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Juvenile Rheumatoid Arthritis (Still's Disease)
JUVENILE RHEUMATOID ARTHRITIS
(Still's Disease) JAMES A. Coss, JR., M.D. \) STILL'S disease has been described as a variety of chronic polyarthritis affecting children and marked by enlargement of lymph nodes, splenomegaly, and irregular fever. The term suggests a distinction between juvenile and adult rheumatoid arthritis which· in practice we avoid. However, enough differences, related to age of onset, exist to make the separation practical as a means of classification. StilP reviewed twenty-two cases of arthritis in children and felt that a small number of them were actually indistinguishable from adult rheumatoid arthritis, while a larger number (twelve of the twenty-two cases) were entirely difFerent because of the characteristics noted above, and because there was less pain, an earlier onset, a lesser preponderance of females, and a liability to inflammation of serous membranes not shared by the rheumatoid arthritis of adults. At present Still's disease is considered to be simply rheumatoid arthritis occurring in young individuals; the apparent differences are due to the varying effect of disease processes in youth and maturity. Several facts lend support to this impression. Lesions similar to those described in children, such as splenomegaly, lymphadenopathy, cardiac and pleuritic lesions, have also been reported in adults with rheumatoid arthritis. 2 ,3 The age of onset is not a reliable index. It is very low in many cases of "adult type" of arthritis, and high, over 12 years even, in some cases that otherwise fit Still's pattern. Pathologic findings do not differ in youth or maturity except for certain skeletal changes to be mentioned later. In a large series the sex distribution is the same for juvenile and adult rheumatoids. Systemic reaction is less severe in adults, but this is true of most disease processes. Changes in various systems reported in adults suggest that inflammation of serous membranes and multiple system involvement are not confined to children. Subcutaneous nodules have been seen in any age group.4 Despite these discrepancies, and others unmentioned, it is convenient to consider Still's disease as rheumatoid arthritis beginning in children of the age of 12 years or less. We usually refer to these cases as juvenile rheumatoid arthritis .
•
From the Edward Daniels FaulKner Arthritis Chnic of the Presbyterian Hospital and the Department of Medicine, College of Physicians and Surgeons, Columbia University, New York City. " Assistant in Medicine, College of Physicians and Surgeons, Columbia University.
568
JUVENILE RHEUMATOID ARTHRITIS
569
The sex distribution shows a female preponderance of five to one just as in adults. 5 • 6 Still's disease may begin in children as young as 15 months of age, but in our experience the highest incidence is in those between the second and third years of life. It is not a common condition, less than 5 per cent of all rheumatoids in our clinic fell into this group. Previous to an intensive study 'of Still's disease in this clinic, the percentage of rheumatoids below the age of 12 was only 1Yz, which seems nearer the usual incidence. PATHOLOGY
The pathologic findings are much as have been described in adult arthritis. Muscle atrophy, however, is more marked and bony lipping 'or spurring is rarely seen in children. Lymph node hyperplasia, liplenomegaly and hepatomegaly are much more common in Still's disease (60, 30 and 23 per cent respectively in this clinic). Myocardial, endocardial and pericardial lesions similar to those of rheumatic fever are occasionally seen in juvenile arthritis; adhesive pericarditis is a frequent finding in autopsy cases. Such lesions as well as the occurrence of pleurisy are fairly frequent in children. The subcutaneous nodules seen in juvenile and adult arthritis are similar to those in rheumatic fever though grossly they may be larger. Amyloidosis involving liver, spleen, lymph nodes and kidneys has been described as a complication of severe arthritis. It is rarely if ever noted in mild cases. In a fairly large series, 7 over 20 per cent of patients developing amyloid disease were under the age of 12 years. Since this group comprises only about 1 Yz per cent of all rheumatoids, amyloidosis appears most commonly to be a complication of the juvenile form of rheumatoid arthritis. It was present in one of two fatal cases in our series. Relative to the skelet~ system, an interesting group of findings has been reported which results directly from arthritis and which is seen only when the disease begins in early life.6 Frequent descriptions have been given of a generalized lack of physical maturity without mental impairment; bird-like facies and a delicate appearance of many arthritic children. Other than the generalized changes just noted, we have observed three types of localized skeletal change resulting from Still's disease, one or more of which are present in nearly 40 per cent of these patients. Twenty-five per cent have an underdeveJoped mandible (brachygnathia) which gives the so-called bird-like facies. Thirteen per cent have luxation or fusion of two or more cerVical vertebrae. About ten per cent have abnormal shortening of one or more fingers or toes. An occasional patient has shortening of an entire extremity. These changes occurred in normal individuals with no growth disturbances prior to the onset of arthritis. A past history is elicite~ 9f particularly severe disease in those loclllj;zed ilIeilll,
570
JAMES A. COSS,
JR.
