Chapter III: Front Matter (3)

THE MORBID ANATOMY OF ACUTE AND SUBACUTE ARTICULAR RHEUMATISM.--Although opportunities of ascertaining the conditions of the articulations in acute articular rheumatism are rare, yet it is now established that the process is an inflammation involving chiefly the synovial membrane, and to a less degree the cartilages, ligaments, tendinous sheaths, and in some cases even the bones and periarticular soft parts. The synovial membrane is more or less injected and reddened diffusely or in patches, especially where it forms fringe-like folds and at its line of union with the cartilage. It is somewhat thickened, opaque, and devoid of its satin-like lustre, and in somewhat protracted cases covered here and there with a thin, easily detached neo-membranous formation. Within the articulations will be found from a few drops to one or two ounces of a viscid, pale, citron- or reddish-colored fluid, like synovia, but more fluid, and generally turbid and containing transparent or semi-opaque gelatinous masses or albumino-fibrinous flocculi. The {47} microscope reveals in the effusion large detached spherical epithelial cells in various stages of germination or of fatty degeneration, and a variable number of red blood-corpuscles and pus-cells. Very exceptionally, the effusion is mixed with more or less true pus. In two out of the eight fatal cases reported by Fuller, in which the joints were examined, pus in moderate quantity was found along with other products in some, but not in all, of the inflamed articulations, and one of them was complicated with erysipelas, the other with sloughs over both trochanters. In very severe forms complicated with hemorrhagic tendencies the inflammatory products have contained a large proportion of blood. Cornil et Ranvier[118] insist that even in slight cases of rheumatic arthritis the diarthrodial cartilage constantly suffers changes arising from nutritive irritation and proliferation of the cartilage-cells. At first the cartilage loses here and there some of its polished hyaline appearance, and the microscope reveals a finely-striated condition of its structure which gives it a velvety aspect. When the inflammation has been more severe and of longer duration, so that the deeper layers have been involved, the unaided eye will perceive local swellings in which the natural elasticity and resistance of the cartilage are impaired, and its surface is fissured or villous-like in appearance. "In certain rare cases of mono-articular acute arthritis true ulcerations of the cartilage are observed."

[Footnote 118: _Manual d'Histologie pathologique_, Paris, 1869, 406.]

The soft parts in the immediate vicinity of the inflamed joints may be in some cases more or less congested and oedematous, and the tendinous sheaths, and even the bursæ mucosæ, inflamed and distended with inflammatory products like those in the articulations. Charcot,[119] holding the opinion that arthritis deformans is but a chronic variety of articular rheumatism, quotes Gurlt's statement that in acute articular rheumatism "the medullary tissue of the ends of the bones undergoes a great increase of vascularity, with proliferation of its corpuscles," and remarks that Hasse and Kussmaul have also referred to lesions of the bone and periosteum in that disease. But the condition of the osseous parts of the joints in acute articular rheumatism can hardly be said to be known, and it is premature to speak positively respecting it.

[Footnote 119: _Clinical Lectures on Acute and Chronic Diseases_, Sydenham Soc., 1881, p. 148.]

Finally, in subacute rheumatism the alterations in the synovial membrane, and especially in the cartilages just described, are likely to be more marked than in the acute form.

The DIAGNOSIS of acute polyarticular rheumatism is seldom difficult in adults, but when acute rheumatism localizes itself in one joint or occurs in infancy or early childhood, a diagnosis, especially an early one, sometimes cannot be easily established. The considerations by which acute polyarticular rheumatism may be distinguished from acute gout, subacute rheumatoid arthritis, and gonorrhoeal rheumatism will be given in connection with those topics.

Pyæmia has perhaps been confounded with acute articular rheumatism more than any other disease, but the rheumatic affection, unlike the pyæmic, is not necessarily connected with any pre-existing condition capable of causing purulent infection of the blood or system, such as a wound, fracture, abscess, or a local inflammation of bone, periosteum, vein, pelvic organ, or a specific fever (variola, relapsing, typhoid, {48} glanders, etc.); it does not present severe rigors, which recur at irregular intervals and are attended with teeth-chattering and a high temperature, 104° to 105°, rapidly attained; its type of fever is not so intermittent or markedly remittent as that of pyæmia; its profuse sweating continues although the temperature remains febrile, but that of pyæmia coincides with the decline of the temperature; unlike pyæmia, it only very rarely produces profound constitutional disturbance of a typhoid character, and has no tendency to run a rapidly fatal course in eight to ten days or in two or three weeks; its visceral inflammations are chiefly cardiac, pleural, and pulmonary, and tend to resolve; those of pyæmia are especially pulmonary, pleural, and hepatic, although frequently cardiac also, and generally produce suppuration and destruction of tissue. Multiple subcutaneous abscesses and cutaneous blebs and pustules do not occur in acute articular rheumatism, and its articular affection differs in many respects from that of pyæmia; many more joints are involved; the inflammation is erratic, very rarely fixed, and generally resolves without damage to the articulation; the affected joint is usually hotter, redder, more painful, and more sensitive, and the swelling is less diffused, and its outline corresponds more accurately with that of the synovial capsule. Sometimes acute articular rheumatism is complicated with the phenomena of pyæmia, as when so-called ulcerative endocarditis obtains.

The acute inflammations which are occasionally observed in one or several articulations of newly-born infants are generally pyæmic. It is only in the early stage of acute glanders that the severe muscular and articular pains sometimes present in that very rare disease in man might lead to its being confounded with acute articular rheumatism; but the patient's occupation and history, the early and severe prostration, the absence, as a rule, of redness and swelling around the painful articulations, and, in some instances, the early appearance of pustules and blebs on the skin and of abscesses in the deeper tissues, will suggest the real nature of the case.

Acute periostitis frequently occurs in children in close proximity either to one joint, or less frequently to more than one, and may readily be confounded with acute articular rheumatism. But the constitutional disturbance in acute periostitis is prompt and severe at the outset; the swelling increases rapidly, is firmer than that of arthritis, does not involve the joint proper and its capsule, but, like the tenderness on pressure, exists above or below the articulations, especially around the head of the bone; there are no visceral complications, provided pyæmia has not supervened; the constitutional symptoms early assume a typhoid character, and unless an early incision be made a fatal issue soon ensues.

