any symptoms even remotely
reminiscent of gout. Even Magnus Levy, ardent advocate as he is of the
primary renal origin of gout, could not but admit that this salient
clinical obstacle barred the way to acceptance of his otherwise plausible
view. However, he fails to proffer any other solution of the problem.

To our mind, albeit, the disparity carries with it the inevitable
postulate that in gout some other factor intrudes, some _tertium quid_,
something vital, something biological, haply an _infection_. For even if
we grant, for the sake of argument, that _renal retention_, if it were
proved, might explain such anomalies in the excretion of uric acid and
other nitrogenous metabolites as occur in gout, yet, nevertheless, no one
could possibly contend that this factor alone could explain the nature of
gout, could adequately account for its dramatic and protean phenomena.


TO WHAT MAY BE ASCRIBED THE DEFICIENT ELIMINATING CAPACITY OF THE KIDNEY
FOR URIC ACID?

Naturally the advocates of the renal theory had to account in some way
for the alleged functional disability of the kidney. Thus, Sir Dyce
Duckworth, recalling the occasional occurrence in hysteria of _anuria_,
held that, judging from the general phenomena of acute gout, “the
influence of the _nervous system_ ... must not be left out of account as
a possible determining factor for renal inadequacy.”

Others, with whom Duckworth disagreed, propounded the view that the
deposition of urates in the renal tissues was essential for the
initiation of a nephritis in the gouty. Duckworth, on the other hand,
held that nephritis could develop in their absence.

Croftan considers the renal changes in gout identical with those of
chronic plumbism. From experiments with hypodermic injections of
_xanthine_ and _hypoxanthine_ over a prolonged period, he concludes that
the presence of minute quantities of purin bases in the circulation is
capable of producing _marked renal changes_. On the other hand, _uric
acid_, injected into the circulation of healthy animals for a period of
over three months, produced _no renal change_ whatever.

As to this possibility, viz., that the _circulating uric acid_ might lead
to _nephritis_ in the _gouty_, some reflections of Folin and Denis are
instructive. Normal blood, according to these observers, contains not
less than from 1-2 or 2-5 mg. per 100 grams, while that of _gouty_ blood
does not, in their experience, exceed 6 mg. Continuing, they observe,
“There is, however, no reason to suppose that a uric acid concentration
of 4-6 mg. per 100 grams of blood is very much more irritating or
stimulating to the kidney than the somewhat more dilute solution
represented by normal blood. Disregarding the insolubility of uric acid,
the elevation of its threshold of elimination from 2-4 or 6 mg. (per 100
grams of blood) is certainly a small one. Kidneys in which the threshold
of elimination for urea has risen by 10-20 mg. (per 100 grams), or even
more, are extraordinarily common.”

While they consider that such _urea_ and _total nitrogen retention may_
possibly bespeak _latent_ or _incipient nephritis_, they recognise
that no appreciable effects on health have as yet been determined in
connection therewith. But more pertinently to our point, they make the
further pregnant observation, “In the case of uric acid it seems to
be purely a matter of insolubility that corresponding or even smaller
degrees of kidney insufficiency with slight uric acid accumulation should
result in all the serious consequences involved in the development of
gout”!

Again, some have attempted to account for the assumed renal incapacity
as being part of the _tissue peculiarity_ of the gouty subject. “Without
doubt,” says Duckworth, “there are peculiarities of tissue in the gouty,
and with this may very possibly be associated peculiarities of tissue
function and metabolism.”

Naturally this suggests the further question, Are there any distinctive
_histological_ changes in the _gouty_ kidney? On this point Walker
Hall has some apposite reflections. Taking Folin’s figures as a
basis, it transpires that in _acute_ and _chronic nephritis_, also in
_arterio-sclerosis_, there is an average content of 2·5 mg. uric acid
per 100 grams of blood. Now, notwithstanding the fact that in these
conditions an appreciable quantity of the renal tissues is, functionally
speaking, temporarily or permanently out of action, nevertheless “the
extraction of uric acid from the blood and its subsequent excretion are
practically normal.” The inference is that a relatively small moiety of
renal tissue suffices for the excretion of the daily quantum of uric acid
in the urine.

Now in contrast thereto, the blood content in _gout_ and _lead poisoning_
is about 4·5 mg. uric acid per 100 grams of blood, or “an increase of
about 50 mg. in the total blood-stream at any one moment (an increase
from the normal 70 up to 120 mg.).” Continuing, Walker Hall observes
that “the gouty kidney _per se_, even when arterio-sclerotic conditions
prevail, does not show anything like the amount of cellular damage which
occurs in acute or chronic diffuse nephritis.” Thence he argues if
_histological_ changes be taken as a criterion of functional efficiency,
then the _gouty_ kidney should be more capable of excreting freely than
the _diffuse nephritic_ organ.

How does this work out in actual daily life? he asks. “0·5 gram, in
a _normal_ adult, represents the _average daily endogenous uric acid
excretion_ in the urine, while that of a _gouty_ subject is about 0·45
gram. Now, assuming that the type and extent of the endogenous metabolism
is identical in each instance, then the balance, _i.e._, 0·05 gram, is
distributed between the uric acid pent up in the tissues and the uratic
deposits, _i.e._, tophi.” Walker Hall tells us it has been stated that
about 0·01 gram suffices to cover the amount deposited as _tophi_ every
twenty-four hours. The residual 0·04 gram runs to swell the amount in the
blood and lymph-streams. “The increase is 0·0114 to 0·0118 gram per litre
of blood; in other words, the actual increase of uric acid circulating
through the kidneys is about 0·00047 per hour,” which, as Walker Hall
contends, “seems to be a very trifling difference, especially as it is
one of amount and not a type.” In other words, it is _quantitative_,
not qualitative. But, trivial as the disparity is, to what may it be
referred? To Walker Hall’s mind, if we are to appreciate the standpoint
of those who maintain that the gouty _uricæmia_ is referable to _renal
inadequacy_, it is necessary to postulate _the presence of a poison
acting upon the renal tubules specifically_.

In the gouty uric acid excretion is maintained at a “_low physiological
level to the very end_,” and it is easier, he thinks, to adopt the above
hypothesis as to its cause than “to conceive of a poison acting upon the
_nuclear_ processes in such a way as to induce a persistently low uniform
level” of purin excretion.

This view, viz., of a _toxin_ acting specifically upon the uric acid
excreting cells of the kidney, seems to be the only reasonable assumption
available. But even this is difficult of adherence when we recall the
fact that the effect of the toxin is so readily neutralised by a few
grains of _atophan_. Always we have to recollect, too, that under
_normal_ conditions, even given a _constant_ diet, the elimination of
uric acid displays _wide variations_. Also the uric acid output in the
subjects of _chronic gout_, when placed on a _fixed_ diet, differs but
little from that of _normal_ individuals on a like dietary. At most the
excretion but tends to fall to, or slightly below, the lower normal
limits of uric acid elimination.

From the foregoing considerations it is but too obvious that those who
render obeisance to the primary renal origin of gout have not only yet to
prove that the functions of the kidney are defective, but also upon them
lies the _onus probandi why_ gouty subjects should exhibit, or acquire,
such a disability.


URATIC DEPOSITS IN NEPHRITIS

Here, again, we light upon another point of contact between gout and
nephritis, for an interesting feature of the latter disorder is that the
retained uric acid, purins, and other excretory products are deposited in
_cartilage_ and _serous membranes_. At these sites they are frequently
detected post mortem, though they fail of _ante-mortem_ recognition.

Impressed by the fact that, at post-mortems, uratic incrustation of the
articular cartilages was frequently observed in persons who had never
suffered from overt gout, Ord and Greenfield sought to ascertain the
frequency with which such uratic deposits were associated with _renal_
disease. Out of ninety-six cases presenting renal lesions, no less than
eighteen exhibited uratic deposits in the joints.

A still more elaborate research in this sphere was undertaken by Norman
Moore. Out of forty-nine cases of chronic interstitial nephritis, uratic
deposits were present in twenty-two instances. Again, out of nine cases
of chronic parenchymatous nephritis, deposits were found in the joints
in two cases. With respect to the first group he observes that “chronic
interstitial nephritis is not invariably accompanied by deposits in
the articular cartilages, though usually accompanied by traces of
degeneration in some of the articular cartilages.”

Levison, too, an ardent supporter of the primary renal origin of gout,
noted that all the subjects dying at the Communal Hospital, Copenhagen,
of granular kidney disease (during a period of fourteen months) exhibited
uratic deposits in one or other of their joints, although they were never
known to have had any definite attack of gout.

Luff, in the following table, shows the results of the examination of the
joints in seventy-seven cases of _granular kidney disease_.

  -----------------------------+---------------+----------------
                               |               | Uratic deposits
                               | No. of cases. |   in joint or
                               |               |     joints.
  -----------------------------+---------------+----------------
  Known to have had gout       |      10       |      10
  Never known to have had gout |      67       |      31
                               |      --       |      --
          Totals               |      77       |      41
  -----------------------------+---------------+----------------

Of the ten cases known to have suffered from gout, the renal condition
was in every instance defined as “markedly granular,” or “fairly
granular.” Uratic deposits were invariably present in one or more joints.
Of the sixty-seven examples not known to have had gout, uratic articular
deposits were found in 46 per cent., which approximates, more or less
closely, to Norman Moore’s findings. It is noteworthy that in several of
the instances, lacking uratic deposits in the joints, the kidneys were
described as “slightly granular,” or “faintly granular.”

  -------------------------------+---------------+----------------
                                 |               | Uratic deposits
                                 | No. of cases. |   in joint or
                                 |               |     joints.
  -------------------------------+---------------+----------------
  Marked granular kidney disease |      26       |      20
  -------------------------------+---------------+----------------

If of the sixty-seven cases there be selected only those described as
“markedly granular,” or “typical granular kidneys,” the incidence of
uratic deposits in the joints, as revealed by the second table, reaches
no less a figure than 77 per cent.

Another authority, discussing the frequency of incidence of uratic
deposits in the joints in cases of chronic interstitial nephritis, states
that, at post-mortem, from 50-80 per cent. show their presence—this,
moreover, in cases _known not to have had gout_.


DIFFERENTIATION OF URATIC DEPOSITS IN GOUT AND NEPHRITIS

Uratic deposits, it is true, occur in both these disorders. But it is
with a difference. In gout the uratic deposit assumes the form of
_tophi_, whereas in nephritis it is not so. In the latter the uratic
deposit is in the nature of a passive deposition—an uratic incrustation
of the articular cartilages.

Again, in gout the deposition is _sudden_ and associated with an acute
paroxysm; while in nephritis it is _gradual_ and unassociated with
inflammatory reaction.

In gout the uratic deposits are overt, manifest as _tophi_; in nephritis,
occult and unrevealed (ante-mortem).

Uratic deposits in the form of tophi occur in gout, in the absence of
clinically recognisable interstitial nephritis. But tophi do not occur in
nephritis if uncomplicated by gout.

In conclusion, the mere fact that uratic deposits affect such widely
disparate forms in these two disorders is to our mind a sure indication
that their mode of origin and formation is equally diverse—the one vital,
biological; the other passive, mechanical.


CLINICAL ASSOCIATIONS OF GOUT AND GRANULAR KIDNEY

It cannot be denied that gout and granular kidney are frequently met
with in close association. But neither can it be disputed that in these
disorders, as in many others, their outward affinities do but hark back
to inward disparities. The occasional overlapping of the two affections,
the trenching of the one upon the clinical or pathological territory of
the other, must not blind us to the essential distinctness of the two
morbid entities. Doubtless to the earlier advocates of the renal theory
their not infrequent _co-existence_ bespoke some hidden _nexus_, and at
least seemed confirmatory of their views as to the pathogeny of gout.
But, even if we allow that the connexion between the two disorders seems
superficially intimate, it cannot be gainsaid that it is neither constant
nor essential. For we have to recollect that—

    (1) Some gouty subjects never develop granular kidney.

    (2) Some individuals with granular kidney never develop gout.

Also we have to recall that—

    (1) Paroxysms of gout often occur for many years before the
    symptoms of interstitial nephritis develop.

    (2) In persons of gouty stock acute attacks may ensue at an age
    at which nephritis is practically unknown.

Apart from the difficulty of reconciling these disparities, we cannot
overlook the fact that both gout and granular kidney are very common
diseases, sufficiently common, as Samuel West pointed out, to be not
infrequently associated accidentally, without any cause or connection.
Again, both affections, be it observed, are prone to develop in the
middle and later decades of life. In light of this, is it not readily
conceivable that both may arise independently, mere coincidences, both
evidences of _pre-senilism_? Hastings Gilford, indeed, classes gout
with syphilis, lead, and alcohol as amongst “the chief promoters of
pre-senility.”

Again, certain toxic agents which predispose to or initiate renal
mischief also favour apparently the incidence of gout, _e.g._, _lead_
and _alcohol_. Samuel West, discussing the relationship of both gout and
lead to granular kidney, maintains that, though each may produce chronic
change in the kidney, neither of them _causes_ granular kidney. But the
presence of granular kidney, he holds, greatly enhances the liability of
the victim to gout on the one hand and plumbism on the other; also, to
both together and in each affection alike markedly increases the gravity
and the risk.

Sir William Roberts, too, has some wholly relevant observations on this
point. Thus all will agree with him that “it is difficult to conceive
that plumbism induces the same constitutional diathesis as that which
obtains in true gout.” He held that gout and plumbism, though they differ
in all other respects, yet have one point in common, a tendency to
uratic deposition. But such precipitation, he contended, was the outcome
of a gouty tendency, reinforced by lead poisoning; or if, on the other
hand, uratic deposits occurred in plumbism, the same had but accentuated
a pre-existing gouty diathesis. In this connexion, too, it should be
recalled that the frequent association of gout and lead poisoning which
exists in London is not seen in the North of England or in North America.

Is it not clear, then, that reflection on the broad clinical affinities
exhibited by gout and granular kidney does but emphasise the essential
distinctness of the two morbid entities? Inferentially, too, it lends no
colour to the assumption that gout is of primary _renal_ origin.

That the victim of gout, despite uricæmia and those unequivocal tokens,
_tophi_, may, notwithstanding repeated arthritic outbreaks, be in the
intervals in sound if not exuberant health, is a clinical truism. His
kidneys, too, may, as far as can be ascertained, be normal; and his
blood pressure not beyond what might be expected at his age. His output
of uric acid may but touch the lower normal limit or a little less, and
his metabolism of purin-rich foods be but a little protracted. Thus he
runs his course, more frequently than not a strenuous one, chequered
by occasional outbreaks which not seldom he regards as salutary rather
than otherwise. Then, sooner or later, in one, two, or even three
decades, that Nemesis of age, _arterio-sclerosis_ overtakes him with its
correlated _chronic nephritic_ change.

Is not this very reminiscent of what Walker Hall reminds us of,
the sequence of events in _lead poisoning_ and _alcoholism_? “These
poisons affect the general metabolism adversely and are connected with
disturbances of purin assimilation and output. At a later stage they
produce arterio-sclerosis and renal insufficiency.” And as he shrewdly
observes, “It is, therefore, of importance to exactly appraise the stage
of the disease when interpreting the results of experiments upon gouty
individuals. When this obtains widened application, many generally
accepted statements will have to be re-written.”

In conclusion, therefore, we see that the weight of clinical evidence
is against the _primary renal_ origin of gout, for not only are renal
changes frequently slight, but they are often entirely lacking in gout.
Confronted with these difficulties, the question inevitably rises as
to whether there does not exist a special morbid entity, gout, which
develops independently of renal abnormalities?




CHAPTER XI

URICÆMIA IN GOUT


In the summer of 1848, Garrod made his momentous announcement that “the
blood in gout always contains uric acid in the form of urate of soda,
which salt can be obtained from it in crystalline state.” Some eleven
years later in his classic work on gout, he reiterated his affirmation,
but appended thereto the words, “in abnormal quantities.” Garrod’s
analyses were mainly _qualitative_, but, at any rate, in one instance, he
obtained from a gouty patient the equivalent of 5 mg. of uric acid per
100 gm. of blood serum, maintaining, however, that this amount was much
below that really present.

But not until 1895 was a series of _quantitative_ estimates undertaken
when Klemperer in three gouty subjects passing through an attack found
the blood content of uric acid to be 6·6 mg., 8·8 mg., and 9·5 mg. per
100 c.c. of blood. Some years later, Magnus Levy, investigating seventeen
gouty individuals, found that the amount of uric acid in the blood ranged
from 2·1-9·5 mg. per 100 c.c.

Brugsch and Schittenhelm noted that, in gouty victims, uric acid was
still present in the blood even when they had been on purin-free diet for
weeks or months. They held endogenous uricæmia to be a constant symptom
in gout. Even as late as 1913 the former investigator contended that, in
a healthy person on a purin-free diet, the presence of uric acid in the
blood cannot be satisfactorily demonstrated. But it must be recollected
that the _precipitation_ (ammonical silver and cupric bisulphite) method
was beset with disadvantages. An approximate estimate only of the blood
content of uric acid was with difficulty to be achieved even when large
quantities were available.

Fortunately, however, our powers of analysis in this direction became
greatly enlarged with the introduction in 1913 of the colorimetric method
of Folin and Denis.


FOLIN AND DENIS’S METHOD

This colour reaction is so sensitive that one part of uric acid in a
million parts of water can be detected. Moreover, unlike the older
methods which required from 75-100 c.c. of blood or more, determinations
can be made with 20 c.c., and if the blood be rich in uric acid only 10
c.c. Walker Hall observes that the procedure “has many advantages and
does not take up much more time than some of the qualitative methods
when once the technical difficulties are overcome.” He described it as
follows:—

Twenty cubic centimetres of blood are withdrawn into a wide-mouthed,
tared bottle containing 0·1 gramme of finely-powdered potassium oxalate.
The flask and contents are then weighed. Five times the weight of
_n_/100 acetic acid is heated to boiling. The oxalated blood is poured
into the boiling acetic acid solution, and the heating continued until
the solution has begun again to boil. The mixture is filtered hot.
The clear filtrate and wash waters are acidified (0·5 c.c. of 50 per
cent. acetic acid) and evaporated to 3 c.c. Five drops of a 3 per cent.
silver lactate solution, two drops of magnesia mixture, and ten to
fifteen drops of strong ammonia hydrate are next added. The mixture
is centrifugalised. The supernatant fluid is removed. To the residue
five drops of freshly-saturated hydrogen sulphide water and one drop of
strong hydrochloric acid are added. The tube is placed in a beaker of
boiling water for ten minutes in order to remove the hydrogen sulphide.
The supernatant fluid is added to 2 c.c. of a solution containing 100
grams of sodium tungstate and 80 c.c. of 85 per cent. phosphoric acid in
1,000 c.c. of water and 10 c.c. of a saturated sodium carbonate solution.
The resultant blue solution is then compared with a standard uric acid
solution, and the result obtained by the following formula:—

    (20_V_)/(_RW_) mg. of uric acid per 100 grams blood,[20]

where 20 represents depth in millimetres of standard solution,

    _R_, the depth of unknown solution,
    _V_, the volume to which the unknown solution is diluted,
    _W_, the weight of blood taken for the determination.


URIC ACID A NORMAL CONSTITUENT OF BLOOD

Up till quite recently it was held that in normal persons the amount
of uric acid in the blood was too small to be detected; also that uric
acid was not demonstrable in the blood of normal individuals when on
a _purin-free_ diet. On the other hand, if the subject’s blood was
found to contain _uric acid_, while on a purin-free diet, it was held a
characteristic feature of _gout_ and of prime diagnostic import.

But, since the introduction of Folin and Denis’s method, it has been
established that uric acid is constantly present, in demonstrable
amounts, in _human_ blood. These authorities, using their _colorimetric_
method, found that the uric acid content of the blood ranged from 0·7-3·7
mg. per 100 grams. They believe that 1-2 mg. of uric acid per 100 grams
of blood is well within the normal variations, but “are not prepared to
say that they represent the full variations.”

However, before applying their colorimetric method to human subjects,
Folin and Denis conducted some researches into the uric acid blood
content of a variety of animals, the results of which appear in the
following table:—


URIC ACID, TOTAL NON-PROTEIN NITROGEN AND UREA NITROGEN IN BLOOD

(The Figures represent Milligrams per 100 grams of Blood.)

  ------------------------------------+-----+-----------+---------
                                      |Uric |Non-protein|  Urea
                                      |acid.| nitrogen. |nitrogen.
  ------------------------------------+-----+-----------+---------
  Rabbit (6 cases)                    |0·05 |    31     |   13
  Sheep (mixed blood)                 |0·05 |    28     |   13
  Pig (mixed blood)                   |0·05 |    32     |   14
  Horse (1 case, anti-toxin animal)   |0·05 |    54     |   28
  Monkey (1 case, poliomyelitis)      |0·05 |    60     |   38
  Beef (mixed blood)                  |0·2  |    24     |   14
  Cat (2 cases, diet, liver)          |0·2  |    60     |   34
  Cat (2 cases, diet, milk and eggs)  |0·2  |    67     |   37
  Cat (2 cases, diet, rice and cream) |0·2  |    31     |   20
  Chicken (6 cases, mixed blood)      |4·9  |    32     |    8
  Duck (4 cases, mixed blood)         |4·8  |    34     |    7
  Goose (1 case)                      |4·8  |    26     |    8
  ------------------------------------+-----+-----------+---------

The most striking feature of these findings is the marked contrast
between the uric acid blood content of _mammals_ as opposed to avians. In
the former the amount is minimal—0·2 mg. or less per 100 grams of blood.
On the other hand, in the blood of _birds_, in whose instance the origin
of uric acid is so different, it is present in relatively large amounts.
As Folin and Denis observe, the small amounts of _urea_ in the blood of
birds, as compared with that of mammals, is also worthy of note.

Reverting now to the findings in human subjects, as observed by Folin and
Denis, these have been summarised as follows by Walker Hall:—


URIC ACID, TOTAL NON-PROTEIN NITROGEN AND UREA NITROGEN IN BLOOD

(The Figures represent Milligrams per 100 grams of Blood.)

  -----------------------------------+----------+-----------+---------
                                     |Uric acid.|Non-protein|  Urea
                                     |          | nitrogen. |nitrogen.
  -----------------------------------+----------+-----------+---------
  Human, group 1                     |   0·8    |    36     |   19
  Human, group 2                     |   1·5    |    34     |   18
  Human, group 3                     |   2·8    |    36     |   19
  Human, with blood pressures of 160 |   2·9    |    50     |   33
  Human, with blood pressures of 200 |   1·2    |    50     |   22
  Human, with blood pressures of 220 |   2·7    |    40     |   19
  Human, with blood pressures of 260 |   3·9    |    52     |   20
  Human, alcoholic                   |   1·0    |    43     |   29
  Human, chronic gout                |   3·9    |    25     |   13
  Human, chronic gout                |   4·4    |    30     |   15
  Human, chronic gout                |   5·2    |    20     |   13
  Human, lead poisoning              |   4·7    |    50     |   31
  Human, lead poisoning              |   4·8    |    52     |   32
  Human, leukæmia                    |   3·1    |    33     |   14
  Human, acute nephritis with        |          |           |
    arterio-sclerosis                |   2·7    |    40     |   19
  Human, chronic nephritis with      |          |           |
    arterio-sclerosis                |   2·5    |    38     |   19
  -----------------------------------+----------+-----------+---------

Interesting and valuable as are the above findings, Folin and Denis are
careful to point out that, even as regards the first three groups in the
above table, “the figures can scarcely be said to represent the strictly
normal variations, for no attempt was made to select physically normal
persons.” The samples of blood were drawn from patients newly admitted to
the Boston _Psychopathic_ Hospital.

It may be noted that of all the _mammals_ examined the blood of _man_
contains by far the greatest amount of uric acid. Also that in humans the
uric acid blood content varies in different persons, and, moreover, as
Walker Hall points out, “the figures lend support to the view that there
may be groups or families exhibiting similar features.” It will be seen,
too, that the blood uric acid in _gout_ and _lead poisoning_ stands at a
high level, though not so elevated as was formerly maintained. From the
figures, too, it may be gleaned that apparently no relationship obtains
between the amount of uric acid and that of the urea or total non-protein
nitrogen in the blood.

At the same institution in Boston, Adler and Ragle conducted a similar
series of investigations, though on a more extended scale. These
observers, taking 156 unselected _psychopathic_ patients, found that in
107 examples the uric acid content of the blood was from 1-2 mg., in
thirty-eight more than 2 mg., and in eleven instances less than 1 mg. To
sum up, the uric acid content varied from 0·7-4·5 mg. per 100 grams of
blood, an average of 1·7 mg.

As before stated, it was until recently maintained that in the blood
of _normal_ individuals, on a _purin-free_ diet, _uric acid_ was
undemonstrable. But McLester, utilising Folin’s method, found uric
acid in the blood of fifteen _healthy_ individuals, who had been on a
_purin-free_ diet for at least three days, and this in amounts ranging
from 0·5-2·9 mg. per 100 grams of blood, an average of 1·4, as contrasted
with 1·7, the average amount in Adler and Ragle’s series. Pratt,
discussing these findings, considers that the fact that the _average_
amounts approximate so nearly in the two series is worthy of emphasis.
This especially as all McLester’s examples were young healthy adults on a
_purin-free diet_, while the patients studied by Adler and Ragle were of
all ages and on a _mixed_ diet.[21]


EFFECT OF EXOGENOUS PURINES

As we are aware, the amount of uric acid excreted in the _urine_
increases markedly on a _purin-rich diet_. But recent researches appear
to raise doubts as to whether the uric acid content of the _blood_ rises
correspondingly. Thus, according to Walker Hall, “a state of _uricæmia_
is said to exist if the amount of uric acid in the blood exceeds 0·8 mg.
per 100 c.c.” The figure he considers is probably too low for, after an
average meat breakfast, the blood uric acid rises to 1 or 2 mg. per 100
c.c. _in normal_ adults, or even higher after an excessive intake of
_purin-rich_ foods.

On the other hand, Denis, investigating the effect of ingested purin on
the uric acid content of the blood, found that in _normal_ individuals
_no increase in the circulating uric acid_ follows the intake; in other
words, the kidney, in _normal_ persons, is quite capable of excreting any
excess of uric acid presented to it, thereby keeping the uric acid of
the blood at the same level as obtains when only the _endogenous_ moiety
thereof has to be eliminated.

Moreover, another factor, according to Folin and Denis, that operates
in the same direction is the _binding capacity of the tissues for uric
acid_. Pratt of Boston’s observations, too, appear to indicate “That the
uric acid derived from exogenous purin does not accumulate in the blood
unless there is a disturbance in the uric acid metabolism.”

On the other hand, given damage to the _kidney_ (even when this has not
progressed to the point when nitrogen retention is apparent, as shown
by the non-protein nitrogen values), an accumulation of uric acid takes
place in the blood after a short period of purin feeding.[22]

Now, as to the second regulating factor, the _retention capacity_ of the
_tissues_ for _uric acid_, it may be said that the amount, in _normal_
subjects, would appear to be small. But Fine, it may be noted, found that
the uric acid content in divers tissues was relatively proportionate to
that of the blood, whether normal or increased in amount.

But, to resume, Denis also demonstrated that the uric acid content of
the blood in patients suffering from various _chronic diseases other
than gout_ was also not increased on a purin-rich diet. To sum up, the
researches of Denis would appear to indicate that:—

    (1) In _normal_ subjects _no increase_ in the _uric_ acid
    content of the _blood_ follows exogenous purin intake.

    (2) The uric acid content of the blood in patients suffering
    from chronic diseases, other than _gout_ or _renal_ disease, is
    similarly _not_ augmented on a _purin-rich_ diet.

    (3) The _uric acid content_ of the _blood_ is _increased_ more
    or less markedly, after a short period of purin feeding, in the
    presence of defective _renal elimination_.

In amplification of the second of the foregoing postulates some
observations by Pratt may be quoted. This authority is of opinion
that the low amount of uric acid present in the blood of unselected
_psychiatric_ patients on a mixed diet (Folin and Denis, Adler and Ragle)
shows that a retention of uric acid in the blood in any considerable
amount for twenty-four to twenty-eight hours rarely occurs. For, as he
informs us, these patients at the Boston Psychopathic Hospital, when on
ordinary diet, are eating purin-containing food daily, and they might
take as much or more purin during the forty-eight hours preceding the
blood analysis as is contained in a single sweetbread meal. Now, as Pratt
argues, if the uric acid thus derived accumulated in the blood, the
amount found would be considerably greater than that of individuals on a
_purin-free_ diet. But, on the contrary, it transpires that the average
amount of uric acid found by Adler and Ragle in the blood of patients on
an ordinary diet was only 0·3 mg. more than that found by McLester in
normal individuals on a _purine-free_ diet. The diagnostic significance
of these observations will be better appreciated when we come to discuss
the sequential increase of the uric acid content of the blood in _gouty_
subjects after the ingestion of purin-rich substances.


URIC ACID CONTENT OF BLOOD IN GOUT

Taking 1-3 mg. per 100 c.c. as the normal, the uric acid content of the
blood, in typical cases of gout, according to MacLeod, rises to nearly 10
mg. Gudzent, from his studies, maintains that the blood, in almost all
cases of gout, contains as much or even more _mono-sodium urate_ than
it can hold in solution (1-8 mg.), in other words, it is in effect a
supersaturated solution of the relatively insoluble _lactim_ urate.

Pratt, working in Folin’s laboratory, investigated a series of cases of
gout, selecting only those in which (1) Tophi were found, (2) A history
of characteristic attacks of acute gout was obtained, or (3) Typical
symptoms developed while under observation.

At the time of examination the average uric acid content, irrespective of
the diet or condition, was 3·7 mg. In three patients on _ordinary diet_,
who were seen during attacks, the amounts were 4·5, 4·8 and 5·7 mg. of
uric acid. In two other patients, also seen during attacks, and while on
a _purin-free_ diet, the uric acid in four estimates ranged from 2·4-5·1
mg., viz., an average of 3·6 mg. None of these patients were taking
atophan.

Seven patients, on a _mixed_ diet, and free at the time from symptoms of
gout, contained on the average 4·3 mg. of uric acid in their blood.

On the other hand, examination of the blood in six patients on a
_purin-free_ diet, at the time manifesting no acute symptoms of gout,
revealed an average uric acid content of 3 mg.

From the foregoing considerations it may be deduced that:—

    (1) In gout there is a condition not of uricæmia, but of
    _hyper-uricæmia_.

    (2) That on the average the blood in _gouty_ subjects contains
    twice as much uric acid as that of _non-gouty_ subjects, as
    evidenced by comparison of the average uric acid content of the
    blood in Pratt’s series of gouty cases (4·5 mg.) with Adler and
    Ragle’s non-gouty examples (1·7 mg.).

    (3) In contrast with non-gouty subjects, the uric acid content
    of the blood in _gouty_ subjects is augmented on a purin-rich
    diet.

    (4) Both in the inter-paroxysmal periods and during attacks
    the uric acid content of the blood, when on a _mixed_ diet, is
    higher than when on a purin-free diet.


HYPER-URICÆMIA IN NON-GOUTY ARTHRITIS

Pratt, of Boston, has found that a condition of hyper-uricæmia is
sometimes demonstrable in joint disorders other than gouty; but he
maintains that the following distinction obtains, viz., that while in
gout the hyper-uricæmia is generally _constant_, in other forms of
arthritis it appears to be _transient_.

He cites a case of _infective_ arthritis, not exhibiting the clinical
features of gout, in which the first analysis of the blood by Denis
revealed a uric acid content of 7·6 mg.; but on a subsequent examination,
seven months later, only 0·8 mg. was found, this, though the patient
at the time was on a _purin-rich_ diet. This difference is response to
exogenous purins in gouty, as opposed to _non-gouty_ arthritics, is well
illustrated in the following table.

  According to Walker Hall, the following example illustrates the
  effect of purin-free as opposed to purin diet on the uric acid
  blood content in a gouty subject:—

  --------------------------------+-------+-------------+-------------
                                  | Uric  | Non-protein |   Urea
                                  | acid. |  nitrogen.  | nitrogen.
  --------------------------------+-------+-------------+-------------
                                    Mgs. per 100 gms. of blood.
  Gout with purin dietary         |  5·5  |     52      |    36
  Gout with purin-free food       |  3·4  |     40      |    18
  --------------------------------+-------+-------------+-------------

                         GOUTY POLYARTHRITIS (PRATT).
  ---------------------------+----------+-----------------------+----------
                             |Milligrams|                       |Milligrams
                             |    of    |                       |    of
                             |uric acid |                       |uric acid
                             |  in 100  |                       |  in 100
                             | gms. of  |                       | gms. of
                             |  blood.  |                       |  blood.
  ---------------------------+----------+-----------------------+----------
  D. N. Gout. Purin-free     |   3·1    |52 hours after eating  |   5·8
    diet.                    |          |  280 grams haddock    |
                             |          |  roe.                 |
                             |          |3 days after eating    |   6·2
                             |          |  300 grams roast beef.|
  K. Gout. Purin-free diet.  |   2·4    |24 hours after eating  |   3·0
                             |          |  270 grams roast beef.|
  H. Gout. Purin-free diet.  |   1·7    |3 days after eating    |   3·6
                             |          |  150 grams thymus.    |
  P. Gout. Purin-free diet.  |   2·1    |3 days after eating    |   3·4
                             |          |  160 grams thymus.    |
  J. N. Gout. Purin-free     |   2·2    |48 hours after eating  |   8·7
    diet.                    |          |  190 grams thymus.    |
                             |   ---    |                       |   ---
          Average            |   2·2    |        Average        |   5·1
  ---------------------------+----------+-----------------------+----------

                       NON-GOUTY POLYARTHRITIS (PRATT).
  ---------------------------+----------+-----------------------+----------
                             |Milligrams|                       |Milligrams
                             |    of    |                       |    of
                             |uric acid |                       |uric acid
                             |  in 100  |                       |  in 100
                             | gms. of  |                       | gms. of
                             |  blood.  |                       |  blood.
  ---------------------------+----------+-----------------------+----------
  McC. Chronic polyarthritis.|   1·7    |24 hours after eating  |   2·2
    Purin-free diet.         |          |  100 grams of thymus. |
  M. Chronic polyarthritis.  |   2·0    |24 hours after eating  |   1·8
    Ordinary diet.           |          |  225 grams of thymus. |
  H. Chronic polyarthritis.  |   2·9    |47 hours after eating  |   2·5
    Ordinary diet.           |          |  190 grams of thymus. |
                             |   ---    |                       |   ---
          Average            |   2·1    |        Average        |   2·2
  ---------------------------+----------+-----------------------+----------

As Pratt points out, if the figures in the two tables be compared,
it will be seen that, prior to the sweetbread meal, the average uric
acid content of the blood in the gouty and the non-gouty patients was
identical. But twenty-four hours to three days, after the purin intake,
the average uric acid content of the blood in the _gouty_ was 5·1 mg.,
while in the _non-gouty_ subjects it was only 2·2 mg.; in other words,
in the five gouty individuals a pronounced hyper-uricæmia was produced
from one to three days after a purin meal. On the other hand, in the
_non-gouty_ subjects the uric acid content was found to be practically
unaltered twenty-four to forty-eight hours after the same purine intake.

It would seem, therefore, that some _diagnostic_ importance may be
attached to the _hyper-uricæmia_ that is induced in _gouty_ subjects
after exogenous purines, as compared with its non-occurrence in non-gouty
subjects.

Another interesting point elicited by Pratt was that in his _gouty_
examples, although, after a purin meal, the uric acid content of the
_blood_ rose markedly, yet there was no apparent _delay_ or _diminution_
in the output of _exogenous purin_ in the _urine_. Thus, in one example,
after the intake of 190 grams of thymus gland, the uric acid in the
blood, in the first twenty-four hours, rose from 2·2 mg. to 4·4 mg.,
reaching, on the third day, a maximum of 8·7 mg., which, on the fourth
day, sunk to 2·7 mg. Nevertheless, 26·2 per cent. of the ingested purin
nitrogen was excreted as uric acid. Now, as pointed out in the preceding
chapter, it has been shown by many observers that in _gouty_ subjects
the excretion of _exogenous_ purin is _diminished_ and _retarded_. But
Pratt’s study of the blood shows that a marked increase and retention of
uric acid in the _blood_ may result from the ingestion of purin bases,
even when no evidence of retention is found on the examination of the
_urine_.[23]

The clear inference from this is that it is desirable that our _urinary_
findings in respect of _uric acid_ should be reviewed and controlled in
light of _blood examinations_ to the same end.


VARIATIONS IN URIC ACID CONTENT OF BLOOD INDEPENDENTLY OF DIET

Considerable variations in the uric acid content of the blood, according
to Pratt, may occur both in _gouty_ and _non-gouty_ subjects, and which
cannot be attributed to any _purin intake_. Such oscillations, moreover,
may ensue within a short time. A patient of his, admitted to hospital
suffering from a severe attack of _gout_, was placed upon a _purin-free_
diet. Twenty-four hours afterwards examination revealed only 2·7 mg. of
uric acid in his blood. Subsequently, after having had no food containing
purins for fifteen days, it contained 5·1 mg.

Marked variations in the uric acid content of the blood may likewise
occur in _non-gouty_ subjects. After being on a _purin-free_ diet for two
days, a patient of Pratt’s, with _recurrent iritis_, had 2·2 mg., while a
few months after, when on a mixed diet, his blood contained only 0·8 mg.

Again, great oscillations in the blood content of uric acid, independent
of diet, are sometimes found in cases of _non-gouty arthritis_. Thus, in
one chronic case of this nature, the blood when first examined contained
7·6 mg. of uric acid, but a few months later, when on a purin-rich diet,
only 0·8 mg. were present. In another instance of _primary polyarthritis_
the same was strikingly exhibited. Aged twenty-two years, the subject in
October was on ordinary diet. His blood at that period showed 2·7 mg. of
uric acid per 100 mg. of blood; in December, on a purin-free diet, 5·0;
and in May, on a similar dietary, 1·6 mg.

As to whether in healthy individuals, on a purin-free diet, similar
variations in the uric acid content of the blood occur, is not
sufficiently ascertained. The solitary example that may be cited is
by McLester, who, as a result of four examinations of the blood in a
normal person on a purin-free diet, found that its uric acid content was
practically constant.

The deductions that may be drawn from the foregoing findings are:—

    (1) That in _gouty_ subjects pronounced variations of the uric
    acid content of the blood may occur which are not attributable
    to the purin content of the food.

    (2) That in _non-gouty_ arthritis similar fluctuations in the
    blood content of uric acid, irrespective of diet, also occur.

    (3) That in _normal_ persons, on a purin-free diet, the blood
    content of uric acid, as far as is ascertained, does not show
    such variations.


WHAT RELATION, IF ANY, EXISTS BETWEEN THE URIC ACID CONTENT OF THE BLOOD
AND ATTACKS OF GOUT?

If uric acid be _causally_ related to gout, it would seem reasonable to
expect that the blood content thereof would stand in some clear relation
to the _incidence_ or _intensity_ of attacks.

But, according to Pratt and others, no variations indicative of such
a relationship obtain. For, independently of _acute_ attacks, and,
moreover, in the absence of any pronounced _renal inadequacy_, the blood
of gouty subjects, even on a _purin-free_ diet, contains, as a rule, 4-9
mg. of uric acid.

More pertinently to our point, in the experience of Daniels and
McCrudden, it transpires that, contrary to the usually accepted teaching,
typical _acute_ attacks might occur without any variation in the _uric
acid content of the blood_ or its _excretion_.

Nor did their iconoclastic findings cease here, for, _mirabile
dictu_! attacks ensued even when the uric acid blood content was at a
_sub-normal_ level; this latter, owing to the victims being at the time
on _atophan_, which increases uric acid elimination. In this connection
it is worthy of note that, according to Pratt, the uric acid content of
the blood may at times be low, even when atophan has not been taken. In
one of his cases, on a purin-free diet, only 1·7 mg. was present, and in
another case, on a mixed diet, 1·9 mg.

Daniels and McCrudden, too, note that the uric acid content of the blood
in gouty subjects may be _persistently_ lowered, _even under the normal
average_. His, again, has recorded an instance of a gouty subject,
with multiple tophi, whose blood did not contain an excess of uric
acid. Bloch, also, took 200 c.c. of blood from a man, aged twenty-five,
suffering at the time from a typical attack of gout in the big toe; but
uricæmia was not present.

Bass and Herzberg injected uric acid into the blood of gouty subjects
until its content thereof reached 10 mg. per 100 c.c., this without
any joint symptoms supervening. The same observers, aspirating _joint
fluids_ in _non-gouty_ subjects, noted that the uric acid content was
approximately the same as that of the blood. But, in contradistinction
thereto, in two _gouty_ subjects, victims of _uræmia_, they found in the
joint fluids 18·5 and 20·8 mg. of uric acid, while the blood content was
only 10 mg. and 8·2 mg.

Furthermore, intravenous injection of uric acid engendered a lesser
degree of _uricæmia_ in the gouty—this despite _impaired renal
excretion_. To their mind, therefore, the inference was that the _bodily
tissues_ in gout display an enhanced capacity for taking up uric acid.

Lastly, Walker Hall, discussing the question as to whether any relation
obtains between the degree of uricæmia and the onset of acute attacks,
observes that, “the evidence is more general than specific.” Thus he
reminds us that excessive intake of purin food has sometimes been
followed by, or associated with, an acute outbreak. Also, that the
leucocytic destruction which occurs during acute lobar pneumonia and
after the use of X-rays has occasionally coincided with an acute
paroxysm. To this, again, must be added the fact that atophan curtails
the duration of acute attacks, apparently by exciting an increased
uric acid output. Superficially regarded, these facts might appear to
be conclusive; but, as Walker Hall states, it must be recalled that
overeating, overdrinking, trauma, mental disturbances, atmospheric
vicissitudes, and bacterial infections have also preceded acute outbreaks.

To sum up, the main conclusions deducible from the foregoing clinical and
experimental findings would appear to be that:—

    (1) No constant relation has as yet been established between
    the uric acid content of the blood and acute attacks of gout.

    (2) No variations in the same apparently herald or accompany
    typical acute paroxysms.

    (3) Attacks may occur with a _sub-normal_ uric acid blood
    content.

    (4) The tissues of gouty subjects apparently possess an
    enhanced binding capacity in respect of uric acid.

    (5) _Given impaired renal excretion in gouty subjects_,
    the uric acid content of the _joint fluid_ rises markedly,
    exceeding that of the blood.


DISCUSSION OF THE FOREGOING DATA

While the researches of the past decade have proved distinctly
encouraging, yet we must not blind ourselves to the fact that the
foregoing findings, and alike our deductions therefrom, are largely
provisional; for we stand in grave danger of over-emphasising the
significance of the results forthcoming from the investigation of
isolated samples of blood from different individuals. The recorded
estimates of the uric acid content of the blood in _strictly normal
persons_ are all too few, the findings in _diseased_ subjects too
conflicting, to warrant dogmatic inferences, wide generalisations. In
truth, the problem is by no means as simple as may at first sight appear,
and this but a slight digression will suffice to make clear.

_The Significance of Uricæmia._—It is generally maintained that the
blood content of uric acid in gout is above normal. Yet the _excretion_
of _uric acid_, save during acute attacks, rests within physiological
limits. Again, _à propos_ of our claim that the _blood_ is _surcharged_
therewith, we have the awkward fact, as yet inexplicable on chemical or
physico-chemical grounds, that the blood-stream can hold in suspension
far more uric acid than has ever yet been met with in gout, according to
Bechhold and Ziegler no less than 50 mg. of _uric acid_ per 100 c.c. of
blood serum before deposition tends to occur. On the other hand, _urates_
are less soluble therein, not exceeding 2·5 mg. per 100 c.c. How remote
from the limit of saturation the highest figures observed in gout! What a
large margin of solubility is still available!

Again, the uric acid blood content in gout is far less than was formerly
thought. Only by a few milligrams does it transcend that found in normal
individuals. Can this slight disparity have such profound potentialities
as to determine the incidence or not of _gout_? and this with the
saturation point still so remote. The urates, too, being practically
non-toxic, how difficult to conceive that the almost trivial excess of
the uric acid blood content over the normal is adequate to produce the
fulminant and dramatic phenomena of acute gout.

Again, though we speak of uricæmia as a dominant characteristic of
gout, we are uncertain whether the alleged increase in the uric acid
content of the blood is _real_ or merely _apparent_. We can, it is true,
extract _uric acid_ and _urates_ from the blood-stream, but it does not
necessarily follow that it is as such that they circulate _in vivo_.
We need walk circumspectly here for, despite the most modern methods
of blood analysis, we are still ignorant as to the exact form in which
uric acid exists in the blood-stream; whether the purins of the food
appear in the blood-stream as _sodium monourate_, or in _organic fusion_.
Accordingly, in the interests of progress, it were well to bear in mind
the pitfalls that beset uric acid estimation, the insufficiently eclectic
capacity of even the most modern tests, and to consideration of these
more chastening aspects we now proceed.

_Sources of Fallacy in Uric Acid Estimation._—With Folin’s findings as
his basis, Walker Hall estimates that, excluding the lymphatics and
lymph spaces, the entire blood-stream contains normally 70 mg. of uric
acid, _i.e._, 2 mg. of uric acid per 100 grams of blood, 3,500 c.c.
(total quantity of blood).

Thence he argues that, inasmuch as about 1 litre of blood traverses
the kidney per minute, the total content thereof of _uric acid_ would
gain access to the renal organs in three and a half minutes. Now the
average total output of the kidneys is 500 mg. per twenty-four hours.
Accordingly, assuming that the blood arriving at the kidneys contains as
a constant the above 70 mg. uric acid, the total daily output would pass
through these organs in twenty-five minutes.

Now, given immediate extraction of all the uric acid by the renal cells,
then the blood in the renal veins will become _free of uric acid_. If so,
the estimates of the uric acid content of the blood will reflect exactly
the measure of the _endogenous_ or _exogenous_ nuclein metabolism. But,
“if the renal vein blood is not _purin-free_, then the _estimations will
fail to yield a true picture of the activities of nuclein exchange_.”

Again, as to the precise import of isolated estimates of the uric acid
blood content, we must recollect that the _excretion of purins_ is
not distributed evenly over the twenty-four hours, varying as it does
under the influence of food, exercise, sleep, and other factors. _A
propos_ of this, Pratt’s observations clearly show that both in _gouty_
and _non-gouty subjects fluctuations in the uric acid blood content_
also occur, and this independently of _diet_. To what, then, may these
variations be referred? Obviously a question of great moment, especially
when we recall the eccentric behaviour of the _blood uric acid_ in
relation to the incidence of _acute gouty attacks_. For, until the inward
meaning of these vagaries is revealed, the value of recorded estimates
must necessarily be discounted considerably.

We must recall, too, that a certain moiety of the purins derived from
nuclein metabolism lags in the _lymph_ spaces and _lymphatics_, and
this, as Walker Hall reminds us, must reduce the quantity present in the
blood-stream at any one time. Also, as the same authority reflects, the
lymph stream being probably richer in _sodium ions_ than the blood, the
entry of the nucleins therein may be retarded and so lead to a still
further reduction of the blood content.

There is yet another possibility, he reminds us, viz., “that the
purin content of the blood varies in the peripheral pulmonary hepatic
and osseous streams, and that, while in some parts the purins are
being carried to the kidneys for excretion, in others they are being
transported from one organ to another for further metabolism.”

For, as before pointed out, the enzymes responsible for the ultimate
disruption of the _nucleosides_ are scattered in different organs, and
Walker Hall suggests that “a transport of half metabolised nucleotides
from one organ to another may form a part of the normal processes of
nuclein metabolism.” This may well lead us on to consider the limitations
that beset even the most modern tests in use for uric acid determination.

_Disabilities of Modern Tests._—With all its outstanding advantages, even
the Folin method of uric acid estimation has its drawbacks. As Curtman
and Lehrman have pointed out, different workers have, even on _identical
blood samples_, arrived at results which vary widely. Nor, disconcerting
though it be, do the limitations of this mode of hæmo-analysis cease here.

Thus we know from Gudzent and Apolant that the soluble but unstable
biurate is constantly being transmuted into an insoluble stable type,
in other words, metamorphosis from one _isomer_ into another. But,
unhappily, the tests to hand fail of differentiation of the several
_tautomeric_ forms of uric acid. Also, as isomers of uric acid actually
exist, then _quâ_ Walker Hall, why not isomers of _purins_ and
_pyrimidins_ also? But here again our tests are insufficiently eclectic.
They give us no clue as to the affinities or blends of purins or
pyrimidins for or with other substances.

Again, as our criteria fall short of identifying the exact form of the
“purin combinations” it follows, therefore, that they tell us nothing as
to whether “the increase is due to a more active transport of purins from
one organ to another for further metabolism or simply to a transport to
the kidneys for elimination.”

In other words, hampered by the above disabilities in our tests, it is
beyond our power to determine whether “the increases denote a supernormal
nuclein metabolism or an unusual type of nuclein cleavage.” Should it
ultimately transpire that the increase in the purin blood content is a
_real_ one, viz., made up of “an excess of normally formed and normally
bound purins,” a great step forward will have been achieved. For, to
account for the same it will, as Walker Hall observed, be necessary to
postulate a _supernormal nuclear activity_ of _generalised or_ localised
distribution.

_Need for Further Investigations._—While none can doubt that, by means of
chemical investigation of the _blood_, the clinical problem of gout will
be elucidated to a much greater extent than has been possible by means of
_urine analysis_, still much remains to be done before recent findings
can be applied to the solution of the etiology of _gout_.

The results of _blood analyses_ up to now have afforded us no clue as to
the intimate nature of the warp in _nuclein metabolism_. At the most,
the researches in this sphere do but make it increasingly clear that
uricæmia is _not the cause but the result_ of gout.

Albeit, this conclusion does not justify us in putting out of court all
thought of _uric acid_ in connection with gout. Any tendency thereto
will be immediately checked when we recall that uratic deposits, _i.e._,
_tophi_ constitute the solitary unequivocal token of gout, and to this
aspect of the question the ensuing chapter will be devoted.

Meanwhile, systematic investigations of the purin content of the blood,
not only in gouty but in _normal_ subjects, would surely dissipate much
of the obscurity that envelops this complex question. It were well, too,
that _blood_ and _urine_ analyses go hand in hand in our investigations.
How illumining these have been in connection with _atophan_, the
increased urinary output of uric acid having been found to be correlated
with a simultaneous sinking in the level of the uric acid of the blood.

Again, the _excretion of urinary purin_ ebbs and flows with the intake
of food and the degree of muscular activity, while sleep also exerts an
influence, not to mention constitutional disturbances, _e.g._, fever
infections, etc.

Can it be doubted that the _blood_ content of uric acid varies with these
same vicissitudes? Walker Hall tells us that the data to hand, “as to
the rapidity of the appearance of purins in the blood-stream after food,
infections, fever, etc.,” though few in number, yet suggest that “the
excretion by the kidney is _tidal_ in character, and that the blood uric
acid has similar characteristics.” In light of these possibilities, we
may well pause before attempting to appraise exactly the significance of
isolated blood examinations.

What, too, as the above authority observes, of the influence on the
_gouty uricæmia_ of infancy, puberty, the menopause, and for that matter
the pre-senile and senile periods of life with their associated vascular
lesions? The researches of Uffenheimer prove that even in young children
the disorders of purin metabolism distinctive of gout are to be met with,
_i.e._, “infantile gout.”

We stand also in urgent need of knowledge as to the uric acid blood
content in the _early_ as opposed to the late stages of gout; in need,
too, of further examinations of the blood to this end, not only during
the passage of _acute_ attacks, but even more under those conditions
which are presumed to determine their incidence.

But, despite these gaps in knowledge, these disabilities of technique,
there is no need for despair. “It is a slow progress along the zigzag
which leads to the centre of the ‘gouty maze,’ but the researches of the
last decade have opened up many new and possible pathways thereto.”




CHAPTER XII

URATOSIS IN RELATION TO GOUT


The two salient features of the gouty diathesis are:—

    (_a_) The tendency to excess of uric acid in the blood, _i.e._,
    _hyper-uricæmia_, and

    (_b_) The tendency to uratic deposition, _i.e._, _uratosis_.

With the former we have dealt, but before passing to discuss the latter,
it will, we think, be advisable to review both these morbid tendencies in
relation to gout.

Hyper-uricæmia and uratosis, though they both occur in gout, are
by no means of identical pathological valency or significance. In
hyper-uricæmia the uric acid, either in a free state or combined,
circulates in the blood and lymph. In uratosis the uric acid is anchored
in solid form in the substance of the tissues. In the former, then, the
uric acid, if it be noxious, acts as a chemical poison, in the latter as
a mechanical irritant.

But the more striking contrast is that while hyper-uricæmia is not
restricted to gout, but occurs in many other disorders; on the other
hand, uratosis is absolutely confined to the gouty state, constituting
its pathognomonic stigma.

Again, hyper-uricæmia may exist for prolonged periods without producing
uratosis. But uratosis cannot, as far as is ascertained, occur without a
co-existing hyper-uricæmia. From these disparities it may legitimately be
inferred that the factors responsible for the genesis of hyper-uricæmia
and of uratosis, are not identical; in other words, that in uratosis some
other agency or agencies are at work over and beyond those that beget
hyper-uricæmia.

Lastly, inasmuch as uratosis stamps the seal of specificity upon gout,
it follows, from this and the above considerations, that there is a
more intimate relation between gout and uratosis than between gout and
hyper-uricæmia, and that the factors which make for uratosis have a more
intimate bearing upon the pathogeny of gout than those which lead to
hyper-uricæmia.


CONSTITUTION OF TOPHI

    “Et tophus scaber, et nigris exesa chelydris Creta.”

                            _Virgil, Georg._, ii., 214.

The view that tophi were composed of chalk prevailed for centuries. As
we see such was the conception of Virgil, and in our own country John
Hunter entertained the same erroneous notion, while amongst the laity
this view as to their nature is held widely even to-day as it was in the
time of Dryden.

    “Knots upon his gouty joints appear,
    And chalk is in his crippled fingers found.”

                                 _Dryden, Pers._

Albeit, the term “chalk-stones” is a misnomer, as tophi, when pure,
may be wholly devoid of lime. Modern analyses, too, have failed to
demonstrate the presence of calcium carbonate, the essential ingredient
being _urate of soda_.

On the authority of Rendu, we have it that Tennant and Pierson were the
first to demonstrate the presence of uric acid in gouty deposits, which
discovery was later confirmed by Fourcroy and Wollaston (1797), these
latter observers showing that they consisted almost exclusively of urate
of soda.

Subsequently to Wollaston’s day, many analyses have been conducted, by
Marchand, Lehmann, Wurzer, and Langier, L’Heretier, Ebstein and Sprague.
Of the various findings we append those by Marchand, Lehmann and one of
later date by Ebstein and Sprague.


MARCHAND’S ANALYSIS

  Urate of soda           34·20
  Urate of lime            2·12
  Carbonate of ammonia     7·86
  Chloride of sodium      14·12
  Animal matter           32·53
  Water                    6·80
  Loss                     2·37
                         ------
                         100·00
                         ======


LEHMANN’S ANALYSIS

  Urate of soda           52·12
  Urate of lime            1·25
  Chloride of sodium       9·84
  Phosphate of lime        4·32
  Cellular tissue         28·49
  Water, loss, etc.        3·98
                         ------
                         100·00
                         ======


EBSTEIN AND SPRAGUE’S ANALYSIS

  Uric acid               59·70
  Tissue, organic matter  27·88
  Sodium oxide             9·30
  Potassium oxide          2·95
  Calcium oxide            0·17
  MgO, Fe, P₂O₅, S       Traces.

It will be seen that all of them agree more or less closely as to the
essential ingredients being uric acid and soda. According to Ebstein and
Sprague they consist usually of almost pure _biurate_ of _sodium_ and
_potassium_. But, as a rule, after a time _calcium_ salts are deposited.
Dunin, it may be noted, has found deposits resembling gouty tophi, which
contained only calcium salts. Kahn, again, claims that tophi do not
always consist solely or even largely of urates, but that these may be
replaced by _calcium_ salts. It may be added, too, that M. B. Schmidt has
recorded, under the designation of “Calcium gout,” a case in which there
existed a generalised deposition of calcium, and this in tissues other
than those usually involved in “metastatic calcification.” But, to sum
up, although there may be admixture of lime salts and organic matter, the
salient chemical constituent of tophi is _biurate of sodium_.


MODE OF FORMATION

Gouty tophi, like all pathological concretions, are laid down in
accordance with a definite law. In the first instance, a central nucleus
is essential. To this must be added a “binding substance” or structural
framework of different nature from the main mass of the concretion.

Garrod, discussing the intimate structure of “chalk-stones,” observes
that, “the large amount of phosphate of lime occasionally met with is
probably derived not only from the tissue in which the chalk-stones have
been developed, but likewise from secondary deposition, the result of
ordinary inflammation around the original nucleus (urate of soda) which
acts as a foreign body.”

It is, however, quite possible that some substance other than _urate of
soda_ constitutes the primary nucleus, for, as we now know, concretions
most frequently gather around masses of mucin, clumped bacteria,
desquamated cells, precipitated proteins, etc. Thus, the renal _uric acid
infarcts_, supposed to result from disruption of the nucleo-proteins
of the _fœtal nucleated red corpuscles_, take origin around injured
_epithelial_ cells, which latter form the nucleus.

As to _gouty tophi_, too, it has been suggested that they form in
response to any _toxin_, resistance to which may involve death of the
tissue cells with consequent disruption of their _nucleins_ and formation
of _urates_. Such was the view held by Woods. Hutchinson, who also
thought that the calcareous accretions might be regarded as “protective,”
analogous to the formation of shells in the invertebrates, the process
here consisting in the deposition of lime salts in cells already
saturated with uric acid and urates.

In any case, whatever be the exact nature of the nucleus, the urate of
soda collects thereupon, the acicular crystals tending to assume the
form of radiating needles. But the successive depositions not being of
regular incidence, the surface of the crystals, in the intervals of
quiescence, becomes covered by _mucin_, animal or earthy matter. Hence,
the concretions display not only a _radiating_, but a _concentric_ or
_laminated_ structure.

The mucin acts as the “binding substance,” the crystals lying in its
meshes, and, moreover, remaining as the framework of the concretion even
after the crystals are dissolved out; in other words, the gouty tophus
is made up of a blend of _crystalloids_ and _colloids_, evolved from
solutions of the same character.

The importance of recognising the true nature of this binding substance,
_i.e._, mucin, merits a brief digression, in light of Ebstein’s view that
local tissue _necrosis_ is a necessary antecedent to uratic deposition.
Now, exhaustive studies of the histology of uratic deposits, both those
experimentally induced and of spontaneous gouty origin, have been
conducted by Freudweiler, His, Krause, and Rosenbach.

All their results, according to Gideon Wells, “indicate that uric acid
and urates excite some slight inflammatory reaction, cause a slight
local necrosis, and seem to act as a weak tissue poison.” According
to Rosenbach, however, this sequence is not invariable, inasmuch as
he noted that such deposits may occur without inducing necrosis. More
pertinently to our contention, however, is it that Krause’s experience
seems to indicate that errors of interpretation were possible. Thus, he
suggests that part of the material in the areas of uratic deposits merely
constituted the _framework_ of a crystalline deposit, though such were
currently regarded as _strands_ of _necrotic tissue_.

But, to resume, tophi being blends of _crystalloids_ and _colloids_, we
must recollect that the suspension capacity of _colloidal_ solutions for
crystalloids is much superior to that of simple solutions, by reason of
the fact that at the surface of each colloidal particle there exists a
zone in which the crystalloids are much more closely aggregated than
elsewhere, thus permitting more crystalloids to be dissolved in the
solvent between the colloidal particles. But, be it noted, this same
tendency to concentration of the crystalloids at the surface of the
colloidal elements leads to the colloids acting as determinants of
_precipitation_ when _crystalloids_ are in excess. Accordingly, when the
crystalloids pass out of solution, they form crystals or precipitates
intimately blended with the colloids. Thus, for example, when uric acid
crystallises out of urine it carries with it the colloidal pigments. On
the other hand, if the colloids are precipitated, the solvent capacity
of the solution being consequently depreciated, the crystalloids are
deposited in intimate relation with the colloids.

Again, Schade has pointed out that colloids may precipitate in reversible
form or not. If in irreversible (_e.g._, fibrin) form, the concretion
will remain permanent. But if the colloidal precipitate is reversible,
it may be redissolved, as happens with the uric _acid infarcts_ of the
infant’s kidney. In conclusion, we see, therefore, _re_ crystalloids and
colloids in animal juices, that the conditions of their solubility are
most complex, and though they do not explain the nature of gout, the
variations doubtless stand in intimate relation to the _formation of
tophi_.


LOCALISATION OF URATIC DEPOSITS

Uratic deposits evince a decided predilection for _cartilages_, tendons,
muscles, and skin. This localised distribution of the depositions would
seem to suggest their dependence on _local tissue peculiarities_. Now
the presence of _sodium_ salts in a solution diminishes the solubility
of urates therein. Consequently, in seeking to explain the incidence of
_tophi_, it was suggested that _cartilage_ and _tendons_, being richer
in _sodium ions_ than the _blood_, this might account for the fact that
urates tend to be precipitated in these particular structures.

Again, Almagia, working in Hofmeister’s laboratory, noted that thin
sections of _cartilage_, if left for some hours in a solution of sodium
urate, will take up _uric acid_. Direct inspection readily reveals the
presence of white foci and diffuse opacities due to uratic deposits. The
marked affinity of normal cartilage for uric acid is again attested by
the fact that, given injection thereof in quantity into the peritoneal
cavity of rabbits, the uric acid may often be detected by the murexide
reaction in _joint cartilage_, though apparently not in other tissues.

This behaviour would appear to justify the conclusion that the observed
accumulation of uric acid in the cartilages in the presence of states
of _uricæmia_, may be explicable on this same basis. In any case, this
marked affinity of even _normal_ cartilage for uric acid seems to
disprove the necessity of Ebstein’s postulate, viz., that the dissolved
uric acid sets up inflammation, and that an _antecedent necrosis_
precedes the _deposition of urates_. Still, even if we concede the fact
that _normal cartilage_ has a marked affinity for _uric acid_, how is it
that in _leukæmics_, despite their high blood content of _uric acid_,
no _uratic deposits_ ensue? Does not such disparity seem to indicate
that in gout some other factor intrudes? in other words, that the excess
of _sodium ions_ in particular tissues, while it may favour deposition
therein, is inadequate of itself to actually determine the formation of
tophi.


THE CAUSATION OF TOPHI

Many and divers are the theories that have been propounded to account
for the genesis of tophi. For some their incidence would appear to
predicate something abnormal in the conditions of uric acid solution and
circulation. Others have pinned their faith to some affinity on the part
of the bodily tissues for uric acid—an enhanced retention capacity on
their part for this substance. Some again, impressed by the objective
changes that mark the clinical evolution of tophi, have been led to
regard them as _concomitants_ or _sequels_ of _gouty inflammation_. But,
be the true explanation what it may, we may well preface our discussion
of the various theories by the obvious comment, viz., that the origin
of tophi must doubtless depend in the ultimate upon _constitutional_ or
_systemic_, as well as _local_, factors.


SOLUBILITIES OF URIC ACID

In the older conceptions of the pathology of gout the hypothesis that
found most vogue was that the separation of uric acid from the blood into
the tissues was due to _diminished alkalinity_ of the blood and tissue
juices; but, as before pointed out, it has been established that the
alkalinity of the blood is _not_ reduced, and the theory has consequently
been abandoned.

But, with the advent of Gudzent’s findings, viz., that uric acid
existed in two forms—one soluble and unstable, and the other insoluble
and stable, and that the former is constantly changing into the
latter—another conception of the origin of tophi arose. It was supposed
that, by reason of the disparity in solubility of these _tautomeric_
types of _uric acid_, the blood in gouty subjects must at times be
in a state of _super-saturation_ with uric acid; and, moreover, that
equilibrium could only be restored through abstraction of the urates by
crystallisation.

Unfortunately for this theory, it has been shown that the blood of gouty
subjects is not _super-saturated_ therewith; indeed, over and above the
highest increments hitherto met with in gouty blood, a considerable
margin of solubility for uric acid is still available. In truth, the
problem is by no means so simple; for the conditions governing the
solvency of uric acid in the blood are bewilderingly complex, subject
as they are to the manifold variations in solubility exhibited by
crystalloids in the presence of the many divers colloids.

But, to resume, Minkowski, it will be recalled, noted that from a
mixed solution of _uric_ and _nucleinic acids_ the former cannot be
precipitated by either acetic acid or alkaline ammonio-silver-magnesia
mixture. Accordingly he advanced the view that uric acid “primarily
exists in the blood and the tissue juices in combination with nucleinic
acid, and that, not only the conversion of the purin bases into uric
acid, but also the solubility and transportation, as well as the further
changes of the uric acid in the living body, is regulated by this linking
with a nucleinic acid rest.”

But, unfortunately for the value of this hypothesis, there is no proof
that _nucleinic acid_ is actually present in the blood; for, as Fürth
remarks, is this inhibition of the precipitation of uric acid, in the
presence of nucleinic acid, “necessarily indicative of a true acid
combination with nucleinic acid,” “but such inhibition of precipitation
is rather to be referred to the general group of variations of solubility
which are manifested by crystalloid substances in the presence of all
sorts of colloids.”

Complex phenomena of solubility of this nature must be considered in
connection with the circulating uric acid. Nucleinic acid is not the only
important substance, but “the general mass of the blood proteins must be
particularly thought of.”

Continuing, Fürth reminds us that uric acid is much more soluble in
_blood serum_ than in water, and forthwith envisages this disparity in
light of the factors that affect solubility of uric acid in the _urine_.
The latter is markedly influenced by the presence of urea and di-sodium
phosphate, and the relation of this to mono-sodium phosphate. Nor, he
reflects, is there any doubt “of the importance of such inter-relations,
too, in the formation of _uric acid deposits in the tissues_.” But he
adds, “Although the importance of these complex conditions of solubility
as they prevail among colloid and crystalloid substances in the animal
juices may be accepted in relation to the formation of uric acid
concretions, there is no real reason for seeking the explanation of gout
in this sphere.”


TOPHI IN RELATION TO URICÆMIA

It might be thought that some relationship might be established between
uratic deposits and the degrees of uricæmia, but the data to hand give
no countenance to the assumption. Thus, His has recorded the case of a
gouty subject with multiple tophi whose blood did not yield an excess
of uric acid. Pratt, again, could trace no relation between the amount
of uric acid in the blood and the severity or character of the disease.
Two of his patients had numerous and widely distributed large deposits
of sodium urate beneath the skin, yet the _blood content_ of _uric
acid_ in both was less than the average amount found in gout. Thus, on
a purin-free diet, one had 2·4, the other 2·2 mg. These findings, he
considers, show that the presence of _multiple tophi_ is no indication
that a state of _hyper-uricæmia_ exists.

Walker Hall, discussing this same question, holds that there is but
little evidence “as to the relation of uricæmia to the formation of
tophi.” He asks the question whether the deposition is the outcome of
abnormal purin combination in the blood and lymph stream? which latter at
present, he states, are regarded as passive carriers of the urates. For,
he says, the small purin increase in gouty blood cannot surely make all
the difference, seeing the large volume of solubility still available.
The physico-chemical hypothesis, he claims, is inadequate to explain the
relationship between uricæmia and the tophi, and hazards the suggestion
that after all it may be that “the uricæmia plays little or no part in
the depositions, and that these are due to the defective removal of
substances resultant from local nuclear activities.” He asks, moreover,
whether such substances differ in type from those of normal nuclein
metabolism and so fail to be suspended in the surrounding lymph in such
a way as to ensure their entrance into the blood-stream? Like others,
he notes that atophan brings about a removal of some of the deposited
urates. But such diminution of the tophi may, of course, he says, be
due to increased flow of serum to the inflamed part; though, on the
other hand, the more massive deposits “are surrounded by layers of young
granulation tissue and phagocytes and peritophal fibrous tissue, and
these in turn offer some hindrance to the permeation of serum or drugs.”

In reviewing the foregoing views as to the formation of tophi, it is
obvious we stand in urgent need of more knowledge. Neither the chemical
nor the physical theory or a combination of the twain seems adequate.
This for the salient reason that, as far as the existing evidence permits
us to draw conclusions, it would seem probable that not only local but
constitutional or systemic conditions play an important _rôle_ in tophi
formation.

But as far as our discussion has advanced, we may, we think, be justified
in the following deductions:—

    (1) That tophi are blends of crystalloids and colloids and
    subject to the complex conditions of solubility attaching to
    such combinations.

    (2) That the relatively high sodium content of certain tissues,
    _e.g._, cartilage, favours the incidence of uratic deposits
    therein.

    (3) That tissue necrosis is not necessarily an antecedent to
    uratic deposits.

    (4) That no relationship can be established between the
    incidence or multiplicity of tophi and uricæmia.

It will be seen from these conclusions that the proximate cause
responsible for the genesis of tophi is yet to seek, and in pursuance of
our quest we turn to another aspect of this complex subject.


TISSUE AFFINITIES FOR URIC ACID

Injecting uric acid intravenously into _gouty_ subjects, Umber noted
that at times the whole was retained, but on some occasions was excreted
in fractional portions. On the other hand, a _normal_ individual under
similar circumstances eliminates it completely. In explanation thereof,
he proffered the opinion that this failure on the part of gouty persons
to excrete exogenous uric acid was due to a _special affinity of their
tissues for uric acid_.

As to intravenous injection of uric acid, however, modern investigation
has established that, both in normal as well as gouty subjects, its
excretion is spread over several days, and the _whole_ is _not_
recoverable from the urine. Now this incomplete excretion or _retention_
of uric acid was attributed to _defective elimination by the renal
cells_; but, as shown in a previous chapter, this conception fails of
demonstration. Nor, for that matter is there any proof either that the
retention is due to _fixation of the uric acid in the blood serum_.
Accordingly, to our minds, it is permissible then to canvass the further
possibility adumbrated by Umber, viz., that an _increased affinity of
the tissues for uric acid_ may haply account for the diminished purin
excretion, the excess of uric acid in the blood, lymph, and tissues, and
that these same may lead to _uratic deposition_.

This last hypothesis derives colour from the findings of Schmoll, Magnus
Levy, Vogt, Reach and Bloch, who noted that, after giving thymus to
_gouty_ persons, they found far less uric acid in the urine than in
the case of normal subjects. Also, that the ingestion of thymus by the
victims of _chronic_ gout repeatedly resulted in acute outbursts of
the disease. Moreover, as we saw when discussing the _sources_ of uric
acid, there are cogent reasons for avoiding a too restricted conception
which would make the leucocytes, the muscles, or the digestive glands
alone responsible for the _endogenous production of uric acid_; in other
words, that a more catholic attitude on our part is indicated, one which
would envisage it as the outcome of continuous and _general cellular_
wear and tear. That an _increased cellular destruction_, as induced
experimentally, _e.g._, by exposure to Röntgen rays, is capable of
raising the _blood content_ of _uric acid_ in a _gouty_ subject, and of
precipitating a gouty paroxysm, may be inferred from the researches of P.
Linsen.


RETENTION CAPACITY OF TISSUES FOR URIC ACID

It may be recalled that Wiechowski and others observed that in man, of
_parenterally_ introduced uric acid, 80-90 per cent. reappears in the
urine. Accordingly, Schittenhelm and Wiener argued that, if uric acid is
indestructible in the human body, then, given _retarded elimination_, the
_tissues_ should contain considerable quantities thereof. Subsequently,
in 1914, they sought to investigate human tissues as to their content
of uric acid. Their studies were conducted on three examples, a case of
anuria, one of pernicious anæmia, and one of gout.

The case of _anuria_ occurred in a male, aged sixty-two, in sequence to
thrombosis of both renal veins following operation. Two-hundred gram
samples of the following tissues, lung, heart, spleen and liver, were
examined for uric acid with wholly negative results. The residue of
the organ was worked up together, but only 0·01 gram of uric acid was
isolated.

In the case of _pernicious anæmia_ no uric acid was demonstrable. The
_gouty_ subject had for twenty-five years suffered from typical attacks
and exhibited many auricular tophi. The following organs, in their
entirety, were analysed, the _liver_ (1,550 gram), no uric acid; _spleen_
(290 gm.), 10 mg. uric acid (3·5 mg. per 100 gm.); _kidney_ (270 gm.),
no uric acid; _lung_ (930 gm.), 15 mg. uric acid (1·6 mg. per 100 gm.);
_muscle_ (440 gram), no uric acid; and _intestine_ (420 gram), no uric
acid.

It will be seen that _uric acid was either absent or present in minimal
amounts_, and these results Schittenhelm and Wiener interpreted as
confirming their long advocated contention as to the _destructibility of
uric acid_ in the human organism.

Morris S. Fine, from the results of similar investigations, considered
the failure of these observers to isolate _uric acid_ in these cases of
_anuria_ and _gout_ as most remarkable. He considers “their results may
in part be ascribed to the use of hot sodium hydroxide previous to the
precipitation of the proteins in the extraction of the tissues, as the
instability of uric acid in alkaline solutions is a well-known property.”

In this criticism Fine would appear to be fully justified, in view of the
marked contrast between the findings of Schittenhelm and Wiener, and his
own data is recorded in the tables on p. 159.

While it is unfortunate that Fine’s theory contained no instances
of _gout_, his findings are a definite proof that, to quote his own
words, _uric acid can be demonstrated in considerable concentrations
in human tissues_. Incidentally, also, his tissue analyses are flatly
contradictory to Schittenhelm and Weiner’s persistent contention, viz.,
that the human organism _can decompose uric acid_.

Gideon Wells states that in normal individuals the tissues contain but
little uric acid, and this not in quantities sufficient to permit readily
of its isolation in a pure state. Albeit, Wells found considerable
amounts of uric acid in the tissues of a young woman who, in sequence to
poisoning with HgCl₂, died after complete suppression of urine for nine
days.


TABLE I.—CONCENTRATION OF URIC ACID IN HUMAN TISSUES AND FLUIDS PER 100
GRAMS OF MATERIAL

  ------------------+-------+-------+-------+---------+---------+
        Case.       | E. E. | T. D. | S. H. |  M. F.  |  C. M.  |
                    |Uremia.|Uremia.|Uremia.|Diabetes.|Diabetes.|
  ------------------+-------+-------+-------+---------+---------+
                    |  mg.  |  mg.  |  mg.  |   mg.   |   mg.   |
  Blood             | 15·4  | 14·3  | 17·0  |   0·7   |   0·7   |
  Pleural fluid     | 16·7  | 15·9  |       |         |         |
  Ascitic fluid     | 18·0  |       |       |         |         |
  Pericardial fluid |       | 14·3  | 18·0  |         |         |
  Subcutaneous fluid| 18·0  |       |       |         |         |
  Spinal fluid      |  2·8  |  2·0  |  4·7  |         |         |
  Skeletal muscle   |  8·0  |  3·9  |  5·8  |   0·7   |   2·6   |
  Heart muscle      | 10·0  |  7·3  |  8·8  |         |   1·2   |
  Liver             | 18·0  | 15·6  | 11·5  |         |   5·0   |
  Spleen            | 12·6  | 14·3  |  9·1  |         |   1·2   |
  Skin              |       | 13·0  |       |         |         |
  ------------------+-------+-------+-------+---------+---------+

  ------------------+-----------+----------
        Case.       |   S. T.   |  H. J.
                    |Amputation.|Pneumonia.
  ------------------+-----------+----------
                    |    mg.    |   mg.
  Blood             |    0·7    |
  Pleural fluid     |           |
  Ascitic fluid     |           |
  Pericardial fluid |           |
  Subcutaneous fluid|           |
  Spinal fluid      |           |
  Skeletal muscle   |    2·0    |
  Heart muscle      |           |
  Liver             |           |   4·0
  Spleen            |           |  Trace
  Skin              |           |
  ------------------+-----------+----------


TABLE II.—CONCENTRATION OF URIC ACID IN MISCELLANEOUS HUMAN TISSUES PER
100 GRAMS OF MATERIAL

  -----------------+------------
       Tissue.     | Uric acid.
  -----------------+------------
                   |    mg.
  Pectoral muscle  |    2·5
  Uterine muscle   |    2·0
  Uterine muscle   |    2·5
  Uterine muscle   |    1·2
  Mixed tonsils    |    1·7
  Thyroid          |    0·0
  -----------------+------------

Again, as before alluded to, Bass and Herzberg found that intravenous
injection of uric acid caused less _uricæmia_ in the _gouty_, despite
diminished renal excretion. Hence, they concluded that _in gout the
retention capacity of the tissues for uric acid is augmented_.

Fürth, an ardent advocate of Umber’s hypothesis, emphasises the fact
that Wiechowski was never able to detect any evidence of _uricolysis_
in the human body. Continuing, he observes, if we reject all idea of
_uric acid retention in the tissues_, “It would be a particularly
difficult thing to understand why gouty patients do not simply expel by
a compensatory hyper-excretion the uric acid which is accumulated from
a supposed failure of uricolysis; precisely as in leukæmia the patient
compensates simply by an exaggerated excretion of the excessive uric acid
which is mobilised in the body from the excessive purin decomposition.”
His conclusion, therefore, is that, “_In the gouty individual there
must exist some cause which makes a compensatory uric acid excretion
impossible; and that is plainly a retention affinity of the tissues,
because of which the uric acid is actually held in the tissues._”

In light of Fine’s revelations the retention capacity of the bodily
tissue for uric acid may, we take it, be considered as fairly well
established. But, in view of the _precipitation or anchoring of urates
in the tissues in gout_ it is most desirable that further investigations
be made to discover whether in _gouty_ subjects the _tissue retention
capacity_ for _uric acid_ is _enhanced_.

“The impression,” says Fürth, “grows on one that this hitherto little
considered factor, of an increased affinity of the tissues for uric acid
in the gouty subject is very much closer to the real kernel of the gout
problem than, for example, the question of the fixation of uric acid in
the blood about which there has been so much contention, and with which
of necessity we are compelled, at least, to some little extent to concern
ourselves.” The results of modern researches tend to support this more
catholic conception. We would recall that Lewis and his co-workers,
seeking the source of the _increased endogenous purin excretion_ that
follows ingestion of _purin-free_ food, were forced to reject the view
that it was solely derived from katabolism of the _nuclear_ substance
of the _digestive glands_, and to refer it instead to “wear and tear”
of the _body cells as a whole_. Precisely the same change in attitude,
we may remind our readers, has overtaken us in regard to the site of
_urea_ formation, viz., that not only the _liver_ cells, but those of the
muscles also participate in its production.

While admitting that dogmatism is out of place, still to our mind this
theory of _tissue retention_ makes strong appeal. In light of it the
nebulous “gouty diathesis” seems on its way to become incarnate in some
_inborn peculiarity_ of _tissue-function_, a falling short of full
physiological activity, or, as M. Rendu termed it, a “_primordial vice of
nutrition_.”

In other words, in gout there is no rift nor lack of finish in the
orderly sequence of enzymatic reactions that eventuate in _uric acid_.
Uric acid is formed and, as far as we know, after a normal fashion.
But, here comes the flaw, viz., the uric acid, when formed, fails of
transport and elimination. It is _precipitated_ and _anchored_ in the
_tissues_, from whose grip it fails to detach itself. In short, it is not
the formation of uric acid, or its failure of further metamorphosis, but
the _retention_ of uric acid, and more pertinently, its _fixation in the
tissues_ that constitutes the salient feature of gout.

Now, all modern research tends to indicate that uric acid is not an
intermediary, but a _terminal_ product of metabolism, and, moreover,
that there are no _uricolytic_ ferments within the body whereby its
destruction can be accomplished.

If we grant that—

    (1) Uric acid is not an intermediate but an end-product of
    metabolism; and

    (2) That the human body is devoid of uric acid-destroying
    enzymes,

then it follows that man, _ipso facto_, is _potentially liable to uric
acid retention and deposition_, the same objectivated as _tophi_. In this
innate potentiality of and to _uratosis_ resides the “gouty” diathesis.

If the postulates (1) and (2) be established, then, though it sound rank
heresy, it follows that gout is not, chemically speaking, an “error of
metabolism.” Not, at any rate, in the ordinary acceptation, viz., not
a failure in the transmutation of uric acid into urea and intermediate
products. If uric acid be an _end-product_, then no further cleavage into
_urea_, etc., occurs, and in this connection the failure to discover
_uricolytic enzymes_ is significant.

We have before proffered the suggestion that not only local, but
_constitutional_, or systemic influences also play a part in the origin
of tophi. Provisionally, therefore, we would infer that—

    (1) The tissues of gouty subjects display an abnormal affinity
    for uric acid, _i.e._, an increased retention capacity for the
    same;

    (2) That certain chemico-physical factors, previously alluded
    to (content of sodium ions, etc.), favour the incidence of
    uratic deposits in particular tissues.

In other words, we have in these two elements haply the constitutional
and local factors that we postulate as essential to the formation of
tophi. Albeit, they represent but _latent tissue potentialities_,
inadequate of themselves to determine the eruption of _tophi_.

Moreover, be it recalled that the _causa causans_ of gout must be
responsible not only for the incidence of _tophi_, but also for the more
dramatic features of gout, its _arthritic_ outbreaks, etc. To dissociate
the cause or causes of the uratic deposits from that of the joint
inflammations would indeed appear impermissible.

But, taking this view, it is clear that, apart from the constitutional
and local factors above postulated, tophi and, alike, the arthritic
phenomena of gout, demand for their production the intrusion of some
further element, some _tertium quid_, vital and biological. To this end,
therefore, we purpose reviewing tophi in their _clinical_ aspects, as
herein possibly we may find some further clue to their exact mode of
genesis.


CLINICAL EVOLUTION OF TOPHI

As to the clinical characters that mark the genesis and maturation
of tophi not a little conflict of opinion seems to obtain. Do tophi
arise painlessly or not? Do the uratic depositions occasion any local
inflammatory reaction? Or, are they merely concomitants or sequels
thereof?

With what wearisome iteration has the same question been propounded in
regard of _gouty arthritis_. Are the attacks of pain and inflammation due
to deposits, or do the deposits take place at the site of inflammation?

But, restricting our enquiries to tophi, we may remind the reader
that Aretæus, writing in the second century, A.D., made the following
observations: “Callosities also form in the joints; at first they
resemble abscesses, but afterwards they get more condensed, and the
humour being condensed is difficult to dissolve; at last they are
converted into hard white tophi (Πῶροι στερροὶ λευκοὶ), and over the
whole there are small tumours like _vari_ and larger, but the humour is
thick white and like hailstones” (Περὶ Αρθριτιδος). To our mind, it would
be difficult to emulate, much less to surpass, the succinct and, as we
believe, accurate picture here drawn of the various stages that mark the
life history of tophi. It will be noted that Aretæus says that in their
initial stages they “resemble abscesses,” and, turning to the writings of
the elder Garrod and others, we find abundant evidence that it is so.

Discussing the more frequent incidence of tophi in the hands than in
the feet, Garrod describes the physical characters presented by tophi
in the making as seen in one of his examples of gout. “On the dorsal
surface of the second phalangeal joints of three fingers, small rounded
protuberances were observed, the skin over them being red; these
bulgings appeared soft, as if containing a thick fluid, but not the
slightest indication of white matter could be seen through the skin;
they might have been either gouty concretions in their early stage of
formation or some other form of swelling; from a simple inspection
I could form no opinion as to their true nature, but their history
convinced me that they arose from a deposit of urate of soda. Upon
puncturing one of the little swellings, full light was thrown upon
the case, as a thick white fluid immediately exuded, a drop of which
placed, under the microscope, with the use of polarised light, gave the
appearance represented in Fig. 1; the crystals were proved by analysis to
consist of urate of soda.”

We see, therefore, that Aretæus and Garrod were at one in their
observation that tophi in their initial stages are betokened by _small
red swellings_; in other words, as Aretæus says, they “resemble
abscesses.” Garrod also held that uratic deposits probably form during an
attack of gout, but occasionally they appear shortly afterwards. Thus,
in one of his cases no auricular tophi were found when the subject left
hospital, but within ten days, on re-examination, a deposit was detected.
“Perhaps,” he reflects, “some fluid was effused during the fit, but being
at first transparent, could not easily be distinguished.”

That Garrod held the swellings to be _inflammatory_ in nature is clear
from his writings. Thus, he says, “When tissues little liable to take
on inflammatory action become infiltrated (with urate of soda), but
slight vascular disturbance is produced. This is especially the case with
the fibro-cartilage of the ear, and although we now and then meet with
patients aware of the formation of these little nodules, who experience
in fact a gouty fit in the ear, yet in the majority of cases attention
has never been directed to the part, so slight has been the inflammation
caused by the effusion.”

Again, James Moore, whose graphic description of tophi formation is
quoted by Garrod, also held that “this process is usually preceded and
accompanied by inflammation.” Hilton Fagge, too, says, “it appears
probable that the deposition of lithate of soda causes inflammation in
other tissues besides the joints. It does, as we have seen, in the ear
and occasionally in the skin.” But, he also states, “in the pinna of the
ear, in fact, gouty concretions commonly form without any indications of
previous inflammatory action. In some instances the patient experiences
sensations of heat and pricking, and the part is tender, but more often
he is quite unconscious of the fact that such concretions in the pinna
are present.”

Duckworth also noted that uratic deposits are _not always painless_
during their formation, and he noted that not only may auricular tophi
be painful at this stage, but that, following the subsidence of acute
gout in a joint, painful swellings may develop in its vicinity, which
subsequently proved to have been tophi in process of formation.

For myself, I am of opinion that each and every process of tophus
formation is preceded by local inflammatory reaction of varying grades
of severity. In a matter of this sort, positive is more valuable than
negative evidence. We see that all the authorities quoted admit that
_tophi_ are associated with _inflammation_ and some measure of _pain_,
though they add the reservation that in many instances, if not the
majority, these phenomena have apparently been absent. Apparently, we
say advisedly, for conceding that the pain attending the formation of
auricular tophi is but slight, how all too easy for the subject to have
wholly forgotten it when he comes later under notice. By this time
the tophi, from being latent, have become overt. The initial soft red
swellings, their nature probably misinterpreted at their initiation, are
now transmuted into pearly concretions of hard or semi-solid consistence.
Small wonder, then, that attempts to elicit the history of slight pain
and pricking or tenderness often prove barren; for, be it noted, tophi
take months to mature, as Garrod long since pointed out.

Moreover, we would emphasise the fact that _tophi_, more often than is
thought, occasionally precede by some years the outbreak of _arthritic_
attacks. Both Duckworth and Garrod are quite definite on this, and we can
confirm them.

In such instances, then, even granted that our attention be drawn to them
in their initial stages, how easy to misinterpret their true nature!
Thus, we have known tophi in their early stages of formation confused
with _chilblains_. In this connection we might remind the reader that,
according to Duckworth, amongst the peculiarities of tissue in those
goutily disposed is feebleness of the peripheral capillary circulation,
“a condition leading to disorders of chilblain-type, the vessels filling
slowly after being emptied.”

We repeat that the cause or causes of tophi and, alike, of the arthritic
phenomena of gout are, and must be, one and indivisible, for the process
of tophus formation is but an attack in miniature of gout. Although he
may never have had an arthritic outbreak, the individual who exhibits
a tophus undeniably has gout. More certainly so than if he had had an
inflammatory outbreak in his great toe; for this, at any rate, may be of
_non-gouty_ origin, but the tophus, never!

Reflecting on the foregoing considerations, we would submit—

    (1) That tophi are always preceded by local inflammatory
    reaction of varying grades of severity, and that the uratic
    deposits are sequels thereto;

    (2) That in their early stages their presence is betokened by
    soft red swellings associated often with sensations of pricking
    and tenderness;

    (3) That their transmutation into white pearly concretions is a
    process that takes months to mature;

    (4) That tophi and arthritic outbreaks have a common causal
    origin.

The question that now thrusts itself upon us is,—What, then, is the cause
of the inflammatory phenomena which determines the eruption of tophi, and
alike of the arthritic outbreaks?


THE CAUSE OF THE INFLAMMATORY PHENOMENA

Garrod’s discovery that uric acid was present in the blood in gout not
unnaturally led to the assumption that herein lay the origin of its
symptomatology, and what else than confirmatory could be the deposition
of uratic deposits here and there in the body. The corollary seemed
obvious that, given the presence of a certain proportion of uric acid
in the blood, then gout must result. But, unfortunately, it was not so;
for, lo! and behold, an excess of uric acid in the blood is in no sense
pathognomonic of gout.

Thus, the blood in _leukæmia_ contains a high percentage of uric acid,
in some cases exceeding that found in gout, and enduring, moreover, for
a longer period. Yet no symptoms distinctive of gout appear, nothing
that can be referred to _uric acid_. But it was contended the reason why
gout does not ensue is because simultaneously with increased formation
there is increased elimination of uric acid. But, unfortunately, despite
augmented excretion, the percentage of uric acid in the blood is still
maintained at a high level, and still no gout occurs.

Moreover, it is met with also in nephritis, simple and pernicious anæmia,
intestinal inflammation, certain fevers, notably in malaria between
attacks, and in typhus after the febrile stage, pneumonia, plumbism, etc.
Indeed, the ubiquitousness with which uric acid is found in the blood,
and this in conditions wholly distinct from gout, would of itself seem
sufficient to dissipate any lingering doubts as to its being anything
more than a symptom of gout and not its proximate cause.

Obviously, with these revelations the uric acid theory was within
measurable distance of being uprooted. Deposed from its high estate as a
causal agent, and accredited with only a symptomatic value, the question
arose whether indeed this bogey, “uric acid,” was even capable of
fulfilling a minor _rôle_, of originating any symptoms, much less gout,
in its entirety. In other words, is uric acid toxic or non-toxic?


NON-TOXICITY OF URIC ACID

The adherents of the uric acid theory did not hesitate to attribute to
its toxic action, not only the severe phenomena of acute attacks, but
even all the functional disorders of so-called _irregular_ or _visceral_
gout. By the more ardent advocates, such as Haig, we were treated to
a word picture of how solid crystals of uric acid erupted out of the
blood-stream, and anchoring themselves in nerve sheathes, the renal
substance and the mucous membrane, gave birth to chronic neuralgias,
nephritis, rhinitis, and so forth. But, alas, there is very serious doubt
as to whether uric acid or the urates are capable of acting even as
mechanical, much less as true _toxic_ irritants.

Perhaps the most cogent evidence of the slight toxic effects of uric
acid or urates is that derived from a study of the _uric acid infarcts_
so frequently noted in infants dying within the first two weeks of
birth. According to Gideon Wells, “little or no change occurs in the
renal tubule as a result of these depositions, except such as can be
attributed to their mechanical effect.” This same observer, discussing
this question of the toxicity of uric acid, observes, “It may be safely
stated that at the present time there exists no good evidence which makes
it probable that uric acid is responsible for any pathological conditions
whatever, except uric acid calculi, uric acid infarcts in the kidneys,
and certain manifestations of gout.” His further conclusion is that uric
acid possesses but a very slight degree of toxicity, and that an actual
intoxication of the organism with this substance probably never occurs.

Again, we have the fact that in instances of _malnutrition in children_
excess of uric acid may occasionally be found in the blood. Yet no
symptoms comparable to _gout_ occur, even though uric acid _calculi_
form. Also, as has been pointed out, showers of uric acid may be present
in their urine, and yet no symptoms arise, save those referable to
_mechanical_ irritation of the renal or vesical tissues.

Turning to experimental researches, the evidence is cumulative as to the
_non-toxicity_ of uric acid. Rabbits and dogs seem quite irresponsive,
either to its ingestion in large quantities in their food, or to repeated
intravenous injections of 1 or 2 grammes thereof, save only that the
urine showed a large increase in uric acid.

Again, Ransom, of New York, found that no systemic disturbance ensued in
two cases of _chronic nephritis_, following the taking by the mouth of
3 grammes of uric acid per diem for three days in succession. All that
resulted was a notable increase in the uric acid output. In one case, he
went further, and on the fourth day administered 6 grammes, but nothing
happened.

Walker Hall, with commendable devotion, took large doses of uric acid
with resultant headache and malaise, which endured for some hours. But
as Luff shrewdly observes, “almost any substance, however (common salt
for example), will produce toxic effects if taken in very excessive
quantities.” Despite his brief indisposition, Walker Hall maintains that
uric acid is rather a symptom of, than the precise _materies morbi_ in
gout.

Nor, apparently, even in gouty subjects can aggravation of the condition
be induced by intravenous injection of uric acid. Bass and Herzberg did
so until the blood content of uric acid reached the high level of 10 mg.,
and yet no joint attack supervened. Neither, for that matter, has it been
possible to establish any relationship between degrees of uricæmia and
the incidence or severity of gouty paroxysms.

Again, taking a typical instance of acute gout in the big toe, how
difficult to conceive that the same owes its origin to uric acid
circulating in the blood especially when we realise that the blood
content of uric acid in gout exceeds but by a few milligrammes that in
_normal_ blood. Moreover, if it does so, then why does it fail to ensue
in leukæmia and in other states associated with uricæmia. Also, we
like to think that the penchant of acute gout for the toe is that the
circulation is inefficient at this peripheral site. But how often is the
circulation all too vigorous in gout, and for that matter frequently
feeble in leukæmia and in ill-nourished children. But, notwithstanding
that in the two latter conditions, _uricæmia_ exists yet, despite
favouring circulatory conditions, they develop no gout.

Garrod contended that the violent pain, intense inflammation, and
profound constitutional disturbance of acute gout were due to
_mechanical_ irritation occasioned by the sudden deposition of biurate
crystals in the delicate interior of the implicated joint. Also, that the
absence of constitutional disturbance in the inter-paroxysmal periods was
because the deposition of urates, being gradual, the tissues acquired
tolerance, and yet, forsooth, this same substance is held responsible for
the fulminant outbreak that ensues anon.

But it is, as Ringrose Gore shrewdly observed, “against the usual laws
of nature that, if an irritant foreign body remains in any organ the
symptoms should quickly subside, while the irritant actually increases,
for after each attack, and during the intervals between the attacks, the
deposits of such biurate enlarge.” In conclusion, is it not infinitely
more probable, as Gore states, that the inflammatory reaction _precedes_
the deposition of urates and that these latter, in short, are the
_consequence_ and not the cause of the gouty arthritis?

Reverting to tophi, their experimental production, it is claimed,
has been achieved by His.[24] Administering alcohol to dogs and
simultaneously injecting them locally with sodium mono-urate, he produced
deposits which seemed identical with tophi produced spontaneously in
gout. But, unfortunately, up to the present, it has been found impossible
to induce their formation by flooding the circulation with urates. The
utmost, indeed, that His and other workers in this sphere feel able to
postulate is that uric acid is a “weak tissue poison.”[25] Scarcely the
words in which to describe the poison responsible for gout! for, as we
have before stated, the agent that is responsible for _tophi_ must also
be capable of inducing the arthritic phenomena and other features of the
disorder.

The sum of our reflections is that the _toxicity_ of uric acid has
been grossly over-estimated, and that, like its relative _urea_, it is
practically _non-irritating_ and _inert_; in other words, it cannot any
longer be regarded as the _essential cause_ of the _acute_ or _chronic_
forms of _gout_, whether of _articular_ or _ab-articular_ site. Moreover,
far from its presence in excess in the blood being pathognomonic of gout,
it must, as Walker Hall contends, be held merely “as symptomatic of
conditions which help or prevent its solubility and excretion and does
not itself cause lesions which accompany uricacidæmia.”


ARE THE PRECURSORS OF URIC ACID TOXIC?

Naturally the upholders of the uric acid theory were loth to find their
fetish uric acid was allotted a meaningless _rôle_. That it should be
deemed inert was to dislodge the very corner-stone of the imposing
superstructure they had been at such pains to raise. Uric acid not
responsible for the genesis of gout! But, haply, maybe their position was
still unassailable; for what of the purin _bases_, the forerunners of
uric acid? Might not the blame lie with these?

Straightway _xanthin_, _hypoxanthin_, _adenin_, etc., were credited with
pernicious potencies.[26] Nor did they lack apparent support from the
experimental side. Thus, Mandel affirmed that purin bases, apart from
infection, might originate pyrexia. Others, again, noted that in dogs and
rabbits fed on adenin, degenerative changes in the _kidneys_ ensued, with
deposits resembling uric acid and urates in their substance. The fact,
too, that _guanin-gout_ was occasionally met with in swine, also lent
colour to their views.

Moreover, that ingestion of these congeners of uric acid led in animals
to renal lesions, seemed to support the contention of many, that renal
disorder might be the primary cause of gout. But, unfortunately, Kolisch
and Weintrand’s assertion that the alloxur bases were found in increased
quantities in the urine of gouty patients was contradicted by Schmoll,
His, Laquer, and others.

Still more cogent, apparently, the announcement in 1910, by Brugsch and
Mallory, that they had seen a typical attack of gout ensue in a gouty
patient in sequence to a dose of 0·5 gram of _hypoxanthin_. Nor did this
reaction of gouty persons fail of confirmation, as in the same year,
Brugsch and Schittenhelm, in gouty patients, noted attacks of arthritis,
after the administration of _nucleinic acid_.

Nevertheless, we must beware of laying too much stress on isolated
experiments of this nature, so hypersensitive are some of the victims
to any strange or unaccustomed ingesta. Were all the myriad other
determinants of gouty attacks eliminated, over-drinking, trauma,
mental disturbances, etc.? for be it recollected, all the victims of
these experiments with _hypoxanthin_ and _nucleinic acid_ were _gouty_
subjects, _i.e._, potentially liable to attacks at any moment.

Even admitting the ingestion of, _e.g._, hypoxanthin was followed by a
gouty outbreak, it must be insisted that mere sequence does not establish
causation. Clinically, on the whole, there is little or nothing to
support the contention that the _purin bases_ have much to do with the
pathogeny of gout. “The proof of the pudding is in the eating,” and
contrary to the view, at one time so prevalent, that purin foodstuffs
were most deleterious, it has been found that, for the average gouty
person, a purin-free dietary is not only not essential, but prejudicial.
Those, therefore, who may be inclined to see in the above sequence proof
of a _causal_ connection, would do well to recall Bacon’s dictum that
“there is in the human mind a peculiar tendency to dwell on affirmative
and to overlook negative instances.”

In conclusion, we must affirm our belief that _neither uric acid nor
its precursors_ is responsible for the fever, local inflammation, and
general constitutional disturbance in gout, for uric acid and the urates
are themselves practically non-toxic. Albeit, though holding this view,
I do not for one moment suggest that _uric acid_ has nothing whatever
to do with gout. The fact that _tophi_, its pathognomonic stigmata, are
compounded of biurate of soda, would _per se_ stamp such an attitude as
untenable. On the other hand, _uric acid_ must be viewed in its proper
perspective as a concomitant or sequel of gout, the essential _cause_ of
which must be sought elsewhere.




CHAPTER XIII

THE RISE OF THE INFECTIVE THEORY


With the abandonment of the uric acid theory of the causation of gout
we see a reversion, curiously enough, to the hypothesis held by the
ancient physicians as to its pathogeny. Like Cælius Aurelianus and
Paulus Ægineta, we now incline to refer the origin of the disorder to
some derangement of the _gastro-intestinal_ tract. This conception
indeed endured up to the latter half of the eighteenth century, and was
definitely maintained by Van Swieten in his commentary on the aphorisms
of his great preceptor, Boerhaave. For him the _fons et origo mali_ in
gout was disturbance of the functions of the alimentary tract.

    “Indigestio viscorum pro origine proxima hujus morbi habitur.”

The English Hippocrates, too, Sydenham, in his classic treatise observes:
“The more closely I have thought upon gout, the more I have referred it
to _indigestion, or to the impaired concoction of matters both in the
parts and juices of the body_.”

Not only in regard of the initial site are we reverting to the views of
old-time physicians, but the tenor of our reflections upon the _nature_
of the disorder exhibits a like trend. Thus the older physiologists,
doubtless impressed by its fulminant onset and clinical features, ranked
gout amongst the fevers, describing it indeed as a “tertian fever
terminating in fourteen days.”