Fluid accumulates in joint spaces just as in adult rheumatoid arthritis and these accumulations are similar in all respects in those noted in the adult form of the disease. ETIOLOGY
The etiologic basis of Still's disease, as of adult rheumatoid arthritis, has not been determined. Certain predisposing factors common to patients of both age groups are: 1. Influence of climate. Arthritis is rare in the tropics and most common in temperate zones particularly if the region is fairly humid. 2. Season. Early spring artd especially March brings the greatest number of recrudescences and new cases. 8 3. Heredity. Thirty per cent of juvenile arthritics give a family history of rheumatic fever, arthritis, arthralgias, etc. 4. Constitutional factors. The children afflicted usually were not robust or vigorous even before the arthritis developed. Precipitating factors are: 1. Trauma. A history of recent injury mayor may not be elicited. Injury may only serve to light up a pre-existing quiescent focus. 2. Infection. Recent upper respiratory infection, pharyngitis, tonsillitis, otitis or other localized infection is recorded in about 50 per cent of juvenile rheumatoid arthritis. 3. Operations occasionally precede rheumatoid activity despite the fact that removal of definite foci of infection is a rational therapeutic measure. 4. Exanthematous infections, such as scarlet fever or measles, occasionally seem to precipitate arthritis. Hemolytic streptococci (group and type not determined) have been obtained from the nose and throat of 60 per cent of patients studied bacteriologically in this clinic. This fact together with the high antistreptolysin titers obtained and the frequent association of an acute upper respiratory infection suggests a bacterial origin which cannot be dismissed without further study. X-RAY FINDINGS
Bony changes are not the earliest finding and a person may have definite arthritis without any significant changes manifest on x-ray films. There are four stigmas which may be demonstrated in rheumatoid arthritics 9 regardless of age of onset. 1. The earliest and most common finding is soft tissue change be it atrophy, swelling or effusion. Shadows of varying contour and density often enable the experienced observer to distinguish between swelling of tissue and effusion. 2. Next in frequence is decalcification, a decrease in bone density without loss of form which may be local or generalized.
JUVENILE RHEUMATOID ARTHRITIS
571
3. Joint-space narrowing or obliteration is seen only when the articular surfaces are damaged. 4. Bone destruction, like the above change, is late in appearance~_ It consists of localized areas of loss of calcium seen on x-ray plates as punched-out areas near epiphyseal lines. In addition to thes.e general changes seen in patients of any age group, some features peculiar to juvenile rheumatoids have been observed. 1. The previously mentioned growth changes (brachygnathia. brachydactylia and cervical fusion or luxation) are well demonstrated by x-ray. 2. Thickening of periosteum on the shaft of metacarpals or metatarsals and phalanges often gives a heavy appearance to these bones. 1o 3. Thinning of the shaft of phalanges, etc., occasionally gives a delicate appearance quite opposite to the above. 4. Accelerated growth of epiphyses may result in a disparity between the length of long bones. SYMPTOMATOLOGY
Three types of patients present themselves with juvenile rheumatoid arthritis. If the onset is insidious with no known preceding infection, the child may complain of pain in a knee or ankle or begin to limp for no apparent reason. Afternoon temperature is normal or slightly elevated; fatigue, anorexia and failure to gain weight may be noted. Pain in the joint increases and spreads to other joints. On examination there is frequently a tachycardia out of proportion to the low-grade fever. A soft systolic murmur may be heard which, without other symptoms, would be unimpressive. Moderate cervical, axillary, epitrochlear, inguinal or popliteal lymph node enlargement may exist. The spleen or liver may be enlarged. If the process is not recent, joint effusion and swelling together with local muscle atrophy present a striking picture. Fusiform swelling about proximal interphalangeal joints is seen. Terminal interphalangeal involvement is more common in Still's disease than in adult arthritis. As a rule, cases with such an onset are characteristic and easily diagnosed. The second type of patient has a history of an acute onset of migratory polyarthritis often following some infection such as tonsillitis or pharyngitis. At first, joint involvement is minor but systemic reaction is marked with temperature fluctuating to 103° F. or higher, a high e~rocyte sedimentation rate and marked leukocytosis. A distinct systolic murmur and an altered electrocardiogram pattern may exist, suggesting myocardial damage. These cases are easily confused with rheumatic fever, the diagnosis usually made on preliminary examination. Gradually the acute episode subsides; the temperature may continue elevated in the afternoon but at much lower levels. Now joint involvement becomes a prominent factor. Painful fusiform fingers and
572
JAMES A. COSS,
JR.