The enlarged ends of the long bones and the pains in the limbs of rickets might lead to a suspicion of acute articular rheumatism, but the early age of such children, the absence of pain and swelling in the joints, the beaded condition of the sternal ends of the ribs, the late dentition and locomotion, the peculiarly shaped head, and other evidences of that affection, would prevent a careful observer from making a mistake. Inherited syphilis in infants, like rickets, may produce fusiform swelling and thickening at the ends of the long bones, especially the humerus and femur, and sometimes pain in the joints on movement; but at first the swelling {49} is confined to the epiphyseal line, and only later extends to the joint; there is a pseudo-paralysis of the limb, and but little pain or fever; bony osteophytes may often be felt under the skin at the line of union of the epiphysis with the shaft; the epiphysis often becomes separated from the shaft, and suppuration may ensue around the bone and in the articulation; sometimes adhesions and perforation of the integument take place, allowing of the escape of disintegrating osseous and cartilaginous tissue; and there will coexist either on the skin or mucous membrane some of the ordinary evidences of inherited syphilis.[120] The acute and subacute articular inflammations occasionally observed in cerebral softening and hemorrhage, in injuries and inflammation of the spinal cord and caries of the vertebræ, may be distinguished from acute and subacute articular rheumatism by the following circumstances: the existence of some one of these diseases of the brain or cord, the articular affection being usually confined to the paralyzed limbs; its invasion about the time of the setting in of the late rigidity, or even still later; the absence of cardiac complications and the presence of other trophic or neuro-paralytic lesions, such as acute sloughings, rapid atrophy of the palsied muscles, cystitis, ammoniacal urine, etc.[121]

[Footnote 120: Vide Parrot, _Archives de Physiol. Norm. et Path._, 1872 and 1876; R. W. Taylor, _Bone Syphilis in Children_, New York, 1875.]

[Footnote 121: See J. K. Mitchell, _Am. Jour. Med. Science_, vol. viii., 1831, and _ib._, 1833; Scott Alison, _Lancet_, i., 1846, 276; Brown-Séquard, _Lancet_, i., 1861; Gull, _Guy's Hosp. Repts._, 1858; Charcot, _Archives de Physiologie_, t. i. p. 396, 1868, and many others.]

Acute articular rheumatism in children presents peculiarities. It often affects but one joint, and has little tendency to become general; the joints of the lower extremity, ankle, and knee are most obnoxious; the local signs of inflammation, redness, swelling, and pain, are feebly developed, and the child may walk as if nothing were wrong; the disease is usually subacute; the temperature rarely very high; the perspiration not profuse; the urine not scanty, and not often loaded with lithic acid. Cardiac and the other internal complications, except the cerebral, are more frequent than in adults; endocarditis is especially frequent, pericarditis and pleuritis not rare. It is almost exclusively in childhood that acute articular rheumatism becomes associated with or followed by chorea, and yet the delirium, coma, and convulsions frequently observed during rheumatic fever in the adult are very rarely seen in the child. Muscular rheumatism, however, in the form of torticollis, frequently coexists, and so do erythema nodosum and the subcutaneous fibrous nodules previously described.

Mono- or Uni-Articular Acute and Subacute Rheumatism.

It is very rarely indeed that acute rheumatism invades a single joint to the exclusion of the rest; and it is perhaps impossible to be certain that such an arthritis is rheumatic unless some of the other symptoms or complications of articular rheumatism supervene, or unless it have succeeded a polyarticular rheumatism, which it very rarely does. Mono-articular rheumatism is very generally of the subacute type, and unattended with fever from the outset, or only a moderate pyrexia obtains for a few days; there is generally considerable effusion into the joint, with {50} swelling, pain, and moderate local heat; visceral complications very rarely arise, but the local inflammation persists most obstinately for six or eight weeks or three or four months, and often leaves the joint tender, stiffs, and weak for a long time or even permanently. In both the acute and subacute forms, before concluding that the uni-arthritis is rheumatic, we must exclude the probability of its being traumatic, strumous, syphilitic, gonorrhoeal, neurotic, or, above all, of the nature of rheumatoid arthritis, which many such cases really are.

PROGNOSIS.--The disease is rarely directly fatal during the attack, yet as the frequency of the complications varies unaccountably from time to time, so the mortality may be exceptionally large or small for even prolonged periods. It may be said that the average mortality ranges between 1.16 and 4 per cent. in the experience of modern authors. The average mortality in the Paris hospitals for four years (1868-69, 1872-73) Besnier fixes at 1.65 per cent.;[122] in St. Bartholomew's, London, Southey found it for fifteen years (1861-75) to be 1.16 per cent.;[123] Pye-Smith fixes the rate at 4 per cent. in 400 cases treated in Guy's;[124] W. Carter gives 2.5 per cent. as the rate during ten years at the Southern and Royal Southern Hospitals of Liverpool.[125] The death-rate appears to vary remarkably with age, as Southey's figures show:[126] under ten years, 3.40 per cent.; between ten and fifteen, 1.5 per cent.; between fifteen and twenty-five, 1.4 per cent.; between twenty-five and thirty-five, 0.9 per cent.; between thirty-five and forty-five, 0.8 per cent., the mortality declining very greatly after the tenth, after the twenty-fifth, and after the forty-fifth year of life.

[Footnote 122: _Dictionnaire Encyclopédique_, Troisième serie, t. iv., p. 463.]

[Footnote 123: _Barth. Hospital Reports_, vol. xiv., p. 4.]

[Footnote 124: _Guy's Hospital Reports_, xix. p. 327.]

[Footnote 125: _The Liverpool Medico-Chirurgical Journal_, July, 1881, p. 88.]

[Footnote 126: _Lib. cit._, p. 4.]

