Chapter VII: Front Matter (7)

It is generally supposed that there is a greater frequency of inheritance from the male ancestors and in the male descendants. This may be explained by the fact that men are more exposed to the other predisposing and to the exciting causes of gout. My own experience leads me to suspect that if we took into consideration the irregular manifestations of this morbid inheritance, we should find it as frequently in the female, both in the ascending and descending line; of the greater frequency of acute articular gout, however, in the male, there can be no question. While it is true that acute attacks are comparatively rare in women, both before and after the menopause, it is undeniable that the subacute and chronic forms of gouty arthritis are by no means rare in them, both before and after the cessation of menstruation. The Hippocratic proposition that women enjoy immunity from gout by reason of the menstrual flux can hardly be entitled to much consideration in view {110} of the fact that they are commonly less exposed to the exciting causes of the disease, and that when they subject themselves to the same vicious habits which entail the disease in men they suffer like men.

Statistics as to the age at which articular gout is most often 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.

The frequency with which the metatarso-phalangeal joint of the great toes is affected in gouty persons has always been noted. In Scudamore's tables the proportion of the first attacks in this joint was 72 per cent., and in 66 per cent. one or both great joints were affected to the exclusion of other joints. This frequency is due to the fact that this joint is the most vulnerable one in the body, bearing as it does the weight of the body and being exposed to most frequent shock. The phalangeal joints of the hands and the wrist-joints are also often the seat of acute gout, though these joints are more frequently affected by the subacute form of the disease. The larger joints may also be the seat of true gouty inflammation; indeed, no joint, not even the intervertebral, can be said to enjoy immunity, and the hip and shoulder are occasionally attacked to {117} the exclusion of others. The cartilages of the ear and the arytenoid cartilages are sometimes the seat of gouty deposits.

The great frequency of arterial sclerosis, and the subsequent fatty and chalky metamorphosis in persons who have suffered from chronic gout, are well recognized. Next to syphilis, gout seems to be the most common cause of these arterial changes. The influence of these lesions in the arteries and capillaries in determining cardiac hypertrophy and cerebral hemorrhage is often seen in the accidents which terminate the lives of gouty patients.

In the heart a gouty endocarditis is of not uncommon occurrence, according to Ebstein, who cites Lancereaux as having found uric acid in concretions on the valves. Garrod, however, after examining a number of cases in which cardiac disease existed with gout, states that in his opinion the valvular changes are not due to a gouty deposit, he never having been able to demonstrate the presence of uric acid in them.

Some years ago Sir James Paget called attention to the frequency of adhesive phlebitis as a gouty lesion. This is observed in connection with articular gout, but may also occur independently of joint-lesion. It is observed most frequently in the lower limbs, is generally symmetrical, and shows a disposition to metastasis.

Neuritis and sclerotic lesions of the nerve-centres are not uncommon in the history of acquired and inherited gout. The neuralgias and other temporary dysæsthesias which constitute a considerable category in the symptoms of gouty persons are doubtless due to transient central and peripheral lesions.

The so-called gouty kidney is the most striking illustration of the effect of the gouty dyscrasia in the production of a characteristic visceral lesion. The changes which occur in the kidney as a result of gout are--a contraction of the organ, the result of interstitial inflammatory processes, and a deposition of uratic salts, occurring mainly in the papillary portion. The views as to the exact locality where these deposits occur still differ considerably. Garrod is of opinion that it occurs in the fibrous interstitial tissue. Virchow, on the other hand, regards the lumen of the tubuli as the seat of the deposit, and in this he is supported by Charcot and Cornil and Ranvier, Lancereaux and Wagner. Dickinson inclines to the view of Garrod, and believes that it is the deposition of the urates in the interstitial tissue which gives rise to the chronic inflammation which results in cirrhosis of the kidney--the granular kidney of gout. Ebstein seems to think that the interstitial connective tissue, having previously undergone a state of necrosis, as in cartilage and other connective tissues, is the seat of the deposit. As in cartilage, he regards this necrotic state as typical of gouty deposits. About the necrotic area in which the deposit has occurred a secondary inflammation takes place, leading ultimately to contraction of the new fibrous tissue formed. He calls attention to the fact that (1) the kidneys may be perfectly sound in gout; (2) the kidneys may be the seat of chronic interstitial inflammatory changes, with cirrhosis, without any urate deposits of any kind being demonstrable; (3) there may be chronic interstitial nephritis, with crystallized urates in the urinary tubules.