joint fluid accumulations, muscular atrophy and early limitation of motion persist. Cardiac findings disappear and the electrocardiographic pattern reverts toward normal. The disease which had been a diagnostic problem is now obviously rheumatoid arthritis. The usual laboratory guides of adult arthritis are valueless in Still's disease, for the antistreptolysin titer is high and the streptococcus agglutination titer is normal just as in rheumatic fever. 6 Fortunately the differentiation is not imperative in the acute phase for the treatment indicated is the same. The last type of patient is easily recognized because he is seen for the first time after the systemic reaction has subsided and he is left with only smoldering characteristic joint changes. There may be muscle atrophy, enlargement and limitation in motion of large joints, fusiform fingers with early flexion and extension contractures, limited motion in temporo-mandibular or cervical articulations. A shortened finger or two may be seen, the patient may limp because of old hip or knee involvement or an affected limb may be smaller in circumference than its opposite member. Subcutaneous nodules are occasionally present. Roentgenograms are typical. LABORATORY FINDINGS
Most patients with Still's disease have an anemia (hemoglobin 70 to 80 per cent), and there is a general tendency to slight leukocytosis which may be marked in acute cases. Extremely severe leukocytosis is associated with a poor prognosis. In two fatal cases from this clinic the leukocyte count was over 30,000 per cu. mm. of blood. The urine is normal except the occasional patient in whom amyloid nephrosis develops. Electrocardiograms show evidence of no abnormality in most cases despite the common occurrence of tachycardia. Some patients develop T-wave changes and a long P-R interval suggestive of rheumatic carditis. In those patients in whom arthritis persists and other symptoms subside, the electrocardiogram usually reverts to a normal pattern. The erythrocyte sedimentation rate is moderately or markedly increased (30 to 130 mm. in one hour-Westergren method). As noted before, the streptococcus agglutination titer is rarely elevated, whereas in adult rheumatoids it is positive in from 50 to 66 per cent of the cases. The antistreptococcus hemolysin titer is significantly elevated in Still's disease (mean of 250). Joint fluid obtained by aspiration is no different from that obtained in adults. l l DIFFERENTIAL DIAGNOSIS
The major difficulty is the differentiation of juvenile rheumatoid arthritis from rheumatic fever. The lack of response to salicylates is helpful in ruling out rheumatic fever and severe cardiac damage is
JUVENILE RHEUMATOID ARTHRITIS
573
uncommon in Still's disease. Persistent joint symptoms with subsiding reaction in other systems usually indicate the diagnosis which may be possible to determine only with the passage of time. The antistreptolysin and streptococcus agglutination tests are of no value because results are similar in these two conditions. Still's disease and rheumatic fever are in many ways so similar that some observers suggest the name of rheumatoid or rheumatic state to encompass them both. Tuberculosis occurs in older individuals and is usually monoarticular. Haverhill fever may simulate arthritis of acute onset but the presence of a rash, the lack of chronicity and presence of a demonstrable causative organism distinguish it. l Brucellosis is less common in young children but must be considered when the diagnosis is in doubt. The agglutination or skin tests should be diagnostic. PROGNOSIS
Two patients of the fifty-six in our experience died. Death results from some complication as a rule. The most directly associated condition is perhaps amyloidosis. '~ Morbidity is definitely less in children than in adults. Children do well as a rule if proper supportive care is given; most are left with minor deformities when the process has burned itself out, while a very few have progression of changes until they are hopelessly crippled and confined to bed or wheelchair. Recurrences after a maximum period of activity are not often seen in children, but we occasionally see a patient who has repe~ted bouts of renewed activity extending well into adult life. . TREATMENT
There is no specific treatment for Still's disease and until we arrive at a clearer concept of the etiologic factor such a treatment may remain undiscovered. The same measures tried in adult rheumatoids have been tried in the juvenile patients, including vaccines, vitamins, cod liver oil, bee venom, foreign protein, artificial fever, induced jaundice, chrysotherapy, etc. Because the process tends to be self-limited, some nonspecific measures are important. Rest is necessary during the acute phase with high fever, leukocytosis, suggestion of myocardial damage. A child in this stage should be handled'like one with rheumatic fever. Later, as improVement occurs, restriction is governed by the temperature, erythrocyte sedimentation rate and the patient's sense of well-being. On return to school, any excess activity such as gymnasium classes should be eliminated. In the transition period when school attendance is not practical, it is desirable to employ a home teacher.