Indeed, the great Boerhaave avowed his belief that gout was
_contagious_—a forecast, we may take it, of the modern theory of
_infection_. Subsequently his pupil, Van Swieten, went a step further,
maintaining that sometimes wives, while nursing husbands afflicted with
gout, contracted the malady!

Passing now to relatively modern times, it will be noted that in 1864
Laycock classed acute gout with rheumatic fever as an “excretory fever,”
while Parkes even prior to this, in 1860, wrote: “I define gout after
Garrod as a febrile infection with inflammation about the joints leading
to a deposition of urate of soda.”

But it must be freely acknowledged that, subsequent to Garrod’s discovery
of _uric acid_ in the blood in gout, the spell exercised by the _uric
acid theory_ was such that it dominated medical thought almost to the
exclusion of all other possibilities. All energies were forthwith
centred upon endless laborious researches into possible modes of uric
acid formation, but which, alas, did little to purge men’s minds of their
obsession that _uric acid_ was the _proximate cause_ of gout.

Still it would be unfair to infer that the disabilities attaching to the
uric acid hypothesis were wholly unrealised. Indeed, it may be fairly
said of Duckworth’s reflections on the pathogeny of gout that they
definitely foreshadowed the _infective_ theory. His views postulated
what may be termed a _toxic tropho-neurosis_, wherewith to explain the
paroxysmal nature, the periodicity and protean symptomatology of the
disorder.

But in the early part of 1900 we may, I think, discern in some words of
Chalmers Watson a change coming over our thoughts as to the pathology
of gout, this as the result of some studies of a series of examples of
_acute gouty polyarthritis_. The results of his researches were such
that he challenged the accuracy of Garrod’s original observations as to
the lowered alkalinity of the blood during acute attacks, also his claim
that the uric acid content of the blood was increased and the uric acid
excretion diminished during the paroxysm. If these points be accepted, he
says we must start _de novo_ in search of the cause of the acute paroxysm.

He noted also the interesting fact that during acute attacks of gout a
very marked _leucocytosis_ was present. Another outstanding feature was
the presence in large numbers of peculiar myelocyte-like cells, half
as many in number as the ordinary finely granular oxyphil leucocytes.
Reflecting on these findings, he observes: “It would, I think, be well
if much less attention were centred on the excretion of uric acid alone
as the all-important factor in the disease, whether in its acute or
chronic form. The results obtained by the line of investigation here
followed suggest the advisability of more attention being devoted to the
histo-chemical characters of the blood, the ratios of uric acid to other
important products of metabolism, and, if opportunity be afforded, an
examination of the bone marrow.”

To other interesting features of these researches of Watson’s we shall
allude later, but, concerned here more with tracing the evolution of the
infective theory of gout, we would hasten to add that in September of
the same year Ringrose Gore, discussing the inadequacy of the uric acid
theory, boldly avowed and ably propounded his belief in the _infective_
origin of the disorder.

Thus he writes: “I consider a toxin to be the cause of this disease. If
so, such toxin must be formed in the intestine. As the symptoms of gout
are constant, it must be a definite toxin, the product of a definite
bacillus acting upon the intestinal secretion. As gout is capable of
being caused in any subject, it must be one of the bacilli normally found
in the intestinal canal.”

Nor did Gore lack supporters in his suggestion that the alimentary tract
was the primary source of the changes in the metabolism of gout. For in
the same year Minkowski, Le Gendre, and in this country Watson, hazarded
the view that intestinal derangements, through the medium of their
resultant toxins, initiate disturbances in the liver, and these in turn
determine those obliquities of metabolism typical of gout.

At the same time their contentions derive colour from the researches
of Grübe, who, despite traditional views, maintained that in gout the
hydrochloric acid of the gastric juice, far from being increased, was
in most cases _diminished or wholly lacking_, while, on the other hand,
lactic acid was present in some instances.

In 1903 Woods-Hutchinson ably contended that “gout and lithæmia are mere
symptom names for a miscellaneous group of _chronic toxæmic processes_
of widely varied origin, characterised by the production of uric acid
and the urates.” He held that the uric acid in gout as well as the
associated phosphoric acid are merely a criterion of the measure to
which the nucleins of the body cells (chiefly probably of leucocytes)
have undergone destruction in consequence of their invasion by a toxin
or toxins of organic or inorganic nature. He furthermore contended that
the _rôle_ of the _liver_ in gout was purely negative, consisting in its
inability “to absorb or transform into harmless excretory substances the
excess of toxins brought to it by the portal vein.”

In 1904 Falkenstein furnished collateral evidence that the starting
point of gout lay in a diseased condition of the _gastric glands_, those
responsible for the secretion of _hydrochloric acid_. The supply of
hydrochloric acid being deficient in the gouty, their digestive capacity
is distinctly lowered. Abnormal fermentation ensues with insufficient
oxidation, and “the substances containing quantities of nuclein are
partly prevented from being further split up, and partly favour the
synthetic formation of uric acid.” He would thus refer the excessive
formation of this latter directly to the diseased glands. He further
observes that, despite the deficiency of hydrochloric acid, the gastric
juice is often hyperacid, this being due to the presence therein of
organic acids, such as butyric, lactic, and acetic acids.

In the same year Chalmers Watson, as the outcome of investigations into
gout as it occurs in the _fowl_, held that:—

    (_a_) There is ample evidence to prove that the uric acid in
    the blood is not the primary factor in gout, and

    (_b_) Uric acid can be deposited in cartilages and other
    tissues, even in considerable amount, without the association
    of any inflammatory phenomena.

He concludes that the last-mentioned point clearly proves that:—

    (_c_) Uric acid is not the factor which causes the inflammatory
    phenomena characteristic of the acute attack.

He then proceeds to inquire as to the nature of the toxic principles in
the blood, and the factors that influence their passage thence into the
tissues. In connection with these queries he emphasises the necessity
of envisaging the all-important part played by the _alimentary canal_,
holding that herein doubtless resides the clue to the solution of the
problem.

_Post-mortem_ examination of the fowl revealed marked catarrh of _ileum_,
_duodenum_ and _large intestine_, while the pancreatic duct was filled
with catarrhal products. The congested _spleen_, apart from proliferation
of its endothelial elements, exhibited a marked increase in the number
of _granular leucocytes_ in the capillaries and sinuses as compared with
the features of the control sections, which, as Chalmers Watson observes,
is the characteristic reaction of this organ to invasion by bacteria or
their products. The kidneys on examination revealed here and there uratic
deposits surrounded by inflammatory tissue. The relationship of these to
the inter-lobular arteries was such as to suggest an _infection_ by the
_blood stream_.

The collecting tubules in the deeper part of the cortex and medulla
were markedly dilated and choked with granular leucocytes. Sections of
the organs were examined bacteriologically by Muir, the necrosed areas
revealing the presence of “rod-like bodies of the size of large bacilli
massed together in dense clusters; the appearance suggested that these
rods were either degenerated cell products of an unusual character,
degenerated bacteria, or crystalline in nature.” Examination of the
same by polariscope by Marshall disposed of the possibility that they
were crystalline. Finally it was thought that the appearances generally
favoured the view that the rods in question were bacteria which had
lost their reaction to bacterial stains owing to bacteriolytic or other
changes.

As to the inference that the defunct fowl fell a victim to acute
gout, Watson based it on the existence of the _uratic deposits_ in
the tissues, the changes in the synovia, the widespread thromboses,
and the renal necroses. As to the other lesions, the chief interest
centres in those located in the intestine, pancreas and kidney. The
state of the _pancreatic duct_ raises the question as to whether it
points to any connection between these changes and the common occurrence
of _glycosuria_ in gouty subjects. The alteration in the _leucocytes_
merits notice in that similar changes were found by Watson in the blood
in _acute gouty polyarthritis_, the same, moreover, being subsequently
confirmed by Bain.

Chalmers Watson’s final conclusion was that “the clinical features
of gout—regular or irregular, acute or chronic—are more adequately
explained by the light of our present knowledge of infections, relapses,
and immunity than by any other theory. The distinctive feature of this
infection in gout is that the toxin or toxins have a special property of
disturbing nitrogenous metabolism in a manner favourable to the deposit
of uric acid in certain tissues.”


SUGGESTION OF A SPECIFIC INFECTION

It will have been noted that, despite the growing number of adherents
to the infective theory, no attempt had been made to saddle any
particular organism with the responsibility of initiating gout. But
in 1905 Trautner, holding _mucous colitis_ to be one of the initial
manifestations of gout, affirmed his belief that the _bacillus coli
communis_ was the responsible microbic agent.

He claimed that this particular organism, during its passage through the
system, gives rise to a reducing agent which is subsequently transmuted
into _xanthin_ and _uric acid_. This is, of course, but a variant of
Gore’s original view that the toxin of gout is a product of certain
bacteria normally present in the intestine, but which under certain
conditions take on a pathogenic action.

The microbic theory fast gained ground. Thus Luff, who in the first
edition of his work advocated the renal origin of gout, subsequently
renounced the same in favour of its infective origin. To sum up,
the opinion generally was that it was more than probable that
_gastro-intestinal derangements_, with their altered secretions, exert
an influence on the intestinal flora with resultant formation of toxins,
and that these same, acting chiefly on the liver, put in motion those
obliquities of metabolism which eventuate in gout.

Sikes, however, in 1907, discussing the _rôle_ of gastro-intestinal
disorders, expressed a doubt as to whether the same are primarily or
secondarily related “to the actual chemical processes at the base of the
disease.”

He thinks it at least as probable that the gastro-intestinal disorders
are due to an alteration in the intestinal secretions from an internal
cause as that they are due to bacteria in the formation of toxins, or, he
suggests, to some alteration in the epithelial cells, so that they take
up chemical compounds of different nature from the ordinary. To him it
does not seem at all probable that gout will ever be found affiliable
to any specific micro-organism, inclining rather to the belief that a
solution of the riddle will only be found in a closer and more extended
study of that most difficult subject, the actual _chemistry of the cell
protoplasm_.




CHAPTER XIV

GOUT AS AN INFECTION


“The old order changeth, giving place to new,” and the uric acid
theory having failed us, it is essential that we cast round for some
other solution of the problem, carrying with us, however, this guiding
principle, that _uric acid_, having lost its _etiological_ status, be
viewed in its right perspective as not the cause, but the _consequence_,
of gout.

Happily, with the advent of bacteriology our views, or rather our
hazards, as to the nature of joint diseases underwent profound
modification. But, strange to say, though quick to apprehend the
significance of infection, its causal relation to other joint disorders,
we still seem unaccountably loth to discard our time-worn conception of
“gouty” arthritis as of purely _metabolic_ origin. This, to my mind, is
the more remarkable in that the onset, clinical phenomena, and course of
acute gout, and no less the life history of the disorder as a whole, are
emphatically indicative of the intrusion of an _infective_ element in its
genesis.

In developing this hypothesis I purpose devoting the present chapter
to consideration of the frequency with which local foci of infection
are met with in gout, the frequency, too, with which exacerbations of
the disorder are presaged by acute glandular affections of undeniably
infective source. The latter part of the text will concern itself with
the rival claims of _auto-toxæmia_ and _infection_ or _sub-infection_. In
the subsequent chapter we shall analyse critically the component elements
of the acute paroxysm of gout, their compatibility or not with an
infective origin. The affinities between gouty arthritis and the specific
infective arthritides will then be noted, and, finally, an endeavour made
to link up the specific stigmata of gout—its uratic deposits—with the
postulated infective element.


LOCAL FOCI OF INFECTION

The extreme frequency with which _infective foci_ are met with in the
victims of gout is by no means adequately realised. Moreover, we are only
now beginning to appreciate the grave significance of such “nests” of
infection and how devious are the ways in which they work their malign
influence. For our forefathers gout began, and, forsooth, often ended,
in the “stomach,” or it was the “liver” that was impeached. But the
portal to the alimentary canal was for them only a cavity, the contained
structures of which, albeit, to their mind often betrayed evidences of a
“gouty diathesis.” They distinguished “gouty” teeth, “gouty” tonsillitis,
“gouty” pharyngitis, even “gouty” parotitis; but all these they classed
as tokens or sequelæ of gout—not possible causes or excitants thereof.

Nevertheless, their observations on “gouty” teeth are of deep interest,
though their significance was misinterpreted.

Thus, Duckworth, for example, wrote: “The tendency to shed sound teeth
has been noted with some frequency in middle or later life in goutily
disposed persons, and they are more than others liable to occasional
and fugitive attacks of pain in several sound teeth at a time, with a
sensation as if these were starting from their sockets, being tender to
bite upon.” In truth, a succinct picture of _pyorrhœa alveolaris_, of
unprejudiced source, hence the more valuable.

Garrod again tells us that he saw an initial attack of gout supervene
after extraction of a tooth, a sequence attributed by him to loss of
blood. How interesting this, in light of the fact that exacerbations of
joint disease have frequently been seen to follow the removal of septic
teeth. The same authority also noted the incidence of a primary attack of
gout following _epistaxis_, and the same after copious _hæmatemesis_, and
Todd several times observed such articular outbreaks after _venesection_.

Lastly, says Garrod, “cases illustrative of the effects of the
suppression of an habitual hæmorrhoidal discharge are by no means
uncommon, and ... numerous instances arising from _boils and carbuncles_
have come under my notice.” By Garrod and his contemporaries all these
various determinants of gouty paroxysms, _i.e._, loss of blood, etc.,
were believed to exert their influence _viâ_ the _nervous_ system, with
consequent disturbed equilibrium of nutritive processes throughout
the body. But while it may be admitted that depression of the _vis
resistantiæ_ plays a part, it does so, I believe, by favouring the
occurrence of _infection_.

Let us turn now to modern findings, and we shall see that they do but
confirm those of the older clinicians. Lambert in 125 cases of gout found
the teeth unsound in 82 per cent. of males and 1 per cent. of females,
while in 9 per cent. of the former and 17 per cent. of the latter there
was associated _chronic dyspepsia_. Two years after (1909) Wynn, Wirgman
and Turner noted the invariable correlation of gout with local foci of
infection. In the majority, _pyorrhœa alveolaris_ was present. _Tonsillar
sepsis_, too, was not uncommon, and much more rarely _nasal_ disorders.
Again, out of fifty-two examples of so-called “gouty” throat Edward
McCracken found _pyorrhœa alveolaris_ to be present in thirty-nine, and
Fenner also tells us that this affection is common in the subjects of
gout.

In truth, the victims of _gouty_ arthritis are no more immune from
_dental_ lesions than those of other types of joint disease. Thus, Mr.
Macdonald, dental surgeon to the Royal Mineral Water Hospital, Bath,
informs me that this form of _oral sepsis_ is extremely common in _gouty_
individuals, and in my experience it is but rarely that evidences of its
presence are not forthcoming in these subjects. The desirability of early
recognition of such foci—in light of their highly probable _etiological_
significance—can scarcely be overestimated. For their consequences, both
local and remote, are of paramount importance.

Thus, G. I. Stewart’s recent observations have conclusively demonstrated
that “bad teeth” are causally related to _tonsillar_ affections. How
illumining this, in view of McCracken’s experiences in “gouty throats.”
As we saw, _pyorrhœa alveolaris_ was present in more than half the
examples. But, more pertinently to the point at issue, he comments on the
frequency with which the victims of gout develop _acute tonsillitis_, of
lacunar or parenchymatous type, also that such attacks frequently precede
outbreaks of _arthritic_ gout. Duckworth again noted the same liability
of the gouty to unsound teeth and tonsillitis, and that the latter was
often followed by articular outbreaks. Luff also observed that “gouty”
tonsillitis was occasionally a precursor of articular gout, always
subsiding on the appearance of the latter complication.

Again, acute and chronic _pharyngitis_ are proverbially common in “gouty”
subjects. Moreover, in both types the subsidence of the throat affection
has frequently been signalised by an articular outbreak of classic site.
_Parotitis_, too, has been repeatedly met with in gout, and, according to
Luff, “rapidly subsides on the appearance of regular gout in one or more
joints.”

In truth, whether we peruse recent or older works on gout, we cannot
fail to remark the unanimity of opinion as to the frequency of incidence
of these _glandular_ affections—these states of _oral sepsis_—in the
subjects of _gout_. Equally noteworthy is their insistence on the
constancy with which such local affections have proved harbingers
of oncoming _articular_ outbreaks. Lastly, the mere fact that our
forefathers dignified these local disorders with special appellations,
“gouty” tonsillitis, pharyngitis, etc., is cogent proof that they
regarded them as among the integral features of gout.

Now, as to the true significance of these acute _glandular_ affections,
held by clinicians of repute to be of “gouty” origin. What of “gouty”
tonsillitis, pharyngitis, etc.? Still more, what of our deductions
regarding the relationship of these same when met with in association
with other joint disorders? Do we not hold them each and all as evidences
of _infection_—“acute rheumatism,” “gonorrhœal arthritis,” etc.?—and we
may well ask, Why not in _gout_?

Says Duckworth, “Angina tonsillaris—very painful but not suppurating—may
in the gouty suddenly yield to an acute articular attack.” Is it not
here more than likely that the tonsil was the initial site or portal of
_infection_, and the arthritis _secondary_ thereto? Is not this same
interpretation in all probability true also of all forms of “gouty”
throats when followed by _arthritic_ outbreaks?

The marvel, then, is that not only have we held, but apparently many
still hold, that the tonsillitis, pharyngitis, even the gingivitis—like
the subsequent articular lesions—are one and all attributable to the
underlying _gout_. We certainly would not do so in the case of any
arthritis other than “gouty,” and to my mind the time is ripe for a
change of attitude. The “gouty” throats, like the “gouty” teeth, should
be regarded not as symptomatic of gout, but _etiologically_ related
thereto. We should cease to talk of “gouty” throats, teeth, etc., should
renounce the prefix, for there is nothing _specific_ of _gout_ either
in the tonsillar, pharyngeal, or dental lesions. We should instead view
these various local disorders in their true perspective as _foci of
infection_, _causally_ related to the subsequent and _secondary_ “gouty”
arthritis.

_Gastro-Intestinal Disorders._—It is a matter of common experience
that acute attacks of gout are often preceded by or associated with
flatulence, heartburn, acidity, loss of appetite, confined bowels,
scanty, high-coloured urine, and a feeling of lassitude. In short,
nothing is more certain than that exacerbations or relapses very commonly
follow symptoms referable to gastro-intestinal and hepatic disorders.

How well established is it that these subjects after unusual, though
not necessarily excessive, indulgence at the table, almost inevitably,
and sometimes almost immediately, suffer twinges in the big toe, if
not frank outbreaks of gout. Such reaction seems to indicate clearly
that the functional disturbances in the alimentary tract stand in some
causal relation to the subsequent arthritic phenomena. The assumption
gains colour, too, from the very certainty with which freedom from such
gouty manifestations is attained by abstinence from, or more moderate
indulgence in, articles of diet predisposing to such ebullitions.

So much by way of prelude as to the probability—attested by clinical
observation and the results of treatment—that the _intestinal canal_ is
often the source of the responsible microbe or toxin. Let us now pass
to consider what factors other than an _oral sepsis_ may favour the
incidence of _functional_ disorders of the _alimentary_ tract.

_Variations in Free HCL._—Some years ago Grübe and Falkenstein found
that in gout the hydrochloric acid of the gastric juice, far from being
increased, was in most cases _diminished or wholly wanting_.

Now, as we know, the gastric juice when of normal acidity is quite
capable of dealing with moderate quantities of pathogenic bacteria. But
in the presence of _oral sepsis_ it is probable that a greater number are
swallowed than can be satisfactorily coped with.

Given therefore excess of pathogenic organisms and _relative
insufficiency of free HCL_, conditions favourable to the growth of
bacteria ensue, while incidentally the chance of such reaching the
intestine is materially enhanced.

When, however, the defensive barrier is wholly withdrawn, viz. when there
is an absence of free HCL, then of course the necessary inhibition of
microbic growth fails of achievement. Moreover, also owing to diminished
acidity, ill-digested protein substances gain access to the intestine,
and their subsequent putrefaction is favoured.

In opposition to the foregoing, many hold that an _excess of free HCL_
in gout is not uncommon, and unquestionably some are thus troubled. The
pernicious effects of the hyperchlorhydria are accentuated by the fact
that intestinal indigestion ensues secondarily, owing to the acid chyme
completely antagonising pancreatic secretion and thus impairing digestive
capacity.

_Intestinal_ rather than gastric indigestion is, I think, more typical
of the gouty subject. It will be recalled that the food nucleins are
unaffected by the gastric juice, and though the protein moiety is split
off from the nucleinic acid by the pancreatic ferments, yet neither the
poly- nor the mono-nucleotides are thereby acted upon. It is in truth the
_succus entericus_ with its nucleotidase that plays the most important
digestive _rôle_ as regards nucleins, breaking them up into nucleosides
which are, to a large extent, absorbed as such.

To resume, this condition of _intestinal indigestion_ may arise from
a variety of causes: excess or deficiency of gastric juice, defective
motility, and diminished secretion of intestinal juices, and in all cases
improper food may determine such _intestinal derangement_.

The clinical features presented are very variable. It is often
difficult, if not impossible, on the basis purely of the subjective
symptoms, to decide in any given instance how far the symptoms are
referable to _intestinal stasis_, or to a _chronic infection_, with a
resultant catarrhal state of the mucosa, or to both causes combined in
varying proportions.

But, be the explanation what it may, in our experience the most common
antecedent or concomitant of gout is _intestinal dyspepsia_. Its
secondary consequences are far reaching, especially if the small bowel be
involved, catarrh of which may lead to _reduction_ in the secretion of
_bile_ and _pancreatic juice_.

How commonly in these cases do we meet with symptoms indicative of
sluggishness of the hepatic functions, such as turbidity of the urine, a
pale or abnormally dark colour of the alvine evacuations. Also, whatever
be its true etiology, they exhibit not so uncommonly _sugar_ in the
urine, the so-called “gouty” _glycosuria_.

Now, as a mere glance will show, diminution and impairment of the biliary
and pancreatic secretions have far-reaching consequences. Foodstuffs
undergo abnormal changes, are less easily absorbed, and simultaneously
chemical products are formed which irritate the intestinal mucosa. Nor
do the baneful effects cease here, for, owing to the unusual nature and
reaction of the intestinal content, the _bacterial flora_ in the bowel
undergo modifications.

Thus, organisms normally present only in small numbers in the small
intestine find the altered medium more suitable for their growth and
multiplication; while others, whose usual habitat is the large bowel,
migrate upwards, and infect the ileum and duodenum, and ultimately the
biliary and pancreatic passages.

In the presence of such deficiency in the intestinal juices, proteins are
imperfectly digested, and putrefaction under microbic action favoured. At
the same time the digestion of carbohydrates is impaired, organic acids
are formed, and gases in larger amounts liberated. Ultimately, owing to
absorption of these irritating products, a condition of _chronic toxæmia_
results.


SUMMARY

It now devolves upon us to decide whether the phenomena of gout are best
explicable as the outcome of _auto-intoxication_, or of _infection_ or
_sub-infection_. The uric acid theory was in truth one of _auto-toxæmia_,
the varied manifestations of gout being attributed to mechanical or toxic
irritation by _uric acid_, the end-product of purin metabolism. But, as
we hope to have shown conclusively, uric acid is _not toxic_, and _per
se_ is apparently as innocuous as those other and intermediary products
of metabolism which give rise to cystinuria and alkaptonuria.

The question then arises, Is gout haply due to a retention of other
metabolites? That outbreaks of gout follow fast on the heels of dietetic
irregularities is proverbially true. But there is no certain evidence
that the symptoms generally ascribed to auto-toxæmia are referable to
substances derived from the foodstuffs under the action of the digestive
juices. Toxic as are peptones and primary proteoses when they gain direct
access to the tissues, the symptoms produced in no way resemble those
affiliated to alimentary toxæmia, much less those of _gout_. Rather,
according to Adami, do they approximate to those typical of _anaphylactic
shock_.

Normally, too, the mucous membrane proves an efficient barrier, these
poisonous bodies during their passage through it being transmuted
into harmless substances. Nor can we refer the symptoms of gout to a
toxæmia secondary to _intestinal stasis_ or other causes. In other
words, it cannot be attributed to assumed toxic action on the part of
the intermediary and terminal products of protein disintegration. For
seemingly these chemical outcasts of the economy become progressively
less toxic on their downward path to effete matter.

The diamines, too, produced by bacterial action on foodstuffs, are so
minimal as to be negligible, while the toxicity of cholin and neurin is
unestablished; and as for indol and skatol, they are with difficulty
absorbed from the healthy colon. Experimental researches on carbohydrate
and fatty disintegration have likewise proved sterile, while there is
no evidence that the anaerobes present in the digestive tract produce
ecto-toxins, or undergo lysis with release and absorption of their
endo-toxins.

In short, it is but too clear from the foregoing brief _résumé_ of recent
experimental findings that, if _uric acid_ cannot be held responsible for
the causation of _gout_, there is no evidence likewise that the disorder
owes its genesis to any other of the as yet isolated _chemical_ products
of gastro-intestinal digestive activities. Having dealt with this aspect
of the question, we shall now pass on to consider whether the phenomena
of gout can be more adequately explained on a basis of _infection_ or
_sub-infection_.

_Infection or Sub-infection._—Our knowledge as to the exact manner in
which _local foci of infection_ work their malign effects almost daily
undergoes expansion. It will be recalled that Stewart has shown that “bad
teeth” are often etiologically responsible for tonsillar inflammation. It
further is well established that _streptococci_ are of common incidence
in the _tonsils_, and Rosenow and Brown from experimental observation
have established that these hemolysing organisms, migrating _viâ_ the
blood stream, exhibit a marked predilection for forming a fresh nidus
in the _gall bladder_. Here they may initiate a _cholecystitis_, and
secondly gallstones, and in sequence thereto the symptoms associated
with _gall-bladder-dyspepsia_. The same formidable list of sequels may
follow infection of the gall bladder from the _teeth_, _stomach_, or
_intestines_, notably from the vermiform appendix.

In like fashion the origin of _appendicitis_ may be traced back to
_septic foci_ in the _mouth_, _tonsils_, _naso-pharynx_, or to the
_gastro-intestinal tract_. Here again there ensue the symptoms of
so-called _appendix-dyspepsia_. As in the case of the gall-bladder
variety, the _primary lesion_ in the _appendix_ may be _latent_, and the
exact diagnosis may be a matter of great difficulty, often indeed only
to be achieved _retrospectively_, viz., when abatement of the symptoms
follows ablation of the appendix.

We see, therefore, how far-reaching are the consequences of _local foci
of infection_ in the _mouth_ or elsewhere. Now, the _gouty_ subject
enjoys no immunity from the remote sequels of local sepsis. But as a
rule, unfortunately, whatever be the nature of his _dyspeptic_ symptoms,
they are, like his _dental anomalies_, his _tonsillar inflammations_,
forthwith dismissed as _symptomatic_ of gout, not etiologically related
thereto.

Now, I have seen pyorrhœa and chronic appendix-dyspepsia running side
by side in the same subject with recurring classical attacks of gout in
the big toe. The faulty teeth were extracted, and later the chronically
inflamed appendix removed; and though he had an attack of gout shortly
after the operation, there has as yet been no recurrence thereof.

Again, by the older writers “gout in the liver” was most firmly believed
in—as one authority puts it, “a subacute catarrh of the intrahepatic
biliary system which may lead to a subacute parenchymatous hepatitis”!
But more pertinent to my point is the insistence of older authors upon
the frequent association of gout and _gall-stones_. Senac, of Vichy,
claimed indeed that out of 166 cases of _biliary lithiasis_ 95 had gout
or an hereditary predisposition thereto. Judging by modern experience,
this is probably a gross over-estimate. In contrast, our own countryman
Murchison dwelt upon the frequency of jaundice in gout independently of
biliary colic. And, as we shall see later, Brinton held that many of the
dramatic phenomena accredited to “retrocedent gout” were unrecognised
examples of _biliary colic_.

But, controversy aside, the point I would lay stress on is, that we
should refrain from labelling offhand “dyspeptic” symptoms in a “gouty”
subject as _gouty_, this when we are so constantly confronted with
_local foci of infection_ in the _mouth_, or elsewhere, which afford
us an explanation of the gastro-intestinal symptoms at once more
obvious and more rational. This also the more especially in that—as
far as subjective symptoms go—those deemed typical of so-called “gouty”
dyspepsia are indistinguishable from those met with in _appendix-_ or
_gall-bladder-dyspepsia_. Indeed, I might go further and point out
that the _variations in free HCL_ in the gastric juice—as observed in
_gout_—conform to those met with in the above disorders. Thus, in “gouty”
dyspepsia, the free HCL may be normal, in excess, or wholly absent, as
in gall-bladder or appendix-dyspepsia. I would therefore plead that in
any “dyspepsia” arising in a genuinely _gouty_ subject we endeavour to
elucidate the exact nature of the _underlying lesion_, but to this we
shall return again when discussing diagnosis.

Again, the fact that gall-bladder or appendix lesions may be the outcome
of septic foci in the mouth enables us the more easily to explain the
not infrequent co-existence of gout and _glycosuria_. For an infected
gall-bladder may by extension determine a chronic _pancreatitis_.

Lastly, what of the relationship of local foci of infection to _“gouty”
synovitis_ and _arthritis_? Is one focal infection more than another
particularly related to arthritides? Whatever be the true inference,
if we take _arthritides_ as a whole, nothing seems so efficient a
cause of their production as _oral sepsis_. Accordingly, some are
inclined to think that organisms, _e.g._, _streptococcus viridans_, at
the roots of the teeth or others in the tonsillar crypts, pass, _viâ_
the blood-stream, _direct_ to the _joints_. Others, again, hold that,
given oral sepsis, infection of the stomach and lower levels of the
alimentary tract and its accessory cavities ensues. And in sequence
thereto infection of the joints may take place from local foci throughout
gastro-intestinal tracts.

Those who favour the view that _direct infection viâ_ the blood from foci
of oral sepsis is the more probable _modus operandi_ are wont to produce
the following points in support of their view. Arthritis, they say, is
relatively rare in _enteric fever_. In yet another disorder, _dysentery_,
which gives every chance of absorption from the intestine, arthritis when
it occurs is seldom very acute, while in _appendicitis_ it is distinctly
uncommon.

On the other hand, we must recall that even in normal animals the
alimentary and respiratory tracts, and alike the liver and kidneys,
constantly afford cultures of pathogenic and non-pathogenic bacteria.
Such was established by Adami and his co-workers, who moreover found that
such organisms, through the agency of leucocytes, continually pass into
the system, where subsequently in the healthy animal they as constantly
undergo destruction.

If, however, inflammatory processes are at work, their migration into the
tissues is favoured. For under such conditions leucocytes aggregate at
the reactive focus, and concurrently, their migration being more active,
larger numbers of bacteria achieve entry into the system. The subsequent
course of events is determined by the number and virulence of the
organisms that effect a lodgment in the tissues, where under favourable
conditions they originate other foci of infection or sub-infection.

By _sub-infection_ is understood the fact that microbes carried into
the system undergo slight, if any, numerical increase, and do not set
up _foci of suppuration_. Here we may note that “gouty” inflammation,
however intense, never ends in _pus formation_. But, to resume, the
bacteria, instead of multiplying, undergo lysis, and, their endo-toxins
being released, the more highly specialised tissue cells in the vicinity
are destroyed. Coincidently the lower grade connective tissue elements
are by the self-same poisons stimulated to proliferate, and an area of
_chronic interstitial fibrosis_ is formed.

Incidentally this is interesting, inasmuch as the _visceral_ organs in
gout evince a tendency to _fibrosis_. But, as Gideon Wells observes,
“the actual increase of uric acid in the blood and tissues in gout is
so slight that we are not warranted in saying that the usual tendency
to sclerosis in all the organs in gout is due to the action of uric
acid rather than to some other unknown agent or agents.” In view of
these revelations, is it not infinitely more likely that the chronic
interstitial fibroses in gout are the outcome of such _sub-infection_?

The assumption gathers weight in light of the experimental proof adduced
by Adami that not only tubercle bacilli, but _streptococci_ and other
organisms, _taken orally_, can gain an entrance into the system. Upon
this basis we get a clear conception of the possible relationship of gout
to _local foci of infection_. Thus, whether it be a condition of oral
sepsis—pyorrhœa alveolaris, tonsillar sepsis, sinus disease, intestinal
disorders, constipation, and so forth—we see that it is highly probable
that organisms at any one of such infective foci may gain access to the
blood-stream with subsequent installation of local lesions in _joints_ or
other structures.

Now, as pointed out, inflammatory states or _functional_ derangements
of the _alimentary_ tract, whether focal or diffuse, favour the ingress
into the tissues of organisms. Is it not reasonable, therefore, we ask,
to suppose that the functional derangements which so commonly precede
or accompany gout may modify the character of the _intestinal flora_,
and promote their migration inwards in greater numbers? The inevitable
swiftness with which relapses or exacerbations of this disorder follow
even venial dietetic indiscretions distinctly favours this assumption,
one, moreover, substantiated by the amelioration or immunity which
follows abstention from the offending foodstuffs. The often prolonged
course, too, of gout, and its marked liability to periodic recurrence,
would be explicable as the outcome of a continued or intermittent series
of sub-infections.

My conclusions then are that:—

    (1) The majority of cases of gout are marked by the presence
    of _local foci of infection_, pyorrhœa alveolaris, tonsillar,
    pharyngeal or nasal sepsis, etc., or by gastro-intestinal
    derangements, constipation, etc.

    (2) The said local foci should be regarded not as symptomatic
    of, but _etiologically_ related to, gouty arthritis, and that
    the same is strongly indicated by the fact that

    (3) Acute _glandular_ affections of undeniably _infective_
    source—tonsillitis, pharyngitis, etc.—frequently and
    immediately _precede_ acute paroxysms of _articular_ gout, and,
    lastly,

    (4) The gastro-intestinal defects, secretory or motor, which
    chequer the course of gout, enhance the pathological activities
    of the intestinal flora, and incidentally the liability to
    infection, at various sites of the alimentary tract.




CHAPTER XV

GOUT AS AN INFECTION (_continued_)


ANALYSIS OF THE ACUTE PAROXYSM

If we reflect on the general features and local characters of an
initial outbreak of gout they are precisely such as would, did they
occur anywhere but at the classic site, _the big toe_, suggest an
_infection_. The abrupt onset, the local signs, the crisis, and no less
the subsequent swift restoration to health, how strikingly reminiscent
of an _exanthematous_ fever! Moreover, does not this outward clinical
resemblance seem to predicate an inward pathological similarity? And
now to scrutinise more narrowly the component elements that make up the
content of a paroxysm of gout.

Its fulminant _onset_, with shivering, if not a definite rigor, in a
person in sound and sometimes exuberant health, irresistibly reminds one
of the sudden onfall of an infective disorder. Doubtless, as Duckworth
says, “the conditions leading up to the attack have been some time
previously in operation.” But, as he rightly contends, “some determining
factor must now be invoked to explain how, as it were, the train is
fired.” Quite so, and what more likely to call into the open these latent
morbid potentialities than an _infection_?

_The constitutional disturbance_ is often profound, certainly out of all
proportion to the severity and extent of the local phenomena. Especially
prominent are the _nervous_ concomitants—the excruciating pain, the
irascibility, etc. Viewing these in light of the paroxysmal nature and
periodicity of gout, Duckworth postulated a kinship between the disorder
and the _paroxysmal neuroses_. But, given an infective element, what
more plausible than to attribute the nervous phenomena of gout to the
simultaneous action of its _toxins_ on the higher centres?

The _temperature_ curve, again, is obviously compatible with this
conception. It begins abruptly, its course punctuated by daily
remissions. No specific peculiarities apparently differentiate it from
other arthritides of established or assumed infective origin, but its
relatively low grade pyrexia recalls that typical of _gonococcal_
arthritis. Its most striking feature, however, is the disproportion
between the level of the pyrexia and the intensity of the general
and local phenomena. Moreover, the temperature is not only low, but
relatively ephemeral in duration, while the inflammatory reaction in its
violence emulates that of the most sthenic forms of arthritis.

Albeit both the febrile disturbance and the local reaction display
infinite grades of severity. Thus, _acute gouty polyarthritis_ may be
_afebrile_ and the _asthenic_ varieties of the affection marked by little
inflammatory reaction. All these vagaries, however, are quite compatible
with infection—the reflex, as it were, of varying degrees of _toxæmia_.

Says Duckworth, “The pyrexia proper to acute gout is paroxysmal
with remission, and the pain of gout is likewise paroxysmal. One is
reminded of the influence of marsh poison upon the nervous centres.
This paroxysmal no less than periodic element in gout stamps a
nervous character upon the malady and binds it in alliance with other
well-recognised neuroses.”

How interesting these reflections by this distinguished physician in
light of latter-day revelations! For, in so far as these features in gout
are reminiscent of _malaria_, they disclose an affinity, not for a malady
of nervous, but one of established _infective_, origin.

Simultaneously with the onset of _pyrexia_ the pulse quickens. The blood
shows that increase in fibrin characteristic of inflammation, a fact
noted by Gulland, Cabot, Buchanan and others. But more significant is the
presence of _leucocytosis_. It may be of high grade. In a case of acute
gouty _polyarthritis_ recently under my care the leucocyte count reached
27,000. Even in a _subacute_ example of the classic _monarticular_
type the leucocyte count attained 25,920. It was of _leucoid_ type and
attended by moderate anæmia due to deficiency of red corpuscles.

Nor is leucocytosis restricted to the periods of exacerbation, but it
may be met with in the _inter-paroxysmal_ stages. In my experience, even
in cases of definitely _chronic_ type it may reach 14,000. The higher
grades of leucocytosis are obviously very suggestive of an _infection_,
and that lesser degrees should be encountered in examples of definitely
chronic type seems to point to gout being of the nature of a _chronic_ or
_serial_ infection.

I would here add also that the converse of leucocytosis, viz.,
_leucopenia_, is sometimes met with in chronic cases. Dr. Munro and I
have met with two instances of such in chronic gout in the intervals
between paroxysms. This decrease in the number of leucocytes (leucopenia)
is, of course, deeply interesting and, needless to say, quite compatible
with infections, _e.g._, enteric, malaria, tuberculosis. In fact, it
suggests that gout may be the outcome of divers infections, and not due
to any specific organism.

_Enlargement of the lymphatic glands_ was, by older authors, believed not
to occur in gout. But obviously the lack of macroscopic evidence does not
exclude the possibility of microscopic changes in these structures. The
likelihood of such, moreover, is enhanced by the occasional occurrence
of _lymphangitis_ in connection with the inflammatory articular lesions.
Buzzard, indeed, long since claimed that there was “clinical evidence of
subacute gouty inflammation of lymph spaces in certain regions due to
uratic deposit and influence.”

As a matter of fact, enlargement of the lymphatic glands does occur.
Thus, my colleague James Lindsay cites an instance thereof. The subject,
a painter, fifty-three years of age, had gout of some three years’
standing. During an acute paroxysm thereof “there was a mass of glands
in the right groin, synchronous with an acute inflammation affecting the
right knee and periarticular tissues. On the subsidence of the gouty
inflammation the glands became smaller, but never entirely disappeared
during the four weeks he was subsequently under observation.”

_Splenic enlargement_, states Duckworth, has been met with in many cases
of gout, and occasionally infarcts. But such splenic enlargement is, he
thinks, _not specifically_ related to gout, but is due to associated
conditions. Personally, I have not as yet met with splenic enlargement in
gout.

This aside, is it not palpably significant of infection that Paget,
Garrod, and others, repeatedly noted the incidence of acute _phlebitis_
in a limb the seat of acute articular gout? Did we observe such a
complication in any arthritis other than gouty, should we not inevitably
regard it as indicative of the spread of an _infection_ from the joint to
the related veins?

Reverting to the _local articular phenomena_, they are not only
compatible with, but emphatically suggestive of, an _infective source_.
The typical signs of inflammatory reaction are swiftly installed in
acute classical gout, and this with an intensity unrivalled save by the
most sthenic types of acute arthritis. Witness how insistent were our
forefathers, _e.g._, Scudamore, on the differentiation of acute gout,
not so much from acute rheumatism as from _erysipelas_ or _phlegmon_.
Garrod, indeed, held that “if a medical man, by chance entirely ignorant
of the nature of gout, were to see a toe affected by this disease in its
full intensity, swollen, hot, red, and tender, he would probably think
that the affection must of necessity terminate in suppuration, yet I
believe this never happens as the result of simple gouty inflammation.”
This leads us to note a salient feature of gouty inflammation, viz.,
it never results in _pus formation_. Now, allowing for the increased
powers of discrimination that happily to-day are ours, is it not, I ask,
significant that the disorders deemed most likely of confusion with acute
gout belong to the frankly _infective_ category?

That Garrod’s _caveat_ was not uncalled for I feel sure, having myself
known an acute gouty arthritis incised in the hope of evacuating pus.
Sometimes the error in judgment is reversed and _pyæmic_ or _septic_
conditions in or near the great toe joint confounded with gout. Thus, Sir
James Paget tells of an instance in which a pyæmic abscess forming near
the great toe and consequent upon ligaturing of piles was thus confused.
I recall, too, another example in which the supposed gouty arthritis of
a great toe was of pyæmic nature, the outcome of a suppurating otitis
media. Garrod, it may be recollected, ranked _pyæmia_ as one of the
disorders to which gouty subjects were especially liable.

Gouty inflammation resembles most other forms of the same morbid change,
but some, however, contend that the association of _œdema_ therewith is
pathognomonic. Indeed, by some of the older authors this concomitant
feature of gouty inflammation ranked as a criterion differentiating it
from “true rheumatic inflammation.” Œdema, of course, is not distinctive
of gouty as opposed to other forms of inflammation. But its occurrence
therein is, we would submit, but another token of its affinity with the
_infective_ arthritides. We need but recall the constancy with which
local œdema is met with in, _e.g._, _gonococcal_ arthritis. More typical
of gout, however, is the _desquamation of the cuticule_ that follows
the subsidence of the acute arthritis. Here we are reminded of the
similar peeling of the skin that occurs in another _infective_ disorder
associated with arthritis, _i.e._, _scarlatina_.

Acute gout is _definitely paroxysmal_. The attack, at any rate when
primary, is relatively ephemeral, lasts but a few days, and after it
has passed, as Cullen says, “leaves the person in very perfect health,
enjoying greater ease and alacrity in the functions of both body and mind
than that for a long time before experienced.”

In short, acute gout would appear to be a self-delimited disease, its
fleeting duration predicating that if an organism be responsible, the
same is short-lived. Even in _chronic_ gout, though it never quite loses
its grip of those it has made its prey, yet nevertheless there are
intervals of respite between the attacks, however long the latter may be.
In other words, the disease never loses its paroxysmal character, which
to my mind is very suggestive of a serial infection.

The _periodicity_ of gout was, as we have seen, well known to the
ancients. Its recurrence in early spring and late autumn has even been
celebrated in verse:—

    “On whose sacred internodial Altars I
    Each Spring and Fall at least will sacrifice
    Morbifick, painful loads of Matter tartarous,
    With recrements of nervous juice impregnate.”

                       “The Honour of the Gout,” by _Philander Misaurus_.

Scudamore referred its prevalence at these particular seasons to their
attendant vicissitudes of heat and cold (the strongest of all the
exciting causes of gout). Trousseau states that “gout with successive
paroxysms shows itself early or late in the year, at the beginning of
spring or late autumn, the wherefore I know not.”

This tendency on the part of acute gout to seasonal rhythm is ultimately
lost. For, once the disorder is established, no period of the year
confers absolute immunity. Whatever be the explanation of the vernal and
autumnal incidence of gout in its early stages, this peculiarity is at
any rate not incompatible with its _infective_ origin. In this connection
it may be recalled that it was once described as “a tertian fever
terminating in fourteen days.”

Again, further evidence may be obtained from the action of colchicum,
our sheet-anchor in the treatment of gout. Thus, Dixon and Malden have
shown that _colchicine_ has no action on the metabolism of _purins_ or on
the _kidney_. On the other hand, it causes a primary diminution followed
by a _marked increase_ in the number of _leucocytes_, which suggests
the possibility that it exerts its beneficial effects by combating
_infection_.

Lastly, turning our attention to the anatomical changes as disclosed
after death during an acute articular paroxysm, these present appearances
quite compatible with their infective origin. Dr. Munro, in one of my
examples of _acute gouty polyarthritis_, aspirated the knee joint. The
results of _cytological_ examination were precisely such as are deemed
characteristic of arthritides of infective source.

The results of our analysis of the component elements of an acute
paroxysm of gout are, for the following reasons, strongly indicative of
the intrusion of an _infective_ element:—

    (1) The onset, temperature curve, the character of the local
    phenomena, and course of the disorder.

    (2) The presence of _leucocytosis_ with secondary anæmia, and
    exceptionally of _leucopenia_.

    (3) Enlargement of the lymphatic glands, and possibly of the
    spleen.

    (4) Occasional complication of the acute articular disorder by
    _lymphangitis_ and _phlebitis_.

    (5) The paroxysmal nature and periodicity of the disorder.

    (6) The compatibility of the morbid anatomical changes and the
    cytological content of aspirated joint fluid with their genesis
    by infection.


THE EVOLUTION AND LIFE HISTORY OF GOUT

If the onset, phenomena, and course of acute gout are reminiscent of
infection, so, also, does a review of the life history of the disease, as
a whole, carry with it the same inference.

For the course of gout, like other arthritides of chronic type, is
not one of steady, uninterrupted progress, but one marked rather by
_periodic_ or _intermittent_ advances, as if seemingly due to a series
of successive _infections_ or _sub-infections_. One is reminded of
_gonococcal_ arthritis in its more severe forms, the acute exacerbations
which chequer its course being generally referred to intermittent
absorption of fresh doses of the toxin from some smouldering infection in
the prostatic urethra.

Now, if the general course or evolution of _gouty_ arthritis is notably
similar to that of the specific infective arthritides, so, also, do the
clinical features approximate. Thus its _onset_, more often than not, is
_abrupt_ and attended by pyrexia of _irregular_ or _septic_ type, with an
occasional _leucocytosis_.

Again, that not all cases of gout are of _acute fulminant_ type may
be admitted. We know that it may assume the guise of a fleeting
_arthralgia_ or “flying gout,” a transient _synovitis_, as well as an
acute _arthritis_ of _mono-_, _oligo-_, or _poly-articular_ extent.
This same _polymorphism_ in respect of the joint lesions in gout is a
replica of that met with in the _specific infective arthritides_. The
milder varieties betokened by arthralgia or synovitis tend commonly to
disappear, as it were, spontaneously in precisely the same manner as the
arthralgias or synovites that follow the exanthemata, and we presume
that, comparably with these latter, the source of infection dries up and
_restitutio ad integrum_ of more or less completeness follows.

But with repeated attacks, as in the specific infective arthritides,
progressive infiltration and thickening of ligaments, capsule, and
related tendinous and aponeurotic structures ensue. As far as these
anatomical changes are concerned, gouty arthritis and the specific
arthritides are at one, but with this outstanding difference, the
associated _uratic deposition_. Save in respect of this last, the analogy
is complete, and herein resides the specificity of gouty arthritis.

Chalmers Watson, from his observations of “gouty deposits” in human
subjects in their relation to _tendons_, _cartilage_, and _bone_, came to
the conclusion that the _tout ensemble_ of the pathological lesions was
very reminiscent of that typical of the more chronic types of _infective_
disorders. Thus necrotic areas in gouty tendons stood in such clear
relationship to the vascular supply as to suggest some infection _viâ_
the blood-stream. Again, areas of erosion in the cartilage were found to
be due, not to uric acid, but to the disintegrating action of small round
cells of the nature of granulation tissue.

As to uratic deposits located in the _bones_, it was noted that their
vicinity was characterised by marked vascularity, the existence of
giant cells, and an accumulation of the small round cells so commonly
correlated with the action of bacterial toxins.

In reviewing the foregoing clinical and pathological data and, alike, the
inferences as to their significance, it cannot, we think, be gainsaid
that, collectively, they are more readily explicable as being due to an
infection than to any other morbid source.


ANALOGIES BETWEEN GOUT AND THE SPECIFIC INFECTIVE ARTHRITIDES

A striking parallel can be drawn between the varied manifestations of
gout and those met with in _specific infections_. But, to begin with, we
must recall that our attitude towards infective disorders, _e.g._, acute
rheumatism, gonorrhœa, etc., is altered in that we regard them now, not
as local, but _general_, systemic infections.

Thus, following the revelations of bacteriologists, we now, for
example, recognise that in _gonococcal_ infection not only may there be
_articular_ involvement, but that _muscular_ and _nervous_ lesions may be
associated therewith. This same, also, in _acute articular rheumatism_.
True, its causal organism is still _sub judice_, but data accumulate as
to the frequency with which the _muscles_ are involved, and, to a less
extent, the sheaths of _nerves_.

Take _dysentery_, again; it, too, as Sydenham pointed out, may be
complicated, not only by _arthritis_, but by _myalgias_, while more
recent experience emphasises the frequency with which _neuralgias_
are associated therewith. In _syphilis_, also, the association of
_articular_, _muscular_, and _nerve_ lesions is well attested; and by
French physicians it is insisted that, in _tubercle_, myalgias and
neuralgias, as well as joint disorders, are infinitely more common than
is generally realised.

To sum up, this _triad_ of _arthritic_, _muscular_, and _nerve_ lesions,
either serially or simultaneously, is the most common complication of
_specific infections_. Now, is not this same congeries of articular,
muscular, and nerve disorders precisely the clinical content of _gout_?

Thus its _articular manifestations_ constitute the most striking feature
of the disease. As to the _muscular_ troubles, there is a consensus of
opinion as to their relative frequency. Inflammatory foci with associated
uratic deposit have been found in muscles and tendons. We may here recall
that the purin bases of the body exist, not only in the bound form
(nucleic acid), but also _free_, especially in _muscular_ tissue, also
that from such free purin bases _uric acid_ can be as readily formed as
from those liberated by disruption of nucleic acid.

Clinically, one meets with all forms of fibrositis in actual association
with acute articular gout. Such may affect either the neck, shoulder,
loin, or sciatic nerve. In their work on “Fibrositis,” Bassett Jones
and Llewellyn have shown that the disorder develops with significant
frequency in the victims of gout. This but confirms the conviction held
by Gowers, Garrod, Hilton Fagge, and others, viz., that the muscular and
nervous types of fibrositis are frequently and obviously related to gout.

How noteworthy the well-established proclivity of gout to involve
bursæ, tendon sheaths, and fasciæ, especially the plantar! Is not this
exactly paralleled in certain _infections_? Note the predilection of
post-scarlatinal rheumatism for bursæ and tendon sheaths; that of the
gonococcus for these structures as well as fasciæ, not to mention the
frequency with which bursal enlargements are traceable to syphilitic,
tuberculous, and other infections.

We see, therefore, that in virtue of its tendency, not only to
_arthritic_, but also to _muscular_ and _nerve_ disorders, gout falls
into line with the _specific infections_. Its predilection for bursal and
fascial structures is but another evidence of affinity with this group of
disorders. In view of these similitudes, one may well ask, Are not these
_gouty_ manifestations, all of them, susceptible of a like explanation,
viz., that they are the outcome of an _infection_?

For, in reviewing the foregoing analogies, it cannot, we think, be denied
that in the aggregate they are emphatically suggestive of an infective
origin.


CORRELATION OF THE METABOLIC PHENOMENA OF GOUT WITH THE POSTULATED
INFECTIVE ELEMENT

In essaying this difficult task, we must recall to the mind of the reader
our findings or deductions from the data disclosed in preceding chapters.

The outstanding conclusions that we felt justified in formulating were
that:—

    (_a_) Uric acid is not the cause but the _consequence_ of gout.

    (_b_) _Inflammatory reaction_ is, we believe, an invariable
    precursor in all gouty processes.

In other words, we suggest that, although abnormalities of metabolism
form an integral part of gout, they are of themselves inadequate to
achieve its efflorescence. Thus, when we came to consider the elemental
manifestations of gout, _i.e._, uratic deposits or _tophi_, we saw that
neither the purely physical nor the purely chemical theory of their
origin would suffice, nor, for that matter, could any solution of this
complex problem be gleaned from even a blend of the twain. In short, such
hypotheses are too _mechanical_. The intrusion of some other factor,
“some vital something biological,” seems essential for the elucidation
of _uratosis_, _i.e._, uratic deposition. For this, _not uricæmia_, is
the specific characteristic phenomenon of gout. If we cannot explain
uratosis on physical or chemical grounds, then how much less, in view of
the _non-toxicity_ of _uric acid_, can we, on this basis, account for the
_inflammatory_ phenomena of the disorder?

_Inflammatory reaction_ is, we hold, an invariable _antecedent_ in all
gouty processes, whether of _articular_ or _ab-articular_ site. Granted
that inflammatory reaction is a necessary prelude, the specificity of
gout is attested by the fact that this same is followed by the deposition
of urates. But while the sequential uratic deposition invests all forms
of “gouty” inflammation with a specific character, unshared by any other
disease, it follows that the cause of the said inflammation must, if
possible, be ascertained.

For Walker Hall “the contention that gout lowers the general tissue
resistance, and so opens the way to bacterial infections, is so
obvious that it need hardly be formulated.” In light of this, we need
have the less diffidence in hazarding our opinion that the morbific
agent responsible for “gouty” inflammation is an _infection_ or
_sub-infection_. Now, in all forms of arthritis other than gouty, the
intrusion of a germ is held to be self-explanatory and final; in short,
all the local morbid changes and constitutional disturbances are held
satisfactorily accounted for by the organism or its toxins.

The problem of gout, however, is not so simple. Its arthritis is peculiar
in that it is always accompanied or followed by _uratic deposition_,
which, be it noted, is not an ordinary sequel of inflammation. It is, in
short, the outcome of inflammation supervening in an individual of _gouty
diathesis_. What do we know of this latter?

The researches of the bio-chemists reveal that _uric acid_ is the
end-product of nuclein metabolism—the summation of a long chain of
enzymatic reactions. Some indeed have thought to find an adequate
explanation of gout in _enzymatic abnormalities_. Thus, Adami and McCrae
suggest that gout is the outcome of _insufficient oxidation_, whereby the
precursors of uric acid and similar bodies are not fully oxidised, and,
by their accumulation and toxicity, set up morbid changes, and the uric
acid formed is, in its turn, imperfectly oxidised and accumulates. This
diminished oxidation is due to a constitutional deficiency of _oxydases_,
inherited or acquired.

This opens up the old problem as to whether uric acid is an intermediary
or a terminal product of metabolism. But, from evidence cited in
preceding chapters, it appears probable, if not certain, that uric acid
is an end-product. Moreover, as Gideon Wells observes, “the failure
of recent studies on the enzymatic transformation of purins to locate
anywhere in the human body an enzyme-destroying uric acid makes hazardous
the attempt to explain gouty metabolism as a result of enzymatic
abnormalities.”

Indeed, in view of this, as hitherto ascertained, _absence of uricolytic
enzymes_, there can, as Wells says, “be little doubt that the fundamental
reason for the existence of uric acid gout in man lies in the inability
of the human organism to destroy uric acid. Consequently, inasmuch as
man, unlike other mammals, cannot destroy uric acid rapidly by oxidation,
he is always a potential victim of uric acid retention and deposition.”

Now we have, we hope, shown that there is no evidence that the _uric acid
retention_ in gout is due to functional inability on the part of the
_kidney_ to excrete uric acid. This being so, we have, as Von Noorden
rightly says, no right to do violence to the facts by assuming that, in
a case lacking any other evidence of _nephritis_, a condition of “latent
nephritis” is the cause of the uric acid retention and deposition.

Similarly, there is at present no evidence forthcoming that the retention
of uric acid is due to _abnormal purin combinations_ in the _blood_. Nay,
according to Wells, on the best evidence obtainable, uric acid exists in
a _free_ state in the blood, and not combined, as has been urged by many
workers in this sphere.

But if the cause of _uric acid retention_ lies neither in the _kidneys_
nor in the _blood_, there must exist something abnormal in the gouty
individual which renders impossible what may be termed a _compensatory
uric acid excretion_. Now, as disclosed in the previous chapter,
experimental research, in diseases other than gout, has shown that the
_bodily tissues have an appreciable capacity for retention of uric
acid_ (Fine). This, moreover, gains probability from the fact that
Wiechowski, in his prolonged studies as to the possibility of uric acid
decomposition in the human body, was never able to detect any evidence
of _uricolysis_. Furthermore, on the clinical side, the fact that
_intravenous injection of uric acid_ does not produce a corresponding
degree of _uricæmia_ seems, as Bass and Herzberg suggest, to indicate
that in gout the _retention capacity of the tissues for uric acid is
augmented_. Lastly, in the precipitation and anchoring of urates in the
tissues in gout, we have objective proof, _i.e._, tophi, that the uric
acid is actually held in the tissues.

Does not this seem to indicate that there are _peculiarities of tissue in
the gouty_? What, then, the subtle change that determines the _retention
and deposition_ of urates in the tissues in gout?

May we not, with Walker Hall, hazard the reflection that there may be
differences between the _nucleotides_ of normal and gouty tissues? For,
doubtless, if there be peculiarities of tissue in the gouty, these will
be reflected in abnormalities of _tissue function and metamorphosis_.

Gowlland Hopkins, discussing the metabolism of purins, holds that in gout
there is some disturbance or defect in the _fermentative functions of the
tissues_. Of a verity the range of _intranuclear_ activities offers scope
enough when we recollect that the cells of all tissues contain not only
_nucleinase_, but also _nucleotidase_ and _nucleosidase_. Even so, the
resultant nucleins, the nucleotides, and nucleosides, have still further
changes of deaminisation and oxidation to undergo, these carried out in
the liver and elsewhere!

We may talk of defects in the enzymatic functions of the tissues, but,
viewing gout clinically, and more particularly the hypersensitiveness
of its victims to the most varied stimuli, dietetic and other, one
inclines rather to predicate in their instance an inherent _instability_
of _nuclein metabolism_. For in the gouty, as Walker Hall observes,
“a slight injury or indiscretion of diet, an overloaded intestine,
or increased toxicity of the intestinal flora, may be followed by a
disturbance of the general nuclein metabolism, and a local reaction in
certain tissues.”

With this pronouncement all clinicians will be in accord, and herein,
too, we may, I think, discern how the latent tissue idiosyncrasies of the
gouty are evoked, _i.e._, by _infection_; in other words, that, under the
influence of these morbific agents, the innate morbid potentialities of
the gouty become overt and manifest.

The exact _modus operandi_ whereby the assumed organisms or their
toxins determine the _efflorescence_ of gout is uncertain. We know
that, following the intake even of _non-purin-containing foodstuffs_,
an _increase in uric acid excretion_ ensues, and that the same is the
outcome of the stimulation of _general_ nuclein metabolism. Is it not
conceivable that the responsible toxin acts in like fashion, and haply by
disturbing the orderly sequence of those exquisitely delicate enzymatic
reactions which culminate in the formation of uric acid, and with which
potentialities every living cell in the organism is dowered? Further than
this we, pending future researches by the bio-chemists, may not go, for
“the positive material is much too insufficient, and much too ambiguous.”

In conclusion, I would postulate that in _gouty_ subjects:—

    (1) There is an inherent abnormality or instability of
    _nuclein_ metabolism, and conjoined therewith an enhanced
    tissue affinity or augmented retention capacity for uric acid.

    (2) These latent tissue peculiarities, through the agency of
    _infections_ or sub-infections, become manifest as gout.

    (3) The said organism or organisms excite inflammatory reaction
    with sequential uratic deposition, either of articular or
    ab-articular site.

    (4) The predilection of such uratic deposition for certain
    particular tissues is determined by their greater content of
    sodium ions as compared with the blood.

    (5) The local and general phenomena of gout, its paroxysmal
    nature and tendency to periodicity, are most readily explicable
    on the basis of a _chronic infection_ supervening in a subject
    the victim of those innate peculiarities of tissue with their
    correlated obliquities of function which connote what we term
    the “gouty diathesis.”




CHAPTER XVI

CLINICAL ACCOUNT


ACUTE LOCALISED GOUT

If we would clarify somewhat the obscurity that enshrouds the genesis of
disease, our watchword must here, as in other spheres, be “Despise not
the day of small things.” We know not the proximate cause of gout, it
is true, nor the exact _modus operandi_ of those agents, infective or
other, which bring to fruition the latent morbid potentialities of its
victims. But, even if so handicapped, we should be quick to descry those
portents of the coming storm, those minor backslidings from physiological
righteousness, that doubtless foreshadow the outbreak of the disorder.

For it cannot be doubted that the evil potentialities which make for
gout are for long in operation before their definite installation in its
chosen seat, the joints, ensues. As Trousseau puts it, “The diathesis is
in action before there is time for the local affection to show itself in
a precise form.” In short, given imminence of an attack, the whole system
is charged with gout, or, as Sydenham laconically expressed it, “Totum
corpus est podagra.”


PRODROMAL SYMPTOMS

While we recognise that local inflammatory reaction in the joints is more
particularly characteristic of gout, it is no less necessary that we take
cognisance of the general precursory symptoms that often, if not always,
usher in its onfall. Gout begins in a disorder of _function_.

Uncomfortable sensations may obtain days and weeks before the incidence
of the fit. To old time sufferers they are sufficiently alarming. But
their significance, as heralds of an initial attack, by victim and too
often by physician also, is usually only appreciated when the threatened
fit becomes an actuality. Speaking of premonitory phenomena in gout,
Sydenham remarked, “Its only forerunner is indigestion and crudity of the
stomach, of which the patient labours some weeks before,” and doubtless
this is in the main true.

As Trousseau long since observed, the patient’s appetite often becomes
capricious. He likes his meat strongly spiced, and craves for acids. But
his satisfaction is short-lived. For eating is followed by drowsiness,
feelings of oppression and fulness, with unpleasant eructations, or
more rarely definite retching. The bowels are generally costive, but in
exceptional instances diarrhœa has been noted. The state of the urine is
variable. Generally scanty and high-coloured, it may in some be copious
and pale.

Uneasiness in the right hypochondrium and even slight swelling of the
liver was noted by Trousseau and also by Scudamore. Such congestion
of the portal system and hepatic enlargement may be only fugacious,
but often the same is permanent, a penalty of the same cause—free
living—which leads to the production of gout. For in many instances but
too true is it that “for years together,” as Sydenham said, “a man has
drunk and feasted, has omitted his usual exercise, has grown slow and
sluggish, has been over-studious or anxious, in short, has gone wrong in
some important point of life.”

But more palpable to his friends than to himself are the concomitant
changes in his disposition and character. From being good-natured and
easy-going he becomes morose and irritable. The irascibility of the
gouty is proverbial, and the explosive mental outbursts to Duckworth
appeared at times to be “a metamorphic substitution for a more overt and
regular attack,” or, as Sydenham expressed it, “Non rectius podagræ quam
iracundiæ paroxysmus omnis dici potest.”

Sometimes his mental vagaries are exchanged for or accompanied by
neuralgia, painful cramps in the limbs, etc. In truth, the premonitory
phenomena of gout are protean, inasmuch as, given any prior weakness or
functional derangement of any viscus, the symptoms of oncoming gout are
masked by aggravation of the same, it may be by cardiac irregularities,
vesical irritability, or in an old bronchial subject by increase of
cough, etc.

But it may be objected, there is nothing _specific_ about these various
_functional_ disturbances. They are not more common in the _gouty_ than
in others. Moreover, the habits of life productive of gout favour the
development of gastric and hepatic derangements. The mental irritability,
the gastric disturbances, etc., may be quite as well accounted for by
overeating and overdrinking as by gout.

Now, if there be nothing _specific_ of gout in these so-called
prodromata—“heartburn, acidity, flatulence, etc.”—then what is their
true significance? For, obviously recognition of their true import is
most essential. Now to my mind the said “dyspeptic” symptoms should
be regarded not as symptomatic of gout, but as _etiologically_ related
thereto.

For, though the etiology of gout is still much debated, the same
obscurity will certainly not be clarified, if we merely content ourselves
with dubbing such “dyspeptic” symptoms as “gouty.” On the other hand, if
we, at this early stage, endeavour to elucidate the _true origin_ of the
“dyspeptic” symptoms, who will deny that this is the more rational and
scientific mode of procedure? The timely elimination of _septic foci_
in the mouth, tonsils, and naso-pharynx conjoined with modification
or restriction of food intake and recognition betimes of the signs of
intestinal infection and constipation would perhaps stave off or avert
the threatened articular outbreak.

It has been suggested that there is some statistical evidence that
“acute rheumatism” has declined in frequency since the introduction
of _tonsillectomy_. In the same way, I cannot help thinking that the
growing infrequency and attenuation of gout is in part due to increasing
appreciation by the laity and the profession of the vital importance
of _oral hygiene_ and timely and radical treatment of _local foci of
infection_. The fact that in _children_, victims of so-called _infantile
gout_, the _purin metabolism_ may show those same derangements held
typical of the subjects of gout, is surely an indication that the
disorder begins betimes, and that we too must not tarry if we would
prevent these evil potentialities coming later to fruition.

Now, if there be nothing _specific_ of gout in the “dyspeptic”
derangements held _prodromal_ thereof, the reader may well ask the
pregnant question, Are there any symptoms or signs that will enable one
to identify the victim of these minor discomforts as being “actually” or
“potentially” a “gouty” subject? In attempting to answer this reasonable
query one would emphasise the fact that _tophi in the ears or at other
sites sometimes antedate articular outbreaks_.

Now given that an individual exhibits _auricular tophi_, one or many, can
anyone deny that he is “gouty,” nay more, that he has _gout_, this even
though he never has had, or may never have, an _articular_ outbreak? In
truth, the eruption of a _tophus_ in the _ear_ is as essentially a “fit
of gout” as if it had occurred at the classic site, the _big toe_.

How vivid the light then thrown upon the import, the _etiological_
significance, of otherwise inexplicable _functional_ derangements!
How grim the potentialities of, _e.g._, “dyspeptic” symptoms as
revealed by detection in the subject of a _tophus_! Whether viewed
from the _diagnostic_ or _prognostic_ aspect, its importance cannot
be overestimated. For let us not forget that the _tophus_ is the one
incontrovertible token of the “gouty diathesis.” This morbid localisation
is the sole outward expression of the inward and dominant pathological
trend.

The great Charcot did not despise its aid. He narrates the case of a
man thirty-five years of age, a sufferer for some months from “acid
dyspepsia,” in whom he predicted a fit of _gout_ from noting an _uratic
concretion_ in one _ear_. Is not the moral obvious that in an individual
complaining of gastric or hepatic disturbances, etc., we should, at any
rate, examine the ears for _tophi_?

For, far more often than is currently realised, their eruption
_antedates_ the _articular_ outbreaks.[27] Moreover, they may not be
solitary, but numerous, the _cutaneous gravel_ of older authors. In
truth, these cases of tophi, _uncomplicated_ by _articular_ lesions,
seem to merit some distinguishing term, representing as they do a purely
_ab-articular_ form of gout.[28] They constitute what might be termed
primitive elemental gout, of which the subsequent _articular_ outbreaks
are but an extension, a further manifestation of the “gouty diathesis.”
For it is just this same tendency to _uratosis_ or deposition of sodium
biurate, and this alone, that to our mind constitutes _gout_, this
“primordial vice of nutrition,” not the congeries of distempers that with
the passing ages have clustered around the primitive gout, well-nigh
submerging its identity.

_Premonitory Symptoms of Tophus Formation._—While tophi may _antedate_
articular attacks, we do not always meet with them as _mature_
concretions easily recognisable as such. We must have regard therefore
to the symptoms and signs indicative of their impending eruption.
Consequently in a patient complaining of the various functional
disturbances that so frequently anticipate gout we should never dismiss
as trivial any complaints of _pricking_ or _tenderness_ in the _ears_.

Sometimes the pain in the ears is _acute_, the tenderness such as forbids
their pressure on a pillow. Graves, of Dublin, not only noted that the
pain in some instances was agonising, lasting a few hours, but he himself
suffered also from such attacks of auricular pain, which only disappeared
when gout supervened in his _fingers_. I have myself frequently known the
pain and soreness referred to chilblains, though later their tophaceous
nature was disclosed.

Given such auricular pain and tenderness, we should examine the _pinna
for small red swellings_.[29] These, when definitely localised, should be
punctured and the thick white fluid which exudes examined microscopically
for _urate of soda_ crystals. In some instances the creamy-like exudate
does not yield a crystalline deposit, and Dr. Munro and I are inclined
to believe that there is a _pre-uratic_ stage in the evolution of tophi.
We have observed this absence of crystalline deposits in apparently
unmistakable tophi, as evidenced by the usual pearly white concretions
in the rim of the ear. I recollect that the late Sir William Osler, when
visiting our laboratory, was deeply interested in this possibility,
as suggested by Dr. Munro, of a _pre-uratic_ stage. Needless to say,
all local sources of fallacy—Woolner’s tip, fibroid nodules, sebaceous
cysts—were excluded, while, in the lack of _crystalline_ proof, the
evidence in favour of the associated _arthritis_ being gouty rested
on its being at the classical site, the _great toe_. Moreover, as an
alternative explanation we have the possibility of _reabsorption_. We may
recall Duckworth’s well-known example where a man had two attacks of gout
in the right great toe joint, yet autopsy revealed no speck of uratic
deposit. We know, too, that, following an _acute_ attack, tophi may
diminish in size or even disappear, while coincidently fresh tophi form
at other sites.

_Premonitory Articular Pains._—Again, when, in association with
indigestion or other premonitory symptoms, twinges in the toe recur from
time to time, especially after consuming wines or certain articles of
food, these same are very suggestive of impending gout. Garrod is very
definite on this point: “I have no doubt that many persons experience
extremely slight attacks of gout before the development of the affection
in an acute form, and several of my patients have assured me that for
years before their first severe attack in the great toe they have felt
slight periodic twinges. I am of opinion that when such twinges occur
deposition has already taken place.”

In conclusion, we would urge that, given _gastric_ or _hepatic_
disturbances, etc., in a subject predisposed by _heredity_ or _habits_ to
gout, we should note the presence or absence of the following:—

    (1) Pain, pricking, or tenderness in the ears, with or without
    small red swellings.

    (2) Similar sensations at site of finger joints, with dorsal
    swellings over which the skin may be red or unchanged.

    (3) The existence or not of pearly white concretions, _i.e._
    mature tophi (as tested microscopically), at the above sites or
    elsewhere.

Further signs that may be sought for in cases of doubtful nature, _i.e._
_unevidenced by tophi_, would be:—

    (4) The presence of _uricæmia_.

    (5) A lowered or sub-normal output of uric acid in the urine.

    (6) Diminution or retardation of the output of exogenous purin.

To take up the thread of our narrative regarding the _prodromal_ symptoms
which at any moment may give place to an _articular_ outbreak. The
_determinants_ or _exciting_ causes having been already dealt with in
the section on etiology, we shall here only note those symptoms or signs
that portend the _imminence_ of the paroxysm. These are very variable.
But it is suggestive if without any change in the habits the “dyspeptic”
symptoms abate somewhat or disappear.

Indeed, it is well recognised that, whatever the nature of the prodromal
phenomena, they all tend to cease just before the oncoming attack.
Occasionally a pre-existing depression gives way to a feeling of
exuberant health or well-being. We recall the instance of a celebrated
physician whose lectures always just prior to an attack took on an added
brilliance.

Reverting to more definite harbingers, it has been noted that the _urine_
becomes _scanty_, and its content of _uric acid_ much _diminished_, some
three or four days before the paroxysm, though such is not invariable.
Easier of note and widely recognised is the fact that in those exhibiting
tophi _pricking pains or tenderness_ are experienced at their site.
Scudamore, Garrod, and Duckworth are all agreed on this point. Another
sign noted by Sydenham was that the _veins_ of the _part_ about to
be affected become _engorged_—a feature confirmed by Trousseau and
others.[30]


THE ACUTE PAROXYSM

A brief interlude, lasting a few hours or a day, frequently intervenes
between cessation of the prodromal discomforts and the onset of the
attack. This delusive sense of well-being deceives none but the
uninitiated, for to the old time sufferer it is but the truce before the
threatened assault.[31]

Still the subject feels better and more placid than his wont, seeks
his bed, and sinks to sleep (“sanus lecto somnoque committur”). But
suddenly, more commonly an hour or two after midnight, he awakes to a
pain in the foot, usually in the ball of the great toe, though more
rarely in the heel, instep, or ankle. Simultaneously he becomes chilly,
shivers, or has a rigor. But as the pain, at first bearable, grows in
intensity, these feelings lapse, giving way to feverish restlessness.
Posture after posture is renounced, but, toss as he will, he strives in
vain to find a place of ease for the tortured limb. Even the pressure of
the bedclothes is intolerable. But towards morning (“sub galli cantu”)
the pain remits as suddenly as it began. Anon the sufferer breaks into
a gentle sweat, falls asleep, and wakes to find the painful part red,
swollen, tense, and shiny, surrounded with œdema and turgid veins.

The same series of events recurs, though often in mitigated form, for
some days and nights. During the day his pain is lulled, but towards
evening it gathers in intensity to cease or diminish towards morning.
The cycle continues from eight to ten days; then pain ceases, redness
fades, œdema subsides, and the inflamed cuticle peels, with itching.
The temperature meanwhile has sunk to normal, the local tenderness and
stiffness gradually pass off, and health is restored. “Gout is the cure
of the gout,” said Mead long since, and certainly recovery from the
first attack of gout is usually speedy and complete. A renewed sense
of _bien-être_ ensues, free from the discomforts that led up to the
outbreak. Indeed, in exceptionally rare instances the disease seemingly
exhausts itself in a single paroxysm, or decades may pass before
another visitation. Sir William Roberts tells of a Yorkshire squire who
sustained a classical attack in his twenty-seventh year, the next in his
eighty-ninth year. Frequently a second attack may not occur for one, two,
or even three years. But the tendency to recurrence usually becomes more
and more pronounced as the years roll on, and eventually the gouty man
resigns himself to the doleful expectation of an attack once or twice a
year, during spring or fall, with some approach to periodic regularity.

Initial attacks of gout are usually _monarticular_, but consideration
of the polyarticular variety will best be postponed until we come to
consider _acute gouty polyarthritis_. Also we think it will be more
convenient for us to defer discussion of _retrocedent_ gout to the
chapter dealing with the irregular or anomalous types of the disorder.
Meanwhile we will now proceed to detailed description of the individual
phenomena that make up the clinical content of acute gout.


DETAILED CONSIDERATION OF PHENOMENA

_Onset._—From Sydenham’s classical account it might be inferred that the
onfall of gout is always fulminant. But this is far from being the case.
For I find myself in agreement with Hilton Fagge that in many, if not
the majority of instances, even the _initial_ outbreak of the disorder
is installed in a far less dramatic manner. Certainly in not a few cases
its manner of approach is insidious, not to say stealthy. At onset then
the nature of the case is therefore frequently misinterpreted both by
victim and physician. The free liver, fearing that Nemesis has overtaken
him, is fertile in suggestion. He has overwalked, his boot pinched
him, or it is a sprain. Local appearances may be non-committal. There
may be no swelling nor redness, and no access of pain at night. Still
there is discomfort when he walks. The so-called sprain lingers, and one
morning the great toe, instep, or ankle, is swollen, tender, flushed,
and the victim’s fears and the physician’s suspicions are converted into
certainty: it is gout!

Still in this matter of the onset I must not overlook the findings of my
colleague James Lindsay. In 569 cases, the onset was sudden in 458, and
in the remaining 111 examples gradual. It was noted that only 14·5 per
cent. of the male cases were of gradual onset. But no less than 47·1 per
cent. of the female cases developed after this fashion.

Again to resume, it is by no means invariably the case that the onset is
_nocturnal_. For, as Duckworth has pointed out, many attacks begin during
the day, and this is perhaps more often the case after the disorder is
fully established.

_Locality._—Gout in its classical form is _monarticular_ in distribution.
In 375 out of 512 _initial_ seizures, Sir Charles Scudamore found that
the metatarso-phalangeal joint of the great toe of one or other foot was
the joint affected. Garrod, too, noted that, excluding the great toe,
in not more than 5 per cent. were other joints implicated. As to the
frequency of incidence in joints other than the big toe, opinions differ.
For Scudamore it is the ankle, for Garrod the instep, and afterwards the
outer side of the foot and the knee. In contrast, Hilton Fagge holds that
next to the great toe gout vents its initial fury with greatest frequency
upon the _metacarpo-phalangeal_ joint of the index finger, adding,
“certainly not the thumb.” Most authorities however agree that gout in
its early stages rarely attacks the joints of the _upper_ limb, and even
in its most inveterate form the _shoulder_ and _hip_ joints are immune.
Personally, I have never seen a case of gout in the shoulder or hip; such
cases are usually examples of _osteo-arthritis_.

Exceptionally, even in first seizures, more than one joint may be
affected. Thus it may migrate from one big toe to its fellow, or
travelling further afield, may invade ankle, knee, wrist, or elbow, or
small joints of hand. W. Gairdner held that in gout the joints of the
_left_ were more commonly attacked than those of the right limb. But
James Lindsay’s figures would appear to indicate precisely the reverse,
viz. a predilection for the _right_ side of the body.

_Pain._—If we may accept the lurid imagery of its victims, even the
tortures of the Inquisition failed to transcend in agony the—

                “... pangs arthritic
    that infest the toe of libertine excess.”

                                    _Cowper._

Sydenham said that at its onset the pain was as that of a dislocation
(_ossium dislocatio_). At its zenith it was as if the flesh was being
gnawed, squeezed in a bootscrew, or scalded by molten lead or boiling
water. Sensory perversions are superadded, and, as Ambrose Paré said,
“some patients say they burn, while others complain of icy coldness.”

Its peculiarly exasperating nature is well illustrated by Hosack, an
old time Professor of Medicine of New York, who thus delivered himself:
“Some compare it with the gnawing of a dog, the pressure of a vice, or
the pain of the actual cautery; this probably is not far from the truth,
judging from the anecdote I have heard of a man subject to gout. This man
falling asleep barefooted before a large fire, the fire fell, and a large
coal found its way to his foot; half awake and half asleep, he cried
out: ‘There’s that d——d gout again!’ He at length awoke, when he found
a large coal frying his great toe. The sensation of the two evils was
probably the same.”

The pain is aggravated in that frequent “startings” of the limb prevent
the victim keeping the foot at rest. The slamming of a door, or the
incautious shaking of the bed, so quickens its throbbing intensity as
provokes a literal frenzy of rage. But fortunately it is not always
so. For though the pain of gout is unquestionably severe, at times
excruciating, yet it presents infinite grades of severity. Also one must
recollect that but too many of its victims are already in a high state of
irritability before the outbreak. Moreover, their powers of self-control
are too often sapped by unbridled self-indulgence, and they have but
slight reserves of patience and fortitude to draw upon.[32]

Apart from the personal factor, in _subacute_ cases the pain is notably
less severe than in the _acute sthenic_ form. The pain of gout, as a
rule, is more intense than that of _acute rheumatism_, and, I fancy, than
that of all other varieties of acute arthritis.[33] Sir Thomas Watson in
his fascinating lectures tells of a witty Frenchman who, comparing acute
gout and acute rheumatism in respect of pain intensity, remarked: “Screw
up the vice as tightly as possible, you have rheumatism; give it another
turn, and that is gout.”

Lastly, in respect of the duration of the pain, it is not always
true that it wholly _intermits_ at the approach of dawn. It does so
frequently, it is true, but in some instances pain, more or less severe,
continues during the day as well as the night. Occasionally, on a
_crescendo_ scale, it continues increasing almost up to the crisis.
Generally speaking, too, the shorter the duration of the paroxysm the
more intense the pain, and the more prolonged the less the degree of
suffering.

Following the crisis, the pain gradually becomes less and less, giving
place to a feeling of numbness of the toe, which in older subjects may
endure for some days.

_General Phenomena._—Symptoms, other than those referable to the affected
part, vary widely in different cases. In this respect the acute _sthenic_
forms contrast with the acute _asthenic_ types. In the former the pulse
quickens; the temperature rises, but rarely exceeds 101°-102°, though
Garrod saw it reach 104°. The tongue is furred, the breath foul, with
anorexia and thirst. Though the appetite is frequently impaired or lost,
yet in some instances it is retained. Dyspeptic symptoms, hiccough,
eructations, etc., are sometimes prominent, but often wholly lacking.
The bowels are constipated, as a rule, the stools pale, or dark and
extremely offensive. The urine is generally scanty, high-coloured, with
a lateritious sediment on cooling. It may contain a trace of albumen.
Severe _cramps_ affecting muscles of the leg, thigh, and upper parts of
the body, are more or less prominent symptoms in a considerable number of
instances.

The _pyrexia_ appears to be _symptomatic_, more or less in proportion to
the acuteness of the local phenomena. Comparably the highest temperatures
are usually met with in _sthenic_ forms in relatively young or robust
middle-aged subjects. Duckworth noted the interesting point that “a
preliminary rise is commonly noted for one, two, three or four days
before a joint is actively involved.” With the articular outbreak the
febrile movement becomes more active. The temperature runs up to 100° or
over, but with the morning abatement sinks to normal or nearly so. The
following evening it rises again frequently to a higher level, 102° with
a morning remission, and so it continues for a variable number of days,
it may be only two or eight to ten. It then subsides, and frequently for
a few days remains sub-normal. Lastly, the _acute asthenic_ forms, that
occur often in women (Garrod), may be wholly _afebrile_.

_Changes in the Blood._—Apart from its increased content of uric acid,
further morbid changes take place in the blood in gout.

Neusser in 1894 described what he termed “perinuclear basophilic
granules” over and about the nuclei of the leucocytes in the blood of
gouty patients. He held that the dark granules constituted the mother
substance from which uric acid was derived, and that their presence
in the blood was distinctive of the “gouty diathesis.” Subsequent
researches, however, by Futcher and others appear to have shown the
absence of any interrelationship between the amount of these granules and
uric acid elimination, though Neusser claimed that cases showing them
excreted uric acid in excess.

More significant, however, is it that the blood in acute gout may show a
high grade _leucocytosis_ with _secondary anæmia_.

In a case under my care of _acute gout_ at classic site, though by no
means of unusual severity, the following was the content of the blood
picture:—

                            BLOOD COUNT.

  Red corpuscles, per c. mm.    3,692,000 =  73·8 per cent.
  Hæmoglobin                                 80      ”
  Colour index                                1·08   ”
  Leucocytes, per c. mm.           25,920

                        DIFFERENTIAL COUNT.

  Lymphocytes           8·0 per cent.  =  2,074 per c. mm.
  Large mononuclears    3·5    ”       =    907     ”
  Polymorphonuclears   87·0    ”       = 22,550     ”
  Eosinophiles          0·5    ”       =    130     ”
  Mast cells            1·0    ”       =    260     ”
                      -----
                      100·0

  The salient feature of the blood picture is the high grade
  _leucocytosis_ of leucoid type with moderate anæmia—appearances
  quite compatible with, and suggestive of, an _infective_
  arthritis. To these interesting blood changes we shall again
  refer when dealing with the acute polyarticular variety, the
  above case being of monarticular type, _i.e._, the big toe.

_Uric Acid Excretion._—If when on a _purin-free_ diet a gouty subject
develops a paroxysm, the curve of uric acid excretion in the urine is
so characteristic as to be almost pathognomonic of the disorder. As His
pointed out, immediately before the onset of the paroxysm the endogenous
uric acid sinks to a lower level (termed by Umber the _anacritical
stage of depression_). With the onset of the attack the uric acid
content of the urine quickly increases, to reach its zenith on the
second or third day. F. Pfeiffer, who first noted this point, termed
it an _uric acid wave_. Subsequently, with the gradual subsidence of
the paroxysm, it again drops into what Umber termed the _post-critical
stage of depression_. While this curve of endogenous purin excretion
may be modified by oft recurring exacerbations, still Umber holds that
nevertheless it is of decided value in differential diagnosis.

_Local Phenomena._—The site and character of the pain having been dealt
with, we now pass on to consider the objective changes in the affected
part. The local _engorgement_ of veins that _precedes_ the _articular_
outbreak becomes more pronounced, extending from the vicinity of the
painful joint as far as the leg. The overlying skin of the joint
quickly becomes red and tumid. It is not a bright, but a dark red, the
superjacent skin taking on a shining smoothness that has been compared to
the peel of an onion. Indeed, in its more violent form it resembles but
too closely the ordinary appearance of an _abscess_, over which the skin
is becoming thin. The redness is not strictly confined to the surface of
the joint, but spreads a little beyond, and where it ceases _œdema_ is
perceptible.

The redness in its intensity attains its zenith in from twenty-four to
forty-eight hours, and then in hue becomes more violaceous. On the other
hand, the _œdema_ may go on increasing for some days. At first, owing to
tension, the presence of œdema may not readily be elicited. But with the
subsidence of inflammation the swollen parts readily pit on pressure. It
is scarcely possible to detect _intra-articular effusion_ unless it be
the ankle joint that is involved.

According to Duckworth, in the more _sthenic_ forms there may be local
_ecchymoses_. With the crisis the redness, œdema, and venous turgescence
die down. The previously distended skin becomes wrinkled, and with
complete subsidence of inflammation _desquamation_ ensues. This process
is generally attended with troublesome _itching_. It is most noticeable
about the _feet_ and _hands_, but more rare at other sites. Scudamore
said that in seventy-eight out of 234 cases no peeling occurred, but, as
Garrod observed, it may readily be overlooked unless especially sought
for.

The exquisite sensitiveness of the parts, as before noted, gives way to
_numbness_. The diminished sensibility, coupled with _stiffness_ of the
joint, renders walking difficult for some days, and, indeed, a month or
more may elapse before the joint, even in favourable cases, recovers its
customary mobility.

In acute _asthenic_ forms great contrasts appear. Pain and tenderness in
the toe may be moderate, but there may be little local heat or redness
and no _pyrexia_. But _œdema_ is generally in evidence, and the usual
_desquamation_ of skin follows.

_Tophus Formation._—To the local changes that mark their eruption at
ab-articular sites we have already alluded. Here we would only reiterate
that their formation _follows_ the local joint inflammation. Consequently
if a few days after the attack local pain or tenderness, with or without
swelling in the vicinity of the joint, should be complained of, it should
not be dismissed as of no account, but the affected parts should be
scrutinised carefully and, where possible, at short intervals. This in
the interests of diagnosis of a joint affection which may at the time
have been of doubtful nature, more especially if the primary attack occur
elsewhere than at the classical site. Some observations of Trousseau
are well worth quotation: “Physicians who have watched the progress of
the evolution of tophus believe that it is formed during the paroxysm of
gout. They are mistaken: the deposit appears during the interval between
attacks, or at least when the attacks have not been of long duration,
and when they do not recur in such rapid succession as to run into
one another, in which cases their secretion has commenced during the
preceding and continued during the succeeding attack.”




CHAPTER XVII

CLINICAL ACCOUNT (_continued_)


ACUTE GENERALISED GOUT

While gout may throughout its life history confine its ravages to the
_foot_, if not solely to the _toe joints_, it may, even in the _initial_
attack, involve many articulations. Such cases usually, if not always,
occur in persons of marked _gouty heredity_. In its simplest forms the
orthodox _monarticular_ seizure is simply exchanged for a sequential
implication of each big toe joint. If so, as Trousseau pointed out,
the joint that is the last to be involved is least affected, and the
soonest to get well again, while the accompanying œdema is of shorter
duration. But in more severe cases not only the big toe, but the _tarsal_
joints, the _knee_ and the _hand_, may be invaded in the _first_ attack.
Occasionally, too, the disorder displays concomitantly its tendency
to involve other structures, _tendons_ and _aponeuroses_, _e.g._, the
_tendo Achillis_, _plantar fascia_. Such _widespread initial involvement_
is usually preceded by _prodromal_ phenomena of unusual severity
and prolonged duration. These _initial_ attacks of _polyarticular_
distribution are extremely rare.

Far more commonly acute gouty polyarthritis supervenes after several
attacks of classic location have been suffered. The gouty inflammation
in these cases invades the joints after a serial fashion. But each joint
as it becomes involved goes through the same painful cycle. Thus, for
five or six days the pain goes on increasing, then abates, and finally
the wished-for crisis comes. So it happens that the gout may be raging
simultaneously in several articulations, though in each at different
stages of evolution. Consequently the symptoms do not pursue an even
tenor, but are made up rather of a series of little attacks—_series et
catena paroxysmulorum_, to invoke Sydenham’s expression.

Frequently periods of apparent recovery take place. The temperature
remains normal for some days, and welcome convalescence seems
established, when, to the victim’s despair, the temperature again rises,
and the same weary cycle, though perhaps shorter, is yet to be endured.
Running this chequered career, the disorder may last for six weeks or two
or three months.

In such attacks not only the _feet_, _knees_, _hands_, and _elbows_,
may be promiscuously involved, but often also the _ligaments_, _bursæ_,
_tendon sheaths_, and _aponeuroses_. The suddenness with which the
disorder shifts its seat from one joint to another, or from joints to
bursæ or muscles, often leads to its confusion with _acute rheumatism_.
In other words, that _fixity_ distinctive of gout in its monarticular
forms is here exchanged for _mobility_, that specific quality of acute
rheumatism.

Naturally, the implication of so many varied structures casts its impress
on the clinical picture, inasmuch as the physical characters vary
with the different textures involved, their capacity for inflammatory
distension, etc. On the _dorsum_ of the _hand_ and _foot redness_ and
_œdema_ will be prominent, and Scudamore noted that the flush might be
widely diffused, simulating _erysipelas_, with here and there small
_ecchymoses_.

When structures more deeply placed, _i.e._, _tendon sheaths_ at ankle,
knee, and wrist, are singled out for attack, swelling is less marked and
redness of the skin more patchy in distribution. The _bursæ_ at the elbow
or back of the knee may swell with extraordinary rapidity. The parts
become exquisitely tender and painful, while the overlying skin takes on
an angry blush. They may subside, but more often continue permanently
enlarged, defiant of reduction.

Involvement of the _olecranon bursa_ is very typical of gout. Pratt,
of Boston (1916), tells of a case in which the subject had during
twenty-seven years suffered from recurring attacks of _acute gouty
polyarthritis_. The eight or ten physicians who had treated him had
all regarded the disease as _rheumatic fever_. Pratt himself observes:
“I did not feel sure of the diagnosis until I saw the swelling on his
elbow, which presented the typical picture of a chronic _gouty olecranon
bursitis_.”[34] Occasionally the bursæ when filled with uratic deposit
undergo _suppuration_ following injuries. The bursa in connection with
the great toe frequently becomes acutely inflamed, and Scudamore in a
gouty hand saw an old ganglion take on the same inflammatory reaction.

The tendon sheaths when involved lead to great disablement, as even the
most tentative attempts at movement give rise to sudden and agonising
cramp. The _tendo Achillis_ is a favourite site, or the tendons of
the wrist, or the ligament of the patella. The same is true of the
_aponeuroses_, the predilection being for the lumbar or gluteal fascia,
in which instance it may extend to the sheath of the sciatic nerve. These
extensions of gout to tendon and nerve sheaths frequently outlast the
articular lesions, and may become the dominant element in the clinical
picture.

Naturally, when not only joints, but _bursæ_ and other structures, are
involved and implicate both upper and lower limbs, the victim presents a
pitiful spectacle, one of almost complete helplessness. Œdema and general
venous turgescence may be very pronounced in one or more members, giving
a subjective sensation of almost overwhelming weight in the limb.

Reverting to the _constitutional_ symptoms, the outstanding feature is
that, notwithstanding the widespread involvement of joints with manifest
local inflammatory reaction, the _pyrexia_ is of _moderate_ grade, and
so frequently, indeed, is it _afebrile_ that this peculiarity is of
diagnostic significance.

_Changes in the Blood._—The findings are extremely interesting in view of
the high grades of _leucocytosis_ to be met with both in _pyrexial_ and
_apyrexial_ examples.

In a case of _acute gouty polyarthritis_ under my care the blood picture
was a very striking one. The patient had suffered from gout for some
eleven years, with recurrent acute exacerbations. There was widespread
involvement of the joints both in upper and lower limbs. On the dorsum of
the mid-phalangeal joints small semi-solid swellings were present, the
exact nature of which was somewhat puzzling. But inasmuch as the pinna
in both ears was studded with _tophi_, this seemed to provide a clue.
The auricular tophi were verified microscopically. The extra-articular
phalangeal swellings were then aspirated with a hypodermic syringe. A
turbid straw-coloured fluid issued, which microscopically was found to
contain _biurate_ crystals. His temperature rose nightly from 101° up to
102° F., with morning remissions. The left knee and wrist were the seat
of _effusion_, and some of the small finger joints were inflamed.

                             BLOOD COUNT.

  Red corpuscles, per c. mm.       4,432,000 = 88·6 per cent.
  Hæmoglobin                                   60      ”
  Colour index                                   ·68   ”
  Leucocytes, per c. mm.              27,200

                         DIFFERENTIAL COUNT.

  Lymphocytes                    9 =  2,450
  Large mononuclears            13 =  3,540
  Polymorphonuclears            78 = 21,220
  Eosinophiles                   0 =      0
  Mast cells                     0 =      0
                             -----
                             100·0

The left knee joint was aspirated by Dr. Munro. A clear fluid of straw
yellow tint was withdrawn, which yielded some fibrin on standing. The
cytological examination gave the following results:—

                             TOTAL COUNT.

  44,800 per c. mm. (nearly all leucocytes).

                         DIFFERENTIAL COUNT.

  Polymorphonuclears               92
  Lymphocytes                       7
  Large mononuclears                1
  Eosinophiles                      0
  Basophiles                        0
                                  ---
                                  100

Attempts at culture on broth and agar proved _sterile_. In addition three
separate blood cultures, taken at intervals of a few days, on agar slopes
and broth, all gave _negative_ results.

In another instance of _polyarticular_ distribution the subject was seen
during the _inter-paroxysmal_ period. He displayed auricular _tophi_, the
crystalline content of which was verified microscopically.

                             BLOOD COUNT.

  Red corpuscles, per c. mm.            5,732,000 = 194·6 per cent.
  Hæmoglobin                                         65      ”
  Colour index                                         ·57   ”
  Leucocytes, per c. mm.                   13,200

                         DIFFERENTIAL COUNT.

  Lymphocytes                      34 = 4,490
  Large mononuclears                3 =   400
  Polymorphonuclears             61·5 = 8,120
  Eosinophiles                     ·1 =   130
  Mast cells                       ·5 =    66

Chalmers Watson some years previously investigated the blood in cases
of _acute gouty polyarthritis_ both during an exacerbation and in the
_inter-paroxysmal_ period. His findings were as follows:—

During the _attack_ the films showed very marked _leucocytosis_. Also
there was present a large number of peculiar myelocyte-like cells, these
more than half as numerous as the ordinary finely granular oxyphil
leucocytes.

    “Each of these cells contained a large oval or horse-shaped
    nucleus, poor in chromatin. The nucleus occupied about half
    of the total area of the cell. It did not stain uniformly,
    and it was usually situated to one side, coming right up to
    the cell outline, and occupying from a third to a half of the
    total circumference. In many of these cells the nucleus was
    almost round, with but one slight indentation; in others the
    indentation was pronounced. The whole cell stained a pale blue,
    presented a degenerated appearance, and contrasted markedly
    with the ordinary leucocyte seen in the same film, with its
    brilliant blue nucleus and bright red eosinophil granules. The
    special cells under description were also remarkable for their
    size, measuring about 15 m. in diameter, a few being smaller,
    about 10 m. Some of them contained vacuoles in the cytoplasm.
    The general appearance of these cells suggested exhaustion
    in so far as the cytoplasm did not contain the typical fine
    oxyphil granules characteristic of the myelocyte. From the
    character of the nucleus and cytoplasm, they were undoubtedly
    distinct from lymphocytes. The large lymphocytes were scarce;
    small lymphocytes were numerous. True eosinophil cells were
    also scarce. The main bulk of the leucocytes consisted of the
    ordinary finely granular oxyphil leucocytes and the peculiar
    myelocyte cells described.

    “_Blood plates._—Some of the blood-plates were large (4 m. in
    diameter), and often formed very irregular torn-looking masses.
    The red cells were apparently normal.”

Shortly after Chalmers Watson, Bain published his results of blood
examination in _acute gouty polyarthritis_. He also noted the presence
of a distinct _leucocytosis_. A differential count disclosed a marked
increase of the eosinophil cells, and he adds: “There was present a
moderate number of the peculiar myelocyte-like cells originally described
by Chalmers Watson.”

Dr. Munro, though he carefully examined the gouty blood films to this
end, was unable to identify the myelocyte-like cells noted by these
observers.

Recently, through the kindness of my colleague Dr. Waterhouse, Dr. Munro
and I had again an opportunity of examining the blood in a case of this
kind during the _inter-paroxysmal_ period. The subject, a male, had had
repeated attacks at the classic site, with subsequent extension to other
joints. Multiple tophi were present in both ears, and the crystals of
uric acid were demonstrated microscopically.

                             BLOOD COUNT.

  Red corpuscles                  7,364,000   =   147 per cent.
  Hæmoglobin                                       74    ”
  Coloured index                                    0·5  ”
  Leucocytes                         21,400

                         DIFFERENTIAL COUNT.

  Lymphocytes                28·5 per cent. =  6,099 per c. mm.
  Large mononuclears          2·5    ”      =    535      ”
  Polymorphonuclears         64      ”      = 13,696      ”
  Eosinophiles                3·5    ”      =    749      ”
  Basophiles                  1·5    ”      =    321      ”

The blood picture, it will be seen, is one of erythræmia—a marked
leucocytosis, a normal differential percentage count, pronounced
secondary anæmia.

Da Costa also notes, in a case of gout, erythræmia (7,125,000) with a
leucocyte count of 14,000. Ewing, too, records an instance of chronic
gout with huge tophi, seen in an acute exacerbation, in which the blood
gave a leucocyte count of 21,000 with 70 per cent. hæmoglobin. In another
severe instance of subacute type the same observer again met with
leucocytosis (15,000).

In regard to these interesting blood findings, it is to be cordially
hoped that as the somewhat rare opportunities occur they will be taken
full advantage of.

As to the other general clinical features the _nervous_ system, as might
be expected, is often greatly perturbed, and the mental distress and
anxiety in some instances appear to cause even more irritation than the
bodily pain. Febrile movement when present accords with that observed
in _monarticular_ sites, save only in the tendency to _relapses_.
Sweating is not a common feature, as in _acute rheumatism_. Neither does
acute _endocarditis_ occur in gout. On the other hand, as this acute
polyarticular form may recur throughout years, it may in its later stages
be complicated by _nephritis_.

Furthermore, in its differentiation from acute rheumatism the more
advanced age of the sufferer, always over thirty-five and more often
nearer fifty or over, will be of help. The presence of an hereditary
taint, the nature of the occupation and personal habits, and more
pertinently the history of a classical attack in the great toe, may give
a clue.

But in this, as in all other varieties of gouty arthritis, the one and
only unequivocal objective proof of the nature of the disorder is the
_presence of tophi_. Lamentable indeed is the frequency with which this
fact is forgotten, to our confounding and the patient’s detriment. As
Hilton Fagge, discussing the diagnosis of gout, long since observed: “All
those parts which are apt to be the seat of tophi should be examined. If
a single deposit of urate of soda can be found it settles the question.”

In conclusion, before passing to consideration of _chronic articular
gout_, it will be convenient here to discuss certain _concomitant
phenomena_ of the acute types. We refer to the muscular and nerve forms
of fibrositis, which, we hasten to add, are of common occurrence also in
the chronic types of articular gout.


COLLATERAL PHENOMENA OF GOUT

The liability of acute articular gout to be complicated by _muscular_
and _nerve_ disorders has already been briefly alluded to. Also it was
pointed out that in respect of this tendency gout displayed an analogy
with the _specific_ infections, viz., in that these latter too are prone
not only to arthritic, but to muscular and nerve, lesions also.