As regards changes in the liver, few satisfactory accounts exist. {118} Portal originally called attention to the fact that in gout and rheumatism indurations of the liver caused by the deposit of a phosphatic earth occurred, and Charcot has recently referred to the fact. Ebstein cites a case in which in a gouty patient he was able to make a diagnosis of moderate hypertrophic hepatic cirrhosis, but so far he had not been able to confirm it by post-mortem examination.[6]

[Footnote 6: Gout in Animals.--Of the occurrence of gout in animals not many reliable reports exist; Ebstein has collected a few. Thus, he cites a case where in an old hunting-dog uratic concretions were found in the articular ligaments and in the periosteum of the epiphyses of many joints, but especially those connecting the ribs with their cartilages. In the toes of falcons and of parrots kept in confinement deposits of urates have been observed, and in an alligator dying in captivity deposits were found in the muscles as well as the joints which consisted of free uric acid together with sodium urate.

Experimentally, Ebstein was able to produce gouty lesions having all the characteristics of those occurring spontaneously in man by injecting subcutaneously small quantities of the neutral chromate of potash into the blood of cocks for a considerable period of time. By this method changes in the epithelial elements of the kidney were produced, preventing the elimination of the urates from the blood and causing their consequent accumulation in the system. He obtained in this way typical deposits of urates in the joints, tendons, muscular sheaths, heart, and other organs, while the birds emaciated and finally died. But these experiments, which are extremely valuable and interesting, still need confirmation.

The experiment of tying the ureters of fowls is an old one. Galvani who was perhaps the first to perform it, employed it in his investigations on the kidney, and since then Zalesky, Pawlinoff, Von Schroeder, Colosanti, and others have made use of it in their experimented studies on the site of origin of uric acid. As a result of this operation deposits of urates occur in various organs. Ebstein, however, does not regard them as analogous to the gouty deposit in human beings, as they lack the feature of necrosis, which, as mentioned above, he considers as alone characteristic of the true gouty lesion.]

SYMPTOMATOLOGY.--The development of true gouty lesions, whether of the acute or subacute form, is usually preceded by a period, more or less protracted, in which characteristic derangements of the health present themselves. These derangements may be conveniently classified as disturbances of primary digestion and as manifestations of malnutrition.

The disturbances of primary digestion are repeated attacks of flatulent dyspepsia, with pyrosis, colicky pains, alternate constipation and diarrhoea, and a scanty, high-colored, and heavy urine with uratic sediments. This dyspepsia may be accompanied with a variety of reflex nervous symptoms, such as pain in the nape of the neck and occiput, insomnia, palpitation, sighing respiration, singultus, and nausea. These symptoms are commonly described as due to biliousness, and are provoked by excesses in diet, and not unfrequently by moderate indulgence in certain common articles of food, such as sweets, fruits, farinaceous foods, and the fermented preparations of alcohol.

Derangements of nutrition are shown by a disposition to erythematous and catarrhal affections of the skin and mucous membranes, to affections of the sebaceous glands, and to premature falling of the hair. There is often a more or less marked tendency to obesity. Accompanying these derangements there may be a loss of energy, both physical and mental, manifesting itself in indolence and fatigue on slight exertion, in irritability of temper, with diminished intellectual activity and hypochondriasis. Neither the primary indigestion nor the nutritive derangements invariably precede the development of acute gouty lesions, nor are they necessarily followed when they exist by the articular signs {119} of gout; but they are so commonly associated with the evolution of what are regarded as the specific lesions of gout that they may fairly be described as constituting its prodromal period.