574
JAMES A. COSS,
JR.
A high-vitamin, high-caloric diet is essential. Added cod liver oil is of value if tolerated. Physiotherapy is used when the acute process subsides. Gentle massage, dry or moist heat, and baths help depress muscle spasm and pain. Lightweight, posterior, molded plaster splints are made to prevent contractures and subsequent deformity of the knees, hips, elbows, wrists and fingers. Splints are worn all night and part of the day. If neck pain develops or flexion begins, a light plaster collar is used or in extreme cases head traction may be tried. Deformities already present must be corrected with skin traction, wedge casts or skeletal traction so that proper splints may then be applied. 12 If skeletal chanr,es such as ankylosis or cervical fusion have occurred, the only measure left is operative interference to correct the deformity or improve posture. If anemia exists, repeated small transfusions and maintenance doses of iron are given. Barbiturates are valuable for restless, sleepless patients particularly when given with salicylates. Salicylate given as the enteric-coated sodium salt often relieves pain more than any other one measure. In children we prescribe 0.6 gm. or more three or four times daily as needed. The enteric coating causes fewer gastric upsets. Simultaneous sodium bicarbonate is not given as it has been shown to reduce the level of salicylate in the blood. 13 Our results with gold treatment have not been promising in children but we feel that this therapy merits a trial in patients not benefited by the usual supportive measures. In this clinic we have used a preparation of sodium aurothioglucose (Solganol B Oleosum, Schering Corporation). The initial dose is 3 to 5 mg., increased to 25 mg. but we no longer give larger doses even though children's tolerance is better than adults'. The usual checks for toxicity must be employed and 600 mg. constitutes an average course. Some very young patients have received not more than 200 to 300 mg. in a course. A rest period of six weeks or more is given before gold is again instituted. If there is no benefit from three courses of 600 to 800 mg. each, the therapy is pursued no further. It goes without saying that a knowledge of possible toxic effects and careful clinical and laboratory control of the patient is essential if chrysotherapy is instituted. We have seen only two cases of moderately severe toxicity, both of which rapidly cleared on withdrawal of the drug. There have been no fatalities with chrysotherapy. REFERENCES 1. Still, G. F.: Tr. Roy. Med.-Chir. Soc., 80:47, 1897.
2. Chauffard, A. and Ramond, F.: Revue de Med. (Paris), 16:345, 1896. Felty, A. R.: Bull. Johns Hopkins Hosp., 35:16 (Jan.) 1924. 3. Kuhns, J. G. and Joplin, R. J.: New England J. Med., 215:268, 1936. Baggenstoss, A. H. and Rosenberg, E. F.: Arch. Path., 3.5:503 (April) 1943. 4. Dawson, M. H.: J. Exper. Med., 57:845 (May) 1933. 5. Colver, T.: Arch. Dis. Childhood, 12:253 (Aug.) 1937.
JUVENILE RHEUMATOID ARTHRITIS
6. 7. 8. 9. 10. 11. 12. 13.
575
Coss, J. A.: Reported at the New York Rheumatism Assoc., May 9, 1945. Trasoff, A., Schneeberg, H. and Scarf, M.: Arch. Int. Med., 74:4, 1944. Dawson, M. H.: Nelson New Loose-Leaf Medicine, 1935, p. 628. Taylor, G. D., Ferguson, A. B., Kasabach, H. and Dawson, M. H.: Arch. Int. Med., 54:979, 1936. Caffey, J.: Pediatric X-ray Diagnosis. Chicago, Yearbook Publishers, 1945, p. 771. Kling, D. H.: The Synovial Membrane and Synovial Fluid. Los Angeles, Medical Press, 1938, p. 202. Swain, L. T. and Kuhns, J. G.: The Prevention of Deformities in Chronic Arthritis. I. J.A.M.A., 93:1853, 1929; II. J.A.M.A., 94: 1123, 1930; Ill. J.A.M.A., 94:1743, 1930. Smull, K., Wegria, R. and Leland, J.: J.A.M.A., 125:1173 (Aug.) 1944.