Our forefathers, greatly exercised by this apparent overlapping of
“gout” and “rheumatism,” in their efforts at discrimination drew fanciful
contrasts between the subjective sensations produced by gout and
rheumatism, but all to no end, for said Heberden, “It must be owned that
there are cases in which the criteria of both are so blended together
that it is not easy to determine whether the pain be gout or rheumatism.”

Gradually, however, a change in attitude made itself felt. It became
no longer customary to regard such examples as blends of gout and
“rheumatism,” but to hold the _muscular_ and _nerve_ disorders as also
attributable to the underlying gout. Thus, so impressed was Garrod
with the frequency of the incidence of _lumbago_ and _sciatica_ in
_gouty_ subjects that he was doubtful as to whether they ought to have
been classed by him as among the “diseases to which gouty persons are
particularly liable.” He thought “they might perhaps have been properly
classed among the forms of _irregular_ gout.”

Duckworth, again, felt sure “that much so-called ‘muscular’ rheumatism
is really gouty,” and forthwith ranked its manifestations among the
_irregular_ forms of gout. Hilton Fagge was likewise convinced that the
muscular types of fibrositis are frequently and obviously related to
gout; while Sir William Gowers, discussing this same muscular fibrositis,
is even more explicit: “It is currently associated with gout, and the
truth of the belief is soon impressed upon the practitioner. But it
is gout with a difference: it may occur in those who are gouty in the
common sense of the word, but some of the most severe cases I have seen,
especially the brachial form, have been in those who have inherited a
tendency to gout, but have not merited its development.”

Turning to the _nerve_ manifestations, Charcot long since pointed out
that gout and sciatica might co-exist, while Gowers is insistent that
“underlying most cases of sciatica is either the state of definite gout,
or that ‘rheumatic diathesis’ in which the fibrous tissues suffer,
especially those that are connected with the muscles, a form closely
connected with common gout by co-existence or descent.”

As to my own opinion, I have, in collaboration with Bassett Jones,
discussed in detail this relationship of gout to fibrositis in our
monograph on the latter disorder, and I shall largely transcribe our
remarks therein on this vexed point.

Of all the conditions reputed to be etiologically related to fibrositis,
in none of them is the connection more obvious or more easily traceable
than between this affection and _gout_. Whether or no the hyperplasia of
the connective tissues be directly due to the gouty toxin must perforce
for the present remain uncertain. But there is no doubt as to the
relatively frequent incidence of fibrositis in “gouty” subjects. It is
as true to-day as when Scudamore wrote it that occasionally “a patient
when he has gout in the regular situations suffers, in consequence of
some partial exposure to cold, a rheumatism in other parts, as in the
muscles of the neck, or in the shoulder joints; and a seizure of lumbago
at the time of the invasion of the gout is also not uncommon.”

Apart from the _simultaneous_ incidence of gout and _fibrositis_ in
the same subject, it is equally certain that the victims of a “gouty”
heritage are unusually prone to develop fibrositis.

Thus, in a series of 1,000 cases hereditary or acquired gout was present
in no less than 281—viz., a percentage incidence of 28·1. While this
taint was more in evidence in fibrositis of the joints, it obtained
appreciably in regard to all muscular types of the affection, more
especially _lumbago_, its influence also being very obvious in the case
of _sciatica_ and other types of nerve sheath involvement.

In light of this, we must admit being somewhat nonplussed by those who
confidently affirm that “gout” plays little or no part in the production
of “fibrositis.” Speaking from an extensive experience, we confidently
believe the reverse is the case, and that the _gouty_ element is but too
frequently overlooked in examples of this affection.

Approaching another aspect of this vexed question of the relationship
of gout, what of the ambiguous attitude of those who, while denying it
any share in the causation of _lumbago_ and other types of _muscular_
fibrositis, yet at the same time attribute to gout an important
etiological _rôle_ in the allied conditions _sciatica_ and _brachialgia_?

Thus, they maintain that the fleeting attacks of lumbar fibrositis or
lumbago which ensue after dietetic indiscretions have no relation to
gout, but are simply indicative of some digestive disability on the part
of the individual for certain articles of diet. Hardly to our mind a
satisfactory mode of differentiation; much less can it be held to put
out of court the influence of _gout_. For are not the gouty precisely
the very persons who display this inability to cope satisfactorily with
unusual or excessive meals? Hence the frequency with which in their
instance attacks of lumbar fibrositis, often transient, almost invariably
ensue when any unwonted excess of purin-containing food has to be
disposed of, and especially when at the same time katabolic changes have
been stimulated in the body by the ingestion of alcohol, not necessarily
excessive in amount.

That the _lumbar_ regions should have been singled out is the more
remarkable, for, if there be one form of fibrositis more than another
prone to be associated with gout, it is precisely _lumbago_.

Our difficulty, moreover, in appreciating the cogency of this plea for
excluding the influence of gout in muscular fibrositis is the more
accentuated in that those who advocate it claim that this very gout is
the salient etiological factor in _sciatica_ and _brachialgia_.

This position is untenable, and for the following reasons: the
pathological lesion in both instances is the same—viz., _fibrositis_; in
lumbago and deltoid rheumatism it implicates the sheaths and interstitial
tissues of the _muscles_, in sciatica and brachialgia the similar
investments of the _nerves_.

Strictly speaking, therefore, any differentiation that we can effect
between muscular and neuralgic types of fibrositis is perforce merely
_topographical_. To draw _etiological_ distinctions is well-nigh
impossible, for the very continuity of the fibrous tissues favours the
passage of one type into the other. Hence clinically we find that the
bulk of our cases of sciatica are preceded by lumbago, and similarly many
cases of brachial neuralgia or neuritis develop by extension out of a
pre-existing deltoid fibrositis.

In light of such transitions of _muscular_ into _neuralgic_ types of
fibrositis, it seems inconsistent to postulate a gouty origin for the
latter and at the same time to deny it any share in the production of
the former. For ourselves, we fully recognise gout as the most potent
predisposing factor in sciatica and brachialgia, and _ergo_ in the
closely associated and often antecedent muscular types of fibrositis.

While insisting on the importance of gout as a _predisposing_ factor in
_fibrositis_, we feel called upon to emphasise the fact that we are not
sheltering ourselves under that nebulous term “latent” gout, for our
contention is based on the ground that in the vast majority of the cases
for which we claim a gouty origin unequivocal proofs of gout, such as
_tophi_, etc., were present.


INCIDENCE OF GOUTY STIGMATA IN VARIOUS TYPES OF FIBROSITIS

Out of 343 instances of fibrositis of the _joints_ such stigmata of gout
were present in 118 males and nine females. Of _muscular_ types, taking
as our example _lumbago_, we find that out of twenty-seven examples no
less than ten displayed definite evidences of a gouty taint. Similarly,
out of thirty-eight cases of lumbago complicated by other manifestations
of fibrositis eleven males and one female were of gouty habit. Also in
twenty-three cases of lumbago associated with arthritic fibrositis six
males, but no females, displayed the same proclivity. Lastly, out of
thirty-eight cases of lumbago complicated by right or left sciatica ten
were of the same diathesis.

Passing in turn to consider this same factor in relation to _sciatica_,
we note that out of 142 examples twenty-four men and three women were
gouty. Occasionally, too, apart from _glycosuria_, it appears to be
responsible for bilateral sciatic pains, for in three examples of this
nature gout was present.

James Taylor is also very definite on this point, that, glycosuria aside,
affections of individual peripheral nerves occur frequently in the gouty.
There is little doubt, he says, that sciatica is “frequently present in
the gouty and is sometimes directly due to that state.” While admitting
that in many, if not most, cases of sciatica there are associated
arthritic changes in the _hip joint_, he yet affirms his belief that
“there are some in which the neuritis is a primary condition.”

With this statement my own experience accords, but with a reservation,
viz., that the _sciatic neuritis_ is apparently _secondary_ to a lumbar
or _gluteal fibrositis_, with sequential involvement of the _sciatic
nerve sheath_ and extension to the nerve trunk.

Taylor holds also that _anterior crural_ and _brachial neuritis_ may be
directly due to _gout_. As to brachial neuritis, he says: “I have known
it occur apart from any recognisable arthritic change in a patient who
was the subject of gout.”

Having regard to the flippant manner in which the term “neuritis” is
but too frequently bandied about, it is refreshing to note that in all
Dr. Taylor’s cases “the existence of the neuritis” was shown “by the
tenderness of the nerve trunks, the spontaneous, often severe, pain, and
atrophic changes both in the skin and the muscles—the glossy skin and
atrophied muscles.”

As for the involvement of other nerves, trigeminal neuralgia is held
to be the most common; but, for myself, I have never felt justified in
claiming any such example as gouty. Nor am I satisfied that persons of
gouty habit are more prone than others to attacks of migraine.

Lastly, I cannot confirm out of my own experience Duckworth’s statement
that “_herpetic_ attacks in all varieties of ‘gout’ are common.” Nor have
I seen _shingles_ co-exist with acute gout, neither have I come across
any examples of so-called _gouty spinal meningitis_!

In conclusion, I would submit that:—

    (1) Acute articular gout is not infrequently complicated by
    fibrositis.

    (2) The same infection that determines the articular outbreak
    is responsible for the concomitant muscular and nerve phenomena.

    (3) Persons of gouty heritage are especially liable to
    fibrositis, notably _lumbago_ and _sciatica_.

    (4) Gout predisposes to fibrositis in that the inherent
    pathological attributes of gouty tissues favour the incidence
    of _infection_.

In regard of this last postulate, it is well known that _gouty_ persons
who contract _gonorrhœa_ are more prone than the _non-gouty_ to develop
_gonorrhœal rheumatism_, in other words, to sustain a widespread
infection involving the fibrous tissues, not only of the joints, but of
the muscles and even of the nerve sheaths. With this concrete example to
hand, is it not reasonable to suppose that such a constitutional taint
will favour the incidence also of other infections or sub-infections,
and that this may explain the relative frequency of fibrositis, not
only in the actually gouty, but in those of gouty heritage, this the
more cogently having regard to the fact that so much exact evidence is
forthcoming in favour of local infection as the cause of all types of
fibrositis?




CHAPTER XVIII

CLINICAL ACCOUNT (_continued_)


CHRONIC ARTICULAR GOUT

In delineating the features of the _acute polyarticular_ variety, we have
to a certain extent trenched on the clinical territory of the _chronic_
form; this is scarcely avoidable, inasmuch as the line drawn between
acute and chronic gout is purely arbitrary. Thus one authority remarks
of acute gout: “If the disease continue beyond three or four weeks, it
is to be considered as persistent or chronic” (Flint). Trousseau, again,
discussing the acute variety, more particularly the acute polyarticular
type, states that it “may last for some weeks, or even for three months,”
adding: “Should it extend beyond that period, it is no longer acute gout;
it is chronic gout.”

The truth is that articular gout in this respect is very prone to
vagaries. Thus, in rare instances an attack of _acute_ or _sub-acute_
gout, more particularly the latter, may merge without break into the
_chronic_ form of the disease.[35] Far more commonly the tragedy is more
slowly played out. The unfortunate victim, after passing through several
more or less classical attacks, finds that the intervals become shorter
and shorter until they merge, as it were, one into the other. Fortunately
its course is not one of continuous uniform severity. _Remissions_, but
not complete _intermissions_, occur, and every now and again intercurrent
acute attacks take place.

But, the reader may observe, surely this is very reminiscent of _acute
gouty polyarthritis_, with its serial content of acute paroxysms?[36]
Quite so; but there is this difference, that, although such may last six
weeks or three months, still there is a period put to the sufferings.
A respite of months or years of immunity, and relative health may then
supervene.

Not so, unfortunately, when such paroxysmal waves sweep over the subject
of long-standing or _chronic gout_. Not only do the recurrent acute
outbreaks occur with _increasing frequency_, but also with _increasing
length of duration_. It is here no longer a question of the intercurrent
acute attack lasting days, but _weeks_. Also during such exacerbations
either four, five, or six joints are simultaneously attacked, or in such
rapid sequence that before one joint is free another is involved.

But a word here as to the variations in _distribution_ of the _articular
lesions_ in _chronic gout_. The well-marked _penchant_ of _acute_
gout for the _great toe_ continues throughout the life history of the
disorder, the predilection for this site being equally a characteristic
of the _chronic_ type. As to the subsequent articular involvement, Garrod
held the sequence to be as follows: _heels_; _ankles_; _knees_; the
smaller articulations of the _hands_; lastly, the _shoulders_ and _hips_.
It has never been my lot to see either the shoulders or hips involved;
but I have seen _osteo-arthritis_ of the _hip_ in _men_ displaying
_auricular tophi_, and I am inclined to think that, in the presence of
the latter, it has sometimes been assumed that the hip mischief was of
_gouty_ nature—the “hip gout” of the older authors.

Moreover, the _order of sequence_ is by no means invariable, for
oftentimes a local circumstance, _i.e._, _injury_ or _sprain_, determines
the location. Again, chronic gout is very erratic in respect of the
_number_ of joints implicated. In some almost all the joints may be
affected, while in others, no matter how ancient the disorder and how
oft its recurrence, it remains localised to but a few joints; or it may
progress after a leisurely fashion, with each attack invading different
joints in succession.

Naturally, if the disorder confine itself to a few joints, and these, and
these alone, are the seat of the oft-recurring attacks, permanent changes
sooner or later make their appearance. Nor are the morbid effects limited
to the joints, but they invade the continuity of the limb, for the
oft-repeated inflammatory reactions lead to engorgements of persistent
nature. The contour of the affected members is distorted by the œdematous
tumefaction, which, more pronounced at the level of the joints, extends
in lesser degree beyond their confines. The skin, too, especially over
the fingers, undergoes a change in texture, often becomes smooth and
glossy, and through its dusky pink subjacent uratic deposits may be
discerned.

Old gouty subjects are often of sallow or parchment-like complexion.
The _blood_ in these cases of polyarticular gout conforms in attenuated
degree, in the matter of leucocytosis and secondary anæmia, to that
observed in the more _acute_ types, as witness the following blood
pictures.

All were males, the subjects of chronic articular gout of many
years’ standing. They all exhibited _tophi_, which were verified
microscopically. The examinations were conducted during the
inter-paroxysmal periods.

                           (1) BLOOD COUNT.

  Red corpuscles, per c. mm.   4,832,000 = 96·6 per cent.
  Hæmoglobin                             =   64    ”
  Colour index                           =  ·66    ”
  Leucocytes, per c. mm.          11,000

                         DIFFERENTIAL COUNT.

  Lymphocytes                  42   = 4,620
  Large mononuclears            4   =   440
  Polymorphonuclears           52·5 = 5,775
  Eosinophils                   0   =     0
  Mast cells                    1·5 =   165

                           (2) BLOOD COUNT.

  Red corpuscles, per c. mm.   5,040,000 = 100·8 per cent.
  Hæmoglobin                             =  72      ”
  Colour index                           =   0·72   ”
  Leucocytes, per c. mm.          13,400

                         DIFFERENTIAL COUNT.

  Lymphocytes                  15   =  2,010
  Large mononuclears            2·5 =    335
  Polymorphonuclears           78   = 10,452
  Eosinophils                   1   =    134
  Mast cells                    3·5 =    469

                           (3) BLOOD COUNT.

  Red corpuscles, per c. mm.   4,280,000 = 85·6 per cent.
  Hæmoglobin                             = 66      ”
  Colour index                           =  0·77   ”
  Leucocytes, per c. mm.          12,000

                         DIFFERENTIAL COUNT.

  Lymphocytes                  23 = 2,760
  Large mononuclears            3 =   360
  Polymorphonuclears           74 = 8,880
  Eosinophils                   0 =     0
  Mast cells                    0 =     0

In these chronic forms, save during exacerbations, there may be little or
no febrile movement, and local pain, heat, and redness may be slight or
wholly lacking. But the articular swellings never wholly disappear, and
the mobility of the joints is never entirely regained. The articulations,
few or many, become stiff, ankylosed, and deformed, by the growth of
_tophaceous deposits_. But to detailed description of these latter we
shall return later.

In inveterate cases of this nature the victim grows more and more
crippled and infirm, the inroads of the disease upon the constitution
more and more palpable. Pelion is heaped upon Ossa, as one ailment sets
in after another, now of the digestive organs, now of the heart, or of
the kidneys. These subjects of chronic gout are more often than not
dyspeptic, show signs of _arterio-sclerosis_. Their _blood pressure_ is
_raised_, their vessels tortuous and thickened, and the left ventricle
enlarged.

As to the _variations in uric acid excretion_, these, as before remarked,
show no appreciable deviation from normal. Occasionally, however, there
is a tendency to _uric acid gravel_. Of more sinister significance,
albeit, is the fact that in many of these cases the urine is copious,
of low density, paler than normal, and shows a trace of _albumen_ with
hyaline casts.

As the disease marches to its fell end the appetite becomes impaired,
gastric catarrh and diarrhœa may sap the waning strength, or
palpitations, fits of dyspnœa, or angina-like attacks, sometimes
fleeting, but often of organic source, may portend a fatal issue. Ripe
for the sickle, a kindly “stroke” perchance puts an end to his protracted
misery. Or symptoms, long since manifest, of progressive _renal_
failure may usher in the closing scene, and happy the victim if he pass
muttering, half conscious, into that dream-like stupor drifting by
insensible graduations to death.

                        “The life of all his blood
    Is touched corruptibly, and his pure brain
    (Which some suppose the soul’s frail dwelling-house)
    Doth by the idle comments that it makes
    Foretell the ending of mortality.”

                                           _Shakespeare._

So much in attempted portraiture of the long-drawn-out tragedy of
inveterate chronic gout. But, fortunately, it is not always thus, and
nowadays, at any rate, the evils wrought on the constitution by the
malady are seldom so malignant. For not only, as before stated, has
gout become less frequent, but its virulence also much attenuated.
States of so-called “gouty cachexia” were, however, more familiar to our
forefathers. It more commonly ensues in subjects of strongly _hereditary_
tendency, and particularly in those in whom the _initial_ attacks ensue
before thirty years of age. I recall the instance of a colonel who
sustained his first attack of gout when a subaltern of but eighteen,
brought on, as he thought, through exposure while shooting snipe in
Peshawur. It is in such cases that this so-called “gouty cachexia” may
overtake a man while yet in his prime, and vest him untimely “with all
the characters of age.”

As to the milder types of regular chronic gout, such usually arise, not
in youth, but in men past the meridian of life. In their instance the
recurrence of gouty paroxysms is often erratic. Periodicity becomes less
pronounced or wholly lost. The life history of the disease may be summed
up in a few sporadic outbreaks, occurring irregularly throughout a long
life. Even when at first the attacks occurred regularly in the spring and
fall the rhythm of incidence becomes broken. An attack comes before its
time, is belated, fails of appearance wholly, or an intermediate paroxysm
comes as a surprise. Moreover, in many such the gouty manifestations with
the passing years tend to become more and more attenuated, maybe even to
extinction. Thus, a man who in the middle decades was a martyr to gout in
old age gains freedom from its visitations, the disease having apparently
exhausted its vicious potentialities.

Reviewing articular gout as a whole, one cannot but realise that it does
in respect of the recurrence of gouty paroxysms exhibit inexplicable
vagaries, inexplicable in that, as Sir William Roberts long since said,
“in many instances they are dependent neither upon medical treatment nor
upon altered dietetic habits, but are due to spontaneous changes in the
constitution. They form part of the natural history of gout; and it is
important to bear their existence in mind when we seek to estimate the
value of therapeutic means in order to prevent ourselves from becoming
the dupes of misinterpreted sequences.”

Albeit, we would not end on too sombre a note. For, in respect of the
graver consequences of gout, it is unquestionable that right living,
aided by efficient therapy, may arrest the course or mitigate the
severity of the disorder. Moreover, as long as the attacks do not follow
quick upon each other, but are separated by long intervals, there is
little fear of a cachectic condition supervening. Life may not be
appreciably shortened, and such textural degenerations as may ensue,
though frequently attributed to gout, may often with at least equal
plausibility be assigned to advancing years, but this with reservation,
for, as Duckworth says, “the wilful libertine is likely soon to become
cachectic, while the prudent man may altogether avoid this state or avert
its evils for many years or decades of years.”


THE JOINT DEFORMITIES OF CHRONIC GOUT

The palpable changes in the affected joints differ widely in different
cases, and why is not apparent. Thus, the first attack, if of prolonged
duration, may bequeath a legacy of crippledom comparable to that met with
after repeated paroxysms. On the other hand, some, although they have
suffered from the disorder off and on throughout their lives, yet escape
those consecutive deformities which in others deform and cripple the
hands and feet, though the disease may be of relatively brief duration.

But in the less fortunate cases the continued ravages of gout lead to
a pitiful disablement of the affected limbs, reaching its acme in the
_hands_ and _individual fingers_, flail-like and semi-paralytic as they
so frequently become.

Not only are the digits variously distorted, their joints more or less
ankylosed, but the overlying skin, distended by the ever increasing
subjacent uratic deposits, becomes thinned and purplish red in hue,
and occasionally ulcerates. Similarly at ankle, knee, wrist and elbow
thickening and deformity ensue as the concretions accumulate in and
around the affected joints, these further accentuated by the correlated
inflammatory and degenerative processes. Coincident deposits in the
tendon sheaths and related bursæ contribute their quota, and at knee and
elbow the bursal masses may reach extraordinary dimensions. Not only do
the joints become deformed, but distorted also, through reflex muscular
spasm and instinctive adoption of unnatural attitudes for the avoidance
of pain.

So much for the broad outline of the picture presented, but a still
closer scrutiny is called for. The deformities produced are the outcome
of uratic deposits, which, as Charcot long since pointed out, take on the
shape of “irregularly rounded or ovoid swellings, bunched, and either
large at the base or just the opposite, _i.e._, provided with a pedicle.”

As shown in the coloured plate, the favourite site for their
development is the _dorsum_ of the _hand_ or the vicinity of the
_metacarpo-phalangeal_ or _mid-phalangeal_ joint. The resultant
disfigurement of the hand is very characteristic. Irregular tuberous
swellings surmount the knuckles, and spreading laterally, obliterate the
fossæ between them and their fellows. The same extend forward over the
first phalanges, from nigh the distal end of which again arise similar
bossy excrescences over the mid-phalangeal joints. Encroaching thus
upon the length of the first phalanx from either end, but little of its
shaft is ultimately left exposed. In like fashion the mid-phalanx may be
buried in uratic deposits, its contour wholly lost; and, the terminal
phalanx participating, the digits become almost pedunculated, the nails
projecting from the ends thereof—the “parsnip hand” of Sydenham. Such is
the appearance presented in inveterate chronic gout.

Fortunately such examples are relatively rare, and a study of the
condition in its earlier stages reveals some interesting features. The
uratic deposits, it is important to note, _are not located exactly at
the level of the articulation_. Unattached as they are to the _articular
ends_, they are not compelled to, nor do they in any way, adapt
themselves, as it were, to the contour or shape thereof. In short, the
tophaceous formations are _erratic_, are not like _osteo-arthritic_
nodules, erupted from and continuous with the articular bone ends. Again,
relatively independent of the contiguous tissues, they, unlike osseous
outgrowths, are slightly _movable_ in lateral directions.

When of _recent_ incidence, their consistence is _soft_, and, be they
never so ancient, they do not attain the _density_ and _hardness_ of
_bony outgrowths_. The overlying skin, to which they are sometimes
adherent, takes on a peculiar glossy and satin-like texture, its dusky
pink blotched with spots of dead white colour, _i.e._, subjacent uratic
deposits.

In other particulars also they differ from bony outgrowths. The
tophaceous masses may _soften_ and _disappear_ after exacerbations of
_arthritis_, and others may form at different sites. Following such
absorption or difference in their location, some increase in joint
_mobility_ may happily ensue. This same fortunate occurrence may follow
discharge of the uratic masses through _ulceration_ and _perforation_ of
the skin.


TOPHI: THEIR EVOLUTION AND DISTRIBUTION

In our chapter on _Uratosis_ we dealt with the chemical nature and mode
of formation of tophi. Also we affirmed our belief that tophi, whether
_articular_ or _ab-articular_ in site, were always _preceded by local
inflammatory reaction_, and to the clinical tokens of their impending
eruption we need not recur. Albeit this point, _i.e._, _antecedent_
inflammation, is of such prime importance that we have not hesitated to
append to our text a lengthy footnote,[37] this because, as Garrod, who
quotes the same _in extenso_, rightly claims, the genesis and evolution
of tophi has never been so graphically depicted as in Moore’s description.

It will be seen that this observer holds that tophus formation “is
usually preceded and accompanied by inflammation.” Garrod, as we know,
believed uric acid to be the _cause_, and not the consequence, of gouty
inflammation. But he emphasises the fact that the phenomena attendant on
the eruption of auricular tophi are “exactly the same as when a joint is
affected, and constitute, in fact, a true gouty paroxysm, commencing with
infiltration of the tissue and subsequent inflammation.” Still, though
venturing to differ as to the sequence of events, we gladly invoke this
authority’s observations in proof of the fact that the _inflammation_
even in the _ear_ is not always of negligible grade: “I have seen many
cases in which the ear symptoms have proved very annoying, so that
patients have been unable to rest their ears on the pillow.” _Subacute
gout_ sometimes occurs in the ears, says Duckworth, who furthermore
believed that the _indurations_ in the _cartilage_ observed by him
in _gouty_ subjects were the outcome of such attacks. Laycock, too,
long before noted that the ears of gouty subjects often appeared to be
“soldered.”

_Pain or discomfort in auricular tophi often presages an oncoming
articular paroxysm._ “Those gouty persons,” said Scudamore, “who are
affected with concretions (chalk-stones), experience for a short time
before the fit pricking pains in the parts where they are situated. This
is described even by those who have minute points of concretions in the
lobes of the ears and in no other parts of the body.” Hence tophi have a
_prognostic_ as well as diagnostic valency in that the incidence of pain
at their site may foretell the oncoming of _articular_ outbreaks.

While, as before emphasised, the eruption of tophi may _antedate_ the
occurrence of _articular_ gout, on the other hand tophi may be present at
the joints, but lacking in the ears and all other _ab-articular_ sites.
Auricular tophi, extracted occasionally by patients, are sometimes shed
_spontaneously_. According to Duckworth’s statistics, in one-third of
all well-marked cases of gout the ears present tophi in the _helix_, the
_anti-helix_ and its _fossa_ and the _lobule_, and in some cases they may
be situated on the _posterior_ surface of the _pinna_.


OTHER SITES OF TOPHI

Apart from the external ears, tophi are apt to form in various
localities. Most frequently they are situated in the vicinity of the
_joints_ and _bursæ_, especially that over the _olecranon_. As attack
follows attack at short intervals the tophaceous matter is heaped up
around the joint, and in this way many articulations may be involved,
even all of them, says Trousseau, “as happened to Gordius, who composed
on himself the following jocular epitaph:—

    “‘Nomine reque duplex ut nodus Gordius essem.’”

Uratic deposits sometimes attain a prodigious size. I have seen them the
equivalent of a small hen’s egg. The largest tophi are invariably found
in the neighbourhood of some joint, and the upper extremities furnish the
most marked examples. But even when of considerable magnitude they may be
non-adherent, the skin gliding freely over their surface. As John Hunter
wrote: “The chalk shall remain for years without producing inflammation,
and seldom produces it at all but from quantity.”

Often, however, their presence at length induces irritation of the
overlying integument. As they approach the surface the skin assumes a
purple hue, becomes thin, and ulcerates. The uratic ulcers thus formed
have generally an indolent fungous base. As the deposits extrude or are
removed they are continually redeposited, and in this manner ounces
of urates may be discharged. The same is followed by great relief and
diminution of deformity.

Discussing such lesions, John Hunter tells us that “when the interior
surfaces are exposed they hardly take on common inflammation and
suppuration, healing more readily than a sore of the same magnitude from
any other cause; even a joint shall be exposed, yet common inflammation
shall not come on, nor shall it suppurate: only a watery fluid shall
come out, bringing the chalk with it occasionally, and it shall heal up
kindly.”

A glance, too, at the preceding footnote shows that Moore also agreed
with Hunter as to the absence of common inflammation and suppuration.
Moreover, even of recent years it has been suggested that, because
gouty tophi do not suppurate even when ulcerated through the skin,
the _urates_ have _antiseptic_ properties. But Bendix (_Zeit. klin.
Med._, 1902) failed to demonstrate such qualities experimentally. The
truth would appear to be that, though gouty inflammation never ends
in _suppuration_, yet _abscess formation_ very commonly occurs in the
_peri-tophal_ tissues. Such more often ensues in subjects of frail health
or of definitely cachectic type. Garrod saw as many as five or six open
at one time in each hand, and others on the feet. In his experience they
give rise to but little constitutional disturbance. Scudamore, speaking
of the same, says the sores produced are “unusually tender, aching, and
sometimes very painful as the fit is making its approach.”

Ultimately the gouty ulcers thus formed dry up, and this indifferently
whether or not the uratic deposits are wholly extruded in the discharging
pus. The wound then closes, leaving a small scar, which, however, given a
fresh attack of gout, is but too likely to break down, and this process
may occur repeatedly. Bursal sacs containing tophi not infrequently
suppurate, constituting abscesses containing urates.

An interesting fact noted by Garrod was that so long as such abscesses
were discharging freely the subjects enjoyed comparative immunity from
overt gout. But, given healing of the same, in several instances he had
seen it the signal for a sharp outbreak. Duckworth, too, states that
“whenever ulceration and flow of tophaceous matter occurs it is rare to
meet with paroxysmal attacks anywhere in the body. With the cessation of
the discharge renewed fits may intervene.”

While they tend to aggregate themselves round the joints, yet tophi
sometimes invade the _integument_ of the _limbs_. They have been seen in
the skin over the _ulna_ and _tibia_, and commonly over the _olecranon_
and _patella_. Pye Smith recalls the instance of a man in whom a number
of small ulcers, discharging urate of soda, formed in the middle of his
_thighs_ and _legs_. The case is not an isolated one, but the incidence
of subcutaneous uratic deposits in the limbs, save over _articulations_,
is exceptional.

In the _palms_ of the _hands_ and the _pulps_ of the _fingers_, the
knuckles and phalanges, tophi are found not infrequently; and Trousseau
tells of a lady of sixty in whom the cutaneous _palmar folds_ of both
hands were “marked with radiating white lines such as are seen in those
who have long been employed in tempering plaster.”[38] Similar deposits
have been noted in the _plantar surface_ of the _feet_.

Reverting to the _trunk_, uratic deposits have been found in the
_scapular_ region, also in the _perineum_. I have twice seen tophi
in the _corpora cavernosa_ of the penis. In the face, apart from the
ears, they have been found in the _alæ_ of the nose. In the _eyelids_
Duckworth noted uratic deposits in streaks resembling xanthoma; they
were chemically tested, and proved to be of this nature. Speaking of
“gout in the eye,” Garrod states: “I have witnessed many cases in which
conjunctivitis and sclerotitis appear to be distinctly connected with the
gouty diathesis, and in two cases there existed _deposits_ of _urates_ on
the surface.”

As before stated, we recognise only one type of gout, viz., the
tophaceous variety. But even so it must be noted that in some instances
the process of tophus formation is greatly accentuated. In other words,
the tophi may not only be of prominent size, but of unusually widespread
distribution. Indeed, poetic exaggeration has it that one Baylas and
one Acragas were entombed while alive in their own uratic deposits.
But, apart from such imaginative flights, there are unquestionably some
cases in which tophi are most widely diffused. Thus Plater tells of a
patient whose whole body, even the eyelids, was studded with them: “ex
toto corpore, per poros, adeo ut etiam palpebræ oculorum non exemptæ
fuerint, ejusmodi materia gypsœa, circa poros cutis mox in tophos mutata,
prodisset.”

These cases of multiple tophi are far more common in men. Duckworth met
with some well-marked cases in women. They may occur also in persons who
have been lifelong abstainers. Sometimes trauma seems to have played
a part in determining their localisation. Garrod held that, given
prodigious uratic deposition, the kidneys might be held as unsound and
undergoing sclerosis; and, according to Duckworth, the rule commonly
holds good.


AFFINITIES BETWEEN GOUT AND OTHER DISEASES

Whatever be the explanation, no fact in practical medicine is better
established than this, viz., that certain disorders are peculiarly liable
to arise in gouty subjects. Of these the more noteworthy are glycosuria,
phlebitis, certain cutaneous disorders, and nephritis. While, for
myself, I prefer to regard these affections as merely diseases to which
the gouty are especially subject, nevertheless each and all of them,
by one authority or other, have been classed as among the _irregular_
manifestations of gout.

This, on the assumption that these several morbid entities may precede,
alternate with, or follow arthritic seizures, frequently also on the
basis of their alternation in hereditary transmission with arthritic
gout. Thus, in a family of marked gouty proclivity, while one son,
despite a temperate life, may have severe articular gout, on the other
hand his brother may suffer only with _irregular_ manifestations, _i.e._,
phlebitis, eczema, etc.

As to whether these particular disorders, phlebitis, glycosuria, etc.,
are directly caused by the toxin of gout, or whether their not infrequent
association with gout is merely accidental, is a moot point. But to the
sources of fallacy in this connection we shall allude more in detail when
dealing later with irregular gout. Meanwhile extended knowledge of the
intimate etiology of phlebitis, glycosuria, etc., tends to an attitude
more critical than that of our forefathers, who, _faute de mieux_,
relegated a large number of conditions whose pathology was inexplicable
to the nebulous domains of irregular gout.


GOUT IN RELATION TO GLYCOSURIA

That some obscure link existed between glycosuria and gout was long since
suspected. Prout noted it as far back as 1843, and Bence Jones discussed
the subject under the title “Intermitting Diabetes” (1853), while in the
following year Gairdner announced that he had long surmised the kinship
between the two disorders. About the same time Claud Bernard remarked
that gout and glycosuria might alternate, and so did Trousseau, and many
since that day have ranked glycosuria as one of the forms of _irregular_
gout, whether legitimately or not is an open question, but at any rate it
does not affect the established clinical fact that glycosuria occurs with
significant frequency in gouty individuals.

Gouty glycosuria is more common in males than females. The subjects
are usually robust, middle-aged, and of full habit. Sugar is found
intermittently in their urine in small amounts, but no acetone bodies. It
is as a rule unaccompanied by thirst or wasting. It quickly responds to
dietetic restrictions. As Gull long since observed, gouty glycosuria does
not “discover itself,” but is “not uncommonly discovered.” This tersely
sums up the clinical difference between this affection and true diabetes,
albeit, as in all glycosurias, there is always the risk that carbohydrate
excess, mental strain, or other adverse circumstances may aggravate the
disorder and the case merge into one of true _diabetes_.

Following the installation of glycosuria, the tendency to paroxysmal
_articular_ outbreaks often ceases. The converse also has been observed,
viz., that when, in sequence to dietetic restrictions, the sugar
disappears, the articular pains may reappear. The fact that attacks of
glycosuria may alternate with attacks of gout led to the assumption that
a positive antagonism existed between the two disorders. Hence the phrase
“the more sugar the less gout,” and _vice versâ_. This, however, with
reservations, for a fugitive glycosuria has been seen during an acute
articular paroxysm, and a classical outbreak in the toe has been known to
supervene in the course of a well-established glycosuria.

It is generally held that glycosuria is most commonly associated with
_irregular_ forms of gout. But, in view of our ignorance of the intimate
nature of even _regular_ gout, I should myself deprecate affixing the
prefix “gouty” to any glycosuria other than one that has supervened in
sequence to, or alternates with, gouty _arthritic_ seizures. Moreover,
the glycosuria of gout is usually the alimentary glycosuria of fat
elderly people, in whom the sugar excreted represents the unconsumed
surplus of carbohydrate food. But fat elderly people are not necessarily
“gouty,” neither is every so-called benign glycosuria inevitably linked
on to a gouty diathesis. In fact, the relegation of glycosuria to the
gouty category is but too often not a matter of diagnostic certainty, but
rather an inference. Hence my plea that the prefix “gouty” would best be
restricted to glycosurias occurring in individuals who suffer _regular_
attacks of gout, or those displaying those objective tokens pathognomonic
of the disorder, _i.e._, _tophi_.

Again, James Taylor has recently reminded us that, if nerve affections
are relatively common in true _diabetes_, the same may be met with in
_gouty glycosuria_, even when of temporary duration. Thus symptoms
indicative of _peripheral neuritis_ may occur, _i.e._, lost knee jerks,
paræsthesiæ, and paresis of the lower limbs. Now, as this authority
pertinently observes, the subjects of _gouty glycosuria_ are frequently
given to _alcohol_. Consequently the question whether or not the
symptoms are due, not to sugar, but to _alcohol_, arises forthwith.

In some undoubtedly the alcoholic factor plays a _rôle_, but such
symptoms may, on the contrary, arise in very abstemious individuals.
This notwithstanding, James Taylor holds that the clinical complex
differs substantially from that met with in true _alcoholic neuritis_.
It is slighter in degree, the paresis usually restricted to lower limbs,
while the exquisite tenderness to pressure on nerve trunks so typical
of alcoholic neuritis is little or not at all in evidence. Nor is
there the same tendency to contractures in muscles as met with in the
alcoholic variety, and withal there is an absence usually of the mental
changes—loss of memory—associated therewith. Accordingly Taylor holds
that we must recognise the existence in the _gouty_ of a true _glycosuric
peripheral neuritis_ quite independent of _alcoholic peripheral neuritis_.

Other concomitant nerve troubles noted in this association are _severe
intercostal neuralgia_ and, even more commonly, _neuralgia_ of the _fifth
nerve_, and to this may be added _migraine_ and that other neurosis
_asthma_. Intense mental irritability and depression is not an infrequent
sequel in gouty glycosuria. According to James Taylor, melancholia even
may result, especially if the glycosuria have merged into true diabetes—a
sequel, he says, especially prone to occur in Jewish subjects.

Having seen and suffered many painful disillusionments through too
flippant relegation of neuralgias or neuritides to diatheses “gouty”
or “rheumatic,” I would emphasise the necessity for great caution. In
other words, before labelling a neuralgia or neuritis as “gouty,” all
possible causes, _infective_ or _other_, should be excluded, this always,
but pre-eminently so in _brachialgia_, _sciatica_, and _trigeminal
neuralgias_. Nor even, should there be a history of classic _outbreaks_
or blatant _tophi_ present, should we be less vigilant.

By all means recognise the _gouty diathesis_. It often avails much
in treatment, but not if, _e.g._, _dental caries_, _antral disease_,
_cervical rib_, or _pelvic growth_ be overlooked, not to speak of recent
or concurrent sources of _infection_ or _toxic absorption_.

Lastly, we should always recollect that gouty glycosuria, as Gull said,
“does not discover itself”; it is not writ large on the subject like
true diabetes. But given the incidence of _nerve_ troubles in a _gouty_
person, _i.e._, a paræsthesia, itching, neuralgia, etc., we should always
suspect its presence.[39] Incidentally our search may reveal not only
sugar, but also _albumen_, and the latter may explain much that appeared
inexplicable.


GOUT IN RELATION TO PHLEBITIS

It is to Sir James Paget that we are indebted for recognition of the fact
that phlebitis occurs with significant frequency in gouty subjects. This
great surgeon held that the disorder was the outcome of a modification
or transformation of gout, the result of “morbid conditions changing and
combining in transmission from parents to offspring.” At the present time
some regard it merely as a complication of gout, others as one of the
_irregular_ manifestations of the disease.

It occurs most commonly in men, women being rarely the subjects of
gouty phlebitis. It may install itself insidiously with but mild local
discomfort, and yet on examination a cord-like hardness is detected. In
others it announces itself with pain, in rare instances intense, this
more commonly if the deep veins of the calf are its seat.

Its predilection is for the veins of the lower extremity, the superficial
rather than the deep vessels. If the former, a faint blush over the
affected veins may be seen, but if the deep veins, then œdema and
tenderness may be the sole token of its presence.

Frequently the phlebitis is patchy in distribution and migratory. Thus,
as Paget says, it may on one day be located in a short length of the
saphenous vein, flitting the next day to some other portion thereof, or,
it may be, to the corresponding vein of the opposite limb. This tendency
on its part to metastasis and symmetry led Paget to the conclusion that
“the essential and primary disease is not a coagulation of the blood, but
an inflammation of portions of the venous walls.”

Its duration is not uncommonly prolonged, and it displays a marked
tendency to recurrences, the latter determined by blows, unusual
exertion, or, according to some, exposure to cold. Most cases end
favourably, but death from embolism sometimes occurs. Occasionally, given
occlusion of the large veins, some degree of swelling lingers permanently.

The instances most indicative of a _gouty_ origin are those in which the
veins of a limb, the seat of _acute gout_, are simultaneously attacked
by phlebitis. In three cases of this nature recorded by Garrod, the
subjects, despite their suffering from acute articular gout, persisted in
leaving their beds to record their votes in the parliamentary election
of 1884. This type of case, according to Garrod, is usually confined
to men, and, with the exception of the cases above noted, a _varicose_
condition of the veins of the legs of long standing existed in his series
of examples.

Garrod recognises in addition a second type, in which phlebitis,
“usually of a much less acute character, ensues without the previous
development of gouty inflammation in the neighbourhood of the part.”
Here we may recall that, according to Paget, the incidence of phlebitis
in an elderly person without any external cause warrants the suspicion
of gout. Perhaps the chief justification for such an assumption rests on
the fact that phlebitis appears sometimes to be _hereditary_. Paget cites
the instance of a man who suffered from phlebitis of both saphenous veins
during an attack of acute gout. On the maternal side his mother, two
uncles, a grandmother, and two cousins had been the subjects of phlebitis.

In conclusion, for myself, I would suggest that the term “gouty”
phlebitis be restricted to those instances in which a limb, the seat of
_acute articular gout_, is complicated by _phlebitis_ of the veins of the
affected part. Here we are dealing with what is palpably an extension
of the gouty inflammation from the affected _joint_ to the _veins_, and
which, I venture to assert, is strongly confirmatory of the view that
an _infective_ element intrudes in “gouty” arthritis. We may recall
that, _e.g._, _gonorrhœal phlebitis_ of the lesser saphenous veins is
not so uncommon, while the frequency with which phlebitis complicates
_infections_ calls for no emphasis.

Leaving aside these rare instances of _acute gout complicated by acute
phlebitis_, I think there is a too flippant tendency to regard any
phlebitis occurring in middle-aged or elderly subjects as being of this
nature, this often in the absence of any evidence, hereditary or other,
of a gouty element in the case. Frequently, too, the subjects are women
with _varicose veins_ of long standing, and _ipso facto_ potentially
liable to phlebitis. But why, in the absence of ancestral or acquired
gout, dub such cases forthwith as “gouty”? We may, it is true, as in
Paget’s classical instance, elicit a _familial_ tendency to phlebitis,
but even so I doubt the legitimacy of the inference that the phlebitis
is necessarily “gouty.” Is it not equally true that the tendency to
_varicose veins_ is hereditary, and _ergo_ predicates an enhanced
liability to phlebitis?


CUTANEOUS DISORDERS

The incidence of tophi in the skin naturally engendered the conception
that gout was responsible for many and diverse types of cutaneous
affections. In accordance with this, every effort was made to prove that
they were the outcome of uratic infiltrations, but in vain.

Objective proof of this nature being lacking, the older clinicians
found their justification in the alternation of arthritic attacks with
cutaneous disorders, and their alternation in inheritance was laid great
stress upon, this especially by French dermatologists, notably Bazin,
but at the present day Jacquet’s non-committal pronouncement is probably
representative of the attitude of the French school as a whole towards
“arthritic” affections of the skin: “Le lien admis entre le groupe de
maladies dites _arthritiques_ est très mal connu dans son essence, mais
il serait tout aussi contraire à l’esprit scientifique de le nier avec
rigueur que de l’affirmer avec presomption.”

As to the skin disorders associated with _acute_ types of gout, perhaps
the most interesting and well ascertained is _herpes_. It may precede
an acute attack, may alternate with it, or be a sequel thereof. Rendu
noted that acne, boils, and carbuncles also might occur prior to, in
alternation with, or in sequence to acute attacks, and Scudamore noted
the same in respect of erysipelas.

The noteworthy liability of the gouty to these disorders is but another
proof that gout predisposes its victims to _infections_. The fact that
acute gouty arthritis might follow acne, boils, etc., lends colour to our
contention that the same may be of infective origin. But unfortunately
the suspicion also intrudes that some of the arthritides occurring in
such association may, on insufficient grounds, have been diagnosed as
“gouty,” this especially if the joint disorder were located anywhere save
at its classic site, the _big toe_.

Passing to skin affections associated with _chronic_ gout, it must be
admitted that as a whole the contention that they are “gouty” in origin
is, to say the least of it, doubtful. French dermatologists claimed
that the cutaneous eruptions of the “gouty” might be recognised by
their polymorphism, circumscribed location, etc., but these are no more
distinctive peculiarities than the concomitant pricking, hyperæsthesia,
and hyperalgesia upon which Bazin laid such emphasis in their diagnosis.

In short, sequences, coincidences, and alternations are the basis of
much that has been written upon so-called “gouty” cutaneous affections,
criteria all of them fruitful sources of fallacy.

As to _psoriasis_, I have met with it so frequently in association with
non-gouty arthritides that I have never felt justified in claiming any
example as “gouty.” So-called “gouty” _pruritis_ and _prurigo_, these
when they occur in the “gouty” are frequently referable to an associated
glycosuria, and when this is not the case, it is frequently a senile
prurigo. The claim that urticaria is “gouty” may be dismissed without
comment.

As to frequency of incidence in the “gouty,” _eczema_ undoubtedly must be
awarded the palm. But whether the scaliness of skin on extensor surfaces
of arms and legs and back of neck, which ultimately, under the influence
of skin infection through scratching, develops into a dermatitis which
assumes the character of eczema, can be, strictly speaking, held as of
“gouty” origin, is questionable. Certainly, whatever be the origin of the
pruriginous scaliness of the skin, there can be no doubt that the later
dermatitis is the outcome of infection by skin organisms. Frequently the
presumption that the eczema is “gouty” rests upon general rather than
specific grounds, on “goutiness” rather than “gout.” Accordingly I think
it would be wiser to regard eczema as an occasional complication of gout
rather than an integral element thereof.

Lastly, there can be no doubt that many of the so-called “gouty”
cutaneous disorders ensue at what may be called the arterio-sclerotic
stage of life. It is when renal and cardio-vascular changes are
present that we meet with exudative erythema, pityriasis, exfoliative
dermatitis, and purpuric eruptions. All these have at one time or another
been foisted upon gout, whereas they are far more closely related to
the cardio-vascular and renal changes with which the disorder is so
frequently associated.


GOUT AND NEPHRITIS

The association between gout and renal disease is admittedly intimate,
in so far as gouty subjects often have granular kidneys, while gout is a
frequent complication of this type of renal disorder. Nevertheless, the
clinical relation between the two diseases is ill defined and, moreover,
somewhat erratic. In most instances the renal defect is engrafted
upon the antecedent gout, or the sequence is reversed; and, again,
the two conditions may arise contemporaneously. Lastly, in sharp and
disconcerting contrast to this mutual overlapping of the two disorders,
we have the awkward fact that more commonly _gout_ and _granular kidney_
run to their fell end quite _independently_ of each other.

Thus, Sir William Roberts observed: “It is quite common to see articular
gout, even of chronic and inveterate character, run its entire course
without any accompanying signs of structural disease of the kidneys.” The
same, to be sure, is equally true of _granular kidney_, which may pass to
its close without any suspicion of gout.

Now, as we have seen, the primary _renal_ origin of gout fails of
demonstration. Is _gout_, then, _causally_ related to _granular kidney_,
or is there some less direct relation between them?

As to this, to begin with, it is extremely rare that a “gouty” subject
develops _acute_ nephritis. In the exceptional instances when it
does occur it is either purely accidental or else the outcome of an
_exacerbation_ of a _previously existing interstitial nephritis_.

The question then arises, Can gout when long continued originate _per
se_ the condition we are pleased to term “gouty kidneys”? As seen above,
such renal lesions are by no means an inevitable sequel or concomitant of
long-standing gout. Moreover, there is nothing _specific_ of _gout_ in
the so-called “gouty” kidney. It is an _interstitial nephritis_, which
may assume the appearances of the ordinary “contracted kidney” or the
“arterio-sclerotic” type. There may be _uratic_ deposits at the apex of
the pyramids, or even an _uric acid calculus_; but even so that of itself
constitutes no proof of the renal changes being “gouty” in origin. In
short, the prefix “gouty” as applied to these types of renal lesion is
just as unscientific and unwarrantable as used in regard of “phlebitis,”
“eczema,” and so forth.

Nor, _quâ_ _gout_ as a _causal_ factor, are we in better case if the
renal disorder be of the “arterio-sclerotic” type. No direct relationship
is established between gout and arterio-sclerosis beyond the fact that
both are usually met with in middle-aged or elderly people. Moreover,
a man may develop arterio-sclerosis and arterio-sclerotic kidneys, yet
never have any vestige of gout.

There being nothing _specific_ of _gout_ in the lesions of so-called
“gouty” kidneys, we must revert to the clinical findings to refute or
establish any _causal_ connection between gout and the renal disorder.
Now, gout is a disease of middle and late life, and rarely of itself
proves mortal. On the other hand, it appears increasingly probable that
the seeds of granular kidney are laid in earlier life, and, on the
average, its course is shorter than that of gout. Also the two disorders
have clinical _facies_ absolutely distinct the one from the other.

From the above considerations it is, I think, clear that, whatever the
hidden nexus between gout and “granular kidney,” it is neither essential
nor constant. It is rather, I believe, of the nature of a coincidence.
Furthermore, as applies to so many problems pertaining to gout, and,
for that matter, to “granular kidney” also, we labour under the grave
disability that both terms are, especially “gout,” very vaguely applied
and when used are often a matter of personal opinion. Consequently, as
Samuel West shrewdly observes, “it is difficult to discuss satisfactorily
the relation of two conditions to each other when neither condition
admits of precise definition, for some authorities are more easily
satisfied in the diagnosis of gout than others; and, while some place all
forms of chronic interstitial nephritis in one and the same category,
others are not so comprehensive, and regard granular kidney as a
definite clinical disease, of which the interstitial nephritis is only a
part.” Under these circumstances, the need for further and more exact
researches in this sphere is but too obvious.

Meanwhile, accepting the general opinion as to the frequency of the
co-existence of gout and granular kidney, is there any explanation
thereof? For myself, I am inclined to believe that the common overlapping
of the two disorders is in large measure due to this, that the factors,
_i.e._, excess in alcohol, overeating, etc., that make for the eruption
of gout, are largely identical with those that promote the development
of _granular kidney_. Hastings Gilford holds “there is very little doubt
that syphilis, lead, and gout do not so much originate Bright’s disease
as excite it into activity when it already exists in a smouldering or
latent condition.”

With this view I feel much in accord, and if to the malign effects
of gout be superadded the effects of alcohol or, haply, lead also,
how incalculably greater the chances of fanning into flame any latent
tendency to nephritis—a legacy, perhaps, of some long bygone infection.


PROGNOSIS IN GOUT

Gout _per se_ rarely, if ever, proves fatal. Certainly, as Sir Thomas
Watson long since said, “_gout in the extremities_ is not a mortal
disease.” When death did occur during or in close relation to an
_acute_ paroxysm, it was by our forefathers attributed either to its
_retrocession_ or to some _misplaced_ or _irregular_ manifestation.
Indeed, their attitude was very much that of the French physician who
observed: “La goutte articulaire est celle dont on est _malade_, et la
goutte interne est celle dont on _meurt_.”

But, as we shall see later in our chapter on _Irregular_ Gout, most,
if not all, of their instances of the assumed translation of the
_materies morbi_ of gout to some vital organ are without foundation. The
demise, often dramatically sudden, was not due to _gout_, but to some
insidious, unguessed-at organic degeneration, or to one of the accidental
intercurrent maladies to which these subjects seem especially liable. To
sum up, the immediate danger to life from regular gout when uncomplicated
is slight.

Not that gout is salutary, lessens the liability to other diseases, or
promotes longevity. Very much the reverse—“a tendency to _recurrence_ is
a law of the disease.” Broadly speaking, the more pronounced the tendency
to recurrence of articular outbreaks, the more protracted the isolated
paroxysms, the worse the outlook, the more sombre, too, the greater
the number of joints involved. Conversely, if the disease, though it
recur, restrict itself to the classic site, the big toe, the longer, as
a rule, the intervals of freedom, the brighter the prospects of long
life. Lastly, the more the subject is crippled, the more pronounced the
tendency to tophaceous deposits, the more likely is the disease to pursue
a downward course, the greater the risk of associated degenerations in
renal and vascular tissues.

While these reflections are in the main, we think, justifiable, we must
recollect that in gout, as in other maladies, the elements of _prognosis_
reside in the _individual_, not the disease. Does he come of a long-lived
stock?—not uncommonly a feature of gouty families. If so, the outlook is
favourable. If he come of a short-lived breed, then in all probability,
no matter how carefully he lives, he will not likely make “old bones,”
this, certainly, if the gout makes its appearance early in life, say
under thirty.

As to the axiom, generally accepted, that the earlier in life gout makes
its _début_, the more unfavourable the outlook, there are exceptions.
Where _longevity_ marks the stock, they usually are true to type. Thus,
even if the first outbreak occurs in the twenties, I have known them
reach the allotted span and over. Nor if their urine show traces of
_albumen_ is this necessarily of grave import, for these gouty veterans
may for many years, even to old age, exhibit traces of albumen without
apparently developing genuine Bright’s disease.

“There dies not above one of a thousand of the gout, although I believe
that more die _gouty_,” wrote Graunt long years since; and this contains
a kernel of truth, for the _prognosis of gout_ rests in the main not on
the _gout_, but the _conditions correlated therewith_—the absence or not
of _complications_. For, be it always remembered, gout, though it may
appear in youth, is chiefly an appanage of the middle and later decades,
in short of the _regressive_ period of life.

This last is, I think, apt to be forgotten, and gout vicariously
saddled with all the infirmities of age. Thus, out of 2,680 examples
of _arterio-sclerosis_ Huchard held _gout_ and lithiasis responsible
for no less than 693. An appalling indictment, but what of the long arm
of _coincidence_? For _age_ unquestionably is the chief factor in the
production of arterio-sclerosis, though many allot gout a dominant _rôle_
in its genesis. This certainly is by no means proven. Still, whatever be
the relationship, _gout_ and _arterio-sclerosis_ are very often found
_in association_. If so, the prognosis will obviously rest, not on the
gout, but on the _vascular_ disease—the pulse tension. If therewith
be correlated _albuminuria_ and a displaced apex beat, the outlook is
unfavourable.

Again, is the subject lean or obese? If the former, so much the better,
for _corpulency_ and _gout_ are a sinister combination. Gout in
itself, as previously observed, favours microbic invasion, and obesity
accentuates the liability. Moreover, the gouty obese are prone to
_arterio-sclerosis_ and _granular kidneys_, with sometimes a superadded
_glycosuria_, or even true diabetes. In such subjects also the presence
or absence of signs of cardiac mural degeneration must enter into our
forecast, which at best is but gloomy.

Apart from arterial degeneration, we have to recollect the tendency to
_phlebitis_ of _recurrent_ type. This when present always carries with
it the risk of _embolism_ and sudden death. Cases therefore displaying
this proclivity to phlebitis must be judged accordingly. The gouty
_glycosuric_, too, is always subject to the risk that the condition may
develop into one of true diabetes. The absence of response to dietetic
restrictions, viz., persistent sugar in the urine, the onset of thirst,
polyuria, or other concomitants of diabetes, will darken the prognosis.

Also I myself believe that the presence of local foci of infection
gravely prejudices the course of gout, accentuates any tendency to
recurrence of the attacks, and incidentally reinforces any latent
proclivity to vascular and visceral degenerations.

Last, but not least, what of the subject’s habits? The “internal
environment” of the tissue cells of the gouty is presumably of itself
none too good; but if to this be added the poison of _alcohol_, lead, or
the toxic products of gluttony, it is incalculably worse. The painter
or the plumber, if he can, would be wise to change his calling. If the
alcoholic be deaf to remonstrance or the glutton continue to gorge, their
chances of life dwindle proportionately, and if given to both vices,
still more so.

In conclusion, the prospects of long life in gout depend in the main
on the presence or absence of associated morbid states. If there be no
complications such as I have indicated, the disease, in my experience, is
not likely to shorten life materially, always provided that the victim is
amenable to what should be the watchword of the gouty,—

    “The rule of not too much, by temperance taught
    In what thou eat’st and drink’st, seeking from thence
      Due nourishment, not gluttonous delight.”

                                                  _Milton._




CHAPTER XIX

ETIOLOGICAL AND CLINICAL DIAGNOSIS


ARTICULAR GOUT

The intimate cause of gout is unknown—a humiliating reflection, albeit
salutary, if it but engender a more catholic attitude on our part
when seeking to unravel the nature of this obscure joint affection.
For, to secure ideal ends, diagnosis must be, not only clinical, but
_etiological_. This is the more likely to be attained if we shed all
preconceived ideas and prejudices.


ETIOLOGICAL DIAGNOSIS

Confronted, then, with a suspected case of gout, whether acute or
chronic, what shall be our way of approach? Not the easy and hazardous
path of lightning diagnosis affected by those who plume themselves on
their so-called clinical “instinct,” but the slow, laborious route of
clinical “observation,” that leads more surely to the vantage ground
of truth, this assuredly in all diseases, but in none more so than in
_joint_ disorders, whose outward resemblances so oft hark back to inward
disparities.

First, as to the manner of man, while one would not decry the hints
obtainable from _physiognomical_ peculiarities, it is often hard, if not
impossible, to fit the subject to the so-called “gouty diathesis.” They
are not all of the John Bull type; not a few are spare in build. Hence
the danger of too ready inference from so-called “gouty” traits, to be
regarded rather as ancillary to, but not substitutes for, more exact
criteria.

Now, as to heritage, for, despite the fallacies that surround inquiries
into family predispositions, they often furnish valuable hints as to
the metabolic trend of the stock. True, ancestral stories often prove
indefinite, but fortunately less so in the “gouty” than in those of
“rheumatic” tendency. For, as Sir Dyce Duckworth points out, even the
laity are quick to recognise what they term “chalky” gout, and so “if
a history be given of ancestors or relatives thus affected, there need
be no hesitation in pronouncing for true gout amongst them, and for the
probably gouty nature of such arthritic ailments as may be complained of
by the patients under examination.”

Turning to the individual himself—for the subjects of regular gout are
rarely women—what is his age? If he is over thirty-five and has never
previously had an arthritic disorder, it is much more likely to be _gout_
than rheumatism, this only as a broad generalisation.

What occupation does he follow? What are his habits? Is he of the “idle
rich” who “fare sumptuously every day”? Is he a plumber, a painter, or a
butler, coachman, or club waiter, these last being men who, as Sir Thomas
Watson observes, “often live more luxuriously and more idly a great
deal than their masters”? In short, we must search for any evidence of
overeating, overdrinking, and indolence. For of this triad of vices is
gout too oft begotten.

As to illnesses, his past may tell of classic outbreaks, one or more in
the great toe, and if to this be added a visible _tophus_, we stand face
to face with a “gouty diathesis.” More eloquent this than a “cloud of
witnesses” as to previous attacks of migraine, asthma, eczema, etc. All
these and more may emerge during the subject’s recital, and by all means
let them be ascertained. But forget not that they often arise in the
_non_-gouty. Above all, though, miss not the significance of heightened
blood pressure, a cardiac lesion of degenerative type, sugar or albumen
in the urine. For these are of the things that will out, but let it not
be to our discomfiture!

Even presuming that all facts and observations up to now point to a
“gouty” origin of the arthritis, the end is not yet. What has evoked the
arthritis? We seek a cause. For to call an arthritis “gouty” is but to
restate the problem. How clear the need then for a meticulously careful
investigation, in the hope of achieving not a merely nosological, but an
_etiological_, diagnosis.

To narrow our field, we should, in the first place, exclude _gonococcal_
infection, and failing this, influenza, syphilis, or any of the zymotic
or other disorders prone to be followed by or associated with _joint_
affections.

If none of such be forthcoming, we should search for _local foci of
infection_. The mouth and its accessory cavities first claim attention.
It should be closely scanned for the presence of oral sepsis, the most
fruitful source of which is _pyorrhœa alveolaris_. If _dentures_ are worn
it is wise not to take the subject’s word that all his teeth have been
extracted. Like others, I have in such found the broken-off stumps still
_in situ_. The condition of “bridges” should be noted, fruitful sources
of sepsis as they are. Clinical examination of the mouth may prove
inadequate, as _buried roots_, _cysts_, or _abscesses_, not to mention
_alveolar rarefaction_, etc., demand for their detection _radiographs_.

The _pharynx_ and _tonsils_ should be thoroughly investigated, for
disorders of these same are by no means uncommon in “gouty” subjects.
Any history of _aural_ or _nasal_ discharges demands the same careful
local examination; and, needless to say, the same course must be pursued
in regard of any _local infections_ of the _genito-urinary passages_. In
short, in _gouty_, as in _non-gouty_, forms of _arthritis_, thorough and
routine examination of every patient by modern _bacteriological_ methods
is imperative.

Ignorant of the precise _etiology_ of _gouty_ arthritis, we can ill
afford to overlook any associated _infective_ foci which may prejudice
the well-being of the victim, as, for aught we know to the contrary, we
may be overlooking the very _fons et origo mali_. Compare our attitude
towards other arthritides of cryptic origin, how systematic our search
for _infective_ foci, and what a light has thereby been shed on their
intimate etiology!

Here may we lodge a plea for routine examination of the blood in all
cases of _gout_? For, as shown, the findings, _leucocytosis_, etc.,
have doubtless some profound significance. Apart from this, the routine
employment of _complement-fixation_ tests for the organisms responsible
for local infections might illumine the obscurity that overhangs this
complex problem of their relationship to remote pathological lesions.

If up to now our search for local foci prove futile, it remains for us
to note the presence or absence of _functional derangements_ of the
_alimentary tract_, or its _accessory glands_. We must not, because we
think perhaps that the patient “looks gouty,” assume that his _dyspeptic_
symptoms are of like origin. It is our duty to ascertain, if possible,
the precise nature and origin of the dyspepsia.

We know that, given _oral sepsis_, sequential infections of the
_appendix_ and _gall bladder_ are not uncommon. Recently it has been
remarked that many _gouty_ patients suffer with attacks of pain in the
region of the appendix, and simultaneously tenderness over the gall
bladder. That the subjects of gout enjoy no immunity from appendix or
gall bladder disorders is certain, and at this we need not be surprised,
seeing the frequency with which they suffer from alleged causes thereof,
_i.e._, dental sepsis, etc.

But what we would insist upon is that we should not be content merely
with dubbing these symptoms “gouty,” as they are much more likely to be,
not symptomatic of gout, but _etiologically_ related thereto. If then we
are to arrive at the exact nature of the underlying lesion, the probable
site of infection or toxic absorption, we must invoke all modern methods
of investigation. Thus, how valuable the existence of an X-ray barium or
bismuth meal in furnishing positive evidence of gastric or duodenal ulcer
on the one hand or of _gall bladder_ or _appendix_ disease on the other.
What an aid to the location of adhesions the demonstration of _ileal_
and _cæcal_ stasis, etc.!

In obscure cases the _fæces_ may have to be scrutinised for evidences
of _pancreatic_ inefficiency, viz., bulky pale stools, undigested meat
fibres, and excess of neutral fat. Their _bacterial_ content, too, if
abnormally high, should be noted. As in other arthritides of unknown
origin, the results following the administration of _vaccines_ prepared
from the predominant organisms have been such as to suggest a causal
connection.

The urine should be subjected to _chemical_ and _bacteriological_
examination. As to _uric acid_, the delusion still widely prevails that
gouty subjects excrete large amounts thereof. How frequently is “the
degree of acidity” of the urine or “its content of uric acid” held to
justify a diagnosis of gout. The deduction is quite unjustifiable.
Equally so the assumption that the reverse, a defective excretion of uric
acid, is an invariable feature of the gouty diathesis. For though when
on a _purin-free_ diet the output of uric acid in the gouty is low, it
rarely, if ever, falls below the level of normal. The truth is that we
cannot _on the mere basis of the variations in uric acid excretion in the
urine_ presume to diagnose gout.

To have any semblance of diagnostic value, the patient should be on a
_purin-free_ diet, and a long series of exact quantitative examinations
made. C. v. Noorden, to gauge the limit of tolerance of his patients,
gives them increasing amounts of purin, and so determines the quantity
the subject can deal with without showing retention. But, as Von Fürth
satirically observes, “when a physician allows a quantitative analysis to
be made of any arbitrarily collected specimen of urine of his patient and
then makes a diagnosis of the presence or absence of a ‘gouty diathesis’
after a glance at the list of data of the analysis, he is really not
proving by his actions his possession of diagnostic acumen as much as he
is laying bare his total ignorance of bio-chemical matters.”

So much for the diagnostic valency of uric acid estimates in chronic
gout, but if the patient be on purin-free diet, and an acute attack
ensue, the curve of uric acid excretion is fairly characteristic. In
other words, for a day or two preceding the outbreak, the uric acid
output falls below the usual level, but early in the attack rises
markedly, to be followed by a secondary fall.

Some aid in diagnosis has been afforded by the fact that after ingestion
of purin-containing food the gouty individual does not, like a normal
person, eliminate the excess of uric acid, but the excretion is “spread
out over a number of days.” But this retardation and diminution in the
excretion of exogenous purins has been seen in non-gouty forms of
arthritis, not to mention some cases of nephritis and chronic alcoholism.
Hence delayed nuclein exchange, though highly suggestive of gout, is not
infallibly diagnostic thereof.

_As to uric acid in the blood_, it will, I fear, not for long, if ever,
be easy to prevail on patients to submit to withdrawal of the amount of
blood necessary, even by modern methods, for its estimation. Fortunately,
our American _confrères_ appear to be more successful in securing such
opportunities. Pratt states that in his twenty-one cases of genuine gout
the uric acid content of the blood, irrespective of diet, was 3·7 mg. per
100 grams, as opposed to 1·7 mg., the average amount in 156 non-gouty
cases studied by Adler and Ragle. Still Pratt noted that in a few cases
of undoubted gout the uric acid content of the blood was within normal
limits, though it never fell, even on a purin-free diet, below 1·4 mg.
Nevertheless he holds that there is conclusive evidence that the uric
acid content of the blood is in gouty individuals notably increased both
in the intervals and during attacks.

He has found the sweetbread meal an aid in diagnosis, and the following
is his method of procedure: “The patient is placed on a purin-free diet,
and the daily output of uric acid in the urine determined. After having
been on this diet for at least four days the blood is analysed for uric
acid, and 150 to 300 grams of sweetbread (weighed raw) are fed. The
purin-free diet is then resumed. The blood of gouty subjects forty-eight
to seventy-two hours after the sweetbread meal has shown in every case
examined an abnormally high amount of uric acid, while in control
subjects this was not found. It is not improbable that this rise in the
uric acid content of the blood may occur in certain cases of nephritis
and other pathological conditions.”

A _bacteriological_ examination of the _urine_ should be undertaken.
Trautner held _mucous colitis_ as one of the initial manifestations of
gout, and believes that the _bacillus coli communis_ is the primary agent
in gouty affections. He suggests that it produces a reducing substance
which during its passage through the body is transmuted into xanthin
and uric acid. Be this as it may, there is increasing evidence that an
etiological potency may attach to coliform bacilli, streptococci, and
other organisms. Dr. Munro in his researches at the Royal Mineral Water
Hospital, Bath, noted that the blood serum in one of my cases of acute
gout agglutinated _B. coli_. He has also found streptococci in the urine
in acute gout, and these subjects certainly enjoy no immunity from other
forms of bacteriuria.

It is beyond the scope of this volume to outline the methods of
differentiating and determining the exact organisms which may be
responsible for gouty arthritis. But if we aim at rational as opposed to
purely haphazard serum or vaccine therapy, we must effect a differential
specific diagnosis in a bacteriological sense. How searching our
investigations must be in these cases we learn from Adami’s brilliant
address on _sub-infection_ when he laid down the axiom that in all
cases “there ought to be routine blood cultures, routine examination
and reports on the stools and their predominant bacterial types, blood
counts, hæmoglobin examination, in fact the full clinical study of each
case, so that nothing is neglected.”

No apology is needed for our insistence on the imperative necessity
of routine systematic investigation from all sides of these cases of
gouty arthritis. For its origin still remains hidden, and who can doubt
that, to remove this long-standing reproach, we must approach our
study of these cases in a more catholic attitude of mind, one bent on
_etiological_, not merely nosological, diagnosis?


CLINICAL DIAGNOSIS


_Introductory Remarks_

The word gout itself is void of offence, innocent of scientific
pretensions, neither expressing nor violating any article of pathological
belief. But let us not forget that the term is neither self-explanatory
nor final. Derived through the French _goutte_ from the Latin _gutta_,
it but expresses laconically the fanciful doctrine of those who so
christened it.

What the old humoralists saw was the _tophus_, and would that they had
clung more steadfastly to this as their sheet anchor in diagnosis! but
casting their moorings, they launched forth on the uncharted seas of
abstract philosophy. Even in the writings of the nineteenth century
physicians we trace the influence of their disquisitions, and we are
tempted to think that some even of our day still bide beneath their
thrall.

But, with the advance of pathology to the dignity of a natural science,
we must assert our independence of misty hypotheses, rendering obeisance
only to facts. What then, may we ask, is the outstanding fact of the
“gouty diathesis”? It is, in a word, the _tophus_! Even as the vague
and shadowy constitutional warp known as the “rheumatic diathesis”
finds expression, or rather becomes incarnate, in fibrous _nodule_ and
_induration_, so also does the equally nebulous “gouty diathesis” become
objective, crystallised in the _tophus_.


THE DIAGNOSTIC STATUS OF TOPHI

This problem calls for more critical consideration than is usually
accorded thereto. The tophus is, in truth, the touchstone of gout, yet
not a little controversy obtains as to the frequency of its incidence in
“gouty” subjects.

At one extreme we find Sir Charles Scudamore maintaining that tophi have
occurred in only a few individuals “of particular ‘gouty’ idiosyncrasy,”
in, according to him, less than 10 per cent. of the victims. At the other
Sir Alfred Garrod, discussing these figures, observes: “From my own
experience I consider these numbers far below the real proportion, from
their being deposited in parts of the body scarcely to be expected.”

Now as to these distinguished physicians, who shall doubt that of the
twain Garrod stood on firmer ground than his predecessor? In arriving at
their diagnoses of gout, Scudamore rested on clinical “instinct,” Garrod
on clinical “observation.” To the more scientific mind of the latter the
tophus appealed with all the insistence of a fact, while the former was
yet in bondage to abstract philosophy, dominated too much by crude and
unproven hypotheses.

_Given the presence of tophi, the diagnosis of a “gouty diathesis” is
assured; in their absence it is but speculative._

It is upon this dictum that we would take our stand, and this without
depreciating in any way the pioneer researches of Garrod. For it must
be recognised that the increasing differentiation of joint diseases has
proceeded apace. How many are now affiliated to specific germs, not
to mention the undreamt-of light thrown on their inward characters by
X-rays! Scudamore’s work appeared exactly a century ago, Garrod’s in
1876. The conclusion then seems inevitable that many of their alleged
cases of _gout_—at any rate, those _unattested by tophi_—would now be
relegated to widely different categories.

But this zeal for infinite cleavage and subdivision, so characteristic
of the modern school, far from diminishing, does but _accentuate_, the
_diagnostic_ valency of the tophus. It still remains _the_ infallible
criterion of diagnosis, and, for myself, I feel convinced that infinitely
more good than harm would ensue if we refuse to recognise any individual
as being of the “gouty diathesis” unless he exhibit these objective
stigmata thereof.

Of course to some such a rigid attitude will spell anathema. I hear them
say in oracular tones: “Never forget gout, or awful indeed will be your
awakening.” More harm, say they, is wrought by failure to recognise
gout than by diagnosing gout where none is. Doubtless they are right in
counselling us not to forget gout, but not to the exclusion of all else.
For, at issue with them, I hold it better to miss gout than to miss
_syphilitic_, _gonorrhœal_, and other forms of arthritis.

“A name being so readily found for an obscure disease, the practitioner
considers himself as excused from the difficult task of nicer
discrimination.” Thus wrote Scudamore a century since, a rebuke and a
warning for all time.


TOPHI IN RELATION TO ARTHRITIS

How elated we are, and rightly, when in an obscure form of arthritis
we pounce on these objective criteria of gout, how apt to deem our
diagnostic quest as ended, and with what fatal glibness the time-worn
“gout” slips from our lips, sure, alas, of ready and almost complaisant
acceptance. Fallacious inference, all too prevalent, that the presence of
_tophi_ stamps any _concomitant arthritis_ as “gouty.”

True, tophi are pathognomonic of gout, but their existence does not
confer on their host _immunity from all other forms of arthritis_. In
view of the increasing light shed upon joint disorders, who can doubt
that (and this not only for our forefathers) the _tophus_ has too often
proved a veritable snare, allaying all diagnostic doubts, lulling us into
false security? For an individual may, for example, exhibit _auricular
tophi_ and be the victim also of an _arthritis_, but the latter is not
inevitably “gouty.” All that can be assumed at sight is merely that the
joint disorder, whatever its nature, has ensued in a subject of “gouty
diathesis.”

For it may be of specific infective origin, _gonococcal_, syphilitic,
pneumococcal, etc. _Quâ_ a concomitant arthritis, then, the diagnostic
significance of tophi, at any rate when of _ab-articular_ site, must not
be overrated. It is at once a beacon and a warning. In other words, the
diagnosis of a co-existent arthritis as “gouty” should not be entertained
pending the exclusion of all other forms of arthritis.

_Conversely, in the absence of tophi, the diagnosis of an arthritis as
“gouty” is not absolute, but presumptive._

For in the lack of these objective stigmata how can the authenticity of
our diagnosis be established? Is it not when achieved a _nosological_
rather than a diagnostic feat? Put otherwise, is not our diagnosis,
especially in _initial_ attacks, largely _topographical_? Not that we
would for one moment decry the advantage of realising the predilection of
certain organisms for this or that particular joint: of the gonococcus
for the sterno-clavicular, of typhoid for the hip, post-scarlatinal
rheumatism for the phalangeal joints, etc. But we would drive home the
fact that our diagnosis in _initial_ attacks of “gout” is very largely
_topographical_. Let but inflammatory trouble ensue in the _big toe_, and
forthwith we assume it gout, as if, forsooth, this particular joint were
immune from all other forms of disease, this, too, while in the same
breath we comment on its extreme liability to injury. So, indeed, we
maintain, is the marked predilection of gout for the toe joint explained.
Is not this a little crude? Does not the same circumstance increase
its liability to _infection_ and, we may add, not less important, its
proneness to _static deformities_? But to this we shall recur when
discussing _differential_ diagnosis.

To return, how often, apart from the above pitfalls, is the diagnosis
“gout” arrived at without any search for tophi wherewith to support the
assumption. Our contention is that even in primary attacks of gout our
search for _tophi_ should be exhaustive. If undiscoverable, why not be
honest with ourselves and recognise that our diagnosis is _presumptive_
pending their development?

Sir William Roberts on this point observes: “As a rule, diagnosis of
acute articular gout is easy, but exceptional cases of difficulty occur.
The _gouty_ character of the inflammation is _affirmed by the discovery
of uratic concretions_ in the rim of the ear or elsewhere.”

Again, Sir William Osier, discussing the diagnosis of acute gouty
polyarthritis, remarks: “We have had of late years several cases admitted
for the third or fourth time with involvement of three or four of the
larger joints. The _presence of tophi_ has settled the nature of a
trouble which in previous attacks has been regarded as ‘rheumatic.’”

One may, we think, gather from these two statements the inference
that both these distinguished authorities hold _tophi_ to be the
_only infallible criterion_ upon which to base a diagnosis of _gouty
arthritis_. In my own practice I must affirm that I never feel justified
in christening any arthritis as _gouty_ unless I have discovered _tophi_,
and then only when to the best of my ability _all other known causes of
arthritis_ have been excluded.


FREQUENCY OF TOPHI IN TRUE GOUTY ARTHRITIS UNDERESTIMATED

In reviewing the statistics of authors as to the frequency of the
incidence of tophi in their cases of assumed gouty arthritis I am
inclined to think their relative infrequency is apparent rather than
real, in other words that many of their cases of alleged “gouty”
arthritis which _lack tophi_ would, if investigated by modern methods,
have been shown to be due to other causes of arthritis, this especially
as regards their assumed cases of _chronic_ gout. For who can doubt that
prior to the discovery of X-rays many cases of _osteoarthritis_, etc.,
were thus erroneously labelled? Nor indeed, as we hope to show later, is
it improbable that similar fallacies obtained even in regard to _acute_
types of gout, particularly when of _polyarticular_ distribution.

It will be noted that we confine our criticisms to those examples of
“gouty” arthritis _unassociated with tophi_. But if, as we maintain,
our scepticism be justifiable, then it follows that it _diminishes_ to
an unknown extent the _percentage of cases of genuine “gouty” or uratic
arthritis which lack tophi_.


DIFFICULTY OF DETECTING TOPHI

Apart from the probability of such erroneous relegation to the “gouty”
category of _non-gouty_ arthritides, there remains this further
consideration, the ease with which tophi, even when superficial, may be
overlooked. We look for pearly white concretions, and if none are seen we
straightway assume that _tophi_ are _absent_. This, I am sure, is a very
common pitfall. At their inception tophi are neither white nor hard. They
are largely fluid and soft to touch. The skin over them may be unchanged
in colour or reddened. Only when mature, and the overlying skin is thin,
do they assume the ordinary aspects of a tophus. These observations
apply not only to tophi in the ears, but to those in the vicinity of
the small joints of the hands and feet or elsewhere. I would urge that
in the case of all soft localised swellings of dubious nature in the
neighbourhood of the phalangeal joints aspiration with a hypodermic
syringe will often prove very helpful. If fluid can be withdrawn and the
same microscopically examined, it will more often than is supposed reveal
the presence of biurate crystals.

More information is badly needed as to the relationship of their
formation to acute attacks of gout. Garrod on this point remarks: “The
deposits are probably formed during an attack of gout, but occasionally
they appear shortly afterwards. In one case, of which I have notes,
the ears were carefully examined without result when the patient left
the hospital, but within ten days, on re-examination, a deposit was
found. Perhaps some fluid was effused during the fit, but being at first
transparent, could not be easily distinguished.” Sir Dyce Duckworth,
too, observes: “After acute attacks of gout have passed off there may
follow renewed pain in the neighbourhood of the joint, and later there
is discovered a nodular or soft swelling. In the latter case there may
be fluctuation, indicating a liquid collection of urates. This should
never be opened. In a few weeks this tumour tends to indurate, grow more
compact, and a so-called ‘chalky’ concretion is established.”

Reflection upon the foregoing considerations leads me to the conclusion
that not only was Garrod right in his affirmation that “_gouty
inflammation is invariably attended with the deposition of urate of
soda_,” but more that _examples of true uratic arthritis which lack tophi
are exceptional_, and that _in their absence their diagnosis as such
cannot be with certitude established_.

We have now, we trust, sufficiently defined our attitude towards the
tophus, the salient objective stigma of a “gouty diathesis,” and the
indispensable _rôle_ it plays in enabling us to establish the diagnosis
of articular gout.




CHAPTER XX

CLINICAL DIAGNOSIS (_continued_)


ACUTE ARTICULAR GOUT—LOCALISED VARIETY

The nonchalance with which not a few writers dismiss the diagnosis of
_acute gout_ when located in the _great toe_ or elsewhere in the foot
is, to say the least of it, somewhat remarkable. “It is a very easy
matter,” say they, and as an earnest of their good faith are silent
as to the many pitfalls that await the unwary. Should they deign to
_differential_ diagnosis, they are at pains to discriminate between it
and _acute articular rheumatism_, which _re_ classical outbreaks in the
_toe_ seems a little superfluous! But not a word of _traumatic_ lesions,
_infective_ processes and _static_ deformities, all infinitely more
likely stumbling-blocks.

Did all cases conform to the classic type, _acute sthenic gout_, it might
be held relatively easy. But such are not, to say the least of it, common
nowadays. More often than not our examples are, as Garrod terms them, of
acute _asthenic_ character. As he observes: “There may be indeed pain and
tenderness in the toe, and some amount of swelling, but accompanied with
little heat or redness, and all febrile disturbance may be absent; still
œdema is generally observed and itching and desquamation follow.”

That diseases, like their victims, alter with environment is but too
clear. Who can doubt that the gout of the Regency has to-day assumed a
milder clinical _facies_? Physicians of those days were haunted with the
fear of confounding it with _erysipelas_ and _phlegmon_. Still, while no
such fears apparently beset us to-day, it were well to walk circumspectly.

Thus, recently a friend of mine came across an instance of what he deemed
_acute gout_ in a _metacarpo-phalangeal_ joint. Its failure to respond to
colchicum and the growing intensity and extent of the local inflammation
suggested incision, when, lo, pus issued, to the subject’s comfort, but
to his own chastening!

There are, however, many more likely sources of fallacy, these, too, of
the most diverse type, inasmuch as they differ according to the exact
location in the foot of the assumed gouty process. For while the _big
toe_ is the _site of predilection_ for the _initial_ manifestation, it
is not always so. The _primary_ outbreak may be located in any of the
smaller joints of the foot, or outside them in related structures: in
the _heel_, the _sole_, or the _tendo Achillis_. These vagaries greatly
enhance the difficulties of diagnosis. For the process of differentiation
will vary according to the particular joint or structure involved, the
predilections of certain infective processes, not to mention the marked
liability of the foot to painful disturbances of static origin.


DIFFERENTIAL DIAGNOSIS

Inasmuch as the primary outbreak may be located in any part of the foot,
we purpose, for reasons just cited, dealing _seriatim_ with gout in (1)
the big toe; (2) the instep; (3) the heel; (4) the sole.


GOUT IN THE BIG TOE

_Infections._—There is no _â priori_ reason why any of the infections may
not find a nidus in the _first metatarso-phalangeal_ joint. Thus, Garrod,
as we know, held gouty subjects specially liable to _pyæmia_. In rare
instances, the primary focus has been in or near the _great toe_, and has
consequently been mistaken for _gout_. The rapid progress of the disease
would of course soon clear up the nature of the case. But if the subject
has previously suffered from gout, such a diagnostic error at first
sight is quite excusable. Accordingly, as a safeguard in all doubtful
cases, inquiry should be made as to the existence of _bladder_ troubles,
_piles_, etc., especially _any recent operation_ in this or other regions.

Again, while gout in its _articular_ form is rarely, if ever, met with in
children, it must be recalled, on the authority of Sir James Goodhart,
that _rheumatism_ in their instance is occasionally limited to _one_
joint. Moreover, this distinguished physician actually saw it localised
in the _great toe_, “in a case in which the subsequent course of the
disease showed that it was acute rheumatism.”

_Acute Gonococcal Arthritis._—We may recall that Van Swieten, a disciple
of Boerhaave, held that sometimes a wife while nursing her gouty husband
had contracted the same disorder. A tribute, we fear, to Van Swieten’s
diplomacy rather than to his clinical acumen—an euphemism for gonorrhœal
rheumatism!

Of course in adolescents or in young adults _monarticular_ pain, with or
without swelling, heat, or redness, should not suggest “gout,” but an
_infective_ disorder either in the _joint_ or the related _bone-ends_. At
the same time middle-aged men enjoy no immunity from gonorrhœa, and we
may add that _gonococcal infection_ of the _metatarso-phalangeal_ joints
is not so uncommon. When located in that of the great toe, it is easy
to see how readily the acute arthritis may be confused with gout. But,
unlike the latter, its duration is measured by months or weeks rather
than by days. It is well to recollect, too, that “gouty” persons are
more prone to develop arthritis following gonococcal infection. Given
therefore a history even remote, we should in doubtful cases recall the
longevity of the organism, its persistence in the prostatic recesses, and
the need for bacteriological investigation.

_Traumatic Lesions._—Its exposed situation renders the big toe very
liable to trauma. Often, too, the injury being slight, and not followed
by any immediate consequences, the connection may easily be overlooked.
A blow or a fall may readily bruise the synovial membrane without at
first any external sign. But given trivial hæmorrhage into the cavity or
subjacent tissues, an acute synovitis with effusion is induced.

Again, joint disorder following _injury_ is usually _monarticular_,
whereas the same when the outcome of so-called “constitutional” causes is
generally _oligo_- or _poly_-articular. The relevancy of this is obvious
when we recall that _initial_ attacks of _gout_ are _monarticular_.
Accordingly, given a history of definite injury to the toe joint, the
question arises, Is it _acute gout_ or _acute traumatic arthritis_? this
especially if the subject has not had a previous attack of gout at this
site.

Here I would lay stress on the fact that _indirect_ rather than direct
traumatisms are more common antecedents or determinants of gout, viz.,
sprains or strains. Moreover, in reviewing the writings of the older
physicians one is driven to the conclusion that frequently a septic
cellulitis, synovitis, or a frankly traumatic arthritis was confused with
acute gout.

The following examples cited by Scudamore are, we contend, susceptible of
such an explanation: “A gentleman much subject to gout, when considering
himself unusually well, underwent the slight operation of having the
nail of the great toe cut on account of its improper growth. The toe was
much pressed, and gouty inflammation was the immediate consequence.” In
another case “the patient, never before having suffered the gout, tore
off a broken portion of the thumb-nail, so as to make the part tender.
Very soon the thumb and part of the hand put on a swollen and shiny
appearance, and was exquisitely painful. A poultice was applied. Suddenly
on the third evening the pain quitted the thumb and seized the toe, next
the ankle, then the knee, and lastly the great toe of the other foot.
Throughout he secured ease and sleep till the first light of the morning
appeared, and hence facetiously observed that the gout in this respect
assumed all the behaviour of a ghost.” Was not this probably a case of
_septic absorption_ with _cellulitis_ and a mild degree of sapræmia,
evoking _arthralgic_ pains?

In conclusion, without denying the potentialities of trauma, whether
direct or indirect, in determining an outbreak of gout, we would submit
that its diagnosis under such circumstances should not be hastily arrived
at, but by the slower process of elimination, this especially if the
trauma has involved slight abrasions with the possibility of sepsis. A
quick response to _colchicum_ would of course be highly suggestive of
_gout_.

_Acute Osteoarthritis._—It is perhaps not so widely recognised
as it should be that osteoarthritis not uncommonly attacks the
metatarso-phalangeal joint of the great toe. It becomes enlarged owing
to the hypertrophy of the articular ends. Like similar lesions in the
small joints of the hand, the big toe joint from time to time undergoes
exacerbation, with increased vascularity and local heat, which, though
of minor degree, may by a superficial examiner be readily misinterpreted
as _gout_. The parts are painful, somewhat swollen, hot, and tender, but
the local symptoms are never intense, and constitutional disturbance
is lacking. The presence of osteoarthritic lesions elsewhere and the
revelations of _skiagraphy_ will suffice for differentiation of such
cases from _asthenic articular gout_.


STATIC FOOT DEFORMITIES

_Hallux Valgus with Inflamed Bunion._—Scudamore in his “Treatise on Gout”
observes that “the bursal disease over the first joint of the great toe,
which is familiarly known as _bunion_, is a very common complaint with
gouty persons.” In view of the fact that no reference is made in the
context to the absence or presence in such cases of a condition of hallux
valgus, one is led to believe that Scudamore overlooked the deformity and
regarded the local bursitis as the outcome of a gouty inflammation of
this structure.

Bradford and Lovatt, discussing hallux valgus, observe: “There may be
pain and irritability in the great toe joint, and in severe cases extreme
pain and difficulty in walking, which is usually attributed by the
patient to _gout_.” We would only qualify this statement by the fact that
the local heat, redness, and swelling that in this condition so often
follow slight injuries or excessive walking is not only so interpreted by
the patient, but far too frequently also by his _medical attendant_.

Routine examination of the bare foot will minimise the chance of such a
fallacy, though of course it must be borne in mind that a _gouty_ subject
may present this deformity. But when we recollect that _hallux valgus_ of
_slight degree_ “is almost universally present after middle childhood,”
we see that, given the presence of this static foot deformity, any
inflammatory process in the superjacent structures is infinitely
more likely to be due to an _inflammatory bursitis_ than to a _gouty
arthritis_.

Given an inflamed bursa with cellulitis spreading over the dorsum of
the foot, confusion with _acute sthenic gout_ is all too easy. But in
our experience, _mirabile dictu_, the ordinary more or less chronic
circumscribed redness over the bunion is but too commonly misinterpreted
as gout, this particularly in women, despite the rarity with which
gout attacks their _toe_ and the frequency with which their footgear
is precisely adapted to produce _hallux valgus_. Given therefore the
presence of this static foot deformity, we should in the absence of
objective stigmata of gout, viz., _tophi_, suspend our diagnosis pending
observation of the results obtained by local treatment of the displaced
toe.

_Hallux Rigidus._—This deformity is but too often overlooked,
and if marked by pain and more or less rigidity of the first
_metatarso-phalangeal_ joint, it may, in lack of adequate examination,
be flippantly dismissed as “gout,” this more particularly in its later
stages, when, in addition to pain and stiffness therein, the joint is
swollen, tender to the touch, and the bony ends actually enlarged. Here
again local examination, if carefully carried out, will suffice to
obviate such errors, while the quick response to rest and appropriate
applications, with correction of the frequently associated sunken arch,
will sufficiently attest its true nature.

_Metatarsalgia._—As pointed out in our previous work on Fibrositis, “this
painful condition is more often than not confused with rheumatism or
gout.” We have known subjects wander to nearly every spa on the Continent
under such a misconception. Not to mention the financial expense, the
dietetic penances imposed, the consequences of such faulty diagnosis, are
by no means trivial, for the intensity of the suffering may reduce the
walking capacity to a minimum.

The neuralgic pain radiates into the toes and often upwards into the
leg, usually comes on while walking, and is relieved by the removal of
the boot. For its detection any altered relationship in the position of
the third, fourth, and fifth metatarsals, especially their displacement
to a lower level than normal, should be noted, and any limitation of the
power of dorsal flexion of the foot likewise estimated. The presence of
_callosities_ under the _heads_ of the _metatarsals_ is very suggestive
of this painful condition.


GOUT IN THE INSTEP

Next to the metatarso-phalangeal joints, the _tarsal_ articulations are
the most frequent site of _initial_ attacks of gout. Here again we would
insist on the necessity of excluding _infections_ of the _tarsal joints_
or _shafts_ and even more important, _static foot deformities_.

_Gonococcal Arthritis._—In a table compiled by Garrod from those of
Foucart, Brandes, Rollet, and Fournier, the relative frequency of the
implication of individual joints in gonorrhœal arthritis shows that out
of a total of 119 the _tarsus_ and _metatarsus_ were attacked in five
instances. In the more acute cases the periarticular swelling, local
heat, and pink blush may be confused with _acute gout_. The resemblance
is enhanced in that, as in gout, the overlying _tendon sheaths_ are
liable to become inflamed and distended with fluid.

_Tuberculous and Syphilitic Disease of the Tarsal Joints or the Related
Joints._—In cases of obscure pain and inflammatory trouble in the instep
the possibility of arthritic and bony lesions of this nature should not
be overlooked, especially if there be suggestive lesions elsewhere, or if
the history afford evidence of the possibility of such contingencies.

_Pes Planus._—In all cases of pain and swelling, with or without redness,
in the instep, it is well to recollect that, though flatfoot may for a
long time exist without giving rise to symptoms, it frequently happens
that, in sequence to some unusual strain on the plantar arch, the static
disturbance in the foot enters quite _abruptly_ on a _painful_ phase.
Congestion and swelling of the foot is common, and actual teno-synovitis
of the tibial and peroneal muscles is not infrequent. Tenderness, too, at
points of ligamentary strain is almost always present, and more or less
constant pain.[40]

The frequency with which the _local_ and _referred_ pains of _flatfoot_
are misinterpreted as “gout” and dietetic restrictions and other useless
and uncalled-for methods of therapy enjoined is well exemplified by a
case which has just left our consulting room.

The subject, a middle-aged spinster of lean kind, came to Bath for
treatment of her supposed gout, and for which indeed she had previously
received spa therapy. Her feet when bared showed a condition of double
_hallux valgus_ with related _bursal thickenings_. The occasional
inflammation of these latter structures and the recital of doubtful
ancestral proclivities were the sole evidence on which was based the
diagnosis of _gout_. In addition, as is so frequent in hallux valgus,
there was associated therewith a _bilateral flatfoot_, and it may be
added that in the left foot a _hammer-toe_ had been removed some years
since. Unfortunately the neglected symmetrical flatfoot had, as so
frequently happens, initiated, through the erroneous deflection of a body
weight, a condition of _chronic villous synovitis_ in both knees. This
again was misinterpreted as but another proof of her assumed “gouty”
diathesis. Reflecting upon human nature, how curious the reluctance with
which such subjects elect to part with their “gout.” Women especially
hold tenaciously thereto, even those of austere type, clinging to the
taint handed down to them from some far-off ancestor whose “superfluity
of naughtiness” was a by-word among his generation. To exchange gout,
_morbus dominorum_, for “flatfoot” and inflamed “bunions,” savours of
degradation, and to couple it with aspersions on their footgear is
well-nigh insupportable. Nor are the “lords of creation,” we fear, exempt
from this failing. We recall during the War being consulted by a highly
placed officer who complained of gout. A well-preserved man of nigh sixty
years of age, he obviously prided himself on being immaculately booted.
As such patients frequently do, he brought his own diagnosis of “gout.”
Removing his footgear, manifestly too small, his crucified toes stood out
with bunions in a state of hot resentment. But impeachment of his boots
was too much for him. Persuasion and argument were futile, and I doubt
not he walks to-day stiff, a martyr to his vanity. “Il faut souffrir pour
être belle.”


GOUT IN THE HEEL

In some instances the first manifestations of gout occur in the heel,
while in others the sheath of the neighbouring tendo Achillis is the part
first invaded. Probably there is no region of the foot in which there
exist more pitfalls, and doubly careful should we be before concluding
that any painful or inflammatory condition thereof is one of “gout.”

_Referred Pain._—Pain in the heel affords many loopholes for
misinterpretation. It may, as Sir James Paget pointed out many years
ago, be symptomatic of a _renal calculus_. In my own experience it is
sometimes complained of by the subjects of _internal hæmorrhoids_, the
pain waxing and waning with the variations in the rectal trouble, and
only disappearing permanently when the piles have been radically treated.
It is, again, a symptom sometimes complained of by the victims of
_enlarged prostate_.


LOCAL SOURCES OF FALLACY

If the pain and tenderness be located on the _under_-surface of the os
calcis, there are several misconceptions possible.

    (1) Careful examination may reveal a tendency to flatfoot, the
    pain being referable to strain on the posterior insertion of
    the plantar fascia.

    (2) The root of the trouble may be a gonococcal inflammation of
    the plantar fascia, or of the periosteum covering the os calcis.

    (3) A skiagram may show the existence of a bony spur on the
    inferior surface of the os calcis.

    (4) The bursa under the os calcis may be inflamed.

    (5) Also, as Tubby has pointed out, pain in the heel may be
    referable to shortening of one leg or constant standing, and
    more rarely to tuberculous disease of the os calcis.

If the pain and tenderness be located on the _posterior_ surface of the
os calcis, or in the tendo Achillis, the following should be excluded
before assigning the trouble to “gout”:—

    (1) _Post-calcaneal Bursitis._—Inflammation of the bursa lying
    between the os calcis and the tendo Achillis is not uncommon.
    It may be uni- or bi-lateral, and in the majority of instances
    is attributable to violent exercise, or chafing of the heel
    by ill-fitting boots. The local swelling and tenderness at
    the site of the inflamed bursa and its aggravation by plantar
    flexion of the foot will afford a clue to its true nature. (An
    exostosis projecting from the hinder surface is sometimes a
    cause of post-calcaneal bursitis.)

    (2) _Synovitis of the Tendo Achillis._—Symptoms very similar to
    those above described have been met with in a teno-synovitis
    of the tendo Achillis, as evidenced by swelling of the sheath,
    tenderness, and silky crepitus.


GOUT IN THE SOLE

There is a wide disposition to regard all painful or unpleasant
sensations in the sole of the foot as evidences of “goutiness.” It may
be recalled that Strabo, according to Plutarch, apostrophised heat or
itching of the feet at night as “the lisping of the gout.” Duckworth,
too, emphasised the frequency of this symptom in the gouty, and Sir
Charles Scudamore also held heat and dryness of the sole as frequent
harbingers of acute attacks. Now, did we but confine our hazards as
to gout only to cases marked by heat or itching in the sole, possibly
little harm might result; but unfortunately there is a flippant readiness
to relegate all obscure pains or abnormal sensations in the sole to
the “gouty” category. Needless to say, this is quite unjustifiable. We
need not reiterate the bounden necessity of excluding all static foot
deformities, but we should in addition recall the various types of
_plantar neuralgia_.

_Plantar Neuralgia._—Occasionally, as we have pointed out elsewhere,
the pain is of almost unendurable severity. It constitutes one of the
types of so-called _partial sciatica_, the pain and paræsthesia being
confined to the plantar nerves. Indeed, pain, numbness, hyperæsthesia,
or sweating of the sole are often symptomatic of a definite neuritis.
Such may follow typhoid fever or caisson disease, and in this latter be
of aggravated type. When we realise that the pain in these cases may be
limited to the tips of the toes or the _ball of the great toe_, we see
how readily it may be confused with “gout.” Fortunately plantar neuralgia
is exceptionally rare; but even after exclusion of the foregoing causes
we should, before pronouncing any such neuralgia to be “gouty,” recollect
that plantar neuralgia or hyperæsthesia is very common in _alcoholism_
and _hysteria_.

_Erythromelalgia._—Among the exceptional cases that find their way to
spas are examples of this rare disorder. Almost invariably they come
under the diagnosis of “gout” or “rheumatism.” When we reflect that in
the majority of instances the initial burning pain typical of the disease
is located in some part of the sole of one foot, and that the associated
redness and vascularity may be delimited to the _ball of the great toe_,
the heel, or outer or inner side of the foot, we see the danger of its
being too easily referred to “gout.”

If seen at the zenith of an attack, the severe pain, the local heat,
the intense purplish redness, the distension of the veins, and in some
instances œdema, how close the resemblance to gout! Precisely also, as
in gout, the simulation of a deep-seated inflammatory process is very
pronounced. Indeed, in not a few examples of erythromelalgia fruitless
incisions have been made. Accordingly in all cases of pain, redness, and
swelling in the sole of the foot, we should canvass the possibility that
we may be face to face with an instance of erythromelalgia, a disorder
which, like gout, is most frequently met with in men of middle age.

In drawing to a close our remarks on the diagnosis of _acute gout_ in
the _foot_, we would emphasise the fact that in all such cases the
bare feet should be thoroughly examined. For, apart from _infective_
and _traumatic_ lesions, the frequency with which the various _static
foot deformities_ are confused with “gout” is incredibly common. That
_gout may co-exist with hallux valgus_ or other distortion we readily
admit, but this does not absolve us of our responsibility—correction of
the static deformity. Combine this, if you will, with constitutional
treatment if there be evidence, _i.e._, tophi, of a “gouty” diathesis,
but, we repeat, correct the mechanical defect. For gout may come and go,
but static errors remain. In so doing, the victim will be saved much
preventable suffering, and, for aught known to the contrary, the removal
of irritation and local congestion may haply minimise the chances of
subsequent gouty outbreaks.


ANOMALOUS SITES FOR INITIAL OUTBREAKS

While _primary_ attacks are in the vast majority of instances localised
to the _foot_, if not actually to the _toe_, it is well to recollect
that very rarely the _knee_, the _wrist_, _elbow_, or _ankle_ may be the
chosen spot. In such cases there is need for exceptional caution before
committing oneself to a diagnosis of _gout_. Certainly not until all
other known causes of _acute arthritis_ of _monarticular_ type have been
excluded.