ACUTE ARTICULAR GOUT.--A typical attack of acute gout is usually sudden. It seizes its victim without warning, and often rouses him from sleep with a vicious agonizing pain in the joint assailed. Examination will reveal a slight redness, heat, and puffiness of the part affected altogether disproportioned to the intensity of the pain; the tenderness is exquisite, and the torture is often aggravated by the occurrence of reflex spasms of neighboring muscles. There is usually moderate fever, and if the surface be exposed there may be a chill. Sleep is impossible and the restlessness uncontrollable. As the morning advances slight perspiration occurs, and sleep may become possible. With the abatement of pain there is coincident increase in the signs of inflammation: the joint swells, the skin becomes red and oedematous around the joint, and the superficial veins are distended. But, though the pain subsides with the occurrence of swelling, and usually in proportion to its degree, the tenderness and pain on any attempt to move the joint continue to be extreme. The day is passed in comparative ease, but the evening generally brings an exacerbation of pain and fever, and the night another paroxysm of agony--not as severe as the first, but severe enough to make the daylight a benison. The progress of the disease after the second day, provided it is confined to one joint, is usually marked by a steady and regular decline in the severity of the symptoms. If the attack is confined to a single joint, a week may elapse before the inflammatory signs subside, and it may be a fortnight before pressure can be borne or the mobility of the joint is restored. Occasionally the sufferings of an acute attack of gout may be protracted by successive seizures for several weeks. The fever during the attack is distinctly remittent, the evening exacerbation rarely exceeding 103° F.

The urinary symptoms before, during, and after an acute paroxysm of gout are interesting and important in their bearing upon the uric-acid theory of the disease. Garrod's statements upon this point are generally accepted, and have been confirmed by other observers. He says that previous to the attack the amount of uric acid in the urine is below the average--that during the paroxysm the proportion grows smaller, and only rises to the normal standard with the termination of the seizure. The reaction of the urine is strongly acid during the paroxysm. This is due probably to the increased excretion of acid phosphates. The quantity of the urine is generally diminished, the specific gravity increased, and the color deepened.

Attacks of acute gout are generally followed by improved health and capacity for physical and mental work and enjoyment. The blood seems to be purified, the processes of digestion and assimilation are once more normally performed, the equilibrium of the nervous centres is restored, and the evolution of all the vital energies proceeds with ease and vigor. This state of well-being may continue for a year or two years, or even a longer period, after the first attack, the immunity varying according to the intensity of the inheritance or the habits of life. The subsequent attacks are apt to occur at increasingly shorter intervals, and, as a rule, the acuteness of them tends to diminish. Gradually the dyscrasia becomes more {120} profound, and the constitutional symptoms and structural changes which belong to the atonic and irregular forms of the disease are developed.

ATONIC GOUT.--Though subacute, irregular, or atonic gout is often the sequence of repeated attacks of the acute disease, it is not necessarily preceded by them, nor is acute gout invariably followed by a marked gouty dyscrasia. It is not uncommon for a well-characterized gouty habit to exist, manifesting itself by many and varied gouty phenomena, without the occurrence of any acute lesions, and repeated attacks of acute articular gout may occur without the development of the progressive impairment of health and the tissue-changes which distinguish the chronic malady. The recognition of this fact is important, inasmuch as the occurrence of acute gout is commonly regarded as an essential element in the diagnosis of the gouty dyscrasia. Acute articular attacks, as already noted, are very rare in women, in whom the subacute and irregular forms of the disease are by no means infrequent. So far as acute articular gout is of value in the diagnosis of the constitutional vice, it is perhaps as significant if established in the history of a near relative as in the individual in whom the disease is suspected.