The danger of the case is usually proportionate to the youth of the patient, the degree of the pyrexia, the number of the joints involved, and the number and the character of the complications, the habits, and previous health of the patient. A fatal issue is most frequently observed in connection with hyperpyrexia alone, or in combination with delirium or coma. A rapid rise of temperature and a temperature over 105°, especially if cerebral disturbance coexist, indicate danger; and so does arrested perspiration while the temperature is high. In a much smaller number of cases death is due to some other complication, especially to purulent pericarditis or to that combined with pleuritis or pneumonia; in not a few cases the prior existence of chronic valvular disease, with fibroid induration of liver and kidneys, renders a fresh rheumatic endo- or pericarditis, occurring as part of acute articular rheumatism, fatal. There is good if not conclusive evidence that rather sudden death in acute articular rheumatism is occasionally due either to diffuse myocarditis or to fatty degeneration of the muscle of the heart. In Greenhow's 2 deaths out of 50 cases treated by sodium salicylate the pericardium was universally adherent and the heart's fibre fatty in one and pale and flabby in the other. Sudden death in this disease is very rarely due to embolism of the pulmonary artery or of the cerebral vessels, while ulcerative endocarditis is very exceptionally one of the sources of a fatal issue.[127] But although acute articular rheumatism rarely kills {51} directly, it frequently lays the foundation of subsequent ill-health, and ultimately proves fatal through organic disease of the heart and its many consequences. However, it is an interesting circumstance that while acute rheumatic inflammation is prone to damage the heart permanently, it very rarely, quite exceptionally, impairs the structure or functions of the articulations. It is almost solely the subacute form that now and then becomes chronic or renders a joint for a long time painful, swollen, and crippled in its movements. Whether acute rheumatism, however intense per se, ever ends in destructive suppuration and ulceration of a joint is doubted by some authorities, notwithstanding the cases published by Fuller and others. No doubt some of the cases were really pyæmic, or perhaps gonorrhoeal; and it must be borne in mind that acute articular rheumatism occasionally develops pyæmia, and then an arthritis might be considered rheumatic when truly pyæmic. The question of acute rheumatic arthritis exciting a chronic rheumatoid affection will arise hereafter.

[Footnote 127: See an article on the mortality among rheumatic risks by A. Huntingdon, M.D., in _N.Y. Medical Record_, 1875, p. 195.]

TREATMENT.--Owing to our imperfect knowledge of the real nature of acute articular rheumatism, its treatment is still largely either empirical or intended to combat certain prominent symptoms or complications of the disease. Of the various methods of treatment which have been employed space will not permit a description; even of those advocated by authorities of the present hour only very few will be considered.

The method which is now unquestionably the favorite one in both Europe and America, and which in its power of promptly relieving the articular and muscular pains and reducing the fever of acute rheumatic polyarthritis may without exaggeration be compared to that exercised by quinia over the paroxysms of ague, is that in which salicylic acid or salicylate of sodium is given in repeated and full doses. It was in July, 1875,[128] that Buss first asserted that salicylic acid was a specific for rheumatism, and in March, 1876,[129] Maclagan, after having employed salicine from 1874, published his experience of it as a valuable remedy in the treatment of acute rheumatism, its beneficial action being "generally apparent within twenty-four, always within forty-eight, hours of its administration in sufficient dose." Perhaps a sufficient time has now elapsed to permit of a just opinion of the power of these new remedies, the salicyl compounds, over acute articular rheumatism. The facts presented at the discussion recently held at the Medical Society of London[130] are sufficiently numerous and authoritative to justify, at least provisionally, some definite conclusions as to the remedial relations of the salicylates to acute articular rheumatism.

[Footnote 128: "Die Antepyr. Wirkung der Salycylsäure," _Centralbl. f. d. Medic. Wissenschr._, 1875, 276.]

[Footnote 129: _The Lancet_, March 4 and 11, 1876.]

[Footnote 130: _The Lancet_, Dec. 17, 24, 31, 1881; Jan. 7, 14, 28, 1882.]

1. The articular pain and the fever of acute rheumatic polyarthritis are more or less speedily removed by the salicyl remedies (salicylic acid, sodium salicylate, and salicine); the pains very frequently persist after the temperature has become normal. Both symptoms were removed by five days' use of such agents in 50 per cent., and by eleven days' use in 80 per cent., of 355 cases treated at Guy's Hospital, and tabulated by Fagge,[131] and by five days' use in 60 per cent., and by eleven days' use {52} in 66 per cent., of the 60 severe cases treated and severely criticised by Greenhow.[132]

[Footnote 131: _Ibid._, ii., 1881, 1031.]

[Footnote 132: _Clinical Society's Transactions_, vol. xiii., 1880. See Dr. Fagge's table iv., _Lancet_, ii., 1881, 1032.]

Again, in 190 cases of acute and subacute rheumatism the average duration, under salicyl remedies, of pyrexia was 5.5 days and of joint disease, 5.3 days (Warner[133]); in 156 cases at St. George's Hospital the average duration of pyrexia was 3.66 days, of pain 4 days (Owen[134]); in 82 at the Middlesex the average duration of pyrexia was 5 days, of pain 5.6 days (Coupland[135]); and in 55 at the Westminster the average duration of pyrexia was 7 days, of pain 7.25 days[136]--that is, a general average duration in the whole series for the pain and pyrexia of 5.4 days.

[Footnote 133: _Ibid._, p. 1080.]

[Footnote 134: _Ibid._, p. 1081.]

[Footnote 135: _Ibid._, i., 1882, 10.]

[Footnote 136: _Ibid._, ii., 1881, p. 1080.]

Further, 36 per cent. of Fagge's cases and 58 per cent. of Greenhow's were relieved of both the above symptoms on the fourth day; 24.8 per cent. of Fagge's and 50 per cent. of Greenhow's on the third day; and 13.5 per cent. of Fagge's and 26.6 per cent. of Greenhow's on the second day. In Clouston's 27 cases, treated in private, 66.6 per cent. were free from pain and 59 per cent. from fever within three days, and 85.2 per cent. were devoid of pain and 72.7 per cent. of fever within four days.[137] Finally, all who have had much experience of this method of treating acute rheumatism will agree that the first or second dose frequently relieves the articular pains like a charm, and the local swelling then frequently subsides in from sixteen to forty-eight hours.

[Footnote 137: _The Practitioner_, i., 1882.]