If in the _knee_ or _wrist_, any possibility of _injury_ or _strain_
should be thoroughly canvassed. To make assurance doubly sure, a
radiograph should always be taken. Specific infective forms of arthritis
then call for careful elimination—_i.e._, gonococcal, etc. If there be no
history of such, a painstaking search should be made for any local foci
of infection, _e.g._, mouth and accessory cavities. If any be found, they
should be radically treated, as it is much more likely that the arthritis
is due thereto than to gout.

If, notwithstanding a meticulously careful investigation, no cause can be
assigned, we may entertain the possibility of its being _gout_, the more
legitimately if the subject be a middle-aged man coming of gouty ancestry
and exhibiting himself tokens of this diathesis, _i.e._, _tophi_. It
would be confirmatory, too, if, apart from its exceptional localisation,
the joint disorder in its course conformed to that typical of gout in the
toe, in other words if it was of sudden nocturnal onset, showed marked
daily remissions in temperature and pain, responded swiftly to the action
of colchicum, and was not protracted beyond the usual week or ten days.

Sir Hale White, discussing the diagnosis of acute gout of unusual
localisation, remarks: “The real difficulty in acute cases comes when
it is suggested that an acute arthritis with pyrexia and swelling and
redness of a joint other than that of the great toe is caused by gout.
I have recently seen the difficulty in one patient in the wrist, in
another in the knee. Such cases, if they are not gout, are some bacterial
arthritis.”




CHAPTER XXI

CLINICAL DIAGNOSIS (_continued_)


ACUTE GOUTY POLYARTHRITIS

In the pathways of medicine, as in other walks in life, we are apt
to become stereotyped, to fall into grooves, and sooner or later the
inevitable rude awakening comes. Thus, so prone are we to think of gout
as belonging, so to speak, to the foot, that when it erupts elsewhere
it is often the last contingency to dawn upon us. If we diagnose it too
often and too readily in the foot, we do so too seldom when it appears in
joints remote.

Now, while in _initial_ outbreaks of gout it is exceptional for more than
_one_ joint to be affected, it is not always so. For sometimes in those
strongly predisposed by _heredity_ not one, but _many_ joints, may be
implicated in the _primary_ attack. Such cases, however, are extremely
rare.

As a rule, this _acute gouty polyarthritis_ occurs in individuals who
have already experienced articular paroxysms at the classic site; but
in the subsequent polyarticular attacks the _toe_ joints are often
unimplicated, and the disease is located in the larger articulations—the
knees, ankles, wrists, or elbows. Herein resides the difficulty of
diagnosis in these cases: the likelihood of confusion with other
polyarthritides.

Confronted then with an _acute polyarthritis_ of obscure nature marked by
pain, redness, swelling, and pyrexia, what are the points necessary to
establish it as being of gouty origin?

The sex and age should be noted, also the heritage, habits, and
occupation. A history of _previous attacks located in the big toe_ would
be of prime value. The presence of a cardiac _valvular_ lesion, while it
would suggest a previous attack of _acute rheumatism_, would in no wise
negative the possibility of the subject developing _gout_ in later life.
Here I may say that if the subject is over thirty-five and has never
had acute rheumatism or acute gout, it is much more likely at his time
of life that his _acute polyarthritis_ is of _gouty_ than of rheumatic
origin.

As to the character of the pyrexia, it is usually of _low_ grade; but
if the condition be _afebrile_, it is even more suggestive of a _gouty_
arthritis. But recollect, too, that the pyrexia in _gonococcal_ arthritis
is also of low grade or absent.

There is nothing distinctive of _gout_ either in the character or
distribution of the articular lesions. The ankles, knees, hands, wrists,
are most commonly involved, much more rarely the elbows, shoulders, or
hips. Naturally the local changes will differ according to the joint
involved and the structures implicated; but these local variations
in appearance, including œdema, may all be met with in any form of
_infective_ arthritis.

As to _uric acid excretion_, Osler, who was deeply interested in this
type of arthritis, held that any _lowering_ of the ratio of the _uric
acid_ to the _urea excretion_ would be significant of gout. Also we
should, as these cases of acute gouty polyarthritis are of the nature
of successive paroxysms (“series et catena paroxysmulorum,” to use
Sydenham’s expression), note _any variations in the uric acid output_
ensuing _pari passu_ with their rise and wane.

Last, but most important of all, a thorough search must be instituted
for _tophi_, not only in the ears, but elsewhere. If anything could
emphasise the indispensable _rôle_ played by _tophi_ in the diagnosis
of gout, it would be our utter inability to effect in their absence
a diagnosis of these _acute_ types of _gouty polyarthritis_. The
establishment of the existence _in situ_ of such _articular uratic
deposits_ disposes forthwith of all possible doubts as to the true nature
of the case; but if, as so frequently happens, the tophi when present are
of _ab-articular_ site, then we must withhold our decision pending the
exclusion of certain other joint disorders, to the differentiation of
which we now proceed.


DIFFERENTIAL DIAGNOSIS

The class of disorders that call for discrimination are those of
infective origin. In the first place, _acute articular rheumatism_
must be excluded; nor is it less necessary that we should eliminate
_gonorrhœal_ and _syphilitic_ types; while, last, but not least, that
vast group, the _undifferentiated infective arthritides_, is but too
often a source of confusion.


ACUTE ARTICULAR RHEUMATISM

Unquestionably many cases of _acute gouty polyarthritis_ have been
confounded with _acute articular rheumatism_, and _vice versâ_. Garrod on
this point remarks: “That many cases of acute gout have been mistaken for
acute rheumatism I do not doubt, and, on the other hand, that some few
cases of acute rheumatism have been regarded as of a gouty nature I am no
less certain. I may refer to the oft-quoted case related by Dr. Haygarth
in which gout was supposed to have been transferred from the extremities
to the heart as an example of the latter error.”

It is only, of course, with that type of acute gouty polyarthritis
accompanied by _pyrexia_, and not the _afebrile_ variety, that confusion
with acute articular rheumatism is possible. What then are the points of
discrimination?

                      ACUTE ARTICULAR RHEUMATISM.        ACUTE GOUTY
                                                        POLYARTHRITIS.

  Age and sex         Most common between ages         Maturity and old
                        of fourteen and thirty.          age. Males.
                        Predominance of males            Females markedly
                        after twenty.                    exempt.

  Heredity            Very disputable.                 Very pronounced.

  Onset               Usually abrupt and often         Insidious, with
                        with tonsillitis.                premonitory
                                                         gastro-intestinal
                                                         symptoms.

  General symptoms    High fever, sometimes            Moderate pyrexia.
                        hyperpyrexia. Profuse            Marked daily
                        acid sweats.                     remissions.

  Distribution of     Preference for large joints      Small joints, hand
    lesions             and markedly mobile.             or foot often
                                                         involved. Fixity
                                                         typical.

  Local characters    Joints exhibit slight reddish    Scarlet hue and
                        flush. No subsequent             œdema with later
                        desquamation. No residual        peeling of cuticle
                        change.                          and itching.
                                                         Tendency to
                                                         involvement of
                                                         bursæ and tendons.

  Pain                Chiefly evoked by movement.      Spontaneous, more
                                                         intense.

  Duration            Twenty to thirty days,           Six weeks to three
                        sometimes longer.                months.

  Associated          Cardiac lesions common.          Tophi. Occasionally
    phenomena                                            glycosuria and
                                                         albuminuria.

  Therapeutic test    Salicylates a specific.          Not so in gout, but
                                                         colchicum takes
                                                         this _rôle_.


ACUTE GONOCOCCAL ARTHRITIS

This disorder, as we know, is sometimes of oligo- or poly-articular
distribution. Moreover, as the attendant pyrexia may be slight or absent,
it may readily be confounded with the _afebrile_ variety of acute _gouty_
polyarthritis. Osier, discussing diagnosis of the latter condition,
observes: “A patient with three or four joints red, swollen, and painful
in acute rheumatism has fever, and while _pyrexia_ may be present, and
often is, in gout, its absence is, I think, a valuable diagnostic sign.”

This is of course true, but it still remains necessary, for reasons
above cited, to eliminate _acute gonorrhœal arthritis_. The tendency
to such confusion has been emphasised by Sir Rose Bradford and Sir
William Roberts, and I would urge the necessity of being alive to
this possibility even in middle-aged men. One thing is certain, viz.,
we should be extremely chary of pronouncing any coincident urethral
discharge to be a so-called “gouty urethritis”; nor should we translate
any coincident _conjunctivitis_ or _iritis_ as further evidence of
the articular affection being “gouty.” It is far more likely to be
_gonococcal_. Apart from these inflammatory ocular affections, the relics
also of previous attacks—viz., irregularity in contour or inequality in
size of the pupils—have before now put me on the right track in obscure
types of polyarthritis.

To sum up, the following are distinctive characters of _generalised_
gonorrhœal arthritis:—

_Etiology._—History or presence of urethral discharge and isolation of
the gonococcus.

_Onset._—Insidious, seldom acute.

_General Symptoms._—Absent or slight relatively to extent and severity of
joint mischief. Pyrexia, low grade or absent.

_Distribution of Lesions._—Preference for large joints. Special liability
of sacro-iliac, chondro-costal synchondroses, sterno-clavicular,
tibio-fibular, and temporo-maxillary joints.

_Local Characters._—Persistent passive effusion or peri-articular boggy
swelling, with redness and local heat. No tendency to migrancy. Joint
swelling very persistent.

_Associated Phenomena._—Involvement of fasciæ, especially plantar,
and of tendon sheaths, very distinctive, while coincident iritis or
conjunctivitis is almost diagnostic.


SECONDARY SYPHILITIC ARTHRITIS

The ease with which a subacute arthritis of this nature may be confounded
with “gout” or “rheumatism” calls for comment. We have met with cases
despatched to spas under this impression. The customary _intermittent
fever_ of _secondary syphilis_ is usually present. The detection of
periosteal nodes in addition to the joint swellings should arouse
suspicion, while the presence of _secondary syphilides_ and the rapid
response to _specific_ treatment will be confirmatory.

I well recollect some years ago a young farmer being sent to me by a
medical man as suffering from _gouty arthritis with gouty eczema_. The
eruption was a typical _roseola_, and the condition promptly cleared up
under _anti-syphilitic_ treatment.


ACUTE RHEUMATOID OR ATROPHIC ARTHRITIS

While the old term “rheumatic gout” still clings to this affection, it
has now achieved its isolation from gout on the one hand and rheumatism
on the other. The fact that it occurs in young women in whom gout never
occurs, and has a very marked clinical _facies_ of its own, should almost
preclude the possibility of its being a source of confusion. Still, for
the sake of completeness, we append its chief characteristics.

_Age and Sex._—Most common in young women.

_Onset._—More or less acute.

_General Symptoms._—Continuous low grade pyrexia, quick pulse, and rapid
emaciation, and commonly concomitant gastro-intestinal derangements.

_Distribution of Lesions._—Polyarticular. Beginning in the small joints,
it spreads centripetally, with a tendency to symmetry. No migrant trend,
but a steady, progressive involvement of joint after joint, including
temporo-maxillary and cervical articulations.

_Local Characters._—Overlying skin of affected joint white or
semi-asphyxial in tint. Contour spindle-shaped, but in terminal stages
shrinkage from atrophy of articular structures sets in. Muscular wasting
and contracture conspicuous features.

_Associated Phenomena._—Trophic and vasomotor changes prominent, but _no
tendency to cardiac lesions_.


INFECTIVE ARTHRITIS OF UNDIFFERENTIATED TYPE

It were well in approaching any acute polyarthritis of obscure
nature to bear in mind the axiom that _any or all infections may be
complicated by arthropathies_, also that if the said polyarthritis does
not respond quickly to colchicum or salicylate of soda we are almost
certainly dealing with an infective arthritis either of specific or
undifferentiated type. The _specific_ forms of infective arthritis, as
far as seems necessary, have been dealt with, but those rarer forms
not referred to, viz., _influenzal_, _pneumococcal_, _dysenteric_,
_meningococcal_, etc., have also to be borne in mind, if the history
reveal any recent occurrence of these disorders.

Still far more common than any of these are the _acute infective
arthritides_ of _undifferentiated_ type. As we before remarked, an
extraordinary general clinical resemblance obtains between these types of
joint disorder and _acute gouty polyarthritis_. Indeed, _in the absence
of tophi_, their differentiation is well-nigh impossible. Even the blood
picture in both types of the disorder is strikingly similar in the matter
of _leucocytosis_ and _secondary anæmia_.

Recently Dr. Henry A. Christian, lecturing at a clinic of the Harvard
Medical School, emphasised this clinical similarity and the difficulty
of discriminating between these two types of joint disorder. As he
rightly says, “while there is a definite _acute gouty polyarthritis_
(as evidenced by external tophi or deposits in bone or cartilage with
variations in uric acid output) and also an equally definite _infective
arthritis_, yet between those two there is a very considerable number of
cases that present some of the factors suggestive of _gout_ and other
factors suggestive of an _infectious arthritis_, and there is where the
difficulty comes.”

This is precisely the state of affairs, and one may well ask where _gout_
ends and _infection_ begins. Let us take an example. A man exhibiting
_tophi_, the subject also of _pyorrhœa alveolaris_, develops an _acute
polyarthritis_. What then is the nature of the joint disorder? There is
a gouty element in his case, as attested by _tophi_, also an infective
element, as evidenced by _oral sepsis_.

Now are we to regard such a case as one of _infective arthritis_ of
_undifferentiated_ type occurring in a _gouty_ subject, or are we to
proceed on the assumption that the presence of _tophi_ negatives the
possibility of infection and forthwith to class it as a case of _acute
gouty polyarthritis_ of so-called _metabolic_ origin?

This is no theoretical quibble. In the Royal Mineral Water Hospital,
Bath, one constantly meets with cases in which the very elect would be
puzzled as to whether they should be placed in the category of _gouty_
or in that of _infective_ arthritis. I have at present in my wards a
middle-aged man, stout of body, rubicund of face, with well-marked
auricular tophi and widespread arthritis. There are no tophi round his
joints. On X-ray examination his phalanges show Bruce’s nodes, and his
phalangeal joints show changes indistinguishable from those constantly
met with in infective arthritides occurring in _non-gouty_ subjects.

Indeed, this overlapping may proceed still further, the gouty and the
infective characters neighbouring in such proximity as to suggest actual
fusion, a community of origin. What else in truth can be the inference,
when one meets with examples in which the _peri-articular_ tissues are
the seat of demonstrable _uratic deposits_, while the X-ray changes
within the joint proper, the bone and cartilage, are typically those met
with in _infective_ arthritis?

Now, who will deny that if tophi were absent in such a case we should
without hesitation hold the case to be one of infective arthritis? My own
contention is that even in the presence of tophi the same appellation is
indicated. In other words, I submit that _acute gouty polyarthritis_ is
itself but a form of _infective arthritis_ which derives its _specific_
character from the associated _uratic deposits_.

As to differentiation of the latter from these cryptic infective
arthritides, this will rest mainly on—

(1) The presence of tophi;

(2) A history of previous attacks in the great toe;

(3) A swift response to colchicum.

In addition, acute gouty polyarthritis is confined to _middle-aged
males_, while no period of life is immune from infective arthritis, and
both sexes are equally liable.

Again, acute gouty polyarthritis may be _afebrile_. Pyrexia when present
is moderate in grade, its curve undulating as the paroxysms rise and
wane. In infective arthritis the temperature curve is irregular and
erratic.

Lastly, the _uric acid output_ in acute gouty polyarthritis drops a day
or two before the paroxysm, rises markedly after its inception, then
sinks again. Also we may add that occasionally glycosuria or albuminuria
is present.

In conclusion, I would allow myself a brief digression regarding these
infective arthritides of undifferentiated type. They constitute the
bulk of the cases of arthritis that find their way to the Royal Mineral
Water Hospital, Bath, under one or other of the appellations “gout,”
“rheumatism,” and “rheumatic gout.” It is within this category that most
of the cripples met with at spas fall, and their obduracy to “drug”
treatment accounts for their belated despatch thereto.

I would that I could sufficiently emphasise the imperative necessity
of early recognition of the true nature of these cases. Colchicum is a
most valuable drug, and so is salicylate of soda. But they have their
limitations. They act swiftly or not at all. Persistence with them in
the absence of any response is worse than futile: it is definitely
prejudicial. Because of our unreasoning devotion, our almost fetishistic
addiction, to these drugs, I often feel that these agents, especially
salicylate of soda, have made more cripples than they have saved. For,
unfortunately, unqualified reliance on these drugs is apt to blind us
to the surgical necessities of these cases. Foci of infection pass
unnoticed, joints stiffen at unfavourable angles, and not infrequently a
potential bread-winner is lost.

I make no apology for this digression, for it is, strictly speaking,
wholly apposite, this in view of the fact that failure of quick response
to the action of colchicum or salicylate of soda, say within a week,
speaks in favour of the infection having ensued in a _non-gouty_ as
opposed to a gouty subject.




CHAPTER XXII

CLINICAL DIAGNOSIS (_continued_)


CHRONIC ARTICULAR GOUT

If the diagnosis of acute types of articular gout often presents
difficulties, these same are, if anything, accentuated when we approach
its chronic manifestations. For, _apart from uratic deposits_, the
anatomical lesions that ensue in joints the seat of long-continued gout
have no _specific_ character. In short, there is nothing pathognomonic of
gout in the changes produced, and which, as a matter of fact, we know to
be capable of production, by many different morbid agencies. Surely this
lack of specificity in its structural lesions should make us very chary
of admitting to the category of chronic articular gout any examples of
arthritis _destitute of uratic deposits_.

In our chapter on _classification_ we emphasised the desirability of
restricting the usage of the term chronic articular gout to that type
long since known as _tophaceous_ gout, this because there is little,
if any, doubt that that variety known as chronic deforming gout (syn.
arthritis deformans uratica) is largely made up of examples of rheumatoid
or atrophic arthritis and hypertrophic arthritis or osteoarthritis.[41]

As to _osteoarthritis_, I do not for a moment deny that _uratic
deposits_ may be met with in its victims. One frequently meets with
patients, the subjects of osteoarthritis of the hip, who at the same time
exhibit tophi in the ears.

But such to our mind are to be regarded as merely instances of
_osteoarthritis_ occurring in subjects of “gouty diathesis.” This
apparent blending of the two disorders must not be allowed to impair
the clarity of our conception as to the essential distinctness of gouty
arthritis and osteoarthritis.

Sir W. Hale White has some pregnant observations on this point. Many
patients, he says, “with chronic arthritis are quite wrongly said to have
gout; usually they have osteoarthritis. The presence of bony outgrowths
is strongly against gout, though it is not conclusive, for such may occur
in true gout either more or less all round the joint or in the form of
little nodules, but they never attain the considerable size common in
arthritis,” and he adds: “If no urate of soda is visible anywhere the
diagnosis may be very difficult.”

To proceed, the general and local phenomena of chronic articular gout
are such as scarcely lend themselves to succinct definition, and for
their description we would refer the reader to the chapter dealing with
its clinical aspects. As that careful observer Sir Alfred Garrod states:
“Chronic gout is at times confined to one or two joints, but sometimes
numerous articulations are involved.” In other words, chronic articular
gout may be mono-, oligo-, or poly-articular in distribution; and
naturally the process of differentiation is modified accordingly.

This being so, I purpose dealing in the first instance with chronic
monarticular gout, and in succession with the types of oligo- and
poly-articular location.


CHRONIC MONARTICULAR GOUT

Occasionally gout in its recurrences clings obstinately to the great
_toe_ and _tarsal_ joints. But since the advent of _radiography_
there should be little or no difficulty in differentiating a chronic
gouty arthritis of the great toe from the only other arthritic
lesion with which it is likely at this stage to be confounded, viz.,
_osteoarthritis_. But at the same time we would refer the reader back
to the chapter dealing with the differential diagnosis of the localised
variety of acute gout, as therein we dealt fully with other possible
sources of fallacy, _i.e._, _static deformities_, etc. We shall therefore
now proceed to discuss those exceptional cases in which chronic gout
is located not in one of the small, but in one of the _larger_,
articulations.


MONARTICULAR GOUT IN LARGE ARTICULATION A RARITY

Given a chronic arthritis of one of the larger joints, say the ankle,
knee, or elbow, we should be careful not to jump too readily to the
conclusion that it is of “gouty” nature. The more obscure it appears the
more need for caution. Needless to say, if the objective changes be but
minimal and the condition be, so to speak, practically a mere arthralgia,
there rests upon us the paramount necessity of careful discrimination
before labelling it as “gouty” in kind.

Thus, if it be the knee, it may be a referred pain due to hip disorder,
_e.g._, _osteoarthritis_ or _tuberculous_ disease, or it may be
symptomatic of an inflammatory process, or, having regard to the usually
mature or advanced age of the subject, it may be a _neoplasm_ in the
bones.

On the other hand, suppose the subject come complaining not much of pain
in his joint, but more troubled because of its _enlargements_. If now
on examination we find also that there is little or no tenderness, but
simply a condition of _peri-articular thickening_ or _intra-articular
effusion_, what shall be our method of procedure? Certainly not to leap
forthwith to the conclusion that it is gouty. No, not even if he exhibit
_tophi_ in his ears.

Now, as to pain and tenderness, it is a blessed feature of gouty
arthritis that, generally speaking, in the chronic forms pain becomes
much attenuated. But let us at the same time recollect that _syphilitic_
arthritis, both secondary and tertiary, is relatively _painless_. But it
is the much rarer _tertiary_ form, be it remembered, which is usually
_monarticular_. By the bye, too, we should never forget that a _Charcot’s
joint_ is also painless.

Coming now to the _objective_ phenomena, is the case predominantly one
of peri-articular infiltration or intra-articular effusion? As to the
former, while you never know, still _tuberculous_ joint disease is
exceptionally rare at the age at which we usually meet gout. On the
other hand, _gummatous synovitis_, with or without osteoperiostitis,
is occasionally met with. It is just such a case as this that may be
confounded with gout, the irregular lumpy thickening of the sub-synovial
tissues with effusion being wrongly attributed to a gouty process with
uratic deposits. Do not be misled if a history of injury be forthcoming
in such cases, for it is not uncommon and may be given in good faith.

Now what if synovial effusion of chronic or recurring form be the
striking objective feature of the case under review? In this event always
recollect that of all the causes of _monarticular_ disorder _injury_
is far and away the most frequent. Not a few cases of monarticular
joint disease come annually to the Royal Mineral Water Hospital,
Bath, under the diagnosis of “gout” and “rheumatism.” But in all
too many the symptoms are referable in truth to ligamentary strain,
displaced cartilage, or foreign bodies, lesions always to be sought for
and excluded in monarticular joint affection. Duckworth has it that
_hydrarthrosis_ is met with in chronic articular gout, in his deforming
variety. He states that “hydrarthrosis is less commonly due to gout than
to rheumatism,” but, we would remark, apart from traumatic lesions, more
commonly due to _gonorrhœa_ or _syphilis_ than to either of them.

But the reader may say, this dissertation notwithstanding, Where does
_gout_ come in? Precisely so, and if his experience tallies with mine, he
will find that chronic articular gout localised in _one_ of the _larger_
joints, and one only, is exceptionally rare. Personally, I should never
feel justified in making the diagnosis unless I had elicited a history of
(1) recurring classic outbreaks in the great toe with (2) an absence of
traumatic infective and nerve arthropathies and, on the other hand, (3)
demonstrable existence of _uratic deposits in situ_ in the peri-articular
tissues, the cartilage or bones as revealed by _skiagraphy_, or in the
related bursæ.

In conclusion, if all these various pitfalls have been avoided, it will
almost without exception be found that the final differentiation in
doubtful cases will rest between gout and _osteoarthritis_; and in the
vast majority, I had almost said all, it is the latter morbid process
that will be found responsible.

This all too lengthy disquisition will not have been in vain if it instil
caution. For it is in the monarticular types of joint affection that
errors of catastrophic proportion occur more commonly than in any other
form of joint disorder.


CHRONIC GOUT OF OLIGO-ARTICULAR DISTRIBUTION

The course of chronic articular gout, as has been observed, may be
chequered by acute outbreaks involving three, four, or more of the larger
joints. But, apart from this, there are those so-called _asthenic_ and
_afebrile_ types of gout in which two or more joints may be the seat of a
chronic gouty arthritis. In my experience it is the _knees_ that are most
frequently attacked. The joints are enlarged, the seat of more or less
effusion, but the distinctive feature is the presence of deformity due to
the irregularly rounded or ovoid swellings produced by _uratic deposits_.
Enlargement of the patellæ is also present, and they lose their sharp
edges, and sometimes they as well as the neighbouring articular ends are
studded with small bony outgrowths, but of minimal size compared with
those met with in _osteoarthritis_. The related _bursæ_, too, are often
the seat of _deposits_, a valuable clue to diagnosis. Needless to say,
such marked cases are nearly always the outcome of oft-repeated attacks,
the ultimate deformity being the result of successive accretions of urate
of soda laid down in the trail of the exacerbations.


ITS CONFUSION WITH CHRONIC VILLOUS SYNOVITIS

The frequency with which this misconception occurs is very noticeable. If
a _middle-aged_ woman of florid complexion and _corpulent_ habit begins
to complain of pain and stiffness in her knees with more or less swelling
thereof, there is a very prevalent tendency to attribute not only her
joint disorder to _gout_, but any gastric or nervous symptoms that she
may simultaneously complain of are translated as being confirmatory of
the assumption. It gathers weight too from the traditional and widespread
belief that “the change of life” is the period _par excellence_ at which
women develop the morbid vagaries associated with “irregular gout.”

Now, as Bassett Jones and I have pointed out in a previous work, this
condition, _symmetrical villous synovitis_ of the _knees_, is a very
common joint disorder in _women_ at or near the _menopause_. Frequently
they give a history of numerous _pregnancies_, or of _rapidly increasing
obesity_, while with or without this latter they display a _faulty
postural attitude_, indicative of lowered muscular and ligamentary tone.
Following in the wake of these, the subject develops a _symmetrical
flatfoot_, which, according to the stage at which it is seen, may be of
flexible or rigid type.

Now, such is the mutual _static interdependence_ of the component parts
of the lower limb that this condition of flatfoot promotes or favours
the incidence of _villous overgrowths_ in the proximal joints, the
_knees_. As to the _modus operandi_ we have put forward the following
explanation: “The everted foot, with its sunken arch, as before stated,
determines an alteration in the normal coaptation of the articular
surfaces in the knee, and this incongruence is revealed in skiagraphs by
the marked prominence laterally of the external tibial tuberosity beneath
the external femoral condyle. Coincidently, and for the same reason,
additional strain is thrown upon the internal lateral ligament. This in
turn favours a state of passive congestion or hyperæmia of the synovial
membrane, which becomes relaxed and thrown into folds, especially at its
reflexions near the edges of the cartilages. If, as often happens, the
individual is the subject of _varicose veins_ or suffers from a _general
lack of tone in her muscular or ligamentary structures_, this tendency to
venous engorgement of the knees is much enhanced.”

“Under the influence of these mechanical factors and their associated
circulatory disturbances, _thickening and enlargement of the synovial
fringes ensue_. The inflammatory condition thus produced tends to
increase automatically, as, owing to the articular incongruence, the
enlarged fringes are very prone to become caught between the joint
surfaces; in other words, a vicious circle is produced, as with the
increasing villous hypertrophy the liability to internal traumatisms
increases _pari passu_.”


VILLOUS SYNOVITIS STATIC AND NON-GOUTY IN ORIGIN

In short, the joint disorder is fundamentally of _static or mechanical_
origin, and, this being so, the results of _anti-gouty_ treatment are
open to a further misinterpretation. The victims, as we have said,
exhibit very generally a tendency to _obesity_. Now, Ebstein and many
others hold the view that _obesity and gout have affinities_. Ebstein,
moreover, believes that treatment directed to the reduction of body
weight will check the appearance of gouty arthritis or ameliorate the
same when avowed. What happens is this: these corpulent subjects are
placed on a special dietary. Hydrocarbon foodstuffs are limited, bread,
amylaceous food and liquids being also restricted. Naturally, _pari
passu_ with reduction in their body weight, their overburdened joints
become more equal to their office. But those who assume that the chronic
arthritis is of _gouty_ origin attribute, and, we think, wrongly, the
beneficial results attained to correction of the underlying “gouty” habit.

We prefer to subscribe to the simpler or mechanical theory, and in view
of the widespread and, as we believe, erroneous belief in the gouty
nature of this arthritis, we take the liberty of appending the salient
features of these cases, while adding further a few remarks on the
differential diagnosis of other symmetrical affections of the knees which
may also be wrongly attributed to gout.


CLINICAL SYMPTOMS OF VILLOUS SYNOVITIS

The onset is gradual and insidious. Stiffness is the salient symptom,
but sometimes the subject is more distressed by a sense of weakness,
distension and unreliability. Pain is slight or absent, save when during
walking pseudo-locking occurs. The mobility of the joints is usually
unimpaired, and if any limitation exist it is the power of full extension
that is usually restricted.

Objectively the joint shows either general enlargement or swelling
localised to the _supra_- or _infra-patellar_ regions. Intra-articular
effusion which comes and goes is a very characteristic feature. On
palpation a peculiar soft silken crepitus will be heard and felt as the
patient alternately flexes and extends the limb. The enlarged fringes
are also easily to be felt as knots or nodules which can be moved up or
down on the underlying bone. The ease with which they can be appreciated
depends upon the degree of effusion present at the time. Judging from
their symptomatology, it seems probable that some of the cases included
in Sir Dyce Duckworth’s category, chronic deforming gout, are of this
description.

The diagnosis of villous synovitis should not be considered complete
without _skiagraphy_ being undertaken to reveal or exclude osteophytic
outgrowths. For the subjective symptoms and signs of _early_
osteoarthritis are practically identical with those of villous arthritis,
and although the presence of osteoarthritic lesions elsewhere would be
suggestive, skiagraphy alone will enable us to effect a differentiation
with certainty. Indeed, Bassett Jones and myself are strongly of the
opinion that the life history of osteoarthritis involves two stages: (1)
a _primary_ or _pre-osteophytic_ phase, often of prolonged duration,
whose clinical characteristics are those of villous hypertrophy; (2)
a _secondary_ or _terminal_ stage, in which bony and cartilaginous
outgrowths make their appearance.

Other symmetrical disorders of the knees that may be wrongly ascribed to
gout are hydrarthrosis and gummatous synovitis.

_Bilateral Hydrarthrosis._—Given effusion into both knees which is
_passive_, _copious_, and _persistent_ rather than recurrent, then its
possible _infective_ origin must be carefully canvassed. The common
sources are _gonorrhœa_, _syphilis_, and _tubercle_. The history or
presence of an urethral discharge and detection of the gonococcus will
identify the first named. In syphilis the existence of other lesions, the
response to Wassermann’s test and specific treatment are the points on
which to rely, and in tubercle, the detection of visceral foci and the
sero-reaction will give the clue.

As to the _intermittent_ type of hydrarthrosis, the remarkable
_periodicity_ in incidence of the effusion will suffice to obviate any
possibility of confusion.

_Peri-synovial and Peri-bursal Gummata._—Affecting as they do commonly
the knee joints of adults, these may, in the absence of a history
of infection, be a source of error. The uneven and nodular swelling
may quite easily be confounded with uratic deposits. Pain is slight
and mobility but little impaired. The presence of neighbouring
scars, a positive Wassermann reaction, and a favourable response to
anti-syphilitic therapy will clear up the diagnosis.


CHRONIC GOUT OF POLYARTICULAR DISTRIBUTION

The clinical portrait of tophaceous gout when of widespread distribution
is one of the most striking to be met with in the whole domain of
medicine, but for the broad outlines of the picture presented we would
refer the reader to the chapter dealing with the clinical description of
chronic articular gout.

In these polyarticular forms the most distinctive joint deformities are
those met with in the _hands_ or feet, more particularly the former. The
excrescences produced are the outcome of successive _uratic deposits_.
These latter when massive can scarcely be confused with any other
disorder, for the superjacent skin, distended by the ever-increasing
underlying uratic deposits, becomes thinned and purplish red in hue, and
occasionally ulcerates. I have at present in my wards a case of this
nature, and the subject hoards up the exuding “chalk” in a small bottle.

Fortunately such marked examples are relatively rare, though easily
recognised; but it is the less marked types that occasion difficulty
in diagnosis. The point at issue of course is the differentiation of
moderate-sized or small tophaceous swellings from bony outgrowths.
Frequently the task is impossible of achievement without resorting to
puncture, when, if anything can be withdrawn, microscopic examination may
reveal the presence of _biurate_ crystals.

For the rest, attention to the following points will prove helpful in
enabling us to differentiate clinically between gouty arthritis and other
chronic joint disorders attended by deformities:—

    (1) Tophi when of recent incidence are _soft_, and when of long
    standing are never so dense or so hard as bony outgrowths.

    (2) The overlying skin is thin, and through its substance the
    subjacent white concretions may sometimes be discerned. It may
    be adherent, or the seat of ulcers.

    (3) Uratic deposits are _not located exactly at the level of
    the articulation_. They do not adapt themselves to the contour
    or shape of the bone-ends.

    (4) Unlike osseous growths, they may be slightly movable in
    lateral directions.

    (5) Tophi may _soften_ or _disappear_ after exacerbations of
    arthritis.


DIFFERENTIAL DIAGNOSIS

The conditions likely to be confused with chronic polyarticular gout are
osteoarthritis, rheumatoid arthritis, and the multiple arthropathies met
with in affections of the central nervous system.


OSTEOARTHRITIS

Its chief characteristics may be summarised as follows:—It is a disease
rarely met with under forty years of age. The mode of onset is generally
insidious, never really acute. In this respect it contrasts with gout,
the initial outbreak of which is invariably acute. Osteoarthritis
attacks both sexes equally. Although it may be polyarticular, its
specific tendency is towards a mono- or, more accurately speaking,
oligo-articular distribution, with no marked leaning to symmetry. It has
a pronounced predilection for attacking the _hip_, the _shoulder_, and
the _spine_—sites rarely, if ever, attacked by gout.

Unlike gout, constitutional symptoms, pyrexia and so forth, are generally
absent; muscular atrophy is slight, hardly ever pronounced, likewise
muscular spasm and contracture.


LOCAL CHARACTERS OF JOINT SWELLINGS

These are best appreciated in the small joints of the hand.
Osteoarthritis has an affinity for _terminal_ joints—the so-called
Heberden’s nodes. Another favourite site is the carpo-metacarpal joint of
the thumb, while the preference of gout is for the metacarpo-phalangeal
joint thereof and for the same articulation in the other digits.

The overlying skin, as a rule, is unchanged, and never assumes, as in
gout, a dusky red or purplish hue. The margin of the articular surfaces,
instead of being smooth and rounded, is broken and irregular, its nodular
contour being due to osseous outgrowths studding the line of junction of
the bones entering the articulation.[42]

In this respect they contrast with tophi, which are located near to,
but not at, the level of the joint fissure. Again, unlike tophi,
bony outgrowths are fixed, immutable, undergoing no change save in
the direction of progressive enlargement. While the tendency of an
osteoarthritic joint is to expand and increase, still the enlarged and
gnarled joints never attain the colossal bulbous appearance presented by
inveterate examples of tophaceous gout.


RHEUMATOID ARTHRITIS

This affection differs from the foregoing disorder as well as gout
in that it is most commonly met with in persons under forty years of
age. Moreover, it attacks women much more frequently than men. Of
polyarticular distribution, it evinces a marked tendency to symmetrical
invasion. Like gout, it has a pronounced preference for the smaller
joints, while, similarly, it avoids the hip and shoulder.

Constitutional symptoms are conspicuous: pulse quickened, temperature
raised, extreme wasting not uncommon. Intense and widespread muscular
atrophy with contracture is a prominent feature, also trophic
disturbances of varied nature and degree.


LOCAL CHARACTERS OF JOINT SWELLINGS

In early stages the skin over the joint is waxy white or semi-asphyxial
in tint, outline of joint smooth, rounded, and spindle in shape, with, as
a rule, no irregular bony projection at the level of the articulation.
If seen at a later stage, the swollen joint will be found shrunken from
atrophy of all the articular structures as well as the skin. Ultimately
it becomes reduced even below its normal size, the small “end-joint” of
atrophic or rheumatoid arthritis. The deformities due to muscular spasm
are usually in the direction of luxation and hyperextension, and differ
from those of gout and osteoarthritis, in which there is more generally
lateral displacement.


NERVE ARTHROPATHIES

The joint disorders incidental to tabes and syringomyelia do occasionally
find their way to spas for treatment under the mistaken conception
that they are instances of “gout,” “rheumatism,” or “rheumatic gout.”
In the case of tabes the mistake is often referable to the confounding
of its lightning pains with “gout” or “rheumatism,” with subsequent
relegation of the swollen joints, whether single or multiple, to one
or other of these categories. In the syringomyelic it is, I think, the
close resemblance that obtains between the joint lesions and those of
osteoarthritis or so-called “rheumatic gout” that accounts for their
uncalled-for and utterly useless transference to spas. I have known a
case of syringomyelia with multiple arthropathies in the hands sent to
Bath under the mistaken idea that they were of “gouty” origin.

These remarkable joint affections will be distinguished by their
fulminant onset with marked effusion and absence of _pain_, tenderness,
and heat. In addition, associated phenomena will be present, viz., ataxic
pupillary changes and lost knee-jerks in tabes, while syringomyelia is
characterised by dissociated anæsthesia, trophic disturbances of bones,
progressive muscular atrophy with paralysis.


HÆMOPHILIC ARTHRITIS

It will be recalled that Rieken held the view that so-called “bleeders”
were prone to attacks of gout, and that sometimes these alternated
with intra-articular hæmorrhages. Nor was he devoid of supporters, for
Sir Dyce Duckworth maintained that a definite hereditary relationship
obtained between gout and hæmophilia, while that astute observer Jonathan
Hutchinson also contended that the vascular weakness was the outcome of
gout and aggravated by serial hereditary transmission. Wickham Legg,
however, in his masterly contribution questioned the correctness of
Rieken’s proposition.

Personally, I cannot out of my own experience confirm or rebut the view
that “bleeders” come of gouty stock, nor have I ever met an avowed
gouty subject who was likewise the victim of hæmophilia. _Quâ_ its
joint complications, hæmophilia to our mind would appear to display
closer affinities with peliosis rheumatica than with gout; but, in
view of Duckworth and Hutchinson’s claims, it were wiser on our part
to withhold judgment, while paying them the deference of being alive
to the possibility of there being some obscure connection, though not
proven, between the two disorders. Again, as emphasising the necessity
for discrimination, we would draw attention to the fact that Konig
recognised three stages in hæmophilic arthritis: (1) hæmarthrosis; (2) an
inflammatory process, with pyrexia and spindle-shaped swellings apt to be
confused with tuberculosis; (3) extensive arthritic changes reminiscent
of arthritis deformans. Confusion with gouty arthritis clearly is only
likely in the second or third stages, and in the matter of diagnosis the
_personal and family tendency_ to hæmorrhages is the most important clue.




CHAPTER XXIII

CLINICAL DIAGNOSIS (_continued_)


SKIAGRAPHY

As an aid to the differentiation of _gouty_ from _non-gouty_ forms of
_arthritis_ skiagraphy has scarcely fulfilled the somewhat optimistic
claims at one time made on its behalf. As to _acute_ gout, radiography
reveals nothing abnormal in the bones, though Tousey holds that this of
itself at once enables us to exclude _osteomyelitis_, which, he says,
“these cases sometimes resemble.”

Turning now to _chronic articular gout_, Huber in 1896 drew attention
to certain _focal areas of rarefaction_, or diminished density, in the
distal extremities of the phalanges. These localised transparent areas
in the bone-ends are discrete, circular, or oval in shape. When located
near the edges of the bones, they are of segmental contour, and, viewed
in profile, give the appearance of small punched-out holes, simulating
syphilitic dactylitis. Despite their proximity to the diseased joints,
they apparently do not communicate with the articular cavities.

These bony changes Huber held distinctive of gout, and Koehler,
Drinberg, and Jacobsohn and other subsequent writers confirmed Huber’s
findings, and, like him, held these areas of rarefaction to be the
result of _uratic deposits_ at their sites. Strangeways has dissected
bones in which these transparent areas were demonstrated by X-rays. The
examination revealed that the bone was definitely excavated, filled with
a gelatinous-looking substance, and in advanced cases of gout, moreover,
a characteristic deposit of urates clung, as it were, to the margins of
the cavities.

Similar focal areas of decreased density were noted by Strangeways in
certain cases of _rheumatoid arthritis_, and both he and Burt found it
impossible on the X-ray findings to differentiate between these and gout,
_i.e._, without invoking the aid of clinical data.

[Illustration: Radiographs of the Foot and Hand, showing extensive bony
and other changes in long-standing Gout.]

Apart from these transparent areas, Wynne many years ago pointed out that
small _nodes_ or _bony deposits_ are sometimes met with flanking the
sides of the phalanges. More recently Ironside Bruce by _radiography_
has again drawn attention to these bony outgrowths near the extremities
of the phalanges (Bruce’s nodes). At first these were thought by Bruce
to be composed of _urates_, but Strangeways from a study of macerated
specimens has demonstrated their true _bony_ nature, and also that
_uratic deposits are not opaque to X-rays_, as was formerly thought.

In skiagrams of chronic gout all stages of _ankylosis_ may be seen in
the interphalangeal joints. In some it is merely fibrous, in others
merging therefrom into bony, and not infrequently true synostosis is
observed. Deflections or subluxations are frequent features, due either
to the thrust of tophi or small bony outgrowths or to peri-articular
contractures.

So much for the skiagraphic findings in chronic gout, and now to discuss
their valency as aids to diagnosis of this arthritic disorder. The
chief controversy centres around the significance of the _focal areas
of rarefaction_ which have been found in the bones of the wrists,
hands, ankles, and feet of gouty subjects. Here we may comment on one
grave handicap, viz., the lack of certainty as to whether the cases
radiographed by different observers were true instances of _gouty_
arthritis.

To justify our expression of doubt we may take, for example, the series
reported by Drinberg and Jacobsohn. The said “transparent areas” were
present in all the eighteen cases, but the presence of _tophi_ was only
established in three. Now, as McClure and McCarty rightly contend, “since
the tophus is the only universally accepted pathognomonic sign of gout,
for studies of that disease only those patients should be chosen in whom
tophi are found, and sodium urate crystals from them microscopically
demonstrated.” No one can, I think, gainsay the legitimacy of this
stipulation.

In accordance with their contention, McClure and McCarty record their
radiographic findings in a series of cases all of which exhibited
_tophi_, and from which sodium urate crystals were isolated. Now, in all
these cases the _focal areas of diminished density_, generally held to be
peculiar to gout, were present; but they add that “similar changes were
present in two other cases which were clinically gout, but in which no
tophi were demonstrated.” Also “in another case without tophi, but which
was clinically gout, the focal areas of decreased bony density were not
found.”

In addition, they examined the skiagrams of 100 cases of _chronic
arthritis_ which “had not been diagnosed clinically as _gout_.” In
thirteen of the examples “the focal areas of decreased density, the
so-called gouty bony changes, were found, and were fully as well defined
as in the cases of true gout.”

Judging from the skiagraphic appearances, there seemed no reason to
suppose that the factors responsible for the production of these
rarefied areas were in any way different from those at work in true gout.
Now, most authorities have claimed that the bony changes were due to
_uratic deposits_ in the bones; but it is at least possible that their
origin may be otherwise explained.

Thus Nichols and Richardson have shown that, given _focal absorption of
lime salts_, changes apparently identical with those currently attributed
to the presence of _tophi_ may result. These same, though they may not be
demonstrable either macroscopically or microscopically, are detectable by
X-rays.

Such foci of absorption, viz., areas of decreased density, frequently are
located in regions subjected to _pressure_. Thus they may occur at the
inner surfaces of the heads of the first metatarsal bones, or they may
form underneath large tophaceous deposits in the soft tissues.

Now, Strangeways has shown that it is impossible by radiography to detect
_tophi in bones_. Accordingly we have at present no means of deciding in
any given case whether the localised _transparent areas_ in the bones
are due to _tophi_ or to _focal absorption_ of lime salts. If we are to
cling to the conception that they are due to _tophi_, then it is clear
that _tophi in the bones_ are more common than is currently suspected,
and that, _ergo_, the frequency of gouty arthritis is underestimated.
For these transparent foci in bones, according to McClure and McCarty,
occur in from 10 to 12 per cent. of cases of chronic arthritis “which
clinically are not gout.”

Yet these authorities hold that, despite the fact that they occur in
cases of _non-gouty_ arthritides, they have some diagnostic significance.
For, taking the work of other observers in conjunction with their own
observations, they come to the following conclusions:—

    (1) The focal areas of decreased density, heretofore considered
    as peculiar to gout, are rarely absent in that disease.

    (2) Their absence would be some evidence against the existence
    of gout in a given case.

    (3) On the other hand, their presence is no more than
    suggestive of gout, since they are found in from 10 to 12 per
    cent. of cases which clinically are not gout.

    (4) The focal areas of decreased density, usually held due to
    tophi, are probably very often merely focal areas of absorption
    of lime salts.

In continuation these authorities have endeavoured to identify the nature
of the _arthritis_ that occurs in _gout_. Like other workers in this
sphere, the study of the radiographs obtained of gouty joints reveals
that a variety of changes occur in the bones and joints of the hands
and feet in gouty subjects. These, they consider, may be classified
conveniently as follows:—

    (1) Cases marked by _focal areas of rarefaction_, without any
    other perceptible change;

    (2) Cases presenting, in addition to these translucent areas,
    minor degrees of lipping at the articular margins;

    (3) Cases in which the changes in (1) and (2) are conjoined
    with either localised atrophy of the bones entering into an
    affected joint, or with generalised atrophy of all the bones in
    the affected limb;

    (4) In addition to all the above changes, narrowing of certain
    joint spaces with marked proliferative and atrophic changes
    occurs.

In reviewing these findings of McCarty and McClure, it is important
to recollect that they were found in a series of cases all of which
exhibited _tophi_. Moreover, it will be seen that the radiographic
changes in some are reminiscent of _atrophic_ or rheumatoid arthritis,
in others of _hypertrophic_ arthritis or osteoarthritis, while,
lastly, the appearances typical of _infective_ arthritis are also
represented. In addition, if we recall that _focal areas of rarefaction_,
indistinguishable from those met with in _gout_, also occur in all types
of _non-gouty_ arthritis, we at once see how impossible it is to detect
anything in the _radiographic_ findings distinctive of _gouty_ as opposed
to _non-gouty_ arthritides.

McClure and McCarty, comparing the radiographic changes in gouty as
opposed to _non-gouty_ arthritis, observe that, though _rarefactive foci_
occur in all varieties of _non-gouty_ arthritis, they are conjoined with
_other bony or joint changes_. On the other hand, _translucent_ areas
_unassociated with any bone or joint alterations_ have been found only
in _gout_. But whether this can be claimed as distinctive of _gouty
arthritis_ is, they think, uncertain, since relatively few opportunities
for X-ray examination of _non-gouty_ arthritis in its _early_ stages have
been forthcoming.

Continuing, of their four radiographic types of gouty arthritis the
second resembles osteoarthritis; but the third and especially the fourth
group, they consider, “fall into a peculiar class,” this inasmuch as
their characters resemble the _infective_ type of _non-gouty_ arthritis.
They claim, however, that a differentiation, radiographically speaking,
can be effected, this because of the “sharply localised” extreme
degree of bony atrophy which occurs in the infective type of non-gouty
arthritis. However, as they admit that radiographs of the latter
(infective non-gouty arthritis) have been noted which “closely resemble”
the “atrophic and proliferative changes occurring in gout,” their final
conclusion is that in the skiagrams even of typical gouty arthritis there
is nothing in the bony or arthritic changes that is _diagnostic_ of gout.

For myself, I must admit that I have come to the same conclusion as
McClure and McCarty, viz., that the skiagraphic findings in _gouty_ and
_non-gouty_ arthritis trench so much the one upon the characters of the
other that I should be loth indeed to base a diagnosis of gout simply
on the revelations of _skiagraphy_. The chief interest to my mind,
as I have previously observed, centres round those examples in which
_peri-articular tophi_ are associated with underlying bony and arthritic
changes (as revealed by X-rays) indistinguishable from those typical of
_infective_ arthritis of _non-gouty_ type.

We have seen also that _local foci of rarefaction_ may be met with in
_infective_ arthritis of _non-gouty_ type. Moreover, the _proliferative_
and marked _atrophic_ bony changes found in some instances of gouty
arthritis are quite compatible with their _infective_ origin. Witness
how impossible it is to differentiate skiagraphically between _atrophic_
arthritis and _gouty_ arthritis, and at the same time let it not be
forgotten, on the other hand, that the dividing line between the
_infective_ arthritides and the more acute forms of _atrophic_ or
rheumatoid arthritis is by no means sharply defined. Review this also in
light of the fact of the close resemblance that obtains between _acute
articular gout_, especially the polyarthritic variety, and types of
arthritis of avowedly _infective_ origin, and we see at once how close
is the clinical similitude. We turn to _radiography_, and here again
we are met with the same family resemblance, suggestive of a probable
community of origin. How clear then the inference that it is on _tophi_,
and tophi alone, that we must base an absolute diagnosis of _gouty_
arthritis. Moreover, since tophi are not detectable by _skiagraphy_, our
mainstay must be physical examination directed to their detection. As for
those cases of so-called “clinical gout,” viz., unattested by tophi, it
is probable that their absolute identification, as such, will never be
attainable on purely clinical, but on _bacteriological_, data, which, it
is to be hoped, will before long be forthcoming.


DIFFERENTIAL DIAGNOSIS

_Infective Arthritis._—According to Goldthwait, of Boston, no changes can
be detected by skiagraphy in bone or cartilage in infective arthritis.
The density of the former is in no way diminished, while the cartilage
retains its normal thickness. If, however, the infective arthritis is
of destructive character, new bone may be thrown out in the process
of repair. If then in such cases sole reliance be placed on the X-ray
appearances without any reference to the clinical history and course of
the disorder, then, as Goldthwait says, this irregular formation of bone
is likely to be confused with the X-ray findings in osteoarthritis. It
is, however, possible, according to him, to distinguish the nature of the
case by careful scrutiny of the skiagraphs.

The new formation of bone in these destructive forms of arthritis
conforms in every way to that seen as a result of _septic osteitis_ or
periostitis. In other words, the osteophytic outgrowths take origin at
the _focus of infection_, wherever that may be, and not, as in _gout_
and _osteoarthritis_, at the _margin of the cartilage_. Still one must
recollect that in gout _exostoses_ (Bruce’s nodes) develop sometimes at
the _sides_ of the phalanges. These outgrowths are not peculiar to gout,
but may be met with in _infective_ forms of arthritis. I am inclined
therefore to refer their origin to a local osteitis or periostitis of
infective source. That Bruce’s nodes, though not diagnostic of gout, are
frequently met with therein, is, I submit, but further evidence of the
intrusion of an _infective_ element in the genesis of _gouty arthritis_.

_Hypertrophic or Osteo-arthritis._—This is marked by proliferative
changes at the margins of the articular ends of the bones. With
the advance of the disease the shafts of the related bones become
increasingly dense. In _chronic gout_, too, the margins of the cartilages
may be studded with little nodules. Radiographically speaking, they
cannot be distinguished from those met with in osteoarthritis, save only
that they never attain the massive size met with in the latter disorder.
The diagnosis in doubtful cases will practically always rest on the
clinical history, and more pertinently on the presence of _tophi_.

_Rheumatoid or Atrophic Arthritis._—If the changes in the cartilage
and bone in osteoarthritis are active and proliferative, these same in
rheumatoid arthritis are retrograde and passive in character. In short,
hypertrophy of these structures in the former, atrophy in the latter,
constitute the distinguishing features.

The morbid process in the articular ends in rheumatoid arthritis is
one of rarefaction and softening. The cartilage may undergo total or
partial absorption, a change to be detected in the very early stages.
The bones participate in the pathological change, the first evidence of
which is an abnormal translucency to the rays, usually, but not always,
confined to that portion of the shaft entering into the joint. Eventually
the articular ends of the phalangeal and metacarpal bones may undergo
erosion, in some cases to a very marked degree, the bones more or less
telescoping into each other.

Now, owing to the fact that in _gout_ also considerable disintegration of
the bone may result, the appearances in some instances may resemble those
found in the skiagraphs of _rheumatoid_ joints. Stress has been laid
on this similarity by Strangeways, and it was also previously remarked
by Goldthwait. The latter, however, claims that while in _atrophic_ or
_rheumatoid_ arthritis the bone, though thin, maintains its outline, on
the other hand in _gout_ the outline of the bone is not distinguishable
owing to its more complete destruction by the morbid process. Goldthwait
holds that the resemblance of chronic articular gout to rheumatoid
arthritis is most noticeable when the _articular ends_ of the bone in
both instances are the seat of the disease. In other examples, however,
the _shafts_ of the bones being affected by the gouty disorder, they
may show punched-out areas. These latter, however, are but _focal areas
of rarefaction_ seen in profile, and inasmuch as they may be met with
in infective arthritides of non-gouty type, too much reliance cannot be
placed on their presence as distinctive of gout, much less as a criterion
of differentiation from other arthritides.

We have to remember, too, that marginal proliferative changes may occur
in rheumatoid arthritis. They are, like those met with in gout, miniature
replicas of the bony outgrowths of osteoarthritis.

In conclusion, the resemblance between the skiagrams of chronic gout
and rheumatoid arthritis is so close as absolutely to forbid our sole
reliance on skiagraphy to effect a differential diagnosis. In short,
skiagraphy, though of great and probably increasing value, cannot for one
moment be allowed to usurp the place of careful clinical observation, to
which it must be held always subsidiary. Last, but not least, pending
fresh radiographic revelations, our diagnosis of chronic articular
gout and alike its differentiation from rheumatoid arthritis and other
arthritides must rest on the one unimpugnable criterion, the presence of
_tophi_.




CHAPTER XXIV

IRREGULAR GOUT


“It is not a sacred disease. There will therefore be no profaneness in
handling it freely,” affirmed Benjamin Rush of gout some hundred years
since.

Nevertheless one approaches with diffidence this debatable ground, so
hedged in by high sanction and tradition. Albeit reverence for authority
must, in the interests of progress, be tempered by that spirit of
inquiring scepticism which would sift the chaff from the grain, this the
more emphatically in that of all morbid conditions “irregular” gout, by
the very vagueness of its clinical content, lends itself the more easily
to unbridled inference, hazardous conjecture, and fanciful surmise.

As for the unlicensed freedom too often exercised in relegating disorders
to this category, Rush would appear to have out-heroded Herod, _pace_
the following rhetorical reflections, for they could scarcely rank as
clinical observations. “The great toe and the joints of the hands and
feet are no more its exclusive seats,” said Rush, “than the stomach is
the throne of yellow fever. In short, gout may be compared to a monarch
whose empire is unlimited. The whole body crouches before it.... The
gout affects the glands and lymphatics. It produced a salivation of a
profuse nature in Major Pearce Buller, which continued for two days. It
produced a bubo in the groin in a citizen of Philadelphia. He had never
been infected with the venereal disease. Of course no suspicion was
entertained by me of its being derived from that cause.... Scrofula and
all the forms of dropsy are the effects in many cases of a disposition
of the gout to attack the lymphatic system.... A distressing collection
of air in the rectum, which renders frequent retirement from company
necessary to discharge it, is likewise a symptom of gout.”

It is difficult to conceive that any such pronouncement could have
emanated from a physician of Rush’s standing and repute, a contemporary,
be it noted, of Heberden, to whose masterly commentaries on the history
and cure of gout all posterity is indebted. Nevertheless as recently as
1854 Sir Spencer Wells claimed that “any attempt to describe the nervous
diseases of females caused by gout would lead to an enumeration of
almost all forms of their diseases, especially those usually considered
as hysteric. The intestinal derangements with tympanitis, neuralgia, or
colic, the hysteric pain in the right epigastrium, the cardialgia and
gastrodynia, the hysteric vomiting and epigastric spasms, the morbid
sensibility of the pharynx and fauces, hysterical palpitation, asthma
or bronchitis, loss or alteration of the voice, some forms of hysteric
paraplegia or hemiplegia more or less complete, chorea or tetanus,
some of the curious paroxysmal affections observed in hysteria, and
all the varieties of neuralgia and simulated inflammation, commonly
called hysteric, frequently arise from the presence in the blood of the
impurities which are the true characteristics of gout.”[43]

Truly, in light of this heavy indictment, one scarcely wonders that Rush
classed the domain of gout as limitless. But one must recollect that,
_nosologically_ speaking, our forefathers were sadly hampered. Anomalous
symptoms and disorders had to be referred to one or other of the
available titles of disease, and what term more elastic than the timeworn
“gout,” so easy to saddle with vicarious responsibilities?

But _pari passu_ with advancing knowledge of the pathology of the
_nervous_ system and the rise of _hysteria_ to the status of a clinical
entity gout was shorn of the excrescences heaped on it by Laycock, Wells,
and others.

But nevertheless the emancipation of gout from nervous and other alien
disorders was slow of achievement, and largely, I think, through the wide
acceptation of Murchison’s theory of a pathological state allied to gout
and termed by him “lithæmia,” or the “uric acid diathesis.”

According to this authority, the deposit of _lithates in the urine_ is
a “manifestation of a morbid condition of the blood and of the entire
system,” the outcome of a _functional derangement of the liver_. Such
hepatic disturbance might endure for years without manifesting any other
symptom than a frequent _deposition of urates_ and occasionally _uric
acid in the urine_. But, added Murchison, the same if neglected “may
ultimately be the means of developing gout.”

Clinically it manifested itself by a variety of symptoms—depression of
spirits, irritability, lethargy, headache, pains and aches in the limbs,
vertigo, insomnia, dyspepsia, palpitation, raised blood pressure. Such
were the motley group of disorders affiliated by Murchison to _lithæmia_.
But his disciples, more ardent, set no limit to the manifestations of
_uric-acidæmia_.

Not only gout, but _rheumatism_ and allied disorders, were amongst its
progeny, and Osler tells us that one writer enumerates not fewer than
thirty-nine separate morbid conditions associated with _lithæmia_. But
leaving aside the extravagant claims of Haig and his followers, the
impression even now is but too prevalent that _gout_ and _lithæmia_ are
convertible terms. There is little or nothing to justify the assumption
that an increased output of uric acid in the urine or deposition of
urates therein is diagnostic of gout. Such, moreover, presupposes the
further assumption that _uric acid_ is the _cause_ of gout.

We may affirm that certain symptoms betoken malassimilation of food or
defective tissue metabolism. But it is by no means certain, as Murchison
held, that a _functional disorder of the liver_ is the _fons et origo
mali_, much less that _uric acid_ is the sole noxious substance. Yet in
a masterly discussion of the subject Pratt, of Boston, tells us that as
recently as 1895 a “leading clinical teacher” affirmed that “headache,
migraine, depression of spirits, shooting pains, cramps, palpitation,
vertigo, are a part of the symptomatology of lithæmia.”

Surely, if we are to make any pretence of reducing the phenomena of
_lithæmia or irregular gout_ to a scientific precision worthy of the
present status of medicine, we should fight shy of such sweeping
assertions. The _caveat_, we fear, is not superfluous. For as that
judicial physician, Austin Flint, once satirically observed, “the
designation ‘uric acid diathesis’ is used by some physicians in a rather
indefinite way to describe various morbid states which may not at any
time be accompanied by deposits of urates, and in which there is no proof
of an excess of uric acid in the blood.”

Caustic as was this stricture, it was no less prophetic than apposite.
For recent _blood analyses_ have, as Pratt states, demonstrated that
there is _no increase of uric acid in the blood_ in that medley of
disorders attributed by Murchison and his followers to “lithæmia,” or
“the uric acid diathesis.” Here we would inveigh strongly against the too
prevalent habit of stigmatising as “gouty” such symptoms as headache,
vertigo, palpitation, etc., not only without any evidence of their
being of this nature, but frequently when no attempt has been made to
eliminate “errors of refraction,” aural disorder, etc. Moreover, granted
that such possible sources have been excluded, we have no justification
in invoking “gout.” For, as noted, all modern observations fail to
demonstrate the presence of _uricæmia_. Under such circumstances, given
that the anomalous symptoms are inexplicable, would it not be wiser to
content ourselves with the assumption that their presence postulates,
not lithæmia, but a _toxic condition of the blood plasma_? This at least
carries with it the inference that a search should be made for the focus
of toxic absorption, whereas for but too many the term _lithæmia_, even
when undemonstrated, is held to be self-explanatory and final.

Turning to another aspect of this subject, we are reminded by Duckworth
that Hutchinson “directed attention to various maladies affiliated with
what he terms rheumatic gout and gout, but differing somewhat from both,
and these include various eye troubles, such as iritis, hæmorrhagic
retinitis, and some forms of glaucoma, lumbago, sciatica, chronic
rheumatoid arthritis, Heberden’s nodes, and possibly hæmophilia.”

As to the so-called “gouty” origin of the various eye troubles, these
will be dealt with separately by Mr. Beaumont in his section. For the
rest, hæmophilia may, we think, be safely discarded, Heberden’s nodes
relegated to osteoarthritis, while rheumatoid arthritis has long since
vindicated its claim to clinical individuality.

But as to lumbago and sciatica, these cannot be so easily disposed of, as
a reflection of Heberden’s brings home to us. “It must be owned,” says
he, “that there are cases in which the criteria of both are so blended
together that it is not easy to determine whether the pain be gout or
rheumatism.” Our own attitude towards this vexed point was precisely
defined in a previous chapter in which we dealt with the affinities
between gout and other diseases.

Having dealt with the broader and more extravagant claims made on behalf
of the clinical content of _irregular gout_, we now restrict our purview
to those disorders, chiefly _visceral_ in site, which even to-day are
referred by some to this category. We shall in the first instance deal
with that variety known as retrocedent gout, and shall subsequently
proceed to discuss other so-called irregular manifestations of the
disorder.


RETROCEDENT GOUT

The term retrocedent or suppressed gout still lingers in medical
nomenclature, largely, we think, as a tribute to tradition, for rarely
indeed is it invoked in current literature. Known since the days of
Galen and Aretæus, it originally signified a condition in which sudden
_inhibition_ of the _acute joint affection_ is followed by or coincides
with the development of serious _internal_ symptoms referable either to
the gastro-intestinal, cardio-vascular, or nervous system. Thus, there
may be, _e.g._, vomiting, diarrhœa, dyspnœa, cardiac arrhythmia, cerebral
hæmorrhage, delirium or coma.

Naturally for our forefathers the abrupt subsidence of the joint disorder
with the incidence, as fulminant, of severe and alarming _visceral_
symptoms appeared to be an example of true _metastasis_. That death,
tragically sudden, so often ensued, but rendered more imperious the
necessity for explanation; and, in the then state of knowledge, the
proffered assumption could hardly be regarded as anything other than a
perfectly legitimate and useful hypothesis.

The retrocession of the articular affection in _acute_ examples of gout
ensues _abruptly_, but in chronic types it usually transpires more
gradually. Often no cause is assignable, but frequently the so-called
metastasis has followed exposure, chill, or the imprudent application
of cold to the inflamed joints. The late Dr. Parry, of Bath, in one
winter saw two instances of apoplexy follow “the removing of gout in
the extremities by immersing the feet affected in cold water.” In some,
following the same revulsive procedures, severe _cardiac_ pain has ensued
with syncopal attacks, sometimes fatal, while in others _gastro-enteric_
symptoms of like gravity have developed.

It is the _asthenic_ types of gout that, according to Duckworth, are most
prone to _metastasis_. When the phenomena occur rapidly, flitting from
place to place, they have been designated “flying gout.” Nevertheless, as
before said, the most dramatic examples arise in _acute sthenic gout_,
though in their instance less likely to occur spontaneously than in
sequence to depressing external agents, _e.g._, cold lotions, etc.

Reviewing the recorded examples of _retrocedent gout_ in the light of
latter day experience, it is, we think, most significant that no such
dramatic examples apparently occur nowadays, at least none to which the
term “_retrocedent gout_” appears applicable. The designation, indeed,
bids fair to become obsolete. What then is the explanation? That even
to-day cases of acute articular gout yield to, or are replaced by,
functional _visceral_ disturbances, of varying degrees of gravity, is
certainly true. But, partly through increase of knowledge and partly
through the growth of a more critical attitude, we seldom, if ever, feel
justified in ascribing them to _gouty metastasis_.

Take “gout in the stomach,” to which organ, in the days of the Regency,
it appeared to fly on the slightest pretext, a “vulgar belly-ache taking
rank by courtesy” as such, before Sir Thomas Watson pricked the bubble
of these pretentious ailments by his suggestion that “gout” (so called)
in the stomach sometimes turned out, under the test of an emetic, to
be nothing more than _pork_ in the stomach. A caustic stricture, but
doubtless well merited. For the symptoms held typical of “gout in the
stomach” are but those of _gastric irritation_, with nothing to suggest
that they are of “gouty” origin.

Again, as Brinton in his classic exposure of this clinical myth observes,
some of the recorded instances doubtless derive their melodramatic
aspects from unrecognised _biliary colic_. As he rightly says, some
of the cases instanced by Scudamore were jaundiced _usque ad unguem_.
Gallstones, too, are among the many derivatives of the so-called
“gouty” habit. The age incidence of both disorders is identical, whence
doubtless the conception of the relationship. But what of the abdominal
catastrophes attached to _gallstones_, all wholly unguessed at in
those days? What, too, of the unrecognised and doubtless frequently
coincident _renal_ disease, with its menace of _uræmia_—pain, vomiting
and prostration, not to mention Buzzard’s reflection that some cases of
gout in the stomach were probably referable to gastric “crises,” _i.e._,
_tabes dorsalis_?

If we recall that none of these sources of fallacy—and we have named but
the more common—were eliminated, and also the absence of any _anatomical_
proof _post mortem_ of gastric lesions, one may well ask with Brinton,
“Is there any ‘gout in the stomach’ left after the subtraction of
these various affections?” Personally, I can say with Brinton that “I
know of no such case; have never seen one; have never been able to get
trustworthy evidence of one from some of the most accomplished physicians
living, or from the best records.”

Reverting to the _cardiac_ and _cerebral_ phenomena that have sometimes
followed the _retrocession_ of acute gout, the same difficulties confront
us. The conclusion that they are examples of _retrocedent gout_ is drawn
from premises which really do not support it. Strictly speaking, there is
nought but the _time relation_ to go upon, and the laconic comment “Non
sequitur” is obvious.

To continue, the more we know of the causes and effects of disease,
the less relevant becomes the time relation, and the nearer do our
conceptions of cause and effect approximate to the more truly valid
conception of ground and consequence. But what _grounds_ have we for
assuming that the anginal, the syncopal attack, or the apoplexy is the
_consequence_ of gout, that it is exclusively due to the _materies morbi_
of gout?

The very disparity between the local lesions seems to exclude the
possibility of their being due to one and the same cause: in the joint,
acute _inflammation_; in the heart and brain, _degenerative_ changes.
Where then the nexus? Surely it is but a _time relation_, a coincidence,
the outcome of, _concurrent_ though _unrelated cardiac_ and _vascular_
lesions. In short, the cases of so-called retrocedent “cardiac”
and “cerebral” gout usually resolve themselves into _cardio-mural
degeneration_, _arterio-sclerosis_, or _renal disease_.


OTHER IRREGULAR MANIFESTATIONS

The more dramatic examples of retrocedent gout, as before stated, occur
mainly in the _acute_ varieties of the disorder. But the same visceral
metastases are occasionally linked up with the less severe articular
manifestations, or with that vague clinical entity known as “goutiness,”
the same being frequently known as “wandering” or “flying” gout. Most of
the examples met with in the present day belong to the last category.
This may possibly find its explanation in the growing infrequency of the
more acute or sthenic types of gout.

Both of the mild and of the severe forms of metastasis the same
pathological interpretation is hazarded. The gout is described as
“suppressed” or “retrocedent.” According to the former conception,
the gouty process itself suffers _inhibition_, while the latter term
signifies _deflection_ of the _materia peccans_ of gout from the joint
into the viscera. Of the twain the former hypothesis seems to me the
more plausible. Thus, given an acute gout at its inflammatory zenith, it
is conceivable that, if _abruptly checked_, the same might _reflexly_
precipitate the occurrence of internal lesions in structures undermined
by insidious and _pre-existing degenerative_ changes. In other words,
the aborted attack is not the cause, but the _occasion_, of the cardiac
failure, the apoplectic stroke, the uræmia, etc.

On the other hand, given that such were due to actual _transference_
of the gouty poison, one would expect that it would induce the same
_inflammatory_ phenomena in the viscera as in the joint. But there is no
_anatomical_ proof that such occurs, no evidence of an actual invasion of
the impeached viscus by the _gouty inflammation_. _Uratic deposits_ have,
it is true, been found _post mortem_ at the site of visceral lesions,
but, be it noted, generally in _degenerating_ tissue altered by other
morbid processes. Some, however, affirm that in such the gouty process
has _quâ_ the uratic deposits left, so to speak, its attestation behind
it.

But any _degenerative_ focus may in a _gouty_ subject become the seat of
such a _deposition_. Yet it would be presumptuous to infer its gouty
origin from this fact alone. Such are common in _chronic nephritis_, and
this apart from gout. What need for wonder then that the same should
occur in gouty subjects, with their blood surcharged with uric acid?

Were such uratic deposits located at the site of _inflammatory_ as
opposed to degenerative visceral foci, it would to our mind give more
colour to the assumption that they were the outcome of a true gouty
process; in other words, that, as in the joints, they were the _sequel_
or concomitant of _acute gouty inflammation_. But it is not so.

As for the structural or organic degenerations met with in gouty
subjects, very many, if not all, as Longstreth rightly says, “belong to
some one of the great general classes of tissue changes, some of which
are due to special causes, but the most of them own many causes. One of
these many causes can be under certain circumstances gout, but there is
really nothing special in the appearances by which we can unequivocally
pronounce them of gouty origin.” With this view few would join issue,
save only the reservation that the _scleroses_ so commonly met with in
_gout_, if due thereto, must owe their origin to some more vital agent
than _uric acid_, a few milligrammes more or less in the blood content
thereof.

It will be seen then that the _anatomical_ evidence that gout can affect
the _internal_ organs is wholly lacking. The criteria then upon which
the assumption is based that this or that functional disturbance is a
manifestation of irregular or _visceral_ gout are wholly _clinical_.

Doubtless the conception of irregular gout was derived from “the unaided
operation of custom.” Thus, when one clinical event, A, was noticed
frequently to precede another, B, the idea of an association between A
and B was generated, and by virtue of this association A was said to
be the cause of B. But obviously the fact that B has followed A does
not establish any necessary connection between the two clinical events.
In other words, the idea of a causal relation is in a sense a purely
intellectual feat, a clinical inference _presumptive_ and _retrospective_.

The evidence that a relationship exists between _irregular_ and
_regular_ manifestations of gout rests upon the following sequences and
alternations of clinical events:—

    (1) The subsidence or disappearance of functional visceral
    derangements following the development of articular gout;

    (2) Their occurrence directly after an articular paroxysm has
    been apparently suppressed;

    (3) Their recurrence and alternation with arthritic outbreaks,
    this in some instances repeatedly;

    (4) Lack of any appreciable cause for the functional
    derangements and their indefinite anomalous character;

    (5) Their favourable response to specific gouty therapy.

As before noted, _digestive_ troubles frequently precede the initial
outbreak of articular gout. The same likewise are frequent in chronic
cases between the intervals of arthritic seizures.

Now it has been customary to regard the _alimentary_ or other
disturbances that precede an initial _articular_ attack as “gouty,”
and likewise those that intervene between the gouty paroxysms in
long-standing cases. In other words, in light of the subsequent
_articular_ outburst, what was mysterious ceases to be a mystery. All the
vague “acidities, flatulencies, megrims, and biliousnesses, of whatever
occult kind,” are forthwith hailed as “gouty,” this merely upon the
ground of the _sequence_ of clinical events, because the symptoms have
disappeared from, _e.g._, the stomach to reveal themselves in the joint
or joints, or _vice versâ_.

Now my own view is that the antecedent hepatic or digestive disturbances
that so frequently precede initial attacks of gout are in all
probability, nay assuredly, _not_ gout. They should rather be regarded
as the _cause_, the foundation, of the malady than its effect, a
cause inoperative save in the presence of individuals victimised by
inherent morbid tissue potentialities. For similar symptoms are but
too common in the _non-gouty_. They are very common _antecedents_ of,
_e.g._, _rheumatoid or atrophic arthritis_. Nevertheless we do not when
the _arthritic_ disorder _subsequently_ manifests itself talk of the
preceding digestive disturbances as “rheumatoid” dyspepsia. Then why this
presumptive and retrospective diagnosis of similar prodromal phenomena
as “gouty” dyspepsia? For there is pending the articular outbreak
nothing distinctive in the digestive derangements, nothing that would
enable us to diagnose them as “gouty.” They might, for aught we know, be
significant of oncoming _rheumatoid arthritis_.

Now in the case of the latter we regard the _prodromal_ digestive
phenomena as probably indicative of some _infection_ located somewhere
in the _alimentary tract_. It would be wiser, I think, to adopt the
same attitude in regard to our “gouty” examples. Moreover, as we know,
such dyspeptic symptoms recur from time to time throughout the life
history of both rheumatoid and gouty arthritis. In the former disorder
we regard them as indicative of _recurring infection_, followed as they
so uniformly are by _exacerbations_ of the _joint_ trouble. Is it not
time we adopted the same attitude towards the _gastric_ or _hepatic
functional_ disorders that punctuate the course of _chronic gout_ with a
periodicity that rivals that of the articular paroxysms?

Unquestionably to my mind when we have regard to the extreme frequency
with which _local foci of infection_, _e.g._, oral sepsis, etc., are
found in gouty subjects, this would be the more rational attitude, the
one more in conformity with modern medical thought.

But if we would condemn those who, in the presence of unequivocal tokens
of gout, label _antecedent_ or _intercurrent dyspepsias_, etc., as
“gouty,” what are we to say of those that even in patients who have never
had _regular gout_ or exhibited _tophi_ yet presume to classify their
associated digestive troubles as “gouty”? This, I contend, is wholly
unjustifiable. I would say more, that such conjectures are hazardous in
the extreme, this both in the overtly gouty as well as in the non-gouty.
I recall the instance of an individual who suffered from classical
articular gout which palpably alternated with attacks of abdominal pain,
but the clue to the true nature of the latter symptoms, as revealed at
operation, was a _chronically inflamed appendix_. If so in this case,
how many so-called “gouty” acidities have resolved themselves into
_appendicular or gall-bladder dyspepsia_!

My conclusion then is that the _gastro-intestinal_ disorders attributed
to gout cannot legitimately be regarded as examples of _irregular gout_.
They should not be held “symptomatic” of, but _etiologically_ related to,
_gout_, a view more calculated to lead to exact diagnosis and rational
therapy, and incidentally to elucidate the true nature of gout.

In respect of other organs and the symptoms connected with them in
“gouty” persons the case is very much the same. Always and ever are we
confronted with the same difficulty, inability to determine whether
_antecedent_, _co-existing_, or _consecutive_ affections in certain
examples of gout, are not associated merely by _coincidence_.

Disturbed _cardiac_ action is not uncommon in gouty subjects,
_palpitation_ and _arrhythmia_ and _syncopal_ threatenings, and
frequently symptoms difficult of differentiation from true _angina
pectoris_.

I am reminded of an old physician whom I saw in consultation some years
ago, who suffered from alarming attacks of _precordial_ anxiety. He
was well on in the sixties, and very obese. He was convinced that his
cardiac irregularities, etc., were of _gouty_ origin, and often exclaimed
regretfully: “If I only dared to take two bottles of port, and got it
in my toe, all would be well.” He had never had an articular outbreak,
and based the diagnosis of his case on the fact that from time to time
his _urine_ for long since contained _excess of urates_. Having suffered
much of many physicians, he at last grew restive, took the bit between
his teeth, rushed to a spa, and forthwith embarked on a very strenuous
course of “waters and baths.” At once he got a severe attack of acute
polyarthritic gout, and _mirabile dictu_, all his cardiac troubles
straightway ceased.

Retrospectively viewed, many would regard the preceding cardiac condition
as of “gouty” source. That the old gentleman, of florid countenance,
plethoric build, and lethargic habit, was potentially “gouty,” there is
no doubt. But he was also abnormally fond, not of alcohol, but, curiously
enough, of sweetmeats and cakes of all sorts, hence “dyspeptic.” He had a
feebly acting heart, but no detectable _valvular_ lesion, though _mural
degeneration_ seemed likely. My own diagnosis was _flatulent dyspepsia
with secondary cardiac disturbance_, and finally _acute gout_, the
exciting cause of which, as I have so frequently seen, was a course of
_hydrotherapy_. The patient never regretted his venture, and, I am glad
to say, lived for some years.

Such cardiac paroxysms are not uncommon in the “gouty,” and, alarming
though they are, I question if purely _functional_ disturbances of
this nature ever prove fatal. As to the _valvular lesions_ and _mural
degenerations_ observed in the “gouty,” there is little or no evidence
that they are dependent on gout. Indeed, the lack of a tendency to
_endocarditis_ is one of the criteria distinguishing gout from acute
rheumatism. I note that in one textbook _pericarditis_ is classed
among the cardiac manifestations of irregular gout. But it must not
be forgotten that _renal_ disease, a frequent concomitant of gout,
predisposes to _pericarditis_, which, indeed, occurs in granular kidney
even when unassociated with gout.

As to the _respiratory organs_, such chronic maladies as _bronchitis_
and _asthma_ are very frequent in the “gouty,” but I question if they
are more so than in non-gouty subjects. In any case their symptomatology
and course are the same whether gout be present or not. Much, too, has
been made of the fact that _asthmatic_ and _arthritic_ manifestations
may _alternate_. But we must recollect that _asthma per se_ has a
_paroxysmal_ tendency; it has a tendency to _periodicity_ and a liability
to be excited or aggravated by much the same factors as favour outbreaks
of gout. It is said, too, that there is a “gouty” _pneumonia_, and that
the same has been replaced by an acute articular paroxysm. But, in
respect of all these alleged “gouty” respiratory disorders, would it not
be more scientific to cease talking of them as “gouty” and instead to
speak of them as bronchitis and asthma occurring in “gouty” subjects?
This, I may remark, is not to say that we should take no count of the
reigning diathesis in our _treatment_ of all associated affections.

Of the _nervous_ phenomena relegated to gout we hear nowadays less
and less. “Gouty” headaches are almost a thing of the past. The acute
“gouty” delirium of older writers in many cases was but an euphemism
for _alcoholism_, and likewise the _spinal paralyses_; while the
_convulsions_ and _comas_ were certainly almost always attributable to
_uræmia_. It would be held rash to-day to speak, like our forefathers, of
“gouty” _cystitis_, _urethritis_, or _orchitis_, for there is no evidence
of any pathological connection between them; and the same stricture is
also applicable to the many _cutaneous_ affections affiliated without
sound pretext to the _materies morbi_ of gout.

In the early part of the nineteenth century the French school were most
insistent on the prevalence and variety of the cutaneous manifestations
of _l’arthritisme_; but even by them the all-pervading influence of gout
in the etiology of skin disorders is no longer held even as a working
hypothesis.

_Conclusions._—The sum of my experience and reflections on so-called
“irregular” gout leads me to regard it as an “abstraction” rather than
as a proven clinical fact. Moreover, if I may judge by the “admission
certificates” to the Royal Mineral Water Hospital, Bath—a fair test,
as I maintain—many are of the same mind as myself, for during the past
ten years I do not recall a single instance in which a patient sought
admission thereto as suffering from “irregular” gout.

But some writers on gout—indeed, I think I may say all—whatever doubts
they entertain as to the propriety of retaining the term, yet qualify
their pronouncement in favour of some particular variety of anomalous
gout, _visceral_, _cutaneous_, or other. Still, in justification of my
own uncompromising attitude, I must say that dispassionate analysis of
their eclectic claims, in light of present day knowledge, to my mind
fails to show any adequate reason for the faith that is in them. Of some
of them I feel sure that sub-consciously they have been influenced by a
respect for tradition, forgetful of Pliny’s sentiment,—

    “Quamvis enim cedere auctoritati debeam, rectius
    tamen arbitror, in tanta re, ratione quam auctoritate
    superari.”—_Lib. i., Ep. 20._

But, to resume, this much at any rate may be affirmed, viz., that
there is no proof that visceral disturbances or cutaneous disorders
are due to _uric acid_. On the other hand, in view of my contention
that the inherent morbid potentialities of the “gouty” demand for their
fruition the intervention of an _infection_, the reader may rightly ask
whether the same agent may not be capable of evoking the _visceral_ or
_cutaneous_, as opposed to the arthritic, manifestations of gout.

Trousseau, a whole-hearted advocate of irregular gout, drew an analogy
between gout and syphilis. Somewhat contemptuously he observes: “To
those physicians in whose eyes localisation constitutes the particular
disease the differences in appearances are so many different diseases,
while to those who consider that the disease consists much more in the
aggregate of the general phenomena, in their evolution, in their progress
(and that, thank Heaven! is the direction in which sound observation
leads), these affections, differing in appearance, are only multiplied
expressions of the same species of morbid action. To the real physician
exostosis, alopecia, psoriasis, roseola, bubo, and chancre are always
syphilis—syphilis in different garbs.” In the same way he held that the
infinitely varied manifestations of _irregular_ gout were all affiliable
to one and the same morbid agent. He claimed, too, that visceral gout was
“the result of a sort of imperfect inflammation analogous to that which
manifests itself in the joints.”

Unfortunately for the cogency of the argument, there is no proof that
such visceral inflammations as do occur in the “gouty” are of gouty
origin. Unfortunately, too, the microbic agent that we postulate as
responsible for “gouty” _arthritis_ is as yet unisolated. If this
disability be removed, it might be found that the said organism was
capable of originating, not only the arthritic, but the alleged visceral,
forms of gout. But pending such discovery I am of opinion that the term
“visceral” gout should be abandoned, in other words that we should
cease to talk of, _e.g._, bronchitis, dyspepsia, etc., as “gouty,” and
should talk of them as bronchitis or dyspepsia occurring in the gouty.
In this way we may escape, or, better, render uncalled for, the scathing
criticism of Pye Smith:—“It has become common to ascribe bronchitis,
dyspepsia, gastralgia, iritis, gravel, cystitis, and even psoriasis to
the ‘gouty’ diathesis; but the evidence is very slight, and the ‘gout’
to which such evidence as there is applies is the distillation of morbid
humours which belong to a bygone pathology.... There is no reason to
believe that gout ever flies to the stomach, but over-indulgence at the
table may produce acute dyspepsia as well as inflammation of the great
toe. Elderly people are liable to gravel, gout and cough; and while
lead and drink may lead to gout and chronic Bright’s disease, cirrhotic
kidneys favour an attack of gout.”


INFANTILE GOUT

While subjects of gout have told me that they had had an attack in their
teens, I have never myself seen an instance. Still less can I claim to
have seen what I felt justified in calling “gout” in children. On the
other hand, if, as one authority states, “tonsillitis (quinsy), enlarged
tonsils, granular states of the pharynx, and catarrhal conditions of the
throat and respiratory mucous membranes are not infrequent expressions of
gouty inheritance in children,” then, of course, all of us must be quite
familiar with “infantile gout.”

But even this formidable list of legacies from gouty parents is eclipsed
by a more recent writer, J. Comby (1902), who, discussing “infantile
arthritism,” divides children coming of gouty stock into two types:
the “lymphatic” and “nervous.” The children of the former class suffer
from fleeting swelling of the lymphatic glands, rhino-pharyngitis,
tonsillitis, and, if they be girls, from chlorosis. Also they are given
markedly to tachycardia, bradycardia, and vasomotor ataxia. They are also
especially liable to asthma and the crises of dyspnœa, and pulmonary
congestion may alternate with urticarial and eczematous eruptions. Truly,
their lot is hard, for they fall a ready prey to colic, constipation, all
varieties of dyspepsia, not to mention nocturnal and diurnal enuresis!

Comby also claims that these gouty children are especially liable to
recurrent or _cyclical vomiting_. In this matter he is confirmed by J.
Thomson, who noted that these children not infrequently give a history
of having had asthma, urticaria, eczema, stammering, and other nervous
complaints, also that in many instances _uric acid crystals_ or a copious
deposit of _urates_ have been noted in their urine.

As to the “nervous” type, they labour with insomnia, night terrors,
convulsions, and when older with migraine. To these liabilities must
be added undue proneness to acne, seborrhœa, psoriasis, chilblains,
angio-neurotic œdema, urticaria, etc., not to mention muscular and joint
aches and pains.

Whether this medley of distempers can with any pretensions to scientific
reason be affiliated to a gouty heritage, or whether they can be regarded
as expressions of a budding “gouty diathesis,” is, I submit, of the
nature of pure speculation. That the child who suffers with cyclical
vomiting may show uric acid crystals or urates in his urine is certainly
no proof that he has inherited gout, much less that he is actually
“gouty.” In uro-lithiasis the uric acid is precipitated in the urinary
passages, viz., strictly speaking, _outside_ the body, whereas in _gout_
the pathological error originates _within_ the organism. More apposite is
Uffenheimer’s observation, previously noted, that children of this type
suffer the same disturbances of _purin_ metabolism as are met with in
adult gouty subjects.

If the fact is confirmed that the _output of exogenous purin_ in such
children is _diminished_ or _retarded_, it would certainly be a most
interesting finding, possibly with a now unguessed-at significance. But
we should recall that even in the subjects of _regular_ gout such is _not
invariable_, and, moreover, occurs in diseases other than gout. Pending
further exact investigations I think it would be wiser not to indulge in
such vast generalisations, mindful of the sentiments expressed by the
illustrious Sydenham in his letter to Dr. Gould:—

    “I have bin very careful to write nothing but what was the
    product of careful observation. So when the scandall of my
    person shall be layd aside in my grave it will appear that I
    neither suffered myselfe to be deceived by indulging in idle
    speculations nor have deceived others by obtruding anything to
    them but downright matter of fact.”




CHAPTER XXV

OCULAR DISEASE IN THE GOUTY

BY W. M. BEAUMONT


With the passing of Jonathan Hutchinson disappeared the premier British
exponent of _l’arthritisme_, that generic term so attractive to our
French _confrères_. Whether gout and rheumatism are branches of one
common stem need not detain us, for it is an abstraction more suitable
to the philosophic age of medicine before pathology emerged as an exact
science. Be this as it may, there has been in the past, and there still
remains in the present, as a bond of union, a universal belief that both
are subtle causes of disease of the eye. But the age of hypothesis is
giving place to the era of facts, and we find in recent writings a more
cautious expression of individual opinion, a less dogmatic positivism
regarding the relationship of gout and rheumatism to ocular disease.

In referring to modern text-books we find Parsons[44] describes gout as
one of the “alleged causes” of iritis. In rheumatic iritis he states that
the patients “are often gouty.” The gouty nature of iritis is indicated
by the similarity of onset of some cases of iritis with that of gout.
“Iritis in an elderly patient is likely to be gouty, often starting
suddenly in the night and sometimes ushering in an attack of gouty
arthritis.” In episcleritis “rheumatism and gout are commonly indicated
as the chief causes.”

Werner[45] includes gout in a list of disorders of metabolism which
produce iritis “by means of toxins of a chemical nature.”

Sim[46] considers that iritis occurs in gout “as the result of some toxic
influence”; and in addition he says, “Iritis is to be met with in gout.”

These authors express accurately, I think, the present views with regard
to gout as it affects the eye; with each there is a tone of restraint
and suggestion rather than of boldness and assertion, and the contrast
to Hutchinson’s emphasis is noteworthy: “I believe,” he tells us, “that
iritis due to the arthritic diathesis is a common malady.”

Among the many and indiscriminate diseases of the eye which have been
considered to be due to gout are included blepharitis, conjunctivitis,
episcleritis, scleritis, orbital cellulitis, neuro-retinitis,
retro-bulbar neuritis, optic neuritis, optic atrophy, iritis, cyclitis,
choroiditis, glaucoma and retinal hæmorrhage. Truly an all-embracing
rather than an eclectic list, a medley of diseases without any melody.

_Evidence of Gout in the Eye._—When we inquire what is the evidence which
justifies the belief that gout causes ocular disease we find little more
than a traditional hypothesis inherited in a long line of succession
from the Fathers of Medicine. Nevertheless the opinion that there is a
connection is widespread, not only in Europe, but also in America.

In considering this relationship we cannot overlook the effects of the
diathesis on other viscera. How in these is a diagnosis of gouty origin
arrived at? It would appear that the assumption of an irregular form of
gout is based upon the following observations:—

    (i.) That it sometimes happens that an undoubted attack of
    articular gout aborts and is followed by symptoms referable
    to a grave visceral disorder, _e.g._, gout in the stomach
    (retrocedent gout);

    (ii.) That sometimes the converse occurs, viz., that an attack
    of visceral disorder may suddenly be replaced by an acute
    articular manifestation;

    (iii.) That such visceral derangements may alternate, not
    only with articular, but also with other, such as cutaneous,
    outbreaks;

    (iv.) That eye disease has been known to wax and wane in unison
    with concurrent arthritic gouty manifestations;

    (v.) That occasionally in gouty people an attack of iritis of
    sudden onset in the night has been followed by remission of the
    symptoms in the day[47];

    (vi.) That visceral symptoms in the gouty are anomalous and
    inexplicable on any other basis;

    (vii.) That the treatment usually advocated for gout has a
    favourable influence.

_Deposition of Urates._—Two cases are recorded by Garrod in which there
was a deposit of urates in the sclera. These instances do not appear
to have been confirmed by other observers, and they may be regarded as
exceptional cases, occurring, it should be noted, in the outer envelope
of the eye. But though these tophaceous deposits may occur in the sclera
and in the eyelid, they have never been known to invade the intrinsic
structures, such as the iris or ocular media. The eye, in fact, is on all
fours with the sites of urates elsewhere—deposition occurs in parts of
relatively low vitality.

Although urates are not found within the eye, there is in other morbid
ocular conditions quite frequently a deposition of foreign matter, such
as alien crystals, of varied description. For instance:—

In the _sclera_ on rare occasions we find osteomatous degeneration.

In the _choroid_ there may be true bone which forms a cup so extensive
that it can be felt by the finger, or, again, there may be calcareous
plaques.

The _retina_ may undergo colloidal changes or be the site of carbonate of
lime or of cholesterin.

The _vitreous_ may sparkle with showers of cholesterin.

The _lens_ may contain both tyrosine and cholesterin.

The _aqueous_ shows similar crystals.

In the _iris_ degenerative calcareous or osseous deposits are
occasionally seen.

The _cornea_ may be affected by hyaline degeneration with deposition of
lime salts.

The _conjunctiva_ may be calcareous.

In all these cases the foreign particles, whether crystals or otherwise,
are usually the retrogressive changes of senescence proclaiming that the
forces which make for degeneration are more potent than those which make
for regeneration.

But _urates_ are not found _in_ the eye, even though the patient is
gouty. On the other hand, both in gouty joints and in other similarly
affected parts of the body we find a deposition of urate of soda.

_Gouty Diathesis._—From the days of Sydenham—himself a martyr to
gout—diathesis has been a name to conjure with, and an all-sufficient
diagnosis. In the podagrous patient any intercurrent disorder, any
inexplicable ache or pain, was ascribed to gout, and patient and doctor
were alike satisfied. “Tempora mutantur,” but still we are prone to call
morbid conditions gouty when they occur in gouty people.

If we accept the theory that gout is due to an excess of uric acid in the
blood, the view which I have expressed elsewhere[48] that gout does not
cause iritis is directly challenged. For if it be granted that a sudden
outpouring of so non-toxic an acid _causes_ an acute inflammation—for
instance, in the synovia of the great toe—why should not our faith
incline us to go further and find in this malevolent, though bland, acid
a source of inflammation affecting the fibro-muscular meshwork of the
iris?

If, however, we adopt the infective theory, then the association of
the uratic deposits no longer dominates our creed—we view them as mere
clinkers and by-products erupted from the furnace.

The infective theory of gout also lends plausibility to an association
with iritis, for this latter is a disease of infective origin. For the
intimate relationship of all forms of asthenic arthritis with iritis is
of very frequent occurrence, but is practically never seen in the more
sthenic arthritides: rheumatic fever, acute gout and traumatic arthritis.

Nearly fifty years ago Jonathan Hutchinson drew up a “Report on the Forms
of Eye Disease which occur in connection with Rheumatism and Gout.”[49]

At the present day it is not easy to differentiate his 117 cases
according to modern classification, but he includes gout, rheumatism,
rheumatic arthritis, etc. The differential diagnosis between gout and
rheumatism was simplified by the creation of a mule—“rheumatic gout”—and
upon its back were packed the doubtful cases.

Hutchinson’s views regarding the essential difference between gout
and rheumatism are crystallised in his statement that in rheumatism
there is an arthritic susceptibility to weather, in gout an arthritic
susceptibility to diet.

Osteoarthritis also seems to have been included as one of the gouty
diseases, probably because _post-mortem_ examination revealed uratic
deposits in the disorganised cartilage. This, however, would appear to
be an epi-phenomenon, and must not be allowed to obscure the essential
distinction between true gout and osteoarthritis. It is a sign of
articular disorganisation of _long standing_, and is the homologue of the
similar deposition of crystals, etc., already referred to as occurring in
the eye as the result of chronic disease therein.

_The significance of tophi_, as the touch-marks of gout, is undoubted,
but even if they are detected in the eyelids or elsewhere, we are skating
on thin ice if we rashly declare that a coexisting intra-ocular disorder
is gouty. Most forms of iritis betray the same clinical _facies_,
although the etiological causes are diverse. But in none do we find any
appearances pathognomonic of gout.

The argument that because a patient has tophi therefore the iritis
is also gouty does not hold good, for gout does not confer immunity
from other diseases, and even though we cannot prove an alibi for the
diathesis, we can often in these cases also indict gonorrhœa, pyorrhœa or
some other pathogenic agent.

The favourite site for tophi is one in which blood-vessels are sparse;
but, although the cornea is void, imbibition of blood from the marginal
looped plexus of capillaries and an abundant lymph supply provide amply
for nutrition, and tophi are not found in this locality. The sclerotic,
however, has a meagre supply of vessels, and for some unexplained reason
tophi rarely invade it. In the eyelids, on the other hand, possibly from
the cartilage being rich in sodium, tophi are occasionally seen. If we
accept the tophus as the one unequivocal criterion of gout, we are not
justified in labelling an iritis as gouty in its absence. If we do,
our diagnosis is presumptuous and not absolute. Strictly speaking, the
diagnosis cannot be made. We may the more readily admit our limitations,
inasmuch as they are a blessing in disguise, and suggest a further
etiological search.

In Hutchinson’s list of eye diseases which occur in association with
rheumatism and gout there is a history of gonorrhœa in twenty-six cases,
syphilis in seventeen, of both gonorrhœa and syphilis in six. Herpes
occurred in two, pustular acne in one, eczema in one, albuminuria in
one, ague in one. Bad teeth are reported in two. In all the total was
fifty-seven cases out of 117 (48·7 per cent.) in which there was a
possible source of infection. It is probable that this percentage would
have been materially increased if at that time it had been recognised how
great is the influence of pyorrhœa and other sources of infection in the
etiology of irido-cyclitis.

With regard to all infections it is only in the present day that full
advantage is taken of bio-chemical and bacteriological methods of
differentiation. How frequently the true origin of disease must have been
overlooked when the pallid spirochæte was unknown, when the Wassermann
test was not applied, and when the complement fixation test for gonorrhœa
was not recognised.

With regard to a combined cause it has been maintained that gonorrhœa
is always more severe in the gouty than in other people, and it may
be that the more intense the gonorrhœa the more likely may it be to
produce constitutional symptoms, of which iritis is one. In all such the
combination of gout and iritis would indelibly impress upon the mind
of the surgeon the intimate association of joint and eye. It was long
ago recognised that many forms of joint disorder were associated with
iritis, and, as the cause of the arthritis was not always gout, Mackenzie
introduced the generalisation “arthritic iritis.” “Not being able,”
he tells us,[50] “to determine the diathesis which predisposes to this
ophthalmia” (iritis), “I use _arthritic_ as a conventional term, without
adopting it in the strict sense of gouty.” The expression is well worthy
of retention for the reason that it warns us to be prepared for an attack
of iritis in many forms of arthritis and arthralgia.

In the following articular diseases the triad joint, muscle and nerve
disorders is not uncommonly linked with iritis:—

    Tuberculous arthritis;
    Syphilitic arthritis;
    Gonococcal arthritis;
    Certain forms of specific arthritis: malarial, dysenteric, etc.;
    Infective arthritis of undifferentiated type, as yet unaffiliated to
      specific germs.

In the following forms of arthritis iritis is less common:—

    Acute articular rheumatism;
    Acute gout;
    Osteoarthritis (hypertrophic);
    Rheumatoid arthritis (atrophic).

Iritis occurring in these last suggests the possibility of error in the
diagnosis of the putative parent disease. Especially is the clinical
similarity of gonorrhœal (polyarticular) rheumatism to rheumatoid
arthritis to be borne in mind.

_The Relative Incidence of Iritis._—In the text-books it is often stated
that the syphilitic form of iritis is the one most frequently met with,
and that gouty iritis, if it is met with at all, is much more rare. But
in these comparative statements we have no clue to the frequency of
iritis with syphilis, nor of iritis with gout. For a true analogy we do
not want the syphilographer to tell us the aggregate number of cases of
iritis that he has seen, but what is the percentage of cases of syphilis
in which iritis occurs, and we want the gout physician to state his
percentage of iritides in gout, or, negatively, what is the percentage of
cases in which iritis does not occur.

If gout is a more prevalent disease than syphilis, it does not follow
that “gouty” cases of iritis will be more numerous than those due to
syphilis. Let us suppose, for the sake of clearness, that 1 per cent.
of people suffering from gout get iritis, and that also 1 per cent. of
people infected by syphilis get iritis, and that in a certain town there
are two hundred people who are gouty and one hundred people who are
syphilitic. It is probable that there will be two persons suffering from
gouty iritis (always supposing there is such a disease), but only one
from syphilitic iritis. The absolute totals will differ, but the relative
will be identical. It is clear, then, that infectivity cannot be gauged
by the statistical enumeration of the consulting-room. Gout is a rarer
disease than our patients would have us believe, but accepting their
views, even then we should expect to see more cases of iritis caused
by it, if such existed; we should expect to find more definite proof
of a causal connection, and less frequently a history of gonorrhœa, of
pyorrhœa, and of syphilis.

_No Uratosis, no Gout._—If we pin our faith to the equation

    Hyperuricæmia + Uratosis = Gout,

we can at once exclude all cases of ocular disease as gouty in the
absence of either factor. According to Garrod, “true gouty inflammation
is _always_ accompanied with a deposit of urate of soda in the inflamed
part.” We should therefore expect that uratosis would occur _in situ_
if an iritis were gouty. But it does not: the touch-mark is absent, and
there are no chemical, pathological or clinical signs of urates in the
iris after the inflammation has subsided. What then is the alternative?
Either Garrod’s aphorism is inaccurate or iritis is never gouty. In other
words, we must postulate that an iritis may be regarded as gouty without
uratic deposits. If this be the case, the so-called gouty iritis may well
rank with the occult migraines, flatulencies and acidities which are
termed irregular, suppressed or latent gout. Strictly then it would be a
latent gouty iritis fit to rank with that last refuge of the uric acid
enthusiasts, the “latent nephritis” which they worship as the _fons et
origo mali_ of gout.

_Metastasis._—The predilection of the gonococcus for synovial membranes
is seen not only secondarily to urethral infections, but also in
ophthalmia neonatorum, in which the joints of infants are affected
sequentially to the eyes.[51]

The gonococcus also has been found in cases of peritonitis, pleurisy,
pericarditis, etc., but it is said to have only once been isolated in the
eye in iritis.[52]

It is not only the gonococcus which can initiate a metastasis from the
eye to the joints, to the peritoneum, or elsewhere. The same process
may be started by the _bacillus typhosus_, by the streptococcus of
erysipelas, and by that of puerperal septicæmia.