(Still's Disease) JAMES A. Coss, JR., M.D. \) STILL'S disease has been described as a variety of chronic polyarthritis affecting children and marked by enlargement of lymph nodes, splenomegaly, and irregular fever. The term suggests a distinction between juvenile and adult rheumatoid arthritis which· in practice we avoid. However, enough differences, related to age of onset, exist to make the separation practical as a means of classification. StilP reviewed twenty-two cases of arthritis in children and felt that a small number of them were actually indistinguishable from adult rheumatoid arthritis, while a larger number (twelve of the twenty-two cases) were entirely difFerent because of the characteristics noted above, and because there was less pain, an earlier onset, a lesser preponderance of females, and a liability to inflammation of serous membranes not shared by the rheumatoid arthritis of adults. At present Still's disease is considered to be simply rheumatoid arthritis occurring in young individuals; the apparent differences are due to the varying effect of disease processes in youth and maturity. Several facts lend support to this impression. Lesions similar to those described in children, such as splenomegaly, lymphadenopathy, cardiac and pleuritic lesions, have also been reported in adults with rheumatoid arthritis. 2 ,3 The age of onset is not a reliable index. It is very low in many cases of "adult type" of arthritis, and high, over 12 years even, in some cases that otherwise fit Still's pattern. Pathologic findings do not differ in youth or maturity except for certain skeletal changes to be mentioned later. In a large series the sex distribution is the same for juvenile and adult rheumatoids. Systemic reaction is less severe in adults, but this is true of most disease processes. Changes in various systems reported in adults suggest that inflammation of serous membranes and multiple system involvement are not confined to children. Subcutaneous nodules have been seen in any age group.4 Despite these discrepancies, and others unmentioned, it is convenient to consider Still's disease as rheumatoid arthritis beginning in children of the age of 12 years or less. We usually refer to these cases as juvenile rheumatoid arthritis .
•
From the Edward Daniels FaulKner Arthritis Chnic of the Presbyterian Hospital and the Department of Medicine, College of Physicians and Surgeons, Columbia University, New York City. " Assistant in Medicine, College of Physicians and Surgeons, Columbia University.
568
JUVENILE RHEUMATOID ARTHRITIS
569
The sex distribution shows a female preponderance of five to one just as in adults. 5 • 6 Still's disease may begin in children as young as 15 months of age, but in our experience the highest incidence is in those between the second and third years of life. It is not a common condition, less than 5 per cent of all rheumatoids in our clinic fell into this group. Previous to an intensive study 'of Still's disease in this clinic, the percentage of rheumatoids below the age of 12 was only 1Yz, which seems nearer the usual incidence. PATHOLOGY
The pathologic findings are much as have been described in adult arthritis. Muscle atrophy, however, is more marked and bony lipping 'or spurring is rarely seen in children. Lymph node hyperplasia, liplenomegaly and hepatomegaly are much more common in Still's disease (60, 30 and 23 per cent respectively in this clinic). Myocardial, endocardial and pericardial lesions similar to those of rheumatic fever are occasionally seen in juvenile arthritis; adhesive pericarditis is a frequent finding in autopsy cases. Such lesions as well as the occurrence of pleurisy are fairly frequent in children. The subcutaneous nodules seen in juvenile and adult arthritis are similar to those in rheumatic fever though grossly they may be larger. Amyloidosis involving liver, spleen, lymph nodes and kidneys has been described as a complication of severe arthritis. It is rarely if ever noted in mild cases. In a fairly large series, 7 over 20 per cent of patients developing amyloid disease were under the age of 12 years. Since this group comprises only about 1 Yz per cent of all rheumatoids, amyloidosis appears most commonly to be a complication of the juvenile form of rheumatoid arthritis. It was present in one of two fatal cases in our series. Relative to the skelet~ system, an interesting group of findings has been reported which results directly from arthritis and which is seen only when the disease begins in early life.6 Frequent descriptions have been given of a generalized lack of physical maturity without mental impairment; bird-like facies and a delicate appearance of many arthritic children. Other than the generalized changes just noted, we have observed three types of localized skeletal change resulting from Still's disease, one or more of which are present in nearly 40 per cent of these patients. Twenty-five per cent have an underdeveJoped mandible (brachygnathia) which gives the so-called bird-like facies. Thirteen per cent have luxation or fusion of two or more cerVical vertebrae. About ten per cent have abnormal shortening of one or more fingers or toes. An occasional patient has shortening of an entire extremity. These changes occurred in normal individuals with no growth disturbances prior to the onset of arthritis. A past history is elicite~ 9f particularly severe disease in those loclllj;zed ilIeilll,
570
JAMES A. COSS,
JR.