2. Relapses are more frequent--probably considerably more frequent--under treatment by salicylates than under other methods. Thus, the average of relapses in eight different tables of cases treated by the salicyl remedies ranged from 16.6 per cent. to 35 per cent., giving a general average of 26 per cent.;[138] while under other methods in three different tables the average ranged from 5.4 per cent. to 27.6 (this last under the full alkaline), giving a general average of 16 per cent.[139] Relapses appeared to recur less frequently in those cases which yielded to the salicylates within five days than in those which took from six to eleven days to yield, in the ratio, according to Fagge's figures, of 26.6 per cent. for the first, and 29.4 per cent. for the second day; and, according to Hood's, as 18.4 per cent. to 24.4 per cent. There does not appear to be any regularity in the order of occurrence or recurrence of relapses, nor is Southey's definite statement that in "relapsing cases the temperature is nearly or quite normal on the eighth evening, and a slight relapse occurs on the thirteenth morning," borne out by the statistics produced at the London Medical Society. Moreover, W. Carter's cases[140] have not confirmed Southey's precise statement respecting the gradual remission of the temperature on the eighth and ninth days of illness in the continued or non-relapsing, uncomplicated forms. Irregularity and inconstancy are the typical features of articular rheumatism. The relapses under the treatment by the salicylates have been referred to the premature disuse of those remedies, but they do occur notwithstanding {53} the continued employment of them. It is a general opinion that exposure to cold, errors in diet, and an early return to work are frequent causes of relapse; and Broadbent refers the increased liability to relapse under the salicyl compounds to the rapidity with which those remedies relieve the acute symptoms of articular rheumatism, in consequence of which sufficient care is not observed either by the patients or their nurses, and they are exposed to some of the above exciting causes of relapse. All the above causes do probably play their part so long as the materies morbi (if that really exist either as a chemical principle or as a germ) has not been wholly eliminated or destroyed. Indeed, the short intervals which frequently obtain between the primary invasion of the so-called relapses, and the failure of the salicyl compounds to prevent peri- and endocarditis, render it probable that what are commonly spoken of as relapses are not due to a new infection, as in the case of the relapse of typhoid fever, but to the recrudescences of a disease not yet terminated, but over some of the manifestations of which--the articular inflammation and the pyrexia--the salicylates exercise some control.

[Footnote 138: Fagge's, 26.2 per cent.; Greenhow's, 35; Warner's, 33.6; Owen's, 30.2; Hood's, 18.8; Coupland's, 35.3; Broadbent's, 16.6; Powell's, 18.7; total, 214 ÷ 8 = 26 per cent.]

[Footnote 139: Hood's, 5.4; Warner's, 14.9; Owen's, 27.6; total, 47.9 ÷ 3 = 16 per cent.]

[Footnote 140: _The Liverpool Med.-Chirurgical Journal_, July, 1881, p. 101.]

3. Authorities are generally agreed that the salicyl compounds do not arrest or control rheumatic inflammation of the endo- or pericardium or pleura, or subdue the pyrexia, if these complications in well-marked degree exist; and there is strong evidence to show that they do not at all constantly prevent the disease from involving those organs, even after the articular affection has subsided under their use. Inestimable as is the benefit conferred by these remedies in promptly relieving the articular pain and fever, they do not secure the great desideratum in the treatment of acute articular rheumatism--protection of the heart.

In 352 cases treated with salicylate of soda at the Westminster Hospital, heart disease developed in 13.6 per cent.; in 267 treated without the salicylate, heart disease developed in 14.2 per cent. (Warner's cases).[141] In 350 cases treated with salicylates at Guy's, heart complications obtained in 68 per cent., while in 850 treated without them, the cardiac complications occurred in 58.8 per cent. (Hood).[142] Gilbart-Smith collected a large number of cases from several of the London hospitals, and analyzed them with the following results: Of 1727 cases of acute rheumatism treated before the introduction of the salicyl compounds, the proportion of cardiac complications was 54.4 per cent.; in 1748 cases treated subsequently to their introduction, the cardiac affections obtained in 63.4 per cent.; and in 533 cases treated by the salicyl compounds, those affections obtained in 68.4 per cent.[143]

[Footnote 141: _The Lancet_, ii., 1881, 1080.]

[Footnote 142: _Ibid._, ii., 1881, 1120.]

[Footnote 143: _Ibid._, i., 1882, 136.]

These facts certainly seem to prove that the salicyl compounds do not prevent the occurrence of the visceral complications or manifestations of acute articular rheumatism; and if space permitted instances might be quoted from many authors in which either endo- or pericarditis or pleuritis or pneumonia or other visceral manifestation had set in after the patient had been taking the salicylates long enough to have produced their usual physiological effects; some of these will be mentioned under the next section.

It may be objected that in the above estimates sufficient attention has not been paid to the period of the disease at which the treatment by the {54} salicylates was begun, the time it was continued, the doses given, the age of the patient, the severity and other characters of the illness, such as whether acute or subacute, first or second attack, complicated or not.

4. It must be admitted that there are a few facts which render it very probable that the salicyl compounds do really reduce the frequency of these complications, and thus give some protection to the heart in rheumatism. Of Powell's 32 cases, 19 = 60 per cent. had heart disease when admitted; and of the remaining 13, 6 = 46 per cent. developed cardiac disease after admission and while under the salicylates.[144] Of Dr. Jacobi's[145] 150 cases, 78 = 52 per cent. were admitted with unsound hearts, and of the other 72, only 5 = 6.9 per cent. developed cardiac disease after beginning salicylate treatment. Of Southey's 51 cases, 24 = 47 per cent. were admitted with diseased hearts; and of the remaining 27, only 4 = 14.8 per cent. developed a cardiac affection subsequent to beginning treatment by the salicylates.[146] Of the Boston Hospital cases, 38 per cent. were affected with heart disease at entrance, and only 4.76 per cent. afterward. No heart affection was developed in any of Clouston's 27 private cases--a result he attributes to the early period at which the remedies are given in private practice. But the number is too small to permit of any conclusion being drawn, and 4 of the cases were examples of recurrence of the disease at short intervals (three and four weeks) in the same patient, in whom there appears to have existed no proclivity to cardiac complication, for he had had four attacks before he came under Clouston's care. Moreover, his cases were mild, but 16 of them being acute, and of these only 3 attaining a temperature of 103° and upward. Finally, Herman[147] estimates the percentage of heart affections that developed after beginning the salicylates in the London Hospital at 18.7 per cent., and after other treatment at 30 per cent. Omitting Clouston's, the general average of the above results is, that in 49.2 per cent. cardiac disease existed before the patients began the salicyl treatment, and that in 18.2 per cent. it developed after that, while 30 per cent. of cardiac disease developed after other methods of treatment were begun.