De Grandmont[53] records the case of a young man recovering from typhoid,
complicated with jaundice and nephritis, who was attacked by iritis with
posterior synechiæ and hypopyon. Paracentesis was done, and the pus of
the anterior chamber was transferred to agar-agar. Two days later a pure
culture was obtained presenting all the reactions and characteristics of
the bacillus of Eberth. Of this culture a small quantity was injected
into the vitreous of a rabbit. A month later the rabbit was killed, when
the liver and intestines were found to be infiltrated with the same
bacillus of Eberth.

_In erysipelas_ de Grandmont has seen a hyalitis from which a culture was
grown on gelatine that presented all the morphological characteristics of
erysipelas.

He has also met with a case of hyalitis associated with puerperal
septicæmia, and he has no doubt that it was the result of a similar
microbic invasion of the vitreous.

Gout does not render patients immune from tuberculous, syphilitic or
gonococcal disease, and when in such so-called diathetic stocks an iritis
occurs, especially in gonorrhœa, years after the primary disease, it is
probable that gout, rather than lues, will be assigned as the cause.

The local appearances of iritis are identical in gonococcal and other
infective iritides; they resemble clinically those seen in syphilis and
tubercle except that in these there are sometimes condylomata of the iris
in the one and tuberculous nodules in the other. To be comparable a gouty
iritis should be characterised by iritic tophi.

_“Arthritic” Iritis._—Forty-eight is a large percentage in Hutchinson’s
cases of ocular disease associated with gout and rheumatism, and it is
justifiable to assume that there was something more than coincidence
in the triple _entente_ of diathesis, arthritis and iritis. But the
fact that the poisons of syphilis and gonorrhœa, etc., are potent
causes of iritis is indisputable, and therefore the patients might have
suffered from it even if they had never had either gout or “rheumatism.”
Consequently these articular diseases are both superabundant and
superfluous, and they may have no etiological status. A patient afflicted
with arthritis is very susceptible to an associated attack of iritis
provided that there is a septic focus anywhere in the body.

A practical point to remember, especially in gonorrhœa, is that the
onset of joint trouble should warn us to anticipate the possibility of
an associated iritis and should prompt us to instil atropine at an early
stage. We should forestall the disease by treating the suspicion. The
frequency with which gonorrhœa is followed sooner or later by iritis
entitles this ocular phenomenon to be considered a secondary symptom of
gonorrhœa, as it is of syphilis.

Before the potency of distant infective foci (for example, in nasal
disorders, pyorrhœa, sinusitis, etc.) to produce ocular disease was
recognised, there was justification for the inclusion of a so-called
idiopathic iritis, but it is seldom now that we have to be satisfied
with this negative diagnosis. Nevertheless the assignment of a toxæmic
etiology must be based on a definitely ascertained focus of toxic
absorption, or failing this, at least on symptoms of general malaise
which render such a focus highly probable.

_Frequency a Factor in Diagnosis._—It was known a century before the
birth of bacteriology that gonorrhœa caused iritis. It was also noted
that certain constitutional symptoms occurred in syphilis, and that among
them not infrequently iritis was one. Observation and deduction was the
process with our forefathers, and it seldom led them astray.

If in any sequence of events cause and effect are to be established when
there is no obvious proof of connection, we may have to be content with
an empirical diagnosis, and this was the position before the discoveries
of bacteriology enabled us to place the etiology of iritis on a firm
basis. How then did our ancestors know that syphilis and gonorrhœa caused
iritis? Was it not—

    (1) _That the frequency of the association was the essence of
    the diagnosis_,

    (2) _That there was absence of any other recognised cause_, and

    (3) _In the former disease the effect of anti-syphilitic
    therapy_?

Applying these rules to gout, we find—

    (1) _No marked frequency of association of ocular disease and
    gout_,

    (2) _That when iritis does occur there is often some other
    possible source of origin_, and

    (3) _That anti-gout treatment has only a doubtfully beneficial
    effect_.

_“Gouty” Iritis is not a Clinical Entity._—Before a symptom or affection
can be classed as secondary to a primary disease there must be evidence
of a connection stronger than _post hoc, ergo propter hoc_. For instance,
in syphilis an iritis _frequently_ follows which may be of the specific
condylomatous type, and a laboratory examination of the inflamed iris
may demonstrate the presence of the spirochæte. On the other hand, an
iritis occurring in a gouty patient is indistinguishable from that form
which results from infections of undifferentiated type. Moreover, iritis
so _seldom_ occurs associated with gout, and when it does there are so
often present other well-recognised possible causes, such as pyorrhœa or
gonorrhœa, that the doubt about the paternal relationship of gout to the
iritis is overwhelmingly strong.

In the following table a comparison is made between types of iritis:—

IRITIS.

  -----------------+-------+--------------+------------------+---------
                   | Gout. |  Syphilis.   |     Tubercle.    |Toxæmia.
  -----------------+-------+--------------+------------------+---------
  Pathognomonic    |   0   |Gumma of iris.|Tubercles of iris.| 0
  symptoms.        |       |              |                  |
  -----------------+-------+--------------+------------------+---------

If pathognomonic symptoms were always present the differentiation of the
various causes of iritis would be less difficult. But this is not the
case, and consequently, whatever the primary cause, the appearances of
the iritis, in spite of the pathogenesis, objectively resemble each other
in very many instances.[54]

Medical authorities call certain cases (not varieties) of iritis gouty;
they are content to rest the diagnosis on the ground that they occur
in gouty people. Yet there is not a single _ocular_ symptom which
differentiates the disease from a similar one in _non-gouty_ subjects.
Before the dogma can be accepted that because a gouty man has iritis it
is therefore a gouty iritis and, like the poet’s primrose, nothing more,
it must be shown that irido-cyclitis is proportionately more frequent
in people who are gouty than in those who are not. Even then it is
suggestive, but not conclusive, for it is conceivable that, although gout
is not strictly the cause, yet it may so reduce the resisting power of
the iris that it becomes a readier prey to some lurking organism.

It is commonly reported that the existence of a gouty diathesis gives to
any inflammatory condition of traumatic origin—synovitis, for instance—a
special tendency to chronicity, and I would not deny that it may have the
same influence in the case of iritis of traumatic endogenous origin.

If then a gouty man is not immune from other possible causes of iritis,
one of these, and not gout, may be responsible for it. Especially is a
gouty diagnosis doubtful when there is a focus of suppuration in the
tonsils, teeth or elsewhere. Also the prolonged hibernation of the
gonococcus, for many years after the attack of gonorrhœa, is apt to
be overlooked. The presence of excess of uric acid in the blood, which
sometimes occurs in these patients, may mislead us into the belief
that we have a true gouty iritis to deal with. But even although it is
ascertained that a hyperuricæmia of 4-8 mg. of uric acid is present, it
is no proof that the co-existing iritis is necessarily gouty. We might
have an even higher content of uric acid in the blood in leukæmia, and
yet no iritis be present. It may be admitted that on rare occasions
iritis occurs in leukæmia, but no one suggests that the leukæmia or the
associated iritis is due to uric acid toxæmia. We should be on infinitely
surer ground if not uricæmia, but uratosis, were present. We could then,
at any rate, confidently assert that, whatever the origin of the iritis,
it had supervened in a subject of gouty habit. I do not think that we,
as clinical observers of iritis, should go further than to say: “The man
is gouty; his iris is inflamed.” Here in Bath, among hecatombs of gouty
people, irido-cyclitis is one of the rarer associated diseases requiring
treatment. When it does occur it is usually of obviously septic genesis
rather than of gouty origin.

Contrasting gonorrhœa with gout, we find in the former when there is
systemic infection, as shown by arthritic complications, there may be
also iritis, so often, in fact, that it is legitimate to bracket it as
a related symptom. It is a toxæmic condition in which we rely on the
_frequency_ of the combination to diagnose the cause.

In writing on iritis in 1908,[55] I referred to the rarity of the
association of gout and iritis. In an analysis of 17,197 cases of
“rheumatism” and rheumatoid arthritis occurring at the Royal Mineral
Water Hospital, Bath, in twenty years, there were twenty patients who
suffered from acute or subacute iritis. During the same period there
were 2,159 gouty patients not one of whom had iritis. In a special
hospital it is possible that the diagnosis of gout might be limited by
a stricter nosological differentiation than occurs in private practice.
It is, moreover, not uncommon for ophthalmic surgeons to see patients
who call themselves gouty, or who say that their doctors have told them
that they are, and yet on examination no corroboration is found, no
clinical outbreak, or, more pertinent, no tophi. They come to us with an
attribution of iritis to gout without the filmiest shadow of evidence.

In considering the correlation of cause and effect it not infrequently
happens that we find no obvious connection between the one and the other.
In syphilis, for instance, alopecia is a usual secondary symptom, and we
rely on the frequency of the sequence to satisfy ourselves that it is
no mere coincidence. If it could be shown that alopecia did not occur
more frequently in syphilitic people than in non-syphilitic we might
justly doubt the connection. The same reasoning may be applied to iritis
and gout: the association is so rare that it is negligible. To justify
a causal connection between diseases the possibility of a fortuitous
concurrence must be excluded, for when the double event occurs only very
exceptionally, it is difficult to exclude the long arm of coincidence.

A man has iritis and tophi; _ergo_ we say he has gouty iritis. But why?
They co-exist, it is true, but where is the link of attachment of cause
and effect? How different is our attitude if we know in another case that
our tophaceous iritic patient has gonorrhœa. We then say, gonorrhœal
iritis in a gouty subject. Would it not also in the first case be more
scientific if we frankly confessed that it was an infective iritis of
undifferentiated type occurring in a person of gouty diathesis?

In considering the iritides in relation to gout there are two types which
demand our attention. With the possible exception of traumatic iritis,
this grouping embraces all the etiological varieties of the affection.
In the first are those cases which are due to specific infection,
such as syphilis, gonorrhœa and tuberculosis. In the second are those
infections of undifferentiated type in which the causal germ has not
yet been isolated. Now clearly we must read the latter in the light of
their analogues, the specific iritides. In them the modes of onset, the
clinical course, are duplicated, presenting similar variations, and they
are doubtless the reflexes of the varying grades of intensity of the
causal organism.

Concussion iritis would fall into line, for it is possible in this case
that the iris is rendered a _pars minoris resistentiæ_ by the blow, and
that the iritis which follows is due to a cryptic focus, it may be in
the gastro-intestinal tract or elsewhere. The chief sources of iritis
are syphilis, gonorrhœa, tubercle and infections from undifferentiated
organisms of low grade. If these said iritides occur in a person of
gouty diathesis they are unmodified by it clinically or pathologically,
macroscopically or microscopically, save possibly in the direction of
chronicity—a result, it may be, of those inherent peculiarities of tissue
metabolism ingrained in a gouty subject, and in which presumably the iris
shares.

And that which has been said of iritis in the gouty applies equally
to other forms of so-called gouty ocular manifestations. There are no
statistics available to show that there is any differential frequency
in those who are gouty compared with those who are not. Authors have
laboriously recorded cases of eye diseases which have waxed and waned
in unison with podagrous toes, but the publication of these cases is in
itself a confession of the rarity of the coincidence, a rarity which
destroys the authenticity of any communal kinship. Coincidence is merely
another name for the rigid and immutable law of chance, for a cycle of
events which occurs with irregular regularity. If it could be shown that
a diet rich in purins brought on an attack of ocular disease in gouty
people, and if the experiment could be repeated with a similar result and
sufficiently often to exclude all probability of coincidence, scepticism
would no longer be justified. But until more definite evidence is
forthcoming “gout” in the eye is nebulous.

In attempting to define the relationship of gout to ocular disease, there
is one author to whose opinion we turn with the respect due to a master.
Garrod’s judicial summing up supports the view that there is a connection
between gout and ocular disease, but his cautious statement seems to
imply that the affection of the eye is modified by rather than due to
gout. His statement is as follows[56]:—

    “_Gout of the Eye._—A form of ophthalmia connected with gout
    has long been recognised, and appears to be tolerably well
    established, but as rheumatic inflammation of the eyes is
    equally allowed to exist, difficulties may at once arise in the
    diagnosis. I have witnessed many cases in which conjunctivitis
    and sclerotitis appeared to be distinctly connected with the
    gouty diathesis, and in two cases there existed deposits of
    urates on the surface; gouty iritis also occasionally occurs.
    I once saw a case of acute inflammation of the sclerotic coat
    and iris which supervened a few days after the operation for
    cataract in a gouty subject. By active treatment the disease
    was arrested, but distinct articular gout soon manifested
    itself.

    “Our information on this subject may be thus summed up:
    patients having a well-marked gouty diathesis now and then
    experience attacks of inflammation of the different structures
    of the eye; and it is important to bear in mind the fact that
    the state of the habit considerably modifies and keeps up such
    affections, and also that treatment directed to the gouty
    condition of the system proves very effectual in curing the
    local mischief.”

It will be observed that Garrod tells us that his two important cases
of sclerotitis “appeared to be distinctly connected with the gouty
diathesis.” With the reticence of the careful and accurate observer,
he does not say they were due to it even though there were deposits
of urates on the surface. He would seem to recognise that cases
of sclerotitis with uratic deposits were unusual events, and that
generalisations cannot be based upon exceptional cases. A gouty man is
gouty to his innermost cells, and the eye, like every other part of the
body, is a potential uratic site. We must grant therefore that the course
of an iritis, however caused, may be influenced, though not necessarily
dominated, by the diathesis. Consequently it may be necessary that cases
of iritis of undoubted gonococcal or other infective source occurring
in gouty people should be treated by iodides, salicylates, atophan or
colchicum.

From the academic point of view ocular gout may exist, but from the
practical point we should invariably seek, and we shall probably find,
some still more important source of infection requiring treatment.

_Ocular Symptoms in Hyperuricæmia._—The popular view that gout depends
upon uricæmia is so generally accepted that the expressions “uric
acid diathesis” and “gouty diathesis” are tantamount to tautology.
Nevertheless they are different, the first postulating the supposed
cause, the second the inferred result. There is a commingling of cause
and effect. Uricæmia is a normal condition of the blood, but in certain
diseases—gout, leukæmia, plumbism, pneumonia, etc.—a considerable excess
of urates is found. No form of ocular disease is included as an associate
of hyperuricæmia unless one or other of the ancillary diseases is also
present.

_In leukæmia_ when severe there is an extremely pale fundus, with a
yellowish tint; hæmorrhages, when they occur, are often pale; the
choroidal vessels also, if they can be seen, are pallid; the veins in
the retina are full and tortuous. There may also be yellow foci, and
occasionally retinitis with white spots. In a word, the leaking vessels
tell of vascular disease.

_In lead-poisoning_ we find paralysis of ocular muscles, amblyopia,
contracted fields of vision, papillitis and retro-bulbar neuritis. It is
the nervous system upon which the stress principally falls.

_In pneumonia_ we do not expect to find any ocular complications; in
spite of the uricæmia, the eyes are scatheless.

It seems unlikely that hyperuricæmia can produce such widely different
signs in the eyes. Rather, on the other hand, the ocular symptoms conform
to the type we should expect to find associated with leukæmic blood in
the first and with lead-poisoned nerves in the second.

In this congeries of ocular symptoms, marked by hyperuricæmia, we do
not find iritis included, and yet this is a commonly accepted _gouty_
affection of the eye.

_False Gout._—It often happens that patients tell us that they are gouty
although they do not claim to suffer from attacks in the old-fashioned
way. With them there is a wide difference between the substantive “gout”
and the adjective “gouty,” the latter apparently implying an attenuated
form of the former. Such patients are seen at health resorts and are
very frequently those in whom obesity and plethora are present to a
marked extent. The full-blooded appearance involves the head, body and
limbs, but the eyelids, for some unexplained reason, may escape. The
patients have lived not wisely, but too well. On examination an increased
quantity of uric acid in the urine is found, and is supposed to justify
the diagnosis of gout. Sometimes the malassimilation, is associated with
arterio-sclerosis, with diabetes, or with albuminuria. But the patient
is almost invariably convinced that he has gout, that it is hereditary,
that it has been handed down to him through a long line of ancestry from
primeval days, and that an ascetic life would not have prevented it in
his case.

Should such a one be attacked by iritis, the circularity of the argument
is complete: he has iritis, therefore he is gouty; he is gouty, therefore
he has iritis. But usually in the early days of this so-called gout
we see no ocular changes; the time for organic disease (inflammatory
and hæmorrhagic) has not yet arrived; auto-intoxication has not yet
begun. But sooner or later with the maturation of disease come ocular
degenerative signs, retinal hæmorrhages, and so on. The sequence is
malassimilation, “goutiness,” sub-infection, ocular disease. Thus in
diabetes melitus (omitting toxic and traumatic forms) we find pancreatic
disease, nutritional changes, and not usually until late retinitis,
cataract, iritis, etc. In renal disease retinitis is also late and often
ushers in the final scene.

If in these cases of so-called gout we implicitly accept the patient’s
nomenclature of disease, we shall find plenty of gouty iritis, but we may
overlook the fundamental condition of his arteries, of his kidneys, and
of other organs.

The sins of repletion in such patients may be relieved by the virtue of
abstinence, not by colchicum.

_Retinal Hæmorrhage._—That retinal hæmorrhage may be caused by gout was
firmly maintained by Jonathan Hutchinson.[57] This opinion was shared by
Gowers, who states that the “influence seems well-established.”[58]

Hutchinson pointed out that in cases of retinal hæmorrhage of renal
origin, stellate white deposits occurred, whereas in gouty cases they
were absent. By this criterion he classified his cases. In his first
patient Hutchinson relates that he can only state from memory that there
was no albumen, but that “he seemed in good health and that there was
reason to suspect gout, although he had not had a definite attack.” In
his second case, a woman who had suffered from rheumatic gout and true
gout, there were numerous hyaline casts in the urine, but no albumen. In
both cases the hæmorrhages were flame-shaped, and Hutchinson lays stress
on the shape in gouty retinitis hæmorrhagica. The group consisted of
fifteen patients, eleven men and four women. “Gout had been positively
present in six, and was strongly probable in four or five others. In
one the gout was complicated, and probably in part produced, by lead
poisoning, and this is the only instance in which the urine contained
much albumen. In another in which no history of gout was obtained, the
patient, a man _æt._ 67, had diabetes, which was the probable cause of
the retinitis.... In about a third of the cases albumen was found in the
urine, but it was usually a mere trace and only present occasionally....
In four, including the case of diabetes, white deposits characteristic of
renal retinitis were present in small quantity, and in all these albumen
was found in the urine.”

Hutchinson sums up his cases with the catholic observation that retinitis
hæmorrhagica is a malady the boundaries of which are very indefinite.
And when we bear in mind the changes of modern medical opinion with
regard to the influence of arterio-sclerosis on the retinal circulation
and the effects of vascular hypertension the etiological difficulties
regarding retinal hæmorrhages are hardly less illimitable than they were
when Hutchinson penned his valuable contribution. In all his cases (as
in those which we see now forty-two years later) there are many factors
which may have been responsible for the hæmorrhages apart from gout.

In renal disease gout is widely recognised as a possible precursor. So
we are again in the same quandary that we experience in considering the
relationship of gout to iritis. Are the retinal hæmorrhages due to gout
or to the resulting renal disease? The claim of gout to be the _deus ex
machina_ once more seems to be superfluous, for retinal hæmorrhages are
an end result which may be reached by a variety of pathological routes.
Gout may be one, but if so it acts _viâ_ interstitial nephritis. In other
words, hæmorrhagic retinitis is the apanage of nephritis and the appendix
of gout.

It is impossible to affirm that a retinitis is gouty, for there are no
distinctive features, but it occurs in gout when vascular disease has
supervened, not gouty retinitis, therefore, but retinitis in the gouty.
This is all that can be affirmed when we find albumen in the urine and
tophi in the ears, eyelids, etc. Moreover, it is wiser in the interest
of the patient to take this broad view. There may be a link between the
kidney and the diathesis, but it is invisible.

Neither are we absolved from searching for some other cause of renal
disease. The case may be fundamentally one of arterio-sclerosis with
a secondarily induced sclerotic kidney, or, on the other hand, the
hæmorrhages may be symptomatic of pernicious anæmia and due to toxins.
With regard to prognosis it is helpful to remember that retinal
hæmorrhages, especially when they are isolated, suggest the possibility
of death ensuing suddenly from cerebral hæmorrhage; but albuminuric
retinitis is itself frequently a terminal stage of chronic renal disease.
We have not sufficient proof to call retinitis gouty, and we should
adhere to the more catholic appellation “nephritic retinitis.”

James Taylor, writing on neuro-retinitis in the gouty,[59] states that—

    “Commonly, of course, it occurs in association with
    albuminuria, yet it is met with apart from this even in
    cases where no very obvious cardio-vascular changes can be
    demonstrated in other regions. And thromboses in retinal veins,
    apart from cardiac hypertrophy and demonstrable changes in the
    arteries or in the blood pressure, are of frequent occurrence.
    In such cases gout is possibly—in many cases demonstrably—a
    very important factor in the etiology.”

The opinion that cases of neuro-retinitis may be gouty is based upon
(_a_) the fact of the apparent absence of cardio-vascular disease
elsewhere, (_b_) the lack of any other ostensible cause. Doubtless many
cases of retinal hæmorrhage are seen for which we are unable to assign
a cause; in some of these there is no suggestion of gout and nothing
to support a postulation of a latent form of that diathesis. Taylor’s
statement that gout in many cases is demonstrably a very important factor
in the etiology cannot be lightly set aside, but as the appearances of
neuro-retinitis are similar whether gout is present or absent, it is
legitimate to question if the diathesis is really necessary.

_Glaucoma._—Brudenell Carter, Hutchinson and Nettleship have claimed
that gouty people are more apt than others to suffer from glaucoma, but
no convincing argument has been brought forward in proof of any definite
nexus.

_The conclusion_ I would arrive at is that it is unwarrantable to speak
of “gouty” ocular disease, for there is nothing in the character of the
inflammation specific of gout. We renounce the prefix in order—

    (1) That we may not be lulled into false etiological security,
    and

    (2) That we may approach the elucidation of the case and the
    treatment thereof free from preconceptions. The mouth and its
    accessory cavities are the primary sphere of our investigation.
    This is no mean task, including as it does the radiography
    of the teeth, even though these are apparently healthy. In
    the tortuous route of elimination we look for concealed
    dental roots, rarefying osteitis, buried tonsils, post-nasal
    infections, antral disorders.

The view that non-traumatic iritis is only a symptom imposes upon us a
wide outlook in our search for a diagnosis. In this no viscus can be
overlooked, no organ forgotten. All are members one of another, and the
wise physician takes cognisance of their interdependence. The recognition
of an inflamed iris is only the first stage in the diagnosis, for iritis
is the sequel of a story written elsewhere. It is a question, not an
answer.

But we know not what the future has in store, and though, with our
present knowledge, I affirm that I can find no evidence that the
eye is a _locus signi_ for gout, the day may come when, either from
bacteriological or other sources of progress, it may be shown that
there is a mystic source of intercommunity. In other words, it may yet
happen that the mysterious _materies morbi_ of gout, whether microbic or
chemical, may be demonstrated experimentally as capable of inducing, not
only the arthritic phenomena, but also those inflammatory lesions in the
eyes which provisionally are sometimes called “gouty.”

Lastly, I would enter a plea for more systematic, more scientific,
investigation of the true link, if any, between iritis and arthritis.
The war has taught us the value of “team-work”; it has taught us that
the clinician must be reinforced by the bio-chemist, the bacteriologist
and the pathologist. The work and the workers must be co-ordinated in
our daily struggle with disease as we meet with it in our individual
patients. The realm of medicine, with ever widening borders, is too
vast for single control. In the foregoing pages I have said much about
iritis, and it is a good example of what I mean. In justice to our
patient, we may call for a Wassermann or a complement fixation test;
we may require the teeth-roots made visible by an X-ray expert, or,
it may be, the passage of a bismuth meal radiographed, hidden tonsils
explored by the laryngologist, or the antrum illuminated; the fæces may
need bacteriological examination. A gynæcologist may help us regarding a
leucorrhœa or a possible ovarian abscess.

With many of our patients, alas! considerations of expense compel us to
forego our aspirations.

What is the remedy? Is it not State help, central clinics staffed by
highly trained experts engaged in research work? Here the poor could be
examined and reports supplied to the attendant doctors free, and less
impecunious patients at an inclusive fee. Centres such as these would do
much to advance the science of medicine and thereby raise the standard of
health and make the sick and ailing healthy citizens of a great empire.

_Salus populi suprema lex._




CHAPTER XXVI

TREATMENT OF GOUT


Adaptation is the keynote to progress in therapy—adaptation of our
therapeutic measures to the ceaseless advances of pathology. In
the history of gout it has ever been so, the changing, oftentimes
contradictory, vogues in treatment, always the reflex of equally mutable
and conflicting views as to its pathogeny. For who can doubt that the
facts of pathology supply the indices of rational as opposed to empirical
methods of therapy?

Albeit, much remains to be done before we can claim to fulfil the demands
of ideal treatment of gout. For we are still ignorant of its exact
etiology, cannot yet boast of our control of the morbid potentialities
that constitute the pathological groundwork of the malady. We cannot
obliterate the diathesis, and must still deplore with Sydenham that “as
for a radical cure, one altogether perfect, and one whereby the patient
might be freed from even the disposition to the disease, this lies, like
truth, at the _bottom of a well_; and so deep is it in the innermost
recesses of nature that I know not when or by whom it will be brought
forward into light of day.”

But although we cannot dissipate the inherent proclivities to the
disorder, we can, I think, claim to fulfil the humbler _rôle_, viz.,
obviate their coming to fruition. Haply in the fulness of time we may
be able to influence the _endogenous_ factors that make for gout, may
through the labours of the bio-chemist be able to translate or assess
them in terms of _functional inefficiency_ of this or that particular
viscus. But meanwhile we must perforce content ourselves with the
eradication or control of the _exogenous_ factors of gout—the _excitants_
whereby or through whose agency the malady from being _latent_ becomes
manifest and overt.


RADICAL TREATMENT OF LOCAL FOCI OF INFECTION OR TOXIC ABSORPTION

When discussing the etiology of gout we emphasised the probability of
the intrusion of an _infective_ element in its genesis. We commented,
too, on the extreme frequency with which local infective foci are
encountered in _gouty_ subjects and the imperative necessity of their
early recognition and radical treatment. In doing so, we but conform
to what should be regarded as the salient canon in the treatment of any
form of _arthritis_, viz., a diligent search for a _focus of infection_.
A _monarticular_ arthritis, such as gout in its initial outbreaks
almost invariably is, calls for the same painstaking investigation as a
polyarticular, for one never knows when the former may merge into the
latter. Nor, if we find one focus, should we rest content, assuming that
this is the only one of significance. For in many instances there are
probably several foci. Thus, how frequently are septic teeth conjoined
with tonsillar and aural troubles, and, as modern investigation shows,
these, again, may be associated with remote foci in gall bladder,
appendix, etc.

To begin with, a thorough examination of the mouth and nasopharynx
is essential. During the inspection any artificial dentures must be
removed, lest we overlook concealed and septic stumps. “Bridges,” again,
are a notable source of sepsis. The roots upon which they are fixed or
the related gums may be infected. _Phlebitis_, as we know, is a common
associate of gout, and C. A. Clark, emphasising the septic potentialities
of bridges, cites an obstinate case of phlebitis which only cleared up
after removal of a filthy device of this nature.

Again, _devitalised teeth_ that have been “crowned” should always be
suspect. Infection at the root is common, with abscess formation. Such
are not necessarily painful, and may give no indication of their presence
until they find an exit of discharge, maybe by a gumboil or _viâ_ the
antrum, etc. These abscesses around the apices of non-vital teeth are
difficult of diagnosis in their early stages. Even the X-rays may fail
to detect them when minute, this owing to the small amount of pus, or
because abstraction of the lime salts from the bone has not proceeded to
an extent that may be appreciable by skiagraphy. The first indication of
their presence is a small area of rarefaction in the bone around the apex
of the root.

It is important to recognise that teeth that appear sound upon external
examination are not necessarily so. In short, ordinary clinical
examination may be quite inadequate. Not only must the condition of the
“crowns” of the teeth, but that of their _roots_ also, be ascertained.
For when we reflect that, in addition to _abscesses_, _cysts_, _buried
roots_, _inflamed_ and _impacted molars_ may be present, we see, if we
are to achieve a full and accurate diagnosis, _radiographs of the jaws_
are essential. A single-plate negative is practically of no value. A
_series of films taken all round the mouth_ is the only satisfactory
procedure. Such give finer detail, and show up the interstices of the
teeth—the sites of predilection for _periodontal disease_ or _pyorrhœa
alveolaris_.

Passing to pyorrhœa alveolaris, which has been defined as the twentieth
century scourge, it cannot be denied that if all the evils attributed
thereto are to be nipped in the bud, then _X-ray examination_ of the
_teeth_ must be resorted to at a much earlier stage than it commonly is.
Clean as well as unclean mouths fall a prey thereto, and, as a rule,
investigation of the teeth is an after-thought, this particularly in the
subjects of _gouty arthritis_. Usually the gout has been in full swing
for years. The patient’s _dyspeptic_ symptoms have been dismissed as
“gouty,” and “alkaline stomachics,” etc., have been his lot, though his
teeth may be in a foul condition—one which would not have been tolerated
probably in any form of arthritis other than “gouty.”

But if to diagnose pyorrhœa alveolaris in its early stages we must
needs invoke radiography, on the other hand we should be careful not to
overlook its presence when advanced. The gums may be pale and shrunken,
at other times red and swollen and very prone to bleed. When pockets form
round the teeth, pus and blood may be expressed. Probing may not reveal
their true depth, whereas X-rays do.

Sometimes only one or two teeth are affected, at other times many, and
these not necessarily adjacent to each other. Thus it happens that the
disease is more advanced at one part of the mouth than at another.
Exacerbations frequently occur—a blessing in disguise. The affected teeth
become tender to bite on and loose in their sockets, but often pain
lessens, and the tooth again tightens up, and the all-necessary visit to
the dentist is again and again postponed. Sometimes abscesses form, which
discharge into the peridental pockets. Eventually the teeth may drop
out almost painlessly. Herein resides the danger of the condition, its
relative _painlessness_. Hence the ease with which _secondary infections_
may ensue, _e.g._, in the _tonsils_, the _gastrointestinal tract_, etc.,
while the original source may be altogether overlooked.

The subjects of gout are often middle-aged or old. We should recollect
then that chronic _periodontitis_ may in their instance ensue in sequence
to _senile atrophy of the alveolus_. Recently in a patient of mine nearly
eighty, a sufferer from gout and sciatica, a persistent _pyrexia_, of
apparently cryptic origin, forthwith ceased after extraction of his
teeth. He lived some considerable time afterwards, but I often regret
that his septic teeth had not been drawn long before.

Unfortunately no specific germ can as yet be saddled with the
responsibility for _pyorrhœa alveolaris_, though some would convict
the _endamœba buccalis_. _Spirillæ_ and _staphylococci_ form a
large proportion of the bacterial flora met with in _oral sepsis_,
but the results of _vaccine_ treatment would seem to indicate that
_streptococci_, _diplococci_, and _staphylococci_ are the most frequent
causes of complications. Still it must not be forgotten that the
_streptococcus viridans_ is by some held to be specially related to
_arthritis_. Hartzell (1915) invariably found it in the teeth and
peridental tissues in 220 patients suffering from arthritis. This
_streptococcus hæmolyticus_ frequently leads to _secondary tonsillar
sepsis_, and, as previously noticed, to subsequent _gall bladder
infection_, etc.

Passing to _local treatment_, if oral sepsis or pyorrhœa alveolaris
exists, carious teeth when present should be extracted, or their cavities
cleansed and filled. Accumulations of tartar should be removed, and
unhealthy gums attended to. Thus “pockets” should be swabbed, syringed,
or subjected to ionisation. Exacerbations frequently follow the
extraction of teeth. Acute paroxysms of gout have followed this simple
operation. In cases where the extraction of many teeth is called for,
it should be preceded by as thorough a cleansing of the mouth as can be
assured. It is a matter of common experience that severe exacerbations of
arthritis follow neglect of this precaution, owing to the enhanced toxic
absorption from the extensive raw surface.

Unquestionably, whether it be a matter of _curettage_, of “_pockets_,”
_alveolar abscesses_, or _extraction of teeth_, it is wiser to proceed
_gradatim_. Hartzell, when many septic foci exist in the gums and teeth,
allows three to six days to intervene between “treatments,” this in order
to gain full advantage of what may be called _surgical auto-inoculation_.
For, as he contends, any local measures, curettage, etc., necessarily
involve inoculation of the subject with a large number of organisms,
thus producing an effect similar to that of an efficient vaccine, “with
the added advantage that the constant supply is shut off from the focus
disturbed.”

Recurring attacks of _tonsillitis_—well-recognised determinants of
gouty outbreaks—demand thorough local treatment. If this fail, the
propriety of removing the tonsils will call for consideration. But,
as tonsils may be very misleading in appearance, the aid of an expert
is often indispensable. Thus the worst types of tonsillar sepsis may
exist in the small “buried” tonsil. In such cases the indications for
_enucleation_ are the more emphatic when we note the increasing evidence
that _tonsillar sepsis_ may be etiologically related to _appendicitis_ or
_cholecystitis_.

Again, as before pointed out, Wynn Wirgman noted that some cases of gout
are associated with _nasal_ disorder, and certainly in non-gouty forms
of arthritis expert treatment has reacted very beneficially on the joint
condition. Watson Williams has recently drawn attention to “_latent
sinusitis_” as a cause of _systemic infections_. He cites two cases of
chronic _rheumatoid arthritis_ which, previously resistant to treatment,
were greatly improved by operation on the _sphenoidal sinuses_. The
washings from the sinuses were free from pus, but on culture showed
growths, in the one case of _streptococcus albus_ and in the other of
_streptococcus aureus_ and _streptococcus brevis_.

Needless to say, the genito-urinary tract should be carefully
investigated, especially in polyarticular gout, or monarticular when
located in unusual articular sites, this if only to eliminate the
possibility of a latent _gonococcal_ infection. Apart from this, we
should recollect that _cystitis_ is common in gouty subjects, and,
according to older authors, might occur as a result of “_metastasis_,”
not to mention the cases of so-called “gouty” _urethritis_, which, it
is claimed, not uncommonly supervenes at the end of an articular attack
of gout. Nor should we forget the _rectum_, for hæmorrhoids are not
uncommon in these subjects. Years ago Garrod noted that the cessation of
a habitual hæmorrhoidal discharge frequently proved the signal for an
outbreak of gout. Moreover, there is increasing evidence that _rectal
ulcerations_ may be causally related to some forms of arthritis.

When all the foregoing regions have been thoroughly investigated the
lower levels of the gastro-intestinal tract must be thoroughly examined
by all modern methods. Diminution, absence, or excess of free HCL may
call for determination, while X-ray studies may afford us an explanation
of dyspeptic symptoms. Lastly, the urine and fæces may call for
exhaustive investigation.

In conclusion, however, if there be any local focus of infection so
situated as to admit of radical measures, these should be undertaken
prior to resorting to vaccine therapy.

But, obviously for the success of vaccine therapy, it is essential that
an accurate _bacteriological_ diagnosis of the case under consideration
be accomplished, which of course is comparatively easy if we are able to
isolate the particular organism by direct cultural experiment. To this
end cultures should be made from the roots of extracted teeth, the gums,
tonsils, or nasal or other discharges. Albeit, we must never be content
to select haphazard any organism that we may isolate from the patient’s
mouth, nose, urine, fæces, or elsewhere. Doubtless the true clue will
lie in the institution of _complement fixation tests_ for the organisms
responsible for local infections. Research to this end is now in course
of progress at the Royal Mineral Water Hospital, Bath, for it is becoming
increasingly clear that nothing short of “team-” work will suffice for
the full elucidation of the “gouty” and the non-gouty arthritides.


DIET

Truly in respect of diet the gouty have “suffered much of many
physicians,” have been the butt, so to speak, of all the fads and
frailties of medical opinion. Should that chemical outcast “uric acid”
but appear in excess in the urine, it was, and still is for many, an
infallible index, not only of gout, but of gout maintained and nurtured
by improper feeding. The inference seemed obvious: the ideal diet for the
gouty was a diet free from any uric acid-forming material. This achieved,
the gouty “will be free from his leprosy, and henceforward, if he abide
by the prescribed regime, all will be well with him.” But, as Sir James
Goodhart, from whom we take this last passage, pertinently asks, “is this
so?” The answer is, I fear, in the negative. For who has not met with
gouty veterans who, having run the gamut of endless dietetic experiments,
still remain “gouty,” though, _mirabile dictu_, still avid for fresh
ventures?

For myself, I know of no stereotyped diet for the “gouty,” for in this
respect every man is a law unto himself. “Get the acid out of your
system,” is the watchword of many, and, I fear, often to the undoing of
their victims. Bent on the annihilation of the disease, they overlook
the _individual_. But, weary of futile chasing of uric acid out of the
economy, most students of gout now agree that the aim of all dietetic
measures should be to secure, as far as possible, _gastro-intestinal
asepsis_. For, as experimental studies have shown, it is possible, by
means of a judiciously selected and varied diet, to modify the character
and even to inhibit the growth of the intestinal flora. The far-reaching
nature of such an influence is clear when we reflect that all abnormal
fermentative and putrefactive processes in the alimentary canal appear to
be referable to the action of microbial agents.

_Diet in Acute Paroxysms._—The initial outbreak of gout may occur at
any age, and respect must be had to this as well as to other individual
peculiarities. If the subject be young, say in the forties, and a free
liver, he may at the onset experience distaste for food, if not actual
nausea. If so, let him follow his bent, and confine himself to hot water,
barley-water, or hot weak tea. Such a modified process of starvation
is beneficial rather than harmful. Drinking freely of bland diluents
promotes the elimination of toxic or waste materials, while the intake of
hot water stimulates the hepatic cells and promotes the excretion of bile.

Milk, easy of digestion and rapid absorption by a febrile patient, is the
ideal form of nourishment. Moreover, a milk diet constitutes the most
effectual means of attaining a comparative degree of intestinal asepsis.
From two and a half to three pints may be taken in the twenty-four
hours. While some will find no difficulty in assimilating it, others
soon experience nausea, vomiting, and even diarrhœa, from the passage of
undigested curds. It is therefore advisable to begin with small amounts
given at regular intervals. If ill digested, it may be diluted with some
alkaline water, or three to five grains of citrate of soda added to each
tumblerful.

To obviate monotony the intake may be varied by oatmeal or barley gruel,
veal, mutton, chicken, or vegetable broth, but strong soups and animal
extracts must be avoided. There is no objection, however, to bread and
milk, tapioca, semolina, or sago puddings.

With the disappearance of fever and the decline of acute symptoms fish
may be introduced into the dietary, with later on a little white meat or
chicken. This may be safely done when local pain and tenderness decline,
and alike the tension of the parts, as shown by pitting. Moreover, at
this stage the appetite usually asserts itself. Still the return to
regular diet must be made slowly and cautiously, if we wish to combat the
very common tendency in these patients to functional _gastro-intestinal_
and _hepatic_ derangements. Lastly, in acute _sthenic_ gout occurring in
a robust subject there is no need whatever for _alcohol_ in the _febrile_
stage. Also, it may be added, the younger and the stronger the patient,
the better will he thrive on a pure milk or a lacto-farinaceous diet, and
the less urgent the necessity for relinquishing the same until all fear
of a relapse has passed.

On the other hand, in acute _asthenic_ gout in an _elderly_ and perhaps
somewhat _debilitated_ subject one must more than ever have regard to
the individual, especially if he be an old time sufferer, perhaps with
multiple joint involvement. Such a man “has not so much the gout as the
gout has him.” He has to be helped to support his burden. In short, the
diet for the _young_ and _plethoric_ differs from that suitable for the
_old_ and _asthenic_.

Restriction of such to a milk diet is sometimes positively harmful.
The mischief is, that, once begun, every attempt at a more varied diet
immediately provokes a relapse.[60] As Sir Thomas Watson wisely observed:
“They must be allowed a certain quantity of their accustomed good cheer,
or they become an easier prey to the disease. In such cases you must
‘trim’ as well as you can between opposite dangers, between the Scylla of
excess and the Charybdis of debility.” In short, you must maintain their
vigour and their strength. For this a pure milk diet will not suffice.
In addition thereto, pounded or minced chicken, a little fish, sole or
whiting, may be given. When also, as often happens, they have been wont
to take alcohol, two ounces of mature brandy or whisky, well diluted with
Salutaris or other mineral water, may be allowed them every twenty-four
hours.

Indeed, if the subject be old and broken down, it may be necessary to
increase the amount of stimulant. In such cases to go on treating the
_disease_, heedless of long-established habits, is bad policy. Wholly to
withhold alcohol may well precipitate disaster. Homilies on abstinence or
temperance are best postponed pending convalescence.

Moreover, these cases of _acute gouty polyarthritis_, whether in the
middle-aged or old, very commonly run an _afebrile_ course. If then,
as not infrequently happens in these distressing cases, the patient’s
progress is slow and unsatisfactory, there need be no hesitation in
renouncing a strictly lacto-farinaceous regimen in favour of a more
mixed diet: clear vegetable soups, well-made Julienne, mutton, veal, and
chicken broths, lightly boiled fish of the digestible kinds, pounded and
minced chicken, etc.

Even when in these cases _pyrexia_ is present, it is rarely continuous,
but is diversified by _afebrile_ intervals. If then, while the paroxysm
is in full flare, it be deemed advantageous to adopt a milk diet, it is
all the more important that in the _inter-paroxysmal_ stages we take full
advantage of these periods of enhanced digestive capacity.

_Diet in Chronic Gout._—Sydney Smith, writing to the Countess of Carlisle
in his seventy-first year, humorously apostrophises his gout: “What a
very singular disease it is! It seems as if the stomach fell down into
the feet. The smallest deviation from right diet is immediately punished
by limping and lameness, and the innocent ankle and blameless instep are
tortured for the vices of the nobler organs.”

Precisely so, but what constitutes the “right” diet? We are told that
this is good and that is bad for gout. Some would have us eschew red meat
and cleave unto white; for others common salt is the devil that must be
cast out. Some speak ill of all the fruits of the earth. Strawberries
especially, they say, are the bane of gout, yet in these same Linnæus
found salvation. For many, again, sugar is anathema, tea and coffee but
uric acid solutions, and alcohol in all forms rank poison!

What a trial the gouty subject who, obsessed by his “acidity,” has passed
through the furnace of many spas! “Everything I eat turns to acid” is his
plaint. He has been all things by turns—a fruitarian, a vegetarian, no
meat or all meat, etc. Such persons, in truth, are “uric acid” maniacs.
But—forget it not—they are of our making, and often in their multitude
of counsellors have found, not wisdom, but _starvation_! Well would it
be if the evil done ceased with themselves, but unfortunately they seek
converts to whatever cult they affect.

_The Fallacy of Fixed Dietaries._—As Bacon in his “Regimen of Health”
(1597) wisely observes: “Some physicians are so regular in proceeding
according to art for the disease as they respect not sufficiently
the condition of the patient.” The wisdom of this has, I fear, been
overlooked by those who hold that the ideal diet for the “gouty” is one
destitute of the _precursors of uric acid_. Its acceptance makes not for
flexibility in dieting, but rigid, undiscriminating routine.

Apart from the violation of principle, the direct result is, that the
victim runs amok among the _carbohydrates_, with as a frequent penalty
an _acute_ outbreak, this although uric acid is not a direct product of
carbohydrate metabolism; nor, as far as is known, does the carbohydrate
intake influence the rate of formation of uric acid. Thus do theory
and practice come into conflict, and, as usual, the patient pays. How
pernicious this obsession that uric acid is a morbid agent! Uric acid is
not an etiological entity, and, as Walker Hall rightly observes, “it is
high time that every practitioner made a point of fully educating the
public in this respect.”

Any attempt to formulate a set dietary proves but a snare and a
delusion. No regime is applicable to the “gouty” as a class, nor even
to the individual “gouty” subject at all periods of his life history.
His disease persists for an indefinite period, and, like most chronic
maladies, undergoes variations. _Pari passu_ his digestive capacity
rises and wanes. The regime therefore must be adapted and readapted to
his varying necessities. For it is the _patient_, and not the “gout,”
dictates the diet. But only too commonly the _disease_ is dieted, the
victim ignored—_hinc illæ lachrymæ!_

Our dietetic ventures must obviously rest on a sounder basis. This we do
know, viz., that _functional disturbances of digestion_ generally precede
a “gouty” paroxysm, and that their amelioration is followed by relief of
symptoms. The aim of our dietetic measures then is the _prevention of
digestive disturbances_, not the routine withdrawal or reduction of uric
acid precursors.

The dietetic treatment of the “gouty” is that of the “dyspeptic,” with,
if anything, an added discrimination, for an unknown factor intrudes—the
“gouty diathesis”—which has also to be reckoned with, but of this later.
Now “dyspeptics” cannot be dieted by rule of thumb. Whether they be
“gouty” or “non-gouty” matters not. A careful study of the phenomena of
digestion, if not essential in every case, is certainly called for in the
more obstinate and obscure forms. In short, an attempt should be made
to determine the special form of “indigestion.” Is the derangement of
function a disorder of motility or secretion? Is it catarrhal or nervous
in origin?

That such is the proper mode of procedure is undeniable. For are we
not too prone to assume that the “dyspepsias” of the “gouty” are _sui
generis_, all due to _one_ cause, the _materies morbi_ of _gout_, instead
of being merely “_excitants_” of gout and due to a variety of digestive
functional disabilities, and these of equally diverse origin?

_Thorough Physical Examination a Necessary Prelude to Dieting._—When we
recall that the “dyspepsias” of the “gouty” endure through long years,
the suggestion that every effort should be made to localise and establish
the exact nature of the underlying derangement seems almost superfluous.
Yet how often is the question dealt with offhand, though, ideally
speaking, I cannot help thinking that the _primary_ outbreak of _gout_
should be the signal for an exhaustive examination by all modern methods.
The consequences of dyspepsia in the “non-gouty” are bad enough, but
infinitely more so in the “gouty” subject. But it is the former group,
not the latter, that has been the favoured object of study by experts,
which is, I think, somewhat unfair.

There is need of a searching investigation, a more common invoking
of the tests whereby the functional efficiency of the stomach may be
gauged. We know that there may exist on the one hand hyperchlorhydria
and on the other hypochlorhydria. But we need to know more as to
disturbances in gastric motility, delay or hurry in digestion, not to
mention abnormalities in shape, position, size, tone, pyloric end rhythm,
etc. In view of the almost general admission that _gastro-intestinal_
derangements are causally related to outbreaks of _gouty arthritis_,
surely our remissness in this matter is somewhat surprising, the more so
in light of the heroic procedures, viz., _ileocolostomy_ and _colectomy_,
advocated in _rheumatoid arthritis_, a condition by many deemed related
to gout.

Leaving such aside, none will, I think, deny not only the value of _test
meals_ for _free HCL variations_ and experimentation with all kinds of
foodstuffs, but also of X-ray examination of the _alimentary tract_.
How subversive of all preconceptions the revelations of radiography
in _gastric_ and _intestinal_ conditions, of what infinite value in
disentangling the ambiguous significance of purely subjective sensations!
Thus, alterations in _gastric_ tone, motility, and peristalsis may hark
back to remote lesions in _gall bladder_ or _appendix_, and these also
account for variations in free HCL.

“Great eaters,” said Sydenham, “are liable to gout, and of these the
costive more especially”—an observation the truth of which all will
confirm. It may be taken as a maxim that nothing for the gouty is more
prejudicial than _constipation_. Here it is obviously of importance that
we know the site of delay, whether in the lower coils of the ileum, the
colon, or merely the rectum, _i.e._, dyschezia. How else obtain this
information, save through X-ray examination?

Any departure from normal in consistency, colour or content of the fæces
should be noted so as to identify _hepatic_ or _pancreatic_ derangements.
An analysis of the urine should always be undertaken, its reaction noted,
the presence of albumen or casts ascertained. It is important, too, that
we do not overlook _glycosuria_ or _oxaluria_, or substances indicative
of excessive intestinal putrefaction. All these bear far more pertinently
on _diet_ than estimates of _uric acid_.

The behaviour of the _skin_, whether inactive or not, must also be
taken into consideration. Moreover, as the subjects of gout are usually
middle-aged or old, it is highly important to note the general drift of
metabolism, whether in the direction of _obesity_ or undue _leanness_.
Herewith we must take an inventory, as it were, of the subject’s general
mode of living. What are his habits in respect of food and drink? Is his
diet excessive or improper in quality? Are his meals taken at irregular
times? Does he masticate his food properly?

In the matter of _exercise_, his occupation or pursuits require thought.
Do they involve excessive exertion or favour a sedentary habit? For
both these factors bear narrowly on his power or not of disposing of
ingested material. Indeed, all the foregoing reflections stand in close
relationship to the complex processes of digestion and metabolism,
and the efficacy of our prescribed regime will depend on how far our
suggested innovations meet the particular needs of the subject under
review.

_Need for Collaboration of Clinician and Bio-chemist._—Before we shall
be able to lay down a diet for the “gouty” on truly scientific grounds
much remains to be done. Our clinical examinations, in no way to be
despised, must nevertheless be supplemented by the more subtle tests of
the bio-chemist. Consider the complexity of the problem. We have to diet
not only the “gouty,” but the “potentially” gouty.

They shade the one into the other. Even the man who has had gout has
his periods of respite, of apparent unblemished health. If seen at such
a juncture, he may display the relics of his gouty attacks, _i.e._,
_tophi_. But can we say of him that he actually _now_ has gout? He has
crossed the Rubicon, disclosed his morbid trend, but meanwhile he has
apparently recrossed to the vantage ground of normal metabolism. He
stands again with those who are about to, but have not yet developed the
disorder, _i.e._, the “potentially” gouty.

Who will deny that it is when a man is, so to speak, gravid with, but not
yet delivered of, gout that dietetic measures will avail him most? But
this, alas! carries with it as its postulate the diagnosis of _latent_
gout. Now, Walker Hall suggests that “the nuclein metabolism of the
gouty patient is run at high pressure or full capacity, instead of the
usual normal quarter or at half-pressure capacity, in order to cope with
the ordinary processes of assimilation, and that there is very little
reserve energy.” Does not this seem to indicate that a fruitful sphere
of research might be the invoking of “endurance” tests and other methods
of determining the _functional capacity_ or _efficiency_ of the various
_viscera_?

At present we content ourselves with blaming the stomach, the liver, the
kidneys, etc., and often on very inadequate grounds. It would be a great
step forward if we could determine betimes which particular _viscus_ is
_functionally deficient_. There are signs that this boon will not be
long withheld, signs that not only can the functional efficiency of the
_stomach_ be tested, but also of the liver, kidneys, and even the spleen.

Thus Labbe and Daughin study the colloidal nitrogen in the urine, and
find the ratio to the total nitrogen much augmented when the _functional
efficiency of the liver is depressed_. Again, Bauer and Spiegel use
the _bilirubin content_ of the _blood_ to the same end. They maintain
that there is a bilirubin threshold, the assessment of which denotes
the _functional capacity_ of the _liver_. In health the _blood content_
thereof is surprisingly _uniform_. But in passive congestion of the
liver it rises very markedly, and the same after administration of
_cholagogues_.

In like fashion the value of _blood urea_ concentration is extolled by
Kast and Wardell as a satisfactory index of the _functional power_ of the
_kidney_. The _uric acid_ content of the blood is by Baumann, Hansmann,
Davis, and Stevens regarded as a very delicate index of _renal_ function,
though unreliable in the presence of œdema, cardiac decompensation, or
when the urine is highly concentrated in hot weather. These are but a
few of the methods available, and in the same way Frey has devised tests
for the functional efficiency of the _spleen_, while Barton invokes the
administration of urea, chlorides, adrenalin, creatine, etc., to assess
the functional capacity of the _liver_, _kidney_ or _spleen_.

Such is the trend of modern medicine—to link up clinical with laboratory
findings—and in gout perhaps more than in any other disease is this
collaboration urgently called for. For who can doubt that gout is a
malady of mixed intrinsic (endogenetic) and extrinsic (ectogenetic)
origin?

We need to know more about the _endogenous_ factor, the basal perversion
of cell structure or function, that differentiates the tissues of
the “gouty” from those of their fellows. For it is these inherent
peculiarities—structural, physical, or chemical—that give to the disease
its _sui generis_ character. How then in the “living” subject shall
these hidden morbid potentialities be identified? How save through the
medium of _function_, the outward expression of metabolic activities, in
other words by appraisement of the _functional capacity_ of the various
_viscera_? For gout primarily is a disorder of function, or, as Rendu
phrased it, a primordial “vice of nutrition.” Hence our insistence on
the invoking of the various laboratory methods for elucidating the
_functional_ powers, the efficiency or not of the _liver_, _kidneys_, etc.

This satisfactorily achieved, we may, through their reflected functional
disability or disabilities, divine somewhat the nature of the innate
tissue peculiarities of the “gouty,” may hope at long last to translate
the misty “gouty diathesis” in terms of _functional deficiency_,
deficiency of the working capacities of the _stomach_, _liver_, or
_kidneys_, and perhaps find that the basal flaw in some lies in the
_liver_, in others in the _kidney_, and thus the older clinicians be
justified of their claims for “hepatic” or “renal” varieties of gout.

That _exogenous_ factors, _i.e._, _infections_, bring to fruition these
latent morbid tissue potentialities of the gouty, is my belief. Hence
my contention that dietaries for the “gouty” should be such as promote
_gastro-intestinal asepsis_. Albeit, _infections_ are but the “seeds,”
and who can doubt that the ideal diet for the “gouty” should also take
cognisance of the “soil”—the pathological groundwork of gout?

The “soil” in gout is, I believe, one peculiarly favourable to microbic
invasion, and here again recent studies of the _cytology_ of the
blood bid fair to yield us some criterion whereby the “degree of body
resistance” to infections may be gauged.

But until the bio-chemist reveals to us the why and the wherefore of
their peculiar tissue vulnerability our dieting of the “gouty” must
perforce consist largely in diminishing the _exogenous_ excitants of the
malady. Ultimately, when researches now in progress have fructified,
we may be able to influence the _endogenous_ factors, may correct
the functional defect of this or that viscus, stabilise the nuclein
exchanges, and heighten the resistance of the tissues. In short, as Sir
Archibald Garrod puts it, “we must consider the soil as well as the seed
which falls upon it, and that he is the best exponent of the healing art
who treats the individual patient rather than his disease.”

“_The Accessory Food Factors._”—“Due nourishment, not gluttonous
delight,” is the true clue to the rational dietetic treatment of the
“gouty.” But this question of “due nourishment,” how complex it grows
in light of recent revelations. Thus, it is now generally agreed that
to satisfy the animal needs for growth and the maintenance of nutrition
something more than a due admixture of proteins, fats, carbohydrates, and
inorganic salts is essential.

We must, of course, ensure that the caloric value of the food intake be
adequate, and the supply of protein sufficient to maintain the nitrogen
balance, also that the intake of protein suffice for the exigencies of
tissue waste, not forgetting that for this is required a sufficient quota
of the individual primary fractions of the protein molecule.

But this, we now know, is not all, for there are other and indispensable
dietetic components. In the food we eat are substances of hitherto
unguessed-at potency—the “vitamines,” or, as they are now more properly
termed, “accessory factors of diet.”

Of these elusive bodies but three as yet have been isolated: _fat-soluble
A_, _water-soluble B_, and _water-soluble C_. In infancy absence of the
first-named “vitamine” leads to _rickets_. Lack of the second engenders
_scurvy_, of the third _beri-beri_.

But, apart from these well-defined “deficiency diseases,” McCarrison
has pointed out that the absence of these “accessory food factors”
leads to grave _functional_ derangements, especially of the organs of
digestion and assimilation and those subserving endocrine functions,
not to mention malnutrition of the nervous system and the induction of
hyperadrenalinæmia and chronic inanition.

A heavy indictment, but, more pertinently to our subject, McCarrison
inclines to think that _bilious vomiting_, _cyclical acidosis_, _mucous
disease_, and other _metabolic_ disorders met with in _children_ are very
probably due to deficiency of certain “accessory food factors.” In light
of this it is interesting to recall that these same symptom complexes are
by Comby and others regarded as manifestations of _infantile gout_.

More arresting still is McCarrison’s observation that all the clinical
phenomena distinctive of “deficiency diseases” as a whole are apparently
the result of _nuclear_ starvation of all tissue cells. In short, these
“accessory food factors” are essential to _due nutrition of the nuclear
substance_. How interesting this in light of the generally accepted
view that “gouty” individuals are victimised by some inherent defect or
alteration of _nuclein_ metabolism. Does not this seem to indicate that
one of the clues to successful dieting of the “gouty” must be adaptation
of the nuclein intake to the needs of the individual, in short that
we must strive for the stable maintenance or conservation of nuclein
metabolism?

Again, as before stated, one of the results attaching to deficiency
of “vitamines” is _functional derangement of the organs of digestion
and assimilation_. Such disturbances are prominent in _gout_, and that
“errors of diet” play an important _rôle_ in the genesis of the disorder
can scarcely be denied. At the same time there is no proof as yet
that the absence of some mysterious “accessory factor” makes for the
development of the disorder.

Nevertheless reflection on these findings is, I think, wholly apposite.
It should, at any rate, chasten those who affect extreme dietaries on
insufficient grounds. They are not justified of results, for, with Sir
Archibald Garrod, I venture to doubt “whether by dieting our ‘gouty’
patients we achieve nearly as much as we think we do.”

Such good, moreover, as we do compass, is, I think, exerted _indirectly_.
Even in the _inter-paroxysmal_ periods of the disorder, despite good or
perhaps exuberant health, gout is there. Its morbid tissue potentialities
are _latent_, though _functionally inactive_. To maintain this state of
_passivity_ is the aim of all dietetic measures, viz., to diminish or
withdraw the dietetic factors that are _provocative_ of gout.

The diet most void of offence is one the least calculated to excite
_digestive disturbance_—one that makes more surely for _gastro-intestinal
asepsis_. At this juncture it is interesting to note McCarrison’s
observation that although the absence of certain “accessory food factors”
is the essential etiological agent in the genesis of “deficiency
diseases,” yet he holds that _infections_ and parasitic agencies are
often important causes in determining the _onset of symptoms_.

Similarly in the causation of gout, “errors of diet” are not the only
agencies at work. They are in truth but contributory factors in that
such indiscretions favour the incidence of catarrhal states. These again
promote increased toxicity of the intestinal flora with sequential
disturbance of general _nuclein_ metabolism and associated specific local
reactions in certain tissues.

I make no apology for this somewhat lengthy digression. In the sphere of
dietetics, as elsewhere, “a little knowledge is a dangerous thing.” We
need to walk more circumspectly in this matter of dieting; and to this
end reflection on the disabilities that still beset us cannot fail to be
salutary, and will form, I think, a fitting prelude to our suggested mode
of procedure.




CHAPTER XXVII

TREATMENT OF GOUT (_continued_)


REGULATION OF DIET IN THE GOUTY

The victim of gout is easier led than driven. Show no “bowels of
compassion” for his failings, talk to him in the spirit of a dehumanised
disciplinarian, and your tenure of his confidence will likely be short.
You deal with a man more often wise than foolish, not merely a digestive
tube.

The physician must be authoritative and yet tactful. Thus if the victim
be a hearty eater, and you think he eats too much, try and get him
to eat less. But do not bid him straightway live as an anchorite. Be
a little more diplomatic. A good appetite is not a sin. An appetite
over-stimulated by condiments or endless varieties of courses is. He
should eat to satisfy his hunger, not to gratify his palate.

Do not irritate the patient with a strict dietary if avoidable. Far more
often than not it is the _quantity_, not the quality, of the food that is
at fault. Frequently mere reduction in bulk of the pabulum of all kinds
taken will suffice. In short, _restriction_, not elimination, is the
wiser maxim, especially so in indolent or sedentary persons in whom we
may with advantage limit the food intake to the minimum consistent with
the due maintenance of nutrition.

On the other hand, there is a widely prevalent idea among “gouty”
subjects that if they take enough exercise they can eat and drink what
they please and as much as they please. That active habits do counteract
to some extent the evil effects of overeating and overdrinking is
certainly true. Nevertheless, as Sir Thomas Watson reminds us, gout was
extremely common in the old time squire, who not only “rode hard,” but
“lived hard” also. It is so, though to a less extent, even to-day, and
often such subjects prove very refractory. Often a reference to their
“weight” will appeal more than any hygienic considerations. Make use,
therefore, of their sensitiveness on this point, and so by diplomacy
attain your end.

Overeating often goes with overdrinking at meals. I well recall a gouty
old sportsman of bucolic type who was accustomed to swill his food down
with several whiskies and sodas. Very conservative in all ways, it
was not easy to break him of the habit. Fortunately it occurred to me
to ask him, “Did you ever see a horse eat and drink at the same time?”
Reflecting solemnly, with obvious reluctance came the reply, “Damme, I
never did, now that I come to think of it.” That settled the question.
I had no more trouble, neither had he. Not often is one so lucky. But
“Eat your meals dry” is not a bad rule in cases of sheer overeating. The
appetite is sooner blunted.

As to the _quality_ of the food, always recollect that “gouty” people
are very prone to _idiosyncrasies_; but the idiosyncrasy is purely
_personal_, not applicable to the “gouty” as a class. With them it is
very much a case of “What’s one man’s meat is another man’s poison.” The
physician who rides rough-shod over idiosyncrasies in the matter of foods
rides for a fall. Let him rely on his own experience and knowledge in the
matter of general dietetic principles; but when it comes to details—the
eschewing or not of this or that—let him trust, not in his own, but in
his patient’s, experience.

Many of these subjects know perfectly well what suits them and what
does not. Their experience is your best guide. Having elicited this
information, an appeal to their common sense rarely fails. Of the
“gouty” it is especially true that “every man at forty is either a fool
or his own physician.” For the fool there is but one corrective—_dolor
acerrimum naturæ pharmacum_. The wise has only to be reminded of his own
experience, viz., that certain articles of diet infallibly disagree with
him—_verbum sapienti satis_.

In dieting the “gouty” we should never forget that the _main groups
of foodstuffs must be duly represented_. We may reduce this or that,
but never for long will they do well if one or other of the essential
ingredients of human food be wholly eliminated. It is, as Sir Archibald
Garrod remarks, doubtful whether even a minor constituent, such as the
purins, can be continuously withheld with impunity.

Still, even from the more extreme dietaries advocated by some one may
glean this useful lesson, that the temporary benefit that often accrues
points the moral that _simplicity_ of meals is best for these subjects.
If they crowd soup, fish, meat, game, sweets, etc., all into one meal,
they always pay the penalty. As Burney Yeo wisely says: “We should not
mix up albuminates, fats, and carbohydrates, or flesh, vegetables,
fat, and fruit in the same meal. One meal should be composed almost
exclusively of nitrogenous food, another of fats and carbohydrates, and
another of fruit, at proper intervals, and they will all agree and be
suitable, but the contrary will be the case if they are mixed together
in the same meal, one hindering the digestion of the other.”

I have often found the old rule, “One meal of meat, one meal of fish, and
one of neither,” an excellent way of impressing on these patients the
importance in their instance of simple, as opposed to elaborate, meals.
Arrangement of their daily bill of fare along these or similar lines is
well worth the trouble.

If the food of the “gouty” needs to be carefully selected, it is no less
necessary that the cooking be simple and appropriate. For the manner
of the cooking is, I am sure, in many instances, more responsible for
“gouty” outbreaks than the nature or the quantity of protein or other
intake. Twice-cooked food, made-up dishes rich in extractives, are
unquestionably pernicious. Nor are pickled or salted meats desirable.
Similarly, strong meat _consommés_, hare soup, and beef extracts are
best avoided. The same applies to rich gravies, sauces, spices, etc.,
all obviously likely to upset the digestion. Again, as to fish, it is
better boiled or grilled than fried, and still better not fried in fat.
In short, it is the “trimmings” more often than not that do the mischief,
these strongly abetted by “second helpings.”

The physician may well insist upon a sufficient interval elapsing between
meals. To attain due space between lunch and dinner, I invariably forbid
“gouty” subjects to eat anything with their _tea_. The repasts should
be taken in a leisurely fashion, if possible in a cheerful atmosphere.
“Unquiet meals make ill digestions.” The nerve element in these cases
is so pronounced that caution is anything but superfluous, viewing the
inhibitory effects of worry and mental excitement on the secretory
mechanisms of the alimentary tract.

The importance, too, of thorough mastication and regularity in meal-times
should be impressed upon them. The desirability, too, of postponing
the drinking of fluids to the end of the meal, and then only in small
amounts, should be emphasised.

Strenuous exercise, mental or bodily, immediately after a meal is
undesirable, and if, as is so often the case, there be any gastric
disorder, the subject should rest both before and after meals. This is
best taken lying down, especially if there be any tendency to _gastric
dilatation_ or _visceroptosis_. The same in _hyperacidity_, but in this
latter sleep is contra-indicated. For it has been shown experimentally
that the acidity of the stomach content is greater during rest than
movement. But this is just one of those points on which authorities
differ, and decision may have to be left to the patient’s own experience.

Lastly, we should always endeavour to ascertain as nearly as possible
the actual amount of the food intake per diem. This then must be
weighed in light of the subject’s age, body weight, and mode of life.
The middle-aged “gouty” person tends more often than not to obesity,
and it will fall to the physician to decide whether the food intake be
excessive or his habits too sedentary. Far more often than not it will be
found that it is not that he walks too little, but that he eats too much.
The appetite of youth goes ill with the inactivity of middle age. With
these general considerations we will now pass to a discussion of the main
elements of diet.


THE INDIVIDUAL FOODSTUFFS

_Proteins._—Ruthless cutting off of _protein_ foods, though not so
usual as of yore, is still far too commonly practised. The number
of unfortunate wretches who are docked of their red meats is still
astonishing. The “uric acid” bugbear dies hard. Unless red meat is
known to disagree, I never advise a “gouty” subject to abstain wholly
therefrom. I feel sure that it is rarely, if ever, called for, and when
enjoined has frequently wrought much harm. As far as I know, there is
no scientific reason for the very prevalent idea that for the “gouty”
white meat is preferable to red. It is certain that both contain an equal
quantity of extractives, and equally certain that for some, _mirabile
dictu_, white meat, _e.g._, rabbit, is more indigestible than red.

Accordingly let your “gouty” patient eat animal food, at any rate at
_one_ meal, but let it be of _one_ sort only. Let his appetite be his
only sauce, his meat plainly cooked and well masticated. It matters
not if it be red or white. What does matter is whether for _him_ it be
_digestible_. Mutton or lamb are more likely to prove so than beef or
pork, and chicken, turkey, or fresh game more easily assimilable than
duck or goose.

From Walker Hall’s experiments Luff thinks “it would appear reasonable
to administer sweetbread to gouty patients, since its nuclein portion
is only slightly absorbed, for thymus sweetbread contains principally
adenin, which is rapidly excreted, and pancreas sweetbread contains
mainly guanin, an amino-purin incapable of increasing the urinary purin
output and of exerting any injurious effects upon the tissues.”

Nevertheless I still think that “gouty” subjects are better without
thymus, pancreas, and other highly nucleated substances. Despite
our ignorance of the true nature of gout, we do know that there is
generally _an excess of uric acid in the blood_, and that to increase
the content thereof is undesirable. Again, we know that in _normal_ men,
after ingestion of pancreas and thymus gland, the _uric acid_ output
in the urine is _markedly increased_. But, on the other hand, many
observers—Magnus-Levy, Vogt, etc.—have noted that after the eating of
thymus by gouty individuals they found far less uric acid in the urine
than in the case of normal persons. In short, such purin-rich foods in
their instance is followed by _uric acid retention_.

More pointed still is the fact that _acute_ outbreaks of gout have been
repeatedly brought on by administering _thymus_ to the subjects of
_chronic_ gout. Surely, in light of this, it is impolitic to approve of
_sweetbreads_ as desirable ingredients of a “gouty” dietary, this even
if only on empirical as opposed to scientific grounds. That some “gouty”
persons eat sweetbreads with impunity is undeniable. But certainly if on
inquiry a subject overtly gouty admits a _penchant_ for these foods, we
should at any rate advise their restriction or elimination.

_Fish._—This pre-eminently, with certain exceptions, is very desirable
food for the “gouty,” especially those whose digestive powers seem
unequal to coping with the stronger kinds of animal food. The white-flesh
fishes, _i.e._, sole, whiting, turbot, brill, cod, plaice, flounder, are
the preferable. On the other hand, the red-flesh fish, _i.e._, salmon,
mackerel, herring, sprat, pilchard, eel, etc., contain much fat, and are
more likely to upset the “queasy” stomachs of the “gouty.”

But fish, it must be recollected, is less stimulating and satisfying
than the flesh of birds and mammals. If wholly denied butcher’s meat and
restricted to white fish, the subjects soon tire of it. It is best to
prescribe fish for one meal, say lunch, and in addition one type of meat
for dinner. Also it is important even in white fish to choose those most
easy of digestion, viz., sole, whiting, or flounder, in preference to cod
and haddock. Above all, let the fish be fresh, and not “out of season.”
Again, fish which is dried, salted, smoked or pickled, is much less
digestible than when fresh. If, even when taken in moderation and only
occasionally, it has been found to upset digestion, then abstinence is
the better course. Caviare is, I think, best abstained from, and hard or
soft roes generally only taken in strict moderation.

As to shell-fish, they have the reputation of being most unfriendly to
the “gouty.” Toxic symptoms after lobster and crab are held to be more
common in their instance than others. But many are, I fear, ready to
extend a personal idiosyncrasy on the part of some particular “gouty”
subject into a law for _all_ “gouty” subjects. I myself have seen no harm
follow them when taken in moderation, this as regards the fleshy parts,
more digestible in the lobster than the crab. It is, I think, wise to
abstain from the spawn of the female lobster, still more from the sauces
for which it is so largely used. As to oysters, I do not think there is
any objection to a “gouty” individual eating them raw, and when “in
season,” but in moderation.

In conclusion, there is, in the matter of flesh or fish, no rule
applicable to all “gouty” persons. Far from being harmful, it is both
necessary and beneficial if taken in moderation. No small part of the
objections raised to red meat is referable to the other rich foods that
often accompany it rather than to the meat itself.

_Carbohydrates._—If it be wrong to withdraw recklessly all proteins, it
is no less inadvisable, in the absence of special indications, wholly to
eliminate sugar or starchy foods. Nevertheless far more often than not
“gouty” subjects get the impression that if they wholly eschew _sugar_
all will be well. Latterly, too, I have noticed that the ban is being
extended to _starchy_ foods also.

Surely this as a routine procedure is wrong, the more so if, as too often
happens, the unhappy subject is left without any guidance as to how long
he is to suffer this deprivation. As a _temporary_ measure it is often
beneficial. But “gouty” subjects form no exception to the ordinary law
that if nutrition is to be maintained, their diet must contain a due
proportion of the main groups of foodstuffs. A “due” proportion, not
excess, for though _quâ_ _uric acid_ carbohydrates may appear ideally
suitable, yet the “gouty” are unfortunately no more immune than others
from the _dyspeptic_ disturbances that almost infallibly ensue when sweet
foods are taken immoderately.

It is this tendency in some “gouty” subjects to amylaceous dyspepsia that
has been wrongly extended into a law for _all_ gouty subjects, whether
they exhibit any carbohydrate intolerance or not. The only law is that
for the “gouty,” as well as for the non-gouty, carbohydrates, whether
taken as starch or sugar, are harmful if eaten to excess.

With this reservation, bread may be given as crisp toast, or rusks, or in
the form of _Zwiebach_. Nor is there any objection to milk puddings—sago,
tapioca, etc.—always provided that they are found digestible when taken
in moderate quantity. Similarly in regard to sugar there is, as Sir
Archibald Garrod says, “no reason to believe that to a gouty man a lump
of sugar is poison, and provided that it is digestible it must surely be
immaterial whether the allowance of carbohydrates be taken in the form of
sugar or starch.”

_Fats._—Apart from _obesity_, there does not seem to be any scientific
reason why fats should be denied to the “gouty.” All depends on their
_digestibility_, and in this they display variations. The fat of ducks
and geese is well dispensed with in favour of bacon fat and pork fat,
which are much more digestible. The fats of meat, when roasted or
browned, are best avoided.

Similarly there is no harm in a moderate amount of butter or cream,
but fatty sauces and soups are, I think, best refrained from. Ebstein
considered the best form of fat for the gouty was good fresh butter. As
to cream, Sir James Goodhart, discussing the treatment of uric acid,
observes: “In strict moderation it is seldom hurtful, for there is very
little in the common objection that it makes one bilious. Those who avoid
it are commonly ‘bilious’ because all their organs are starved.” But he
makes this further observation for our guidance, that “after middle age
cream taken in any excess may associate itself in some with the output of
uric acid.”

_Vegetables._—The various green vegetables are eminently suitable for the
“gout,” not so much on account of their nutritious qualities, but because
of the important inorganic salts they supply, notably salts of potash.
They give a wholesome variety and relish to food, render the urine more
alkaline, and do not favour the deposit of fat. Their indigestible
residue, too, stimulates the intestinal coat, and so promotes regular
action of the bowels.

Cabbages, greens, savoys, Brussels sprouts, cauliflower and broccoli
are familiar examples. These, provided they are fresh and well cooked,
are preferable to root vegetables, with the exception of potatoes. Nor
must we overlook the fact that green leaves are rich in fat-soluble
vitamine. Fortunately, too, in the case of this particular vitamine,
the loss involved by ordinary cooking is not serious. Spinach, too, is
rich in vitamines, and is laxative, but, being rich in oxalates, is
contra-indicated in oxaluria. Sorrel, by reason of its acid oxalates, is
also undesirable under such conditions, and the same is true of rhubarb.
Tomatoes also in former days were forbidden in gout under the erroneous
idea that their content of oxalic acid was high. Cucumbers, I think, when
eaten raw, are apt to upset “gouty” people. Asparagus and onions should
be taken sparingly, as they are rich in purins.

For “gouty” subjects, of all vegetables, the cruciferous or cabbage tribe
is the most suitable, provided they are young, fresh, well cooked, and
taken in moderation. In addition to its rich vitamine content, cabbage,
like cauliflower and lettuce, is almost _purin-free_. The excessive
intake of meat may often to some extent be counteracted by encouraging
such gluttons to eat freely of green vegetables. In this way we obviate
that sinking sensation which habitual overeaters suffer on limitation of
their pabulum. Lastly, vegetable soups are most suitable, preferably
those easily digestible, relatively poor in purins, or rich in potassium
salts.

Of the roots and tubers even of potatoes the “gouty,” I think, should eat
sparingly. The large percentage of starch in potatoes is apt to upset
those of feeble digestion. Much depends on whether they are “mealy”
or “floury,” and not “waxy” and “watery.” Steaming is the best method
of cooking them. Turnips are best abstained from, and also carrots,
parsnips, beetroot and radishes, save at any rate in minimal quantities.

Lastly, the legumes—peas, beans, lentils—because of their high purin
content, should always be partaken of sparingly, though perhaps it may
yet be found that their purin content may be more than compensated for by
their contained vitamines. The edible fungi, mushrooms and truffles are
best dispensed with.

_Fruits_ are a valuable food for the “gouty.” They impart alkalinity to
the urine, and promote intestinal action, always provided they are not
partaken of immoderately or when unripe or overripe, when they are apt to
set up gastro-intestinal irritation.

Most fresh ripe fruits are wholesome. Their content, too, of vitamines
cannot be overlooked, especially that of oranges. Moreover, the fact
that vitamines, as a rule, are destroyed at cooking temperatures seems
to indicate that some uncooked food should on principle be taken daily
by the “gouty” as well as others. Raw ripe fruits in this respect, like
salads, have an advantage over cooked fruits or vegetables.

In my own experience I do not know that there is any fruit, even
strawberries, that will infallibly disagree with the “gouty.” One
meets now and again with gouty subjects who are unable to eat certain
fruits with impunity, but one meets with quite as many of the same
idiosyncrasies in the _non-gouty_. The objections to certain fruits,
_e.g._, strawberries, as to certain vegetables, _e.g._, asparagus,
are largely theoretical rather than practical. Let the subject’s own
experience be your guide in this matter, or if he be unobservant, teach
him to observe for himself what fruits, if any, disagree with him.

With this reservation I am of opinion that, taken in moderate quantity,
fruits are most useful constituents of diet for the “gouty.” In some
cases it will be found that they cannot take fruit when mixed up with
other food, but both enjoy and derive benefit from it when taken by
itself. It is well, again, in others to restrain their immoderate
indulgence in lemons, as these frequently, as Sir James Goodhart pointed
out, upset gastric or intestinal digestion. It is advisable also to warn
them that plums, currants, gooseberries, and other fruits containing
large quantities of free acids are apt to have the same effect, while
the melon, too, is prone to give rise to gastric disturbance. Peaches and
nectarines, on the other hand, are eminently suitable for the “gouty,”
also apples, pears, oranges, grapes, cherries, etc.

_Condiments._—These substances give a flavour and relish to food, while
their carminative properties stimulate appetite and favour digestion.
On the other hand, their excessive use is a potent source of gastric
irritation. Thus, for example, they are valuable in atonic dyspepsia,
though liable to aggravate a condition of chronic gastritis.

The most important and most extensively used is common salt. Some
incline to think that its use by persons of the “uric acid diathesis” is
prejudicial. But unquestionably it is a necessary and wholesome article
for the “gouty” when taken in moderation. In cases of gout complicated
by _hyperchlorhydria_ strict moderation in or abstinence from salt seems
indicated, this because, the HCL of the gastric juice being wholly
derived from the chlorides of the blood, it seems irrational to increase
the supply. Some therefore forbid its use both as a condiment or in the
cooking of food, making the subject depend on the salts naturally present
in foodstuffs.

Vinegar, I am sure, upsets some “gouty” persons’ digestion, and I think
Sir Dyce Duckworth is right when he counsels abstinence therefrom. Thus
some “gouty” subjects can digest raw cucumber, but not with vinegar.
Others find salmon if combined with the same condiment upsets them,
but not without. As to the various other condiments—mustard, pepper,
horseradish, etc.—there is no objection whatever to their use by the
“gouty” in moderation and in the absence of any definite gastric disorder.

So much for our consideration of the individual foodstuffs—their
suitability or not—for the subjects of gout. That such a general survey
is advisable may perhaps be conceded, but in so far as it may approximate
to _fixed rules_ it savours of evil, this at any rate as far as the
dieting of _dyspeptic_ derangements of the “gouty” is concerned. To bring
into prominence my point, I would lay down the postulate that there is
_no specific form of “gouty” dyspepsia_.

The gastric derangements met with in gout are in no sense peculiar
thereto. In other words, they present no symptoms specific of gout,
despite the term “gouty dyspepsia.” The term “hyperacidity” as commonly
invoked is far too laxly used in regard to “gouty dyspepsia.” The
“acid risings” of the “gouty” are of two kinds. Hyperacidity may be
due to _organic acids_, butyric, lactic, or acetic, the outcome of
fermentation, or the condition may be one of hyperchlorhydria, or
excessive secretion of HCL.

_Hyperacidity_ due to _organic acids_ is met with in some cases of
_atonic dyspepsia_, _chronic gastritis_, and _dilatation of the stomach_.
The free HCL is either diminished or absent. Differentiation of this type
from _hyperchlorhydria_ may be impossible without examination of the
stomach contents.

Hyperchlorhydria _per se_ sometimes occasions pyloric spasm, and minor
degrees of dilatation follow, this the more commonly as the subjects of
gout are middle-aged or elderly. In others the dilatation is part of a
general _neurasthenia_ from which the “gouty” no more than others are
immune.

Again, gout of long standing is often associated with _chronic gastric
catarrh_. Such is very common in beer-drinkers or men employed in
breweries. A state of _atonic dilatation of the stomach_ is a common
sequel. In these cases of chronic gastritis in the “gouty” the free
HCL may be normal, diminished or absent. Eventually, as the result of
oft-repeated gastritis, the parts involved undergo widespread _fibrotic
degeneration_. Also we have to recollect that the “gouty” are very
subject to obstinate _gastralgias_.

We see therefore that the “dyspepsias” of the “gouty” may be not only
of varied nature, but may also demand differential dieting at different
phases of their evolution. The subject in the early stages of his gout
may suffer from hyperchlorhydria, while later chronic gastritis may
ensue, with the reverse condition, _hypochlorhydria_. The _protein_
dietary suitable for the former has in the presence of the latter to be
replaced by _carbohydrates_, despite their tendency to fermentation.
Again, if either condition be complicated by _dilatation_ other
exigencies must be met. The meal content must be light, not bulky, and
the fluid intake restricted.

Again, the foregoing gastric disorders may be complicated by _glycosuria_
or _albuminuria_, each with separate dietetic indications. How inevitably
futile then must be any attempt at stereotyped diet for the “gouty.”
In short, the dyspepsias and other morbid states of the “gouty” call
for eclectic, not routine, dieting, and to this end I append a few
suggestions.


SPECIAL DIETARIES

_Amylaceous Dyspepsia._—Not a few “gouty” subjects suffer from
atonic dyspepsia, with _acidity_ due to _organic acids_ arising from
fermentation. Frequently it appears to be the outcome of some previously
prescribed regimen forbidding all flesh food, or of too frequent or
irregular meals or habitual overfeeding, food-bolting, excessive smoking,
etc. Correction of such faulty habits is an essential prelude to any
dietetic rules.

In such cases it is advisable to reduce the intake of starchy and
saccharine foodstuffs, such as bread, potatoes, pastry, sugar, milk
puddings, and the like. Bread should be stale, or dextrinised by dry
heat, as in thin toast and rusks. Potatoes, if taken, should be in the
form of purées. Sweet dishes should be partaken of sparingly, if at all.
They should be encouraged to take the more digestible forms of meat and
the lighter kinds of fish. Green vegetables and fresh ripe fruit, raw
or cooked, are valuable. _Fats_ of the more digestible sorts are also
desirable. Grilled but not fried fat bacon is easily digested.

As to beverages, light China tea is more suitable than strong Indian
kinds. Frequently I have found substitution of cocoa most beneficial. But
in any case the amount of fluid at meal-times should be restricted.

As a guide to the formulation of a dietary in such cases the following
may be suggested:—

On awaking in the morning a tumbler of hot water should be slowly sipped.
A squeeze of lemon may be added if liked.

_Breakfast._—Boiled or plainly grilled sole, whiting, or flounder, or a
slice of crisp grilled bacon or lean cold tongue, or a soft-boiled egg.
A slice or two of crisp dry toast or stale bread and a little butter. At
close of meal sip slowly one cup of weak China tea, or the same of cocoa
or milk and water.

_Lunch._—Chicken or game, or lamb, mutton, or beef, hot or cold, roast or
boiled. Gravy to be free from fat. One only of the former kinds of meat
to be taken with a reasonable quantity of tender, well-boiled vegetables.
Spinach, kidney or French beans, sea or Scotch kale, vegetable marrow, or
salad may be taken, but without oil, vinegar, or beetroot. Dry toast or
rusks. Half a tumbler of water sipped _after_ eating.

_Afternoon Tea._—One or two cups of weak tea with milk or one cup of
cocoa.

_Dinner_ (two courses only).—Fish of the kinds allowed for breakfast
without potatoes, or a slice of any tender meat, _e.g._, saddle or loin
of mutton or thick part of an underdone chop, or small portion of fresh
game, without bread sauce or crumbs. One or two slices of stale bread
or dry toast. A little well-stewed fruit or custard, junket, or jelly.
Half a tumbler of water with from one to two tablespoonfuls of spirit if
desired.

If there be any suspicion of chronic gastritis, condiments and stimulants
must be renounced, but not in purely atonic dyspepsia, in which they are
of value. In either disorder the patient should abstain from salted and
cured meats, tinned foods, pastry, sweets, raw vegetables, and cheese.
Before retiring a tumbler of hot water with a squeeze of lemon may be
sipped slowly.

_Hyperchlorhydria._—This, the true “acid gouty dyspepsia,” is the most
troublesome type of dyspepsia met with in the “gouty.” Regulation of
the diet is the best means whereby to combat the excess of HCL in the
stomach. All irritating spices or condiments, mustard, vinegar, etc.,
should be avoided. Salt especially should be used sparingly or wholly
abstained from. As a rule, alcoholic stimulants are not well borne, and
may, in the absence of special indications, be prohibited. In a limited
number of instances a light wine may be allowed as a stomachic. To avoid
irritation, hard substances, such as nuts, should be interdicted, and
food thoroughly masticated, and taken neither too hot nor too cold.
Bolting large morsels of food may readily excite pyloric spasm.

In these cases of superacidity the most suitable foods are _proteins_,
which combine and neutralise the excess of acid. A liberal meat diet
consisting in the main of chicken, beef, mutton or ham, is indicated.
Also fish, eggs, hard or soft boiled, are permissible. _Farinaceous_
foods are not well tolerated, and if given must be of the most digestible
kind. Vegetables should be mashed and strained to rid them of cellulose,
and only the more digestible kinds taken, and in the form of purées.
Fats tend to lessen acidity, and are therefore indicated in the form
of butter, cream, olive oil, and such like. Of beverages alkaline and
mineral waters, Apollinaris, Seltzer, and Vichy, prove very beneficial.
Their contained carbonic acid exerts a sedative effect and diminishes the
secretion of acid. Milk or stimulants may be profitably diluted therewith.

Coffee is best abstained from, and cocoa and tea freshly made with half
milk substituted. Soups are best avoided. If with the _hyperacidity_
there be associated any degree of _atonic dilatation_, the fluid taken
at meals should be restricted. Also in this instance the food should be
taken in small quantities and at frequent intervals. Otherwise these
cases of _hyperacidity_ do well on three meals per diem provided they are
separated by an adequate interval.

If the foregoing measures prove ineffectual the _carbohydrate_ content
of the food should be withdrawn, and the patient limited to a strictly
_meat_ diet, taken either raw or very slightly cooked. It goes best
when finely minced or grated on stale bread. According to Osler, an
ample dietary is afforded if three and a quarter ounces of meat and two
medium slices of stale bread be taken three times a day, with a glass
of Apollinaris water or soda-water, or what in this authority’s opinion
is just as satisfactory—spring water. For the bread a little dry toast
or twice baked (_Zwiebach_) bread may be substituted. Some advocate the
meals being taken wholly dry, or with two ounces of fluid only; but two
hours later a half to two pints of hot water should be slowly sipped. A
month or six weeks of such a diet will usually suffice, after which a
gradual return may be made to a mixed dietary.

Apart from the binding of excess of acid by the protein substances
and consequent relief of discomfort, the so-called Salisbury diet has
other advantages. Abstraction of the carbohydrates obviates intestinal
fermentation and flatulence. Also, the food administered being small in
bulk, and taken more or less dry, a dilated or atonic stomach tends to
revert to its normal size.

In conclusion, in regard to these cases of hyperchlorhydria it must
be realised that not only their diet and the manner of their eating,
but their general habits of living, must also be revised. They must be
warned of the great tendency to recurrence and the necessity of orderly
and regular habits and of strict abstemiousness in regard to not only
alcohol, but tobacco. The nerve element in some of these cases is very
pronounced, and sometimes nothing short of a rest cure will suffice.

_Hypochlorhydria._—Chronic gastric catarrh due to overeating and
overdrinking is not an infrequent complication of gout in its later
stages. Such subjects suffer with daily or periodical vomiting of
stringy mucus. In such cases the HCL of the gastric juice is deficient
or absent. Consequently protein foods are digested with difficulty, and
carbohydrates are more easily disposed of. The lighter forms of meat,
such as chicken or fish or raw scraped beef, are indicated. Nor, in view
of the chronic nature of the derangement and the necessity of maintaining
nutrition, should we hesitate to allow such “gouty” subjects other
digestible forms of meat, such as sweetbreads, brains, etc. Fats also and
carbohydrates up to the limit of tolerance should be allowed. Ingestion,
however, of fluid at meals should be reduced as far as possible. Of
beverages milk, and especially buttermilk, is particularly suitable.

Despite the deficiency of HCL, they may suffer much with acid eructations
or flatulency owing to organic acids arising through fermentation. If
so, farinaceous foods must be restricted, particularly potatoes and the
coarser vegetables, while of course pastry and sweet foods should be
prohibited. Bread should be taken in the form of dry toast or rusks.

_Hyperuricæmia._—As far as is known, the endogenous moiety of urinary
uric acid is uninfluenced by diet. On the other hand, as has been shown
in previous chapters, the exogenous fraction can be reduced by suitable
dieting. To this end, in order to prevent the intake of food containing
uric acid precursors, the purin-free dietary was devised. Under such a
regime both red and white meats must be proscribed, also fish and the
legumes—peas, beans, lentils, asparagus, onions and oats—as these last
are all rich in purins. Tea, coffee, and chocolate must also be eschewed.

In lieu of these substances more or less poor in purin bodies must be
exclusively taken: milk sour or curdled, buttermilk and whey, white
bread, butter, cheese, eggs, rice, tapioca, macaroni, sago, cereal foods,
nuts and fruit. Even strawberries are permissible, for Weiss noted
that the addition to an ordinary diet of 1 lb. of strawberries, 1½ lb.
cherries, or 2 lb. of grapes, diminishes the amount of uric acid excreted
by almost 50 per cent. With the exception of those interdicted above, all
vegetables are allowable, cabbage, cauliflower and lettuce being almost
purin-free.

Personally I am not enamoured of purin-free diets for the “gouty,” any
more than I am of the purely vegetarian regime, so extolled by some as
the means of averting gout. The purin-free diet, if I may say so, smacks
too much of the laboratory, its _raison d’être_ the baseless assumption
that _uric acid_ is the _fons et origo mali_.

I am very doubtful of the intrinsic merits claimed for it. I do not
think it exerts a direct or _specific anti-gouty_ influence. Such
advantages as do accrue are referable, in my opinion, to the greater
measure of _intestinal asepsis_ that such a regimen promotes. It is
suitable, therefore, in cases in which there are evidences of _intestinal
putrefaction_. Distinctly unappetising, it is useful, too, as a
disciplinary measure for those prone to overeating.

Its advocates claim that it tends to diminish the _excess of uric acid
in the blood_. But, as was pointed out when dealing with uricæmia,
_variations_ may occur in the _uric acid content of the blood
independently of diet_. Moreover, acute attacks have been observed even
when the uric acid blood content was at a _sub-normal_ level.

To place all “gouty” subjects on a _purin-free_ diet as a routine
procedure is to my mind wholly impermissible. The fact that prolonged
adherence thereto is usually found impracticable is surely an indication
that we are violating nature’s laws. It may prove beneficial in a few
isolated cases, and then only for a time; but in the vast majority of
instances it is frankly prejudicial. Given a carefully revised mixed
diet, it will, in my experience, be rarely, if ever, necessary to subject
“gouty” individuals to this dietetic penance.

_The Reduction of Obesity._—Unfortunately obesity is a common associate
of gout, and with it not infrequently comes _glycosuria_. Middle-aged
“gouty” subjects have in their youth often been given to strenuous
exercise. But notwithstanding that with advancing years their capacity
and disposition for exercise lessens, they nevertheless take the same
amount of food as of yore.

It is most difficult to make them realise that, with the alteration of
their habits, the amount of food which at one time was but adequate is
now excessive. I have found it useful to remind such of Ebstein’s dictum,
“The gouty who have grown old in spite of their disease are almost
always those who have been able to avoid obesity.” Still it is only fair
to add that in some of the gouty obese no accusation of overeating or
overdrinking can be lodged, and their aptitude for fattening seems often
hereditary.

Reduction of the body weight when excessive in gouty subjects is hardly,
I think, sufficiently emphasised. The victim himself is but too often
convinced, however, that he ought not to be “lowered,” and sometimes, I
think, infects the physician with his apprehensiveness on this score.
But, as Harry Campbell rightly observes, “people do not die of starvation
so easily as is generally thought, and it is very difficult for the
physician to kill his patients in this way.” Yes, and, on the contrary,
how often do gouty people “dig their graves with their teeth.”

Again, there is the _static_ element to be considered in these cases. The
articular manifestations of gout are by preference located in the lower
extremities. It is clear then that excessive stoutness, particularly if
of recent development, must inevitably throw increased strain on the
already-hampered articulations. The feet of the “gouty” are their most
vulnerable point, and the number who are flat-footed is noteworthy. In
the presence of this static fault, “strains” or “sprains”—those fertile
excitants of gouty outbreaks—are much more liable to occur, and I myself
feel sure that in this way the frequency of attacks in the feet and, for
that matter, in the knees also, is favoured.

Lastly, the gouty obese is frequently elderly, his vessels somewhat the
worse for wear. Also he may show signs of cardiac weakness or a trace of
albumen or sugar in his urine. Even so his weight should be reduced if
possible. His watchword should, like Falstaff’s, be:—

    “Make less thy body hence, and more thy grace;
    Leave gormandising; know the grave doth gape
    For thee thrice wider than for other men.”

There are so many dietetic methods of treating obesity that they cannot
all be outlined here. The Banting method, like the Salisbury, is too
severe for the average patient, while the Weir-Mitchell method has
one cogent objection to general adoption, viz., the expense entailed.
Nevertheless as regards the last-named, or skim milk, method, it
certainly achieves marvellous results in those cases in which there is a
mere accumulation of fat without any other complication.

Generally speaking, however, one has to be content with the following
suggestions: All varieties of lean meat may be taken, as well as poultry,
game, and fish, subject to idiosyncrasies and digestibility. Meat may
be taken twice daily, not exceeding six ounces at one time. All starchy
and farinaceous food is to be reduced to a minimum or wholly forbidden.
Leaf vegetables may be taken freely, but the roots and tubers, such as
potatoes, abstained from. Bread should be largely reduced in quantity and
thoroughly torrified. Sugar must be prohibited, and saccharine or saxin
substituted. Fresh fruits may be eaten, but milk should be avoided, also
cream, or very strictly limited. Where feasible, it is often a good plan
if the subject can for one day a week content himself with a diet of skim
milk.

Alcohol, as far as possible, should be rigidly excluded, or only a
very moderate quantity of good whisky or a light wine, such as hock
or Moselle, permitted. As a rule, only a little hot water should be
sipped at meals. But I think in these subjects of so-called “uric acid
diathesis” it is well not to restrict their fluid too markedly. A pint
of hot water may be drunk one and a half hours before each of the three
meals, and one pint more half an hour before bedtime. Weak hot tea may
be substituted, as many subjects find a difficulty in drinking so much
plain hot water at one time. If while on this regime the subject lose
weight and _pari passu_ gain strength, all is well. If he lose weight
and therewith lose strength, further reduction or its continuance is
contra-indicated. It should be recollected that the reducing effects of
dieting may be markedly enforced by an open-air life, with riding or
other outdoor exercise.

_Glycosuria._—This condition conjoined with obesity is not uncommon in
middle-aged “gouty” subjects. It is of benign type, and the amount of
sugar excreted is usually reduced to a mere trace by extraction of the
carbohydrates in the food. Thus, we should forbid, _e.g._, sugar, pastry,
sweet wines, and dishes made with flour, rice, or sugar. In these cases
von Noorden considers that it is better after reduction of the amount of
sugar by dieting to a mere trace to be content rather than to get rid of
it wholly by a rigid elimination of all carbohydrates. To this end the
patient may be allowed to eat a limited amount of bread, potatoes, and
other vegetables, while he may eat freely of butter, bacon, and other
fats.

One should recollect also that these “gouty” glycosurics have periods of
enhanced carbohydrate tolerance, this, as Burney Yeo pointed out, quite
“independently of any therapeutic interference.” In short, at times they
can take quite a considerable amount of carbohydrates without passing
sugar in their water.

Needless to say, the regime must be adapted to each individual case.
The urine should be examined frequently, and the influence on the sugar
content of different articles of food noted; also the weight should be
frequently taken. It is certainly unnecessary in gouty glycosurics to
wholly banish the carbohydrates. By such a plan we are more likely to do
material injury than by exceeding by a little their limits of tolerance.
Our remarks of course apply strictly to _alimentary_ glycosuria. But we
should also remember that exceptionally a case of gouty glycosuria may
emerge into one of true _diabetes_.

_Albuminuria._—In the so-called “gouty” contracted kidney, if the amount
of albumen in the urine be very large, or when there are symptoms
of nephritis, a milk diet for a few days or a week at a time may be
given. More often it is unnecessary, or it is frequently badly borne or
rejected. Consequently a modified milk diet has to be adopted, and a
gradual return to a mixed diet permitted, provided no increase in the
quantity of albumen ensues.

But at the same time it must be realised that no rigid rule can be laid
down for “gouty” albuminurics. As a guide to the suitability of a diet it
is better to rely on the _general condition_ than on variations in the
amount of albumen. For, as Professor H. Andrew Smith, of New York, long
since said, “if on changing from a non-nitrogenous diet to a nitrogenous
one we find a general improvement in the patient’s condition, it is an
evidence that the change is beneficial, no matter if the albumen fills
a larger portion of the test tube. On the other hand, if we cut off a
large proportion of animal food from the diet, and our patient grows
more dyspeptic, weaker, more anæmic, more dropsical, it is nothing to
the point that only one half or one-third of the former quantity of
albumen is found in the urine; the change has done harm, and the sooner
we change back again the better. We should, above all things, seek that
diet for the patient which he can best digest and assimilate, for we may
rest assured that the products of faulty digestion and assimilation will
irritate the kidneys more than any amount of normal material they may be
called upon to eliminate, while, at the same time, the general system
will suffer from lack of support.”

Lastly, up to this juncture all our suggested dietetic modifications
have been in the direction of reduction or abstinence. But we must
recollect that in practice we find that not a few gouty persons are
most careful and prudent in diet. They commit no indiscretions, but
nevertheless their gout is still with them. They are of the asthenic
type, thin, pale, sallow, and given to neuralgic forms of fibrositis.
They do not want “lowering”; to curtail their food is harmful. In their
instance, with due respect to digestive idiosyncrasies, a more or less
generous diet should be prescribed. Let them forsake dietetic schedules
and follow their instincts. Let your advice be that of Sir William
Temple: “Simple diet, limited by every man’s experience to his own easy
digestion, and thereby proportioning as near as can be the daily repairs
to the daily decays of our wasting system.”


BEVERAGES IN GOUT

It cannot be gainsaid that the beneficial effects of so-called “water
cures” are in great measure referable to the increased amount of _water_
ingested during their progress. Absorbed in the main in the small
intestine, it passes into the general blood stream, whence it is excreted
_viâ_ the skin, kidneys, lungs, and fæces. Its elimination through these
various channels sufficiently accounts for its value as a means of
flushing the bodily tissues and hastening the excretion of retrograde
and toxic products. Indeed, its efficiency as a depurative agent cannot
be over-estimated, and nothing is more beneficial for the subjects of a
“gouty” diathesis than regular consumption of an adequate quantity of
this admirable solvent.

By general consent, the water ingested should be preferably _hot_. Water
of a higher temperature than that of the blood stimulates the hepatic
cells, and promotes biliary excretion. It has been shown, moreover,
by Glax that while draughts of cold water raise vascular tension and
diminish pulse frequency, on the other hand hot water diminishes arterial
tension and accelerates the pulse rate.

It is also claimed that the increased elimination of water _viâ_ the
kidneys is correlated with an augmented output of the solid constituents
of the urine; that the phosphates, sulphates, sodium chloride, and
likewise urea are for the time excreted in greater amounts.

The point at issue, however, is whether or no this increase in the amount
of _urea_ excreted can be held to indicate enhanced tissue change in the
nitrogenous elements in the body fabric.

Winternitz claims that it does, in contrast to Von Noorden, who holds
that nitrogenous tissue change and the formation of _urea_ and _uric
acid_ are _uninfluenced_ by the amount of water imbibed. In further
contradistinction some contend that following the ingestion of water the
_excretion of uric acid_ is _diminished_.