Fluid accumulates in joint spaces just as in adult rheumatoid arthritis and these accumulations are similar in all respects in those noted in the adult form of the disease. ETIOLOGY
The etiologic basis of Still's disease, as of adult rheumatoid arthritis, has not been determined. Certain predisposing factors common to patients of both age groups are: 1. Influence of climate. Arthritis is rare in the tropics and most common in temperate zones particularly if the region is fairly humid. 2. Season. Early spring artd especially March brings the greatest number of recrudescences and new cases. 8 3. Heredity. Thirty per cent of juvenile arthritics give a family history of rheumatic fever, arthritis, arthralgias, etc. 4. Constitutional factors. The children afflicted usually were not robust or vigorous even before the arthritis developed. Precipitating factors are: 1. Trauma. A history of recent injury mayor may not be elicited. Injury may only serve to light up a pre-existing quiescent focus. 2. Infection. Recent upper respiratory infection, pharyngitis, tonsillitis, otitis or other localized infection is recorded in about 50 per cent of juvenile rheumatoid arthritis. 3. Operations occasionally precede rheumatoid activity despite the fact that removal of definite foci of infection is a rational therapeutic measure. 4. Exanthematous infections, such as scarlet fever or measles, occasionally seem to precipitate arthritis. Hemolytic streptococci (group and type not determined) have been obtained from the nose and throat of 60 per cent of patients studied bacteriologically in this clinic. This fact together with the high antistreptolysin titers obtained and the frequent association of an acute upper respiratory infection suggests a bacterial origin which cannot be dismissed without further study. X-RAY FINDINGS
Bony changes are not the earliest finding and a person may have definite arthritis without any significant changes manifest on x-ray films. There are four stigmas which may be demonstrated in rheumatoid arthritics 9 regardless of age of onset. 1. The earliest and most common finding is soft tissue change be it atrophy, swelling or effusion. Shadows of varying contour and density often enable the experienced observer to distinguish between swelling of tissue and effusion. 2. Next in frequence is decalcification, a decrease in bone density without loss of form which may be local or generalized.
JUVENILE RHEUMATOID ARTHRITIS
571
3. Joint-space narrowing or obliteration is seen only when the articular surfaces are damaged. 4. Bone destruction, like the above change, is late in appearance~_ It consists of localized areas of loss of calcium seen on x-ray plates as punched-out areas near epiphyseal lines. In addition to thes.e general changes seen in patients of any age group, some features peculiar to juvenile rheumatoids have been observed. 1. The previously mentioned growth changes (brachygnathia. brachydactylia and cervical fusion or luxation) are well demonstrated by x-ray. 2. Thickening of periosteum on the shaft of metacarpals or metatarsals and phalanges often gives a heavy appearance to these bones. 1o 3. Thinning of the shaft of phalanges, etc., occasionally gives a delicate appearance quite opposite to the above. 4. Accelerated growth of epiphyses may result in a disparity between the length of long bones. SYMPTOMATOLOGY
Three types of patients present themselves with juvenile rheumatoid arthritis. If the onset is insidious with no known preceding infection, the child may complain of pain in a knee or ankle or begin to limp for no apparent reason. Afternoon temperature is normal or slightly elevated; fatigue, anorexia and failure to gain weight may be noted. Pain in the joint increases and spreads to other joints. On examination there is frequently a tachycardia out of proportion to the low-grade fever. A soft systolic murmur may be heard which, without other symptoms, would be unimpressive. Moderate cervical, axillary, epitrochlear, inguinal or popliteal lymph node enlargement may exist. The spleen or liver may be enlarged. If the process is not recent, joint effusion and swelling together with local muscle atrophy present a striking picture. Fusiform swelling about proximal interphalangeal joints is seen. Terminal interphalangeal involvement is more common in Still's disease than in adult arthritis. As a rule, cases with such an onset are characteristic and easily diagnosed. The second type of patient has a history of an acute onset of migratory polyarthritis often following some infection such as tonsillitis or pharyngitis. At first, joint involvement is minor but systemic reaction is marked with temperature fluctuating to 103° F. or higher, a high e~rocyte sedimentation rate and marked leukocytosis. A distinct systolic murmur and an altered electrocardiogram pattern may exist, suggesting myocardial damage. These cases are easily confused with rheumatic fever, the diagnosis usually made on preliminary examination. Gradually the acute episode subsides; the temperature may continue elevated in the afternoon but at much lower levels. Now joint involvement becomes a prominent factor. Painful fusiform fingers and
572
JAMES A. COSS,
JR.
