developed show that the larger proportion of cases occurs in the decade
from thirty or forty. It is rare before twenty, and the frequency
diminishes rapidly after sixty. Some well-authenticated cases have been
observed before puberty in children in whom the hereditary taint was
strongly developed. Gairdner claims to have seen several cases in
infants at the breast. Trousseau saw a case in a boy aged six, and
Garrod in a youth of sixteen. At the other extreme Garrod reports a
first attack at the age of eighty, and another in the ninetieth year.
The cases at the extremes of age are certainly rare, and other causes
of arthritic inflammation might easily be invoked to explain them. It
is a significant fact that the largest proportion of attacks of acute
articular gout occurs after the period of complete development is ended
and before the period of degenerative changes has begun, when the
necessities of growth have ceased and food is required only for the
nutrition of the tissues, the maintenance of vital energies, and the
demands of work.
Much stress was laid by the earlier writers on the effect of
temperament as a predisposing cause of gout. The vague ideas involved
in the classification of mankind according to temperament may be said
to have lost their influence in the scientific conceptions of modern
pathology. Gout is observed in persons exhibiting the most diverse
peculiarities in physical conformation and physical disposition. The
true interpretation of the facts in regard to the relations of
temperament to gout, so far as those relations exist, would seem to be
that the conditions which give rise to gout are responsible also for
the physical and moral idiosyncrasies of gouty subjects.
A vicious hygiene may be regarded as one of the chief predisposing
causes of gout. The disease is essentially one of advanced
civilization, and is alike the product of the luxury and the misery
which a high civilization entails. It is a common error to suppose that
gout is the consequence only of luxurious living. If the essential
cause of the disease is the circulation of imperfectly oxidized plasma,
then there are two ways in which this defective oxidation may be
brought about: either there is an excess of food ingested beyond the
capacity of the individual, under the most favorable conditions, to
consume, or the conditions of oxidation may be so impaired that the
complete combustion of even a moderate supply of food is impossible.
Perfect oxidation requires an even balance between the amount of food
ingested and the oxygen inhaled. A consideration of this axiom explains
several circumstances in the history of gout. As has been remarked, the
disease is rare during the period of growth and development, when the
processes of nutrition are active and the consumption of food in
excessive quantities is rendered possible by the large demands for the
needs of the growing body and for the development of active energy. It
is common in adult life when the processes of nutrition are less
active, when growth is complete, and when the supply of food must be
regulated according to the amount of energy to be developed. It must
also be observed that while the disease is most frequently caused by
excesses in the consumption of {111} food, it is also often the
consequence of an insufficient supply of pure air; hence we find it
often among those who cannot be accused of gluttony, but whose
occupations or poverty compel them to live and work in a vitiated
atmosphere.
The influence of alcoholic liquors in the production of gouty dyscrasia
is generally acknowledged. There seems to be a striking difference,
however, in the effects of the distilled and fermented preparations of
alcohol in this respect. Gout is certainly more prevalent in countries
where large amounts of fermented liquors are used than in those where
distilled spirits are chiefly consumed. The disease is more prevalent,
for example, in England than in Scotland or Ireland, especially among
the lower classes; it is said also that it is rare in Russia and
Poland, where spirits are more exclusively used. There is a difference
also in the predisposing influence of the different varieties of
fermented liquors in the production of gouty dyscrasia. The heavier
wines, sherry, madeira, and port, are known to be more mischievous in
this respect than the lighter wines of France and Germany, though there
is abundant clinical evidence of the fact that even these wines, and
especially the richer clarets. Burgundies, and Rhine wines, frequently
give rise to acute gout and the gouty habit. There can be no question
as to the pernicious effects of the malt liquors as gout-producers. The
great frequency of gouty diseases particularly among the lower classes
who consume these beverages in large quantities is undeniable. This is
true especially of the stronger English and Scotch ales, and to a less
degree of the lighter English, American, and German beers. The effect
of cider and perry as gout-producers is also well recognized. It has
been observed in certain districts of England where cider is largely
consumed, and, though acute articular gout is said not to be a common
disease in New England, where cider has always been much used, there
can be no question that it often leads to the development of the
irregular forms of gout. As one of the forms of fermented alcoholic
beverages containing, in its fresh state especially, a large amount of
sugar, it favors the production of the acid dyspepsia which is a common
antecedent in the formation of a gouty dyscrasia.