The general symptoms of atonic gout--or, as it may more properly be called, the gouty dyscrasia--are similar to those which sometimes precede the development of the acute form. The difference lies in their persistence, in the subacute character of the local lesions, and in the absence of the relief to the constitutional symptoms which follows acute attacks.

The dyspeptic symptoms are perhaps the most pronounced and uniform in the history of the evolution of chronic gout. These symptoms have been already described, but the fact which seems especially to distinguish them is that they are chiefly provoked by the acid fermentation of the carbohydric elements of the food, the sugar and starches, and especially by the fermented preparations of alcohol; the ability to digest these articles of diet appears to be deficient in the gouty dyspeptic.

The changes in the urine in the gouty dyscrasia are especially important. In the formative stages of the gouty vice the amount of urine may not vary much from the normal quantity, but the proportion of solid constituents, especially of the urea, is increased, so that the specific gravity may rise to 1.030 or 1.035. The acid reaction is intensified by the excess of the acid urates and phosphates upon which the normal acidity depends. Sometimes crystalline deposits of uric acid, urates, and oxalates take place in the tubuli of the kidney and in the bladder, and lead to the nephritic and vesical irritations which are often the source of much inconvenience and pain. Where the urine is free from these crystalline constituents as it comes from the bladder it may deposit them within a few hours after its passage. At a later stage in the development of the gouty dyscrasia the quantity and quality of the urine undergo marked changes. The quantity is increased; the color is pale, partly in consequence of dilution and partly through a diminution in the amount of coloring-matter. The quantity may be so considerable as to constitute a polyuria. The reaction is neutral or only feebly acid; crystalline sediments of uric acid and calcium oxalate may occasionally appear, and the specific gravity may be so low as to indicate not only a relative but an absolute diminution in the daily excretion of urinary solids. Traces of albumen and of sugar are not infrequently observed.

{121} The articular symptoms of chronic gout are subacute. They affect the joints, as a rule, which are most exposed to strain and injury, and hence are most common in the hands and feet, but they may involve the knee and the hips, the elbow and the shoulder, and even the intervertebral joints. The pain is less severe, because the tension is never so considerable; the tenderness is often a source of great discomfort; the swelling varies with the acuteness of the inflammatory process, the joints being more or less permanently enlarged by hypertrophic changes affecting the articular structures and by tophous deposits. The deformities are increased by ankylosis, by contractions, by absorption of the cartilages, by partial luxations, and by the atrophy of disused muscles. Crepitations are often observed in the affected joints. Exacerbations of the local symptoms are often provoked by movements, by imprudence in diet, by changes in temperature or in barometric and hygrometric conditions, and not infrequently by psychical disturbances.

The frequency with which tegumentary affections, mucous as well as cutaneous, are observed as correlative phenomena of arthritic lesions in gouty persons and in gouty families justifies the inference that the same lithæmic vice which determines articular inflammations is often responsible for derangements of nutrition in the skin and mucous membranes. The French school of dermatology, which has always maintained the humoral origin of many cutaneous diseases, has long recognized the arthritic nature of a large class of affections of the skin. Bazin[7] has given the most precise description of the arthritides, as he terms them. He insists upon certain functional derangements of the skin as characteristic of the gouty diathesis, such as excessive perspiration, especially in certain regions, as the head, the axillæ, the hands and feet, and the sexual organs, and also affections of the sebaceous glands, causing the different forms of seborrhoea and the premature falling of the hair. He notes the liability in gouty persons to certain neurotic affections, such as pruritus, general or localized, about the arms and genital organs. Erythematous affections, especially urticaria, erythema nodosum, and the fugitive erythema which occurs about the face, causing sudden and evanescent swelling of the eyelids, cheeks, lips, and even the tongue and soft palate, are recognized by him and other observers as arthritic in their origin. Among the erythemata which are observed in gouty persons the peliosis rheumatica should be mentioned.

