232
CARPAL ARTHRITIS WITH ANKYLOSIS IN LATE ONSET STILL’S DISEASE THOMAS A. MEDSGER, Jr., and WALLACE C. CHRISTY Thirteen patients are described in whom Still’s disease began after age 15. All had objective evidence of arthritis, and 10 developed chronic synovitis of larger joints, especially the wrists. A characteristic evolution of roentgenographic changes was observed in 7 patients. Carpometacarpal and intercarpal joint spaces became selectively narrowed without erosions, and bony ankylosis eventually occurred. These roentgenographicchanges may be a valuable clue to the diagnosis of Still’s disease, regardless of the age at onset. Still’s disease with onset in adulthood was first appreciated and described by Bywaters (1 ) and its close clinical resemblance to Still’s disease of childhood (2) was emphasized. Similar findings have been reported in another group of patients by Bujak et a1 (3) and have been expanded upon in a brief report by Aptekar et a1 (4). The purpose of this study is to report an additional series of patients with late onset Still’s disease and to describe an unusual clinical and roentgenographic pattern of joint involvement that often leads to carpometacarpal or intercarpal ankylosis and appears to be distinctive of this disorder. From the Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Thomas A. Medseer. Jr.. M.D.: Assistant Professor of Medicine, University of Pittsburgh School of Medicine; Wallace C. Christy, M .D.: Assistant Professor of Medicine, University of Pittsburgh School of Medicine. Address reprint requests to Thomas A. Medsger. Jr.. M.D., Department of Medicine, 985 Scaife Hall, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261. Submitted for publication J u l y 28, 1975: accepted October 15, 1975. Arthritis and Rheumatism, Vol. 19, No. 2 (March-April 1976)
MATERIALS AND METHODS During 1971-1975, 13 patients who fit the clinical picture of Still’s disease were seen in consultation or referred to the University of Pittsburgh Health Center Hospitals and Clinics. All had high, spiking fever, arthralgias, and/or arthritis at some time in their illness; and all had negative serologic tests for rheumatoid factor and antinuclear antibody. Each patient also had a t least two additional features, including leukocytosis greater than I 5,000/mms; evanescent macular or maculopapular rash; serositis (pleuritis or pericarditis); or hepatomegaly, splenomegaly, or generalized lymphadenopathy. Each patient was questioned and examined by one of the authors, and the following laboratory studies were routinely performed: roentgenograms of the hands and wrists; complete blood count, differential, and sedimentation rate; serum rheumatoid factor as determined by latex agglutination test and sheep cell agglutination test (SCAT); serum antinuclear antibody by the immunofluorescence method; and quantitative serum immunoglobulins by radial immunodiffusion. In addition synovial fluid was analyzed in 6 cases. All patients were reexamined at least 12 months after the original evaluation in order to exclude other possible disease processes.
RESULTS The clinical findings in this group of 13 patients are presented in Table 1. There were 10 women (1 black) and 3 men in this g r o w. . The age at onset ranged from I 5 to 54; the median age was 19 and only 2 individuals were older than age 27. Only 1 patient (JW) had a childhood illness that might have been Still’s disease; this condition had been diagnosed as rheumatic fever, but information was insufficient for further clarification. High, spiking fever, frequently reaching 105”F,
233
Table 1. Clinical Features in 13 Cases of Late Onset Still's Disease Arthritis Age
Race/
at Onset
Case
Sex
I . HB 2. M A 3.GP
W/F W/F W/F
4. LZ 5. GS 6. H H 7. RJ 8. NC 9.SD
W/F W/F W/F B/F W/F W/F
21 20 18
10. CG II.JW 12. LK 13. DG
W/F W/M W/M W/M
Spiking Fever
Serositib
Carpal Involvement
Rash
Clinical
+ + +
+ + 0
+ + +
16 16
+ + + + + +
+ + + + + +
+ + + + + +
+ +
15 20 17
+ + +
+ + + +
+ + + +
+ + + +
12/13
13/13
11/13
54 41
21
18
15
0 12/13
+ 0
+
0
+ + +
occurred in 12 of 13 patients. The remaining individual had low-grade fever, never exceeding 102°F. A quotidian or double quotidian fever pattern was identifiable in 8 patients. The typical evanescent, macular, or maculopapular rash also occurred in 12 patients and was usually more prominent with the first bout of illness and with high fever. The eruption was most often found on the extremities and trunk, but in 2 patients the face was involved. Arthritis and/or tenosynovitis were always present but often ignored because of the dramatic systemic features. Severe sore throat, also reported by Bujak et a1 (3), was a striking symptom in 6 patients, and mild sore throat was noted in 5 additional instances. Only 1 patient complained of abdominal pain. Lymphadenopathy (6 cases), hepatomegaly (6 cases), and splenomegaly (8 cases) were frequent findings. Pleuritis (3 cases) and/or pericarditis (4 cases) were less commonly encountered. Numerous diagnostic procedures were performed in these patients because of the difficulty in establishing a diagnosis; they included lumbar punctures (seven), biopsies of skin (five), muscle (five), lymph nodes (six), liver (seven), bone marrow (ten), synovium (one), and pericardium (one). N o common o r characteristic histologic lesion was found in those mate-, rials reviewed personally by the authors.
Sore Throat
+ + +
Lyniphadenopathy
Splenoniegaly
Pleuritis
Pericar-
0
+
+ +
0 0 0
0 0
0 0
0
0
+
+ +
0 0
0 0
0 0 0
0
+ 0
+ + + + + +
0
+
+ 0 + 0 11/13
Hepatomegaly
0 0
0
ditis
+
0 0 0
+ 0 +
+
0
0
Other
Coombs neg herno ly t ic a t i em i a: thronibocytopenia Iritis
+
+
+
+
+ + +
0
+ + 0 +
+ + +
0
+
+
6/13
6/13
8/13
0 0 0 3/13
0 0 0 4/13
Keratoconjunctivitis siccii: psoriasis
Laboratory studies performed during the course of the illness are recorded in Table 2. Erythrocyte sedimentation rates were uniformly elevated. During disease flare-ups 11 patients developed a significant normochromic, normocytic anemia. In 1 patient (Case 3) there was evidence of hemolysis (rapid fall in hematocrit, reticulocytosis of 20% without other source of blood loss, and splenomegaly) and a negative direct Coombs test. But in 7 other adequately studied patients, hemolysis was not found. Usually the anemia occurred rapidly but always stabilized and improved promptly as disease activity diminished. Eleven of 13 had significant leukocytosis, ranging from 15,900 to 54,000/mm3. Differential counts in these instances nearly always showed a preponderance of neutrophils and often some immature cells of the granulocytic series. Most patients ( 1 I of 13) were hypoalbuminemic during the initial illness. Only Patient 7, the black female, had an elevated concentration of serum y-globulin. Latex agglutination reactions, SCAT, and ANA tests were consistently negative, both in 1975 and at disease onset. Quantitative serum immunoglobulin levels were performed in 12 instances. There were distinct elevations of IgG i n 5 cases, of IgA in 3, and of IgM in only 1 . Three patients had raised levels of both IgG and IgA (Cases 7, 10, and 13).