In 1854, Garrod called attention to the fact that a considerable
proportion of the gouty patients in hospital practice--at least 30 per
cent.--was represented by painters and other workers in lead. This
statement has since been confirmed by other observers, and the
association of the characteristic symptoms of this form of metallic
poisoning, such as the blue line on the gums, colic, and the different
forms of paralysis, with both articular and visceral gout, especially
the contracted kidney, is certainly frequent. The relation, however, of
saturnine poisoning to gout in this association is not easy to
determine, Garrod himself pointing out that while the women in the
lead-works frequently had the colic, they but rarely had gout. The
difference in susceptibility of different individuals to all forms of
metallic poisoning is well recognized. It is more strikingly observed
perhaps in mercurial and arsenical poisoning than in that of lead. It
is well known that the internal use of lead as an astringent in cases
of hemorrhage and intestinal catarrh is occasionally, though very
rarely, followed by the evidences of lead-poisoning. This difference in
susceptibility is perhaps explicable on the theory that persons
inclined to gout have less power in eliminating the {112} metal than
those who are not gouty, so that it is possible that plumbism is the
effect rather than the cause of gout, as has been commonly supposed.
Tanquerel des Planches found none of those changes in the kidneys as
the result of plumbism such as are frequently met with in gout, and
Rosenstein, who was able to produce saturnine epilepsy in dogs, found
no renal changes to have occurred. Charcot and Gombault in recent
experiments of feeding guinea-pigs with lead found changes in the
kidneys similar to those produced by tying the ureters.
EXCITING CAUSES.--Paroxysms of acute or subacute gouty inflammation of
the joints, skin, or mucous membranes, as well as the neuroses of gouty
origin, are excited by a variety of causes: errors in diet, both as to
quantity and as to specific articles; excesses in the use of fermented
liquors--even moderate indulgence, in persons with strong gouty
tendencies--are perhaps the most common exciting causes. Sudden changes
in temperature, and especially sudden changes in barometrical pressure,
sometimes excite and often aggravate the sufferings of gouty persons.
Blows, contusions, and mechanical strain frequently determine arthritic
attacks; the large proportion of paroxysms affecting the
metatarso-phalangeal joint of the great toe is explained by the fact
that this joint is more exposed than any other to strain and injury.
Finally, nervous exhaustion, from any cause, from overwork or sexual
excesses, from grief, anger, or shock, may provoke any of the
inflammatory or neurotic consequences of this disease.
PATHOLOGY.--It would be impossible in the limits of this article to
review the many theories that have prevailed in regard to the pathology
of gout, or even to discuss fully those that may be said to divide
professional opinion at the present day. Since the discovery, by
Garrod, of the salts of uric acid in the blood-serum of gouty patients,
the humoral pathology of gout has certainly had the largest number of
adherents.
The lithæmic pathology may be said to be based primarily upon the
chemical theory of digestion or food-transformation. This theory
proceeds upon the idea that every atom of albuminous or carbonaceous
food that enters the body, whether it goes to the construction of
tissue or is destined for the direct conversion of potential into
active energy, is finally eliminated, for the most part, as urea,
carbonic acid, and water. This transformation, of course, is supposed
to be effected by a process of oxidation, but neither the exact mode of
transformation nor the share which the different organs and tissues
take in its accomplishment can be said to be certainly known. Recent
investigations seem to indicate that the liver is chiefly concerned,
not only in the metamorphosis of the carbohydrates, but also in the
formation of urea, so that the arrest in the conversion of starches and
sugars which results in glycosuria, and the check in the metabolism of
the proteids which give rise to lithæmia, may both have their origin in
hepatic derangement. The not infrequent association of glycosuria and
lithæmia in the same patient, and the frequent alternation of gout and
saccharine diabetes in gouty families, are significant facts in support
of the common origin of these diseases.