Fortunately for “gouty” subjects, the beneficial effects of water
flushing of their systems occur independently of any _coincident increase
in their uric acid output_. This is true even of mineral waters. Thus
Bain and Edgecombe noted that following the ingestion of the old
sulphur water of Harrogate the excretion of uric acid was diminished.
Nevertheless cases of “gout, especially of the _asthenic_ type, derived
the most marked benefit from its use.” “This fact is mentioned,” they
say, “because some writers attach the greatest importance to an augmented
excretion of uric acid in the urine as a necessary concomitant of
successful treatment. This we firmly believe to be an erroneous view.”

Indeed, ignorant as we are of the exact etiology of gout, we must at
any rate provisionally attribute the proved efficacy of water-drinking
in gout to its flushing action on the tissues, its furtherance of the
excretion of waste products. Nor can we doubt that the ingestion of hot
water, involving as it does equalisation of its temperature with that of
the body, must exert a profound and intimate effect upon processes of
cell nutrition. Moreover, through its solvent and penetrative quality,
its mineral or chemical constituents are enabled to penetrate freely the
interstices of the tissues throughout the economy.

It is, therefore, well to advise “gouty” subjects to drink daily on
rising from eight to ten ounces of hot water, repeating the same half an
hour before lunch and dinner, and finally the last thing at night. For in
my experience “gouty” subjects on the whole do better if they drink some
time before their meals than during their progress. It is an old belief
that hard waters are unsuitable for the “gouty.” Sir Dyce Duckworth
believed so, and Sir Charles Scudamore in 1823 delivered himself as
follows: “The kind of water denominated hard has always been considered
as unfriendly to health, and especially injurious to persons afflicted
with gravel or stone. Many probably imagine that the earthy salts which
it contains assist in making up the mass of the calcareous concretion.”

But more probably, as Sir Archibald Garrod suggests, the old view that
tophi were composed of chalk had probably something to do with the origin
of the tradition. That hard waters may be noxious in so far as they
favour constipation may be granted. But, on the other hand, we have to
reconcile with this the awkward fact that earthy or calcareous waters,
_e.g._, those of Bath, etc., are among those whose efficacy in gout is
beyond question.

Again, how can we reconcile with this view the prevalent practice of
placing “gouty” subjects, temporarily at any rate, on a _milk_ diet, this
although milk is especially rich in lime? That a regime of milk in the
young and robust “gouty” subject is often extremely beneficial is beyond
question. On the other hand, it is equally certain that others do not
thrive thereon. In prescribing it, therefore, we must be guided largely
by _personal idiosyncrasy_.

Lastly, as to _tea_ and _coffee_, there is a theoretical objection that
both contain methyl purins. Albeit, it must be seldom indeed that gout is
met with in pure tea-drinkers who at the same time abstain wholly from
alcohol. Either tea or coffee, if taken apart from food, usually agrees
well with the “gouty,” always provided that they be well made and not
over-strong. Of the twain tea is, I think, more generally suitable than
coffee, and where both disagree cocoa is an excellent substitute.


ALCOHOL IN GOUT

Said Sir Thomas Watson: “I am sure it is worth any _young_ man’s while
who has had the gout to become a teetotaler.” Few will gainsay the
wisdom of this advice. But I would fain go further and impress on _gouty
parents_ the incumbent duty of bringing up their children as _total
abstainers_. For gout, once avowed, has a vicious tendency to recurrence.
The illustrious Sydenham, I think, would have approved of such advice:
“Water alone is bad and dangerous, as I know from personal experience.
When taken as the regular drink from youth upwards it is beneficial.”

When, however, gout attacks a man for the first time in middle or late
life, most authorities agree that an abrupt change of habit in respect
of stimulants is of questionable wisdom. In saying this, I do not for
one moment mean that excess should be approved, but that I do not
believe that the enforcement of total abstinence is prudent. In such
cases restriction, not total elimination, is the better course. One must
recollect, too, that total abstainers are by no means exempt from gout,
while, on the other hand, many, if not the majority, of drunkards are.
The latter have their penalties, cirrhosis, etc., but not inevitably gout.

I agree that gout is infinitely more common in those who take alcohol
than in those who abstain therefrom. But nowadays, at any rate,
the “gouty” as a class cannot with fairness be ranked as among the
confessedly intemperate. With relatively few exceptions, they belong
rather to those given to what may be termed the legitimate use of
alcoholic beverages. My conclusions then are that:—

    (1) The children of “gouty” parents should be brought up as
    total abstainers.

    (2) The incidence of a first attack in a young man should be
    the signal for abstinence from alcohol in all forms.

    (3) Given its occurrence in an older subject who has used
    alcohol but sparingly and stands in no need of it as a
    stimulant, the same total abstinence should be inculcated.

    (4) In middle-aged or old subjects habituated to the use or
    abuse of alcohol _abstemiousness_, not abstinence, is the safer
    course.


THE VARIOUS ALCOHOLIC BEVERAGES

_Malt Liquors._—I think we should distinguish between the “strong” and
the “mild” varieties, even as we do between “heavy” and “light” wines.
“Strong” malt liquors unquestionably are most provocative of gout, and it
is not without significance that most “gouty” subjects have, frequently
on their own initiative, abandoned their use. So much importance, indeed,
do I attach to this, that if I were called to formulate any rule in the
matter of alcohol for “gouty” subjects it would be the unsuitability of
“strong” malt liquors, which not only increase the tendency to recurrence
of the paroxysms, but appreciably lengthen their duration.

The prefix “strong” I use advisedly, as the volume of alcohol contained
in different beers may vary by as much as from 1 to 10 per cent. Thus
Scotch ale contains as much as 8·5 per cent., and, generally speaking,
all “old” ales are usually “strong” ales. Albeit, to condemn malt liquors
unreservedly is, I am sure, inadvisable. The truth is that in respect
of their _gout-inducing power_ malt liquors, like wines, display great
variations.

Thus “strong” malt liquors, like “heavy” wines, are markedly provocative
of gout, whereas the “milder” ales, like the “lighter” wines, are
relatively impotent in this respect. Said the elder Garrod on this point:
“The lighter wines, as claret, hock, and Moselle, although capable of
acting as the exciting cause of an attack in gouty subjects, have when
taken in moderation but comparatively little inducing power, and in this
respect rank with the weaker kinds of malt liquors.” In this connection
is it not significant that gout is extremely rare among agricultural
labourers, who drink freely of that popular and ancient beverage mild
beer? Sydenham on this point is very definite: “This is a rule for the
gouty: they may take those liquors which neither chill the stomach
nor intoxicate in any moderate quantity. Such is the small beer in
our own country, which in foreign countries may be replaced by weak
wine-and-water.”

I hold no brief for alcohol, but of the twain I am sure it is wiser to
advise a poor man, even though “gouty,” to stick to “mild beer” rather
than urge him to betake himself instead to “ardent spirits.” For the rich
man, too, while in his prime and still capable of vigorous exercise, I am
firmly of opinion that, with due deference to _idiosyncrasy_, a _mild_
beer not containing more than from 3 to 6 per cent. of alcohol will do
him not more, but less, harm than _whisky_.

I have yet to learn that the working man who has gout and sticks to
mild, sound beer in moderation gets attacks more often or more severely
than the rich man who affects whisky. “It must,” as Sir Archibald Garrod
observes, “be confessed that among hospital patients who could not, if
they would, follow out any strict rules of dietary, who seldom pay heed
to our advice that they should give up beer, and who, as soon as an acute
attack is over, revert to their previous habits of life, the course
of gout does not seem to differ materially as regards the character,
frequency, and severity of the attacks from that followed in people
who are able to adjust their living according to the best advice to be
obtained.”

I think then in this matter of _malt liquors_, their suitability or
not for “gouty” subjects, we should be well advised to reconsider our
attitude. In other words, I would urge that we draw a distinction between
“strong” and “mild” malt liquors. By all means let us continue to condemn
the “heavy” varieties, while not extending the ban to the “lighter”
forms. I would, however, make the following reservations: that—

    (1) It be a “light” beer, in which the “bitter” principles
    predominate, and the extractives are small in amount[61];

    (2) It be “sound” and not “turned” beer, and of course free
    from any possibility of _lead_ impregnation;

    (3) It be taken in moderation, not exceeding one to two pints
    per diem;

    (4) The “gouty” subjects by whom it is taken be physically
    active;

    (5) Due respect be paid to _personal idiosyncrasy_, reserving
    its use for those in whom its effects are definitely
    _stomachic_ and _tonic_, while discountenancing its use when
    followed by _heaviness_, _drowsiness_, and _biliousness_.

As to _cider_, there is no doubt that the partially fermented or sweet
variety is more harmful than “dry” or “rough” cider. Still there is no
room for dogmatism even here, for a “gouty” man, if he be unaccustomed to
cider, may find that, whether “dry” or not, it may provoke an attack. Sir
Archibald Garrod tells us that he has known not a few gouty patients who
alleged that cider suited them admirably, but he adds: “An experience of
some months has usually modified their opinion on this point.”

_Wines._—When we come to consider _wines_, we are on very uncertain
ground, this especially if we base our opinion too much on the _chemical_
analysis of this or that variety. The current belief is that the most
unsuitable wines are those that contain large amounts of _alcohol_,
_sugar_, or _free acid_. Then we discover it is not the amount of
_alcohol_ in the fluid that determines the incidence of gout and, in
witness to our perspicuity, call to note the rarity of gout in Scotland,
where _whisky_ is the favourite beverage; _ergo_ whisky _par excellence_
is _the_ drink for the “gouty,” and so we find ourselves in this
_impasse_: we fulminate against _alcohol_ as _the_ cause of gout, and
in the same breath advise our “gouty” patients to drink precisely those
fluids containing the highest percentage thereof.

True, when we turn to _wines_ we find that it is precisely those that
are richest in _alcohol_ that most potently predispose to gout, _e.g._,
port. But seeing that _whisky_ contains infinitely more _alcohol_ than
port, and yet is little gout-provoking, we search round for some other
constituent in wine on which to lay the blame. So we decline on the
varying degrees of _acidity_ in different wines. But this again on
reflection, it is decided, is of little moment. For, on the one hand,
port and sherry are among the least acid wines, and yet, like the even
less acid malt liquors, most productive of gout, while, on the other
hand, the more acid clarets and hocks are deemed relatively harmless.
Then the varying quantities of _sugar_ in the different wines come under
the ban. But here again no definite line can be drawn. For some wines
most provocative of gout have a high sugar content, while others equally
potent in this direction contain but small amounts.

Now the most salient deduction from the foregoing considerations is our
inability at present on _chemical grounds_ to determine why certain
_wines_ are productive, and others are relatively nonproductive, of
gout. We can impeach neither the alcohol content, the acidity, nor
the sweetness. For on all these points startling exceptions preclude
dogmatism. Does not the clue to these varying reactions _quâ_ gout reside
in the _individual_, not in the character of the wine? We are far too
prone to say that this or that _wine_ is “gouty,” to say that this wine
gives you gout, and that not.

The evil potentialities that make for gout reside not in this or that
particular wine, but in the _individual_. This or that wine does not give
him gout, but evokes or brings to fruition a morbid tendency already
_latent_ in him. In the absence of this inherent proclivity, it would
not have elicited those specific local reactions typical of gout. But
for those who would interpret this statement as approval on my part
of alcohol or an absolving thereof from any part in the genesis of
gout I would issue this _caveat_: Alcohol will not originate gout in a
_non-gouty_ subject, but it will almost infallibly in those in whom there
exists by heredity an inborn tendency to gout. In short, the “gouty” are
_hypersensitive_ to the evils of alcohol; the greater the need then for
_abstemiousness_ and self-restraint.

But, to resume the thread, in the absence of any absolute chemical
criterion as to the relative suitability of this or that wine for the
“gouty,” what shall be our advice to the _“gouty” individual_ on this
point? In a word, his “palate” and his “stomach” are the best criteria
of the wholesomeness of this or that particular wine in his particular
instance. If he is in the habit of taking wine do not forthwith, as is
so often done, forbid him wine in all forms and order him _whisky_. This
is done so light-heartedly that I do not wonder that the subject goes
away frequently with the idea that _whisky_ is not only innocuous, but
desirable.

_The whisky-drinker is not immune from gout_, and I have no hesitation
in affirming that “light” _wines_ when fine, mature, and of a _good_
quality are, subject to individual idiosyncrasy, quite as suitable
for the “gouty” as whisky. Of the many wise warnings given us by Sir
James Goodhart none is more apt for the present day than the following.
Discussing the “treatment of uric acid,” he observes: “I am as much as
ever an opponent of the prevalent dictum, ‘You must not touch wine;
you must drink whisky,’ which too often means to the patient, ‘A glass
of good wine is poison; I may take as much whisky as I like, and it is
harmless,’ one of the most mistaken and mischievous beliefs that ever
plagued a world.”

Again, if a “gouty” man takes wine, there is always one special variety
that agrees with him, and as certainly one other or more that infallibly
upset him. Putting aside all preconceived ideas, find out his _personal
idiosyncrasies_ in this respect. In this way you elicit and utilise for
your ends the _individual’s_ own experience, the only experience that
counts.

A man of a certain age, he generally by the time he develops overt
gout has arrived at definite conclusions as to what does and what does
not suit him. He will frequently tell you he has had to give up malt
liquors, perhaps port and champagne, and now finds that whisky, gin, or
the lighter wines agree with him better. Or, as like as not, he may upset
all your preconceived ideas. He may be of those gouty subjects—and they
are not so few—who can drink champagne in moderation, or even a glass or
two of port, daily with apparent impunity. On the other hand, a glass of
claret or hock plays the mischief with him. He may, like some individuals
cited by Burney Yeo, be one of those exceptional gouty subjects in whom
even stout is well borne, Yeo thought largely because they habitually
took daily large quantities of alkaline salts.

The sum of these erratic findings is that you must respect
_idiosyncrasy_. It is said that the best wine for a “gouty” subject is
the one that causes most _diuresis_. For myself, I am equally positive
that the worst wine for a gouty man is that which upsets his _stomach_,
which gives him some hours afterwards “acidity” or a feeling of “liver.”
Often, too, it is not the wine, but the _stomach_ into which it is put,
that is to blame. Thus the “gouty” subject with _atonic dyspepsia_ finds
a glass of sound wine helps digestion. On the other hand, if he suffers
from _hyperacidity_ or _chronic gastritis_, the reverse will probably be
the case.

Again, it is not the name, but the _quality_, of the wine that counts. It
makes all the difference whether the wine taken is fine, mature, and of
good quality, or some factitious, mixed, or adulterated product, passing
muster, say, as claret. Fine mature clarets or red Bordeaux wines are
most suitable for the gouty. But, as Burney Yeo rightly says, “a more
injurious beverage than bad claret or imperfectly matured claret—and,
speaking generally, all but the more expensive or most carefully selected
clarets are bad—was never drunk.”

It seems opportune here to lodge a protest against _fashions_ in
wines for the “gouty.” At one time it was claret, then light white
wines, Moselle, etc., and anon whisky, and even cider had its vogue.
Fashions in wines, as in other spheres, postulate uniformity and lack
of discrimination. Any one of the foregoing beverages may suit some
particular “gouty” individual, but not _all_ “gouty” subjects.

We have said that in some instances the wine, in others the stomach,
is at fault. But intrinsically it may lie in neither, but simply in
the _quantity_ of the wine drunk. It may not, as judged by ordinary
standards, be an excessive amount, but it may be excessive for that
particular man. It is here that a medical man may often intervene with
advantage. For a man may, quite unbeknown to himself, be really a heavy
drinker, one of those unfortunates who are peculiarly tolerant of
alcohol. A tactful reminder of the amount he is consuming per diem will
frequently come as a shock, often a very beneficial one.

Apart from this, it is, I am sure, wise to fix the _daily amount_. The
daily habit in the “gouty” is all-important. If accustomed to take one
or two glasses, and they stick to it, all may be well; but it is on
the occasions when the glass grows into a half-bottle that the trouble
comes. Metabolically speaking, the “gouty” subject is most unstable, and
disturbance of what one may call his daily alcoholic rhythm is always
perilous. Unfortunately it works either way, too, both in the matter of
“too little” as well as “too much.” Here experience and sound judgment
will alone enable the physician to decide how far he may tamper with
long-established habits.

At other times the amount, though, strictly speaking, not excessive,
is so when judged in light of the victim’s _habits_. He may be an
intellectual worker, but _sedentary_, and he must either lessen his drink
or increase his exercise, or he may _overeat_ as well as overdrink—a
victim of the prevalent idea that the one evil counteracts the other.
Between the Scylla of overeating and the Charybdis of overdrinking there
is no safe course save by way of _reduction_ of both.

We see therefore that in the matter of the choice of a wine for a “gouty”
subject there are many points to be considered. Of these _personal
idiosyncrasy_ stands first. By this criterion, and none other, can the
_suitability_ of the wine be decided. Then the state of the _digestive_
functions, if deranged, has to be considered. Is the gastric disorder
such as will be benefited or, on the other hand, impaired by wine of any
sort? Again, _glycosuria_, _albuminuria_, _raised blood pressure_, or
_cardiac degeneration_ may intervene to complicate the issue, and so our
policy in regard to alcohol has constantly to be adapted and readapted to
the varying requirements of the organism.

It will be seen that I have largely refrained from specifying the wines
_suitable_ or _unsuitable_ for the “gouty.” To have done so would have
been alien to the general tenor of my remarks, convinced as I am that
our trend in the matter of alcohol for the “gouty” should be more in
the direction of “individualisation” than of “standardisation.” Subject
to the reservations that such an attitude portends, I would proffer the
following suggestions:—

As a general rule, wines which are “dry” are much more suitable for
the “gouty” than those which are “sweet.” Wines are termed “dry” when
nearly all the sugar of the grape is transmuted into alcohol, as in “dry”
sherries. They are termed saccharine or “sweet” when the process of
fermentation is arrested before all the sugar has been exhausted, as in
Malaga. Again, wines which are both “strong” and “sweet,” _e.g._, Malaga,
sweet champagne, Tokay, etc., are more pernicious than those which are
“strong” yet “dry,” _e.g._, port, sherry, Madeira.

Sir James Goodhart, discussing wines suitable for the “gouty,” confesses
to a “personal leaning in favour of the wholesomeness of a glass of
good old sherry in those cases where a little wine seems a judicious
prescription.” With this I fully agree, and would suggest that of
sherries the “gouty” should favour the “Manzanilla” rather than the
“Amontillado” class. The former, save for the addition of a small
quantity of spirit, are mostly shipped in the natural state; also they
are light and “dry” as compared with the latter, which are generally
“sweet” and full-bodied.

It is interesting to recall, too, that Sydenham regarded _sherry_ as
preferable either to Rhenish or French wines. He himself in his own
person found “sack” or Canary the most helpful. “I have during the fits
of the last years tried many things to lessen the symptoms. Nothing,
however, effected my purpose so much as a small draught of Canary wine,
taken now and then, when the faintness or sickness were most oppressive.”
Here one may note that sherry was the first wine to be known as “sack”
in this country, and that the wine shipped in Sydenham’s time was of the
“dry” variety. Chemically the “sweet” sherry differs from the natural
“dry” light wine through its relatively high content of alcohol and sugar.

Turning to _port_, Sir Alfred Garrod absolutely tabooed its usage by the
gouty. But this appears too sweeping, and nowadays, at any rate, it is
well recognised that, especially in _asthenic_ types of gout, a glass
or two of old port is well borne. Consequently in such cases we should
not, in the absence of any adverse symptoms, forbid its continuance. The
bad reputation achieved by port is, I am sure, a relic of the Regency.
But “three-bottle” men are no longer with us, and, allowing for personal
idiosyncrasy, I very much question if sound port taken in moderation
wholly merits the aspersions cast upon it. I do not by that for one
moment suggest its general adoption by “gouty” people, but that where an
old or elderly gouty subject takes port and can be trusted not to extend
his glass to half a bottle his inclination may be respected. The sugar
content of port varies according to the vintage, ranging from 7 to 15 per
cent., and the “gouty” man should favour the “drier” varieties.

As for champagne—a manufactured article rather than a natural wine—there
is no question that, if taken at all, it should be a “dry” brand. Such
contains from 9 to 12 per cent. of alcohol and from 1 to 4 per cent. of
sugar, whereas the “sweet” brands may hold as much as 16 per cent. All
depends on the _quality_ of the champagne, and, as Ewart wisely remarks,
“it is wiser for the ‘gouty’ patient not to incur considerable risks by
trying brands with which he is not familiar, though he may sometimes with
impunity, and occasionally with benefit, enjoy a glass of champagne which
he can trust from personal experience.”

If, on the whole, the most unsuitable wines for the “gouty” are the
strong sweet _spirituous_ or _liqueur_ wines, on the other hand the _red_
or astringent and _white_ wines are the most esteemed. As to the _red_
wines, there is no doubt that the delicate Gironde (Bordeaux) wines are
_par excellence_ the most suitable. They have sufficient body and alcohol
without being heavy or fiery, while their acidity and sugar content are
very low. But of course the quality of the wines varies considerably
with the vintage. Subject to this, sound, well-made clarets taken in
moderation and somewhat diluted with water are the most wholesome wines
we can prescribe for the “gouty.”

The more full, though still not coarse, wines of the Burgundy district
are by some denounced. One authority, I note, states that in elderly
gouty subjects he had often found that two or three glasses of claret or
Burgundy were in the course of a few hours followed by eczema. While such
idiosyncrasies may obtain, it is not true of the “gouty” as a class. I
should consider a “gouty” subject in any case unwise to take two or three
glasses of Burgundy. But I do not hesitate to order _one_ or perhaps two
glasses somewhat diluted with water. Being a stronger and more tonic wine
than Bordeaux, it is useful in the more _asthenic_ types of gout. The
pity is, of course, that the cheaper Bordeaux and Burgundy wines are so
largely adulterated, while the more mature clarets are available only for
the rich. As good substitutes for French wines Burney Yeo commends the
red Hungarian wines, such as Carlovitz, while we may add that some of the
Dalmatian wines are of fair quality and somewhat resemble Burgundy.

Reverting to _white_ wines, these, as compared with the red wines of the
Gironde, contain less tannin and more free acid. According to Burney Yeo,
they exert, too, a more diuretic effect, and to remove their excessive
acidity he advises their dilution with some alkaline table water. Most of
the white wines come from the Rhine or Moselle districts. The Rhenish are
relatively full-bodied and of marked vinosity, while the Moselle wines
are mostly light and of a somewhat delicate nature. Light hocks and still
Moselles are quite permissible, also the white wines of France, such
as _vin de Grave_, all varieties of the latter being fairly “dry” and
light in character. On the other hand, the _white_ wines of Sauterne,
like some of the Hungarian wines—_i.e._, Ruster—are rich in saccharine
constituents. In this respect they contrast with the Rhenish and Moselle
wines. Of these last Johannisberg contains only 0·42 per cent. of sugar,
Rudisheimer 0·39, Zeltinger 0·13, and Stein-Reisling 0·01, while Ruster
contains no less than 21·74 per cent. of sugar.

In conclusion, I would re-emphasise the fact that, if wine be taken,
the patient’s own experience is the best test as to which particular
wine is the most suitable in his case. This elicited, the subject should
be counselled to adhere to it, taking it only at _meal-times_, and
establishing a rigid rule as to _quantity_. The least excess is harmful,
and breaking of the ordinary routine in the matter of the amount drunk is
a fertile source of “gouty” outbreaks. In any case the _quality_ of the
wine should be above suspicion, and if the expense is prohibitive, he had
best eschew wine altogether in favour of mature spirits.

_Spirits._—Brandy, whisky, and gin are the spirits most in vogue in Great
Britain, and it has become an axiom with some that, if alcohol in any
form be requisite for the “gouty,” the least harmful is one or other of
these beverages when adequately diluted. Of the three whisky undoubtedly
has found most favour, and the pernicious and far too prevalent idea is
that whisky not only does not beget gout, but is actually _beneficial_
for gout. The consequence is that many “gouty” people take far more
whisky than is desirable, seemingly oblivious of the fact that, if whisky
in _moderation_ be suitable for the “gouty,” whisky in _excess_ is as
deleterious for them as for the non-gouty. In short, like any other form
of alcohol, if taken immoderately, it will bring to fruition a latent
gout, this, as suggested by Ford Robertson, not by the direct action of
the alcohol, but by the “indigestion toxæmia” it sets up.

In advising therefore a “gouty” subject to take whisky we should insist
that (1) it should be taken only at _meal-times_ and (2) only in
_moderation_. The habit of occasional “nips” at all times of the day
should be unreservedly condemned. As to what constitutes a _moderate_
quantity is often a difficult question to decide.

When feasible, I endeavour to limit the _daily allowance_ to _a
wine-glassful_, distributed over lunch and dinner. But it is quite
impossible to lay down hard and fast rules in a matter in which _personal
idiosyncrasy_ plays such a strong _rôle_. Frequently, in addition to the
above amount, one has to relent to the extent of a “nightcap,” or but
too commonly one has to be content if one can compass reduction to an
amount which for the particular individual under review seems apparently
compatible with no appreciable damage to health.

Sometimes one of the frequent accompaniments of gout comes to
our assistance. It may be _raised blood pressure_, _glycosuria_,
_albuminuria_, _obesity_, etc. In such cases a word in season may reduce
an otherwise recalcitrant subject to reason.

Needless to say, in regard to “ardent spirits,” as to wines or malt
liquors, we must, when determining the quantity to be taken per diem,
review the same in light of the person’s _habits_, whether _active_ or
_sedentary_, whether associated with overeating or not. For manifestly
all these bear on the point at issue.

Lastly, as to whether the subject should take brandy or gin in preference
to whisky is a matter for himself to decide. Whichever suits him best
is the best for him. Albeit, I confess to a leaning in favour of “dry
Plymouth” gin, this being more diuretic than other spirits by reason of
the juniper contained therein. But, in whatever form “ardent spirits” be
taken, it is most essential that it be sound. Brandy should be of the
finest quality, the whisky mature, and inferior kinds of both wholly
eschewed.




CHAPTER XXVIII

MEDICINAL AND OTHER MODES OF THERAPY—ACUTE GOUT


MEDICINAL THERAPY

The illustrious Sydenham, for more than thirty years a sufferer from
gout, was clearly in doubt as to whether a cure of the malady was to be
attempted or even desired. It was Nature’s prerogative, he contended, to
dispose of the peccant matter after her own fashion by depositing it in
the joints, whence it might be dissipated by insensible transpiration.
Evacuant measures were, he thought, frankly prejudicial in that they
occasioned reabsorption into the blood of morbid substances already cast
forth from the system into the joints, with haply deflection of the same
upon the viscera, with all its added perils.

In view of these conceptions, Sydenham naturally discountenanced any
attempt to arrest or control the course of acute gout. “Nay, more,”
said he, “I can confidently affirm that the greater part of those who
are supposed to have died of the gout have died of the medicine rather
than the disease.” Not only were purging, blood-letting, and alike the
use of diaphoretics by him condemned, but, more, a policy of “inert
expectancy” enjoined. The true _rôle_ of the physician was that of the
bystander viewing the workings of the _vis medicatrix Naturæ_, while for
the tortured victim remained the pithy consolation that his gout was to
be regarded as a minister of health, whose presence and stay ought by
all means to be courted. Long years after Sydenham’s death his _laisser
faire_ attitude survived in Meade’s epigram, “the gout is the only cure
of the gout,” and in Cullen’s depressing axiom that “in patience and
flannel alone” lay salvation. Can we wonder that this policy of masterly
inactivity made gout the happy hunting ground of the charlatan?

It may be admitted that an _initial_ attack of gout often leaves the
subject better than before, but the deep remedial forces of Nature,
at first apparently all-sufficing, later prove unequal to their task.
Secondary evils follow the attacks, and “the racking pains, unfitness
of motion and other disorders which afflicted him during the greatest
part of his life” are at once a proof of Nature’s limitations and the
fallaciousness of Sydenham’s doctrines.

So much by way of prelude, but perhaps, as Heberden surmised, the chief
reason why Sydenham and his disciples found it advisable to do nothing to
curb the violence of gout was that they knew nothing wherewith to achieve
such control. Thus, though _colchicum_ had been used from time immemorial
by the ancient physicians, it had in Sydenham’s time almost been
abandoned as a remedy in gout, when, long after, according to Scudamore,
a Mr. Want (“Essays in the Medical and Physical Journals,” No. 185, etc.)
drew attention to its specific value in gout, and restored the drug to
its pristine status.


ACUTE GOUT

In the main the general principles of treatment conform to those
adopted for other inflammatory ailments, with, of course, the important
reservation that our mode of procedure be adapted to the individual case;
viz., due regard must be had to age, the intensity of the attack, and
the presence of complications. For obviously the treatment suitable for
a robust plethoric subject might prove the very reverse of salutary for
a broken-down victim more or less worn out by previous attacks and haply
the subject also of _arterial_ and _renal_ changes.

The medicinal treatment of acute gout necessarily divides itself into
_constitutional_ and _local_ measures. In pursuance of the first, we
seek to control the inflammation and febrile disturbance while assisting
the organism to eliminate those toxic substances in the blood that have
determined the incidence of the paroxysm.

The attack usually supervenes while the subject is in bed, and, generally
speaking, keeps him there. Indeed, rest is imperative, and as far
as possible sources of worry should be excluded. The nature of the
diet suitable for the acute stages has already been adverted to, and,
practically speaking, the first point that calls for investigation is the
state of the bowels. Were they prior to the attack open regularly, loose,
or confined? Constipation is the usual forerunner, and if so, a swiftly
acting purge must be given. Indeed, even if previously the action of the
bowels has been free, they usually, with the onset of the attack, become
bound, the intensity of the local pain presumably exerting an inhibitory
effect.

As to the advisability of initial purgation in acute gout, Sydenham was
definitely opposed thereto. In contrast, others, who held with Scudamore
that portal congestion was an etiological factor, highly eulogised free
catharsis. The truth, as usual, lay between the opposing views. In other
words, we must strike the happy mean between adequate evacuation and
excessive purgation, for there is good reason to believe that the latter
often so to speak, defeats its own end. It may determine more rapid
recurrence of the disorder or its perpetuation in a chronic and asthenic
form.

Incidentally one may recall that the objections unfairly launched against
_colchicum_ took origin in the misconception that its good offices were
referable to its _cathartic_ action. Hence by our forefathers the drug
was pushed until the characteristic “colchicum stools” appeared, with
their attendant nausea and prostration. This of course led to this
valuable drug being looked at askance, whereas the error lay, not in the
drug, but in the method of its administration, for, fortunately, its
specific effect in _gouty arthritis_ may be secured without the induction
of depression, nausea, or purgation. Indeed, as Sir Alfred Garrod long
since pointed out, it “frequently proves of most benefit when its
operation is unattended with increased alvine evacuation.”

Albeit, from the tenor of our digression it must not be inferred that
purgation is inadvisable in gout, but only that this salutary purpose
must not be effected by _colchicum_. At the same time we must not think
that mere _purgation_ will of itself allay the articular inflammation,
for it has been repeatedly shown that it exercises little or no control
in this direction; but, on the other hand, it sweeps out irritating
matter, promotes the return to a healthy state of the alimentary canal,
and in this way reinforces the beneficial effect of colchicum.

My own opinion is that, if seen just _before_ or just _after_ the acute
attack begins, it is wiser to secure a free action of the bowels before
placing the subject on colchicum, this the more imperatively if it be
a case of acute sthenic type supervening in a robust subject evidently
labouring under constipation. If there be no palpable derangement of the
liver, we may content ourselves with ordering at bedtime a full dose of
Gregory’s powder, or Pil. rhei co. gr. 5-8, or Pil. colocynth co. gr.
5-8, followed in the morning by a saline aperient. French physicians,
especially Robin, in such circumstances rely solely on sodium sulphate.
The salt has the advantage of not lessening the secretion of urine, and
the dose advocated is 1 ounce.

If the conjunctivæ show an icteric tinge or the character of the
stools suggests that the liver is at fault, small doses of a mercurial
preparation, such as calomel (gr. 4) or blue pill, may be given at night,
either Pil. hydrarg. gr. 5 or Pil. hydrarg. gr. 1, in combination with
Pil. coloc. cum hyoscy. gr. 4, and the same followed in the morning
by 1-2 ounces of Mist. sennæ co. The nauseating flavour of the latter
is best disguised by 1-2 drachms of Glyl. vanillæ, or for the “black
draught” we may substitute 4-6 drachms of sodium sulphate, a Seidlitz
powder, or a full dose of Carlsbad or Condal water.

When mercurials are contra-indicated or from experience known by the
subject to disagree, podophyllin may be prescribed in some such form as
the following: Podophyllin gr. ¼ c̄, Pil. coloc. hyoscy. gr. 4.

In other instances the cholagogue effect of the mercurial is procured by
substitution for it of a small dose of the Ext. colchici in combination
with the compound colocynth pill. Our forefathers, too, frequently
prescribed colchicum and mercury conjoined with aloes or colocynth, and
the following is an excellent and well-tried formula:—

  ℞ Ext. colchici acet.     gr. ½
    Ext. aloes barb.        gr. 1
    Ext. hyoscy. vir.       gr. 1
    Pil. hydrarg.           gr. 1½
  Fiat pil., 1.

In short, in the matter of the initial purgation the drug chosen must be
suited to the individual and the degree of purgation also graded. The
old rule was that if the belly is hard, the subject can stand purging,
but not otherwise; and it is, I think, a fairly sound index. Mercurials
in aged subjects are best avoided, and likewise in those with defective
kidneys. Salivation in their instance is easily provoked, and Sir Alfred
Garrod held that mercury “in advanced forms of gout should be altogether
avoided.” French physicians think saline aperients preferable to the
English method of giving calomel, and unquestionably they are eminently
suitable for robust and plethoric subjects.


_Colchicum in Acute Gout._

Whatever be its mode of action, colchicum still remains _par excellence
the_ remedy for acute gout. As before noted, Dixon and Maiden hold
that _colchicine_ has no action on the _metabolism_ or _excretion_ of
_purins_, nor on the _kidneys_. On the other hand, it influences markedly
the _leucocytes_, their number in the circulation undergoing a primary
decrease and a secondary increase. Bain, it is true, found that under
colchicum a slight _increase in uric acid excretion_ occurred, but thinks
it extremely doubtful if its influence in this direction is invariable.

That colchicine should exert such a marked effect in gout and yet
apparently be destitute of any influence on _uric acid excretion_ is of
course very striking. It calls, moreover, for more reflection on the part
of those who seem to contend that because a drug _increases uric acid
elimination_ it must necessarily be beneficial both for the gout as well
as for the victim.

_Method of Administration._—In _initial_ attacks the drug must be
exhibited with caution. Some persons are idiosyncratically sensitive
thereto. Attacks of faintness may ensue, or even ordinary doses occasion
purging or nausea and vomiting. Their incidence shows either that the
subject is abnormally sensitive or the dose too large. Such untoward
phenomena indicate its abandonment or drastic reduction. With these
reservations, colchicum may be administered in every primary attack and
most, if not all, of the succeeding paroxysms.

Albeit, the older the subject and the more ancient the gout, the more
warily should we proceed, especially if there is marked irritability of
the digestive system, renal disorder, or cardiac degeneration. Robin
holds that if _visceral_ gout is present, or the urine contains much
_albumen_, no colchicum should be given.

It is notorious that _old_ persons stand colchicum badly. In their
instance we need be the less ready to resort to heroic doses when we
recall that acute gout is a self-delimited disease, and while it would be
improper to do nothing in elderly subjects exhibiting visceral lesions,
etc., it is well that we proceed cautiously, so as to avoid the induction
of circulatory depression or the excitation of nausea or a diarrhœa which
may be, and often is, difficult of control. Moreover, if these untoward
symptoms are allowed to ensue, there is a tendency for the gout to recur
as soon as the effects of the colchicum have worn off.

_Preparations of Colchicum and Dosage._—Those most commonly in use are
the _tincture_ and _wine_ of colchicum, and of these the latter is most
in favour. As to dosage, most authorities agree that a full dose—30-40
minims of the vinum colchici—should be given at the inception of
treatment and followed by smaller amounts, from 10-20 minims two or three
times a day.

By French physicians the tincture of colchicum is preferred, and by Robin
that extracted from the _flowers_ rather than the seeds. The dose of our
own official _Tinct. colchici seminum_ ranges from 5-15 minims, and by
the French Codex the maximum single dose is placed at 25 minims, and the
maximum intake during twenty-four hours at 100 minims approximately. It
may be noted that preparations from the _seeds_ are more purgative than
those derived from the corn. Lastly, we have the official extract of
colchicum and the acetic extract. The dose of the former ranges from ¼-1
grain, and it is frequently given in the form of a pill with ipecacuanha
and mercury. The addition of a small dose of atropine is often advisable,
to obviate the vomiting and diarrhœa often primarily induced by increase
of peristalsis. By many the acetic extract is preferred, J. S. Matthews
holding that the effective dose ranges from 2-6 grains.

Turning now to discuss the most opportune juncture at which to administer
colchicum, certainly in the _initial_ and the earlier paroxysms we may
with advantage postpone the giving of colchicum pending _free clearance
of the bowels_. No harm will follow its being withheld until the _second_
day. Indeed, many physicians, both British and Continental, counsel delay
in its exhibition until the fit is well established.

Again, in _primary_ paroxysms—viz., while ignorant of the personal
equation in respect of _colchicum_—it is well that our maximum dose
should not exceed 20 minims, and when the bowels have not been previously
purged, the drug should be combined with sulphate and carbonate of
magnesia, as in the following prescription:—

  ℞ Magnesii sulphatis     gr. 60
    Magnesii carbonatis    gr. 10
    Potassii citratis      gr. 30
    Vini colchici            ♏︎ 20
    Aquæ menthæ viridis    ad unciam.
  Misce. fiat mistura. Two tablespoonfuls with two of hot water every
    three hours until bowels have been freely opened.

This achieved, the sulphate of magnesia may be omitted, and the mixture
taken every six instead of every three hours; but it is a good plan to
keep the original mixture at hand, giving a dose every morning while the
acute stage lasts. Then during the day the colchicum should be persisted
with either in the form of the wine or the tincture.

Moreover, there are often special indications to be met. Thus the skin
in acute gout is often hot and dry, and the urine unusually scanty and
high-coloured. In this event the colchicum may with advantage be given
with the citrate, bicarbonate or nitrate of potash, so as to produce
a diaphoretic and diuretic effect. In other instances acidity is a
prominent symptom, and here the combination of colchicum with the citrate
of potash and magnesia will be found useful.

As the intensity of the inflammation wanes and the local pain and tension
subside the dose of the colchicum should be gradually diminished;
but even after convalescence is established it may advantageously be
continued for a few days in small doses, say, 5 minims of the vinum
colchici three times a day. The condition of the tongue will usually
furnish a safe index, as rarely will it clean up prior to abatement of
the gouty fit.

In _subsequent_ paroxysms and alike in the _acute exacerbations_
that chequer the course of _chronic_ gout we may, in the absence of
_idiosyncrasy_ or other contra-indication, proceed more boldly. Thus,
if the bowels have not previously been briskly purged, we may at once
prescribe the following formula:—

  ℞ Vini colchici            ♏︎ 15-20
    Magnesii carbonatis    gr. 15
    Magnesii sulphatis     gr. 60
    Aquæ cinnamomi ad ℥j.
  Fiat mistura, ℥ij. statim sumenda et ℥j. quartis horis p.p.a.

The primary dose, as will be noted, will contain either 30 or 40 minims
of the wine, and, though Sir Alfred Garrod prescribed up to a drachm,
it will scarcely, if ever, be necessary to exceed 30-40 minims. The
subsequent dose of from 15-20 minims may after a day or two be reduced,
and instead the mixture given in ½-ounce doses three or four times a day.
Or, if preferred, the mixture in its reduced dosage may be renounced in
favour of a pill containing either the extract of colchicum or, what many
consider even better, the acetic extract thereof. Thus the following pill
may be taken every night for a few days, and then on alternate nights:—

  ℞ Ext. colchici                gr. ¼
    Aloin                        gr. ⅛
    Ext. bellad. alcoh.          gr. ⅛
    Capsicin                     gr. ⅟₂₀
    Ext. rhei                    gr. 1
  Fiat pil., 1.

The acetic extract may be given in larger doses, and was in great favour
as the chief constituent of many so-called “gout pills” in combination
with ipecacuanha and mercury:—

  ℞ Ext. colchici acet.              gr. 1½
    Pulv. ipecac. co.                gr. 1½
    Ext. colocynth co.               gr. 1½
  Fiat pil., 1 nocte sumenda.

An excellent formula, in which the colchicum is combined with mercury,
has already been furnished on a preceding page. Needless to say, it
should, like the above pill, be followed in the morning, if necessary, by
a mild saline purgative.

_Colchicine._—This, the active principle of colchicum, has of recent
years been widely and successfully employed in acute gout, as well as
in exacerbations of the chronic type. By some subjects, especially the
old, it is often better borne than colchicum preparations. The dose
ranges from ⅟₁₀₀-⅟₃₂ grain in a pill. By the French Codex the maximum
single dose is fixed at ⅟₃₂ grain, and the maximum administered during
twenty-four hours should not exceed ⅟₁₆ grain approximately.

The following is a suitable combination in an elderly subject, and it may
be noted that the drug has been found of use, too, in cerebral congestion
and uræmia:—

  ℞ Colchicine                      gr. ⅟₁₀₀
    Ext. belladon. alcoh.           gr. ⅛
    Ext. nucis vomicæ               gr. ¼
  Fiat capsule or cachet, 1 every three or four hours.

In robust subjects the colchicine may be given in larger doses. Luff
states that few patients will tolerate ⅟₅₀ grain, because of the diarrhœa
and griping pains produced. He found that colchicine (⅟₇₀ grain), in
combination with henbane and nux vomica in the form of a pill, rapidly
relieved gout when taken every three or four hours.

Or as a substitute we may use the _salicylate of colchicine_, the dose of
which is ⅟₆₀ grain. Colchicine is readily soluble in methyl salicylate,
and is conveniently administered in the form of capsules, each containing
⅟₂₅₀ gram (Martindale). In acute gout one capsule may be given every
two hours, or two capsules three or four times a day. These doses are
well within the limits of safety, and, if necessary, may be combined
with nux vomica and belladonna; but with the alkaloids, as with the
colchicum itself, it is essential that the bowels should be kept freely
opened. Also with the waning of the pain and inflammation the colchicine
or its salicylate should be given less frequently, so as to obviate any
depression.

_Atophan._—This is a yellowish cream-coloured amorphous powder of the
composition 2-phenylchinolin 4-carbonic acid. Its use has been much
extolled both in _acute_ and _subacute_ gout. The dose ranges from 30-45
grains daily for three to four days, according to some authorities,
but others consider that it may be taken for prolonged periods with
advantage. It is most conveniently exhibited in the form of tablets
containing 4 or 8 grains. _Agotan_, a drug identical with that formerly
sold under the German registered name “atophan,” is supplied in the form
of crystalline powder and in 7½-grain tablets, and appears to be equally
efficient.

Atophan is incompatible with sodium bicarbonate and other alkalies
_in vitro_, but Martindale and Westcott “did not find it incompatible
with potassium iodide.” It has been repeatedly noted that, following
the intake of atophan, the uric acid content of the _blood_ falls and
the _urinary uric-acid output_ increases. Weintraud in gouty patients
on a _purin-free_ diet noted that after atophan the quantity of uric
acid excreted in the urine was more than doubled, but subsequently the
excretion fell below normal.

Even in healthy individuals when taking atophan the urine becomes turbid
from the presence of _urates_. This excess of uric acid in the urine may
in gouty individuals be precipitated in the urinary tract, and so induce
an attack of _gravel_. Consequently Weintraud advises that the drug be
taken with _alkalies_, either sodium bicarbonate or alkaline waters.
Drs. Jansen and Plum, of Copenhagen, during their recent visit to the
Royal Mineral Water Hospital, Bath, informed me that they had met no
instances of _gravel_, but in several of their cases atophan had induced
_urticaria_.

As to the simultaneous intake of _alkalies_, while the precaution is
probably desirable, I have known gouty patients take atophan _without_
alkalies for several weeks in full doses without any apparent ill
effects. Brugsch, indeed, states that in _polyarthritis urica_ the
subjects are able to take 15-30 grains of atophan per diem for a year
without any affection of the kidneys. Moreover, uric acid excretion
was increased throughout the whole period, and when the drug was
discontinued, the pains recurred.

As to the usurpation of colchicum by atophan, I do not think it is at
all likely, for it does not, I consider, exert the specific effect of
the former on the gouty inflammatory process, taking the humbler _rôle_
of obviating the formation or promoting the absorption and elimination
of _uratic deposits_. In other words, colchicum influences the _causa
causans_ of gouty inflammation, atophan only the _consequences_ or
_sequels_ thereof.

The most favourable juncture at which to prescribe atophan is _at the
close of a paroxysm_. I have myself been much impressed with the manner
in which it produces softening and palpable diminution in the size of
tophaceous deposits, so much so, indeed, that I feel sure we have in
this drug a valuable agent wherewith to _prevent the formation of uratic
deposits_.

A two or three weeks’ course of atophan after an acute attack is, I have
found, very advantageous, in doses of 30-45 grains per diem, after meals.
It may, for the special reasons given, be well combined with an alkaline
stomachic mixture taken half an hour or more before food.

  ℞ Potassii bicarbonatis             gr. 15
    Sodii bicarbonatis                gr. 20
    Spts. ammoniæ aromat.               ♏︎ 20
    Tinct. zingiberis fort.             ♏︎ 5
    Inf. aurantii co. ad unciam.
  Fiat haustus, thrice daily well diluted with water.

To sum up, our medicinal treatment of acute gout consists in _initial
purgation_, followed by maintenance of an adequate daily evacuation;
secondly, the exhibition of _colchicum_ or its active principle and
continuance of the same in diminishing doses until pain and inflammatory
phenomena have departed. With the passing of the paroxysm _atophan_
should be resorted to in combination with an alkaline stomachic mixture.
Supervision of the subject should not cease until the digestive and
assimilative functions have, as far as possible, attained functional
efficiency, for it is certain that this is the most important point in
the management of the gouty constitution. Conjoined therewith, the bowels
should never be allowed to become constipated, the urine maintained free
from acid lithates, and the skin active by regular exercise.

_Alternative Remedies in Acute Gout._—Of the various drugs advocated
as substitutes for colchicum the salicylate group alone seems to have
evoked something like enthusiasm. Thus Germain Sée affirmed that sodium
salicylate was the best remedy for gout, whether of acute or chronic
type. In this country Haig strongly upheld its claim. On the other
hand, Ebstein, when he used this salt in acute gout, found that the
inflammation, though it quickly subsided in one joint, immediately
reappeared in another, even though the administration of the drug was
continued.

Lecorche, again, though he found it useful in _acute_ gout, was equally
certain that it was altogether inferior to colchicum. It did lessen
the pain and the violence of the paroxysm, but in no way shortened its
duration. But, on the other hand, he attached a _prophylactic_ value to
it in chronic gout marked by recurring subacute attacks. His method was
to give it in the intervals of paroxysms in doses of from 60-80 grains
a day, whereby he claimed to abort attacks, prevent ankyloses, and
facilitate absorption of uratic deposits.

As to its mode of action, salicylate of soda, both in gouty and healthy
subjects, determines an immediate increase in the uric acid excretion,
30-60 per cent. The increase, however, is but ephemeral, the excretion
of uric acid sinking gradually to normal in about forty hours, and this
whether the drug be persisted with or not. The increase in total nitrogen
excretion does not reach 10 per cent.

Discussing this mode of response, MacLeod (who noted the same after
citrates) is of opinion that salicylate of soda and citrate act, not by
influencing the metabolic processes that originate uric acid, but by
promoting the excretion thereof. Walker Hall and Magnus Levy, albeit,
suggest that the increase is due to diminution in the normal destruction
of purins in the organism, with resulting transmission of the same in
larger quantities to the kidneys for excretion. It is possible therefore
that in the presence of sodium salicylate there is diminished oxidation
of uric acid.

Bain, however, studying the elimination of nitrogen in a gouty subject,
found, contrary to expectation, that after sodium salicylate there ensued
only a small increase in the uric acid, with a slight augmentation of the
alloxur bases relative to the acid. We see therefore that all the above
observers agree that an _increased uric acid output_ in the urine follows
the administration of salicylate of sodium, though they differ in opinion
as to the manner of its production.

As to the employment of salicylate of soda in _acute_ gout, it must, I
think, be seldom called for, save in the presence of _idiosyncratic_
sensitiveness to _colchicum_. Now, though of this latter much has been
written, yet I venture to affirm it is exceptional, and the adverse
symptoms are attributable rather to injudicious dosage of the individual
than to inherent peculiarities on his side in respect to this valuable
drug.

If we should encounter such an instance, there is no objection to our
giving the salicylates of sodium or potassium a trial, especially in an
acute febrile attack occurring in a healthy subject. In isolated cases
the relief to pain may be swift and striking; but, generally speaking,
the results are neither so decisive nor so prompt as those obtained in
suitable cases by colchicum. The potassium and lithium salicylates are
usually given the preference, and they may be combined with citrate or
bicarbonate of potash. If the latter salt be used, the draught will prove
more grateful if given in effervescent form, viz., by the addition of
citric acid or lemon juice.

Frequently it happens that the patient, to begin with, has been placed on
colchicum, and, symptoms of irritation having supervened, the drug has
had to be withdrawn. The tardy resort then to salicylates is fortunately
rather beneficial than otherwise, for, apart from its analgesic effect,
it reinforces the increased uric acid output in the urine that follows
the attack, and so tends to counteract the tendency to uric acid
deposition.

There is yet another contingency in which resort to salicylates may be
indicated, viz., in those long-standing cases of _chronic gout with
recurring exacerbations_ in which the colchicum, formerly beneficial, has
now through acquired tolerance become impotent. Here, either during or
immediately after the acute phases, the salicylates may be exhibited, if
the stomach be tolerant and there be an absence of _cardiac_ or _renal_
degeneration. As to the employment of salicylates in massive doses in the
_inter-paroxysmal periods_ as a _prophylactic_ measure, I think this is
better attained by occasional courses of _atophan_.

Lastly, there are instances in which both colchicum and salicylates
appear to be contra-indicated. In this event we may either rely simply
on _alkalies_—and we have Duckworth’s authority that in many cases of
_acute gout_ they have proved satisfactory—or we may adopt Sir Alfred
Garrod’s plan of giving _quinine_ (2½-5½ grains) suspended by tragacanth
in combination with the bicarbonate or citrate of potash. By this means
the pyrexia is controlled, and, according to the above authority, any
tendency on the part of the disorder to wander from joint to joint; and
he holds it especially valuable in those _subacute_ attacks that so
commonly chequer the course of _chronic_ gout.

_Thyminic_ or nucleotin-phosphoric acid in doses of 5-10 grains has also
been highly eulogised, being held to have an affinity for and a solvent
action on uric acid. But Walker Hall, while he agrees that the results
obtained in gout are encouraging, yet from his own experiments does not
find that “the improvement is at all associated with any change in uric
acid excretion—a result which also applies to citerin.”

As to _quinic acid_ and its synthetic combinations, their popularity
seems to have been evanescent. It is claimed that “urosin” or lithium
quinate speedily controls the acute manifestations of gout, this
apparently without any evidences of cinchonism, even though given in
7½-grain tablets ten times daily in acute paroxysms. Others give quinic
acid in combination with piperazine, _i.e._ “sidonal” in doses of
1-1½ grains per diem. But of these, as well as of many other vaunted
specifics, I feel inclined to say, with Bianca, “Old fashions please me
best; I am not so nice to change true rules for new inventions.”

_Anodynes in Acute Gout._—On this point it may be recalled that such
was the prejudice at one time against colchicum that Ebstein thought it
preferable to relieve the pain of acute gout by hypodermic injections
of morphia, which, he thought, acted “quicker, more easily, and with
less danger.” Fortunately, however, it is only very exceptionally that
colchicum fails to mitigate the pain in acute gout.

In rebellious instances salicylate of soda in full doses for a few hours
sometimes succeeds. Hypodermic injections of morphia must rarely, if
ever, be called for, and I have never had occasion to invoke them. In
fact, opium in any form is best avoided, and if unavoidable is best given
in the form of Dover’s powder in combination with aspirin and phenacetin,
viz., 2½ grains of each in a cachet at bedtime. Luff in some cases found
a full dose of extract of hyoscyamus a very useful anodyne, and if
sleeplessness through pain prevails, advises 7 grains of veronal or 10
grains of trional. Sir William Whitla’s “routine hypnotic in gout” is
paraldehyde.

All these are preferable to opium in any form, for we deal with a
disease in which _defective elimination_ is a prominent feature, and
that we should exhibit unnecessarily a drug which inhibits all excretory
processes save that subserved by the skin seems wholly irrational. Of
this we have an object lesson in the clay stools that in some gouty
subjects, as Burney Yeo remarked, persist for some days after even a very
small dose of morphia. My own rule is to rely on colchicum as far as
possible, and for any extra anodyne effect on local applications, to the
consideration of which I now proceed.


_Local Measures in Acute Gout._

The affected limb must be kept at rest on a firm pillow and slightly
raised above the body level. The inflamed part should be protected from
pressure by a cradle. In the majority of instances, as the elder Garrod
long since pointed out, the only local application needed is cotton wool
covered with oiled silk, evenly and lightly bandaged. By this means the
joint surface is kept both warm and moist, and moisture is important, as
dry heat is not grateful and seems to aggravate the pain. The dressing
soon becomes wet, requires changing two or three times in the twenty-four
hours, when dry warm wool should again be applied, and in this way a
local vapour bath of sorts is provided for the inflamed part.

If pain be marked, hot fomentations or stupes or even a foot-bath may be
substituted. At one time warm spirituous lotions on lint covered with
oiled silk were popular, whisky and water being much in vogue. Others
(Pye-Smith) spoke well of a lotion containing 1 drachm of sulphuric ether
to 6 ounces of water. Some pack the joint with warm alkaline lotions to
which opium or belladonna, or both, are added; but, whether dealing with
spirituous or alkaline lotions, all are agreed that _cold_ applications
should be carefully shunned.

As to anodyne preparations, we suffer from what may be truly described
as _un embarras de richesse_; but the inexplicable variability of
response is such that it is always well to have another shot in one’s
therapeutic locker. Practically all the analgesic remedies in use have
been recommended by some one or other as useful for the relief of pain in
acute gout. The mere enumeration of these might be indefinitely extended,
for in truth every one has a favourite remedy wherewith to meet certain
indications, and the good results obtained are exactly proportional to
the skill displayed in exhibiting their use. We should not, however,
resort forthwith to the more potent analgesics. It is wiser to give the
simpler remedies a prior trial, such as poppy-head fomentations. If these
fail, the liniment or unguentum methyl salicylatis co. may be tried,
applied on lint covered with oiled silk and a flannel bandage. Equal
parts of chloroform and belladonna or of opium and menthol liniment are
also very soothing when sprinkled on lint and covered with cotton wool.

In the more intense cases with great local sensitiveness the following
preparations may be lightly applied to the affected area with a brush.
Anodyne colloid is one of the most reliable, or we may use glycerine of
belladonna or atropine, subsequently covering the part with warm, moist
dressings or spongiopiline enveloped in oiled silk, cotton wool, and a
flannel bandage. In using atropine preparations, however, care must be
exercised, as absorption through the unbroken skin may readily cause
toxic symptoms.

In less acute types or as local sensitiveness declines various ointments
may be gently rubbed into the affected joint, and in this way the
beneficial effects of massage superadded. The most suitable unguents are
those containing methyl salicylate in hydrous wool fat with or without
menthol, or the methyl salicylate may be mixed with equal parts of olive
oil and applied with friction. Used in this way, it is rapidly absorbed,
and is much to be preferred to the natural oil of winter-green, which not
infrequently proves very irritating to the skin.

Under the influence of one or other of the foregoing methods, the pain
in these forms of acute gout is usually quickly subdued. Occasionally,
however, owing to incomplete absorption of inflammatory exudate, the
case proves more obstinate, and a variable degree of pain and stiffness
lingers on in the affected articulation.

If means permit, the ideal course to pursue is for the patient to be sent
to some spa where, conjointly with the general treatment, he may enlist
the advantage of hydrotherapy, massage, and so forth. In default of such
facilities, we must of course fall back upon friction with liniments,
being careful not to induce tenderness of the joint. Of these there
are endless varieties, those containing ammonia, turpentine, camphor,
or capsicum being most in vogue. Inasmuch as their efficacy is largely
referable to the rubbing which accompanies their use, we should favour
preparations containing oleic acid, either alone or diluted with a fatty
oil. As an oily liniment perhaps one of the most useful is the linimentum
succini co., containing equal parts of the oils of amber and clove
combined with twice the quantity of olive oil, or one of the following
excellent combinations may be selected:—

  ℞ Olei origani vel olei terebinthini   Partes æquales.
    Linimenti ammoniæ.
  To be applied with friction to the affected part.

  ℞ Ætheris                              1 drachm.
    Linimenti belladonnæ                 ½ ounce.
    Tinct. capsici                    To 2 ounces.
  To be well rubbed into painful parts night and morning.

When a joint is the seat of fixed pain with definite thickening, it may
be necessary to resort to _blisters_; but frequently they are so utilised
as to merit the aspersion of “adding additional distress to unrelieved
pain.” They are of course unsuitable for cases with _acute serous
effusion_ of recent origin; but are often beneficial when applied over
joints, bursæ, or tendon sheaths, when the seat of _long-standing passive
distension_.

Garrod held them of most advantage in _gout_ of _asthenic_ character with
lingering effusion; but he thought them inadvisable in the later stages
of gout with _defective kidneys_ and where the joints were the seat of
massive uratic deposits, as in the last event sores difficult of healing
may follow.

In the vast majority of instances such drastic counter-irritation is
unnecessary, as the pain usually relents to less strenuous measures. For
the dissipation of exudates and thickening nothing is superior to iodine
and mercurial preparations. Painting with strong iodine may occasion
soreness, but not if the glycerinum iodi be used. Better still is it if
we use iodine preparations that admit of gentle inunction. The iodide of
potassium and soap liniment is of course most reliable, or we may use one
of the proprietary preparations, _e.g._, leukion. The oleate of mercury
(10 per cent.) is often useful, and if pain linger on in the joint, may
be combined with morphia (½ grain to 1 drachm). Ichthyol lanoline also
deserves mention, and is best rubbed in after a fomentation followed by
a dry pack. It is extremely probable that the stimulant and absorbent
action of these agents is markedly reinforced by the _friction_ which
accompanies their usage.

In conclusion, it must be recalled that the swelling, stiffness, and pain
are of dual origin, viz., in part due to _inflammatory products_ and in
part to _uratic deposits_, and it is the former that will be the most
influenced by the foregoing measures. As to the means available for the
reduction or dissipation of _tophaceous_ matter, we shall best postpone
their consideration until we come to discuss the treatment of tophi.

_Ionisation in Acute Gout._—The introduction of medicinal substances
into the interior of the joints by means of an electrical current is
now in extensive vogue, both as a means of relieving pain and promoting
absorption in periarticular and synovial affections. It is of course in
the more accessible or superficial articulations that its beneficial
effects are most easily attainable.

The sensitiveness of the parts in acute gout is such that I have never
felt justified in invoking ionisation therein. Nevertheless Finzi tried
it in two cases of acute gout. Instant relief of pain and diminution of
swelling followed the first _séance_, while in sequence to a second all
local tenderness disappeared. Finzi used a combination of lithium and
iodine, the former at the positive and the latter at the negative pole.
I would only add that in non-gouty forms of arthritis, if relief of pain
be desired, _salicylic_ ions, by general consent, would appear to be the
most reliable. As far as I know, most authorities confine ionisation to
_chronic_ articular gout, and to this I shall refer later.

_Massage._—The success that follows the application of stimulant or
absorbent preparations in the after-treatment of acute gout largely
depends on the skill and persistence with which the rubbing or kneading
is performed. Hence it is that treatment by external medication has been
largely superseded, and rightly so, by skilled _massage_, the outstanding
advantages of which find increasing appreciation.

It need hardly be said that massage is contra-indicated in the acute, and
its use should be confined to the _subacute_, stage. Moreover, I would
suggest that its aid be sought more frequently during the _decline of
acute attacks_, instead of its being reserved, as it very largely is,
for the more chronic varieties of articular gout. In the latter instance
organisation of the inflammatory products has already ensued, and their
dispersal is correspondingly more difficult, whereas in the former the
soft nature of the effused material renders dissipation more easy and,
what is more important, minimises the chances of recurrence. Gentle
massage also will promote the _absorption_ and _resolution_ of _tophi_,
for the uratic deposits, even when pre-existing, are often found after an
attack to be _softened and more mobile_, and now is the time to profit by
these changes, so as to compass their elimination.

In these _subacute_ stages, of course, vigorous excitation must be
avoided, _effleurage_ or _light stroking_ being the only permissible
measure at this stage; and of course it should be exercised
_centripetally_. In presence of any marked sensitiveness, too, it is
advisable that _derivative_ massage of the limb above the joint should
always precede any direct friction of the latter.

The measure of success will depend on the technique of the masseur.
If he be unskilful or rough, aggravation of the inflammatory process
will almost certainly ensue, with prolongation of stiffness and pain.
He should proceed tentatively, the energy displayed being gradually
increased as the parts grow more tolerant of manipulation.

Again, it is at the close of a massage _séance_ that _passive movements_
are most advantageously employed, and where irritation and pain follow
their performance, gentle centrifugal stroking of the actual joint
surface will exercise a grateful, soothing effect.

_Surgical Methods._—The intensity of the inflammation and swelling in
acute gout has, as before said, sometimes led to its confusion with
_purulent arthritis_. It was just such a mishap that led Riedel to
discuss seriously the operative treatment of gout when of _monarticular_
type, _e.g._, in the great toe joint. He cites the case of a man, aged
forty-five, suffering with acute gout of classic site which was operated
on under the impression that the joint contained pus. None issued, but
the synovial membrane was found covered with urates. The latter were
removed, the wound healed in five weeks, and no recurrence of articular
gout followed till fourteen years after. The second example occurred in
a lady seventy years of age, who likewise suffered an acute attack of
gout in the right great toe joint. An incision was made and the revealed
urates removed, and the wound healed in a few weeks, and no subsequent
attacks followed!

Despite the apparent good results obtained, one can scarcely believe that
incision and removal of urates during _acute_ gout will ever be seriously
considered. Nevertheless the apparent impunity, if not actual benefit,
that followed the above operative interference does, I think, indicate
that in these aseptic days we need be less timorous; in other words,
that, while the operative treatment of acute gout is unnecessary, yet in
_chronic_ cases surgery has its sphere. But to this I shall return later,
when discussing the treatment of tophaceous deposits in chronic gout.




CHAPTER XXIX

MEDICINAL AND OTHER MODES OF THERAPY (_continued_)—INTER-PAROXYSMAL PERIOD


TREATMENT IN THE INTER-PAROXYSMAL PERIOD

Despite the fact that _heredity_ plays so dominant a _rôle_ in
the genesis of gout, how relatively scanty the attention paid to
_prophylactic_ measures! It is the _second_, never the initial, attack
of gout that we endeavour to avert. Surely to inhibit the development
rather than to prevent the recurrence of the malady is the better part.
The idea is not wholly utopian, for such shrewd observers as Scudamore,
Austin Flint, and others, were convinced that by timely and judicious
intervention a threatened outbreak might be averted or at least its
severity mitigated.

It was to this end that in a preceding chapter I urged the desirability
of more attention being paid to the _prodromal_ symptoms of gout and
the clarifying light that might be thrown on otherwise inexplicable
derangements by the disclosure of a _hereditary_ tendency thereto. The
failure to elicit such familial predisposition is but too common, and so
those who may be led to expect the gout by inheritance are bereft of all
the benefit that might accrue from a prophylactic regimen.

The indications may, indeed, be more explicit, for, apart from hereditary
proneness, some subjects, even though they may never have experienced
an _articular_ outbreak, yet exhibit _tophi_, and therewith frequently
suffer from gastric or hepatic disturbance. Obviously, is not this
the opportune time for _prophylaxis_—the institution of hygienic and
dietetic rules conjoined with the occasional use of medicines? For the
“potentially” gouty, as Scudamore said, cannot “too early be taught
to pay the most careful regard to their constitution, nor too surely
confirm the best habits by long practice.” We hear much nowadays of the
“beginnings” of disease, and who can doubt that this is a fruitful sphere
for their study?

Unfortunately it is, as a rule, only when the disease has made its
invasion that we wake up to our responsibilities in this respect;
but happily even then we may do much to prevent consolidation of its
tyranny, for even in those who have experienced regular gout there are
derangements to correct, warnings to note, if we do but take heed. Of
these the more common are dyspepsia and costiveness, signs of portal
congestion, etc., not to mention local symptoms, _i.e._, the onset of
pricking and tenderness in already existing tophi, twinges in the toes,
etc.

We see therefore that in regard to the prophylaxis of gout the victims
fall into two main groups, _i.e._, firstly, the “potentially” gouty, who
as yet have not experienced arthritic outbreaks, and, secondly, those
who have, and wish to obviate their recurrence. Happily the premonitory
gastric symptoms, though varied in character, are in both instances
more or less similar; nor need I say that in either alike medicinal
measures are but the smallest part of the _prophylaxis_, whose chief
stay and strength must be the golden rule of _temperance_ in eating and
drinking conjoined with adequate exercise. For, whatever our views as to
the _proximate_ origin of gout, there is every reason to suppose that
the principal _exciting_ cause resides in the _alimentary_ canal. As
Sydenham long since said, “The more closely I have thought upon gout, the
more have I referred it to indigestion or to the impaired concoction of
matters both in the parts and the juices of the body.” Even so to-day do
medical men suffering from gout tell me that they, like Sydenham, have
found by experience that almost invariably _dyspeptic_ symptoms are the
forerunners of attacks, and that their avoidance or timely correction is
the best means wherewith to avert paroxysms.

As to the nature of the “indigestion,” it is of _subacute_ or _chronic_
type, and only very exceptionally is it acute. As to symptomatology,
there is nothing distinctive about the “dyspepsias” of the “gouty,”
save perhaps their marked tendency to recurrence, the facility with
which they are occasioned by trivial causes, their frequent obduracy to
ordinary measures, and their response to such as take cognisance of the
constitutional factor.

Nevertheless such is the frequency and persistence often of gastric
derangements in the “gouty” that it may safely be affirmed that the
treatment of these subjects in their _inter-paroxysmal_ periods is
essentially that of the “dyspeptic.” It is, in truth, the basal
indication in their therapy, for correction of the “gouty” man’s
digestive disabilities is the surest way to prevent articular outbreaks,
or, failing this, to postpone their recurrence or mitigate their severity.

The primary object of medicinal treatment is the restoration to
_functional efficiency_ of the _alimentary_ tract and its _accessory
glands_ and maintenance of the action of the _kidneys_ and _skin_. While
_diet_ and general hygienic regulations are all essential, we often have
to fight the vicious inclination of the victim who is desirous that some
medicine may be found which will avert the threatened gout without his
being obliged to forego his accustomed indulgence.

He must be promptly and firmly disabused of this fallacy. Indiscriminate
drugging is the bane of these cases. They fly from one remedy to another
rather than give up this or that excess, and so frequently superimpose a
“drug dyspepsia” upon the original disorder.

The most common form of indigestion in the “gouty” is _atonic_ dyspepsia.
The primary indication is, of course, to correct the dietetic errors,
_i.e._, to remove the cause, and, secondly, to stimulate the secretory
and motor power of the stomach. To this end, the alkalies and alkaline
carbonates should be administered shortly before meals in combination
with nux vomica, bitters, and carminatives.

  ℞ Mag. carb.                         gr. 10
    Sodæ bicarb.                       gr. 15
    Tinct. nucis vomicæ                ♏︎ 7
    Spts. chloroformi                  ♏︎ 10
  Infus. calumbæ ad unciam, ter in die sumenda ante cibos.

In the milder type of case the above may suffice, supplemented, if
necessary, by some gentle aperient. Unfortunately in many instances the
condition is apt to become complicated by _fermentation_ with _excessive
formation of organic acids_. It is to these that the “acid risings” are
due, and _not to excess of HCL_. Indeed, the reverse is the case, viz., a
_deficiency of HCL_. It is this that is responsible for the fermentation
with the production of butyric, lactic, and acetic acids. Moreover,
in middle-aged “gouty” subjects of sedentary habits there is often
superadded _motor defect_, which may end in _dilatation_.

For treatment of this condition careful _dieting_ alone may suffice.
Indeed, attention to general health often succeeds where _stomachic_
therapy alone conspicuously fails. The medicinal indications in these
cases will vary according to the stage at which they are seen. In the
milder forms we may stimulate the flow of gastric juice by alkalies and
bitters before meals, or hydrochloric acid after food may be taken to
replace the defect.

Now, theoretically speaking, this may sound very simple, but in practice
it is often not so. Moreover, the less the attention paid to correction
of diet and faulty habits, the more bewildering and disappointing the
effect of drugs. Conversely, the more care expended on the selection of
food and hygienic measures, the less need for drugs and the clearer the
indications for such as may be helpful.

Thus simply under a revised diet the acid eructations may wholly
disappear and the subject suffer only with languor, discomfort, or
drowsiness after meals. Here dilute hydrochloric acid combined with
strychnine and pepsine after food will be found useful.

On the other hand, many of these patients are impatient of dietetic
control, yet nevertheless clamour for relief of their “acid” eructations.
In such cases _alkalies_ must be given an hour or so _after_ meals to
correct the excess of _organic acids_. The same may be combined with
antiseptics—carbolic, B. naphthol, creosote, etc.—or some artificial
digestive, such as _papain_, _pancretin_, or _taka-diastase_.

  ℞ Bismuth carb.                           gr. 15
    Calcii carb.                            gr. 5
    Acid. carbol. pur.                      ♏︎ ½
    Oleum cajeput                           ♏︎ 2
  Fiat cachet, 1 or 2 an hour or more after meals.

The _calcium_ and _bismuth_ carbonates are best, inasmuch as, though
they act slowly, they give rise to no _secondary hypersecretion_. Of
digestive adjuvants in these cases, Luff speaks highly of taka-diastase
(gr. 2½) immediately before meals in addition to bismuth and alkalies.
The taka-diastase assists the digestion of carbohydrate foodstuffs,
and so lessens or inhibits the formation of organic acids. But as a
digestive adjuvant in these cases of “dyspepsia” with acid eructations
_papain_ is most useful, acting in acid, alkaline, or neutral media.
This indifference on its part enables us to combine it with alkalies,
and so attain the dual effect of reinforcing the digestive capacity and
neutralising hyperacidity.

  ℞ Mag. carb. pond.                      gr. 15
    Sodii bicarb.                         gr. 10
    Papain                                gr. 3
    Oleum caryophylli                     ♏︎ ½
  Fiat cachet, 1 or 2 after meals when acidity is at its height.

Our forefathers in such cases thought highly of rhubarb and magnesia, and
certainly in hospital patients some such combination as the following is
invaluable in so-called “gouty dyspepsia”:—

  ℞ Mag. carb.                            gr. 10
    Sodii bicarb.                         gr. 15
    Acid. carbol. pur.                    ♏︎ 1
    Tinct. rhei co.                       ♏︎ 15
    Spts. chloroformi                     ♏︎ 15
  Inf. caryophylli ad unciam, ter in die post in cibos.

Almost always in these cases more or less _constipation_ prevails, which
must be corrected. To this end, of course, the magnesia contained in
one of the above cachets may be all that is necessary; but often it is
not so, especially if the subject be taking bismuth. Moreover, inasmuch
as we have to take cognisance of the _constitutional_ taint in these
individuals, we may with advantage give an occasional aloetic pill
containing colchicum or a nightly dose of guaiacum and sulphur. Again, if
the urine be scanty, we may substitute a morning draught of phosphate of
soda (¼-½ ounce), which not only stimulates the liver, but exercises also
an antacid and diuretic effect.

  ℞ Ext. colchici                       gr. ¼
    Aloin                               gr. ¼
    Menthol                             gr. ½
    Ext. rhei                           gr. 1
  Fiat pil., 1 alternis noctibus sumenda.

As soon as the symptoms of fermentation and organic acidity relent to the
above or similar measures we should, if possible, dispense with drugs and
rely wholly on diet and general hygienic regulations; but unfortunately
a case of _atonic_ “dyspepsia,” if of prolonged duration, gradually
merges into one of _chronic gastritis_. Especially in those given to
alcoholic indulgence do we meet with a condition of _mucous catarrh_,
with its associated _deficiency of hydrochloric acid_. Indeed, apart
from _alcoholic_ excess, such is the frequency in “gouty” subjects of
this form of “dyspepsia,” _i.e._, _fermentation with excess of organic
acids_, that I am inclined to think that the _subacidity_ which permits
of such developing is, if I may say so, the inherent digestive disability
in “gouty” subjects. Unquestionably _hyperacidity_—_i.e._, excess of
organic acids due to _hypochlorhydria_—is in their instance infinitely
more common than hyperchlorhydria, or excess of HCL, that is, much more
frequent than the latter as differentiated from organic acidity by the
only possible means, viz., an examination of the stomach contents.

Again, accepting the view that _infections_ are the chief excitants of
gouty paroxysms, the desirability of reinforcing the antiseptic action
of the gastric juice is obvious. In other words, the defensive powers
of the stomach against intruding microbes must be raised by prescribing
_hydrochloric acid_. For this purpose it is well to use _strong_ or
_fuming_ hydrochloric acid in doses of from 5-10 minims, freshly mixed at
the time of administration with 6-8 ounces of water, and the same taken
at every meal. The hydrochloric acid may with convenience be placed in a
drop bottle, and beginning with 5 minims, an extra minim may be added
every few days until 10 or 15 minims are taken at each meal.

Some years ago Armstrong, of Buxton, spoke highly of its value in
_alimentary toxæmia_, which is precisely the condition we are confronted
with in gout. Falkenstein, again, highly eulogises it in the latter
disorder. He gives from 40-60 drops of pure hydrochloric acid in a large
quantity of effervescing water each day. It is taken during meals, and
the dilution with water is arranged so that the patient is struck by the
acid taste. The diet taken was an ordinary one, and yet Falkenstein noted
that the dyspeptic symptoms disappeared and the attacks of gout grew more
rare and much less severe. As an alternative to water, either still or
effervescing, the hydrochloric acid in from 5-15 drops may be given in
mucilage, or, if preferred, we may give the dilute hydrochloric acid in
some such form as the following:—

  ℞ Acid. hydrochlor. dil.                   ♏︎ 10-15
    Glycerin pepsinæ                         dr. 1
    Liq. strych. hyd.                        ♏︎ 3
    Tinct. capsici                           ♏︎ 1
  Inf. aurantii co. ad unciam, ter die sumenda statim post cibos.

Sometimes it so happens that while taking the above acid mixture the
subjects an hour or more after meals complain of acidity. If so, it is
due to fermentation, and at the time of its occurrence must be met by an
adequate dose of an alkali with or without some antiseptic preparation.
It goes without saying that if such can be referred to dietetic
errors—food-bolting, etc.—these also must be corrected.

In these cases, too, the _liver_ is frequently inactive, though often
their attacks of “biliousness” signify nothing but _constipation_; but
when there are definite signs of hepatic torpor we may substitute for
the hydrochloric acid in the above mixture the dilute nitro-muriatic
acid. Simultaneously we may occasionally at night give a pill containing
calomel, iridin, or podophyllin combined with aloes and belladonna, or we
may instead invoke colchicum as a _cholagogue_, following it up in either
case the morning after by a saline purge. As a substitute we may in
suitable cases order every morning for some days a full dose of Rubinat,
Hunyadi Janos, or other bitter water.

So much for the more common derangements of the _inter-paroxysmal_ period
and the measures wherewith to combat them. Collectively their aim is _the
restoration to functional efficiency of the alimentary canal and its
accessory glands_, this to the end that, as far as possible, a condition
of _intestinal asepsis_ may be attained, with its correlated diminution
of the excitants most fertile of outbreaks.

Nevertheless, from time to time, either from failure of the patient’s
co-operation or other mischances, our best efforts at _prophylaxis_
fail, and it becomes clear that an attack is _imminent_. What then, save
brisk _purgation_, can be done to avert the threatened outbreak? Our
forefathers, in cases in which the fits recurred periodically and might
be forecast with tolerable accuracy, were accustomed some time _before
the threatened attack_ to place the subject on a rigorous diet, this in
combination with a course of _alkalies_, those of _soda_ being given the
preference in _dyspeptic_ or _hepatic_ disturbance and those of _potash_
when the _urine_ was _scanty_.

That this was sound treatment and abundantly justified by the results is
well acknowledged, and all I would suggest is that this is yet another
juncture at which _atophan_ is indicated, viz., _immediately before a
paroxysm_. At this particular time the _urinary output_ of _uric acid_ is
often _diminished_, a clear indication for enlistment of atophan, which
_increases uric acid elimination_. I note that both Retzlaff and Brugsch
consider it an especially advantageous time for its exhibition. As a
_prophylactic_ measure the former gives 30-45 grains daily for three days
at intervals of a fortnight, and if cardialgia or heartburn ensues, adds
¼-½ teaspoonful of bicarbonate of soda to each gramme of the drug.

Lastly, we have to recollect, too, that colchicum is credited with some
_prophylactic_ powers. Some, it is true, discountenance its employment
in the inter-paroxysmal period, on the plea that it tends to favour
_recurrence_ and _chronicity_ of attacks. While I think it is better to
reserve it for _acute_ or _subacute_ attacks, still I have not found that
colchicum, given in what Sir Thomas Watson called _alterative_ doses,
is anything but beneficial, provided that it be taken _intermittently_,
not continuously, for long periods. As to special indications for its
employment, I think it is more effectual in aborting a threatened attack
when, in addition to dyspeptic phenomena, the imminence of a fit is
betokened by what may be termed specific harbingers thereof, _i.e._,
pricking and tenderness in existing tophi, twinges in the toes, etc.

In conclusion, are we not in this matter of the _prophylaxis_ of gout
somewhat too prone to resort, both in and out of season, to what we are
pleased to term _special medication_? Almost every week some new and
of course infallible “uric acid solvent” is lauded _ad nauseam_ in the
press. Are not we ourselves, too, somewhat overanxious to go with the
tide in prescribing these vaunted “gout specifics”?

The true aim of _prophylaxis_ is rather to _prevent_ the incidence of
those _functional derangements_ that in some subtle way determine the
disturbances in _nuclein_ metabolism, with _secondary_ accumulation of
_uric acid_ in the organism. That drugs, such as atophan, which diminish
the uric acid content of the blood and increase its urinary output,
fulfil an invaluable _rôle_ in ridding the system of excessive amounts of
this chemical outcast, I fully admit.

Albeit, this achievement does but deal with the _consequences_ or
_sequels_, not the exciting causes, of gout. In truth, there is no short
cut to the cure of gout. Only under suitable treatment, applied to meet
all the necessities of individual cases, will any long immunity from its
onslaughts be secured or their intensity attenuated.




CHAPTER XXX

MEDICINAL AND OTHER MODES OF THERAPY (_continued_)—CHRONIC ARTICULAR GOUT
AND ASSOCIATED MORBID CONDITIONS


CHRONIC ARTICULAR GOUT

The gastric derangements that precede acute gout nearly always become
aggravated when the disease is permanently established. Consequently
from time to time many of the measures outlined in previous paragraphs
must be resorted to. But there is this also to be borne in mind, that
in these later stages of the evolution of the disorder the intervals of
relative health grow shorter and shorter. The victim lies more or less
always under the shadow of the malady, and its peculiar impress on the
constitution becomes more and more ingrained. Therewith his sensitiveness
to the _exciting_ causes becomes more and more pronounced.

To detect and thereafter to eliminate the most fruitful excitant of
articular outbreaks in individual examples will form no small portion
of the task that falls on physician and patient alike. In the majority,
it will be some indiscretion of food or drink; in some, insufficient
exercise; in others, intellectual strain or worry, etc. By determining
the particular nature of the excitant in the individual under review
we arrive at his _personal idiosyncrasy_—a matter of much moment in
_prophylaxis_.

Moreover, with increasing experience the physician cannot help noting
that the vulnerability to assaults varies in different subjects. Thus the
development of gouty paroxysms in some will be found to be associated
with _gastro-intestinal_ or _hepatic_ derangements, in others with
_defects of elimination_ through _kidneys_, _bowels_, or _skin_.

In short, these cases must be approached in a catholic frame of mind, and
the success of medicinal therapy will depend on the judgment and clinical
acumen displayed in meeting the ever-varying necessities of individual
instances, not by an almost flippant prescribing of alkalies or, it may
be, iodides, colchicum, or guaiacum. All these are valuable, but only if
invoked with discrimination, and not after stereotyped or routine fashion.

The _joints_ in these cases are the seat of _chronic_ change, and though
they call for due attention, it is the _constitutional_ taint that is of
paramount importance. How best shall we influence this? How else save
by recognition of the morbid content of the _blood_ and cleansing of the
impurities with which it is charged?

I have before stated my belief that _functional derangements_ of the
_alimentary canal_ are the _determining_ cause. It is through their
agency that the toxicity of the blood plasma ensues. In the vast majority
of cases these constitute the dominant departure from physiological
righteousness. It is to these that the _high uric acid content_ of the
_blood_ may presumably be referred. Yet nevertheless _retention_ of the
same in the form of _tophi_ may be relatively slight. Is it that in their
instance the avenues of _excretion_ are more permeable?

In others, again—not necessarily those with more pronounced dyspeptic
symptoms—the retention of uric acid proceeds apace. Clinically the
explanation appears to be that cases with massive _tophaceous deposits_
often display _renal_ changes. In other words, it is the channels of
_elimination_ that appear to be at fault.

But, more than likely, these superficial differences hark back to
infinitely more subtle inward disparities, to _tissue peculiarities_
of function, with correlated variations in their _retention capacity
for uric acid_. Here again the clinician waits upon the bio-chemist,
and meanwhile must base his differential treatment on somewhat coarser
indices.

Thus in one class of case the toxicity of the blood seems attributable
to dyspepsia or mal-assimilation, and the physician’s efforts must be
concentrated on correction of the same. In another type such may be
absent, and yet uric acid accumulates, tophi multiply, and his attention
turns to the kidneys, the avenues of excretion. In others, again, both
symptom complexes may be combined, and his resourcefulness is taxed to
the utmost to meet these several necessities, for, as Sydenham wisely
said, “the weakness of all the digestions and the loss of natural
strength in the several parts are the essence of gout. Each must be dealt
with.”

Nor must we forget that long-continued gout engenders not only a
depravation of general nutrition, but paves the way also for the
insidious production of structural organic changes. In a word, it favours
the onset of _pre-senilism_, with all that such connotes. So it is that
in these subjects, too often past the meridian of life, we have not only
gout to combat, but the grisly appanage of oncoming age.

It is this larger view of our responsibilities that we must cultivate if
our treatment of chronic gout is to be in any sense rational, and not
wholly haphazard. Also, if my contention be correct that the _alimentary
canal_ is the _fons et origo mali_, the major source of the provocatives
of gout, then the basal and essential part of our therapy must be _diet_
and _regimen_. As to the subsidiary medicinal indications, it will
perhaps be more convenient if I proceed to discuss shortly the use of the
various drugs that experience has shown to have been of most avail in
chronic gout.

_Alkalies._—It was formerly thought that by increasing the _alkalescence
of the blood_ its solvent effect on _uratic deposits_ was enhanced and
their formation thereby delayed or prevented. But subsequent researches
by Sir William Roberts conclusively proved to his mind “that alkalescence
as such has no influence whatever on the solubility of sodium biurate.”

Luff, again, from his investigations, held that administration of
the ordinary _alkalies_, of _lithium_ salts, of _piperazine_, and of
_lysidine_, with the object of removing gouty deposits, appears to
be useless. He also claims that no general acidity of the system is
associated with gout, and no relationship exists between the acidity of
the urine and the alkalinity of the blood.

Nevertheless let us not sin against light, which is exactly what we
are very prone to do if we allow ourselves to be obsessed by _uric
acid_ and overlook the records of clinical experience. Take Sir Thomas
Watson; he, without any reference to uric acid elimination, recommended
as a prophylactic against gout 15 grains of bicarbonate of potash in
combination with tincture of rhubarb and some light bitter, to be taken
_every day_. Fagge, again, observes, “Alkalies are decidedly useful in
gout,” and the same views were held by the elder Garrod, Lecorche, and
Dieulafoy, etc.

In short, forgetting for the moment the existence of uric acid and
shedding all hope of their dissolving _tophi_, we find that _alkalies_
have ample justification besides for their employment. They are valuable
as _antacids_, _diuretics_, and as _alteratives_, and, moreover, their
routine employment has been tried and approved.

In other words, the benefit of alkalies depends, not upon any special
solvent effect upon _uratic deposits_, but upon their remedial influence
upon associated and, I believe, causally related _gastric_ and _hepatic_
disorders, and through these on general metabolism. Albeit, let us be
guided by rational considerations when we invoke their aid.

The fact that alkalies are incapable of dissolving _tophi_ is a clear
indication that that deleterious habit of _continuously_ taking potash
and lithia water is not only unnecessary, but undesirable. Alkalies
should be prescribed in short courses and to meet special indications,
_i.e._, _intermittent_, not continuous, administration.

Thus in the minor _gastric_ disturbances which in chronic gout we are
constantly called upon to treat there is no doubt as to the superiority
of the _sodium_ compounds. Moreover, apart from their value in _gastric_
or _intestinal_ catarrh, we have to note their usefulness in dyspeptic
states complicated by _torpid liver_.

When _constipation_ exists, the sodium bicarbonate may be combined with
magnesia, and all will admit the striking benefit attained by short
courses of these drugs with the addition of rhubarb, some simple bitter
infusion, quinine, or strychnine, all rendered more effective by the
addition of some carminative or aromatic.

Sydenham’s electuary was compounded of gastric tonics, and the more
recent Portland and Pistoja powders are in this respect but an imitation
thereof. Indeed, _stomachics_ are the most valuable tonics in gout.
Lastly, it is in the _inter-paroxysmal_ periods of _chronic_ gout that
the sodium compounds are indicated, when the joints, though enlarged, are
quiescent, and the more prominent symptom in the clinical picture is lack
of _gastric tone_, with or without acidity.

As to the _potash_ compounds, it is during and immediately after
articular paroxysms of acute or subacute gout that they find their
chief sphere of usefulness. Apart from this, they are, because of their
_diuretic_ properties, valuable at all times in cases in which the renal
secretion appears to be deficient. The bicarbonate, citrate, or acetate
of potash are the most valuable. The last-named is the most diuretic, but
is rarely used, the citrate enjoying more favour, being more palatable
and most eligible when no direct _antacid_ effect is desired, in which
case it should be replaced by the bicarbonate.

In those instances in which the _skin_ is notably inactive Garrod thought
highly of the phosphate of ammonium, holding that “there is much clinical
evidence to prove its value in the treatment of chronic gout.” Many, like
Burney Yeo, believe that a combination of soda and potash compounds acts
better than when either is given singly. Thus Garrod in cases in which
the action of the liver was defective frequently used the bicarbonate of
soda in combination with the citrate of potash.

As to the _lithium_ salts, general opinion has it that their value in
the treatment of gout has been greatly over-estimated, and that they
are not so serviceable as the potassium and sodium salts. They are also
more toxic and lowering, and Luff some years ago issued the following
_caveat_: “I constantly meet with patients suffering from cardiac
depression, and even dilatation, as the result of the excessive and
continued consumption of lithia tablets, which are so persistently, so
speciously, and so wrongly vaunted as curative of gout.”

In conclusion, it will be seen that clinical experience testifies with
no doubtful voice to the value of most salines. At the same time it
is clear, also, that we should use discrimination, seeing that some,
as Garrod says, are “certainly more adapted to particular cases than
others.” They should also be given well diluted, in moderate doses,
and not continuously but intermittently. These rules should certainly
be followed when alkalies are invoked in gout, not for local _antacid_
effect, but for their general influence on metabolism. Moreover, at
the close of a course of alkalies for this purpose, we may often with
advantage place the subject on acids in combination with quinine, nux
vomica, or strychnine.

_Alteratives._—Of these the salicylates and the benzoates are, by some,
greatly prized, in that they act especially on uric acid, promoting the
elimination thereof. The benzoates are favoured in examples in which the
kidneys are not above suspicion, the latter disability contra-indicating
the use of the salicylates. Some, like Ewart, advocated a course of
benzoates in alternation for periods of a week or a fortnight with a
saline treatment. By Lecorche and Haig, salicylate of soda in doses of 60
grains or more per diem was advocated continuously for prolonged periods.

In my opinion, salicylates are best used during a paroxysm, when, for
some reason, colchicum is contra-indicated, or immediately after,
to promote elimination of uric acid and to minimise or inhibit the
development of _tophi_. As to the benzoates of sodium and potassium,
they are now rarely, if ever, prescribed, though hexamine is growing in
favour as a “urinary antiseptic diuretic and anti-lithic.” Occasionally
I have met with B. coli infections in gout, and in such cases one of the
preparations of hexamine, with lithium or sodium benzoates, is of value,
whilst among the laity urodonal stands in high repute as a means of
removing uric acid and allied bodies.

_Iodides._—Turning to well-tried alterative remedies, there is no doubt
that the _iodides_ well deserve their high repute in the treatment of
chronic gout. Thus in subacute and obstinate swelling of the joints,
and alike in painful gouty affections of the muscles, fasciæ, and nerve
sheaths, iodine in one or other of its forms is _par excellence_ our most
reliable remedy.

In no type of case is it more serviceable than when the joint
inflammation is of low asthenic type—enlarged, stiff, and painful. It may
be given in some such combination as the following:—

  ℞ Pot. iodidi               gr. 5-10
    Pot. bicarb.              gr. 15
    Spts. ammon. aromat.      ♏︎ 20
    Vin. colchici.            ♏︎ 5
    Tinct. capsici.           ♏︎ 1
  Inf. aurantii co. ad unciam ter in die sumenda post cibos.

If colchicum be contra-indicated, a useful substitute to quell pain is
tincture cimicifugæ in 15-minim doses. The dose of the iodide need not
exceed 3-5 grains, as, from my observation, no appreciable advantage is
gained by larger doses. _Iodine-albumen_ compounds may be substituted
for the alkaline iodides as less likely to cause derangement of the
stomach, inasmuch as assimilation is believed to take place in the
intestine. Thus _iodo-protein_ may be administered in doses from 10-15
grains. A tablet containing 10 grains is equivalent to 1 grain of
combined iodine. Excretion being taken as the measure of absorption, it
has been experimentally shown that, six hours after administration, a
lower percentage of iodine was excreted in the case of iodised protein
than with potassium iodide. In other words, the iodine-albumen compound
yield up their iodine to the system at a slower rate. In short, they
disintegrate more slowly and are, therefore, the more likely to exert a
longer continued activity.

An organic compound of iodine with vegetable albumen, _i.e._,
_iodo-glidine_, has been somewhat extensively used in gout, as being
_non-depressant_. Said to undergo almost complete disruption in the
intestines, it is slowly absorbed without toxic symptoms. Iodo-casein
and seroden, a combination of iodine with blood proteins, are similar
preparations, with which, if necessary, the alkaline iodides may be
replaced.

More recently the advantages of _collosol_ preparations of _iodine_ have
been emphasised, and these colloidal solutions, unquestionably, have an
increasing sphere of usefulness in all cases of gout where iodine is
indicated. It has been truly said, collosols “are not new drugs, they are
simply familiar drugs in a new form—a form in which their therapeutic
potency is greatly heightened while their undesirable properties are
reduced to vanishing point.”

Doubtless, collosols exist in a form very meet for assimilation, inasmuch
as they conform to the essentially colloidal character of all the normal
fluids and secretions of the organism. Moreover, toxins or bacterial
poisons appear also to exist in colloidal form, and also, according to A.
B. Searle, “to a large extent in the reactions which create immunity.”

These physical similarities between collosols and the bodily fluids and
tissues ensure their ready assimilation with minimal constitutional
disturbance. Inasmuch as the colloidal state, too, predicates low
chemical affinity, the combination and absorption of collosol
preparations take place gradually and uniformly.

For internal administration colloidal iodine is prepared in aqueous
suspension. It is stated that the whole of the iodine is absorbed in
molecular combination with protein. An iodo-amino acid results, and
ultimately reaches the blood-stream. Arrived there, it, through its
reducing action on lipoids, exerts an alterative effect.

The dose of collosol iodine ranges from 1-4 teaspoonfuls daily after
meals. It does not cause nausea if the amount be slowly increased, and
only exceptionally does it set up iodism. In these respects it has
an undoubted advantage over the alkaline iodides. As to whether they
will wholly usurp the place of this latter is, I think, very doubtful;
this, if only for the convenience with which the alkaline iodides
lend themselves to combination with other alterative remedies. But
in individuals intolerant of iodide of potassium they are excellent
substitutes when the indication is to improve and modify the general
metabolism.

Lastly, too, apart from their use in _chronic gouty arthritis_, we
have to recollect that the iodides are the most reliable means we
possess of influencing the _renal_ and _vascular_ changes so often
associated with gout. Garrod doubted if they possessed any power of
promoting the dissipation of _uratic deposits_, but their power of
eliminating _lead_ must not be lost sight of when treating gout in the
subjects of _plumbism_. Obviously, when invoked for this purpose or to
arrest or retard degenerative processes in kidneys and vessels, their
administration must be continued for long periods—six to eight weeks.
The same persistence, too, is demanded to remove the inflammatory
products in the joints. Simultaneously or alternately short courses of
_atophan_—30-40 grains for two to three days in a month or oftener in
more severe cases—will also be of help in dislodging articular deposits
in the form of tophi.

_Guaiacum._—Many years ago, Sir Alfred Garrod[62] highly eulogised the
value of this drug in the treatment of chronic gout. Said he, “There is
no remedy of which I can speak so confidently. I have known patients who
have been confined to their beds for many weeks with asthenic chronic
gout so far recover within two or three days under the use of this
remedy as to be able to walk about.” He held that it exerted a specific
action on the fibrous tissues, and advocated its exhibition in chronic
forms of gout with feeble circulation. He adds the further interesting
differentiation regarding the employment of guaiacum as opposed to
iodide of potassium. Both these drugs he held valuable when the fibrous
coverings of the joints were especially affected. If the articular pains
were increased by warmth, iodide of potassium is “peculiarly indicated”;
but, under such circumstances, “the use of guaiacum is either altogether
contra-indicated or, at least, it should be administered in combination
with iodide of potassium or some other saline.”

As to its mode of action, Bain noted that, while the excretion of urea
fell somewhat, that of uric acid was markedly increased. But he found,
also, that “neither the phosphorus pentoxide nor the bases showed a
corresponding increase—thereby denoting that this drug probably acts, not
by increasing the production of uric acid, but by eliminating a part of
that stored in the blood.” Moreover, it was noted that the increased uric
acid excretion did not cease with cessation of the drug, but continued
for some time after, the patient’s condition meanwhile undergoing
amelioration. Bain considers that his researches confirm the opinion
arrived at, on empirical grounds, by Sir Alfred Garrod—that guaiacum was
a powerful prophylactic agent in gout.

Returning to its method of exhibition, it must be admitted that it is
most unpalatable when given in the form of a mixture, and is preferably
prescribed in a cachet or tablet. The resin of guaiacum may be given
in doses of from 5-15 grains, and the larger doses may excite nausea
or purging. In smaller amounts, however, it merely exerts a beneficial
laxative effect; it is also useful in cases where the liver is torpid.
This latter action may be reinforced by simultaneous administration of
calomel in fractional doses.

  ℞ Hydrarg. sub chlor.          gr. ⅟₁₀
    Guaiaci resinæ               gr. 3
    Sulph. precip.               gr. 3
  Fiat. cachet. Ter in die sumenda post cibos.

Such is useful as a corrective in intestinal fermentation when given
for three or four days, after which the calomel may be withdrawn and
the guaiacum and sulphur continued in doses adequate to produce a daily
evacuation.

The compound confection of guaiacum or the Chelsea Pensioner Powder
have also stood the test of time, and may be taken in the appropriate
dose daily for weeks. Personally, I have for years employed a cachet
containing guaiacum, iodide of potassium, colchicum, and cinchona as a
prophylactic measure in the inter-paroxysmal periods of chronic gout.

I would here, too, advance a plea for the use of guaiacum as the most
useful laxative for constipation in the gouty, and in combination with
sulphur where there is inactivity of the skin. The following is an
excellent and well-tried formula:—

  ℞ Sulph. precip.
    Pulv. guaiaci
    Pot. bitart. āā              ʒj.
    Pulv. tragac. co.            ʒij.
  Fiat pulv., ½ to 1 teaspoonful to be taken stirred up in water
    or milk at bedtime.

Such is a useful laxative and, during the day, may be often
advantageously combined, in lingering articular gout, with a mixture
containing iodide of potash, nux vomica, and cinchona. Luff, by the bye,
holds that iodide of potash acts more beneficially when given in the
compound decoction of sarsaparilla—the latter also is lauded by Garrod as
having properties somewhat similar to guaiacum.

In conclusion, the subjects of long-standing gout not infrequently are
anæmic. In such cases iron is often not well borne, and has been said
to favour recurrence of acute attacks. Small doses, however, of a less
astringent form agree well, always provided that the bowels are kept
freely open. The ammonio-citrate, the iodide of iron, or one or other of
the organic iron compounds are most suitable. These may be given alone
or in combination with arsenic. For improving the general condition and
promoting the nutrition of such subjects, Robin speaks highly of the
following:—

  ℞ Acidi arseniosi              gr. ⅟₈₀
    Potassii iodidi              gr. 1
    Pulveris rhei
    Extracti gentianæ            āā q.s.
  Misce. Fiat pilula i. “Two pills to be taken daily at meal time.”

In drawing to a close our discussion of the drugs most useful in the
treatment of chronic articular gout, it will be noted that our usage
of them is largely _empirical_, viz., the outcome of experience. We
do not know exactly their mode of action, but this we do know, that
they have stood the most searching of tests—that of _results_. That we
should be largely, if not entirely, ignorant of their mode of action is
regrettable, but no reason whatever why we should discard them in favour
of newer compounds administered on some pseudo-rational basis.

What we need in gout is, rather, what Harry Campbell calls “a broad
commonsense-rationalism—not a meddling finnicking pseudo-rationalism.”
Ignorant of the intimate etiology of gout, we are not as yet capable of
determining the exact nature of the underlying morbid processes. Much
less are we in a position to devise a rational system of drug treatment
whereby to antagonise the same. For us, then, the wiser, if more
humble, _rôle_ of correcting, if we may, such obvious deviations from
physiological righteousness as we may discern, but ever mindful that we
assist, not thwart, the subtle workings of the _vis medicatrix naturæ_,
whereby the balance of the nuclein exchanges is restored.


_Local Measures in Chronic Articular Gout_

When treating of these in relation to _acute_ articular gout, we dealt
with the topical applications best calculated to achieve the absorption
of _inflammatory_ exudates and mitigation of the pain and stiffness
associated therewith. It now remains for us to discuss the treatment of
that specific product of gouty inflammation, viz., _uratic deposition_.

_Treatment of Tophi._—Subcutaneous tophi in the neighbourhood of joints
sometimes become tense and painful, and restrict the movements of the
adjacent articulations. Garrod held that the continuous application of
pledgets soaked in solutions of carbonate of lithia or of potash to
tophaceous swellings had some power in reducing their size, and even
effecting, in some cases, their total absorption. Also, with the intent
of dissipating collateral _inflammatory_ thickening, he sometimes used a
solution composed of equal parts of iodide of potassium and carbonate of
lithia.

More recently, Robin states that the resolution of tophi may be hastened
by local applications of mineral waters containing magnesia and
sodium chloride or a solution of sodium perborate, these affixed with
considerable pressure over the harder parts of the tophus, gentle massage
of which, he thinks, at other times, will aid absorption.