[Footnote 7: _Affections génériques de la Peau_, Paris, 1862.]

The more persistent inflammatory lesions of the skin, such as eczema and psoriasis, which are characterized by long-continued hyperæmia with hyperplasia, are now recognized as among the possible transformations of gout. They are certainly often observed alternating with arthritic lesions, and associated with all the characteristic derangements of nutrition which belong to the gouty habit. The frequency of the various forms of acne, the inflammatory, as well as those which result from excessive function of the glands, in persons having a strong gouty inheritance, is recognized by many dermatologists. I have noticed these lesions especially in young women belonging to gouty families. They are generally accompanied by marked dyspeptic symptoms, and not infrequently by neurotic derangements.

Garrod, in a paper read at the International Medical Congress in 1881 {122} on "Eczema and Albuminuria in Relation to Gout," affirms that each year strengthens his conviction that gout and eczema are most closely allied. Since his attention was first called to this relation in 1860, he has found a gradually increasing percentage of eczema in the cases of gout that have come under his observation. Dividing all the cases from 1860 to 1881 into ten groups, he found the percentage rose from 10 in the first group to 47 in the tenth. He accounts for this rapid increase in the percentage in the fact that in the first few years the eczema was only observed when it was very patent; during the past two or three years he has had made more careful inquiries as to the presence of eczema or other skin eruption in every case of gout, and by these means has frequently discovered its presence when it might otherwise have been overlooked. Garrod believes that eczema is the special skin-lesion of gouty subjects, and does not regard psoriasis as having anything more than an accidental connection with gout. He admits that the latter is often associated with rheumatoid arthritis. It must be remembered, however, that Garrod does not admit that gout ever exists without lithatic deposits.

In regard to the location of gouty eczema, it appears to affect by preference the more tender and vascular regions of the skin. The eyelids, ears, the scalp, and back of the neck, the fingers and toes, particularly the dorsal and lateral surfaces, and in old people the legs, are especially liable to be attacked. The subjective symptoms of gouty eczema are often the source of great suffering; the burning and itching are sometimes intolerable. This is especially true of persons of highly neurotic constitution.

It is not possible to affirm that there are lesions of the mucous membranes which are strictly analogous in their transient character to the erythematous affections of the skin, but it is not unreasonable to suppose that many of the temporary disturbances of indigestion to which gouty patients are subject are caused by an evanescent hyperæmia corresponding to the vaso-motor derangements which are observed in the external integument. In regard, however, to the more persistent catarrhal lesions, there can be no question as to their analogy with those which affect the skin. The continuity of these lesions at the orifices of the mucous tracts, and the frequent association of external eczemas with catarrhs of mucous membranes, are facts of common experience. Greenhow[8] of London first called attention to the frequency with which chronic bronchitis is associated with the gouty dyscrasia. In an analysis of 96 cases of chronic bronchitis he elicited the fact that in 34 out of the 96 a distinct gouty history attached either to the patients themselves or to some of their immediate relatives. In 14 of the cases the patients were subject to attacks of acute regular gout as well as to bronchitis. He also noted the association in a number of cases of bronchitis and psoriasis with gravel and gout. My own experience confirms these observations, and also the alternations of catarrhal and parenchymatous tonsillitis, of pharyngeal and laryngeal catarrh, and of asthma and chronic bronchitis, with the more common manifestations of regular and irregular gout.

[Footnote 8: _On Chronic Bronchitis_, E. Headlam Greenhow, M.D., London, 1869.]

The occurrence of subacute gastro-duodenal and intestinal catarrhs {123} with hemorrhoidal complications is even more common that the catarrhal affections of the respiratory tract. The lesion, in fact, which gives rise to the manifold dyspeptic symptoms in gouty subjects is doubtless a catarrhal one.