MEDSGER AND CHRISTY
234
Serum glutamic-oxaloacetic and glutamic-pyruvic transaminase (SGOT and SGPT) and serum alkaline phosphatase levels were abnormal in 7 patients and in another an isolated transaminase elevation was noted. The pattern observed was primarily that of hepatocellular injury, with more significant elevations of the transaminase than of alkaline phosphatase. In each case these abnormalities reverted to normal after the patient's illness became quiescent. In one instance a high dose of aspirin had been used prior to the discovery of these changes, but salicylates or other known hepatotoxic agents could not be implicated in the remainder of the cases. Five liver biopsy specimens were reviewed and revealed only focal collections of lymphocytes in periportal areas without hepatocellular injury. All 13 patients had objective evidence of arthritis and/or tenosynovitis. Joint pain was occasionally the first symptom and usually appeared simultaneously with the onset of sore throat, fever, and rash. In 1 patient ( H H ) arthritis appeared after the resolution of prolonged fever on three separate occasions. Prominent systemic features often overshadowed joint complaints, and at first the possibility of a rheumatic disease was considered to be remote or was not included at all in the differential diagnosis. In 8 patients a visceral malignancy, particularly one of the lymphoma group, was the initial working diagnosis. For this reason exploratory laparotomy was eventually performed in 3 cases. Articular manifestations in these patients are
listed in Table 3. In most cases (9 of 13) there was a distinct history of morning stiffness. The pattern ofjoint involvement was usually a bilateral, symmetrical polyarthritis. Although all 13 patients had documented knee arthritis, the parts most prominently affected were the wrists ( I 1 of 13). In addition to inflammation of the radio-carpal joint, at times relatively minor, conspicuous swelling, tenderness, and limitation of motion affected the intercarpal and carpometacarpal joint areas. In order of decreasing frequency, the other affected joints were the MCPs, elbows, cervical intervertebral joints, and others, including smaller joints of the hands and feet. On physical examination the involvement of individual joints appeared to be indistinguishable from that of adult rheumatoid arthritis. Arthrocentesis of the knee was performed on eight occasions in 6 patients. These synovial fluids showed moderate to marked elevation of white blood cell counts, with values ranging from 8,000 to 29,900/mm3 with 80-95% polymorphonuclear leukocytes. In 4 instances serum and synovial fluid complement (C, and C,) determinations were made. All of the serum complement levels were normal, and the simultaneously obtained synovial fluid values measured from 28 to 48% of the serum levels. Although the presence of arthritis was occasionally limited to the periods when patients were febrile, it was most often persistent. Chronic active synovitis remained a problem chiefly in larger joints, especially the wrists, knees, and elbows. Roentgenographic changes developed in 10 patients who were
Table 2. Laboratory Results in 13 Cases of Late Onset Still's Disease Serum Proteins (€76)
Case
I . HB 2.MA 3.GP 4. LZ 5.GS 6. HH 7. RJ 8.NC 9.SD 10. CG II.JW 12. LK 13. DG
* Normal
Lowest Highest ESR Wintrobe Hematocrit (mm/hr) ("lo)
51 58 65 I06t 50 60 55 62 58 50 38 49 36
37 28 28 30 32 30 29 27 29 32 25 32 42
Highest WBC
(permm3)
Lowest Albumin
Highest y-Globulin
Latex
SCAT
ANA
IgG
IgA
IgM
22,300 17,560 20,700 37,400 14.800 32,500 34,300 36,700 15,900 54,000 28,100 22,100 I 1.090
4.50 2.65 2.38 2.60 2.80 2.70 2.70 2.40 2.60 3.00 2.44 3.20 4.40
I .01 0.85 I .40 I .80 I .20 I .30 2.10 I .oo 0.70 ISO I .22 0.80 I .20
neg n eg neg neb2 neg neg t1:20 neg neg neg neg neg neg
neg neg neg neg neg neg neg neg neg neg
neg neg neg neg neg neg neg neg neg neg neg neg neg
1,050 1,464 1,900 1,200 1,080 3.160 1,740 770 2.100 1,200 1,050 1,840
100
93 65 210 120 420 260 140 1 I5 320 200 95 220
values: IgG, 422-1,453; IgA, 56-479; IgM, 50-391
t Westergren method.
Serum Immunoglobulins (mg%)*
riel:
neg
155 135 200 430 740 290 55 500 340 490 540
CARPAL ARTHRITIS IN STILL’S DISEASE
Table 3. Articular Manifestations in 13 Cases of Late Onsef Still’s Disease
Joint Affected* Knee Wrist Radiocarpal Intercarpal or carpornetacarpal MCP Elbow Cervical spine PIP MTP Shoulder, sternoclavicular, midtarsal, DIP
Number Affected 13
II 7
9 9 8 7 6 5 4
*Swelling and/or effusion
followed at least 2 years from onset. In 3 instances juxtaarticular osteoporosis alone was found. In the remaining 7 patients more advanced changes developed, including joint space narrowing and bony ankylosis. Ankylosis between the base of the second and third metacarpals and the adjacent trapezoid and capi-
235
tate ( 6 cases) was the most frequent finding. Diffuse intercarpal ankylosis was present in 3 cases, and in these instances it was impossible to identify the specific bones involved. In 2 other individuals the intercarpal changes affected the trapezium-trapezoid, trapezoid-capitate, capitate-lunate, and capitate-hamate. No radiocarpal ankylosis was found in this series. However 1 patient (Case 9) had bilateral fifth proximal interphalangeal joint ankylosis on roentgenogram. In 8 cases the authors had the opportunity to evaluate serial roentgenograms of the hands and wrists during the first 3 years of illness, and in 4 the evolution of a characteristic sequence of changes was noted. In each case the initial roentgenograms, taken 2 to 13 months after onset, were entirely normal. After an additional period of 4 to 27 months, the carpometacarpal joint spaces became indistinct and narrowed, especially in the spaces bounded by the bases of the second and third metacarpal bones and the trapezium, trapezoid, and capitate (Figure 1 ). Subsequent radiographs revealed bony ankylosis of the carpometacarpal and/or
Fig 1. Diagrammatic representation of the bones andjoints of the carpus. For purposes of simplij5cation. the bone overlapping that would appear on standard roentgenograms is not shown. Metacarpals are marked 1-5: Tm-trapezium, Td-trapezoid, C-capitate, H-hamate, N-nauicular. L - h a t e . Tq-triquetrum. Ppisiform, R-radius, U-ulna. The most Yrequenf sites of bony ankylosis in late onset Still’s disease are illustrated by solid bars bridging joint spaces.
MEDSGER AND CHRISTY
236
intercarpal joints. Ankylosis was found as early as 18 months after the onset of wrist complaints. In the remaining 3 cases this complete sequence took place over periods of 2 I , 24, and 39 months. N o typical rheumatoid erosions were identified during the evolution of the roentgenographic changes in these 4 patients, either in the carpometacarpal or other joints. In fact there was little change in the other hand joints during these first several years of illness. In 2 of 9 patients examined 6 years (Case 10) and 29 years (Case 9) after the onset of disease, bony ankylosis of the tarsometatarsal joints was also seen. Cervical radiographs were obtained in 5 patients and sacroiliac joints were examined roentgenographically in 2; none showed evidence of ankylosis.