Luff, however, on this point, holds that “the application of the
so-called solvents externally to affected joints is useless, as they are
not solvents of sodium biurate,” and I am inclined to agree with him
that but little is to be hoped for from this method of treatment. A more
effectual method of local medication is by the electrolytic introduction
of drugs.

_Ionisation._—We may enlist _cataphoresis_, either for its _analgesic_ or
its _sclerolytic_ effect. If relief of pain be desired, the electrolytic
introduction of the salicylic ion from a cathode of a 2 per cent. sodium
salicylate solution is most valuable. A current of 20-40 milliamperes,
but only gradually raised, should be passed for twenty to thirty minutes.
Too frequent applications of the latter strength may cause injury to the
skin, and, in Lewis Jones’s opinion, are inadvisable oftener than twice a
week.

If we wish to exercise a favourable stimulant effect in alterations of
nutrition and atrophy caused by gouty inflammation, the _chlorine_ ion
definitely accelerates return to the normal state. Six-fold pads of ample
size, soaked in a warm solution of sodium chloride, are used as a cathode
and bandaged round the joint. The other “indifferent” electrode, similar
in nature, is applied to different parts at different sittings, and in
this way the pathway of the current through the joint changed. Currents
up to 100 or even 200 milliamperes may be tolerated when applied to the
knee; but the intensity of the current should only be raised gradually,
as the burns that sometimes ensue occasion no small pain to the subject
as well as discomfiture to the operator.

_Iodine_ has a like sclerolytic action, and is commonly held to be
superior to that of chlorine. On the other hand, the iodine ion is
much less readily tolerated by the skin, and, according to Leduc, the
necessary reduction in intensity of the current employed goes far to
nullify the greater sclerolytic effect it may possess.

In chronic gouty arthritis we are, as before remarked, confronted not
only with inflammatory products, but also with _uratic deposits_.
Fortunately, these latter also are benefited by the electrolytic
introduction of the lithium ion under an anode of _lithium chloride_. The
current serves a double purpose in this case, for it not only drives in
the lithium, but removes the _uric acid_ ion which is to be found in the
electrode. Edison, some years ago, suggested ionisation with _lithium_
in gout, and the good results he obtained have since been abundantly
confirmed by others.

The Schnee four-cell bath may be used where ionisation is indicated. It
possesses obvious facilities for local or sectional application, as drugs
can be added to the water in the cell and carried through the skin by
means of the continuous current. Thus, in cases of large gouty deposits,
the joint may be placed in a bath containing a 2 per cent. solution of
iodide of lithium or of 5 per cent. bicarbonate of potash. The positive
electrode is then located in the bath, while the negative pole, moistened
with hot water, is applied to the lumbar region. Working with lithium in
this manner, Bordier detected the presence of _uric acid_ in the fluid
of the bath, thus demonstrating introduction of the cation-lithium and
removal of the _anion-uric acid_ at one and the same time. In this way
proof is adduced that the lithium penetrates the tissues, and coming
directly into contact with _uratic deposit_, tends partly to dissolve it.

To achieve the dual purpose, viz., _absorption_ of _inflammatory_ and
_uratic deposits_, we may with advantage give the chlorine or iodine
ions, for their sclerolytic effect on the tissues, in alternate sittings
with the lithium ions. When time is no great object, two or three
_séances_ a week will suffice, but where time presses, the sittings,
according to Leduc, may be given daily, always provided that the
position of the electrode and therewith the direction of the current
in its passage through the joint be changed at each application. It is
necessary to emphasise the fact that the use of too mild currents is
futile, and to secure adequate results a prolonged series of _séances_ is
necessary. Also I would suggest that the simultaneous taking of a course
of atophan would appear to be indicated.

_Surgical Treatment._—In pre-antiseptic days, catastrophes, _e.g._,
_erysipelas_, _gangrene_, etc., having occasionally followed the
evacuation or removal of tophi, it was deemed inadvisable to interfere
with them by any surgical methods. But, the danger of sepsis having been
largely removed, it is now regarded as quite permissible to attempt the
removal of uratic deposits for aesthetic reasons, or, more cogently,
when they give rise to pain or restrict the movement of the related
articulations.

Moreover, the old view that incision or evacuation of tophi was followed
by obstinate _ulceration_ is not borne out by modern experience. Thus my
colleague Lindsay found that healing takes place quite naturally provided
the incision is made over the more healthy skin towards the base of the
swelling. With this I am in agreement, and furthermore would suggest that
tophi when of large size and fluctuating are better opened with aseptic
precautions than allowed to evacuate their contents spontaneously, for
in this last event suppuration ensues, the sores become troublesome, and
remain open for a long time. Sir Alfred Garrod in such circumstances
advised touching up of the indolent parts with nitrate of silver.

In my search through the literature I have only come across two instances
in which operation has been undertaken for the removal of gouty deposits
in relation to tendon sheaths, bursæ, and skin. These were performed
by Alexis Thomson. In one the subject was a medical man, aged thirty,
the subject of inherited gout. Multiple tumour-like nodules, ranging in
size from a pea to a cherry, were located over the knuckles, and the
same were attached to the extensor tendons and moved with them. At the
patient’s request, they were removed on account of their unsightliness.
Their dissection from the tendons was achieved with some difficulty, and
healing, though retarded a little by watery discharge from the wounds,
was “in the end quite satisfactory.”

The other example occurred in a tailor, aged thirty-seven, in whom
massive tophi developed at many sites. The larger deposits were located
over the left external malleolus, the left olecranon, and the right
malleolus. Because of their exposure to injury and pressure, removal of
these various gouty tumours was decided upon. In all save the specially
large swelling over the left external malleolus this was easily
accomplished by cutting through the surrounding healthy tissues. But that
at the site named “was so fixed to the bone that it had to be separated
with a chisel; it was then seen that the chalky deposit occupied spaces
in the spongy interior of the bone, and in the substance of the internal
lateral ligament; the removal of the chalky material in the area of
the wound was carried out more satisfactorily by scrubbing the tissues
with gauze and hot water than with the sharp spoon. The peronei tendons
exhibited a very pretty deposit of urates under the endothelium covering
them.”

Healing of the wounds took place very satisfactorily, and nine months
later the general health was excellent; no further tophaceous deposits
had accumulated, and the scars of the wound had remained quite sound.
As Alexis Thomson observed, that though, even as this particular case
showed, _spontaneous disappearance of tophi may follow a subsequent
attack of gout_, still such could not be hoped for in the case of a
massive deposit in the left internal malleolus, invading as it did the
interior of the bone. He sums up his conclusions in the following words:
“My own experience is limited. So far as it goes, it establishes not
only the safety of the removal of gouty tumours by surgical means, but
also the improvement in the general health which follows the removal of
large masses of urates from the exposed parts of the body. So far as
appearances are concerned, the substitution of linear scars for unsightly
tumours is a decided improvement.”

Now, if we take Riedel’s two instances of _acute_ gout and their
tolerance of incision and local cleansing of urates and the equally happy
tolerance exhibited by Alexis Thomson’s two cases of _chronic_ gout, we
see that, in these days of aseptic surgery, even _gouty arthritis_ can no
longer be regarded as outside the pale of operative interference. But,
as a _caveat_ against rash ventures, I would point out that recently I
canvassed the desirability of operation in a case of massive tophaceous
deposits in the hands and feet; but fortunately a skiagraph was taken
which revealed that several of the phalangeal shafts had at some sites in
their length undergone total absorption.

Nevertheless, given sound general health and failure of other modes
of treatment, I think that operative measures should be seriously
considered, for in the more inveterate types of tophaceous gout the
crippledom and painful ulceration renders the victim’s life a misery, and
one incapable of appreciable amelioration by medicinal or other methods
of therapy.


TREATMENT OF ASSOCIATED MORBID CONDITIONS

When dealing with the clinical account, it was pointed out that acute
gout is frequently complicated by symptoms pointing to involvement of
the fibrous tissues in muscles and nerve sheaths; moreover, that both
during _acute_ attacks and alike in the _inter-paroxysmal_ periods
gouty subjects are prone to two special varieties of fibrositis, viz.,
_lumbago_ and _sciatica_. I may add, too, that in these individuals it is
not uncommon for them to suffer with these local varieties of fibrositis
from time to time prior to the advent of _regular_ or _articular_ gout.

_Fibrositis._—As Bassett Jones and I in our work on fibrositis have dealt
exhaustively with the treatment of its various forms, our remarks here
must necessarily be devoted largely to the general principles of therapy,
and for further details we would refer the reader to our treatise on the
subject.

Whatever the type of fibrositis we are confronted with, the therapeutic
indications are precisely similar to those advocated for _articular_
gout. In other words, the indispensable preliminary measures are to
control the production, absorption, and elimination of _toxins_. To this
end, we must secure adequate evacuation of the bowels, free action of the
skin, and diuresis. These ends will the more surely be attained if at the
onset a temporary fast be enjoined, or a suitable dietary with copious
drinking of bland, unirritating fluid. The general malaise and _pyrexia_
indicate clearly that these cases of acute fibrositis must be treated in
accordance with the general rules applicable to the febrile state.

_Acute Lumbago._—Brisk purgatives are here our most efficient allies, for
there is usually marked functional derangement, with high-coloured urine
and dark, offensive fæces. In such cases it is well to give 3-4 grains of
calomel at night, followed in the morning by a saline purge, and the same
often has to be repeated once or twice during the acute stage. Also the
following prescription, preferably rendered effervescent by adding a few
grains of citric acid to each dose, may swiftly abate the intensity of
the suffering:—

  ℞ Pot. bicarb.                 gr. 15
    Pot. nitrat.                 gr. 10
    Vin. colchici                ♏︎ 10-15
  Aquæ ad unciam, quartis horis sumenda.

Or, as in acute gout, we may give an initial large dose of 30-40
minims of colchicum wine, with subsequent attenuation of the same. It
is in cases with scanty, high-coloured urine and costive bowels that
_colchicum_ succeeds best. On the other hand, in some cases of acute
lumbago the urine is copious and light-coloured, and the bowels regular,
and the fæces normal in appearance. Here the value of the initial purge
is not so apparent, and a mixture containing _salicylates_ and alkalies
will be more likely to give relief, aided, if necessary, by nightly doses
of Dover’s powder, followed by a morning draught of some aperient.

Where the case shows some disposition to linger on in a sub-acute form,
and the urine still remains charged with lithates, a mixture of citrate
or nitrate of potash, spirits of nitrous ether, and infusion of buchu
should be given thrice daily. Sometimes, too, in broken-down subjects
with sluggish circulation, we have found the addition of a few minims of
tincture of digitalis most helpful in clearing up the condition.

Next to lumbago, pleurodynia is the most common muscular type of
fibrositis to be met with in the trunk. I have seen its subsidence prove
the signal for an outbreak of acute articular gout in the great toe.
This significant sequence indicates the necessity of being alive to the
possibility of a _gouty_ basis in such cases and the advisability of
combining _colchicum_ with our remedies.

_Sciatica._—This almost invariably is the outcome of a preceding
attack of lumbago, of which, indeed, it is but an extension. If seen
sufficiently early, and certainly when there are febrile symptoms,
a mercurial purge, followed by an alkaline and diuretic mixture in
combination with colchicum or salicylate of soda, should be resorted to
vigorously, so as to abort, if possible, the attack.

If the underlying constitutional anomaly has been correctly diagnosed as
gouty, the colchicum will exert its specific effect, and quickly, and the
more speedily the sooner it is exhibited in the early stage. But even
when seen later it is well worth trying the following combination:—

  ℞ Quin. hydrochloratis                ½ drachm.
    Pot. iodidi                         2 drachms.
    Vin. colchici                       1 ounce.
    Tinct. aurantii                     2 ounces.
    Aquam chloroformi                   To 8 ounces.
  Sig., 2 teaspoonfuls in a wineglass of water twice a day.

Having regard also to the gouty origin, it is hardly necessary to insist
on regular and adequate evacuation of the bowels.

Of all varieties of gouty fibrositis the _acute brachial_ type is the
most difficult to treat, owing to the marked tendency to prolongation
of the acute stages. The only chance of cutting short such an attack
is not to treat lightly its earlier manifestations, but to bear in
mind its evil potentialities; but only too often they do not come under
observation until the condition is well established.

Gowers, who has written so illuminingly on this particular type of
fibrositis, obtained the best results in the early stages from a
combination of nitrous ether, citrate of lithium, and colchicum, with
in addition, in the more intense forms, small doses of perchloride of
mercury. Of the salicylates, salicin and aspirin, he speaks with but
faint praise, and I have myself known them afford but little aid.

In reviewing the foregoing acute types of fibrositis, I would, as to
_relief of pain_, insist on internal medication of all sorts being
held as purely secondary to the infinitely more important matter of
procuring rest and fixation for the inflamed structures. Immobilisation,
indeed, supplemented by thermic and anodyne applications, hardly, if
ever, fails to alleviate the suffering. If these prove futile, aspirin
and phenacetin, either singly or in combination, should be exhibited.
Here I would remark also on the value of cimicifuga, which I have found
strikingly useful. Lastly, only very exceptionally in my experience is
morphia called for.

In _chronic_ or _recurring_ forms of fibrositis we should mark any
deviation from health in the shape of gastro-intestinal or hepatic
derangement, while noting also any inactivity on the part of the
kidneys or skin. As to drugs, chief reliance must be placed on the
iodides guaiacum, arsenic, and sulphur. They are most useful, of
course, when exhibited during the early stages, before organisation of
the inflammatory products ensues. When hard and resistant nodules or
infiltrations have formed, their administration is of little value.

It is for this reason that I have elsewhere advocated early resort to
_local massage_, viz., at the close of acute attacks, as only by this
means can we hope to dissipate these new formations, the persistence of
which determines the inveterate tendency to recurrence. In the space at
my disposal it will be impossible to consider in detail all the special
modes of therapy—electrical, thermal, hydrotherapeutic, etc.—and for this
information I must refer the reader to the next chapter.

_Oxaluria._—This condition is sometimes met with in the gouty. The
subjects are often nervous, irritable, and languid, complaining at the
same time of vague pains, most frequently in the loins and along the
distribution of the sciatic nerve. It occurs more commonly in persons of
sedentary habit, and correction of this, as well as revision of their
diet, is almost the only effectual method of getting rid of the complaint.

All vegetables rich in oxalates, such as rhubarb and spinach, must be
eliminated, and likewise tea. At the same time, as Sir Alfred Garrod
suggests, we should, to influence the proportions of the bases present
in the urine, cut off all foods rich in calcium, _i.e._, milk and eggs.
On the other hand, we should advise the intake of such as are rich in
magnesium and yet poor in oxalic acid, viz., peas, beans, and coffee, and
oxalate-free foods, such as all kinds of meat.

In my own person I suffered for some weeks with obstinate lumbar pain,
the cause of which appeared to be obscure until the existing state
of oxaluria was discovered by a professional colleague. I would here
emphasise the fact that when a case of lumbar or sciatic pain is defiant
of cure by the usual methods of therapy we should always suspect this
possibility of oxaluria, for commonly the urine is copious and clear;
hence perhaps the frequency with which the condition is overlooked.

As to medicinal measures, we should bear in mind that Sir John Rose
Bradford pointed out that the production of oxalates was initially due
to deficient HCL, with secondary fermentation of foodstuffs, _i.e._,
carbohydrates, especially sugar. The primary indication, then, is to
reinforce the digestive capacities by administering hydrochloric acid
or, as many prefer the dilute nitric muriatic acid, in combination with
nux vomica, and in some cases pepsin. As Sir William Whitla remarks, if
organic acidity be prominent, this may be intensified by mineral acids,
in which event alkalies combined with a few grains of papain two hours
after meals are indicated.

In conclusion, the nerve element in these cases is so pronounced that
a thorough change of air and habits is often indicated, combined with
freedom from worry, abundance of exercise, and a stimulating course of
hydrotherapy.

_Glycosuria._—The variety met with in the gouty, being of the alimentary
type, is usually very responsive to dietetic measures, and these have
been already dealt with. A course of spa treatment is often the best
possible mode of therapy for these cases.

As to medicinal measures, these certainly should not be embarked upon
until the effect of dietetic revision has been ascertained. If under
their influence the glycosuria wholly disappears, then drugs may be
uncalled for, save perhaps occasional aperients, antacids, or similar
remedies of like nature. If, on the other hand, the glycosuria cannot
be kept under control by dietetic measures, then recourse must be had
to drugs. Here it may be noted that guaiacum diminishes the amount of
sugar excreted, and it may be given a trial before resorting to codeia.
Generally speaking, when the case requires codeia it has passed out of
the realm of gouty glycosuria into that of true diabetes, the treatment
of which grave disorder is beyond the scope of this work.

_Hyperchlorhydria._—The disorder is rare in gouty patients, and its
diagnosis from organic acidity cannot be made without examination of the
stomach contents. Moreover, when found to be present an endeavour should
be made to elucidate its cause. If gastric and duodenal ulcer can be
excluded and the condition appears to be of the nature of a secretory
neurosis, then the underlying nervous defect will call for treatment.

In some cases the exciting cause lies in errors of diet and habits of
living. These when faulty require correction; very often in these cases
it is not so much the nature of the food as the hurried manner in which
it is bolted that is responsible. At times, when free from hurry or
worry, they can eat any kind of food with impunity. When the attacks
are on, it frequently happens that all types of food, whether easily
digestible or not, are equally provocative of acidity. We see then how
large a part general hygiene plays in the successful treatment of these
cases.

As to diet, this is, of course, of primary importance, the main
indications being the reduction or withdrawal of farinaceous foods, and
for a short period on a Salisbury regimen or some modification thereof.

The medicinal indication is to afford relief during the acute attacks.
Fortunately these are usually _intermittent_, and when the occasion
arises are fairly readily controlled by massive doses of alkalies,
frequently combined with an artificial digestive, _i.e._, papain. While
magnesia and bicarbonate of soda are, as a rule, invoked, others speak
well of sodium phosphate (5 grams) with menthol (0·25 gram), given two
hours after each meal.

Luff, discussing hyperchlorhydria in the gouty, highly extols hopogan
(magnesium peroxide), in doses from 20-30 grains, one hour after food,
the amount to be reduced if it causes purgation. To inhibit excessive
production of HCL, belladonna, in 5-minim doses of the tincture, before
meals results in reduction of acid values, both absolute and relative,
of the stomach contents, and, moreover, relieves spasmodic contractions.
Constipation in these gouty subjects is best combated by an occasional
nightly pill containing colchicum in combination with aloes or other
laxative. Lastly, when digestion becomes more normal nervine tonics, such
as arsenic, valerian, and the like, may be given to correct, if possible,
the underlying nerve element in these troublesome cases.

_Gouty Phlebitis._—To obviate the risk of embolism, absolute
immobilisation of the affected limb is imperative, and it should be
slightly elevated and protected by a cradle. In many cases it will
suffice if the limb be enveloped in cotton wool and a broad, many-tailed
bandage lightly and evenly applied. If the pain be severe, equal parts
of glycerine and the green extract of belladonna should be smeared
along the course of the inflamed vein and hot fomentations applied.
Internally saline aperients should be given to secure daily evacuation
of the bowels, and a mixture containing iodide of potassium and ammonium
carbonate taken three or four times a day, to promote solution of the
clot.

_Gouty Eczema._—In these cases the primary indication is to revise
thoroughly the diet, to the end of correcting a frequently associated
gastro-intestinal derangement, notably any tendency to constipation.
If these the basal indications are not fulfilled, all local forms of
medication will be futile. As to these last, the primary desideratum is
to protect the parts from all accidental irritants, and the chief source
of offence is scratching by the victim himself. Otherwise we should take
every care to prevent irritation by clothing, hard collars, etc.

While cleanliness is essential, the soaps used should be of the neutral
kinds, or bran or barley-water substituted. Ointments and lotions
are best avoided. In the milder cases protection of the parts is the
essential. In the limbs this may be attained by glyco-gelatine zinc; but
on the neck, the groin, the inside of the thighs or lower parts of the
abdomen, the tragacanth pastes or similar preparations are more suitable.
Both the gelatine and the pastes and varnishes may be readily medicated
with drugs of anti-pruritic properties, such as oil of cade, carbolic
acid, resorcin, or salicylic acid.

_Gouty Nephritis._—This must be treated on the lines recognised as
suitable for _chronic Bright’s disease_, the underlying gouty condition
being always borne in mind, as also any contamination with _lead_. As
general measures any excess in eating or drinking must be avoided, the
skin kept active, and the bowels open; and where possible favourable
climatic conditions should be attained.

Frequently the treatment resolves itself into that of the associated
arterio-sclerosis with high blood pressure. This we should endeavour to
control by regulation of the subject’s habits in the matter of diet,
work, exercise, etc., rather than by flying forthwith to the use of
_vaso-dilators_, premature resort to which has often proved the beginning
of the end.

Moreover, I would, like many others, strongly deprecate the far
too prevalent practice of dilating to these subjects on the evil
potentialities of raised blood pressure. Not a few thenceforth literally
walk in the valley of the shadow, and the fear of sudden death is ever
before them. It is not only cruel, but frequently unnecessary. Often
the increase of tension is no more than their age would account for,
and equally often no symptoms indicative of raised blood pressure are
complained of. Why then make the subject miserable?

By all means, take the blood pressure, but say as little as possible
about it. These people, in my experience, need more often to be reassured
than frightened. Only now and again does one meet with individuals who
must for their own sake be gravely warned of the dangers incidental to
their condition, men who, despite the warnings afforded by giddiness,
epistaxis, etc., will not alter their ways of living.

As to medicinal measures, all agree that an occasional blue pill or a
dose of calomel, ½-1 grain, for three or four nights in succession,
and followed in the morning by a saline purge, is one of the most
satisfactory procedures to adopt. Hand in hand with this, a course of
iodides, gr. 10-15 three times a day, for some weeks, is also most
beneficial. After six or eight weeks of the above we may substitute a
course of nitrites, _e.g._, nitro-glycerine, sodium nitrite, or erythrol
tetranitrate. Nothing is better in the milder cases than Sir Lauder
Brunton’s formula, the efficacy of which I have often proved:—

  ℞ Sodium nitrite               gr. ½-2
    Potassium nitrate            gr. 10-20
    Potassium bicarb.            gr. 10-30
  Fiat pulvis, to be taken in a tumblerful of water every morning.

Needless to say, vaso-dilators should not be exhibited if signs of waning
cardiac power are evident. Also when there is much albumen the use of
mercurial purges calls for great discretion, and saline aperients should
be given the preference. Insomnia, a frequent trouble in these cases,
is best met by bromides, and I agree with Luff that in gouty subjects
sleeplessness is better combated by measures which reduce arterial
tension than by resort to hypnotic drugs.

Lastly, symptoms of cardiac dilatation and failure, which should be
suspected when the arterial pressure falls without the previous use of
vaso-dilators, will call for the exhibition of cardiac tonics: digitalis,
strophanthus, and strychnine; and threatened uræmia may be postponed by a
judicious dietary, saline purgation, and diaphoretic measures.




CHAPTER XXXI.

CLIMATO-THERAPY, HYDRO-THERAPY, ETC


CLIMATE AND RESIDENCE

While, naturally, individuals display wide differences in their capacity
of adjustment to variations in climate and season, there is no doubt
that the gouty, as a class, are abnormally deficient in their power of
adaptation in this respect. Said Hippocrates in one of his aphorisms,
“Podagrici affectus vere et autumno plerumque moventur,” and this
peculiar influence of _season_, viz., the aptness of gout to recur in
spring and autumn, especially in its _early_ stages, is a very singular
feature.

The increased incidence at these particular periods of the year is, I
think, a striking proof of their deficiency in the defensive mechanisms
that enable normal persons to withstand with comparative impunity sudden
transitions from cold to heat, dryness to damp, and so forth. So it is
that rapid changes in the surrounding air, in its degree of warmth, or
its motion by wind are fertile of attacks. The east and north-easterly
winds of spring account for no few examples, as likewise inadequate
protection from cold or damp.

In short, a _variable_ climate is the most provocative of gout, that is,
most likely to elicit gouty manifestations in one predisposed thereto.
Conversely, stability in climate favours freedom from attacks. Thus some
obtain exemption from their gout by removing to a hot climate, others
when removed to one of cold, dry character. Doubtless these differences
in response hark back to _individual constitutional peculiarities_.

It is the vigorous plethoric persons, who eat too much, that do well in
dry, cold climates. The low temperature and dryness of the air stimulate
tissue changes, dispose them to active exercise with consequent increased
efficiency of digestion, assimilation, and excretion.

On the other hand, many victims of gout are spare feeders, with feeble
powers of digestion and metabolism, and for them a mild, moderately warm
and not too damp climate is the more suitable, involving, as it does,
less strain upon their capacities of adjustment.

If one may be permitted the generalisation, the ideal climatic
conditions for the gouty are low relative humidity, abundant sunshine,
and a low rainfall. But, alas! too often, permanent residence in such
desirable surroundings is unattainable, and the most that can be
compassed is a brief sojourn in some more congenial environment.

Still, some discrimination must be shown in the matter of choice, and the
physician, while mindful of the gout, must envisage the _individual_ as
a whole; for in advocating a change of climate his hope is that he may
remove or antagonise certain noxious influences and coincidently restore
the physiological machine as near as can be to a state of functional
efficiency.

The former purpose will often be fulfilled by mere withdrawal of the
subject for a time from his usual calling and environment. How frequently
will simple _rest_ and _recreation_ succeed when medicinal and other
forms of therapy have wholly failed! And how largely, may we remark, does
the Vis Medicatrix Naturæ work through the medium of things _psychic_,
not physical, to achieve its beneficent ends!

Still, not always is it _rest_ that is needed, and some regard must be
had to previous habits. Thus, for the _sedentary_, repair to a _bracing_
climate is indicated, some inland resort of moderate elevation, where
oxidation processes are quickened, and where if they eat more they take
more exercise, and so adequate elimination is assured.

On the other hand, for the elderly or old, or those enervated by
long-continued gout, a _sedative_ climate must be sought, one marked by
mildness, dryness, and equability. Bath, with its low diurnal range of
temperature, is eminently suitable for this class of gouty patient, who
often stand but ill the, for them, too stimulating qualities of more
bracing localities, such as Llandrindod, Harrogate, or Buxton, etc.

Frequently, however, our choice is dominated by some _associated morbid
affection_. Our patient may suffer from a so-called gouty _eczema_; if
so, he must avoid cold, damp places, or windy localities, and, for that
matter, sea air often, at first at least, aggravates the affection. Or
it may be that he suffers with “dyspepsia,” some catarrhal condition of
the alimentary canal, or a “sluggish liver.” For him, then, a dry inland
health resort of moderate or high altitude is preferable to one of sea
level, which will likely find him drowsy, indisposed to exercise, and a
prey to what he terms biliousness.

If _renal_ disease be a complication, he should seek a dry, warm climate,
and, if he can, winter abroad, say, in Upper Egypt or Algiers, which,
though it is warm and dry, is nevertheless somewhat marred by the wide
diurnal range of temperature and the not infrequent cold winds. If,
therefore, very sensitive to vicissitudes of temperature, the relatively
dry, warm marine health resorts of the Riviera are open to him.

If to go abroad is out of the question, one of the mild southwestern
seaside resorts at home is eligible, _i.e._, Bournemouth, Sidmouth, or
the more sheltered parts of Torquay, and Falmouth. Again, if he show
a tendency to _cardiac dilatation_, with or without valvular disease,
high altitudes will obviously be unsuitable, and dry, inland resorts of
moderate or low elevation should be given the preference.

Lastly, before despatching any gouty subject for a so-called change, it
is wise to elicit any personal _idiosyncrasies_ that he may be victimised
by. In other words, find out his most vulnerable points. Thus some gouty
persons are able to brave cold and damp with impunity, but pay dearly for
the slightest indiscretion in diet. They must therefore be warned that no
climatic change, however suitable, will absolve from the ill-effects of
improper or immoderate eating.

Others again—the majority—are extremely sensitive to atmospheric changes,
and such good as they might derive from a well-selected climate is
nullified through thoughtless omission of simple precautions against
“chills.” In short, the victims of gout can only ensure for themselves
the beneficial effects of _climatic therapy_ if, at the same time, they
vigilantly shield themselves from what experience has shown to be, in
their particular instance, the most fertile extrinsic or intrinsic source
of relapses or exacerbations of their disorder.

_Choice of Residence._—In these days it may savour of irony to talk of a
choice of residence where none is. Still, much of the benefit accruing
from a change of air will depend not only on the place resorted to, but
the situation of the dwelling or hotel, in which the subject takes up his
temporary abode. Thus in inland resorts some parts of the town may lie in
a hollow, others on adjoining slopes or plateaux at an altitude higher
by some hundreds of feet. Sites like the latter are obviously unsuitable
for the victims of cardiac dilatation, etc. Again, where the patient’s
condition is such that he must perforce spend a large portion of his time
indoors, it is a matter of some moment that the situation and aspect
of the building and, more pertinently, the subject’s suite or room be
ascertained before he takes up residence.

Apart from sanitary and hygienic considerations, the quality of the
cuisine, general comfort, class of society, have all to be thought of, if
the best results are to be obtained. They are not unimportant details.
How often is the benefit of a stay nullified by uncongenial surroundings,
by a gloomy outlook, the fret and jar of ill-assorted or discordant
elements, that forbid that cheerful intercourse that does much to restore
that sense of _bien-être_ so eagerly sought.

In short, attainment of the best results of climato-therapy can only
be achieved through the medium of a closer co-operation between those
who practise at health resorts or spas and the patient’s usual medical
attendant. But, meanwhile, for most of us, our dwelling place doth rest
upon our calling, and we may take this for our comfort that climatic
vicissitudes may be greatly mitigated by a _well-situated_ and _sanitary_
residence. I allude, of course, here to a _permanent_ abode, and the
gouty, if he enjoy any latitude, should live in a house built on a
_well-drained gravel soil on a slope, sheltered from the north and
north-east winds_.

Again, with the question of habitation is bound up the equally important
matter of _clothing_. By our forefathers _flannel_ underwear was deemed
the most eligible, despite its low or deficient power of absorption. But,
without discussing the various arguments adduced in favour of this or
that particular fabric, I would myself favour _silk_ as being, perhaps,
the ideal _underwear_; next to this a single woollen or woven linen
vesture, and it goes without saying that, prone to excessive sweating as
these gouty subjects are, frequent changes are essential. The feet of
the gouty are their weak spot, and, apart from the correction of _static
deformities_, flatfoot, etc., it is extremely desirable that they not
only be well shod, but be especially careful not to sit about in wet
boots or socks.

For the rest, their outer layers of clothing should be light, warm,
easy and not tight fitting. Extremely liable as they are to lumbago and
sciatica, they should be careful to enlist a thicker fabric than is usual
for the back of their waistcoats; while sufferers from sciatica may, with
advantage, insert a silk lining to the seat of their trousers.

Lastly, it is most important that the gouty, and of course all persons,
should dress according to the prevailing weather and not according to the
_time of year_. For them, more than any other class of person, to doff
summer and don winter clothing for no other reason than some arbitrary
date is fraught with mischances, freedom from which would be purchased by
a little commonsense.


EXERCISE

It has been wisely said that “those threatened with gout should imitate
as far as practicable and consistent with comfort the habits of
agricultural labourers,” for sedentary occupations and idle ways not
only favour the invasion of the disorder but hasten its recurrence.

How frequently, indeed, is it the direct outcome of an abrupt change in
habits—a hunting man, predisposed to gout, sustains an accident, can no
longer ride to hounds and takes to motoring. Unless he forthwith curb his
food intake, the disorder overtakes him. Sometimes misfortune proves a
blessing in disguise, as in the case related by Van Swieten of an opulent
and gouty old priest, who, captured by Barbary corsairs and forced to
work as a galley slave, soon lost his gout.

Again, it is notorious that in those in whom the brunt of the disorder
falls on the _lower_ limbs, the outlook is more sombre than in those more
severely crippled in the hands. In short, capacity for and willingness
to take adequate exercise is one of the most potent measures wherewith
to fend off the gout. The amount should be in proportion to the age,
strength, and previous habits. The exercise should be taken not after a
spasmodic but _systematic_ fashion. For erratic, like excessive, exertion
often converts the expected benefit into the exciting cause of an attack.
The aim should be not exhaustion but wholesome fatigue.

Young and fairly vigorous persons, if previously sedentary or indolent
in habit, should take regular exercise, gradually increased. In the
middle-aged, especially if obese, it should be graduated according to the
capacity of their circulatory organs, and more stress laid on respiratory
exercises and dietetic restrictions. For in their instance fatigue or
over-exertion is easily induced, often with grave consequences. Also, in
long-standing cases, neurasthenic from long-continued pain, it is well to
begin more or less tentatively, and in many cases to prescribe a course
of _massage_ before proceeding to active exercise. For not seldom such
subjects have but a small fund of nerve energy to draw upon.

In the gouty, even the malign influence of bad habits of living is
greatly mitigated by active exercise and labour. “The gout very rarely
visits the poor man’s cottage.” Nothing can so effectually counteract a
predisposition to the disorder, and what Sydenham thought of its value
we may guess from his trenchant remarks on horse exercise. “And, indeed,
I have often thought if a person was possessed of as effectual a remedy
as exercise is, in this and most _chronic_ diseases, and had the art
likewise of concealing it, he might easily raise a considerable fortune.”

In conclusion, if healthful exercise of the body is imperative for the
gouty, I need scarcely labour the desirability also of congenial and
adequate exercise of the mental faculties. Adequate, but not excessive,
lest, like Sydenham, it reacts in added sickness. Otherwise absorption
in some honourable pursuit will do much to dissipate that tendency to
introspection and depression so often born of the consciousness of an
ever-constant menace to long-continued health.

    “Orandum est, ut sit mens sana in corpore sano.”


GENERAL MASSAGE

In judiciously prescribed and skilfully applied massage we have an
agent of pre-eminent value in the treatment of gout. Indeed, Sir
William Temple—a martyr to the disease—when speaking of the benefit
of “friction,” frankly stated that “No man need have the gout who can
keep a slave.” In this there is much truth, for the beneficial results
of massage are not confined merely to the affected joints or muscles,
but, as a result of the improved circulation, waste products are more
readily excreted, the nerve centres regain tone, and a general feeling of
_bien-être_ is promoted.

It cannot be doubted that general massage of the trunk and limbs
accelerates the elimination of the chemical outcasts of metabolism, and
simultaneously, by ensuring a more adequate supply of fresh blood to the
tissues, must result in an access of renewed vitality. Many, indeed, have
adduced experimental proof that such a quickening of the vital processes
does ensue after general massage. We should therefore, in elderly or
feeble subjects, or in those of sluggish habits, advocate from time to
time a course of general massage for its _prophylactic_ effects.

It is the more especially indicated in those gouty subjects prone to
attacks of _muscular fibrositis_—attacks of which are undoubtedly
favoured by the retention of the toxic and waste products of muscular
metabolism. Nothing, again, so facilitates the dissipation of exudates,
nodules, or thickenings in these structures, for the treatment and
prophylaxis of which massage is indispensable.

In enlisting the _prophylactic_ action of general massage, it is not
desirable that the _séance_ should exceed forty minutes, and it should in
all cases be followed by an hour’s rest; to practise it too soon after a
meal is inadvisable, and in those cases in which it favours the advent of
sleep it is best undertaken in the late evening.

In conclusion, I would urge the importance of more interest being taken
by the physician himself in the technique of massage, as I am assured
that, if rationally and perseveringly practised, it constitutes one of
the most valuable adjuncts in the prophylaxis of gout.


GENERAL HYDRO-THERAPY

That hydro-therapy constitutes one of the most effective, if not _the_
most effective, methods of treating gout, is almost a truism, if judged
by that most “acid test”—Experience. The particular applications we are
about to discuss entail _exposure of the whole body_. In other words,
those measures directed more especially to treatment of the _underlying
causal state_—the correction of that warp of metabolism or auto-toxic
state of which the arthritic, muscular, or other lesions are but local
manifestations.

It goes without saying that, with this for our objective, there is
much need for discrimination in the selection of measures suitable
for individual cases, and, naturally, the basis of such differential
treatment is _thorough physical examination_ prior to embarking on the
course. Yet how frequently on their own initiative do these subjects
enter lightly upon a series of baths, mingling stimulant and sedative
procedures in haphazard fashion, unwitting that hydriatric measures are
capable of infinite harm when misapplied.

For in hydro-therapy the personal equation is of prime importance,
varying with _individual reactive peculiarities_. In short, the character
of the response differs widely in different subjects, efficiency or not
of the nervous and circulatory functions being the chief controlling
factors. Hence accurate appraisement of the reactive powers of the
constitution to hot and cold applications is the basis of rational
hydro-therapy.

Thus _nervous irritability_ is _the_ outstanding characteristic of
some gouty constitutions. They are therefore intolerant of extremes of
temperature, and for them sedative or sub-thermal baths are the most
suitable.

Others suffer from _torpid circulation_ and _sluggish vascular response_,
and in their instance, stimulant measures, hot or cold, in sequence
or in alternation, are indicated. Again, some are _obese_, and others
_lean_, and while of the twain the former react more feebly, on the other
hand, they stand prolonged courses of hydro-therapy more satisfactorily.
In contrast, the thin, though they react well, are more readily
exhausted, and so apt to suffer from “secondary chill” or other untoward
consequences.

_Prophylactic Measures._—As we have noted, the “gouty,” more than others,
are intolerant of atmospheric vicissitudes. Accordingly, if we would
strengthen their defensive mechanisms in this respect, we must endeavour
to train them to react more adequately to _cold_ or _sub-thermal_
impressions.

Of the value of _thermal_ applications in chronic gout I am
convinced, but, on the other hand, we must not blind ourselves to the
value—_prophylactically_ speaking—of their judicious conjunction with
_sub-thermal_ or _cold_ procedures. For these latter stimulate oxidation
processes, and in chronic gout, according to many, there is deficient
oxidation of protein waste, while, apart from this, in the gouty obese
there is imperfect oxidation of adipose tissue.

Prophylactic measures to be of any real avail must be _continuous_,
and spas or hydropathic establishments should indeed be more alive to
their educational responsibilities in this matter, for the benefits
of hydro-therapy as regards prophylaxis are within the reach of all
possessed of the convenience of a modern bath-room.

They should be taught to inure themselves by taking daily a tepid bath
followed by a cold shower or rain spray. If this be too drastic, let
them, while standing in warm or tepid water, briskly rub the rest of
the body with a coarse towel wrung out of cold water, into which, if
liked, salt has been added to the point of saturation. In this way the
tonic effects upon the skin of hypo-thermal or cold applications may be
invoked, and thereby its undue sensitiveness is reduced and therewith the
liability to subsequent attacks.

It now devolves upon us to consider under what circumstances
hydro-therapy is inadvisable, and, incidentally, those ill-effects that
indicate its modification or abandonment.

_Contra-indications and Untoward Complications._—Authorities generally
seem unanimous on this point, viz., that the chief sphere of
hydro-therapy is in _chronic_ or subacute gout. On the other hand, they
are equally unanimous in proscribing its exhibition in _acute_ forms of
the malady. Speaking for myself of the Bath waters, I am quite convinced
that the distinguished physician, Caleb Hillier Parry’s pronouncement,
“that the Bath waters, in no form whatever, are beneficial during the
paroxysms of gout, or in any inflammatory disposition which may exist in
the interval,” is not only true but capable of extension to all forms of
hydro-therapy as applied at this stage of the disorder.

Nor do I think it advisable if _prodromal_ symptoms suggestive of the
imminence of an attack are present. It is too, I think, impolitic—after
the subsidence of a severe attack—to resort too quickly thereto, the
more especially if there is a disposition to what our forefathers termed
“flying gout.” In either event, an _acute outbreak_ is most likely to
ensue, and, though there is doubtless some truth in the old idea that a
gouty subject feels better after an attack, still it is not, I think, the
physician’s _rôle_ to evoke gout, but rather to prevent its explosion.
Occasionally mischances of this sort will happen, but only exceptionally,
if the foregoing safeguards be respected. Certainly if the patient seems
palpably on the verge of an attack it is but discreet to postpone baths
until the good effects of free purgation and strict dieting have been
derived.

Indeed, I would go further, in that I think that, under all
circumstances, a course of hydro-therapy should be preceded by _free
evacuation of the bowels_. We should then hear less of that disturbance
of the system known as “well-fever” or “poussée-thermale,” which, it
is not sufficiently recognised, may follow not only _internal_ but
_external_ use of mineral waters. I allude to _dyspepsia_, _lassitude_,
or _skin eruptions_, etc., symptoms which formerly were thought to be
of critical or beneficial nature, but which, I agree with Dresch, are
probably the result of an _auto-intoxication_, and, as he thinks, more
or less combined with an infection by the bacillus coli. Should such
symptoms supervene during a course, the baths had better be omitted
for two or three days _pending their disappearance_ under appropriate
measures.

In the same way, there are reservations regarding the suitability of
baths in _chronic_ gout. Thus, if complicated by advanced _cardiac_ or
_renal_ disease, hydro-therapy is often _contra-indicated_, and, in any
instance under such circumstances, has to be undertaken very cautiously.
On the other hand, it is wonderful how well many examples respond if
due discrimination be exercised. Especially suitable are those cases of
gout and _renal_ disease in which the _heart_ is hampered by increased
_peripheral_ resistance. Such cases under Aix massage, frequently, as
Bain and Edgecombe pointed out, improve strikingly through the consequent
reduction of arterial pressure.

Turning now to the _untoward results_ or _complications of
hydro-therapy_, hot baths, if of too high a temperature or too
prolonged, may cause _vertigo_, _fainting_, or _palpitation_—an
indication for reduction in temperature and duration. Or, if douches
are used, the pressure may be excessive. _Insomnia_, again, may follow
over-stimulation, and our measures must be altered accordingly. Loss of
appetite and strength, too, may be the outcome of too drastic treatment
and excessive reaction.

It is well, also, that during a course of hydro-therapy the patient’s
body weight be taken from time to time, and note made whether he is
gaining or losing in muscular strength. If weight sink and, coincidently,
strength increase, all is well with the gouty obese; but if muscular
capacity be waning, excessive demands are being made on the subject’s
oxidising and eliminative processes.

Examination of the _urine_, too, may yield indications of value. A
notable increase in the output of _chlorides_ suggests excessive tissue
waste, and of _phosphates_ too marked excitation of the nerve centres,
and the appearance of albumen or sugar, if previously absent, will
indicate reduction in intensity of the hydriatric procedures. In short,
we should be alive to the profound influence of hydro-therapy on general
metabolism and the consequent necessity of medical supervision throughout
the course.


METHODS OF APPLICATION OF GENERAL HYDRO-THERAPY

Subject to reservations, stimulant hydro-therapeutic procedures are in
_chronic_ gout _the_ special indication. Thermal waters, therefore, are,
generally speaking, the most suitable, and _cæteris paribus_, the higher
the temperature the greater the excitant action. Of natural thermal
baths, those of Bath, Aix-les-Bains, Gastein, Wiesbaden, etc., enjoy
great repute, and, judging from personal experience of the first-named
spa, I doubt not that—given due discrimination—all waters of this group
are unquestionably beneficial.

Having regard to their _radio-active_ properties, the best results are
undoubtedly to be obtained by a combined bath, drink, and inhalation
cure. Simple immersion baths, deep or reclining, with or without massive
under-current douches, enjoy well-deserved vogue for their general and
local effects.

Moreover, as the local douching exerts a sedative as well as a resolvent
effect, they prove most useful not only in articular gout, but in the
treatment of those frequent concomitants, _lumbago_ and _sciatica_. Their
efficacy is much enhanced by coincident or subsequent massage, and to
increase the powers of resistance, such hot baths should be followed by
graduated sub-thermal or cold applications.

Sool-Bader, or natural thermal brine waters, exert a similar effect,
but such are not available in this country. But cold brine baths—given
at temperatures of 98° F. and upwards—are obtainable at Droitwich,
Harrogate, and Builth, and are invoked more particularly in long-standing
cases with great thickening of the arthritic or related muscular
structures.

Again, gouty subjects not seldom suffer with _high blood pressure_,
and our treatment must be modified accordingly. Here we may enlist
what are known as _Aix massage_ baths, which tend to _lower_ arterial
pressure through the profound influence they exert on metabolism, and
the elimination of toxic and waste products. As in warm immersion baths
enervating after-effects are apt to ensue unless the tonic-bracing action
of a _terminal cold application_ be invoked. On the other hand, in some
cases of chronic gout the abdominal musculature is very flabby, with a
tendency to _visceroptosis_ and _low blood pressure_. In their instance,
a _Vichy bath_, inasmuch as it tends to _raise_ the blood pressure, is
preferable to Aix massage.

Another powerful method at our disposal for the elimination of waste
products is the _vapour_ bath. It is not suitable for the old and feeble,
or those with advanced _cardiac_ or _renal_ disease, but it is especially
adapted to gouty subjects with _harsh_, _thickened_ or _irritable_ skin,
and those of _obese_ habit.

While the foregoing procedures, generally speaking, are eligible for the
more robust type of individual, we must have regard also to those of
delicate constitution, whose strength is sapped by long-continued gout,
or who show signs of pre-senilism. In such instances, _sub-thermal_ baths
(82° to 97° F.) have a great sphere of usefulness. Thus in the presence
of _high arterial pressure_, a course of immersion baths, say, at 93° F.,
combined with fan douches, and applied according to the Bourbon-Lancy
method, are very effectual in reducing arterial tension. Of marked
_sedative_ action, such neutral baths are peculiarly eligible also for
all types of gout associated with _insomnia_, irritable skin affections,
or showing signs of vasomotor instability.

Moreover, these sub-thermal baths are valuable in articular gout of
subacute or lingering character if the douches used are of low pressure,
which latter is essential if the joints are sensitive. Their therapeutic
action is of course more pronounced in those _natural mineral waters_
which more nearly fulfil the requirements of a neutral bath. Such
are possessed in high degree by the waters of Buxton, Ragatz, and
Baden-Weiler, the average temperature of which approximates to the point
of thermal indifference.


METHODS OF LOCAL HYDRO-THERAPY

In one form or another, _douches_ have for centuries been used for
chronic joint affections. Three factors have to be considered—the volume,
pressure, and temperature of the impinging water. The size and form of
the stream determine its thermic and mechanical effect, and _cæteris
paribus_, the more massive the volume, the more marked the results
produced.

The pressure, again, is a most important factor, as the influence on
the circulatory and lymph flow in deep-seated tissues is directly
proportional to the force of delivery.

We see, therefore, that in douches we have a weapon of great power for
good or ill, and the results achieved will be exactly proportional to the
judgment displayed in meeting individual requirements in the matter of
their temperature, duration, and pressure.

The space at our disposal forbids entering into great detail, and a few
general principles are all that can be enunciated. Thus, while extreme
pressures are permissible in selected cases, they are contra-indicated
when dealing with regions the seat of pain. In such instances we should
always begin with mild measures, viz., a tepid fan or spray douche (80°
to 92° F.) of low (4 to 8 pounds) pressure. These later may be replaced
by a hot (104° to 110° F.) broken jet, or rain douche, of 10 to 15 pounds
pressure, and by such graduated procedures pain will often be relieved.

For the relief of _stiffness_ and _swelling_ alternating jets or sprays
are most suitable, the hot and cold douches being each of fifteen to
thirty seconds duration. The more remote the extremes of temperature, and
the more abrupt the transition from hot to cold, the greater the excitant
effect.

Simultaneous massage greatly reinforces the stimulating and absorbing
action of douches, which latter also may in various ways be
advantageously combined with other local procedures, viz., local vapour,
hot air, and electric light baths.


TREATMENT BY HYPERÆMIA

Enhanced oxidation and destruction of nitrogen-containing waste and
toxins being one of the primary indications in the treatment of all
so-called auto-toxic states, it is not surprising that hot air baths—both
_luminous_ and _non-luminous_ types—are so extensively employed in gout,
either for their curative or prophylactic action.

For the practical details of their administration I must refer the reader
to special works on the subject, contenting myself with a brief reference
to their therapeutic indications. While all gouty subjects at some period
of their life-history may be eligible for hot air baths, their use is
contra-indicated in _pyrexia_. Nor are they appropriate if the case is
complicated by any irritable _skin condition_, or in the graver forms of
_glycosuria_. They are unsuitable, too, if there are any evidences of
_hyper-thyroidism_, from which the gouty, no more than others, are immune.

Again, in _cardiac dilatation_ they must be exhibited with great caution,
and where extreme, are of course impermissible, as also in the later
stages of _chronic nephritis_. On the other hand, they are eminently
suitable for the treatment of _fibrositis_ in gouty persons, especially
of obese type, nor does the presence of _glycosuria_ in such association
constitute a bar to their use.

Moreover, as a _prophylactic_ measure, they are extremely well adapted to
those victims of gout who lead sedentary lives, as to a limited extent
they counteract the evil effects of muscular inactivity. Here also, by
the judicious use of graduated after-applications of cold or hypothermal
grade, the undue sensitiveness of the skin in these subjects is reduced,
and their liability to so-called “liver chills” diminished.

In conclusion, it is the proper blending of their eliminative and
prophylactic qualities, according to individual needs, that constitutes
the key to rational treatment by hyperæmia. These same postulates are
applicable also to the various peat, mud, and fango baths, whose action
in essence depends on the varying degree of hyperæmia they produce, and
to which, in all probability, their well-established efficacy in gouty
affections is attributable. That there are other valuable accessory
methods of treatment—electrical, hydro-electric, etc.—in vogue at spas,
I am perfectly aware, but the number of special works available for
reference on this point relieves me of the necessity of alluding to them
in detail.




CHAPTER XXXII

MINERAL SPRINGS AND CHOICE OF SPA


MINERAL SPRINGS

Though many have tried, no one has yet been able to define exactly what
does and what does not constitute a “mineral water.” Criterion after
criterion has been suggested—chemical, therapeutic, thermic, cryoscopic,
ionic, etc.—but to all there seem objections, and doubtless will be,
pending the advent of more exact knowledge regarding these—the most
complex pharmacological compounds in our Materia Medica.

Naturally, “mineral waters” being so refractory of _definition_, it
follows that all suggested _classifications_ are equally perplexing. In
fact, all attempts to reduce them to order according to their generic and
specific differences are, it must be admitted, unsatisfactory. Perhaps
the most serviceable differentiation at our disposal at present is one
based on their _chemical_ composition. As Sir Hermann Weber says, “a
statement of the salts contained in a mineral water often tells the
ordinary medical man something of the nature and probable effects of the
water in question, whilst the results of an analysis expressed in ‘ions’
would simply bewilder him.”

“Probable effects,” says Weber, and, I think, advisedly; for in
estimating the effects of spa treatment how difficult to discriminate
between what is due to “mineral waters” and what is due to change of air,
diet, mode of life, and mental occupation. Yet, again, how bewildering
the fact that “waters” of the most varying chemical content prove to be
equally beneficial in gout. Small wonder, then, that physicians sought to
refer their therapeutic efficacy not to their mineral constituents, but
to the vehicle common to all of them, viz., to the diluent and solvent
action of the _water_ itself, its flushing effects in washing out urates
and other toxic substances.

From this it was but a short step to the further assumption that, other
things being equal, the drinking of water at home would do just as well
as resorting to a mineral spring. But, as has been shrewdly said, the
“other things” never are “equal.” What of the daily worries left behind,
the change of air and scene, the modifications of diet, the leisure for
outdoor exercise, not to mention hydro-therapy and other integral or
collateral factors of spa treatment?

But, even frankly admitting our ignorance, the lessons of experience,
nevertheless, can neither be flouted nor ignored, least of all in the
treatment of gout. “Mineral waters” are but used _empirically_, says
the critic, forgetful that the use of _colchicum_ lies open to the same
aspersion. Especially valid the imputation, as he thought, in regard to
the so-called “simple” or “indifferent” thermal waters. These—despite the
testimony of centuries to their worth—must be discarded in favour of some
pseudo-rational method, and this, forsooth, because their mode of action
seems inexplicable! Yet, by the irony of Fate, within a brief span these
“indifferent” waters were found to contain a substance—“radium”—whose
powers few, at present, pretend to gauge or limit. There seems, in truth,
a peculiar fitness in the coincidence that it should be in this very
group that experimental investigations have proved so fruitful.

Is it not, moreover, a striking fact that the waters of nearly all the
natural springs which for centuries have been used in the treatment
of gout are thus dowered, and those which are most lowly mineralised
seem to possess the greatest degree of radio-activity?[63] It was to
their possession in varying measure of this common property that the
therapeutic efficacy of waters so widely different in their chemical
content was presumably in large part attributable, viz., to their
_radio-activity_.

For alike in simple thermal, sulphurous, alkaline, sulphated alkaline,
or muriated waters, the presence of radio-activity has been established.
But if, _e.g._, in the _simple thermal_, their therapeutic potency is
referable to their higher degree of radio-activity and not to their
mineral content, in others their relative deficiency in radio-activity
is compensated for by their _mineral_ constituents—these present in
sufficient quantity to exert a _specific_ action, alterative, aperient,
tonic, etc.

In this matter of _mineral_ content we are reminded of the grievous
controversy that has long obtained with regard to the use of natural
waters, the chief constituents of which are _sodium_ salts. Sir William
Roberts, as we know, from his experiments, ascertained that sodium
salts promoted the conversion of the quadriate into the biurate, thus
augmenting the precipitation of the latter.

This behaviour on the part of the carbonates, bicarbonates, and
phosphates of sodium led him to the sweeping generalisation that all
sodium salts, including the chloride, were, as far as practicable, to be
avoided by _gouty_ subjects. Naturally, in conformity with this view,
such patients were warned to flee those spas whose waters contained these
peccant salts.

Carried to its logical end, this dictum would have cut the gouty off
from, _e.g._, the carbonate of soda waters of Vichy, the chloride of
sodium springs of Homburg, the sulphate of soda waters of Karlsbad, not
to mention the muriated (sodium chloride-containing) sulphur waters of
Harrogate, Llandrindod, etc., despite the overwhelming clinical evidence
as to their efficacy in certain cases of gout.

Fortunately, as Burney Yeo observed, “in spite of all the theoretical
denunciations of the use of sodium salts in gout, the gouty, from all
quarters of the globe, have resorted, and continue to resort, in steadily
increasing numbers, to those Continental springs in which the salts of
sodium are overwhelmingly predominant.”

In short, Sir William Roberts’s experiments, while they dissipated the
fallacious view of the action of alkalies as solvents in the blood of
sodium biurate, have not for one moment imperilled the clinical and
practical estimate, deep-rooted in experience, of their general utility
in gout.

For myself, I incline to the view of the French authors, who would refer
the value of alkalies and alkaline mineral waters in gout rather to
their general influence on metabolism than to the now no longer tenable
conception of their solvent action on _uric acid_.

Reflecting on the varied constituents of mineral springs and the claim
that each and all of them are of value in gout, one naturally looks for
certain conditions common to them all. These are, as Burney Yeo rightly
says,—

    (1) The quantity of water, more or less pure, taken into the
    body under regulated conditions daily.

    (2) The altered mode of life, the regular exercise in the
    open air, the modified diet, the early hours, the absence of
    business cares.

    (3) In many foreign spas there is the drier and hotter
    Continental climate.

    (4) The stimulating effect to excretion and “tissue change”
    which the baths, douches, frictions, and manipulations applied
    at most of them induce.

Now, admitting, as one freely does, the important influence exerted by
these factors on what may be termed the pathological groundwork of gout,
still it is equally certain that some cases of gout do better than others
at certain spas.

This leads me on to the further reflection that the favourable or
unfavourable reaction in different cases depends on the varying nature of
what I may term the “excitants” of gout. For the deviations from health
that evoke the disorder are manifold and diverse, each carrying with it
its own therapeutic indications. Something more is needed than what may
be termed a blind or unintelligent “washing out” process. In every gouty
patient there is some functional flaw or defect, and _cæteris paribus_,
that natural spring will suit him best whose mineral or other content is
best calculated to correct or minimise his particular deficiency.

In short, we must get rid of our too common habit of asserting that this
or that particular water is “indicated in all cases of gout,” and its use
“attended with the most remarkable results.” The question that we should
be more anxious to decide is, whether of _all natural springs_ this or
that particular mineral water is _par excellence_ the one that will most
surely and most swiftly correct or minimise that particular functional
derangement which in the subject under review experience has shown to be
the most fertile source of gouty outbreaks. But to this we shall refer
later when dealing with the _individual peculiarities_ upon which our
_selection of a spa_ will depend.

To sum up, in consonance with these views, the general principles of spa
treatment, as I take it, are:—

    (1) To correct or relieve those functional derangements,
    gastro-intestinal or other, that appear to be the determining
    causes or excitants of outbreaks of regular gout.

    (2) To reduce the toxicity of the blood plasma and tissues by
    promoting the elimination of uric acid and toxins through all
    avenues of excretion.

    (3) To restore the organism as far as possible to a state
    of health or functional efficiency, and therewith to adopt
    such prophylactic measures as shall diminish the liability to
    recurrence of the disorder.

To discuss the application of these principles to all types of mineral
waters is beyond the compass of this work, and I shall perforce have
to confine myself very largely to discussion of the salient properties
of _radio-active_ waters, with subsequently such brief allusions to
the salient therapeutic indications of other varieties as may be
indispensable to intelligent selection of a spa in any individual case.


RADIO-ACTIVE WATERS

As to the physical properties of _radium_, it is, according to the
theory of transformation, a “changing element,” emitting alpha, beta,
and gamma rays, and in addition a radio-active emanation. This latter
product exists in a gaseous form, and is the outcome of the ceaseless
metamorphosis taking place in radium itself, each atom of which
continuously ejects at high velocity an atom of helium.

This expulsion of helium having ensued, the parent atom no longer exists
as radium, but as _radium emanation_, or _niton_, as it has more recently
been designated. Now, from a therapeutic point of view, the salient fact
is that elicited by Lowenthal, viz., that the active agent is not, as
was previously thought, radium itself, but the _emanation_ derived from
it.[64]

Now, as a reference to our footnote shows, the Bath waters are
radio-active to a remarkable degree, and as Maché, Curie, and Laborde
hold that “the higher the emanation from a given spring, the more
striking are the physiological results,” a brief reference thereto seems
called for.

_Physiological Action of Radium Emanation._—When inhaled, radium
emanation swiftly passes from the alveolar spaces of the lungs into the
blood, and thence to the tissue cells, which, according to their specific
solubility, absorb the same. Eventually, if the inhalation is prolonged
sufficiently, saturation of the blood therewith ensues, to be followed by
its escape _viâ_ the lungs, intestines, kidneys, and skin.

Taken orally, radium emanation, according to Lazarus, in large amount,
passes into the arterial blood, an observation confirmed by other
investigators experimenting on animals. Its absorption into the blood
takes place slowly from the intestines, and its exit thence out of the
system is, in like fashion, only slowly effected, taking _hours_ for
complete excretion. On the other hand, when _inhaled_ the emanation is
quickly absorbed and as swiftly excreted, _i.e._, within a few _seconds_.
As to its power of penetrating the _skin_ most authorities are sceptical,
but Engelmann stoutly contends that he has proved that in immersion baths
the emanation does actually pass through the skin; but pending further
researches this question of cutaneous absorption must remain _sub judice_.

Again, radium emanation appears to be endowed with the power of
energising or activating the body ferments or enzymes, in other words,
can stimulate to greater efficiency the _proteolytic_, _glycolytic_,
and _diastatic ferments_ that set in motion that long chain of
cleavage processes in the various foodstuffs, the necessary prelude to
their absorption, assimilation, and ultimate transmutation into live
protoplasm. Nay more, for the same mysterious agent, it is claimed, can
activate those oxidising enzymes which initiate the equally intricate
disruptive processes that mark the disintegration of living protoplasm.

Thus Neuberg, Lowenthal, Edelstein, and others contend that they
have demonstrated such an increase of efficiency on the part of the
autolytic enzymes responsible for cleavage of the protein molecule into
nitrogenous bases and amido-bodies. That radium emanation should exert
such a profound effect on organic metabolism, both in its anabolic and
katabolic phases, would, if established, go far to dissipate the dark
shadow of empiricism that has for so long clouded the practice of mineral
water drinking and bathing. For it is precisely in those conditions
collectively termed “disorders of nutrition” that radio-active waters
have found their traditional _rôle_.


INFLUENCE ON URIC ACID METABOLISM

In 1909 Gudzent, working in His’s clinic at Berlin, affirmed that in
gouty subjects uric acid vanishes from the blood in the presence of
radium emanation; moreover, that under the same conditions tophi had been
observed to melt away. The explanation proffered by Gudzent was, that the
emanation inhibited the transmutation of the unstable and more soluble
_lactam_ into relatively insoluble and stable _lactim_ urate, this latter
being the salt found in the blood of the gouty.

W. His also claims that the gouty individual benefits by this method of
treatment, which, he maintains, not only reduces the uric acid content of
the blood, but dissipates uratic deposits in the tissues. On the other
hand, at the last Congress of Internists at Wiesbaden (1912) Gudzent
and His’s views, though stoutly supported by some, were unacceptable to
others, who, although they admitted the favourable influence of radium
emanation upon the symptoms of gout, yet contended that its effects could
with difficulty be interpreted either in the sense of increasing the
solubility of the monourate of sodium or its decomposition into CO₂ and
ammonia.

Thus E. V. Knaffl-Lenz and Wiechowski, working in the Vienna
Pharmacological Institute, were unable to confirm Gudzent and His’s claim
that treatment by radium emanations resulted in destruction or increase
in solubility of the mono-sodium urate. On the other hand, in view of
the admittedly favourable effect of the emanation on gout, they suggest
that it might be due to what they term activation of an uric acid oxidase
existing in the human tissues. Yet another view is that in some obscure
way radium emanation facilitates the elimination of uric acid through the
kidneys.

In regard to the claim that radium emanation has the power of keeping
uric acid compounds in their more easily soluble forms, it is interesting
to recall the conclusion arrived at by the _Lancet’s_ special commission
for investigation of the Bath waters: “The thermal waters of Bath exert a
distinct solvent action on uric acid; in our experiments, _e.g._, it was
shown that Bath waters dissolved over five times the amount of uric acid
that distilled water would similarly take up at blood heat—_i.e._, just
under 100° F. Since the waters are drunk hot and used hot for bathing
purposes, this fact may have an important relation to the therapeutics of
Bath waters in the treatment of chronic gouty affections and rheumatism.”

_Increased Excretion of Uric Acid._—Delayed excretion of exogenous
purin is held to be one of the most characteristic signs of gout. Now,
following emanation treatment, Lowenthal and others have noted that this
disability on the part of the gouty was apparently removed. For when, at
the close of the course, the capacity for dealing with exogenous purins
was tested by the intake of large amounts of purin bodies, excretion of
the same ensued after a normal fashion. It would seem then that there is
not only increased uric acid excretion actually during the progress of a
_séance_ of emanation, but also that this enhanced power of coping with
purins is maintained subsequently.

_Subjective Phenomena of Gout in Relation to Blood Content and Excretion
of Uric Acid._—Now, as we have seen, it is claimed that uric acid
disappears from the blood in the presence of emanation. But, while in the
majority of instances amelioration of symptoms follows reduction of the
uric acid blood content, in others improvement ensues even though the
amount of uric acid in the blood remains unaltered.

Thus in one of His’s patients under radium emanation striking amendment
followed notwithstanding that the blood contained uric acid. In another,
the subject of multiple tophi, no uric acid was found in the blood
throughout the treatment, and yet the victim had repeated attacks of gout
during this period.

Turning to the _excretion of uric acid in the urine_, similar
discrepancies emerge. Thus Mandel out of seven gouty patients under
treatment by radium emanation found that an increased uric acid excretion
ensued in two subjects. Of the remainder, in two no alteration in average
excretion took place, in two a slight diminution, and in one a marked
increase, to the extent of 50 per cent.

Now in four of the seven cases an undoubted clinical and subjective
improvement was observed, although the uric acid curve showed diminution
rather than increase. It seems, therefore, clear that the _beneficial
effect of radio-active waters in gout_ involves something more than
the _dissipation of the uric acid in the blood_ and _its increased
elimination in the urine_.


THERAPEUTIC ACTION AND APPLICATION

We have in previous sections emphasised the importance of treating _local
foci of infection_, in view of their possible causal relationship to
gout. For, uncertain as we are of the etiology of the disorder, we cannot
afford to neglect treatment of any possible source of toxic absorption.

Now a significant number of independent workers contend that in the
presence of radium emanation the growth of organisms is retarded, if not
actually inhibited. The same bactericidal power has been claimed for
radio-active waters even of low grade. Should recent contentions as to
the efficacy of the same in states of _oral sepsis_ be confirmed, it will
constitute an important weapon wherewith to combat not only the local,
but the remote malign, effects of sepsis in the mouth or its accessory
cavities.

Again, it is recognised that _pharyngeal_ and _nasal_ affections when
present derive benefit from the _inhalation_ of _radio-active waters_
atomised by steam or air. In this connection it may be noted that, by
an ingenious apparatus installed at Bath, the natural “niton” gas is now
extensively used for inhalation or douching of the mouth and neighbouring
cavities.

_Alimentary Disorders._—Accepting the fact that _gastro-intestinal
derangements_ are the most common _excitants_ of gouty outbreaks, it
seems to me highly probable that the good effects of radio-active waters
are partly attributable to their mysterious power of _activating the
body ferments_. Thus, through their stimulating action on the digestive
enzymes, they may inhibit the formation of abnormal substances, or,
through their quickening of the autolytic ferments, may hasten the
disruption and excretion of such when formed.

How frequently in these cases do we find that some functional hepatic or
gastro-intestinal derangement is the prelude to a gouty outbreak. Again,
as pointed out, how often do these subjects suffer with fermentative
dyspepsia and “organic acidity,” with associated lowered tolerance
for carbohydrates. In such cases, if given in copious quantity and
frequently, the radio-active waters prove most beneficial. This is in
part attributable to the mechanical flushing of the alimentary canal
and tissues, and in part perhaps to their activating influence on the
digestive enzymes.

In contrast to the foregoing, such abundant ingestion of the waters
is inadvisable in atonic types of dyspepsia marked by dilatation and
diminished secretion. But here again, if given in small amounts,
radio-active waters undoubtedly exercise a beneficial effect. Also in
those gouty subjects who suffer from neurasthenia and nervous dyspepsia a
similar favourable reaction is frequently observed. This I apprehend to
be due to the fact that radium emanation exerts a _sedative_ effect on
the nervous system. Thus it has been noted that guinea-pigs when exposed
to radium emanation drop into a state of somnolence and torpor. May not
this account for the undoubted fact that highly strung individuals when
subjected to a combined bath, drinking, and inhalation cure become less
irritable and lose their distressing tendency to insomnia?

Again, _intestinal irrigation_ with these radio-active waters after
the Plombières technique is justly esteemed in those cases of gout
attributable to intestinal catarrhs and mucous colitis. The constipation
these subjects so frequently suffer from is counteracted, and the regular
removal of waste and toxic material achieved.

As to the morbid affections associated with gout, notably fibrositis, it
is well recognised that muscular and nerve types of this disorder prove
very amenable to a course of these waters. Here I would lay stress, too,
on the swiftness with which the _glycosuria_ of gouty subjects vanishes
under the same conditions. The pruriginous and eczematous eruptions met
with are also favourably influenced by a combination of internal and
external treatment. I may note, too, that this mode of therapy is not
contra-indicated in _increased arterial blood pressure_. For it has been
shown by Deutelmoser, Saubermann, and others that under the influence of
radium emanations the blood pressure is reduced.

As regards the administration of radio-active waters, it cannot be
doubted that the combined bath, drinking, and inhalation cure is the most
advantageous. The subcutaneous injection of radio-active waters does not
seem to possess any outstanding advantages, while the danger of sepsis
has always to be considered.

As to the relative merits of artificial as opposed to natural
radio-active waters, it does not appear to me that the therapeutic
action of the former is swifter or more infallible than the products
that issue from nature’s laboratory. The limitations and capacities of
the latter have been fixed by centuries of experience, and, as far as
present researches go, the newly born commercial imitation, at any rate
as regards the treatment of gout, has yet to prove itself endowed with a
greater range of therapeutic efficacy.


CHOICE OF SPA

While naturally my attention has been largely centred upon the mineral
waters of Bath, I would by no means convey the impression that a _thermal
radio-active_ spring is the only one that I think beneficial in the
treatment of gout. Far from it, for if, from my description, I appear to
have claimed such to be universally applicable to all gouty subjects, the
explanation really resides in the fact that the resources of most spas
can be readily adapted so as to suit different kinds of cases.

Nevertheless, as I have said, I favour the tendency towards
_specialisation of spas_, as bit by bit the indications for their
differential application become more and more sharply defined. In view,
then, of this trend, it is manifestly only fair to our patients that we
endeavour to select that particular spa that seems most eligible in their
particular instance.

Let us assume, then, that the subject is in such circumstances that a
certain latitude of choice is permissible. This being so, the physician’s
selection will be the more satisfactory if regard is had not only to the
gout, but to the _individual_ himself, and not the least important of
the considerations involved have been already embodied in my remarks on
_climato-therapy_. For the ideal sought, if I may again say so, is not
only _physical_, but _psycho-physical_; and the physician who leaves out
the mental element will scarcely choose wisely.

Narrowing our field to consideration of the _physical_ requirements of
the subject under review, what manner of man is he, _metabolically_
speaking? Is he of _spare_ habit, one in whom katabolic changes hold sway
and “the vital fires blaze more fiercely,” or is he _obese_, one in whom
anabolic processes are dominant, with hoarding up of substance?

Now, I have taken these two types, the _spare_ and the _obese_, as in
gout we are dealing primarily with a “disorder of nutrition.” _Cæteris
paribus_, we wish to correct the morbid metabolic trend, in other words
provide differential treatment. Obviously the salient indication in the
_lean_ individual is that he shall drink of a spring which will tend to
enhance digestive capacity and facilitate assimilation of foodstuffs,
with as its outcome increase of general nutrition.

To compass such effects, _muriated_ chloride or common salt waters are,
other things being equal, most desirable; that is to say, unless they
are taken in such quantities as to produce catarrh of the stomach and
intestines, they _do not cause emaciation_. On the contrary, I have,
for example at Llandrindod, seen an increase of weight in these persons
ensue during, and, moreover, continue after, a suitably arranged course
of these waters. Among other muriated waters in this country may be
mentioned Llangammarch Wells, which, as Sir Hermann Weber suggested, is
suitable in cases of chronic gout, “especially where any emaciation is to
be avoided,” and Woodhall Spa also deserves mention in this connection,
or, reverting to the Continent, the waters of Homburg, Kissingen,
Wiesbaden, Baden-Baden, etc., may be selected.

The _muriated_ (chloride-containing) _alkaline_ waters are also eligible
in cases where loss of flesh is to be avoided, such as Ems, Royat,
Chatel Guyon, or La Bourboule. They should, for this reason, be given
the preference over the _simple alkaline_ waters, such as Vichy, Vals,
Neuenahr.

Reverting now to the _obese_, plethoric type of man, a heavy eater and
often of sedentary habit, what is the end to be achieved? Here loss
of flesh is to be courted, and a spa sought whose mineral waters will
by their action supplement the all-important dietetic and regimenal
treatment of the subject.

The class of waters pre-eminently suitable will be those known as
the _sulphated_ and the _sulphated alkaline_ varieties, which, taken
internally, will through their purgative and diuretic effects assist our
purpose. The stronger varieties of the _sulphated_ waters are chiefly
used as occasional aperients at home, as, generally speaking, at the site
of the spring there is no proper spa accommodation. We allude to Franz
Joseph, Hunyadi Janos, Rubinat, and Condal waters, etc.

In England several _sulphated_ springs exist, but, as far as their use
is concerned, may be regarded as obsolete. Perhaps the best known is the
original spring, no longer used, at Epsom, whence the English term for
magnesium sulphate, “Epsom salts.” According to Weber, in Charles II.’s
reign these native laxative saline waters were taken at the wells early
in the morning, and Pepys in his diary tells how on August 11th, 1667, at
seven o’clock on a very cold morning, he found many people drinking the
waters at Barnet Wells.

It is, however, the _sulphated-alkaline_ springs that have achieved
the greatest reputation in this sphere, notably Karlsbad, Marienbad,
Franzensbad, Tarasp Schuls, etc., and perhaps of these Marienbad is the
most frequented. But in any case, in exercising a choice, we should take
into consideration not only the temperature and mineralisation of the
waters and their balneo-therapeutic resources, but also the climate and
the time of year. Thus, for example, the climate at Tarasp is alpine,
and the altitude of Marienbad is over 2,000 feet, while that of Karlsbad
is but 1,200. Another point to consider is whether the obesity of the
subject is attended with _anæmia_. If so we may with advantage choose
Tarasp, which, in addition to sulphated alkaline, has _chalybeate_
waters, and the same dual advantages are to be found at Marienbad.

For those unable to go abroad the _muriated sulphated_ waters of
Leamington or Cheltenham in this country are available. The flat
contour of these spas is very suitable for those cases in which obesity
is complicated by cardiac debility. I may note, too, that Bain and
Edgecombe, discussing the treatment of obesity at Harrogate, speak well
of the strong _muriated sulphur water_, substituted in anæmic cases by a
chalybeate water in conjunction with an aperient.

So much for the broader indications, _metabolically_ speaking, that
should guide us in our choice of a spa. And now to consider other special
conditions which in the gouty call for consideration, notably digestive
disorders.

_Dyspepsia and Chronic Gastro-intestinal Disorders._—In these conditions
it is especially imperative that we take a broad view, particularly
in respect of climate and altitude. Inland spas at moderate or high
altitudes are generally preferable. Doubtless the beneficial result
is in part due to the influence that change to a mountainous region,
with abundant open-air exercise, exerts on the nervous system. But the
same has its drawbacks in the “gouty dyspeptics,” for often, as I have
observed, they tend at first to overeat. As Weber rightly says: “The
feelings of ‘sinking’ and ‘lowness’ in the gouty and dyspeptic are
frequently mistaken by the patients themselves as indications for taking
food, stimulants, or tonic medicine.” In short, we must in their instance
institute immediately at the commencement of their course the requisite
dietetic innovations. Again, being in these more bracing localities
more disposed to take exercise, the adverse effect on digestion of
_over-fatigue_ must be guarded against.

Indeed, in the more aggravated types of so-called gouty dyspepsia there
is little doubt that sojourn in a _sanatorium_ may at first be advisable,
so that the patient’s digestive disabilities may be thoroughly studied by
the help of test meals, while dietetic treatment can be more readily and
surely supervised.

Passing to the question of _mineral waters_, there is no doubt that a
previous investigation of the _secretory_ and _motor_ functions of the
stomach would supply valuable indications as to the type of “waters” most
suitable. Incidentally, too, researches in this line might tend to clear
up the obscurity that enshrouds the mode of action of mineral waters in
cases of gouty and other forms of dyspepsia. For experimental findings
and clinical observations are here somewhat conflicting.

Thus it has generally been supposed that _simple alkaline_ mineral waters
promote the secretion of acid gastric juice. But Pawlow, experimenting on
dogs, found that alkaline sodium salts tended rather to _inhibit_ than
to stimulate gastric and pancreatic secretions. In order, therefore, to
reconcile his findings with the well-ascertained benefit that follows
their exhibition in gastric disorders, he suggests that they prevent the
too prolonged or excessive secretion that is so often a concomitant of
catarrhal conditions.

Adolf Bickel, again, has confirmed Pawlow’s conclusion that the simple
alkaline group of mineral waters depress rather than stimulate the
secretory activities of the gastric mucous membrane[65]; but Sir Hermann
Weber, discussing Bickel and Pawlow’s deductions, puts forward, as I
think, a more reasonable hypothesis than that advanced by the latter
authority.

Thus he suggests that “a possible explanation of the beneficial
effects of alkaline salts in many digestive disorders (gouty dyspepsia,
irritable hyperacidity, etc.), in tendency to ‘biliousness,’ and in
various so-called ‘gouty manifestations’ is that these salts when
taken up into the circulation exercise a favourable influence on the
metabolic processes generally, thereby improving the general health and
thus indirectly, apart from any special local action, helping to remove
conditions of dyspepsia, gouty bronchitis, etc.”

From his experiments Bickel came to the conclusion that in conditions of
_subacidity_ supervening on chronic gastric catarrh the most suitable are
_muriated_ waters, or _muriated alkaline_ waters, or simple _gaseous_
waters.

_Gastric Insufficiency, or Atonic Dyspepsia._—Now, as I have before
emphasised, this is the functional gastric disorder most commonly met
with in the gouty; the _hyperacidity_ is due to _excess of organic
acids_, and this, again, is the outcome of not excess, but _deficiency,
of HCL_. Now in cases of this nature with _subacidity_ of the gastric
juice numerous observers—Von Noorden, Dapper, Boas, and others—have
reported an increase in the secretion of hydrochloric acid following a
course of _muriated_ waters.

My own clinical experience of the _muriated_ waters of Llandrindod
abundantly confirms the results obtained by these authorities. The
enhanced digestive capacity of the patients is evidenced by relief of
epigastric pain and discomfort after meals and the decline of flatulent
distension. For, following the increased secretion of hydrochloric acid,
their intolerance of carbohydrates, due to subacidity, disappears,
and, fermentation no longer taking place, the over-distended walls of
the stomach gradually recover tone. It is customary for patients to
walk either during or after the consumption of water. But in decidedly
atonic conditions of the stomach with dilatation it is better, as
Ageron suggests, that such subjects lie down after drinking. Nor must
the beneficial effect of muriated waters on the associated constipation
be overlooked. The daily thorough evacuation of the intestinal canal
minimises or prevents toxic absorption, and at the same time depletes the
overloaded portal system.

The sources of blood contamination being removed, the general symptoms of
languor, drowsiness, and mental depression give place to a more cheerful
tone of mind. At the same time relaxation from business, an outdoor life,
and bracing air, with change of scene and society, doubtless contribute
to dissipate those feelings of supreme misery which are the bane of the
dyspeptic.

As to the foregoing remarks, I have but chosen Llandrindod as a type.
Thus some of the Harrogate waters are equally eligible for inclusion in
the _muriated_ as in the sulphurous group. Again, to these may be added
Builth Wells and Llangammarch Wells, the latter distinguished by its
content of chloride of barium, which is said to raise the blood pressure
and promote diuresis through its tonic action on the muscular coat of the
arteries. Woodhall Spa, too, calls for mention, the presence of iodides
and bromides in its muriated waters investing it, according to some,
with special alterative properties; lastly, the strong brine waters of
Droitwich, which find their special sphere in external application by
baths.

As to the Continental springs in this category, the most noteworthy are
Homburg, Kissingen, and Kreuznach, the last decidedly radio-active; while
of _thermal muriated_ waters Wiesbaden and Baden-Baden are the most
representative.

_Chronic Gastric Catarrh._—In this condition, not uncommon in the
gouty, and which Ewald aptly characterises as “the best fostered
and widest spread of this world’s ills,” a deficiency of gastric
secretion with impaired motility is constantly present. With this is
frequently correlated distension of the small intestine, due to abnormal
fermentative and putrefactive changes in the food.

Leaving aside the vexed question as to whether _muriated_ or saline
waters can be regarded as direct excitants of gastric secretion, it
cannot be doubted that the prolonged and systematic lavage of the
stomach, ridding it of viscid mucus and hastening the removal of retained
fermenting foodstuffs, must favour restoration of a healthy state of the
mucous membrane, and thus indirectly promote its secretory activities.
Again, inasmuch as the bulk of saline waters undergoes absorption in
the small intestine, the duodenal catarrh usually associated with
this condition is also markedly benefited by the removal of toxic
accumulations. Indeed, Niemeyer, discussing the therapeutic efficacy
of mineral waters in such states, goes so far as to remark that “the
results obtained are the most brilliant that have ever been attained
in medicine.” To achieve these salutary effects the “waters” must be
taken in amounts adequate to produce copious daily evacuation. For, if
insufficient to ensure this same, discomfort and distension ensue pending
the more tardy removal of the water by the kidneys.

Now, while in these cases the _muriated_ waters above alluded to are
suitable, the _muriated alkaline_ are equally eligible. Of these the
highest in repute are Royat, Chatel Guyon, and Saint Nectaire, and in
Germany Ems, Wildbad, Assmannshausen, and Wildungen.

Here a reservation in regard to Bickel’s researches, viz., it has been
found that in some cases of _chronic gastric catarrh_ in _robust_
subjects _simple alkaline_ springs, such as those of Vichy, Vals, and
Neuenahr, have, despite his experimental findings, proved actually
beneficial. On the other hand, these same waters have this cogent
objection, that long courses are apt to cause depression and emaciation,
and, moreover, may aggravate the gastric trouble. Worse still, these
_simple alkaline waters_ are more likely to produce an attack of _acute
gout_, whereas the _muriated alkaline_ varieties are free from these
objections.

_Hyperchlorhydria._—Bickel’s experiments led him to this further
conclusion, that in organic gastric disorders accompanied by _excess
of HCL_ the _simple alkaline_ and _sulphated alkaline_ group are to be
preferred to the _muriated_ waters.

Now, inasmuch as some authorities hold hyperchlorhydria as due to a
_chronic glandular gastritis_, it would seem that these should be given
a trial. Personally, I have no practical experience that I can draw
upon for substantiation or refutation as to the correctness of Bickel’s
assumption. Nor have I on this question been able to find any reference
in the literature or clinical findings emanating from these spas.

Much controversy, again, obtains in regard of the usage of _muriated_
waters in these cases. Formerly their employment was unreservedly
condemned, but more extended experience has modified this too dogmatic
attitude. Albeit, that the results obtained in hyperacidity (excess of
HCL) are uncertain is undeniable, and unfortunately it is impossible to
foretell whether or no any given case will derive benefit. The pronounced
nerve element in these cases, with probably other unknown factors, has
doubtless much to say to the conflicting clinical results.

But the experience of most of us will accord with that of Dapper and Von
Noorden, that _muriated_ waters, such as those of Homburg, Kissingen,
etc., often prove beneficial in cases of neurasthenia with hyperacidity.
On the other hand, it is equally true that some examples of apparently
the same nature derive no benefit, indeed are aggravated. But, according
to Von Noorden, such are in the minority.

Fortunately this secretion of an abnormally acid gastric juice is
relatively rare in the _gouty_. Being of the nature of a _secretory
neurosis_, it occurs most frequently in those of _neurotic_ or
_neurasthenic_ type. Now, holding the view that many cases of
neurasthenia are due primarily to toxic absorption, secondarily to
alimentary derangements, the beneficial effects observed are, I presume,
probably attributable in large part to the removal of toxic accumulations
through flushing. These deleterious substances not being absorbed in such
amounts as before, improvement in the general nerve tone ensues, in which
doubtless the secretory mechanisms of the digestive system participate.

But, as we have seen, these same _muriated_ waters prove most salutary
in precisely the opposite condition—_hypochlorhydria, or deficiency of
HCL_. That such a beneficial effect should ensue in diametrically opposed
states, viz., _hyper_- and _hypo_-acidity, gives point, I think, to the
contention that the action of _muriated_ waters on the digestive organs
must in great part be exerted not locally, but _indirectly_, that is,
secondarily to improvement of the general health and toning up of the
nervous system.

Indeed, the pronounced nerve element in these cases is probably the
explanation why, especially in instances palpably due to mental fatigue,
insomnia, etc., a course of baths or hydrotherapy at some simple thermal
spa, preferably those at certain altitudes, such as Buxton, Wielbad,
Gastein, Plombière, Ragatz, etc., often suffices without any internal
treatment.

_Functional Hepatic Disorders._—Fothergill held that some persons were
born with “congenitally incompetent livers,” an unwelcome legacy unduly
incident among those of gouty heritage. Now the intimate interdependence
of hepatic and gastro-intestinal disorders has long been recognised;
indeed, the swiftness with which retribution, in the shape of so-called
“biliousness,” overtakes those who fare not wisely, but too well, is
proverbial even among the laity.

Thus chronic hyperæmia of the liver, due to stasis in the portal area,
commonly ensues in those gouty subjects who eat and drink too much,
especially alcohol. The same Nemesis awaits those who lead too sedentary
a life, and in the train of chronic constipation develop such hepatic
congestion, with in some instances attacks of catarrhal jaundice.

As to treatment of these cases by mineral waters, a preference must
be given to _alkaline_, _sulphated alkaline_, or _muriated_ waters,
according to the special indications of individual cases. Thus suppose
the subject is stout and plethoric, and given perhaps to hæmorrhoids or
pruritis ani, then spas with _sulphated alkaline_ waters (Marienbad,
Karlsbad, etc.) may be recommended. But equally good results will follow
a course at home of _muriated_ waters, or _muriated sulphur_ waters, such
as Harrogate, Llanwyrtid, and Strathpeffer, etc.

Bearing in mind that functional hepatic disorders are in large part
secondary to gastro-intestinal derangements, it is probable that the
beneficial effect of the above types of waters on the liver is exerted
indirectly, though we must recollect that the salts of soda have a direct
stimulant action on the hepatic function.[66]

Given in adequate doses, they act as mild, unirritating laxatives,
the daily evacuations thus produced relieving hepatic congestion and
coincidently any tendency to portal engorgement. Through their dual
action of flushing the digestive canal and stimulating hepatic and
gastro-intestinal secretory activities, we find the explanation of the
decided benefit that follows their use in gastric catarrhs, especially of
alcoholic origin, also in catarrhal jaundice, incipient cirrhosis of the
liver, and so-called abdominal venosity.

As we know, Sir Lauder Brunton long since pointed out that the ingestion
of saline mineral waters tends to counteract any tendency to catarrh
of the biliary passages, the biliary secretion tending to become less
viscid; consequently the passage of gall-sand is promoted. Some, like
Hans Kehr, of Holberstadt, advise a course of saline waters _after_
operations for the removal of gall-stones; others advocate their
employment _before_ surgical intervention. It is obvious, however, that
their range of usefulness in this affection must be limited and is
largely to be attributed to their power of mitigating inflammatory or
catarrhal changes in the gall bladder and its related ducts.

_Intestinal Derangements._—Constipation is, as is well known, the _bête
noire_ of the gouty, and, while the basal indications of its therapy have
to be carefully ascertained in every individual, still much may be done
by a properly chosen and adequately supervised course of spa treatment.
This, of course, entails revision of the diet and habits, notably in
regard to exercise; in some of sedentary habit a mere change of air
to a more bracing climate, with its associated increase of exercise,
may suffice; in others of stout plethoric type a visit to one of the
sulphated alkaline spas will be of benefit; while in weaker subjects of
the lean kind muriated waters will be more suitable.

In many the habitual constipation is due to a catarrhal condition of
the intestine. Trautner, as we know, considers that gout originates in
a mucous colitis. In France the gaseous muriated waters of Chatel Guyon
are in great vogue for chronic catarrhal conditions of the intestines,
especially those associated with abdominal plethora and constipation.
Indeed, because of its success in these cases, it is sometimes called the
French Kissingen.

On the other hand, the Plombières Spa is the one that _par excellence_
devotes itself to the treatment of mucous colitis by a combination of
(1) intestinal douches, (2) sedative warm baths, and (3) “under-water”
douches directed against the abdomen. Treatment by the Plombières
method is now available at most English spas, and, while I can speak
highly of its benefits, I think perhaps there is sometimes a tendency to
resort to it after a routine fashion irrespective of the presence of any
special indications for its usage. The after-results in some cases are
not enviable, and recently a distinguished surgeon informed me that he
had met with instances in which ill-advised and prolonged usage of such
irrigation resulted in an atonic condition of the colon.


ASSOCIATED MORBID CONDITIONS

_Glycosuria._—The more chronic and benign forms met with in gout
frequently derive benefit from a course of mineral waters, though,
of course, revision of the diet and regimen in general are essential
concomitants thereof. Indeed, the high reputation achieved by certain
Continental spas—Karlsbad, Vichy, Neuenahr, etc.—in this disorder is in
large part due to the care and attention bestowed on these the basal
indications.

In the gouty obese, with a tendency to piles and abdominal plethora, the
_sulphated alkaline_ and _simple alkaline_ waters, such as Karlsbad,
Vichy, Neuenahr, Brides-les-Bains, etc., are suitable, and in this
country the _muriated sulphurous_ waters of Harrogate and Llandrindod.

In some of the gouty obese their bouts of glycosuria sometimes
alternate with attacks of uric acid gravel, and not infrequently there
is also present a slight degree of albuminuria. In these cases the
_earthy or calcareous_ waters enjoy a considerable reputation, notably
Contrexéville, and not a few with uric acid gravel and slight albuminuria
resort to Wildungen.

I have before alluded to the beneficial effects in glycosuria of Bath
waters, which, like Contrexéville and Wildungen, have an earthy or
calcareous content. For the less robust and lean type of glycosuric
Sir Hermann Weber recommends “simple thermal baths, such as can be
obtained at many resorts of moderate elevation (Gastein, Wildbad,
Buxton, Schlangenbad, and Ragatz).” As an alternative, he states that
“the internal use of muriated alkaline or simple alkaline waters (Vichy,
Neuenahr, Obersalzbrunn, Royat, La Bourboule), in association with
thermal baths or alone, may often be recommended.”

_Oxaluria._—This condition, like glycosuria, is often met with in the
gouty. It is of course often due to faulty diet, but in many instances
there is a strong nerve element in the case. In the former instance
dietetic restrictions are the basal indication. In these cases, if there
be constipation, a visit to the _muriated_ springs in this country
or to Kissingen, Homburg, etc., is advisable. Otherwise, _alkaline_
springs, _i.e._, Vichy, or _alkaline earthy_ springs, such as Vittel,
Contrexéville, or Martigny-les-Bains, may be given the preference. For
those instances in which the nerve element is predominant the character
of the mineral waters is quite subsidiary compared with the all-important
point of procuring the subject freedom from worry.

_Gouty Phlebitis._—It is believed that gaseous muriated waters, both
internally and in the form of baths, are useful in counteracting any
tendency to phlebitis. Obviously, if there be any symptom or sign of
existing phlebitis, any such procedure would be fraught with risk. Still
patients who have had phlebitis frequently resort to such spas, notably
Bagnoles-de-l’Orme, where the resident physicians have made a special
study of the constitutional tendencies to chronic phlebitis. The waters
are but weakly mineralised, and may be classed in the simple thermal
group (81°-84° F.).

_Respiratory Disorders._—While, as I have said, I deprecate any notion
of specific gouty types of bronchitis, asthma, etc., there is no doubt
that gouty subjects, like many others, are prone to bronchial affections,
and for such mineral water treatment at a favourable season of the year,
is equally beneficial. In gouty bronchitics of plethoric type, courses
of sulphated alkaline waters will often do much to relieve the symptoms.
Again, many sulphur, muriated alkaline, and muriated spas, have achieved
a great reputation in the same sphere, _e.g._, Ems, Royat, Eaux-Bonnes,
Baden-Baden, and Soden. Nor need we go outside our own country, for many
of our mountain health resorts are in the summer months equally eligible
for treatment of these disorders of the respiratory system.

_Fibrositis._—Adequately to describe all the methods, internal and
external, in vogue at spas for the treatment of, _e.g._, chronic lumbago
and sciatica, would be quite futile in the space at my command. I have
the less compunction in being unusually brief inasmuch as Bassett Jones
and I have dealt exhaustively with the subject in our work on fibrositis.

The groundwork of successful treatment will rest on the application of
the general principles in force for the treatment of the underlying gout.
They will, of course, include internal and external treatment by simple
thermal waters, the thermal muriated and thermal sulphurous waters, etc.
Frequently, too, cold muriated and other waters artificially heated are
invoked for this dual purpose.

The benefits of external treatment by douches of varying character will
depend on the measure of discrimination exercised in adapting their
application to suit the individual necessities of the case. But I would
here lodge a plea against the far too great frequency with which such
cases are sent to spas during the acute phases, whereas it is only the
subacute or chronic forms that are eligible for treatment by hydrotherapy.

_Gouty Eczema._—The climatic suitability of the spa is of primary
importance, and while, as a rule, cold, damp and windy localities are
to be avoided, still personal idiosyncrasy plays a large part in the
decision, some cases of eczema being aggravated by cold, others by heat
and sunlight.

The spa treatment of gouty eczema has for its aim the correction of the
constitutional taint by the internal exhibition of mineral waters in
conjunction with baths. To this end, the eliminative effects of courses
of alkaline (Vichy, Vals), muriated (Llandrindod), sulphurous (Harrogate,
Strathpeffer, Llanwyrtid), or muriated sulphurous waters (Uriage,
Aix-la-Chapelle, etc.), are often invoked with marked benefit.

Again, the thermal muriated alkaline waters of Royat and the arsenical
springs of La Bourboule have acquired a great reputation in gouty eczema,
and in obstinate but non-pruriginous types the prolonged tepid baths in
vogue at Loèche-les-Bains, in Switzerland.

In many instances of senile or atrophic type a course during the summer
of simple thermal baths is often beneficial. Buxton is suitable, also
Wildbad, Schlangenbad, Ragatz, etc. Lastly, in eczema of seborrhœic
type thermal sulphurous waters, _e.g._, Schinznach, Aix-les-Bains,
Bagnères-de-Luchon, etc., are highly commended.

_Uric Acid Gravel._—Though, as before stated, there is no specific
connection between this disorder and gout, still the gouty no more than
others are immune therefrom. For the stout, plethoric, and constipated,
sulphated and sulphated alkaline springs are indicated. But if, on the
other hand, there is a tendency to diarrhœa, these aperient waters must
be renounced in favour of simple alkaline springs. In those of less
robust type the simple thermal or earthy waters, notably Contrexéville
and Wildungen, are to be preferred, and failing these, the muriated
waters.

_Arterio-sclerosis._—It is hardly necessary to say that in all but the
slightest forms high altitudes are contra-indicated. In these less
advanced cases, if the subject be stout and plethoric, the sulphated
alkaline waters (Karlsbad, Marienbad, etc.) are useful; while in thin
persons the muriated waters are more suitable.

In more advanced cases we may during summer advocate a course of
treatment at some simple thermal spa, such as Buxton, and many of these
cases do well at Bath during the spring, or they may be sent to Bourbon
Lancy, which has been termed the French rival to Nauheim, because of the
excellent results obtained in cases of raised blood pressure.

_Chronic Nephritis._—Clearly in these cases a quiet life, without mental
worry, gentle and not excessive exercise, with residence in an equable
climate, are the primary indications. In the early stage, when the
patient’s condition is good, the tension not high, and the quantity of
albumen small, the subjects derive much benefit from an annual visit
to certain mineral springs. Not that mineral waters have any curative
influence; they merely help the interstitial circulation and promote
flushing.

Of mineral waters the _simple thermal_ or the _weak alkaline_ are
generally considered the most eligible, _e.g._, Vichy, which is useful
also in cases of combined albuminuria and glycosuria. In cases with
cardiac dilatation care should be taken not to prescribe mineral waters
in excessive amount. If complicated by anæmia, chalybeate waters,
according to Weber, are “not rarely useful.”

Bain and Edgecombe, discussing gouty albuminuria, state that the magnesia
water of Harrogate, in combination with the old sulphur, has a marked
effect in reducing the absolute amount of albumen in the urine, _e.g._,
from one-fourth by volume to a mere trace. They add, that if the specific
gravity of the urine be low chalybeate water is indicated with, if
necessary, a morning aperient draught. If glycosuria and albuminuria
co-exist, the “sulphur waters may be tried tentatively” as the specific
gravity does not help us in these cases. “When in doubt, it is safer to
give an iron water and trust to diet and baths for a diminution in the
excretion of these substances.” Not a few of these cases find their way
to Bath and Buxton, often for relief of their increased arterial tension,
and the experience of most is that in the more robust types a course of
Aix massage is advantageous, while for others more advanced in years
baths after the Bourbon Lancy method.


CONCLUDING REMARKS ON SPA TREATMENT

It is well that the potency and complexity of spa treatment be realised,
involving as it does not only drinking or internal treatment, but
also _balneotherapy_, _electro-therapy_, and all the other accessory
therapeutic methods now at command. With all these powerful weapons to
hand, it is obvious that their use demands a corresponding degree of
discrimination, this even in cases otherwise suitable, and here a word
as to the types of gout most suitable for the _internal_ exhibition of
mineral waters.

In this matter the rules laid down for hydrotherapy, or the _external_
use of waters, are in the main applicable. In other words, _acute cases
of gout are always ineligible_, as likewise those instances in which
an attack appears imminent or those in which recovery from an _acute_
paroxysm is barely accomplished. On the other hand, mineral waters are
indicated in _chronic_ gout and in the _inter-paroxysmal_ periods that
mark the _early_ stages of the disorder. Indeed, I know of no other
treatment that is as effectual, and, with Sir William Roberts, “I do not
think, therefore, that gouty patients, if they can afford the time and
expense, should forego the advantages of the time-honoured practice of a
visit to a mineral spring.”

But, to attain the best results of spa treatment, not only should the
cases be suitable, but they should be despatched at the right _season_.
Even in spas that are open all the year round we should try to select
the most congenial month. Thus, if the subject is intolerant of heat, we
should not advise him, say, to go to Bath in July or August, or, for that
matter, during the hottest summer months to Aix-les-Bains, Baden-Baden,
Wiesbaden, Neuenahr, etc. If he has to take his course at this period of
the year, and a thermal spring is indicated, Buxton will be more suitable
than Bath, and we have a large choice of other spas in more bracing
localities, such as Harrogate, Llandrindod, Strathpeffer. In short, some
discrimination must be exercised. Again, if a course be indicated in the
winter, we should favour those spas where the hotels are in proximity
to the springs, so as to obviate unnecessary exposure, _e.g._, Bath,
Wiesbaden, Helouan, etc.

As to _duration_ of a course, there is, I think, in many spas a too
great tendency to be dominated by tradition. Not only is the duration
of the cure arbitrarily fixed, but, still worse, the drinking of the
waters, the bathing, and even the dietaries are frequently in danger of
becoming stereotyped, with, as a consequence, a lack of that eclecticism
necessary in the best interests of individual cases. A certain amount
of routine is unavoidable, and has this advantage, that persons find it
easier to submit to irksome restrictions when they see others conforming
thereto. But even so there is ample scope for such modifications as may
be required, and upon their adoption the success of spa treatment mainly
depends.

If arbitrary rules in respect of drinking, bathing, etc., are to be
deprecated, the same applies with unvarying fixity to the duration of
a cure for all cases. Generally speaking, three to four weeks is the
average stay at spas. But obviously it should be varied to suit the
patient’s condition, and in many instances of chronic gout it may with
advantage be extended to six or eight weeks.

Again, I think perhaps in this country the advantages of an _after-cure_
are insufficiently realised. In this respect our Continental brethren
set us an example, attaching the greatest importance as they do to
an after-cure, especially after a course of laxative waters, _e.g._,
Karlsbad, Marienbad, and Kissingen. Certainly to plunge forthwith into
work immediately after a cure leads but too often to another breakdown
and the undoing of any advantages that may have been reaped. Of late I
have noted, especially in business men, a tendency to interrupt even
their course by travelling considerable distances on _non-bathing_ days
to attend to their affairs. The folly of this is obvious, and the results
are almost invariably unsatisfactory. Indeed, in these all too strenuous
days one almost despairs of _after-cures_, for it is difficult enough
oftentimes to prevail on people to stay even for their course of three
weeks, and frequently one is asked to conduct their treatment after a
more intensive fashion, and so abridge it to a fortnight or even a week!

As to the nature and site of the resorts suitable for an _after-cure_
it is impossible to lay down general rules, as individual peculiarities
have to be considered. But the physician who prescribes such ought, as
Sir Hermann Weber remarks, “to be acquainted with the nature of the
locality recommended, if possible by personal visits, and the reports of
thoroughly judicious people.” For, as he rightly says, there are numerous
places in the British Isles perfectly suitable for an after-cure, to
mention but a few in England, Ilkley, Ben Rhydding, Malvern, Haslemere,
Church Stretton, Crowborough; in Scotland, Braemar, Ballater, etc.; and
in Wales, Llanberis, Llangollen, etc.


