Part 16

The recent advances in neuropathology have revived of late years the views of Cullen on the pathology of gout. Dyce Duckworth 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.

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.

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.

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 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.

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.