Case 7 RJ, an 18-year-old black student, first became ill in January 1969, with fever (103"F), sore throat, arthrdlgias of the knees, and an intermittent, raised, blotchy rash over her face, trunk, and extremities. In February 1970 left-sided pleuritic chest pain developed. Although
the wrists were swollen, roentgenograms (Figure 2A) revealed no changes. Prednisone was required intermittently to control fever and pleurisy. By May 1971 her weight had decreased from 230 to 120 pounds, and she continued to have fever (to 105°F on occasion), swelling, tenderness, and limitation in the carpal area. Latex agglutination and ANA tests were negative. The WBC count rose to 34,300/mm3 and she developed acute pericarditis. The diagnosis of late onset Still's disease was made at that time, and she responded dramatically to therapy with prednisone, 30 mg/day. Wrist radiograms during this admission (Figure 2B) showed loss of cartilage at the carpometacarpal joints bilaterally without erosions. Although fever, rash, and serositis have subsequently been intermittent and controlled with corticosteroids, there has been continued arthritis of the carpal areas. Repeat roentgenograms obtained in May 1973 demonstrated definite ankylosis. The most recent study, in June 1975 (Figure 2C), revealed carpometacarpal and intercarpal ankylosis without erosions. At that time the patient had no pain in her wrists, but the total range of motion was restricted to 25" on the right and 60" on the left.
Fig 2A. Case 7. Normal wrist roentgenogratns taken in February 1970. 13 months after disease onset.
CARPAL ARTHRITIS IN STILL’S DISEASE
Fig 2 0 . Case 7. May 1971: Roentgenograms reveal carpometacarpal joint space narrowing and indistinct cortical margins but no erosions.
Fig 2C. Case 7 . June 1975: Radiograph shows ankylosis across carpometacarpal joints 2 and 3 and diffuse intercarpal ankylosis affecting at least the trapezoid-capitate and capitate-hamate articulations. Note sparing of radiocarpal joints.
237
238
MEDSGER A N D CHRISTY
Case 12 LK, a 17-year-old white male student, was in excellent health until November 1971, when he noted a sore throat and transient stiffness and limitation of cervical spine motion. In July 1972 he developed bilateral and symmetrical stiffness, pain, and swelling of the shoulders, elbows, wrists, MCPs, PIPS, and knees. Simultaneously there was daily spiking fever to 103-105°F and a recurrent blotchy macular rash over the extremities and trunk. Generalized lymphadenopathy was present without hepatomegaly or splenomegaly and the SGOT was elevated to 3.3 times normal. Because of concern about an occult malignancy, in particular lymphoma, the axillary, inguinal, and mediastinal lymph nodes, liver, and bone marrow were biopsied and revealed only nonspecific changes. He was given prednisone, 60 mg/day, and all symptoms and signs improved strikingly. However, when the dose of prednisone was tapered below 20 mg/day (March 1973), arthritis of the wrists and knees recurred along with low grade fever. The spleen tip was palpable for the first
time. The WBC count was 22,100/mm3 and the latex agglutination and ANA tests were negative. The diagnosis of late onset Still’s disease was made at that time. Roentgenograms of the wrists revealed no abnormalities (Figure 3A). During the subsequent months the patient felt well except for persistently painful, swollen wrists which had a decreased range of motion. In August 1973 (Figure 3B) generalized bone demineralization was seen along with significant narrowing of the carpometacarpal joint spaces bilaterally and a “fluffy,” indistinct appearance of the cortical margins in these areas. By April 1974 wrist roentgenograms showed complete loss of the second and third carpometacarpal joint spaces with bony ankylosis (Figure 3C). The peripheral synovitis subsequently responded to a course of gold salt therapy.
DISCUSSION The clinical and laboratory manifestations in these patients with late onset Still’s disease are similar to
Fig 3A. Case 12. Normal wrisr radiographs in March 1973.
CARPAL ARTHRITIS I N STILL’S DISEASE
Fig 3B. Case 12. August 1973: Roentgenograms show marked narrowing of carpometacarpaljoint spaces 2 and 3 and narrowing of the trapezoid-capitate joint space.
Fig 3C. Case 12. April 1974: Complete bony ankylosis at carpometacarpaljoint spaces 2 and 3 has occurred without erosions. In addition. trapezium-trapezoid, trapezoid-capitate. and capitate-hate ankylosis are seen.
239
240
those previously reported by Bywaters ( 1 ) and Bujak, Aptekar, er af (3,4). The most characteristic constellation of features includes fever, rash, arthritis, serositis, hepato-splenomegaly and/or lymphadenopathy, marked leukocytosis, and negative serologic reactions for rheumatoid factor and antinuclear antibodies. The present findings of mild reversible hepatic enzyme abnormalities and minimal histologic changes on liver biopsy closely resemble those described by Bujak er a1 (3). Similar changes have been noted in juvenile rheumatoid arthritis (JRA), especially with the Still’s type of onset (5). Reviews of the roentgenographic changes in adult rheumatoid arthritis indicate that ankylosis of one or more joints is relatively uncommon, ranging from 5 to 27% in several large series (6-9). In the report of the Scientific Advisory Committee of the Empire Rheumatism Council in 1950 (9), ankylosis was found in 17% of 400 patients and ranked eighth in order of frequency of roentgenographic changes. A similar frequency of ankylosis has been reported in JRA patients (7-23%), most commonly involving the cervical spine but also occurring in the wrists (10,ll). In a study of 544 cases, Laaksonen (1 1 ) found that ankylosis was most frequent in children 10 years of age and over and in those who had their disease for at least 2-3 years. The carpometacarpal joints were most often ankylosed; the third (31.3%) and second (27.5%) CMCs were far more commonly affected than the others (fourth CMC: 5.4%; fifth CMC: 4.6%; first CMC: 0.4%). N o further mention of the frequency of intercarpal or radiocarpal ankylosis was made. The only clear-cut association of ankylosis was with functional classes I11 and I V in this study. Martel er a1 (12) described ankylosis of at least one peripheral joint in 15 of 80 J RA patients; in 13 of these, the wrist was involved. Usually one of three components of the total carpal complex (radiocarpal, intercarpal, or carpometacarpal) remained unaffected and thus allowed some motion at the wrist. The relative frequency of ankylosis at these three locations was not stated. Ansell and Bywaters (13), in a review of 316 cases, stated that bony ankylosis of the carpal bones in JRA was “not infrequent” but “not incapacitating.” No data with respect to frequency were given, but these authors did suggest that the carpus is the most commonly ankylosed of all peripheral articulations in JRA. Levinson (14) also reported wrist ankylosis without evidence of finger joint disease as a feature much more common in children than in adults with RA; he has seen 8 such patients. In 1962 Ansell and Bywaters (15) published a 5year followup study of patients previously diagnosed
MEDSGER AND CHRISTY