SPAS FROM A NATIONAL ASPECT

But brief reflection on the foregoing considerations suffices to make it
clear that the various spas and health resorts with which this country,
through Nature’s beneficence, has been so bountifully endowed, are but
members one of another, in short _complementary_, not antagonistic, as
I fear is sometimes thought. This latter is a view to be discarded in
favour of a more rational conception of these various centres from their
collective aspect as integral parts of a therapeutic whole.

Now what, in a word, is the outstanding feature of our national life
to-day? _Co-operation_—a veritable furore of national and international
effort such as the world has never seen. Spas, too, must fall in line
with the national trend, must organise and co-operate, if they would
play their full _rôle_ in the drama of reconstruction. Now, from the
point of view of the State, the true objective in therapeutics is the
achievement and maintenance of national efficiency—the production of
healthy citizens, sound economic units. This then is the high purpose
with which those responsible for spas must ever be animated—an aim only
to be attained by their whole-hearted co-operation one with the other.

The lay custodians, too, of spas must increasingly realise that they
do but hold in trust their healing springs to be safeguarded in the
interests of the community. Mineral waters, like coal, issue from the
bowels of the earth. Both are _natural_ products; both are _national_
assets. I doubt not that the growing movement for effectual popular
control so rapidly obtaining a grip over the political and economic life
of the nation will shortly be extended to our spas, with, as its outcome,
their _unification_ and _co-ordination_ under the controlling influence
of a central body of experts vested with plenary powers to inspect,
control, and inspire the development of these hydrotherapeutic centres.
“Salus populi suprema est lex.”




FOOTNOTES


[1] Ewart, discussing the antiquity of gout, observes that it is
“certainly as ancient as civilisation,” and as far as we can identify
them in the accounts handed down from remote ages, the etiology, the
leading symptoms, the outward characters of the _articular_ gout of the
ancients were practically the same as belong to gout in our own times!
But of its relative prevalence in antiquity we have no means of judging.
Continuing, he holds that “the ultimate lesions of gouty arthritis and
its pathology are presumably as immutable as those of osteoarthritis.”
This may be so, but such objective evidence as we possess certainly
points to the greater antiquity of osteoarthritis as the following
quotation from our work, “Arthritis Deformans,” testifies:—

“During the course of some excavations undertaken by the Survey
Department of the Egyptian Government in that tract of Nubia lying
immediately south of the First Cataract, over 6,000 bodies were brought
to light, comprising among them representatives of all periods from
early pre-dynastic times down to the fifth century after Christ. As the
result of their examination of this vast accumulation of human _débris_,
Professor Elliot Smith, in the Nubian Survey Bulletin, states that “The
disease which shows itself with by far the greatest frequency in the
bodies of all periods is rheumatoid arthritis” (Osteoarthritis).

[2] 920 (S. Eng. Leg.), “There cam a goute In is knee, of Anguische
gret.... So longue, that is kneo to-swal.”

1310 (In Wright Lyric), “A goute me hath ygreythed so, Ant other eveles
monye mo.”

1377 (Langl., P. Pl.), “He ... gyued me in goutes, I may noughte go at
large.”

1400 (Lanfranc’s Cirurg.), “A man that hath arteticam, that is as myche
to seie as a goute.”

1450 (M.E. Med. Bk., Heinrich), “Here wyth anoynte the goutes.”

1566 (J. Alday, tr. Baoystuau’s Theat. World), “Their legges full of
gouts.”

1579 (Langham, Gard. Health, 1633), “For all goutes, seethe Leekes and
Otemeale with sheepes tallow, and apply them hot.”

1590 (Spenser, F. Q.), “And eke in foote and hand A grievous gout
tormented him full sore.”

1697 (Dryden, Virg. Georg.), “From Winter keep Well fodder’d in the
Stalls, they tender Sheep.... That free from Gouts thou mayst preserve
thy Care.”

1704 (Fuller, Med. Gymn.), “There have been some Gouts ... which nothing
could remove but a very low Diet.”

1732 (Pope, Ess. Man.), “So, when small humours gather to a gout The
Doctor fancies he has driv’n ’em out.”

1822 (Ld. Eldon, in Twiss Life), “I found the King in bed yesterday. He
has had a pretty severe gout.”—_New English Dictionary, Oxford_, 1901.
(_Ed. Sir James Murrary._)

[3] Pitt, in one of his last letters to the Marquess Wellesley, deplores
his slow recovery from severe attacks of gout with which, by the bye, the
statesman Fox was likewise affected.

[4] Both Norman Moore and Bowlby subsequently upheld Ord’s view that
uratic deposits only occur in tissues already degenerated. “Ebstein’s
view has been modified by Von Noorden, who holds that a special ferment
leads to the tissue change, to which the deposit of the urate is
secondary.”

[5] _Physiognomy of the Goutily Disposed._—Taking the principles as laid
down by Laycock, the peculiarities of those thus affected fall under the
head of the sanguine arthritic diathesis. (That careful observer did
not fail to note the modifying influences of gout upon struma and other
cachexia.) Thus may be compared the physiognomy of the diathesis and its
associated cachexia (developed in time):—

Blood-vessels numerous; heart large and powerful; blood-corpuscles
numerous; skin over malar bones highly vascular (florid complexion);
skin fair, firm, oleaginous, perspirable; eyes blue; hair thick, not
falling easily; teeth massive, well-enamelled, regular, even, undecayed
in advanced life; malar bones flattened; head symmetrical; nasal bones
well-formed, nose aquiline or of mixed form; lower jaw massive; lips
symmetrical.

_Form._—Figure for the most part tall; thorax broad at the summit; ribs
well-curved; abdomen full; muscles firm, large; limbs large, robust; gait
erect, well-poised. _Nutrition_ active; digestion vigorous; appetite
great for animal food and alcoholic stimuli. _Respiration_ deliberate,
deep; circulation vigorous; animal heat abundant; locomotion active;
aptitude for exercise and outdoor amusements. _Reproductive_ powers
active; innervation abundant, the mental powers vigorous and enduring.

_Physiognomy of the Sanguine Gouty Cachexia._—Blood-vessels largely
developed over the malar bones and varicose; skin oily, yellow from
subcutaneous deposit of fat; hair thick and white; teeth numerous,
discoloured, crusted with tartar; lips bluish, nose reddish,
hypertrophied; arcus senilis; abdomen pendulous; limbs thick; joints
nodose; nodosities on the ends of the fingers, lobes of ears, fascia of
muscles, and tendons; respiration hurried, wheezing; pulse intermittent,
irregular; stomach flatulent; digestion acid; urine loaded with lithates;
temper irritable; mind sometimes enfeebled.

The local diseases of the arthritic cachexia are principally seen
in adult males past the age of forty-five. They consist especially
in chronic inflammation of the muscular and articular tissues; in
calcification of the basilar and coronary arteries, and of the cardiac
valves. These changes give rise to hæmorrhagic apoplexy, angina pectoris,
cardiac hypertrophy and dilation; and to secondary pulmonary affections,
as emphysema, pulmonary apoplexy, and asthma. Irritation of the mucous
surfaces may give rise to nephritis, pharyngeal and laryngeal coughs, and
diarrhœa.—_Med. Observation and Research_, 2nd edition, pp. 96-98.

[6] According to Fischer the protein molecule can be split up into
amino-acids, di-amino-acids, aromatic-amino-acids, nitrogenous
derivatives of the benzene ring, pyrimidine bases, pyrrolidine
derivatives, cystin, and ammonia. During proteolysis the amino-acids
exist in groups, _e.g._, glycine and leucine (glycyl-leucine), two
leucine radicles (alanyl-leucine), etc.—which combinations Fischer
termed polypeptides, and some of which he has been able to produce
synthetically. Furthermore, Fischer proved that nitrogen equilibrium can
be maintained in animals by feeding them upon these polypeptide products
of proteolytic digestion which no longer gives the biuret reaction. The
derivation of amino-acids, etc., from peptone is the outcome of the
action of a special intestinal ferment—_erepsin_. This enzyme is found
not only in the alimentary tract, but in all tissues of the body, its
action being especially developed in the renal tissues.

[7] Glycocoll in solution dissociates more H-ions than OH-ions. In the
presence of alkalies this acid character is more marked, so that it tends
to throw the uric acid salts out of solution. The inhibitory influence of
the urea upon the precipitation of uric acid from solutions is due to its
basic nature.

[8] Recent researches by S. R. Benedict show that uric acid, in the blood
of most mammals, exists in combination, but not in that of the bird.
Fresh ox-blood (Folin method) contains only 0·30005 gram, free uric acid
per 100 grams of blood. But after boiling the protein-free blood filtrate
with hydrochloric acid the uric acid content was about ten times as high.
Moreover, this same augmented uric acid content was found to exist “in
whole blood that had been allowed to stand for some time, indicating
that the _uric acid compound_ can be split by means of an _enzyme_.” The
compound exists, not in the plasma, but in the _corpuscles_. MacLeod, to
whose work on bio-chemistry we are indebted, remarks that “It is of some
significance that after thus setting free the uric acid, there should be
about 50 per cent. more of it present in the blood of the ox than in that
of the bird, where most exists in a free state in the serum, although the
urine of the ox contains only the smallest trace of uric acid, and that
of the blood is loaded with it. Investigation of the condition of uric
acid in human blood is at present in progress.”

[9] According to Sir William Roberts, there are three compounds of uric
acid (H₂U)—the neutral urate, M₂U, in which the metal replaces all the
displaceable hydrogen, the biurate, MHU, in which half the displaceable
hydrogen is replaced by the metal, and the quadriurate H₂UMHU, in which
one-fourth of the displaceable hydrogen of two molecules is replaced by
the metal.

Hutchison and Tidy suggest “that if Roberts’ salt be considered as NaHU.
MH₂U instead of Na. HU, his hypothesis remains unaltered, whilst much
of the criticism urged against it is nullified. The possibility of such
a substance is shown by the existence of the compound LiHU₄HU. Roberts’
theory, or such a modification, is not inconsistent with Von Noorden’s
views if these intermediate salts be regarded as within the tabernacle of
organic combinations from which the kidneys can split off and excrete the
uric acid.”

[10] “If further investigations yield facts which sustain such an idea,
it may be more easy to comprehend the types of the demands which are made
upon the renal functions.... One of the next stages of research will be
the determination of the behaviour of renal tissue to the various purin
isomers. This may lead on to the identification of the types of nuclein
derivations and their precise cellular origin. Perhaps this in turn may
reveal whether there are any differences between the nucleotides of
normal and gouty tissues. To this end progress in the technics of the
cultivation of tissues _in vitro_ may furnish a means for the elucidation
of some of these questions.”—_Walker Hall._

[11] As a further illustration of the differences which may exist in the
purin metabolism in different kinds of animals, in man and the anthropoid
apes the quantity of purin bases in the urine is small in proportion
to the quantity of uric acid. In the pig, which is included among the
animals that form allantoin from uric acid, the purin bases exceed
the uric acid in amount, whereas in the dog, which likewise excretes
allantoin, the purin bases exist in very small amount compared with the
uric acid.—_Stewart’s_ “_Manual of Physiology_.”

[12] The findings of Soetbeer and Ibrahim also indicate that 50 per cent.
of the exogenous purin bodies undergo oxidation to uric acid, and 50 per
cent. undergo further disruption and are excreted as urea or intermediate
bodies.

[13] The subject of the experiments—a healthy male (M. S. D.), 22 years
of age and 58 kilos in weight—was placed for over six months upon a
meat-free low protein diet, free also from purin-containing beverages.
This with the exception of a few meals in the holidays, during which
a small amount of meat was taken. “No attempt was made to secure a
quantitative uniformity of the diet.” On the evening preceding the day
of an experiment a light supper was eaten, and no further food was
ingested until the completion of the day’s experiment, save the substance
whose influence on uric acid excretion was to be studied. The urine was
collected hourly, 200 c.c. of water being ingested hourly throughout the
experimental period.—“_Uric Add Metabolism_,” 11—_H. B. Lewis, M. S.
Dunn, and E. A. Doisy, “Journal of Biological Chemistry,” 1918._

Two other men also served as subjects. Many of the experiments were
duplicated, and similar results obtained with these other subjects, but
inasmuch as the experiments with M. S. D. were more comprehensive and
extended over a longer period of time, the data of these experiments
alone are presented.

[14] Quoting from the same article, _Journal of Biological Chemistry_,
1918, by Lewis, Dunn and Doisy, these authorities observe that—_re_
glycocoll and alanine, Lusk concluded that “the chemical stimulation
of protoplasm which is responsible for the phenomena of increased heat
production (specific dynamic action) results from the action of their
intermediary products, glycocollic and lactic acids, rather than from
the amino-acids themselves. The phenomena of the stimulation of uric
acid metabolism by amino-acids run parallel to those of the specific
dynamic action of the amino-acids (except in the case of the dicarboxylic
amino-acids), and it is possible that the same chemical factors are
responsible for both.”

[15]

    C₅H₄N₄O₃ + O + H₂O------>C₄H₆N₄O₃ + CO₂
    Uric acid.   Uricase.   Allantoin.

[16] Experimenting on a Dalmatian coach-hound, Gideon Wells was able to
confirm Benedict’s observation that it excretes large quantities of uric
acid. But inasmuch as the liver of this same dog was able to destroy uric
acid _in vitro_, the inference is that the presence of uric acid in the
urine of the Dalmatian is not attributable to the _absence of uricase in
its tissues_. “The kidney did not exhibit uricolytic activity. Neither
the liver nor spleen converted xanthine into uric acid, but the liver
deaminised both guanine and adenine.”—_Journal of Biological Chemistry_,
1918.

[17] Wells, in his “Chemical Pathology,” observes that the amount of uric
acid that appears in the urine depends upon a variety of factors which
may be summarised as follows:—

    (1) The amount of purin bodies taken in the food upon which
    chiefly depends the amount of exogenous uric acid.

    (2) The amount of destruction of tissue nucleo-proteins.

    (3) The amount of purin bases formed in the muscle tissue.

    (4) The amount of conversion of purin bases into the uric acid.

    (5) The amount of destruction of uric acid, if any, occurring
    in the body.

    (6) Possibly upon the capacity of the tissues to synthesize
    uric acid; and in case such power to synthesize uric acid
    exists upon the presence of the precursors of uric acid in the
    body.

    (7) The retention of uric acid in the blood and tissues.

    (8) The power of the kidney to excrete uric acid.

    (9) The solubility of uric acid in urine—dependent upon the
    amount of neutral phosphates present, the temperature, reaction
    and concentration thereof.

[18] EFFECT OF ATOPHAN ON EXOGENOUS PURINS. (McLester, in “Archives of
Internal Medicine.”)

  -----+--------------------------+--------+------------------------------
       |                          |        |    Twenty-four Hour Urine.
       |                          | Blood  +-------+-------+-------+------
  Date.|   R. E.                  |Mg. U in| Amt.  |       |  NH.  |
       |                          |100 Gm. | c.c.  |U. Gm. |Gm. N. |N. Gm.
  -----+--------------------------+--------+-------+-------+-------+------
  5/28 | ----                     |  2·9   | 1,150 | ·46   | ·58   |10·26
  5/29 |7 a.m.: 500 grams thymus. |        |       |       |       |
       |  2 p.m.: Blood           |  3·2   |   900 | ·66   | ·69   |10·96
  5/31 |7 a.m.: 500 grams thymus. |        |       |       |       |
       |  9 a.m.: Atophan, 2 p.m.:|        |       |       |       |
       |  Blood                   |  1·1   | 1,280 | ·75   | ·76   |11·16
  -----+--------------------------+--------+-------+-------+-------+------

[19] Walker Hall states that: “Taking the total volume of blood at three
and a half litres, and the volume passing through the lungs as four
and a half litres per minute, and through the kidneys as one litre per
minute, and the solubility of lactim-urate as 0·1 grm. per 4,000 c.c.
of blood, it would seem that the average daily output of 0·5 grm. could
be suspended in the quantity of blood passing through the lungs in five
minutes or through the kidneys in twenty minutes normal.”

[20] Criticising the colorimetric method on the ground that “different
workers obtain on the same blood samples results which vary
considerably,” L. J. Curtman and A. Lehrman have devised a new volumetric
method for the determination of uric acid in blood. The following is the
summary of their researches:—

(1) An experimental study of a number of metallic salts as precipitants
for uric acid in a solution alkaline with sodium carbonate was made. The
results showed that _nickel_ is the best of those tried.

(2) A 0·0004 N iodine solution was found suitable for the estimation of
small amounts of uric acid provided certain conditions are adhered to.

(3) Based upon the above considerations, a new method has been developed
for the determination of uric acid in blood, the chief features of which
are (_a_) the precipitation of the uric acid by means of nickel acetate
in a solution alkaline with sodium carbonate. (_b_) The estimation of the
uric acid in the precipitate by means of a dilute solution of iodine.

(4) The method was applied with good results to aqueous solutions of uric
acid as well as to blood serum to which known amounts of uric acid were
added.

(5) Low and inconsistent results were obtained when the method was
applied to sheep’s blood to which known amounts of uric acid were added.
This was shown to be due to the inadequacy of the procedure generally
employed, for the coagulation and preliminary treatment of the blood.
The colorimetric method when used in the analysis of samples of the same
blood also gave low and inconsistent results for the same reason.

(6) Comparison tests show that the volumetric method is fully as accurate
as the colorimetric method, and possesses the advantage of requiring no
special apparatus.

[21] URIC ACID ESTIMATION IN NORMAL INDIVIDUALS

(McLester, “Archives of Internal Medicine.”)

_Milligrams Uric Acid in 100 grams Blood._

  J. C.   0·5
  H. D.   0·6
  M. D.   0·6
  A. B.   0·8
  R. C.   0·9
  H. D.   0·9
  J. G.   0·0
  S. M.   1·1
  R. D.   1·3
  L. S.   1·4
  L. H.   1·7
  R. O.   2·1
  H. H.   2·5
  J. M.   2·5
  R. E.   2·9

URIC ACID OF BLOOD IN DISEASE. (McLester, “Archives of Internal
Medicine.”)

_Milligrams in 100 grams Blood._

  Mitral lesion                        0·5
  Rheumatic fever                      0·6
  Acute syphilis                       0·8
  Chronic tuberculous pleurisy         0·8
  Pneumonia                            1·2
  Pneumonia                            1·3
  Sciatica                             1·3
  Typhoid fever                        1·4
  Ulcer of stomach                     1·5
  Pneumonia                            1·6
  Amœbic dysentery                     1·6
  Neurasthenia (?)                     1·7
  Acute tuberculous pleurisy           1·7
  Chronic interstitial nephritis       1·8
  Malaria                              1·8
  Pneumonia                            1·9
  Uremia                               2·1
  Polycythemia                         2·2
  Graves’ disease                      2·5
  Pneumonia                            2·7
  Gout                                 3·3
  Arterial hypertension                3·3
  Intermittent gastric supersecretion  3·7
  Gout                                 4·5

[22] However, as Walker Hall reminds us, Taylor, writing in 1912,
stated, “That the margin of safety with regard to renal excretion is an
exceedingly narrow one, that the kidney excretes uric acid slowly, and
that its powers are soon overstepped.”

[23] Magnus Levy and McClure have also noted that the excretion of
exogenous purin is not invariably retarded or diminished.

[24] When experimentally injected, the urates are absorbed slowly by
phagocytic leucocytes and giant cells.—_Gideon Wells._

[25] Because the gouty tophi do not suppurate, even when ulcerated,
through the skin, it has been suggested that the urates have antiseptic
properties. Bendix (_Zeit. klin. Med._, 1902 (44), 165), however, could
not demonstrate such antiseptic properties experimentally.—_Gideon Wells._

[26] Levinthal, in a personal experiment, injected half a gram of xanthin
dissolved in piperazine into his cubital vein. A few days later, after a
moderate strain upon the limbs through dancing, he was suddenly seized
with a fairly acute painful attack in one of his knees, attended with
some swelling and local heat.

[27] “Tophi sometimes precede by some years ... the development
of gouty attacks in joints. The same is true also of auricular
tophi.”—_Duckworth_: “_A Treatise on Gout_.”

[28] “While, however, tophaceous concretions generally show themselves
after attacks of articular gout, cases occur, as I have already told you,
in which the secretion of calcareous matter takes place irrespective of
any arthritic attack. This sort of _cutaneous gravel_, if I may employ a
comparison based on the great analogy between the composition of urinary
gravel and tophaceous concretions, gravel of the skin, constitutes the
sole manifestation of the diathesis, and is accompanied merely by a
slight feeling of pain, of pricking unattended by any disturbance of the
general health.”—_Trousseau’s_ “_Clinical Medicine_.”

[29] _Redness_ of the skin overlying a developing tophus is not
invariable. In a case recently under my care, the dorsum of the
mid-phalangeal joints was the seat of small soft localised swellings.
The superjacent skin was unchanged in colour. Aspiration of the contents
by a hypodermic syringe disclosed the presence of a turbid white fluid,
which, when microscopically examined, was found loaded with the acicular
crystals of sodium biurate.

[30] “Quod in omnibus podagricorum paroxysmis solemne est, insignior
intumescentia venerum membro vexato intertextarum se in conspectu
dat.”—_Sydenham._

[31] Sydenham’s classical description: “Towards the end of January or
the beginning of February suddenly, and with scarcely any premonitory
feelings, the disease breaks out. Its only forerunner is indigestion
and crudity of the stomach, which troubles the patient for some weeks
previous to the attack. His body also feels swollen, heavy, and
windy—symptoms which increase from day to day until the fit breaks out.
But a few days before this torpor comes on, and a feeling of flatus along
the legs and thighs. Besides this, there is a spasmodic affection, whilst
the day before the fit the appetite is unnaturally hearty. The victim
goes to bed in good health and sleeps. About two o’clock in the morning
he is awakened by a severe pain, generally in the great toe, more rarely
in the heel, ankle, or instep. This pain is like that of a dislocation
of the bones of these parts, and is accompanied by a sensation as of
chilly water poured over the membranes of the suffering joint. Then
follow chills and shivers and a little fever. The pain, which was at
first moderate, becomes gradually more intense, and while it increases
the chills and shivers die out. Every hour that passes finds it greater,
until at length at night-time it reaches its worst intensity, and
insinuates itself with most exquisite cruelty among the numerous small
bones of the tarsus and metatarsus, in the ligaments of which it is
lurking. Now it is a violent stretching and tearing of the ligaments, now
it is gnawing pain, and now a pressure and tightening. So exquisite and
lively meanwhile is the feeling of the part affected that it cannot bear
the weight of the bedclothes nor the jar of a person walking in the room.
Hence the night is passed in torture and a restless rolling first to one
side, then to the other, of the suffering limb, with perpetual change of
posture, the tossing about of the body being as incessant as the pain of
the tortured joint, and being at its worst as the fit is coming on. Hence
the vain efforts by change of posture, both in the body and the limb
affected, to obtain an abatement of the pain.

“This comes only towards the second or third hour of the morning (a
whole day and night after the first outbreak of the fit), such time
being necessary for the moderate digestion and dispersion of the
peccant matter. The patient then has a sudden respite, which he falsely
attributes to the last change of position. A gentle perspiration is
succeeded by sleep. He wakes freer from pain and finds the part recently
swollen. Up to this time the only visible swelling has been that of
the veins of the affected joint. Next day (perhaps for the next two or
three days), if the generation of the gouty matter have been abundant,
the part affected is painful, getting worse towards evening and better
towards morning. A few days after the other foot swells, and suffers
the same pains. The pain in the latter regulates the state of the one
first attacked, for the more acutely it is tortured the more perfect
is the abatement of suffering and the return of strength in the other.
Nevertheless, there is a repetition in the second case of all the misery
of the first both as regards intensity and duration. Sometimes during the
first days of the disease the peccant matter is so exuberant that one
foot is insufficient for its discharge. It then attacks both, and that
with equal violence. Generally, however, it takes the feet in succession.
After it has attacked each foot the fits become irregular both as to the
time of their coming and as to their duration. One thing, however, is
constant—the pain increases at night and abates in the morning. Now a
series of lesser fits like these constitute a true attack of gout, long
or short, according to the age of the patient. To suppose that an attack
two or three months in length is all one fit is erroneous. It is rather
a series of minor fits. Of these the latter are milder and more limited
in their extent than the former, so that the peccant matter is discharged
by degrees, and recovery follows. In strong constitutions, when the
previous attacks have been few, a fortnight is the length of an attack.
With age and impaired habits gout may last two months. With _very_
advanced age, and in constitutions _very_ much broken down by previous
gout, the disease will hang on till the summer is far advanced. For the
first fourteen days the urine is high-coloured, has a red sediment,
and is loaded with gravel. Its amount is less than a third of what the
patient drinks. During the same period the bowels are confined. Want of
appetite, general chills towards evening, heaviness, and a troublesome
feeling even in the parts which are free from the attack, attend the fit
throughout. As it goes off the foot itches intolerably, mostly between
the toes; the cuticle scales off, and the feet desquamate, as if venomed.
The disease being disposed of, the vigour and appetite of the patient
return, and this in proportion to the violence of the last fits. In the
same proportion the next fit either comes on or keeps off. Where one
attack has been sharp, the next will take place that time next year, not
earlier.”—_Sydenham._

[32] “Pain is better borne by the poor man, as I have had opportunities
of seeing, than by the man who acquired or promoted his gout with two or
three bottles of port wine daily, with the surroundings which such luxury
implies.”—_Longstreth_, “_On Gout_.”

[33] “The pain is altogether disproportionate to the other signs of
inflammation, and, even more, to the consequent structural changes in the
inflamed part.”—_Paget._

As to the peculiar character of the pain, Duckworth states: “Nothing at
all like it occurs in any other joint disease.”

[34] Sydenham noted that “sometimes the morbific matter is thrown upon
the elbows and occasions a whitish swelling, almost as large as an egg,
which becomes gradually inflamed and red.”

[35] “_Regular gout_ may _supervene suddenly, and be chronic_; that is
to say, its outbreak need not have been preceded by paroxysms in any way
characteristic of acute gout.”—_Trousseau_, “_On Gout_.”

[36] As Trousseau puts it: “Regular chronic gout, in respect of the
frequency of the recurrence of the paroxysms, resembles acute gout with
successive paroxysms, there being this capital difference, however, that
its attacks are longer and during the intervals are not entirely absent.”

[37] Mr. James Moore, surgeon to the Second Regiment of Life Guards
(_Medico-Chirurgical Transactions_, 1809, Vol. I.):—

“This effusion” (meaning the milky fluid containing the urate of soda)
“occurs not only during fits of gout, but likewise in the intervals; and
as the extremities, particularly the hands and feet, are the principal
seat of gout, it is there the greatest accumulation of chalk takes place.
Though this process is usually preceded and accompanied by inflammation,
the chalk is never inclosed in a cyst, like pus in an abscess. It lies
usually in the cellular membrane, in the bursæ mucosæ, or in the cavities
of the joints. I have even seen it thrown out between the cutis and the
cuticle. But, as the gouty inflammation is of the erythematous kind,
there is no extravasation of coagulable lymph, and no new-formed covering
surrounding the chalk. This point is of the first importance, and
explains many of the peculiarities of gout, which is generally considered
as a phlegmon. But the absence of coagulable lymph in the inflamed parts
I consider as full evidence of the inflammation being erythematous.

“The chalky liquid when first secreted gives to the finger the feeling
of fluctuation, and cannot be distinguished from the ordinary serous
effusion of gout. But unfortunately the absorbents cannot suck up the
chalky particles. The consistence of the liquid therefore becomes thicker
and thicker, till at last nothing remains but a hard mass. When even a
considerable effusion of this kind occurs, the quantity of chalk which
ultimately remains is comparatively small, as by far the greater quantity
is merely serum. It therefore usually requires repeated effusions to
form any great mass of chalk, and the consistency depends upon its age
and the activity of the absorbents. The quantity at last accumulated by
repeated paroxysms is in some instances immense, which augments very
seriously the sufferings of the gouty. The distress, however, is not
owing to any irritating quality in the chalk, but to its obstructing the
motion of the tendons and joints, occasioning often complete anchylosis,
and pressing and distending the surrounding parts by its bulk. It acts,
therefore, by mechanically embarrassing the machine of the body, and not
upon the living principle, for it will often remain for years in parts
highly sensible without exciting the slightest pain or inflammation.
Although these concretions are of so mild a nature, they often are the
cause of extensive mischief, bursting externally, occasioning ulcers
very difficult to heal. When a violent fit of the gout attacks a chalky
tumour, the appearance is frequently very alarming, the new paroxysm
being accompanied with a fresh serous and chalky effusion, which, added
to the old deposit of chalk, occasions a prodigious swelling; the cutis
when distended to the utmost opens, yet sometimes the cuticle remains
entire. The chalky or serous liquid may then be seen through the
semi-transparent epidermis. The surrounding integuments appear of a deep
red, or of a purple hue, threatening mortification, while the pain is
excruciating.

“At length the cuticle gives way, a discharge of serum and chalk takes
place, and a remission of all the symptoms usually follows. During the
whole of this alarming process suppuration never occurs; but soon after
the opening has taken place suppuration commences, and pus and chalk are
then discharged from the ulcer. There are several unexpected occurrences
in the progress of such ulcerations. When an opening is formed, the
whole of the chalk never escapes, and its complete evacuation is often
a very tedious process; this is owing to its being diffused through the
cellular membrane, as in the cells of a sponge. One cell must sometimes
give way after another, and small portions of chalk are successively
thrown out, so that months and even years pass away before the whole
is discharged. It also frequently happens that the orifice contracts
and closes over, leaving portions of chalk underneath. This kind of
cicatrix sometimes stands its ground, but more commonly breaks out again
and again to discharge chalk. Even openings into joints, which are so
dangerous when occasioned by other extraneous bodies, are often attended
with no serious symptoms when the joint is filled with chalk. On such
an accident happening a surgeon unacquainted with these peculiarities
might be tempted to propose large openings, or even amputation, as the
only resource for hindering extensive inflammation and carious bones. But
if he treats the disease mildly, he will find that no such severe plans
are requisite, for the parts will probably fall into a very tranquil or
indolent state; a sore will continue for a certain period, discharging
pus, and occasionally a bit of chalk, till at last the orifice will
close up. Independent of the opening formed by a fit of the gout, the
skin, stretched over a mass of chalk, is sometimes thinned, absorbed,
and pierced by mere pressure. At other times this is effected by common
inflammation and suppuration. When openings take place in these milder
ways, a less quantity of chalk is usually evacuated; but this depends
entirely upon the degree of inflammation. When the suppuration is great,
it naturally detaches and washes out a greater quantity of chalk.

“The last peculiarity is the rarest, namely, that a dry, hard piece of
chalk shall pierce the skin, and remain like an excrescence, without
exciting either inflammation or suppuration.”

[38] According to Adler, about one-tenth as much uric acid is excreted in
the sweat as in the urine, sweat containing 0·1 mg. per cubic centimetre.

[39] In this connection the tendency of gouty glycosurics to exhibit
boils and sometimes carbuncles should not be forgotten.

[40] Max Strunsky, of New York, discussing the frequency with which
by the older physicians gouty forms of arthritis were confused with
gonorrhœal, syphilitic, and other undifferentiated forms of infective
arthritis, makes the following observation: “Also flatfeet must have
added herds of cases, for this pathological entity was as yet unknown.
The rich man in pursuit of his pleasure and the poor man from prolonged
standing at his labour strained their arches then as they do now, and
women by their ultra-fashionable shoes, which fashion decreed upon
them in certain periods of history, produced painful feet which were
undoubtedly mistaken for gout. That patients with local foot trouble were
treated for gout the writer can speak from experience. A typical case
is of a woman who came to his office two years ago. She had broken-down
anterior arches. Hallux valgus, hammer-toes, and bunions were present,
and the heels were small and undeveloped. Her feet were one mass of pain,
and they looked infantile, reminding one of a Chinese woman. All her
adult life she wore high-heeled, narrow, pointed, tight shoes. She said
that for twenty years she had been treated for gout.”

[41] In support of this contention, I would note that Charcot, while
he gives us an inimitable account of the _tophaceous_ variety of gout,
introduces also another variant, as he deems it, of _chronic articular
gout_. The joint changes in this latter are marked by what he terms
“a thorough atrophy,” including the superjacent skin, which “is pale,
shining and polished.” With this are associated ankyloses, angular
deflections, and partial dislocations. The joints, he states, “may be
absolutely free from swelling, for example when the extra-articular urate
deposits _either do not exist at all, or only mere traces of them, or
when only the articular cartilages are invaded by the urate of soda_.”
It cannot, we think, be doubted that the clinical content of this group
is largely made up of _rheumatoid_ or _atrophic arthritis_. The evidence
that these examples, _quâ_ _uratic deposits_, are of “gouty” nature, is
obviously very slender.

Reverting to Sir Dyce Duckworth, this authority also recognises two
varieties of chronic articular gout: (_a_) tophaceous gout; (_b_) chronic
deforming gout, with as its synonym _arthritis deformans uratica_. As
to the clinical content of this latter group he writes: “The fingers,
hands, and wrists show various deformities depending on _over-growth_ of
_articulating ends of bone_, _cartilage_, ligaments, and bursæ. _These
may be complicated with visible or invisible tophaceous deposits_.” As to
these anatomical alterations, Duckworth regards them as “similar to, but
not the same as, those induced by rheumatic disease.” But he adds: “It is
very rare for the deformities of true gout to attain the gross characters
peculiar to chronic rheumatic arthritis; they are altogether of lesser
degree in the majority of the worst instances.” From a careful study of
their anatomical characters, I cannot avoid the conclusion that they were
in the main examples of the hypertrophic variety of arthritis deformans,
viz., _osteoarthritis_.

[42] As Sir W. Hale White has pointed out, “pads” not uncommonly develop
on the dorsal aspects of the mid-phalangeal joints. They range in size
from a split pea to a hazel nut. Histologically they are the outcome of
an excessive overgrowth of fibrous tissue beneath the corium. They in
no way involve the joints, but, according to Hale White, they have been
confused with osteoarthritis. Their frequent association with Dupuytren’s
contracture might conceivably lead to their confusion with gout also,
inasmuch as that deformity is so widely attributed to a “gouty” habit.

[43] Sir Spencer Wells in his “Practical Observations on Gout and its
Complications and on the Treatment of Joints stiffened by Gouty Deposits.”

“Of the many cases related by authors as anonymous disease by far the
greater portion were connected with a gouty diathesis, as indicated both
by the formation of calculi, by the occurrence of regular paroxysms
of gout, and by the descent of the individual from gouty ancestors;
they are cases, in fact, which would have been better understood and
better treated if they had been termed ‘anomalous gout’; but as the
subjects are young females, they are of course set down as ‘anomalous
hysteria.’”—_Laycock_: “_Nervous Diseases of Women_.”

[44] “Diseases of the Eye” (1918), p. 258.

[45] “Diseases of the Eye” (1919).

[46] “Diseases and Injuries of the Eye” (1913).

[47] Kruckmann, _Med. Klinik._, 1910, No. 38.

[48] _Proc. Roy. Soc. Med._, Ophth. Section, 1914, p. 66.

[49] _Ophth. Hosp. Reps._, VII., p. 287, 1873.

[50] “Diseases of the Eye” (1854), p. 558.

[51] _Brit. Med. Journ._, 1885, R. Clement Lucas.

[52] _Lancet_, 1920, Vol. I., p. 500, Browning.

[53] _Archives d’Ophtalmologie_, Vol. XII., p. 623.

[54] A very rare form of iritis was described by the late Mr. Doyne as
guttate iritis (_Trans. Ophth. Soc._, Vol. XXX., p. 91) because the
appearances resembled drops of lymph on the margin of the pupil. In his
view it was a true form of gouty iritis, but the diagnosis does not seem
to have been confirmed by other observers. Even if we grant that his
view is possibly correct, we must beware how we generalise on a basis of
exceptions and freaks.

[55] _Brit. Med. Journ._, 1903, Vol. II., p. 138.

[56] “Gout” (1876), p. 450.

[57] _Clin. Soc. Trans._, Vol. XI., p. 132, 1898.

[58] “Medical Ophthalmoscopy,” 3rd edition, p. 267.

[59] _Practitioner_, 1909, Vol. II., p. 61.

[60] Sydenham, discussing a milk diet, observes that “it has done good
as long as it has been rigidly attended to. The moment, however, that
the patient swerves from it a hair’s breadth, and the moment he betakes
himself to the diet of a healthy man (no matter how mild and simple), the
gout returns worse than ever.”

[61] “The lighter beers of Germany, Austria, and Scandinavia, appear to
be harmless for the gouty unless taken immoderately. Residents in towns
goutily disposed, leading sedentary lives, are seldom long tolerant even
of light laager beer.”

[62] Sir Archibald Garrod has suggested that guaiacum has a distinct
effect in reducing the amount of uric acid excreted, _i.e._, it
was thought that the uric acid is eliminated in some other form,
possibly hippuric acid. Accordingly Martindale and Westcott conducted
investigations to determine whether this resin increases or decreases the
elimination of uric acid from the human body.

A normal individual took guaiacum resin in 5-grain doses daily in the
morning, and the uric acid was estimated in the urine the same afternoon.
Hippuric acid was also estimated in specimens of the same urine by the
method given by Allen, “Chemistry of Urine,” p. 186. After a day’s
interval the acids were estimated on several days without administration
of the drug. The two series were then repeated on the same lines after
an interval. Seeing that the diet of the individual could not well be
controlled in weighed amounts of food, as would strictly be necessary for
an investigation of this kind, it was thought that to express the results
in percentage ratios of uric acid to excess of solids (R.U.A.) over water
might yield more comparable results.

Joulie employs this method of indicating the constituents of urine by
ratios; _cf._ Vol. I., p. 736. Thus, taking a specimen of urine with the
following “normal” factors in grams per litre:—

  Specific gravity                      1017·8
  Excess of solids over water             17·8
  Physiological acidity in terms of H₂SO₄  0·849
  Total P₂O₄                               2·083
  Cl                                       6·865
  Urea                                    18·75
  Uric acid                                0·416
  Hippuric acid                            1·3
                                         (_mean_).

One may express the constituents as the following percentage ratios:—

                                                         Normal.

  “R.A.”—Ratio of physiological acidity to excess
      of solids over water                         4·77  0·849 × 100
                                                         -----------
                                                             17·8

  “R.P.”—Ratio of total P₂O₄ to excess of solids over
      water                                               11·17
  “R.U.”—Ratio of urea to excess of solids over water    100·53
  “R.U.A.”—Ratio of uric acid to excess of solids over
      water                                                2·33
  “R.H.A.”—Ratio of hippuric acid to excess of solids
      over water                                           7·3
  “R.P./R.A.”—Ratio of phosphoric acid to ratio of acidity
      (Joulie’s factor, _cf._ Vol. I., p. 737)             2·45

  Ratio of uric acid, for example, is arrived at thus    0·416 × 100
                                                         ----------- = 2·33
                                                             17·8

The results which we obtained are given in the following table:—

_Effects of Guaiacum Resin on the Urine of a Normal Individual._

  -----------------+---------+-------+-----+------+------+--------+--------
                   |   Date. |  Sp.  |Urea.| Uric | Hip- |“R.U.A.”|“R.H.A.”
                   |         |  Gr.  |     | Acid.| puric|        |
                   |         |       |     |      | Acid.|        |
  -----------------+---------+-------+-----+------+------+--------+--------
  With guaiacum    | 28/12/11| 1·0107| 2·29| 0·09 | 0·09 |  4·43  |  4·34
  With guaiacum    | 29/12/11| 1·0247| 1·29| 0·08 | 0·1  |  3·34  |  4·04
  With guaiacum    |   1/1/12| 1·0215| 2·56| 0·015| 0·15 |  4·88  |  6·97
  With guaiacum    |   2/1/12| 1·0141| 2·82| 0·10 | 0·2  |  4·2   |  8·20
  Without guaiacum |   4/1/12| 1·0229| 2·42| 0·06 | 0·1  |  2·62  |  4·36
  Without guaiacum |   5/1/12| 1·0249| 2·42| 0·08 | 0·2  |  3·16  |  8·03
  Without guaiacum |   8/1/12| 1·0255| 3·09| 0·10 | 0·225|  4·11  |  8·12
  With guaiacum    |  11/1/12| 1·0233| 2·56| 0·09 | 0·1  |  3·7   |  4·29
  With guaiacum    |  12/1/12| 1·0213| 1·88| 0·075| 0·1  |  3·05  |  4·69
  Without guaiacum |  24/1/12| 1·0239| 2·42| 0·08 | 0·038|  3·45  |  1·57
  Without guaiacum |  25/1/12| 1·0229| 2·15| 0·06 | 0·05 |  2·61  |  2·18
  -----------------+---------+-------+-----+------+------+--------+-------

          Average uric acid ratio under guaiacum resin         = 3·39
          Average uric acid ratio without guaiacum resin       = 3·19
          Average hippuric acid ratio under guaiacum resin     = 5·43
          Average hippuric acid ratio without guaiacum resin   = 4·49

The quantity of hippuric acid normally found is known to vary enormously,
_e.g._, between 0·02 and 0·25 per cent. From this we deduced, for
purpose of this investigation, a mean normal R.H.A. of 7·3. A number of
other investigations were conducted on analogous lines, but need not be
recorded.

From the results of these experiments one notices an average increase
of uric and hippuric acids during the “+ guaiacum” periods. It is not
possible to draw a conclusion without further corroboration. The amount
of each acid from day to day is seen to be erratic, and the process of
estimation of hippuric acid is not accurate.

[63] “Weakly mineralised thermal muriated waters, such as those of
Baden-Baden in Germany, and Bourbon-Lancy in France, which in character
and action approach the simple thermal group, may also show great
radio-activity. In fact, the Büttquelle of Baden-Baden in this respect
rivals some of the most radio-active springs of Gastein. Of Bourbon-Lancy
springs, according to A. Piatot, the least mineralised are the most
radio-active.”—“_Climato-therapy and Balneo-therapy_,” _by Sir Hermann
Weber_.

[64] SIR WILLIAM RAMSAY’S ANALYSIS OF THE BATH WATERS.

  Density of the water from King’s Well        1·0166

  Osmotic pressure equivalent to that of
    a salt solution containing per litre       1·09 grams NaCl.

Volume of gas in twenty-four hours from—

                                              Litres.
  King’s Well                                  4,927
  Cross Spring                                   218
  Hetling Spring                                 218 (estimated).
                                               -----
                                               5,363
                                               -----

Analysis of gas (King’s Well)—

                                    Parts per 10,000.
  Carbon dioxide                                 360
  Nitrogen, etc.                               9,640
  No oxygen, no hydrogen, no marsh gas.

The nitrogen contains—

  Argon                                        73·63
  Neon                                         23·34
  Helium                                        2·97

From all three wells in twenty-four hours—

                                              Litres.
  Argon                                           39
  Neon                                            12½
  Helium                                           1½

_Gases dissolved in Pump-room Water._—This water contains 18·5 volumes
of gas per 1,000 of water. Its composition is—

  Carbon dioxide                                6·9
  Nitrogen                                     11·6

It had become somewhat aerated on drawing, but allowance has been made
for that.

                                                   Milligrams per
                                                   million litres.

  Radium in the water of the King’s Well                  0·1387
  Niton (radium emanation) in the water of King’s Well    1·73
  ”         ”         ”         ”       of Cross Bath     1·19
  ”         ”         ”         ”       of Hetling Bath   1·70
  ”         ”         ”    in the gas from King’s Well   33·65

[65] Bickel in a series of experiments in which the acid contents as
well as the total amount of gastric juice were considered obtained the
following results: simple gaseous waters (Apollinaris, Giesshübl),
muriated waters (Rakoczy spring of Kissingen, Wiesbaden, Kochbrunnen),
and muriated alkaline waters (Ems, Selters), all of them, as compared to
distilled water and ordinary tap water, rather increased than decreased
the specific secretory activity of the gastric mucous membrane, whereas
simple alkaline waters (Vichy) and sulphated alkaline waters (Karlsbad)
had a slight tendency to diminish, and the sulphated “bitter” waters
(Hunyadi Janos water) decidedly diminished, the gastric secretory
activity, although “bitter” waters sometimes induced a watery flow from
the gastric mucosa, which increased the fluid contents of the stomach.

[66] Bain, of Harrogate, from his observations on a man with permanent
cutaneous biliary fistula, found that the old sulphur spring of Harrogate
increased both the quantity of bile and the bile solids. This, he thinks,
may “fairly be taken as an index of the degree to which it stimulates the
liver, and is, in fact, the most reliable indication of the value of a
cholagogue.”




INDEX


    =A-amino-acids=, 61

    =Aborigines=, gout unknown among, 2

    =Abscess= formation in peri-tophal tissues, 234
      skin resembling, in acute gout, 212

    “=Accessory= food factors” in diet of gouty, 339

    =Adenase=, 100, 101

    =Adenine=, 73, 75, 77, 98

    =Aetius’s= views on gout, 6

    =Age= factor in gout, 40
      influence of, on diet, in acute stage of gout, 333

    =Agotan= in treatment of acute gout, 379

    =Aix= massage baths, 427

    =Alanine=, uric acid excretion augmented by, 89

    =Albuminuria=, diet in, 358

    =Alcohol= and gout, 48
      hypersensitiveness of gouty to, 365
      in febrile stage of sthenic gout, 333
      in gout, 361
      in subjects of gouty glycosuria, 237
      _modus operandi_ of, in induction of gout, 49
      _plus_ overeating, cause of gout, 49

    =Alcoholism=, chronic, purin metabolism in, 115

    =Alexander= of Tralles’s views on gout, 5

    =Alimentary= canal, condition of, and gout, 174
      disorders, effects of radio-active waters on, 439
      tract, functional derangements of, in diagnosis of articular gout,
          249
        X-ray examination of, in treatment of gout, 336

    =Alkalies= in inter-paroxysmal periods of gout, 392
      in treatment of acute gout, 383
      in treatment of chronic gout, 399

    =Alkaline= waters, simple, spas for, 441

    =Alkapton= in urine, 59

    =Alkaptonuria=, 69

    =Allantoin=, 104

    =Alternatives= in treatment of chronic gout, 401

    =Alveolus=, senile atrophy of, 329

    =Amberg= and Jones’ scheme of formation of uric acid, 104

    =America=, United States of, gout in, 47

    =Amino-acetic-acid=, 64

    =Amino-acids= and dicarboxylic amino-acids, 89
      deaminisation of, 62, 63
      fate of, 62
      in portal blood, 62
      in relation to gout, 64

    =Amino-purins=, as source of uric acid, 84

    =Amylaceous= dyspepsia, diet in, 351, 352

    =Anacritical= stage of depression, 211

    =Anæmia= in cases of long-standing gout, treatment of, 406
      retention capacity of tissues for uric acid in, 158

    =Anatomical= alterations in articulations, 54

    =Anglo-Saxon= period, prevalence of gout in, 2

    =Animal= cells, nucleic acid derived from, 98

    =Animals=, various, uric acid blood content of, 135

    =Ankylosis= in chronic gout, 287

    =Anodyne= preparations in treatment of acute gout, 384, 385

    =Anodynes= in acute gout, 383

    =Antiquity= of gout, 1

    =Anuria=, hysteria in, 126

    =Aponeuroses=, gouty polyarthritis in, 214

    =Appendicitis=, septic foci of, 184

    =Appendix-dyspepsia=, 184

    =Arab= physicians’ views on gout, 6

    =Aretæus= the Cappadocian’s views on gout, 4, 5

    =Arterio-sclerosis=, associated with gout, 245
      blood-content in, 127
      spa treatment of, 451

    =Arthralgia=, fleeting, 193

    =Arthritic= attacks, tophi formation preceding, 164
      iritis, 315

    =Arthritides=, specific infective, and gout, analogies between, 194

    =Arthritis= deformans, cleavage into two types, 18
      differentiation of, from chronic gout, 16
      rheumatoid, and osteoarthritis, 20

    =Arthritis=, gonococcal, acute, differential diagnosis from acute
          gouty polyarthritis, 270
          from gout, 259
        of tarsus and metatarsus, differential diagnosis from gout, 263
      gouty, 39
        definition of, 20
        frequency of tophi in, 255
        relation to local foci of infection, 185
      Greek designation, 3
      hæmophilia, differential diagnosis from chronic gout, 285
      infective, of undifferentiated type, differential diagnosis from
          acute polyarticular gout, 272
        skiagraphy in differential diagnosis of, 290
      non-gouty, hyper-uricæmia in, 140
      rheumatoid, 17
        differential diagnosis from chronic gout, 284
        local character of joint swellings, 284
        or atrophic, acute, differential diagnosis from acute gouty
          polyarthritis, 272
        skiagraphy in differential diagnosis of, 291
      syphilitic, differential diagnosis from chronic articular gout,
        277
        secondary, differential diagnosis from acute gouty
        polyarthritis,
          271
      tophi in relation to, 254

    =Arthropathies=, nerve, differential diagnosis from chronic gout,
        284

    =Articular= gout, chronic, medicinal and other modes of therapy, 397
      etiological diagnosis, 247

    =Articular= lesions in chronic gout, distribution of, 226

    =Asphyxias=, local, of hands, in gout, 45

    =Atophan=, effect of, on exogenous purins, 110
        on uric acid excretion, 119
      indicated when gout attack imminent, 395
      in treatment of acute gout, 379
      in treatment of chronic gout, 403

    =Auricular= tophi, 202

    =Auto-intoxication= theory of gout, 182

    =Auto-toxæmia= theory of gout, 182

    =Avicenna’s= views on gout, 6


    =Bacillus coli communis= as causative agent in gout, 175

    =Bacterial= flora, intestinal, modifications in, 182

    =Bacteriological= examination in diagnosis of articular gout, 251

    =Baillon’s= dissociation of rheumatism from gout, 15

    =Banting= method in reduction of obesity, 357

    =Barclay’s= theories of ætiology of gout, 23

    =Bath= as residence for gouty, 419

    =Bath= waters, Sir W. Ramsay’s analysis of, 435

    =Baths= in treatment of gout, method of application, 427

    =Beaumont, W. M.=, ocular disease in the gouty, 308

    =Beauvais’s= work on gout, 17

    =Beer= as beverage in gout, 362

    =Benzoates= in treatment of chronic gout, 401

    =Berkart’s= theory of ætiology of gout, 27
      views on gout, 56

    =Beverages= in gout, 359

    =Bismuth= carbonate in inter-paroxysmal periods of gout, 392

    =Biurate= of soda in gouty tophi, 151

    =Blisters= in treatment of acute gout, 386

    =Blood=, changes in, in acute gout, 210
        in chronic articular gout, 226
        in gouty polyarthritis, 216
      content in gout, 189
      count in acute gout, 211

    =Blood=, examination of, in diagnosis of articular gout, 251

    =Blood=, human, relationship between amounts of uric acid, urea and
          non-protein nitrogen in, 122
      in chronic interstitial nephritis, urates in, 120
      in disease, uric acid of, 137
      portal, amino-acids in, 62
      routine examination of, in diagnosis of articular gout, 249
      uric acid as normal constituent of, 135
      uric acid content of, and gout, relation between, 143
        effect of diet upon, 141
        effect of exogenous purins on, 137
        estimation of sources of fallacy, 145
        in gout, 133, 139
      uric acid in, 24, 34, 78
        discovery of, 21
        Folin and Denis’s method of determination, 133
        forms of, 145
        Gudzent and Schade’s theories, 79
        non-protein nitrogen and urea nitrogen in (table), 136
      variations in uric acid content independently of diet, 142

    =Bodily= conformation, and gout, 44

    =Boils=, gout following, 53, 178

    =Bone=, conditions of, revealed by skiagraphy, in diagnosis of gout,
          286

    =Bones=, changes in, in gout, 53
      focal areas of rarefaction in, revealed by skiagraphy, 286, 287

    =Brandy= in gout, 371

    =Bruce’s= modes, 286

    =Bunion=, inflamed, differential diagnosis from gout, 261

    =Burian= and Schur’s researches on sources of uric acid, 83

    =Bursæ=, involved in gout, 195
      tophi in, 233

    =Bursitis=, olecranon, gouty, 215
      post-calcaneal, in referred pain in heel, 265


    =Cælius Aurelianus’s= views on gout, 5

    =Caffeine=, 85

    =Calcium= carbonate in inter-paroxysmal periods of gout, 392
      salts in gouty tophi, 151

    =Calculus=, urinary, 29

    =Carbohydrates= in diet of gouty, 347

    =Carbuncles=, gout following, 53, 178

    =Cartilage=, morbid changes in, 53
      uratic deposits in, 52, 153
        in nephritis, 128

    =Cataphoresis= in treatment of chronic articular gout, 407

    =Cell= protoplasm, chemistry of, 176

    =Celsus’s= views on gout, 4

    “=Chalk-stones=,” 150

    =Chalybeate= waters, spas for, 442

    =Champagne= in gout, 368

    =Charcot’s= discovery of nerve arthropathies, 18
      joint, differential diagnosis from chronic articular gout, 277

    =Chemistry= of uric acid and purin bodies, 75

    =Chilblains= confused with early stages of tophi formation, 164

    =Chirargra=, Greek designation, 3

    =Cholecystitis=, 184

    =Cider= as beverage in gout, 363

    =Claret= in gout, 369

    =Climate= and gout, 45
      and residence in treatment of gout, 418

    =Climato-therapy= in gout, 418

    =Clothing=, importance of, 421

    =Cocoa= as beverage in gout, 361

    =Coffee= as beverage in gout, 361

    =Colchicine= in treatment of acute gout, 378

    =Colchicum= in acute gout, 192, 374, 375, 378
        contra-indicated, alkalies as substitute, 383
        method of administration, 376
      preparations and dosage of, 376
      used by Aetius, 6

    =Colitis=, mucous, initial manifestations of gout, 175

    =Colloids= in gouty tophi, 152

    =Collosol= iodine in treatment of chronic gout, 402

    =Colorimetric= method of determining uric acid in blood, 133

    =Colour= reaction test in blood analysis, 133

    =Condiments= in diet of gouty, 350

    =Constipation=, effect in gout, 337
      in acute gout, treatment of, 373
      in chronic gout, treatment of, 400
      in inter-paroxysmal periods of gout, treatment of, 393

    =Constitutional= disturbance in gout, 188
      influences in formation of tophi, 161

    =Corpora= cavernosa of penis, tophi in, 235

    =Cramps= in acute gout, 210

    =Cream=, effect of, on uric acid output, 348

    =Creatine=, 63, 67
      in urine of children, 68

    =Creatinine=, 61, 63, 67, 68
      in blood in gout and nephritis (table), 121

    =Crystalline= deposits in synovial fluid, 54

    =Crystalloids= in gouty tophi, 152

    =Cytosine=, 98

    =Cullen’s= differentiation of varieties of rheumatism, 16
      theory of ætiology of gout, 21

    =Cutaneous= disorders in gout, 240
      gravel, 203

    =Cuticule=, desquamation of, typical of gout, 191

    =Cystin= in urine, 59

    =Cystinuria=, 69

    =Cystoid= degeneration in gout, 56


    =Deaminisation= of amino-acids, 62, 63

    =Deficiency= diseases and accessory food factors, 340

    =Degeneration=, theories of, 25, 27

    =Desquamation= in acute gout, 212

    =Diabetes=, glycosuria and, 60

    =Dicarboxylic= amino-acids, 89

    =Diet=, effect of, on blood content of uric acid, 141

    =Diet= on excretion of uric acid, 83

    =Diet= in acute paroxysms of gout, 332
      in albuminuria, 358
      in amylaceous dyspepsia, 351, 352
      in chronic gout, 334
      in glycosuria, 357
      in hyperchlorhydria, 353
      in hyperuricæmia, 354
      in hypochlorhydria, 354
      in inter-paroxysmal periods of gout, 391
      in reduction of obesity, 357
      in treatment of gout, 332
        “accessory food factors,” 339
        carbohydrates, 347
        collaboration of clinician and bio-chemist, need for, 337
        condiments, 350
        fats, 347
        fish, 346
        fruits, 349
        idiosyncrasies of, 343
        physical examination necessary before, 336
        proteins, 345
        regulations of, 342
        vegetables, 348
      variations of blood content of uric acid independently of, 142

    =Dietaries=, fixed, fallacy of, in treatment of gout, 335

    =Digestion=, disturbances of, prevention of, in treatment of gout,
        335

    =Digestive= glands, _rôle_ of, in uric acid excretion, 88

    =Diocletian=, edict by, _re_ gout, 5

    =Dislocations=, signalising attack of gout, 53

    =Douches=, 428

    =Dover’s= powder, with aspirin and phenacetin, in treatment of acute
          gout, 383

    =Drink= and gout, 48

    “=Drug= dyspepsia,” 391

    =Drugs= influencing excretion of endogenous uric acid, 96

    =Duckworth’s= classification of arthritic type of gout, 36
      theory of ætiology of gout, 33

    =Dyschezia= and gout, 337

    =Dysenteric= arthritis, differential diagnosis from acute gouty
          polyarthritis, 272

    =Dysentery=, complicated by arthritis and myalgias, 194

    =Dyspepsia=, amylaceous, diet in, 351, 352
      atonic, muriated waters in treatment of, 444
      chronic, gout associated with, 178
      “drug,” 391
      gouty, no specific form of, 350
      intestinal, preceding gout, 182
      mineral waters in treatment of, 443
      spas in treatment of, 442

    =Dyspeptic= symptoms of acute localised gout, 201


    =Ear=, pricking or tenderness in, 203
      tophus in, 202

    =Ears=, tophi in, antedating articular outbreaks, 203

    =Ebstein= and Sprague’s analysis of tophi, 150

    =Ebstein’s= theory of ætiology of gout, 25

    =Ecchymoses=, local, in acute gout, 212

    =Eczema=, gouty, spa treatment of, 451
        treatment of, 416
      in gout, 241

    =Egypt=, osteoarthritis in, in ancient times, 1

    =Endemic= areas of gout, 46

    =Endogenous= purins, 87
      origin of, 83
      source of, 88
      uric acid excretion, 91
        factors influencing, 93
        increased by purin-free proteid food, 89
        pathological states influencing, 94
        periodic variations of, 94
        physiological conditions, 93

    =Environment= in gout, 40

    =Enzymes=, distribution of, 99
      in intestinal juices and wall, 100

    =Epistaxis=, gout following, 178

    =Epithelial= cells, nucleus in gouty tophi, 151

    =Erysipelas=, gouty arthritis simulating, 215

    =Erythromelalgia=, differential diagnosis from gout, 266

    =Etiological= diagnosis of articular gout, 247

    =Exercise= in gout, importance of, 421
      relation of, to gout, 337

    =Exogenous= origin of purins, 83
      purins as source of uric acid, 84
      uric acid excretion, 85

    =Exudative= diathesis, 116

    =Eye=, deposition of urates in, 309
      gout in, evidence of, 309
      gouty diathesis in regard to, 310

    =Eyelids=, uratic deposits in, 235


    =Fæces=, examination of, in diagnosis of articular gout, 250
      in treatment of gout, 337

    =Fasciæ=, involved in gout, 195

    “=Fat= soluble A,” 340

    =Fats= in diet of gouty, 347

    =Feet=, incidence of tophi in, 162
      plantar surface of, tophi in, 235

    =Fibrosis=, interstitial, chronic, 186
      of visceral organs in gout, tendency to, 186

    =Fibrositis= associated with acute articular gout, 195
      associated with gout, treatment of, 411
      gouty, acute brachial, treatment of, 412
      incidence of gouty stigmata in types of, 221, 222
      muscular, in gouty, massage in, 423
      spa treatment of, 450

    =Fingers=, deformed, in chronic gout, 230
      pulps of, tophi in, 235

    =Fischer’s= researches on protein molecule, 61

    =Fish= in diet of gouty, 346

    =Flatfoot=, pains in, differential diagnosis from gout, 263

    “=Flying= gout,” 193

    =Foci= of infection in gouty, 53
      local, in gout, 177

    =Foci=, relation to gouty synovitis and arthritis, 185

    =Folin= and Denis’s method of determination of uric acid in blood,
        133
      researches into urea formation, 63

    =Food=, cooking of, in diet of gouty, 344
      influence on gout, 48

    =Foods=, various, exogenous urinary purin in, amount of, 85

    =Foot= deformities, static, differential diagnosis from gout, 261

    “=Fot-adl=,” Anglo-Saxon name for gout, 3

    =Fractures=, signalising attack of gout, 53

    =Fruits= in diet of gouty, 349

    =Function=, gout a disorder of, 200

    =Functional= disturbances in gout, 201


    =Galen’s= views on gout, 2, 4

    =Gall-stones=, gout associated with, 184

    =Gall-bladder dyspepsia=, 184

    =Garrod’s= discovery of uric acid in blood of gouty persons, 21
      pathogeny of gout, growing scepticism as to, 32
      theory of ætiology of gout, 22
      views on gout in the eye, 320

    =Gastralgias= in gouty, 351

    =Gastric= catarrh, chronic, gout associated with, 351
        chronic, mineral waters suitable for, 445
      glands, diseased conditions of, and gout, 173
      insufficiency, muriated waters in treatment of, 444

    =Gastro-intestinal= asepsis, importance of, in gout, 332
      derangements in acute paroxysms of gout, 333
      disorders and gout, 180
        attributed to gout, 299-302
        chronic, spas in treatment of, 442
        mineral waters in treatment of, 443
      tract, derangement of, cause of gout, 170

    =Genito-urinary= passages, infection of, examination for, in
          diagnosis of articular gout, 249
      tract, examination of, in treatment of gout, 331

    =Geographical= distribution of gout, 45-48

    =Gin= in gout, 371

    =Glandular= affections in gouty subjects, 179

    =Glaucoma=, gout and, 324

    =Glycocine= and urea, interaction between, 84

    =Glycocoll=, _rôle_ of, 64
      theory of gout, 65
      uric acid excretion augmented by, 89

    =Glycosuria= and diabetes, 60
      associated with gout, treatment of, 414
      diet in, 357
      examination for, in treatment of gout, 337
      gout and, co-existence of, 185
      gout in relation to, 236
      “gouty,” 182
      spa treatment of, 449

    =Glyoxylic= acid in gouty urine, 65

    =Gonococcal= arthritis of tarsus and metatarsus, differential
          diagnosis from gout, 263
      infection, articular involvement, with muscular and nervous
          lesions, 194
        differential diagnosis from gout, 259
        exclusion of, in diagnosis of articular gout, 248

    =Gore=, Ringrose, theory of pathology of gout, 173

    =Gout=, acute, colchicum in, 375
        definitely paroxysmal, 191
        general phenomena of, 210
        ionisation in treatment of, 387
        local phenomena, 211
        localised, clinical account, 200
          dyspeptic symptoms of, 201
          premonitory articular pains, 204
          prodromal symptoms, 200
        locality of, 208
        medicinal treatment of, 372
        onset of, 207
        pain in, 208
        paroxysm of, analysis of, 188
          diet in, 332
          symptoms of, 205
          uric acid variations in, 117
        surgical methods considered, 388
        treatment of, alternative remedies in, 381
          local measures, 384
        uric acid excretion in, 117, 211
        uric acid variations in, 108, 117
      ætiology of, histogenous theories of, 23
        nervous theories, 31
        summary of, 44
        theory of antecedent structural changes, 25
      age factor in, 40
      alcohol in, 361
      amino-acids in relation to, 64
      and fibrositis, incidence of, 221
      and granular kidney, clinical associations of, 130
      and immunity, early fallacies regarding, 10
      and nephritis, 242
      and other diseases, affinities between, 236
      and rheumatoid arthritis, resemblance between, 113
      and specific infective arthritides, analogies between, 194
      antiquity of, 1
      arterio-sclerosis associated with, 245
      articular, acute, differential diagnosis, 259
          localised, clinical diagnosis, 258
        chronic, 225
          alkalies in treatment of, 399
          blood changes in, 226
          clinical diagnosis of, 275
          distribution of, 226
          local measures in, 407
          medicinal and other modes of therapy, 397
          progress of disease, 228
          surgical treatment, 409
        classification of, author’s division, 38
        clinical diagnosis of, 252
        etiological diagnosis, 247
        manifestations of, 195
      as an infection, 177
      auto-intoxication theory, summary, 182
      beverages in, 359
      blood content in, 127
        uric acid and, relation between, 143
      choice of spa in treatment of, 440
      chronic, ankylosis in, 287
        confusion with chronic villous synovitis, 279
        diet in, 334
        differentiation of, from arthritis deformans, 16
        joint deformities of, 229
        of oligo-articular distribution, 278
        polyarticular, clinical features, 282
        polyarticular, differential diagnosis, 282
        tardy dissociation of, from chronic rheumatism, 15
        uric acid variations in, 109
      classification of, 35, 36
      climate and residence in treatment of, 418
      climato-therapy in, 418
      clinical account of, 200
      clothing and, 421
      collateral phenomena of, 219
      constipation and, 337
      cutaneous disorders in, 240
      definition of, 35
        author’s, 36
      derangement of gastro-intestinal tract as cause of, 171
      elimination of infective arthritides from domain of, 19
      endemic areas in, 46
      etiology of, 39
      evolution and life history of, 193
      excretion in, anomalies of, 112
      exercise in, importance of, 421
      false, ocular symptoms, 322
      glycocoll theory of, 65
      Greek physicians’ views of pathology of, 3
      growing infrequency and attenuation of, 12
      guanine, in swine, 100
      heredity and, 41
      hydrotherapy, general, in treatment of, 424
        local, in treatment of, methods of, 428
      hyperpyræmia in ætiology of, 30
      in big toe, differential diagnosis, 259
      infantile, 116, 305
      infective theory of, rise of, 171
        summary, 182, 183
      inflammatory phenomena in, cause of, 165
      initial attacks usually monarticular, 207
      initial outbreaks of, anomalous sites for, 267
        sites of, 37
      in relation to glycosuria, 236
      in relation to phlebitis, 239
      in the heel, 264
      in the instep, 262
      in the sole, 265
      inter-paroxysmal period, treatment in, prophylactic measures, 389
      introduction of word, 6
      irregular, 293
        conclusions regarding, 304
      isolation of acute articular rheumatism from, 15
      lead workers predisposed to, 50
      leanness in, 337
      leucocytosis in, 172, 189
      life history of, 193
      local foci of infection, 177
        treatment of, radical, 327
      local syncopes and asphyxias of hands in, 45
      long-continued, favouring onset of pre-senilism, 398
      lumbago associated with, 221
      massage, general, in treatment, 423
      metabolic phenomena correlated with postulated infective element,
          195
      mineral springs in treatment of, 431
      monarticular, chronic, differential diagnosis of, 276, 277
      morbid anatomy of, 39, 53
      morbid conditions associated with, treatment of, 411
      obesity in, reduction of, 356
      ocular disease in, 308
        frequency a factor in diagnosis, 316
      onset of, symptoms, 188
      organic predisposition to, 43
      other conditions classified as, in early times, 12
      pathogenesis of, earlier theories of, 21
      pedigree of, 14
      periodicity of, 191
      phenomena of, detailed account of, 207
      predisposing causes of, summary of, 52
      prevalence of, in Anglo-Saxon period, 2
      prognosis in, 244
      renal theory of, 117
      restriction of, by elimination of other disorders, 19
      retarded purin elimination in, 118
      retention capacity of tissues for uric acid in, 158
      retrocedent, 39, 296
        irregular manifestations of, 299
      sex incidence of, 41
      skiagraphy in diagnosis of, 286
      specific organism suggested, 175
      sthenic, febrile stage of, alcohol and, 333
      structural changes, 54
      sub-infection theory, summary, 182, 183
      subjective phenomena of, in relation to blood content and
        excretion
          of uric acid, radium emanations and, 438
      “the honour of,” 8
      theory of hepatic inadequacy, 28
      tophaceous, 39
      treatment of, 327
        diet in, 332, 342
        fallacy of fixed dietaries, 335
        gastro-intestinal asepsis in, 332
        hyperæmia, 429
        physical examination necessary before dieting, 336
        prevention of digestive disturbances, 335
      uratic deposits in, 54
        differentiation from nephritis, 129
        localisation of, 153
      uratosis in relation to, 149
      urea excretion in, 66
      uric acid content of blood in, 139
      uric acid excretion in, 108
        anomalies in, 117
      uric acid in relation to, 107
      uric acid theory of, 21
      uric acid, urea and creatine in blood in (table), 211
      uricæmia in, 125, 133
        not cause, but result, of, 148
      variations in excretion in, diagnosis of, 60

    =Gouty= arthritis, definition of, 20
      phlebitis, 240
      polyarthritis, acute, 214
      stigmata in types of fibrositis, 222

    “=Gravel=, cutaneous,” 203
      immunity from, 29

    =Greek= physicians, terms used for forms of gout, 3
      views of pathology of gout, 3

    =Guaiacum= in treatment of chronic gout, 403
      resin, effects on urine, 405

    =Guanase=, 100, 101

    =Guanine=, 73, 75, 77, 98
      gout in swine, 100

    =Gudzent= and Schade’s theories of uric acid in blood, 79

    =Gummata=, peri-bursal, 281
      peri-synovial, 281

    =Gums=, recession of, early, 45


    =Hæmatemesis=, gout following, 178

    =Hæmo-analysis=, 147

    =Hæmophilic= arthritis, differential diagnosis from chronic gout,
        285

    =Hæmorrhage=, retinal, and gout, 322

    =Hair=, premature whitening of, 45

    =Hallux= rigidus, differential diagnosis from gout, 262
      valgus with inflamed bunion, differential diagnosis from gout, 261

    =Haly Abbas’s= views on gout, 6

    =Hand=, gouty polyarthritis in, 214

    =Hands=, deformed, in chronic gout, 230
      incidence of tophi in, 162
      local syncopes and asphyxias in gout, 45
      palms of, tophi in, 235

    =Hare’s= theory of ætiology of gout, 30

    =Heart= affections in gouty subjects, 302

    =Heberden’s= differentiation of rheumatoid arthritis from gout, 17
      nodes, 41, 283

    =Heel=, gout in, 264
      referred pain in, differential diagnosis in, 264
        local sources of fallacy, 265

    =Hepatic= derangement in acute paroxysms of gout, 333
      inadequacy theory of ætiology of gout, 28

    =Heredity= in gout, 8, 28, 40, 41, 214

    =Herpes= in acute gout, 241

    =Hexose= group in vegetable nucleic acids, 98

    =Hippocrates=, aphorisms of, on gout, 4

    =Histogenous= theories of ætiology of gout, 23

    =Historical= survey, 1

    =Horbaczewski’s= experiments on uric acid, 73

    =Hot-air= baths, 429
      contra-indications to use of, 429

    =Hutchinson= on gout and rheumatism, 15

    =Hydrarthrosis=, bilateral, 281
      in chronic articular gout, 278

    =Hydrochloric= acid, secretion of, and gout, 173
      strong or fuming, in inter-paroxysmal periods of gout, 393
      variations in, and gout, 181

    =Hydro-therapy=, general, in treatment of gout, 424
      in acute gout, 385
      in treatment of gout, contra-indications and untoward
          complications, 425
        methods of application, 427
        prophylactic measures, 424
      local, in treatment of gout, 428

    =Hyperacidity= due to organic acids, 351
      in inter-paroxysmal periods of gout, 393

    =Hyperæmia=, treatment of gout by, 429

    =Hyperchlorhydria=, 181, 351
      associated with gout, treatment of, 415
      complicating gout, salt in diet contra-indicated, 350
      diet in, 353
      mineral waters suitable in treatment of, 446

    =Hyperpyræmia= in ætiology of gout, 30

    =Hyperuricæmia=, diet in, 354
      in gout, 140
      in non-gouty arthritis, 140
      ocular symptoms in, 321

    =Hypochlorhydria=, 351
      diet in, 354

    =Hypoxanthine=, 73, 75, 77


    =Indigestion=, intestinal, in gouty subjects, 181

    =Infantile= gout, 116, 305

    =Infection= in gout, local foci of, 177
        examination for in diagnosis of articular gout, 248
      theory of gout, 182, 183

    =Infections=, differential diagnosis from acute localised articular
          gout, 259
      specific, arthritic muscular and nerve lesions associated with,
        195
        diagnosis of, 19

    =Infective= element in gout, correlated with metabolic phenomena,
        195

    =Inflammation= and tophi formation, 164
      gouty, pus formation and, 191

    =Inflammatory= phenomena in gout, cause of, 165

    =Influenzal= arthritis, differential diagnosis from acute gouty
          polyarthritis, 272

    =Immunity= conferred by gout, early fallacies regarding, 10

    =Inosinic= acid, 93

    =Instep=, gout in the, 262

    =Intestinal= canal, source of microbe or toxin in gout, 181
      derangements, mineral waters suitable in treatment of, 448
      dyspepsia preceding gout, 182
      indigestion in gouty subjects, 181
      irrigation with radio-active waters, 439
      juices and wall, enzymes in, 100

    =Iodides= in treatment of chronic gout, 401
      value of, in renal and vascular changes, 403

    =Iodine-albumen= compounds in treatment of chronic gout, 402

    =Iodo-glidine= in treatment of chronic gout, 402

    =Iodo-protein= in treatment of chronic gout, 402

    =Ionisation= in treatment of acute gout, 387
      in treatment of chronic articular gout, 407

    =Iritis=, “arthritic,” 315
      diseases commonly associated with, 313
      gouty, “not” a clinical entity, 316
      in gout, 308
      relative incidence of, 313

    =Irregular= gout, 293

    =Isomeric= forms of uric acid, 81

    =Isomers= of purins, 81
      of pyrimidins, 81


    =Jaw=, formation of, 45

    =Jaws=, radiographs of, in treatment of gout, 328

    =Joint= cartilage, murexide reaction in, 153
      deformities of, chronic gout, 229

    =Joints=, diaphyses of, cystic changes in, 56
      rheumatism of, 14
      stiffness of, after acute attacks of gout, 212
      swellings, local character of, in osteo-arthritis, 283
        local character of, in rheumatoid arthritis, 284
      tophi in, 233

    =Juices=, gastric and intestinal, gout and, 173


    =Kidney= and kidneys, capacity of for eliminating uric acid, 125
      condition of, effect in blood content of uric acid, 138
      disease of, granular, and gout, clinical, association, 130
        joint examination in, results of, 129
      disease of, and gout, 242
      functionally deficient in late stage of gout, 119
      functional disorders of, 27, 28
      functional efficiency of, tests for, 338
      gouty, histological changes in, 127
      guanase in, 100
      uric acid elimination in, 119

    =Knee=, gouty polyarthritis in, 214
      site of primary attack of gout, 267

    =Kossel’s= discovery of purin bases, 73


    =Labile= protein, 59

    =Latham’s= theory of hepatic origin of gout, 29

    “=Lead= gout,” 50

    =Lead=, elimination by iodides, 403
      poisoning, blood content in, 122, 123, 127
        ocular symptoms in, 321
        purin metabolism in, 115
      workers, predisposed to gout, 50

    =Leanness= in gout, 337

    =Lehmann’s= analysis of tophi, 150

    =Leucocytosis=, 24, 27
      during acute attacks of gout, 172
      in gout, 189
      in gouty polyarthritis, 216
      relation to uric acid excretion, 95

    =Leucopenia=, 96
      in gout, 189

    =Leukæmia=, blood content in, 122, 123
      ocular symptoms in, 321
      uric acid in urine in, 95

    =Levy’s= (Magnus) researches on gout, 107

    =Limbs=, integument of tophi in, 235

    =Lime= salts, focal absorption of, in bones, 288

    =Liniments= in treatment of acute gout, 386

    =Literature= of various periods, references to gout in, 3

    =Lithæmia=, 294
      tendency to, 28, 33

    =Lithiasis=, 29

    =Lithium= salts in treatment of chronic gout, 400

    =Lithuria=, 29

    =Liveing’s= theory of ætiology of gout, 31

    =Liver=, diseases of, amino-acids in, 59
      disorders of, functional, mineral waters suitable in treatment of,
          447
      enzymes in, 99
      functional efficiency of, tests for, 338
      glycogenic distension of, 31
      guanase in, 100
      main centre of production of urea, 63

    =Living=, style of, effect on incidence of gout, 2

    =Locality=, factor in gout, 45
      incidence of, in acute gout, 208

    =Lucian= of Saramosta’s views on gout, 4

    =Lumbago=, associated with gout, 221
      treatment of, 411

    =Lung=, guanase in, 100

    =Lymph= spaces, purins in, 146
      stream, sodium ions in, 146

    =Lymphangitis=, co-existent with gout, 58
      in gout, 190

    =Lymphatic= gland, enlargement of, in gout, 190

    =Lymphatics=, purins in, 146


    =Malt= liquors in gout, 362

    =Marchand’s= analysis of tophi, 150

    =Massage=, general, in treatment of gout, 423
      in after-treatment of acute gout, 385, 387

    =McCarrison’s= views on effect of absence of vitamines on functional
          efficiency, 340

    =McClure and McCarty’s= researches on bone conditions as revealed by
          skiagraphy, 288, 289

    =Meat=, over-eating of, functional damage resulting from, 65

    =Meningococcal= arthritis, differential diagnosis from acute gouty
          polyarthritis, 272

    =Menstruation=, effect of, on incidence of gout, 41

    =Mental= over-exertion and gout, 51

    =Metabolic= phenomena of gout correlated with postulated infective
          element, 195

    =Metabolism=, alterations in, 30
      inborn errors of, 69
      nuclein, 71
      protein, 59, 61

    =Metastasis= in relation to ocular gout, 314
      gouty, 297

    =Metatarsalgia=, differential diagnosis from gout, 262

    =Methyl-purins= as source of uric acid, 85

    =Microbic= theory of gout, 175

    =Miescher’s= researches on spermatozoa, 72
      on the nucleus, 71

    =Milk= diet in acute paroxysms of gout, 332

    =Mineral= springs, 431
      waters as beverage in gout, 360

    =Monarticular= gout, differential diagnosis of, 276, 277

    =Morphia=, hypodermic injections of, in acute gout, 383

    =Mouth=, examination of, in diagnosis of articular gout, 248
      in treatment of gout, 328
      local foci of infection, results of, 184

    =Murchison’s= theory of ætiology of gout, 28

    =Murexide= reaction in joint cartilage, 153

    =Muriated= chloride waters, spas for, 441
      sulphated waters, spas for, 442

    =Muscles=, affections of, in gout, 195
      voluntary, relation of creatinine to, 68

    =Muscular= exercise, uric acid excretion increased by, 93

    =Myeloma=, waste of albumoses in, 59


    =Nails=, striated, fluted and brittle, 45

    =Nasal= affections, radium emanations for, 438
      disorders, gout and, 178

    =Naso-pharynx=, examination of, in treatment of gout, 328
      foci of infection, 53

    =Necrosis=, local, in uratic deposition, 152
      relationship to gout, 25

    =Nephritis=, acute and chronic, blood content in, 127
      chronic, spa treatment of, 452
      complicating gouty polyarthritis, 219
      early, blood content of uric acid, urea and creatine, similarity
        to
          gout, 120
      gout and, 242
      gouty, treatment of, 416
      uratic deposits in, 128
        differentiation from gout, 129
      uric acid, urea and creatine in blood in (table), 121
      uricæmia in, 120
      uricæmia not peculiar to, 124

    =Nerve= arthropathies, differential diagnosis from chronic gout, 284
      Charcot’s discovery of, 18

    =Nervous= phenomena of gout, 188, 304
      system, effect of gout on, 219
      theories of ætiology of gout, 31

    =Neuralgia=, plantar, differential diagnosis from gout, 266

    =Neuritis=, alcoholic peripheral, 238
      glycosuric peripheral, 238

    =Neuro-lymphatismus=, 116

    =Neuro-retinitis= in the gouty, 324

    =Neurosis=, gouty, 31

    =Neuroses=, paroxysmal, of gout, 188

    =Nose=, alæ of, tophi in, 235

    =Nuclease=, 100

    =Nucleic= acid, 72, 77
      characteristic constituents of, 78
      disruption of, 100
        in body, 74
      formation of uric acid from, 98
      isolation of, 71
      metabolism of, in gout, 69
      molecules, 101
      of animal origin, structural formula of, 99
      physiological derivation of uric acid from, 73
      uric acid a derivative of, 73

    =Nucleic-acidase=, 100

    =Nuclein=, discovery of, 72
      metabolism, 71
        chemistry of, 60

    =Nucleins=, 77
      phosphoric acid group in, 112

    =Nucleo-proteins=, 77

    =Nucleosidases=, 101

    =Nucleosides=, 87, 100

    =Nucleotidase=, 100

    =Nucleotides=, 100

    =Numbness= after acute attacks of gout, 212


    =Obesity= and gout, 245
        Ebstein’s views of affinity, 280
      in gout, 337
      reduction of, 356

    =Occupation= and gout, 48

    =Occupations= predisposing to gout, 50

    =Ocular= disease in gout, 308

    =Œdema= in acute gout, 212
      in gouty conditions, 191

    =Olecranon= bursa, involved in gout, 215
      tophi in, 233, 235

    =Oligo-articular= distribution of chronic gout, 278

    =Oral= sepsis in gouty subjects, 179
      radium emanations and, 438
      treatment of, in gout, 330

    =Ord’s= theory of ætiology of gout, 25

    =Osler’s= views on gout, 36

    =Osteoarthritis=, acute, differential diagnosis from gout, 261
      and chronic articular gout, 275, 276
      co-existing with gout, 19
      differential diagnosis from chronic articular gout, 278
      differential diagnosis from chronic gout, 283
      in ancient civilisations, 1
      local characters of joint swellings, 283
      of hip, with auricular tophi, 226
      skiagraphy in differential diagnosis of, 291

    =Overeating= and gout, 48
      plus alcohol, cause of gout, 49

    =Oxaluria= associated with gout, treatment of, 413
      examination for, in treatment of gout, 337
      spa treatment of, 449

    =Oxidation= of purin, products of, 77

    =Oxy-purins= as source of uric acid, 84
      formation of, 102


    =Pain= and tophi formation, 164
      in acute gout, 208
      in auricular tophi, 233
      referred, in heel, differential diagnosis of, 264

    =Pains=, premonitory articular, in acute localised gout, 204

    =Painters=, predisposed to gout, 50

    =Pancreas=, enzymes in, 99

    =Pancreatic= inefficiency, evidence of, in diagnosis of articular
          gout, 250

    =Pancretin=, 392

    =Papain=, 392

    =Parke’s= theories of ætiology of gout, 23

    =Parotitis=, acute, gout following, 53
      in gout, 179

    =Patella=, tophi in, 235

    =Pathological= states influencing endogenous uric acid excretions,
        94

    =Paulus Ægineta’s= views on gout, 6

    =Pedigree= of gout, 14

    =Pentosuria=, 69

    =Peri-bursal= gummata, 281

    =Perineum=, uratic deposits in, 235

    =Periodic= variations in excretion of endogenous uric acid, 94

    =Periodontitis=, chronic, 329

    =Peri-synovial= gummata, 281

    =Pes planus=, differential diagnosis from gout, 263

    =Pharyngeal= affections, radium emanations for, 438

    =Pharyngitis=, acute and chronic, in gouty subjects, 179
      acute, gout following, 53

    =Pharynx=, examination of, in diagnosis of articular gout, 249

    =Phlebitis=, gout in relation to, 239
      gouty, treatment of, 415
      in limb in articular gout, 190
      spa treatment of, 450
      treatment of gout and, 328

    =Phospho-nuclease=, 102

    =Physical= examination, necessity for, before dieting, in treatment
          of gout, 336
      over-exertion and gout, 51

    =Physiognomy= of the goutily disposed, 44

    =Pinna=, small red swellings on, 204

    =Planchon’s= views on gout, 6

    =Plantar= neuralgia, differential diagnosis from gout, 266

    =Pleurodynia= associated with gout, treatment of, 412

    =Plumbers=, predisposed to gout, 50

    =Plumbism= and gout, 60
      purin metabolism in, 115

    =Pneumococcal= arthritis, differential diagnosis from acute gouty
          polyarthritis, 272

    =Podagra=, 12
      Greek designation, 3

    =Polyarthritis=, articular, acute, differential diagnosis of, 269,
        270
      gouty, acute, 214
          clinical diagnosis of, 268
          diet in, 334
        blood changes in, 216
        distribution of, 214
        effect on nervous system, 219
        simulating erysipelas, 215
      non-gouty, uric acid blood content in, 141

    =Polyarticular= distribution of gout, 214

    =Poly-nucleotides=, 100

    =Port= wine in gout, 364, 368

    =Portal= blood, amino-acids in, 62

    =Post-critical= stage of depression, 211

    =Potash= compounds in treatment of chronic gout, 400

    =Potassium= in gouty tophi, 151

    =Prescriptions= for use in acute gout, 375, 377, 378, 379, 380, 386,
          391
      for use in chronic gout, 401, 405, 406
      for use in inter-paroxysmal periods of gout, 391, 392, 393, 394

    =Pre-senilism=, long-continued gout favouring, 398

    =Protamine=, 72

    =Protein=, amino-acids in, number of, 64
      chemistry of, 60
      labile, 59
      metabolism, 59, 61
        urine content of urea, etc., in, 59
      tissue, 59

    =Proteins= and their derivatives, 88
      in diet of gouty, 345

    =Pulse= quickened in gout, 189

    =Purgatives= in treatment of acute gout, 374

    =Purin= bases, toxicity of, discussed, 168
      bodies, 34, 48, 63
        chemistry of, 75
      diet, uric acid excretion in, 86
        “free” diet, 355
        uric acid blood content in, 137
        uric acid excretion in, 86
      elimination, retarded, in gout, 118
      metabolism, chemistry of, 60
        in chronic alcoholism, 115
        in other disorders, 113
        in plumbism, 115
      nuclease, 102
      nucleus, arrangement of atoms, 76
      oxidation of, products of, 77
      scheme illustrating probable stages in passage through body, 101
      synthesis in mammals, 97
      unexcreted, fate of, 87

    =Purins=, discovery of, 72
      endogenous, 83, 87
        source of, 88
      exogenous, 83
        as source of uric acid, 84
        effect of atophan on, 110
        effect on uric acid blood content, 137
      isomers of, 81
      of vegetable origin, 77

    =Pus= formation, non-existence of, in gouty inflammation, 186, 191

    =Pyæmia=, differential diagnosis from gout, 259

    =Pyæmic= conditions confounded with gout, 191

    =Pyorrhœa= alveolaris, and gout, 178
      and treatment of gout, 329
      exclusion of, in diagnosis of articular gout, 248

    =Pyrexia= in acute gout, 210
      in gout, 189

    =Pyrimidine= bases, 77

    =Pyrimidins=, isomers of, 81


    =Quadriurate= in blood, 78, 79

    =Quinic= acid in treatment of acute gout, 383

    =Quinine= in treatment of acute gout, 383


    =Race= incidence of gout, 45-48

    =Radio-active= properties of thermal waters, 427
      waters, physical properties of, 434

    =Radium= emanation, increased excretion of uric acid through, 437
      influence on uric acid metabolism, 436
      physiological action of, 435
      subjective phenomena of gout in relation to blood content and
          excretion of uric acid and, 438
      therapeutic action and application, 438

    =Regular= gout, 13

    =Renal= changes in gout, 54
      defect, uricæmia not necessarily due to, 123
      depression, functional, 119
      disease, abnormal protein loss in, 59
      theory of gout, 117
      uric acid infarcts, 151

    =Residence=, choice of, 420

    =Respiratory= disorders, spa treatment of, 450
      organs, affections of, in gout, 303

    =Retinitis=, nephritic, 324

    =Retrocedent= gout, 39, 296

    =Rhazes’s= views on gout, 6

    =Rheumatism=, acute articular, differential diagnosis from acute
          gouty polyarthritis, 269, 270
          isolation from gout, 15
          muscular and nervous lesions associated with, 194
        confused with gout, 215
      chronic, tardy dissociation of, from chronic gout, 15
      differential diagnosis from gout, 259
      early use of term, 14
      muscular, identification of, 16

    =Rheumatoid= arthritis, 17
        and gout, resemblance between, 113
        differential diagnosis from chronic gout, 284
        disturbance of purin metabolism in, 112
      or atrophic arthritis, differential diagnosis from acute
          polyarticular gout, 272

    =Roberts’, Sir William=, views on gout, 36


    =Salicylate= group as alternative remedy in treatment of acute gout,
          381
      of colchicine in treatment of acute gout, 379

    =Salicylates= in treatment of acute gout, contra-indicated, alkalies
          as substitute, 383
      in treatment of chronic gout, 401

    =Salisbury= diet in hyperchlorhydria, 353
      method in reduction of obesity, 357

    =Salt= in diet of gouty, 350

    =Scapular= region, uratic deposits in, 235

    =Scheele’s= discovery of uric acid, 8

    =Schnee= four-cell bath in ionisation, 408

    =Sciatica= associated with gout, treatment of, 411, 412

    =Scudamore’s= definition of gout, 35

    =Seneca’s= views on gout, 5

    =Septic= conditions confounded with gout, 191

    =Serapion’s= views on gout, 6

    =Serous= membranes, uratic deposits in, in nephritis, 128

    =Sex= incidence in gout, 41

    =Shivering= at onset of acute paroxysm of gout, 188

    =Sidonal= in treatment of acute gout, 383

    =Silk= as underwear, 421

    =Sinusitis=, latent, cause of systemic infections, 331

    =Skiagraphy= in diagnosis of gout, 286
      in diagnosis of villous synovitis, 281
      in differential diagnosis of hypertrophic or osteo-arthritis, 291
      in differential diagnosis of infective arthritis, 290
      in differential diagnosis of rheumatoid or atrophic gout, 291

    =Skin=, action of, consideration of, in treatment of gout, 337
      appearances of, and gout, 45
      defective elimination by, in chronic gout, treatment of, 400

    =Sodium= biurate crystals in synovia, 52
      ions in lymph stream, 146
      mono-urate compound, 81
      salicylates of, in treatment of acute gout, 382

    =Sole=, gout in, 265

    =Solubilities= of uric acid and urates in gouty blood, 82

    =Sool-Bader= baths, 427

    =Spa=, choice of, in treatment of gout, 440
      treatment, duration of course of, 453
        in acute gout, 385
        of gout, principles of, 434
        remarks on, 452

    =Spas= from a national aspect, 454

    =Spermatozoa=, Miescher’s researches in, 72

    =Spirits= in gout, 370

    =Spleen=, enlargement of, in gout, 190
      enzymes in, 99
      functional efficiency of, tests for, 338

    =Starchy= foods in diet of gouty, 347

    =Static= foot deformities, differential diagnosis from gout, 261

    =Stone= in Norfolk, 29

    =Streptococci= in tonsils, 183

    =Sub-infection= theory of gout, 182, 183

    =Sub-thermal= baths, 428

    =Succus= entericus, action on nucleic acid, 100

    =Sugar= in diet of gouty, 347

    =Sulphated= alkaline waters, spas for, 442
      waters, 441, 442

    =Sweetbreads= in diet of gouty, effect of, 345, 346

    =Swine=, guanine gout in, 100

    =Sydenham’s= differentiation of rheumatism from gout, 15
      views on gout, 7

    =Syncopes=, local, of hand, in gout, 45

    =Synovia=, appearance in, in acute gout, 52

    =Synovial= fluid, reaction of, 52

    =Synovitis=, gouty, relation to local foci of infection, 185
      gummatous, differential diagnosis from chronic articular gout, 277
      of knees, differential diagnosis from gout, 264
      of tendo Achilles in referred pain in heel, 265
      perforative, 57
      villous, chronic, confusion with chronic gout, 279
        clinical symptoms of, 280
        static and non-gouty in origin, 280

    =Synthetic= formation as source of uric acid, 84
      of uric acid, 96

    =Syphilis=, articular, muscular and nerve lesions associated with,
        194

    =Syphilitic= arthritis, secondary, differential diagnosis from acute
          gouty polyarthritis, 271
      disease of tarsal joints, differential diagnosis from gout, 263


    =Taka-diastase=, 392

    =Tarsal= joints, gonococcal arthritis of, differential diagnosis
        from
          gout, 263
      involved in gouty polyarthritis, 214
      tuberculous and syphilitic disease of, differential diagnosis from
          gout, 263

    =Tartareous= nature of tophi, views on, 8

    =Tea= as beverage in gout, 361

    =Teeth=, characteristic, in gout, 45
      conditions in gout, 178
      devitalised, examination of, in treatment of gout, 328
      foci of infection, 53

    =Temperament=, and gout, 44

    =Temperature= curve of gout, 188

    =Tendo= Achilles, involved in gout, 215

    =Tendon= sheaths, involved in gout, 195

    =Tendons=, gouty polyarthritis in, 214
      uratic deposits in, 153

    =Test= meals for HCL variations, 336

    =Tests=, modern, for uric acid determination, disabilities of, 147

    =Theobromine=, 85

    =Theophyllin=, 85

    =Throat=, gouty, 45

    =Thymine=, 98

    =Thyminic= acid, 80
      in treatment of acute gout, 383

    =Thymus=, enzymes in, 99
      gland, nucleic acid derived from, 98
      in diet of gouty patients, effect of, 345, 346

    =Tibia=, tophi in skin over, 235

    =Tissue= affinities for uric acid, 157
      protein, 59

    =Tissues=, human, concentrations of uric acid in, 159
      retention capacity of, for uric acid, 158
        effect on blood content, 138

    =Toe=, big, gout in, differential diagnosis of, 259
      initial outbreak of gout in, 37, 188

    =Tonsil=, site of infection in gout, 180

    =Tonsillar= sepsis, gout and, 178

    =Tonsillitis=, acute, gout following, 53
      in gouty subjects, 179
      treatment of, in gout, 330

    =Tonsils=, examination of, in diagnosis of articular gout, 249
      foci of infection, 53
      streptococci in, 183

    =Tophaceous= deposits in chronic articular gout, 227
      gout, 39

    =Tophi=, analysis of, 150
      antedating articular attacks, 202
      auricular, 202
        pain in, 233
      clinical evolution of, 162
      constitution of, 149
      constitutional influences in, 161
      diagnostic status of, 252
      difficulty in detecting, 256
      early stages of, confused with chilblains, 164
      early views as to nature of, 7
      evolution and distribution of, 231
      formation preceding arthritic attacks, 164
      frequency of, in gouty arthritis, 255
      gouty, causation of, 154
        formation of, 151
        localisation of, 153
        radiating, concentric and laminated structure of, 152
        urate of soda, 150
      importance of, in diagnosis of acute gouty polyarthritis, 269
      in diagnosis of gout, 38
      in eyes, significance of, 311
      inflammatory nature of swellings in, 163
      in relation to arthritis, 254
      in relation to uricæmia, 155
      sites of, 233
      stage of small red swellings, 163
      treatment of, in chronic articular gout, 407

    =Tophus= formation in acute gout, 212
        premonitory symptoms of, 203
      in ear, sign of gout, 202

    =Trauma=, local, effect on gout, 53

    =Traumatic= lesions, differential diagnosis from gout, 260

    =Trousseau’s= views on gout, 36

    =Tuberculous= disease of tarsal joints, differential diagnosis from
          gout, 263
      joint disease, differential diagnosis from chronic articular gout,
          277

    =Toxæmia=, alimentary, hydrochloric acid, 394
      chronic, 182

    =Toxicity=, low, of chemical products, in gout, 69
      non-, of uric acid, 166


    =Ulna=, tophi in skin over, 235

    =Uracil=, 98

    =Urate= of soda in gouty tophi, 150

    =Urates=, deposition of, in eye, 309

    =Uratic= depositions as criterion of gout, 37
      deposits in gout, 54
        in gout and nephritis, differentiation of, 129
        in gout, localisation of, 153
        in nephritis, 128

    =Uratosis= in gout, 149

    =Urea= and glycocine, interaction between, 84
      end-product of protein metabolism, 63
      excretion in gout, 66
      excretion of ammonia as, 63
      formation of, 62
        Folin and Denis’s deductions, 64
        seat of, 63
      in blood in gout and nephritis (table), 121

    =Ureters=, ligature of, 26

    =Uric= acid, 75, 77
      a normal constituent in blood, 135
      an end-product, 70
      as a derivative of nucleic acid, 73
      blood content of, in various animals, 135
        variations independently of diet, 142
      chemical constitution of, 75
      concentrations in human tissues, 159
      content of blood and attacks of gout, relation between, 143
        in gout, 139
      deposition of, 22, 34
      destruction of, 98, 104
      determination of, disabilities of modern tests, 147
      diathesis, 294, 295
      discovery of, by Scheele, 8
      estimation of, sources of fallacy, 145
      excretions of, amount of, 75
        exogenous, 85
        in acute gout, 211
        in gout, 108
          anomalies in, 117
        increased by radium emanation, 437
        relation of leucocytosis to, 95
      exogenous purins as source of, 84
      formation of, Amberg and Jones’s scheme of, 103, 104
        from nucleic acid, 98
      gravel, spa treatment of, 451
      in the blood, 78
        forms of, 145
        in gout and nephritis (table), 121
        of gouty patients, discovery of, 21
        organic combinations of, 79
      infarcts, renal, 151
      in relation to gout, 107
      isomeric forms of, 81
      kidney capacity for eliminating, 125
      metabolism, influence of radium emanations on, 436
      non-toxicity of, 166
      of blood in disease (table), 137
      output, endogenous, lowered, 111
        exogenous, retarded, 109
      physical properties of, 78
      retention, capacity of tissues for, 158
      solubilities of, 154
      sources of, 83
      synthetic formation of, 84, 96
      theory of gout, 21
      tissue affinities for, 157
      variations in acute gout, 108
      variations in chronic gout, 109
      Wollaston’s researches on, 8

    =Uric-acidæmia=, 295

    =Uricæmia= and gout, 125
      in gout, 133
      in nephritis, 120
      not cause, but result, of gout, 148
      not necessarily due to renal defect, 123
      not peculiar to nephritis, 124
      significance of, 145
      tophi in relation to, 155

    =Uricase=, 87, 104
      absence of, in man, 104

    =Uricolysis=, 104

    =Uricolytic= enzyme, 105
      ferment, absence or diminution of, 106

    =Urine=, alkapton in, 59
      analysis of, in metabolism of gout, 113
        in treatment of gout, 337
      children’s, creatine in, 68
      cystin in, 59
      effects of guaiacum resin on, 405
      examination of, in diagnosis of articular gout, 250
      gouty, glyoxylic acid in, 65
      human, daily excretion of uric acid, amount of, 83
      scanty, before paroxysm of gout, 205

    =Urosin= in treatment of acute gout, 383


    =Vaccine= therapy in treatment of gout, 331

    =Vapour= baths, 428

    =Vegetable= cells, nucleic acid derived from, 98

    =Vegetables= in diet of gouty, 348

    =Veins=, engorged, before paroxysm of gout, 205

    =Venesection=, 4
      gout following, 178

    =Vichy= bath, 428

    =Vidal’s= atrophic form of arthritis deformans, 18

    =Vinegar= in diet of gouty, 350

    =Viscera=, functional capacity of, tests of, 338

    =Visceral= organs, tendency to fibrosis in gout, 186

    =Vitamines=, 340

    =Volumetric= method of determination of uric acid in blood (Curtman
          and Lehrman), 134

    =Vomiting= in acute paroxysms of gout, 333


    =Wade’s= theory of nervous origin of gout, 32

    =Water=, hot, advantages of, 360
      value of, as beverage in gout, 359

    “=Water-soluble B=,” 340

    “=Water-soluble C=,” 340

    =Watson’s= (Chalmers) researches on gout, 107, 172

    =Weir-Mitchell= method in reduction of obesity, 357

    =Whisky= in gout, 364, 370

    =Wines= as beverages in gout, 364
      general rules, 367
      individual and, 365
      importance of quality of, 366

    =Wollaston’s= researches on uric acid, 8

    =Wrist=, site of primary attack of gout, 267


    =Xanthine=, 75, 77

    =Xanthine-oxidase=, 99

    =Xanthosine-hydrolase=, 102

    =X-ray= examination of alimentary tract in treatment of gout, 336


    =Yeast=, nucleic acid derived from, 98


THE WHITEFRIARS PRESS, LTD., PRINTERS, LONDON AND TONBRIDGE.

*** END OF THE PROJECT GUTENBERG EBOOK 69874 ***