The purely chemical theory of gout and diabetes, that they are diseases
of suboxidation--a theory most ably advocated by Bence Jones[2]--has
{113} much to commend it from the valuable suggestions which it affords
in the clinical management of these maladies; but it must be
acknowledged that while a defective oxidation seems to be an essential
factor in the production of gout and diabetes, it is impossible to
reduce the process to the simplicity of a chemical equation. It cannot
be claimed that the complex chain of transformations which organic
chemistry has demonstrated in the destructive metamorphosis of albumen
and starch in the laboratory is represented in the vital chemistry of
the body. All that can be said in the present state of knowledge is,
that the metabolism of food is in its nature a chemical analysis,
modified and regulated by vital force, and resulting in the building up
of tissues and in the conversion of potential into active energy.
Imperfect blood-elaboration must depend upon much besides a disturbance
of the balance between the amount of food ingested and the oxygen
inhaled, though this must unquestionably be an important factor in its
production. Heredity and the mysterious influence of the nervous system
complicate the problem of the malnutrition which leads to gout, in such
a way that while the general proposition may be maintained that gout is
a disease in which suboxidation occurs, it is not possible to affirm
whether suboxidation is the essence of the disease or only one of its
phenomena.
[Footnote 2: _Lectures on Some of the Applications of Chemistry and
Mechanics to Pathology and Therapeutics_, H. Bence Jones, London,
1867.]
It is probable, however, that the pathogenesis of the gouty dyscrasia
involves a much more complex process than the simple accumulation of
uric acid salts in the blood. Uric acid, like urea, is one of the
normal results of the metamorphosis of the albuminous foods and
tissues. In birds and reptiles it takes the place of urea as the final
issue of this metabolism. It has been supposed, as one atom of uric
acid can be split by oxidation into two atoms of urea and one of
mesoxalic acid, that uric acid was the penultimate of urea, the result
of a lower degree of oxidation. It is by no means certain, however,
that it is a necessary antecedent of urea. In birds, who consume by
their rapid breathing an enormous proportion of oxygen, as well as in
the slow-breathing reptilia, the nitrogenous excrements are in the form
of urates; and under such divergent conditions it is impossible to
explain the variations in the proteid metabolism by varying degrees of
oxidation. The only reason that can be assigned for the elimination of
the nitrogenous waste in some animals in the form of urea and in others
in that of urates is the teleological one that the urea is destined for
a fluid and the urates for a solid excretion.
But apart from these physiological objections to the theory that uric
acid is necessarily the offending substance in gout, it is well known
that uric acid salts accumulate in the blood in febrile diseases, in
disorders of digestion, and in anæmia--notably in splenic anæmia--and
do not produce either the symptoms or lesions of gout. Todd maintained
that gout might occur without an excess of uric acid in the blood; and
it is certain that in the atonic and irregular forms of the disease
uric acid may not be found in excess in the blood or appear in excess
in the urine. Another significant circumstance in the history of gouty
persons tending to show that uric acid may be, after all, only an
epiphenomenon in the disease, and not its exciting cause, is that the
power of digesting farinaceous and saccharine foods in this disease is
markedly diminished. To such a degree is this true that sufferers from
the gouty dyscrasia are most {114} promptly relieved of their symptoms
of primary indigestion by restricting their diet very largely to
albuminous foods; and not only does such a diet diminish the dyspeptic
symptoms, but I am persuaded by a considerable experience that it is
one of the surest prophylactics against the recurrence of gouty
lesions. It is well known that the fermented preparations of alcohol
are among the most frequent exciting causes of acute gout, and cases
are by no means infrequent in which indulgence in sweet foods and in
fruits will provoke many of the well-recognized local lesions of the
disease.