as having probable Still’s disease. In one case roentgenograms showed evolution of the wrist changes similar to those found in the present study. This girl had presented with arthritis of both wrists, pericarditis, and fever. At the time of reevaluation 6 years later, she was asymptomatic except for decreased range of motion of the left wrist. Serial roentgenograms showed intercarpal ankylosis at that time and later extensive carpometacarpal ankylosis [Figure 7, p 259 (15)]. Levinson also published an illustration [Figure 5, p 93 (14)] demonstrating carpometacarpal ankylosis in a patient with JRA, but the type of disease onset was not stated. In his initial description of Still’s disease in adults, Bywaters (1) commented on transient but occasionally recurrent inflammation of the peripheral joints. The involvement was typically pauciarticular and most commonly affected the knees, fingers, and wrists. Only 2 cases (Cases 4 and 6) had roentgenographic changes; these involved the carpus in which there was “curiously limited” ankylosis that was not further described. It is interesting, however, that Figure 6 in Bywaters’ article illustrates carpometacarpal joint space narrowing and ankylosis which took place over 2-4 years after onset in Patient 6. Marginal joint erosions did occur in his series, but were extensive in only 2 patients. Two of Bywaters’ patients (Cases 1 and 9) had apophyseal joint ankylosis in the cervical spine. Bujak et af (3) noted roentgenographic changes in only 1 of 10 patients. This individual developed “almost complete obliteration of the intercarpal spaces” over 22 months. Carpal and metacarpal erosions were also present bilaterally on the followup roentgenograms. In neither of these groups of patients was there mention of chronic active synovitis persisting during interfebrile periods. In contrast, the present authors found evidence of continued inflammation of joints in 10 of 13 patients. Although articular findings exacerbated during recurrences of multisystem disease, both clinical and roentgenographic evidence of joint damage progressed relentlessly. At least part of this discrepancy between articular and systemic disease activity may be accounted for by the use of antiinflammatory agents in high doses, especially corticosteroids. This fact is well illustrated by the 2 cases described above, in which limitation of wrist motion and roentgenographic changes progressed despite successful suppression of fever, rash, and serositis by the corticosteroids. The earliest roentgenographic change was osteoporosis and an indistinct appearance of the carpometacarpal and intercarpal cortical margins with joint space narrowing. This change was followed after a variable period of time by obliteration of these joint spaces
CARPAL ARTHRITIS I N STILL’S DISEASE
and complete bony ankylosis. Little or no loss of bony substance within the carpus resulted during this process. Once begun, this evolution progressed to ankylosis in most cases without typical marginal erosions within 1.5-4 years. Roentgenograms in 2 patients (Cases 9 and 10) did show erosions, but these were located at a distance from the carpal areas. After ankylosis, tenderness and swelling of the carpus were usually absent, and these patients were left with painless, reduced range of motion at the wrist. Although other joints were affected roentgenographically, this particular progression of changes was noted only in the carpometacarpal, intercarpal, and tarsometatarsal articulations in the present series of patients. The tendency of ankylosis to affect chiefly the capitate and those bones that border it (Figure 1 ) is unexplained. Several authors (10-12) have speculated that limited mobility at the wrist is in some way important. The capitate in particular is felt to be the center of least motion of the carpal bones in both flexion and extension of the wrist. The literature on ankylosis in rheumatoid arthritis is not sufficiently detailed to allow prediction of which patients stand the highest risk of developing carpal ankylosis. The authors have accumulated the wrist roentgenographs of 57 additional patients with RA of more than 3 years duration (Table 4). These patients were divided according to disease type and their radiographs were reviewed. The frequency of ankylosis in juvenile Still’s disease, juvenile polyarticular RA, and adult RA were all relatively low. Although these results are preliminary, it appears that there is a greater tendency to ankylosis in the systemic (Still’s type) onset variant of RA, regardless of the age at which it begins. Furthermore the carpometacarpal and intercarpal joints seem to be selectively affected, although this finding is not exclusive or pathognomonic. In a disease that has no single diagnostic laboratory feature, the finding of carpal ankylosis may be a valuable clue to diagnosis and ultimately to pathogenesis and etiology.
ADDENDUM Since submission of this manuscript, the authors have seen an additional example of ankylosis in late onset Still’s disease. AL, a 31-year-old white man, had several episodes of high, spiking fever with swelling of the wrists and ankles between ages 3 and 10. There were no apparent articular sequelae. At age 29 he developed intermittent fever (to 103’F) and chronic polyarthritis
24 1
Table 4. Carpometacarpal and Intercarpal Ankylosis in Rheumatoid Arthritis Variants R A Variant
Late onset Still’s disease Juvenile Still’s disease Adult R A
Juvenile polyarticular R A
N o . of Patients
Percent
7/13 2/9 4/38 0/10
54 22 11
0
involving both hips, the right elbow, right wrist, and left ankle. There was no rash. Indomethacin was helpful but no remission was achieved. In August 1975 he had a WBC count of 1 5,200/mm3 and negative latex agglutination and A N A tests. Roentgenograms of the right wrist showed advanced ankylosis between the second metacarpal and the trapezoid and between the third metacarpal and the capitate.
ACKNOWLEDGMENTS The authors are grateful to the following physicians for their cooperation in making the patients and their records available for study: Dr. Carl E. Anderson, Dr. Carolyn Anderson, Dr. Philip Balk, Dr. Thomas G. Benedek, Dr. Robert B. Buckingham, Dr. Paul S. Caplan, Dr. William M. Cooper, Dr. H. Lee Dameshek, Dr. Lawrence D. Ellis, Dr. Marshall S. Levy, Dr. Victor 1. Markson, Dr. John R. Misage, Dr. Lawrence M. Mulhern, Dr. Burton s. Pollock, Dr. Gerald P. Rodnan, and Dr. J. W. Schoolnic.
REFERENCES I . Bywaters EGL: Still’s disease in the adult. Ann Rheum Dis 30:121-133, 1971 2. Still GF: On a form of chronic joint disease in childhood. Med Chir Trans 80:47-59, 1897 3. Bujak JS, Aptekar RG, Decker JL, et al: Juvenile rheumatoid arthritis presenting in the adult as fever of unknown origin. Medicine 52:431-444, 1973 4. Aptekar RG, Decker JL, Bujak JS, et al: Adult onset juvenile rheumatoid arthritis. Arthritis Rheum 16:715718, 1973 5. Schaller J, Beckwith B, Wedgwood RJ: Hepatic involvement in juvenile rheumatoid arthritis. J Pediatr 77:203-210, 1970 6. T a y l o r G D , Ferguson AB, Kasabach H , e t al: Roentgenologic observations on various types of chronic arthritis. Arch Intern Med 57:282-295, 1936 7. Fletcher DE, Rowley KA: The radiologic features of rheumatoid arthritis. Br J Radio1 25:282-295, 1952 8. Soila P: Roentgen manifestations of aduit rheumatoid arthritis with special regard to the early changes. Acta Rheumatol Scand 2:i-144, 1958 (Suppl I )
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9. Report of the scientific advisory committee of the empire rheumatism council. Br Med J 1:799-805, 1950 10. Sairanen E: On RA in children. A clinico-roentgenographic study. Acta Rheumatol Scand 2:l-79, 1958 (SUPPI) I I . Laaksonen AL: A prognostic study of JRA. Analysis of 544 cases. Acta Paediatr Scand [Suppl] 166:l-163, 1966 12. Martel W, Holt JF, Cassidy JT: Roentgenologic manifes-
tations of juvenile rheumatoid arthritis. Am J Roentgen01 Radium Ther Nucl Med 88:400-423, 1962 13. Ansell BM, Bywaters EGL: Rheumatoid arthritis (Still’s disease). Pediatr Clin North Am 10:921-939, 1963 14. Levinson JE: Juvenile rheumatoid arthritis. Postgrad Med 51188-94, 1972 15. Ansell BM, Bywaters EGL: Diagnosis of probable Still’s disease and its outcome. Ann Rheum Dis 21:253-262, I962