[Footnote 144: _Lancet_, i., 1882, 134.]

[Footnote 145: _St. Thomas's Hospital Reports_, New Series, viii. 252.]

[Footnote 146: _St. Bartholomew's Hospital Reports_, xvi. 10.]

[Footnote 147: Quoted by T. G. Smith, _Lancet_, i., 1882, 137.]

The subject is one beset with difficulties, and still needs investigation. It is reasonable to infer that as the salicylates promptly arrest the articular inflammation and allay the fever of uncomplicated acute rheumarthritis, they will prevent the visceral inflammations so apt to develop when the disease runs its course uninfluenced by treatment; but experience has shown that they do not control or arrest rheumatic inflammation of the heart or pleura or the attending pyrexia, although capable of subduing the articular inflammation and the pyrexia that accompanies it. The most eminent therapeutists are divided on the subject. Maclagan, while admitting that the salicyl compounds do not ward off cardiac complications, or cure them when they exist, maintains that their existence is an additional reason for giving those remedies freely and in large doses.[148] Broadbent,[149] while believing in the protective influence of the salicylates "when brought to bear upon the fever in the first days of its existence," finds in the presence of any cardiac inflammation a reason for at once discontinuing those remedies. Flint[150] believes that rheumatic endo- and {55} pericarditis are more common since the introduction of the salicyl treatment than when the alkaline method was relied upon almost entirely, and advises[151] the administration of alkalies with the salicylates to protect the heart. Vulpian[152] thinks the protective power in question probable, but not established; while the latest French authority, Homolle, is of opinion that "cardiac affections are really less frequent in patients treated by salicylate of sodium than in others."[153]

[Footnote 148: _Lib. cit._, pp. 266, 275.]

[Footnote 149: _Lancet_, i., 1882, 138.]

[Footnote 150: _New York Med. Record_, 1882, 66.]

[Footnote 151: _Pract. Med._, 5th ed., 1098.]

[Footnote 152: _Du Mode d'Action du Salicylate du Soude dans le Traitement du Rheum. Artic. Aigue_, Paris, 1881, 11.]

[Footnote 153: _Nouveau Dict. de Méd. et de Chir._, xxxi., 1882, 648.]

5. The occurrence of hyperpyrexia is not always prevented by the salicyl remedies, even when they have produced their full physiological effects. Fagge endeavors to explain away the two cases of hyperpyrexia which occurred under Greenhow and the other two which happened amongst the cases tabulated by himself, and remarks that if the temperature should begin to fall under the use of salicylic acid, and then should change its course and rapidly attain a dangerous height, that would really show that the drug is sometimes incapable of preventing the occurrence of hyperpyrexia. This actually happened in one of Powell's two cases,[154] and the patient died suddenly at a temperature of 107°. In Greenhow's first case the patient had been taking the salicylate for four days, and was deaf and delirious when the temperature became 105.8°.[155] Finney reports a case in which drachm iss of salicine were given daily for two days, and drachm ij on the third day, when pericarditis set in, and on the fourth day hyperpyrexia supervened.[156] Haviland Hall records an instance in which the temperature fell from 103.5° to 100.6° after twenty-grain doses of salicylate soda, every three hours, taken for two days; on the third day the medicine was given every four hours; the temperature rose in the evening to 103.4°, and on the next day it rose rapidly to 108.7°, and the patient became delirious. Patient recovered rapidly after two baths.[157]

[Footnote 154: _Lancet_, i., 1882, 135.]

[Footnote 155: _Clin. Soc. Trans._, xiii. 264.]

[Footnote 156: _Brit. Med. Journ._, ii., 1881, 932.]

[Footnote 157: _Lancet_, ii., 1881, 1082. See also two cases in _Med. Times and Gaz._, ii., 1876, 383.]

Pericarditis is not always present when hyperpyrexia arises during the administration of salicylic acid; it was absent in Powell's cases, is not mentioned in Hall's, and did not ensue in one of Greenhow's until two days after the temperature had reached 105.4° F. However, either pericarditis or pneumonia is very frequently present when the temperature is excessive. It is generally admitted that the salicylates do not control rheumatic hyperpyrexia once it exists.

6. Notwithstanding the prompt removal of the pain and reduction of the fever by the salicyl compounds, the average duration of acute articular rheumatism is not very considerably lessened by those remedies. Thus, of Hood's[158] 350 cases treated by salicylates the average duration of the illness was 35.95 days as against 38.75 under other methods. The average time spent in bed by Warner's 342 cases was 19.5 days under the salicylates, and by 352 patients under other remedies 23.5 days. Both estimates show a curtailment of the duration of the disease by the new treatment of three to four days only; which is not a very material improvement.

[Footnote 158: Calculation from Dr. Hood's Tables 1 and 1_a_, _Lancet_, ii., 1881, 1119.]

{56} 7. Nor do the salicylates materially alter the time spent in hospital by rheumatic patients; some evidence indicates that they actually prolong that period. The following are the average residences in hospital under the salicylates, according to several recent authors, and they are remarkably uniform with two exceptions: Coupland, 36 days; Warner, 34.9; Hall, 34; Southey, 32.5; Broadbent, 31.2; Powell, 31; Finlay and Lucas, 29.7;[159] Owen, 23; Brown, 21.9;[160] or a general average of 30.4 days for the salicyl remedies. Under full alkaline treatment: Owen, 26 days; Dickinson, 25;[161] Fuller, 22.2;[162] Blakes, 24;[163] or a general average of 24.3 days for full alkaline treatment. And if to these we add Finlay and Lucas's results, 27.7 days, under but two to three drachms of alkaline salts in the twenty-four hours--a quantity only the fourth of that given under the full alkaline method--the general average residence in hospital under alkaline treatment was but 25.4 days; that is, five less than under the salicylate.

[Footnote 159: _Lancet_, ii., 1879, 420.]

[Footnote 160: _Boston Med. and Surg. Journ._, Feb., 1877. The four cases excluded by the reports are included in this calculation, that it may more fairly be compared with other reports.]