joint fluid accumulations, muscular atrophy and early limitation of motion persist. Cardiac findings disappear and the electrocardiographic pattern reverts toward normal. The disease which had been a diagnostic problem is now obviously rheumatoid arthritis. The usual laboratory guides of adult arthritis are valueless in Still's disease, for the antistreptolysin titer is high and the streptococcus agglutination titer is normal just as in rheumatic fever. 6 Fortunately the differentiation is not imperative in the acute phase for the treatment indicated is the same. The last type of patient is easily recognized because he is seen for the first time after the systemic reaction has subsided and he is left with only smoldering characteristic joint changes. There may be muscle atrophy, enlargement and limitation in motion of large joints, fusiform fingers with early flexion and extension contractures, limited motion in temporo-mandibular or cervical articulations. A shortened finger or two may be seen, the patient may limp because of old hip or knee involvement or an affected limb may be smaller in circumference than its opposite member. Subcutaneous nodules are occasionally present. Roentgenograms are typical. LABORATORY FINDINGS
Most patients with Still's disease have an anemia (hemoglobin 70 to 80 per cent), and there is a general tendency to slight leukocytosis which may be marked in acute cases. Extremely severe leukocytosis is associated with a poor prognosis. In two fatal cases from this clinic the leukocyte count was over 30,000 per cu. mm. of blood. The urine is normal except the occasional patient in whom amyloid nephrosis develops. Electrocardiograms show evidence of no abnormality in most cases despite the common occurrence of tachycardia. Some patients develop T-wave changes and a long P-R interval suggestive of rheumatic carditis. In those patients in whom arthritis persists and other symptoms subside, the electrocardiogram usually reverts to a normal pattern. The erythrocyte sedimentation rate is moderately or markedly increased (30 to 130 mm. in one hour-Westergren method). As noted before, the streptococcus agglutination titer is rarely elevated, whereas in adult rheumatoids it is positive in from 50 to 66 per cent of the cases. The antistreptococcus hemolysin titer is significantly elevated in Still's disease (mean of 250). Joint fluid obtained by aspiration is no different from that obtained in adults. l l DIFFERENTIAL DIAGNOSIS
The major difficulty is the differentiation of juvenile rheumatoid arthritis from rheumatic fever. The lack of response to salicylates is helpful in ruling out rheumatic fever and severe cardiac damage is
JUVENILE RHEUMATOID ARTHRITIS
573
uncommon in Still's disease. Persistent joint symptoms with subsiding reaction in other systems usually indicate the diagnosis which may be possible to determine only with the passage of time. The antistreptolysin and streptococcus agglutination tests are of no value because results are similar in these two conditions. Still's disease and rheumatic fever are in many ways so similar that some observers suggest the name of rheumatoid or rheumatic state to encompass them both. Tuberculosis occurs in older individuals and is usually monoarticular. Haverhill fever may simulate arthritis of acute onset but the presence of a rash, the lack of chronicity and presence of a demonstrable causative organism distinguish it. l Brucellosis is less common in young children but must be considered when the diagnosis is in doubt. The agglutination or skin tests should be diagnostic. PROGNOSIS
Two patients of the fifty-six in our experience died. Death results from some complication as a rule. The most directly associated condition is perhaps amyloidosis. '~ Morbidity is definitely less in children than in adults. Children do well as a rule if proper supportive care is given; most are left with minor deformities when the process has burned itself out, while a very few have progression of changes until they are hopelessly crippled and confined to bed or wheelchair. Recurrences after a maximum period of activity are not often seen in children, but we occasionally see a patient who has repe~ted bouts of renewed activity extending well into adult life. . TREATMENT
There is no specific treatment for Still's disease and until we arrive at a clearer concept of the etiologic factor such a treatment may remain undiscovered. The same measures tried in adult rheumatoids have been tried in the juvenile patients, including vaccines, vitamins, cod liver oil, bee venom, foreign protein, artificial fever, induced jaundice, chrysotherapy, etc. Because the process tends to be self-limited, some nonspecific measures are important. Rest is necessary during the acute phase with high fever, leukocytosis, suggestion of myocardial damage. A child in this stage should be handled'like one with rheumatic fever. Later, as improVement occurs, restriction is governed by the temperature, erythrocyte sedimentation rate and the patient's sense of well-being. On return to school, any excess activity such as gymnasium classes should be eliminated. In the transition period when school attendance is not practical, it is desirable to employ a home teacher.