The Proceedings of the Conference on Pseudogout and Pyrophosphate Metabolism Edited by Daniel J. McCarty, M.D. will be published as a supplement to the May-June 1976 issue of ARTHRITIS AND RHEUMATISM Subscribers t o ARTHRITIS AND RHEUMATISM will receive the conference supplement a t no extra charge. Additional copies may be purchased by sending your check for $10.00 to: The Arthritis Foundation Attn: A&R Circulation Department 475 Riverside Drive New York, New York 10027
CARPAL ARTHRITIS WITH ANKYLOSIS IN LATE ONSET STILL’S DISEASE THOMAS A. MEDSGER, Jr., and WALLACE C. CHRISTY Thirteen patients are described in whom Still’s disease began after age 15. All had objective evidence of arthritis, and 10 developed chronic synovitis of larger joints, especially the wrists. A characteristic evolution of roentgenographic changes was observed in 7 patients. Carpometacarpal and intercarpal joint spaces became selectively narrowed without erosions, and bony ankylosis eventually occurred. These roentgenographicchanges may be a valuable clue to the diagnosis of Still’s disease, regardless of the age at onset. Still’s disease with onset in adulthood was first appreciated and described by Bywaters (1 ) and its close clinical resemblance to Still’s disease of childhood (2) was emphasized. Similar findings have been reported in another group of patients by Bujak et a1 (3) and have been expanded upon in a brief report by Aptekar et a1 (4). The purpose of this study is to report an additional series of patients with late onset Still’s disease and to describe an unusual clinical and roentgenographic pattern of joint involvement that often leads to carpometacarpal or intercarpal ankylosis and appears to be distinctive of this disorder. From the Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Thomas A. Medseer. Jr.. M.D.: Assistant Professor of Medicine, University of Pittsburgh School of Medicine; Wallace C. Christy, M .D.: Assistant Professor of Medicine, University of Pittsburgh School of Medicine. Address reprint requests to Thomas A. Medsger. Jr.. M.D., Department of Medicine, 985 Scaife Hall, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261. Submitted for publication J u l y 28, 1975: accepted October 15, 1975. Arthritis and Rheumatism, Vol. 19, No. 2 (March-April 1976)
MATERIALS AND METHODS During 1971-1975, 13 patients who fit the clinical picture of Still’s disease were seen in consultation or referred to the University of Pittsburgh Health Center Hospitals and Clinics. All had high, spiking fever, arthralgias, and/or arthritis at some time in their illness; and all had negative serologic tests for rheumatoid factor and antinuclear antibody. Each patient also had a t least two additional features, including leukocytosis greater than I 5,000/mms; evanescent macular or maculopapular rash; serositis (pleuritis or pericarditis); or hepatomegaly, splenomegaly, or generalized lymphadenopathy. Each patient was questioned and examined by one of the authors, and the following laboratory studies were routinely performed: roentgenograms of the hands and wrists; complete blood count, differential, and sedimentation rate; serum rheumatoid factor as determined by latex agglutination test and sheep cell agglutination test (SCAT); serum antinuclear antibody by the immunofluorescence method; and quantitative serum immunoglobulins by radial immunodiffusion. In addition synovial fluid was analyzed in 6 cases. All patients were reexamined at least 12 months after the original evaluation in order to exclude other possible disease processes.
RESULTS The clinical findings in this group of 13 patients are presented in Table 1. There were 10 women (1 black) and 3 men in this g r o w. . The age at onset ranged from I 5 to 54; the median age was 19 and only 2 individuals were older than age 27. Only 1 patient (JW) had a childhood illness that might have been Still’s disease; this condition had been diagnosed as rheumatic fever, but information was insufficient for further clarification. High, spiking fever, frequently reaching 105”F,
233
Table 1. Clinical Features in 13 Cases of Late Onset Still's Disease Arthritis Age
Race/
at Onset
Case
Sex
I . HB 2. M A 3.GP
W/F W/F W/F
4. LZ 5. GS 6. H H 7. RJ 8. NC 9.SD
W/F W/F W/F B/F W/F W/F
21 20 18
10. CG II.JW 12. LK 13. DG
W/F W/M W/M W/M
Spiking Fever
Serositib
Carpal Involvement
Rash
Clinical
+ + +
+ + 0
+ + +
16 16
+ + + + + +
+ + + + + +
+ + + + + +
+ +
15 20 17
+ + +
+ + + +
+ + + +
+ + + +
12/13
13/13
11/13
54 41
21
18
15
0 12/13
+ 0
+
0
+ + +
occurred in 12 of 13 patients. The remaining individual had low-grade fever, never exceeding 102°F. A quotidian or double quotidian fever pattern was identifiable in 8 patients. The typical evanescent, macular, or maculopapular rash also occurred in 12 patients and was usually more prominent with the first bout of illness and with high fever. The eruption was most often found on the extremities and trunk, but in 2 patients the face was involved. Arthritis and/or tenosynovitis were always present but often ignored because of the dramatic systemic features. Severe sore throat, also reported by Bujak et a1 (3), was a striking symptom in 6 patients, and mild sore throat was noted in 5 additional instances. Only 1 patient complained of abdominal pain. Lymphadenopathy (6 cases), hepatomegaly (6 cases), and splenomegaly (8 cases) were frequent findings. Pleuritis (3 cases) and/or pericarditis (4 cases) were less commonly encountered. Numerous diagnostic procedures were performed in these patients because of the difficulty in establishing a diagnosis; they included lumbar punctures (seven), biopsies of skin (five), muscle (five), lymph nodes (six), liver (seven), bone marrow (ten), synovium (one), and pericardium (one). N o common o r characteristic histologic lesion was found in those mate-, rials reviewed personally by the authors.
Sore Throat
+ + +
Lyniphadenopathy
Splenoniegaly
Pleuritis
Pericar-
0
+
+ +
0 0 0
0 0
0 0
0
0
+
+ +
0 0
0 0
0 0 0
0
+ 0
+ + + + + +
0
+
+ 0 + 0 11/13
Hepatomegaly
0 0
0
ditis
+
0 0 0
+ 0 +
+
0
0
Other
Coombs neg herno ly t ic a t i em i a: thronibocytopenia Iritis
+
+
+
+
+ + +
0
+ + 0 +
+ + +
0
+
+
6/13
6/13
8/13
0 0 0 3/13
0 0 0 4/13
Keratoconjunctivitis siccii: psoriasis
Laboratory studies performed during the course of the illness are recorded in Table 2. Erythrocyte sedimentation rates were uniformly elevated. During disease flare-ups 11 patients developed a significant normochromic, normocytic anemia. In 1 patient (Case 3) there was evidence of hemolysis (rapid fall in hematocrit, reticulocytosis of 20% without other source of blood loss, and splenomegaly) and a negative direct Coombs test. But in 7 other adequately studied patients, hemolysis was not found. Usually the anemia occurred rapidly but always stabilized and improved promptly as disease activity diminished. Eleven of 13 had significant leukocytosis, ranging from 15,900 to 54,000/mm3. Differential counts in these instances nearly always showed a preponderance of neutrophils and often some immature cells of the granulocytic series. Most patients ( 1 I of 13) were hypoalbuminemic during the initial illness. Only Patient 7, the black female, had an elevated concentration of serum y-globulin. Latex agglutination reactions, SCAT, and ANA tests were consistently negative, both in 1975 and at disease onset. Quantitative serum immunoglobulin levels were performed in 12 instances. There were distinct elevations of IgG i n 5 cases, of IgA in 3, and of IgM in only 1 . Three patients had raised levels of both IgG and IgA (Cases 7, 10, and 13).