The explanation of this anomaly in the uric acid pathology of gout may
possibly be found in the suggestion of Garrod, that the deposition of
the urates is caused by their insolubility, and, as this insolubility
is increased by the diminished alkalinity of the serum, that the
evolution of the acids in the digestion of the carbohydrates so
diminishes the normal alkaline state of the blood that the uric acid
salts are more readily precipitated. But even if we accept this
explanation, the fact remains that as efficient factors in the
production of the gouty diathesis the carbonaceous foods may play as
large and perhaps a larger part than the albuminous foods. It would
seem, therefore, in view of the conflicting evidence in regard to the
theory of the uric acid origin of gout, that the chemical pathology of
this dyscrasia is still involved in considerable obscurity.
The recent advances in neuropathology have revived of late years the
views of Cullen on the pathology of gout. Dyce Duckworth[3] has lately
advocated the theory that gout is a trophoneurosis. This theory grows
out of the recognition of the protean manifestations of this disease,
and especially of the neurotic element which is so prominently
developed in its evolution. The frequency of purely nervous symptoms in
gouty persons is a fact which is daily brought to the notice of those
who have much opportunity to study the disease. These symptoms may be
said to affect all the functions of the nervous system; among these we
may mention psychical disturbances, such as hypochondriasis and
hysteria; derangements of sensation, such as neuralgias and
dysæsthesias of every variety; and spasms of voluntary and involuntary
muscles, such as cramps, grinding of the teeth, asthma, and vesical
tenesmus. Another fact which arrests attention in the history of gouty
persons is the frequency with which purely nervous influences determine
attacks of gout; the effect of nervous exhaustion, whether provoked by
overwork or mental anxiety, or the more explosive discharges of
nerve-force in rage and great emotional excitement of any kind, is well
recognized as a frequent precursor of gouty lesions. The influence of
certain diseases of the nervous centres also, such as cerebro-spinal
meningitis, Pott's disease, and tabes dorsalis, in determining
arthropathies and lesions of the skin and mucous membranes, furnishes a
striking analogical argument in favor of the possible nervous origin of
the lesions in gout. The recognition of these facts, however, does not
necessarily militate against the commonly accepted humoral pathology of
gout. The healthy action of the nervous centres must depend primarily
upon a normal nutrition, and a normal nutrition depends on healthy
blood-elaboration. That perverted innervation may be an important
factor {115} in the development of malnutrition through the accident of
inheritance is doubtless true, but in the acquired disease it seems
more probable that the lithæmic condition is the primary source of
disturbed innervation. It may be that gouty lesions are determined as
reflex phenomena through the medium of the trophic centres--if such
centres there be--rather than by the direct irritation of the affected
tissues by the gouty blood; and it is not unreasonable to suppose that
nervous exhaustion from any cause may produce in these centres greater
reflex excitability.[4]
[Footnote 3: _Brit. Med. Jour._, March 26, 1881.]
[Footnote 4: Edward Liveing, in his work _On Megrim, Sick Headache, and
Some Allied Disorders_, p. 404, thus expresses his conviction as to the
neurotic theory of gout: "The view which is commonly entertained is,
that the excessive generation or retention of uric acid in the system,
which is regarded as the fundamental fact in the pathology of gout,
exerts a toxic influence upon the nervous centres, while the particular
character of the disorder is determined by the territory involved. This
limited operation of a cause so general in its nature is a real
obstacle to this view; on the other hand, there is much in the history
of gout--its hereditary character, limitation to particular ages and
sexes, periodicity, explosive character, sudden translations, and
remarkable metamorphic relations with nervous disorders--which seems to
stamp the malady as a pure neurosis; and even the fit itself, with its
sudden nocturnal invasion, the late Dr. Todd was accustomed to compare
to one of epilepsy or of asthma."]