574
JAMES A. COSS,
JR.
A high-vitamin, high-caloric diet is essential. Added cod liver oil is of value if tolerated. Physiotherapy is used when the acute process subsides. Gentle massage, dry or moist heat, and baths help depress muscle spasm and pain. Lightweight, posterior, molded plaster splints are made to prevent contractures and subsequent deformity of the knees, hips, elbows, wrists and fingers. Splints are worn all night and part of the day. If neck pain develops or flexion begins, a light plaster collar is used or in extreme cases head traction may be tried. Deformities already present must be corrected with skin traction, wedge casts or skeletal traction so that proper splints may then be applied. 12 If skeletal chanr,es such as ankylosis or cervical fusion have occurred, the only measure left is operative interference to correct the deformity or improve posture. If anemia exists, repeated small transfusions and maintenance doses of iron are given. Barbiturates are valuable for restless, sleepless patients particularly when given with salicylates. Salicylate given as the enteric-coated sodium salt often relieves pain more than any other one measure. In children we prescribe 0.6 gm. or more three or four times daily as needed. The enteric coating causes fewer gastric upsets. Simultaneous sodium bicarbonate is not given as it has been shown to reduce the level of salicylate in the blood. 13 Our results with gold treatment have not been promising in children but we feel that this therapy merits a trial in patients not benefited by the usual supportive measures. In this clinic we have used a preparation of sodium aurothioglucose (Solganol B Oleosum, Schering Corporation). The initial dose is 3 to 5 mg., increased to 25 mg. but we no longer give larger doses even though children's tolerance is better than adults'. The usual checks for toxicity must be employed and 600 mg. constitutes an average course. Some very young patients have received not more than 200 to 300 mg. in a course. A rest period of six weeks or more is given before gold is again instituted. If there is no benefit from three courses of 600 to 800 mg. each, the therapy is pursued no further. It goes without saying that a knowledge of possible toxic effects and careful clinical and laboratory control of the patient is essential if chrysotherapy is instituted. We have seen only two cases of moderately severe toxicity, both of which rapidly cleared on withdrawal of the drug. There have been no fatalities with chrysotherapy. REFERENCES 1. Still, G. F.: Tr. Roy. Med.-Chir. Soc., 80:47, 1897.
2. Chauffard, A. and Ramond, F.: Revue de Med. (Paris), 16:345, 1896. Felty, A. R.: Bull. Johns Hopkins Hosp., 35:16 (Jan.) 1924. 3. Kuhns, J. G. and Joplin, R. J.: New England J. Med., 215:268, 1936. Baggenstoss, A. H. and Rosenberg, E. F.: Arch. Path., 3.5:503 (April) 1943. 4. Dawson, M. H.: J. Exper. Med., 57:845 (May) 1933. 5. Colver, T.: Arch. Dis. Childhood, 12:253 (Aug.) 1937.
JUVENILE RHEUMATOID ARTHRITIS
6. 7. 8. 9. 10. 11. 12. 13.
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Coss, J. A.: Reported at the New York Rheumatism Assoc., May 9, 1945. Trasoff, A., Schneeberg, H. and Scarf, M.: Arch. Int. Med., 74:4, 1944. Dawson, M. H.: Nelson New Loose-Leaf Medicine, 1935, p. 628. Taylor, G. D., Ferguson, A. B., Kasabach, H. and Dawson, M. H.: Arch. Int. Med., 54:979, 1936. Caffey, J.: Pediatric X-ray Diagnosis. Chicago, Yearbook Publishers, 1945, p. 771. Kling, D. H.: The Synovial Membrane and Synovial Fluid. Los Angeles, Medical Press, 1938, p. 202. Swain, L. T. and Kuhns, J. G.: The Prevention of Deformities in Chronic Arthritis. I. J.A.M.A., 93:1853, 1929; II. J.A.M.A., 94: 1123, 1930; Ill. J.A.M.A., 94:1743, 1930. Smull, K., Wegria, R. and Leland, J.: J.A.M.A., 125:1173 (Aug.) 1944.