MEDSGER AND CHRISTY
234
Serum glutamic-oxaloacetic and glutamic-pyruvic transaminase (SGOT and SGPT) and serum alkaline phosphatase levels were abnormal in 7 patients and in another an isolated transaminase elevation was noted. The pattern observed was primarily that of hepatocellular injury, with more significant elevations of the transaminase than of alkaline phosphatase. In each case these abnormalities reverted to normal after the patient's illness became quiescent. In one instance a high dose of aspirin had been used prior to the discovery of these changes, but salicylates or other known hepatotoxic agents could not be implicated in the remainder of the cases. Five liver biopsy specimens were reviewed and revealed only focal collections of lymphocytes in periportal areas without hepatocellular injury. All 13 patients had objective evidence of arthritis and/or tenosynovitis. Joint pain was occasionally the first symptom and usually appeared simultaneously with the onset of sore throat, fever, and rash. In 1 patient ( H H ) arthritis appeared after the resolution of prolonged fever on three separate occasions. Prominent systemic features often overshadowed joint complaints, and at first the possibility of a rheumatic disease was considered to be remote or was not included at all in the differential diagnosis. In 8 patients a visceral malignancy, particularly one of the lymphoma group, was the initial working diagnosis. For this reason exploratory laparotomy was eventually performed in 3 cases. Articular manifestations in these patients are
listed in Table 3. In most cases (9 of 13) there was a distinct history of morning stiffness. The pattern ofjoint involvement was usually a bilateral, symmetrical polyarthritis. Although all 13 patients had documented knee arthritis, the parts most prominently affected were the wrists ( I 1 of 13). In addition to inflammation of the radio-carpal joint, at times relatively minor, conspicuous swelling, tenderness, and limitation of motion affected the intercarpal and carpometacarpal joint areas. In order of decreasing frequency, the other affected joints were the MCPs, elbows, cervical intervertebral joints, and others, including smaller joints of the hands and feet. On physical examination the involvement of individual joints appeared to be indistinguishable from that of adult rheumatoid arthritis. Arthrocentesis of the knee was performed on eight occasions in 6 patients. These synovial fluids showed moderate to marked elevation of white blood cell counts, with values ranging from 8,000 to 29,900/mm3 with 80-95% polymorphonuclear leukocytes. In 4 instances serum and synovial fluid complement (C, and C,) determinations were made. All of the serum complement levels were normal, and the simultaneously obtained synovial fluid values measured from 28 to 48% of the serum levels. Although the presence of arthritis was occasionally limited to the periods when patients were febrile, it was most often persistent. Chronic active synovitis remained a problem chiefly in larger joints, especially the wrists, knees, and elbows. Roentgenographic changes developed in 10 patients who were
Table 2. Laboratory Results in 13 Cases of Late Onset Still's Disease Serum Proteins (€76)
Case
I . HB 2.MA 3.GP 4. LZ 5.GS 6. HH 7. RJ 8.NC 9.SD 10. CG II.JW 12. LK 13. DG
* Normal
Lowest Highest ESR Wintrobe Hematocrit (mm/hr) ("lo)
51 58 65 I06t 50 60 55 62 58 50 38 49 36
37 28 28 30 32 30 29 27 29 32 25 32 42
Highest WBC
(permm3)
Lowest Albumin
Highest y-Globulin
Latex
SCAT
ANA
IgG
IgA
IgM
22,300 17,560 20,700 37,400 14.800 32,500 34,300 36,700 15,900 54,000 28,100 22,100 I 1.090
4.50 2.65 2.38 2.60 2.80 2.70 2.70 2.40 2.60 3.00 2.44 3.20 4.40
I .01 0.85 I .40 I .80 I .20 I .30 2.10 I .oo 0.70 ISO I .22 0.80 I .20
neg n eg neg neb2 neg neg t1:20 neg neg neg neg neg neg
neg neg neg neg neg neg neg neg neg neg
neg neg neg neg neg neg neg neg neg neg neg neg neg
1,050 1,464 1,900 1,200 1,080 3.160 1,740 770 2.100 1,200 1,050 1,840
100
93 65 210 120 420 260 140 1 I5 320 200 95 220
values: IgG, 422-1,453; IgA, 56-479; IgM, 50-391
t Westergren method.
Serum Immunoglobulins (mg%)*
riel:
neg
155 135 200 430 740 290 55 500 340 490 540
CARPAL ARTHRITIS IN STILL’S DISEASE
Table 3. Articular Manifestations in 13 Cases of Late Onsef Still’s Disease
Joint Affected* Knee Wrist Radiocarpal Intercarpal or carpornetacarpal MCP Elbow Cervical spine PIP MTP Shoulder, sternoclavicular, midtarsal, DIP
Number Affected 13
II 7
9 9 8 7 6 5 4
*Swelling and/or effusion
followed at least 2 years from onset. In 3 instances juxtaarticular osteoporosis alone was found. In the remaining 7 patients more advanced changes developed, including joint space narrowing and bony ankylosis. Ankylosis between the base of the second and third metacarpals and the adjacent trapezoid and capi-
235
tate ( 6 cases) was the most frequent finding. Diffuse intercarpal ankylosis was present in 3 cases, and in these instances it was impossible to identify the specific bones involved. In 2 other individuals the intercarpal changes affected the trapezium-trapezoid, trapezoid-capitate, capitate-lunate, and capitate-hamate. No radiocarpal ankylosis was found in this series. However 1 patient (Case 9) had bilateral fifth proximal interphalangeal joint ankylosis on roentgenogram. In 8 cases the authors had the opportunity to evaluate serial roentgenograms of the hands and wrists during the first 3 years of illness, and in 4 the evolution of a characteristic sequence of changes was noted. In each case the initial roentgenograms, taken 2 to 13 months after onset, were entirely normal. After an additional period of 4 to 27 months, the carpometacarpal joint spaces became indistinct and narrowed, especially in the spaces bounded by the bases of the second and third metacarpal bones and the trapezium, trapezoid, and capitate (Figure 1 ). Subsequent radiographs revealed bony ankylosis of the carpometacarpal and/or
Fig 1. Diagrammatic representation of the bones andjoints of the carpus. For purposes of simplij5cation. the bone overlapping that would appear on standard roentgenograms is not shown. Metacarpals are marked 1-5: Tm-trapezium, Td-trapezoid, C-capitate, H-hamate, N-nauicular. L - h a t e . Tq-triquetrum. Ppisiform, R-radius, U-ulna. The most Yrequenf sites of bony ankylosis in late onset Still’s disease are illustrated by solid bars bridging joint spaces.
MEDSGER AND CHRISTY
236
intercarpal joints. Ankylosis was found as early as 18 months after the onset of wrist complaints. In the remaining 3 cases this complete sequence took place over periods of 2 I , 24, and 39 months. N o typical rheumatoid erosions were identified during the evolution of the roentgenographic changes in these 4 patients, either in the carpometacarpal or other joints. In fact there was little change in the other hand joints during these first several years of illness. In 2 of 9 patients examined 6 years (Case 10) and 29 years (Case 9) after the onset of disease, bony ankylosis of the tarsometatarsal joints was also seen. Cervical radiographs were obtained in 5 patients and sacroiliac joints were examined roentgenographically in 2; none showed evidence of ankylosis.