PATHOLOGICAL ANATOMY.--Blood-Changes.--Garrod's demonstration of the
excess of uric acid in the blood of gouty persons constitutes the chief
recognized hæmic change in this disease. That this is a constant
change, and one that is essential to the existence of gout, cannot be
said to be proved. The presence of uric acid in the blood is not always
productive of gout, since it has often been found in the blood of
healthy persons, and its temporary excess during pyrexia, and
especially in the fevers and other morbid states in which spleen is
congested, has already been noted. The excess of uric acid, however, in
gouty blood may reach, according to Garrod, as much as 0.11 grain in
1000 grains of serum. It is probable that other excrementitious
substances exist in the blood in gout which bear a closer etiological
relation to this disease than uric acid, but they have not been
demonstrated. The other blood-changes which are noted by Garrod--the
diminished specific gravity of the serum from loss of albumen, the
diminished alkalinity, and the increase of the fibrin in the
inflammatory forms of the disease--are probably inconstant. In chronic
gout the objective signs of anæmia which are often present would
indicate a marked diminution in the red blood-corpuscles.
The tissues which are the chief seat of gouty lesions are the
connective tissues. In the evolution of the disease the joints, where
the connective tissue is most dense and the least vascular, suffer
earliest; at a later period the connective tissue of the blood-vessels,
nerves, and viscera becomes subject to gouty changes.
According to Garrod, the exudations in articular gout are rich in the
urates of soda, lime, magnesia, and ammonia; they also contain some
phosphate of lime and traces of organic matter. The watery portion is
absorbed and the salts are deposited in crystalline forms. The location
of these deposits varies: they are found on the synovial surfaces, in
the cartilage-cells, and in the intercellular substance; in the
tendons, ligaments, and bursæ, and in the subcutaneous connective
tissue. The urate of soda occurs not on the free surface of the
cartilage, and replacing {116} the latter, as was formerly generally
supposed, but as an infiltration into the substance of that tissue; and
Garrod found that there is always a thin layer of unaffected cartilage
lying between the deposit and the free articular surface--an
observation which has been confirmed by Budd and quite recently by
Ebstein.[5]
[Footnote 5: W. Ebstein, _Die Natur und Behandlung der Gicht_,
Wiesbaden, 1882.]
Very important are the recent investigations of the latter. After
making numerous observations on the cartilages and other affected
tissues of gouty subjects, besides studying the disease artificially
produced in fowls, he has shown that those portions of cartilage and
other tissues in which the deposit occurs are in a state of necrosis,
as is evident from the fact that when the urates are dissolved out by
warm water the area in which the deposit occurred, though apparently
normal to the eye, refuses to be stained with aniline dyes, and lies
plainly visible as a light spot in the midst of stained tissue. Since
the work of Weigert we know that this is a sure sign of that peculiar
form of death of a tissue to which the name of coagulation necrosis has
been given. Ebstein regards this necrosis as primary and the deposition
of the uratic salt as secondary. According to him, the urates
circulating in the blood give rise to necrosis in parts where the
circulation is sluggish (as the articular cartilages, the ears, and the
extremities generally), and where, consequently, they remain a greater
length of time in contact with the tissues. The necrotic portion has,
however, an acid reaction, which causes a deposition, from the soluble
neutral salt, of an acid urate in a crystalline form. Ebstein claims
that this necrotic area, in which there is deposited a crystalline
urate of soda, and around which there is a secondary inflammatory zone,
is characteristic solely of gout. "I have never seen," he says, "in
gout a crystalline deposit of urates occurring in normal tissue."
In addition to these so-called specific changes we find a hyperplasia
of the connective tissue in the fibrous structures of the affected
joints. The thickening thus induced, with the contraction of the new
tissue and the atrophic changes resulting from pressure and disuse, are
the causes of the deformities, subluxations, and impaired movements of
gouty joints. Occasionally, the local irritation provoked by the
pressure of the tophous deposits results in abscesses from which a
mixture of pus and pasty urates may be discharged. These abscesses in
feeble and anæmic subjects are sometimes difficult to heal. More
frequently the skin undergoes gradual absorption and the chalk-like
deposits are exposed.