[Footnote 161: _Lancet_, i., 1869.]

[Footnote 162: _The Practitioner_, i., 1869, p. 137.]

[Footnote 163: _Boston City Hospital Reports_, 1st Series.]

These several estimates of the time spent in hospital under the salicylates, with the exception of Owen's and Brown's, correspond closely with that of the time spent by Gull's and Sutton's patients under mint-water--32.8 days--although the general average of them falls short of the latter by 2.4 days.

The following table (iii.) of Hood's[164] shows that under the salicylate method 45.7 per cent. remained in hospital beyond forty days, and 39 per cent. under other methods, and that about 50 per cent. more were discharged within twenty days under the other methods than under the salicylate:

350 cases treated with salicylates:
Days.
Under 10. Under 20. Under 30. Under 40. Ill longer.
3 = 0.84%. 31 = 8.88%. 76 = 21.7%. 84 = 24%. 160 = 45.7%.

850 without salicylates:
Days.
Under 10. Under 20. Under 30. Under 40. Ill longer.
12 = 1.4%. 105 = 12.35%. 175 = 20.1%. 182 = 21.4%. 331 = 39%.

[Footnote 164: _The Lancet_, ii., 1881, 1120.]

These statistics favor Greenhow's opinion that patients treated with salicylate of sodium regain their strength slowly, and are long in becoming able to resume their ordinary occupations. Some allowance, however, must be made for the precautions against relapse under salicylates observed in hospitals since the great tendency thereto has been recognized.

8. Certain unpleasant or toxic effects are produced by salicylic acid and salicylate of sodium; such are nausea, vomiting, abdominal pain, frontal headache, tinnitus, incomplete deafness, vertigo, tremor, quickened respiration, very rarely amblyopia and even temporary amaurosis, and not unfrequently delirium. A feeling of prostration and general misery is not uncommon. These phenomena of salicylism are in great measure proportionate to the dose employed, but they have followed moderate {57} doses, owing sometimes to idiosyncrasy, and perhaps frequently to retarded elimination consequent upon previous disease of the kidneys or disturbance of their function by the salicylic acid or its salt. Those agents are usually completely excreted in forty-eight hours, but in one of Powell's[165] cases elimination was not completed before the fifth day, and not before the eighth in Byanow's case.[166] Possibly uræmia may in some cases cause the delirium.[167] The delirium, which may be violent or not, is often preceded by dryness of the tongue, restlessness, and rapid breathing. Impurities in the acid may account for the inconstancy with which delirium has been noticed by different observers. While but 2 instances in 82 cases were met with by Coupland, 3 out of 90 cases by Broadbent, and 3 out of 109 by Brown,[168] Charles Barrows[169] encountered 8 instances in 28 cases. In one of these a boy of eleven became delirious in eighteen hours, having taken 10 grs. of salicylate of sodium every three hours. In another instance the drug had been in full use for five days before the delirium manifested itself. These phenomena of salicylism rapidly disappear when the medicine is stopped, and delirium has not always recurred on its resumption. They are less frequent in children, in whom elimination by the kidneys takes place very rapidly and a marked tolerance of salicyl compounds exists. Occasionally more serious effects appear to be produced by the salicylates, owing to their direct action on the heart, impairing its power, as evidenced by feeble impulse and sounds, increased frequency of the pulse, and diminution of the arterial pressure.[170] But, notwithstanding the very large number of cases of acute rheumatism that have been treated by the salicyl compounds, very few clear instances of their toxic action on the heart have been recorded, and even in some of these there were other conditions present that may have played some part, perhaps a chief part, in the production of cardiac failure. In Greenhow's case[171] the autopsy revealed a dilated fatty heart and slightly granular kidneys, and the cardiac failure coincided with a fall of temperature to 97° F. Goodhardt's[172] patient died in nine hours after beginning the salicylic acid, of which she took but one drachm, in divided doses, every three hours. The pulse rose rapidly to 160; she was restless and moaning, but died quietly and suddenly. Recent pericarditis, with one or two points of fatty degeneration of the heart's substance, and sound kidneys were found. The reporter of the case inclines to the opinion that the acid produced sudden collapse and cardiac failure, while Bristowe referred them to the rheumatic poison itself. I have not been able to refer to Hoppe Seyler's paper,[173] in which he relates that having given 5 grammes of salicylic acid to a child of seven and a half years affected with articular rheumatism, shortly afterward there occurred deafness, agitation, profuse sweating, dyspnoea, and finally fatal collapse. The condition of the heart and kidneys before and after death is not given. Weber {58} published[174] an instance in which 15-gr. doses of salicin given to a woman of twenty-seven produced in thirty-four hours a rapid fall of temperature from 103° to 96° F., accompanied by delirium and serious but not fatal collapse. It is well to remember that a similar failure of cardiac power is occasionally observed in other fevers when rapid defervescence occurs, although the salicyl compounds have not been taken; and it is certainly necessary to give these remedies cautiously, and often to administer alcohol with them, when the heart's action is at all enfeebled by protracted pyrexia and pain, or by disease (inflammatory or degenerative) of its substance or envelope. Indeed, if severe cardiac inflammation obtain in rheumatism, the remedies are powerless and perhaps unsafe. The sudden reduction of the temperature when much exhaustion obtains, even in the hyperpyrexia of rheumatic and other fevers, whether by salicylic acid or quinia or the cold bath, may be attended with fatal collapse of the heart.

[Footnote 165: _Lancet_, i., 1882, 135.]

[Footnote 166: Quoted by Wood in his _Therapeutics and Mat. Med._, 1880, from _Centralb. für Chir._, 1877, 809.]

[Footnote 167: See DaCosta's observations in _Am. Med. Journal_, vol. lxix., and Ackland's in _B. Med. Journal_, i., 1881, 337.]

[Footnote 168: _Boston Med. and Surg. Journal_.]

[Footnote 169: _N.Y. Med. Record_, April 29, 1882, 456.]

[Footnote 170: Köhler, _Centralb. f. Med. Wissensch._, 1876, and Dunowsky, _Arbeiter Pharm. Labor._, Moskau, i. p. 190, quoted by H. C. Wood, _Therapeutics, Mat. Med., etc._, 3d ed., p. 639.]