Case 7 RJ, an 18-year-old black student, first became ill in January 1969, with fever (103"F), sore throat, arthrdlgias of the knees, and an intermittent, raised, blotchy rash over her face, trunk, and extremities. In February 1970 left-sided pleuritic chest pain developed. Although
the wrists were swollen, roentgenograms (Figure 2A) revealed no changes. Prednisone was required intermittently to control fever and pleurisy. By May 1971 her weight had decreased from 230 to 120 pounds, and she continued to have fever (to 105°F on occasion), swelling, tenderness, and limitation in the carpal area. Latex agglutination and ANA tests were negative. The WBC count rose to 34,300/mm3 and she developed acute pericarditis. The diagnosis of late onset Still's disease was made at that time, and she responded dramatically to therapy with prednisone, 30 mg/day. Wrist radiograms during this admission (Figure 2B) showed loss of cartilage at the carpometacarpal joints bilaterally without erosions. Although fever, rash, and serositis have subsequently been intermittent and controlled with corticosteroids, there has been continued arthritis of the carpal areas. Repeat roentgenograms obtained in May 1973 demonstrated definite ankylosis. The most recent study, in June 1975 (Figure 2C), revealed carpometacarpal and intercarpal ankylosis without erosions. At that time the patient had no pain in her wrists, but the total range of motion was restricted to 25" on the right and 60" on the left.
Fig 2A. Case 7. Normal wrist roentgenogratns taken in February 1970. 13 months after disease onset.
CARPAL ARTHRITIS IN STILL’S DISEASE
Fig 2 0 . Case 7. May 1971: Roentgenograms reveal carpometacarpal joint space narrowing and indistinct cortical margins but no erosions.
Fig 2C. Case 7 . June 1975: Radiograph shows ankylosis across carpometacarpal joints 2 and 3 and diffuse intercarpal ankylosis affecting at least the trapezoid-capitate and capitate-hamate articulations. Note sparing of radiocarpal joints.
237
238
MEDSGER A N D CHRISTY
Case 12 LK, a 17-year-old white male student, was in excellent health until November 1971, when he noted a sore throat and transient stiffness and limitation of cervical spine motion. In July 1972 he developed bilateral and symmetrical stiffness, pain, and swelling of the shoulders, elbows, wrists, MCPs, PIPS, and knees. Simultaneously there was daily spiking fever to 103-105°F and a recurrent blotchy macular rash over the extremities and trunk. Generalized lymphadenopathy was present without hepatomegaly or splenomegaly and the SGOT was elevated to 3.3 times normal. Because of concern about an occult malignancy, in particular lymphoma, the axillary, inguinal, and mediastinal lymph nodes, liver, and bone marrow were biopsied and revealed only nonspecific changes. He was given prednisone, 60 mg/day, and all symptoms and signs improved strikingly. However, when the dose of prednisone was tapered below 20 mg/day (March 1973), arthritis of the wrists and knees recurred along with low grade fever. The spleen tip was palpable for the first
time. The WBC count was 22,100/mm3 and the latex agglutination and ANA tests were negative. The diagnosis of late onset Still’s disease was made at that time. Roentgenograms of the wrists revealed no abnormalities (Figure 3A). During the subsequent months the patient felt well except for persistently painful, swollen wrists which had a decreased range of motion. In August 1973 (Figure 3B) generalized bone demineralization was seen along with significant narrowing of the carpometacarpal joint spaces bilaterally and a “fluffy,” indistinct appearance of the cortical margins in these areas. By April 1974 wrist roentgenograms showed complete loss of the second and third carpometacarpal joint spaces with bony ankylosis (Figure 3C). The peripheral synovitis subsequently responded to a course of gold salt therapy.
DISCUSSION The clinical and laboratory manifestations in these patients with late onset Still’s disease are similar to
Fig 3A. Case 12. Normal wrisr radiographs in March 1973.
CARPAL ARTHRITIS I N STILL’S DISEASE
Fig 3B. Case 12. August 1973: Roentgenograms show marked narrowing of carpometacarpaljoint spaces 2 and 3 and narrowing of the trapezoid-capitate joint space.
Fig 3C. Case 12. April 1974: Complete bony ankylosis at carpometacarpaljoint spaces 2 and 3 has occurred without erosions. In addition. trapezium-trapezoid, trapezoid-capitate. and capitate-hate ankylosis are seen.
239
240
those previously reported by Bywaters ( 1 ) and Bujak, Aptekar, er af (3,4). The most characteristic constellation of features includes fever, rash, arthritis, serositis, hepato-splenomegaly and/or lymphadenopathy, marked leukocytosis, and negative serologic reactions for rheumatoid factor and antinuclear antibodies. The present findings of mild reversible hepatic enzyme abnormalities and minimal histologic changes on liver biopsy closely resemble those described by Bujak er a1 (3). Similar changes have been noted in juvenile rheumatoid arthritis (JRA), especially with the Still’s type of onset (5). Reviews of the roentgenographic changes in adult rheumatoid arthritis indicate that ankylosis of one or more joints is relatively uncommon, ranging from 5 to 27% in several large series (6-9). In the report of the Scientific Advisory Committee of the Empire Rheumatism Council in 1950 (9), ankylosis was found in 17% of 400 patients and ranked eighth in order of frequency of roentgenographic changes. A similar frequency of ankylosis has been reported in JRA patients (7-23%), most commonly involving the cervical spine but also occurring in the wrists (10,ll). In a study of 544 cases, Laaksonen (1 1 ) found that ankylosis was most frequent in children 10 years of age and over and in those who had their disease for at least 2-3 years. The carpometacarpal joints were most often ankylosed; the third (31.3%) and second (27.5%) CMCs were far more commonly affected than the others (fourth CMC: 5.4%; fifth CMC: 4.6%; first CMC: 0.4%). N o further mention of the frequency of intercarpal or radiocarpal ankylosis was made. The only clear-cut association of ankylosis was with functional classes I11 and I V in this study. Martel er a1 (12) described ankylosis of at least one peripheral joint in 15 of 80 J RA patients; in 13 of these, the wrist was involved. Usually one of three components of the total carpal complex (radiocarpal, intercarpal, or carpometacarpal) remained unaffected and thus allowed some motion at the wrist. The relative frequency of ankylosis at these three locations was not stated. Ansell and Bywaters (13), in a review of 316 cases, stated that bony ankylosis of the carpal bones in JRA was “not infrequent” but “not incapacitating.” No data with respect to frequency were given, but these authors did suggest that the carpus is the most commonly ankylosed of all peripheral articulations in JRA. Levinson (14) also reported wrist ankylosis without evidence of finger joint disease as a feature much more common in children than in adults with RA; he has seen 8 such patients. In 1962 Ansell and Bywaters (15) published a 5year followup study of patients previously diagnosed
MEDSGER AND CHRISTY