The genito-urinary tract exhibits also the tendency to catarrhal affections in sufferers from the gouty dyscrasia. It is certain that gouty persons are especially liable to vesical catarrh, and it is generally admitted that rheumatic and gouty persons are particularly susceptible to gonorrhoea. My own experience leads me to suspect that chronic urethral discharge resulting from acute urethritis is more common in rheumatic persons than in those not having this taint. The etiological relations of gonorrhoeal rheumatism and kerato-iritis are still involved in obscurity, though I am inclined to believe that a careful examination of the personal and family history in cases of these diseases would establish the opinion that has been maintained as to their gouty origin.

The presence of albumen in the urine of persons suffering from acute gout is occasionally observed. Under these circumstances it is transient, and has probably no more significance than is usually attached to this symptom in the course of any acute febrile disease. In chronic gout it is by no means infrequently observed as a more or less persistent symptom. It is associated under these circumstances with a copious discharge of urine of pale color and low density, and with the general signs of what Rayer first described as the néphrite goutteuse.

The importance of this symptom is very great when we consider the insidious development of this form of disease and the difficulty of its early diagnosis. Recent investigations point to the value of the changes in the urine in the progress of the gouty dyscrasia as bearing upon this question. It has already been noted that in the early history of gouty persons the urine is often scanty, high-colored, excessively acid, of high specific gravity, occasionally albuminous and saccharine, and frequently depositing sediments of urates and calcium oxalate. McBride of New York[9] has recently called attention to this condition of the urine and its association with high arterial tension as the functional stage of the granular kidney--as the stage, that is to say, during which the necessity of eliminating large amounts of imperfectly oxidized nitrogenous material maintains a constant state of renal hyperæmia, which finally induces the changes in the tubular and intertubular structures which constitute the anatomical features of this form of disease.

[Footnote 9: _The Early Diagnosis of Chronic Bright's Disease_, T. A. McBride, M.D., New York, 1882.]

The occasional presence of sugar in the urine of gouty persons has already been noted. I have repeatedly observed this symptom in the urine of gouty dyspepsia. It occurs more commonly in obese subjects, and is usually intermittent and easily controlled by dietetic restrictions. In these cases it is not necessarily associated with a very large amount of urine. In chronic gout and in connection with the granular kidney a more serious form of glycosuria is occasionally observed. Under these circumstances it increases largely the polyuria which is characteristic of gouty nephritis, and is sometimes overlooked because it occurs in a urine of a low density, often not more than 1.010. It is not controlled by diet {124} to the same extent that it is in the cases previously described, and is in my experience a prognostic sign of bad import.

Some of the most distressing symptoms to which gouty persons are especially liable are those connected with the passage of gravel from the kidney to the bladder. Where gravel alone passes, it may cause little uneasiness, and the fact is only recognized through the discovery of blood in the urine in connection with uric acid or calcium oxalate crystals. When, however, the sand forms concretions in the pelvis of the kidney, their dislodgment and passage through the ureter are accompanied by the well-known agonies of renal colic.

Dysuria is a symptom from which gouty persons often experience much inconvenience and suffering. It is usually associated with extremely acid urine of high density containing crystalline sediments. It may manifest itself only in frequent and painful micturition, or it may be associated with such a degree of vesical tenesmus as to cause retention and necessitate the use of the catheter.

DIAGNOSIS.--If the term gout be restricted to that form of arthritis in which an excess of urates is found in the blood with tophous deposits in the affected joints, the cartilages of the ear and nose, and in the subcutaneous connective tissue, then the diagnosis of this disease is a simple one. It is a disease with a pathognomonic sign. But if the pathology of gout consists rather in a more complex morbid condition of the blood, of which an excess of urates in the serum is only one of a number of phenomena, and not necessarily the sole and essential cause of the local lesions, then the question of diagnosis involves a consideration of all the correlated morbid conditions which are so frequently associated in gouty persons and gouty families as to justify the inference that they have a common origin in a perverted nutrition, the essential nature of which is imperfectly understood.