[Footnote 171: _Clin. Soc. Trans._, xiii. p. 266, c. iii.]

[Footnote 172: _Ibid._, p. 123.]

[Footnote 173: Quoted by D. Seille, Thèse, _De la Méd. Salicylée dans le Rheumatism_, Paris, 1879, p. 54.]

[Footnote 174: _Clin. Soc. Trans._, x. p. 70, 1877.]

Instead of the frequent weak pulse above mentioned, I have many times found salicylate of sodium render the pulse very slow, labored, and compressible in typhoid fever, and generally at the same time the temperature has been considerably reduced below what it had been.

A temporary albuminuria is not infrequent; excluding mere traces, it obtained in 52 per cent. of cases treated by the salicylates alone or in conjunction with full doses of alkali, and in but 25 per cent. of those in which full doses of alkali, with or without quinia, were employed.[175]

[Footnote 175: Isambard Owen, _Lancet_, ii., 1881, p. 1081.]

Very rarely hæmaturia and even nephritis have occurred. The active principle is chiefly eliminated by the kidneys, which may account for a local irritating influence upon those organs.

Salicine is much preferred by Maclagan to salicylic acid and to salicylate of sodium, on the grounds that it is a bitter tonic and produces less debility and more rapid convalescence than those agents, and that it never produces delirium nor depresses the heart's action. Ringer[176] and Charteris[177] state that they have never seen salicine, even in large doses, cause delirium; and Prof. Gairdner has not found it produce any unfavorable symptoms.[178] On the other hand, Greenhow[179] found that marked depression of the heart's power ensued in 4 out of 10 cases whilst the patients were taking salicine, and entirely subsided after it was discontinued. Further careful and extended observation is needed before the relative value of salicine and salicylate of sodium can be reliably stated. It is probable that the salt is more active and prompt than the bitter principle; and this, with the greater cheapness of the former, may perhaps account for the more general employment in hospitals of the salicylate than of salicine. The latter, moreover, is often tolerated when the former is not.

[Footnote 176: _Handbook Therapeutics_, 8th ed., 1880, 587.]

[Footnote 177: _Brit. Med. Jour._, i., 1881, 229.]

[Footnote 178: _Lancet_, i., 1882, in table giving experience of British hospitals, prepared by Maclagan.]

[Footnote 179: _Trans. Path. Soc._, xiii. 262.]

As regards the doses of these agents required in acute rheumatic arthritis, practitioners are not agreed; Maclagan, Stricker, Fagge, Broadbent, Ringer, Flint, Sée, recommend large doses at short intervals at the outset, with the view of getting the patient rapidly under the influence of the drug. Maclagan gives salicine scruple i-ij at first hourly, then every two hours {59} as the acute symptoms begin to decline; after the second day he allows 20 to 30 grs. every four hours for two or three days; "and for a week or ten days more that quantity should be taken three times a day." Stricker, Fagge, Broadbent, and Sée recommend about 20 to 30 grs. of salicylate of sodium every hour or two for six doses (= drachm ij-iij in the day), and Ringer would employ 10 grs. hourly, and if in twenty-four hours this dose has not either modified the disease or produced its characteristic symptoms, he would increase it to 15 and then to 20 grains hourly. On the other hand, Owen's[180] results show practically no difference in the duration of pain and pyrexia and in the average duration of illness from the commencement, whether drachm iij or drachm ij or drachm iss were given every twenty-four hours; and C. G. Young[181] found that 10 to 15 grs. every one, two, or three hours are sufficient.

[Footnote 180: _Lancet_, ii., 1881.]

[Footnote 181: _Dub. Journ. Med. Sci._, Sept., 1880, 193.]

Indeed, exceptionally good and exceptionally indifferent results are reported under similar doses. No such good results are reported as those of the Boston City Hospital under doses of drachm ij to drachm iv per diem, the average residence in hospital being only eighteen days if four cases which became chronic are excluded, or 21.9 days if they are included.

The plan in vogue at our hospital here and in my own private practice is to give about 15 grains every two or three hours, according to the severity of the case and until the articular pain and pyrexia are relieved. After the pain and pyrexia have yielded, the remedy should be continued in smaller doses, say 10 to 15 grs., three or four times a day, according to the severity of the case, for eight to ten days longer, to prevent relapse, and during this period exposure, exercise, and dietetic excesses must be carefully guarded against.

The salicine may be given dissolved in milk or enclosed in wafers; the salicylate of soda, in a solution of any aromatic water, to which extract of liquorice or syrup of lemon and a few drops of spirits of chloroform may be added. The French add a little rum to flavor the mixture. Should severe cardiac inflammation exist, and, even although not severe, should there exist signs of failure of cardiac power, salicylates and salicine had better be avoided. If the secretion of urine diminish considerably under their use, or hæmaturia supervene, or organic disease of the kidneys exist, they must be employed cautiously, and may require prompt suspension. If marked debility exist, stimulants, especially the alcoholic, should be combined with them.

The oil of wintergreen has recently been well spoken of by F. P. Kinnicutt of St. Luke's Hospital, New York,[182] as a substitute for salicylate sodium. It is itself a methyl salicylate 90 per cent., plus terebene 10 per cent. Its officinal name is oleum gaultheria, and it is given in doses of minim x-xv every two hours except during sleep, and in severe cases of articular rheumatism during the twenty-four hours, either by floating the oil upon a wineglass of water or milk or in capsules or upon lumps of white sugar. It resembles in its influence upon acute rheumatism very closely the sodium salicylate, for which it may perhaps be substituted, and Kinnicutt maintains that it is quite as effectual, pleasanter to take, and free from the intoxicating properties of the salt and the salicylic acid. It requires to be continued during convalescence just like the salicylate.

[Footnote 182: _Med. Record of New York_, Nov., 1882, 505.]

{60} The alkalies--in this country at least--were the favorite remedies in the treatment of acute articular rheumatism before the powers of salicine and salicylic acid became generally known, and there are still authorities who maintain their excellence, if not their superiority over the salicylates, in protecting the heart against the recurrence of rheumatic inflammation (Flint, Dickinson, Sinclair, Stillé).