as having probable Still’s disease. In one case roentgenograms showed evolution of the wrist changes similar to those found in the present study. This girl had presented with arthritis of both wrists, pericarditis, and fever. At the time of reevaluation 6 years later, she was asymptomatic except for decreased range of motion of the left wrist. Serial roentgenograms showed intercarpal ankylosis at that time and later extensive carpometacarpal ankylosis [Figure 7, p 259 (15)]. Levinson also published an illustration [Figure 5, p 93 (14)] demonstrating carpometacarpal ankylosis in a patient with JRA, but the type of disease onset was not stated. In his initial description of Still’s disease in adults, Bywaters (1) commented on transient but occasionally recurrent inflammation of the peripheral joints. The involvement was typically pauciarticular and most commonly affected the knees, fingers, and wrists. Only 2 cases (Cases 4 and 6) had roentgenographic changes; these involved the carpus in which there was “curiously limited” ankylosis that was not further described. It is interesting, however, that Figure 6 in Bywaters’ article illustrates carpometacarpal joint space narrowing and ankylosis which took place over 2-4 years after onset in Patient 6. Marginal joint erosions did occur in his series, but were extensive in only 2 patients. Two of Bywaters’ patients (Cases 1 and 9) had apophyseal joint ankylosis in the cervical spine. Bujak et af (3) noted roentgenographic changes in only 1 of 10 patients. This individual developed “almost complete obliteration of the intercarpal spaces” over 22 months. Carpal and metacarpal erosions were also present bilaterally on the followup roentgenograms. In neither of these groups of patients was there mention of chronic active synovitis persisting during interfebrile periods. In contrast, the present authors found evidence of continued inflammation of joints in 10 of 13 patients. Although articular findings exacerbated during recurrences of multisystem disease, both clinical and roentgenographic evidence of joint damage progressed relentlessly. At least part of this discrepancy between articular and systemic disease activity may be accounted for by the use of antiinflammatory agents in high doses, especially corticosteroids. This fact is well illustrated by the 2 cases described above, in which limitation of wrist motion and roentgenographic changes progressed despite successful suppression of fever, rash, and serositis by the corticosteroids. The earliest roentgenographic change was osteoporosis and an indistinct appearance of the carpometacarpal and intercarpal cortical margins with joint space narrowing. This change was followed after a variable period of time by obliteration of these joint spaces
CARPAL ARTHRITIS I N STILL’S DISEASE
and complete bony ankylosis. Little or no loss of bony substance within the carpus resulted during this process. Once begun, this evolution progressed to ankylosis in most cases without typical marginal erosions within 1.5-4 years. Roentgenograms in 2 patients (Cases 9 and 10) did show erosions, but these were located at a distance from the carpal areas. After ankylosis, tenderness and swelling of the carpus were usually absent, and these patients were left with painless, reduced range of motion at the wrist. Although other joints were affected roentgenographically, this particular progression of changes was noted only in the carpometacarpal, intercarpal, and tarsometatarsal articulations in the present series of patients. The tendency of ankylosis to affect chiefly the capitate and those bones that border it (Figure 1 ) is unexplained. Several authors (10-12) have speculated that limited mobility at the wrist is in some way important. The capitate in particular is felt to be the center of least motion of the carpal bones in both flexion and extension of the wrist. The literature on ankylosis in rheumatoid arthritis is not sufficiently detailed to allow prediction of which patients stand the highest risk of developing carpal ankylosis. The authors have accumulated the wrist roentgenographs of 57 additional patients with RA of more than 3 years duration (Table 4). These patients were divided according to disease type and their radiographs were reviewed. The frequency of ankylosis in juvenile Still’s disease, juvenile polyarticular RA, and adult RA were all relatively low. Although these results are preliminary, it appears that there is a greater tendency to ankylosis in the systemic (Still’s type) onset variant of RA, regardless of the age at which it begins. Furthermore the carpometacarpal and intercarpal joints seem to be selectively affected, although this finding is not exclusive or pathognomonic. In a disease that has no single diagnostic laboratory feature, the finding of carpal ankylosis may be a valuable clue to diagnosis and ultimately to pathogenesis and etiology.
ADDENDUM Since submission of this manuscript, the authors have seen an additional example of ankylosis in late onset Still’s disease. AL, a 31-year-old white man, had several episodes of high, spiking fever with swelling of the wrists and ankles between ages 3 and 10. There were no apparent articular sequelae. At age 29 he developed intermittent fever (to 103’F) and chronic polyarthritis
24 1
Table 4. Carpometacarpal and Intercarpal Ankylosis in Rheumatoid Arthritis Variants R A Variant
Late onset Still’s disease Juvenile Still’s disease Adult R A
Juvenile polyarticular R A
N o . of Patients
Percent
7/13 2/9 4/38 0/10
54 22 11
0
involving both hips, the right elbow, right wrist, and left ankle. There was no rash. Indomethacin was helpful but no remission was achieved. In August 1975 he had a WBC count of 1 5,200/mm3 and negative latex agglutination and A N A tests. Roentgenograms of the right wrist showed advanced ankylosis between the second metacarpal and the trapezoid and between the third metacarpal and the capitate.
ACKNOWLEDGMENTS The authors are grateful to the following physicians for their cooperation in making the patients and their records available for study: Dr. Carl E. Anderson, Dr. Carolyn Anderson, Dr. Philip Balk, Dr. Thomas G. Benedek, Dr. Robert B. Buckingham, Dr. Paul S. Caplan, Dr. William M. Cooper, Dr. H. Lee Dameshek, Dr. Lawrence D. Ellis, Dr. Marshall S. Levy, Dr. Victor 1. Markson, Dr. John R. Misage, Dr. Lawrence M. Mulhern, Dr. Burton s. Pollock, Dr. Gerald P. Rodnan, and Dr. J. W. Schoolnic.
REFERENCES I . Bywaters EGL: Still’s disease in the adult. Ann Rheum Dis 30:121-133, 1971 2. Still GF: On a form of chronic joint disease in childhood. Med Chir Trans 80:47-59, 1897 3. Bujak JS, Aptekar RG, Decker JL, et al: Juvenile rheumatoid arthritis presenting in the adult as fever of unknown origin. Medicine 52:431-444, 1973 4. Aptekar RG, Decker JL, Bujak JS, et al: Adult onset juvenile rheumatoid arthritis. Arthritis Rheum 16:715718, 1973 5. Schaller J, Beckwith B, Wedgwood RJ: Hepatic involvement in juvenile rheumatoid arthritis. J Pediatr 77:203-210, 1970 6. T a y l o r G D , Ferguson AB, Kasabach H , e t al: Roentgenologic observations on various types of chronic arthritis. Arch Intern Med 57:282-295, 1936 7. Fletcher DE, Rowley KA: The radiologic features of rheumatoid arthritis. Br J Radio1 25:282-295, 1952 8. Soila P: Roentgen manifestations of aduit rheumatoid arthritis with special regard to the early changes. Acta Rheumatol Scand 2:i-144, 1958 (Suppl I )
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9. Report of the scientific advisory committee of the empire rheumatism council. Br Med J 1:799-805, 1950 10. Sairanen E: On RA in children. A clinico-roentgenographic study. Acta Rheumatol Scand 2:l-79, 1958 (SUPPI) I I . Laaksonen AL: A prognostic study of JRA. Analysis of 544 cases. Acta Paediatr Scand [Suppl] 166:l-163, 1966 12. Martel W, Holt JF, Cassidy JT: Roentgenologic manifes-
tations of juvenile rheumatoid arthritis. Am J Roentgen01 Radium Ther Nucl Med 88:400-423, 1962 13. Ansell BM, Bywaters EGL: Rheumatoid arthritis (Still’s disease). Pediatr Clin North Am 10:921-939, 1963 14. Levinson JE: Juvenile rheumatoid arthritis. Postgrad Med 51188-94, 1972 15. Ansell BM, Bywaters EGL: Diagnosis of probable Still’s disease and its outcome. Ann Rheum Dis 21:253-262, I962
The Proceedings of the Conference on Pseudogout and Pyrophosphate Metabolism Edited by Daniel J. McCarty, M.D. will be published as a supplement to the May-June 1976 issue of ARTHRITIS AND RHEUMATISM Subscribers t o ARTHRITIS AND RHEUMATISM will receive the conference supplement a t no extra charge. Additional copies may be purchased by sending your check for $10.00 to: The Arthritis Foundation Attn: A&R Circulation Department 475 Riverside Drive New York, New York 10027
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