Under the term the alkaline treatment unfortunately are included two distinct methods of administering the salts composed of potash and soda and the vegetable acids, carbonic, tartaric, citric, etc.--viz.: that in which about half a drachm of one of these salts is given three or four times a day; and the other known as Fuller's method, in which large doses are prescribed, so that from an ounce to an ounce and a half is given in the first twenty-four hours, with the view of rapidly rendering the urine alkaline, and if possible the perspiration also; for I have frequently produced the former effect in less than twelve hours, yet have found the perspiration still redden litmus on the second, and even the third, day and later. A disregard of the essential differences existing between these two methods of employing alkalies in acute rheumatism may partially account for the differences of opinion existing as to the value of the alkaline treatment, and for the differences in the statistical results thereof published by various observers--a remark applicable to other methods and statistics also. Fuller commonly ordered every three or four hours bicarb. sodium drachm iss and acetate of potassium drachm ss dissolved in ounce iij of water and rendered effervescing at the moment of administration by the addition of an ounce of lemon-juice or drachm ss of citric acid. As soon as the urine presents an alkaline reaction--which is usually the case in twelve to twenty-four hours--the quantity of the alkali is reduced by one-half, or to about 8 drachms, during the succeeding twenty-four hours, and provided the urine continues alkaline to 3 drachms on the third day. On the fourth day and subsequently only a scruple to half a drachm of alkali is given three times a day, sufficient to keep the urine alkaline, and to each dose are added 3 grains of quinia dissolved in lemon-juice; and this combination is continued till convalescence sets in. An aperient pill is given whenever needed, but is administered "only under conditions of extreme nervous irritation." The method is not an exclusively alkaline one.

Space will not allow of a lengthened analysis of the statistics that have been published on this subject, and I will give only some of the more important statistical results. While, as we have seen, the average duration of pyrexia and articular pain under salicylate treatment is about 5.4 days, under moderate alkaline treatment, according to the recent statistics of Finlay and Lucas,[183] the average duration of pyrexia was 10.3 days and of articular pain 12.2 days, and of Owen[184] 6.5 days for the first and 8 days for the second, or a general average for the pain and pyrexia together of 9.25 days, or about 3.85 days longer than under the salicylate treatment. Nor can it be said even of the full alkaline plan that the first or second dose frequently relieves the articular pains like a charm. On the other hand, it has been already shown that the average time spent in hospital was five days less under the full alkaline than under the salicylate treatment.

[Footnote 183: _Lancet_, ii. 1879, 420.]

[Footnote 184: _Ibid._, ii., 1881, 1081.]

As regards the relative power of the salicylates and of full alkaline {61} treatment in protecting the heart, the following analysis and calculation deserve attention. The percentage of cases in which cardiac disease set in after the salicylate treatment began was, according to Powell, 18.75; according to Haviland Hall, 37.1; according to Finlay and Lucas, 11.60; Southey, 8; Brown, 4.76; Jacobi, 3.35, or a general average of 14 per cent.; whereas cardiac disease developed after the alkaline treatment had commenced in 13.6 per centum according to Blake;[185] in 10.7 per cent. according to Dickinson;[186] in 7 per cent. according to Owen; in 6.6 per cent. according to Finlay and Lucas; and in 2 per cent. according to Fuller; making a general average of only 7.8 per cent.

[Footnote 185: _Med. and Surg. Reports of Boston City Hospital_, 1st Series, 1870.]

[Footnote 186: This percentage is obtained by adding together all the cases treated by alkalies given by Dickinson in his IX., X., XI., and XII. tables. Their total was 65 cases in which the heart was affected seven times. In table IX. from drachm ii-iv of alkaline salts were given daily, and in table X. about drachm iij daily.--_Lancet_, i., 1869.]

Judging from these statistics, it is not improbable that a combination of sodium salicylate, with full doses of bicarbonate of sodium or chlorate of potassium, will give better results in the treatment of acute rheumatism than either of those classes of remedies singly. Indeed, Flint and others have advised such combinations, and Bedford Fenwick has recently stated, as a result of his experience in 30 cases, that if, after giving a free purge, followed by scruple doses of sodium salicylate hourly for six hours, that salt be stopped, and in twelve hours afterward half-drachm doses of citrate of potassium be administered every four or six hours until the saliva becomes alkaline, relapses will be extremely rare, and that this is the safest and most successful method of treating acute and subacute articular rheumatism.[187]

[Footnote 187: _Lancet_, i., 1882.]

Having spoken somewhat fully upon the remedies of which I have most personal experience, and which have the largest number of advocates at the present time, and having advised the combination of these remedies, I shall only glance at some of the other remedies or methods of treating the disease still more or less employed.

Quinia, given in divided doses to the extent of 15 to 30 grains in the day, is still highly thought of in France in the early stages, during the course of and on the occurrence of relapses, in acute (especially febrile poly-) articular rheumatism. It is claimed by Briquet, Monneret,[188] Legroux, and others that although not a specific for the disease it moderates the general disturbance, diminishes the local affections, and even retards the development or lessens the gravity of the cerebral symptoms--that, although it does not control the cardiac inflammations, it is not contraindicated by them. The only recent English authority who has strongly advocated full doses of quinia in this disease is Garrod,[189] but he mixed the drug, in five-grain doses, with half a drachm of bicarbonate of potassium, a little mucilage, and spirits of chloroform, and gave it every four hours until the fever and articular affection had completely abated. Sufficient facts have not been published to permit of the formation of a reliable judgment as to the actual or the comparative value of either the simple quinia or the quino-alkaline treatment of acute and subacute articular rheumatism. There can be no doubt as to the value of quinia to meet certain conditions incident to the disease, such as debility, lingering {62} convalescence, periodical relapse, excessive perspiration, failure of appetite, and perhaps, in some instances, high temperature. Barclay has found quinia of much service when depression has followed the long continuance of the alkaline treatment and is attended with alkaline urine and a deposit of the earthy phosphates.[190] It may be given by the rectum if not tolerated by the stomach or if the alkalines are being taken.

[Footnote 188: _La Goutte et le Rheumatisme_, Paris, 1857.]

[Footnote 189: Reynolds's _Syst. Med._, 1870, p. 951.]

[Footnote 190: _St. George's Hospital Reports_, vol. vi. p. 111 _et seq._]