125 1 CARPAL ANKYLOSIS IN JUVENILE RHEUMATOID ARTHRITIS JOSE A. MALDONADO-COCCO, OSVALDO GARCIA-MORTEO, ALBERT0 J. SPINDLER, OSVALDO HUBSCHER. and SUSANA GAGLIARDI Forty-seven of 100 consecutive juvenile rheumatoid arthritis patients with wrist arthritis were found to have ankylosis at the carpal joints. This finding was significantly more frequent in juvenile than in adult rheumatoid arthritis patients. The carpometacarpal wrist segment was the most frequently ankylosed. Ankylosis was not related to any particular feature of the disease, but disease duration was longer in patients with ankylosis. A significant association was found between carpal ankylosis and cervical apophyseal joint fusion. Radiologic changes found in children with rheumatoid arthritis (RA) seem to parallel those appearing in adult patients, with the exceptions of growth disturbances and cervical spine involvement (1,2). Carpal bone fusion has been mentioned in several general reviews of radiologic manifestations of juvenile rheumatoid arthritis (JRA) (1-3). However, with the exception of one study in which its frequency was mentioned (3), Presented in preliminary form at the IX Congreso Rioplatense de Reumatologia, Solis, Uruguay, December 8, 1978. From the Section of Rheumatology, Department of Medicine, Instituto Nacional de Rehabilitacion; Universidad de Buenos Aires, Buenos Aires, Argentina. J.A. Maldonado-Cocco, MD: Staff Physician, Section of Rheumatology, lnstituto Nacional de Rehabilitacion; 0. Garcia-Morteo, MD: Associate Professor of Medicine, Universidad de Buenos Aires, and Head, Rheumatology Section, Instituto Nacional de Rehabilitation; A.J. Spindler, MD: Former Fellow in Rheumatology; 0. Hubscher, MD: Staff Physician, Section of Rheurnatology, Instituto Nacional de Rehabilitacibn; S. Gagliardi, MD: Staff Physician, Section of Rheumatology, Instituto Nacional de Rehabilitacion. Address reprint requests to Jost A. Maldonado-Cocco, MD, Secci6n Reumatologia, Instituto Nacional de Rehabilitacion, Echeverria 955, 1428 Buenos Aires, Argentina. Submitted for publication September 4, 1979; accepted in revised form December 20, 1979. to our knowledge there are no observations regarding its relationship with clinical features of the disease. Recently in a study of Still's disease with onset in adulthood, Medsger and Christy (4) have suggested that fusion of the carpometacarpal and intercarpal joints was characteristic of the systemic onset of RA, regardless of the age at onset. Since this particular bony ankylosis has been a rather frequent observation in our JRA population, we decided to investigate its prevalence and characteristics, as well as its relationship with several aspects of the disease. PATIENTS AND METHODS One hundred consecutive JRA patients known to have clinical wrist joint involvement and x-rays available were included in this study. Clinical wrist involvement was defined as swelling of the joint with or without pain and/or limitation of motion. Diagnosis of JRA was made according to the criteria of Ansell and Bywaters (5). Predominant clinical manifestations directly observed by the authors or referring physicians or recorded from the parents' histories served to classify type of onset as either oligoarticular (4 or less joints involved), polyarticular, or systemic (spiking fever, rash, hepatosplenomegaly). All x-rays were specifically reviewed for the presence of joint space narrowing, juxtaarticular osteoporosis, erosions, subchondral sclerosis, periostitis, and bony ankylosis. Special attention was given to the 3 groups of the joints in the wrist: carpometacarpal (CMC), intercarpal (IC), and radiocarpal (RC) components. In 94 patients concomitant cervical spine x-rays were also reviewed. Hand x-rays of 100 consecutively observed adult onset RA patients with clinical wrist involvement were also studied. All adult RA patients fulfilled American Rheumatism Association (ARA) criteria for definite or classic disease (6). Rheumatoid factors (RF) were investigated by the latex fixation and sheep cell agglutination (SCAT) techniques (7,8). In our patients, RF are determined once a year; patients Arthritis and Rheumatism, Vol. 23, No. 11 (November 1980)
1252 MALDONADO-COCCO ET AL Figure 1. Fusion between the second metacarpal to trapezium and trapezoid bones in a 13-year-old male patient with systemic onset JRA. are considered seropositive if at any visit either the latex fixation titer is 1:160 or greater or the SCAT titer is 1:32 or greater. Serum antinuclear antibodies (ANA) were investigated by a standard indirect immunofluorescent technique (9). Statistical methods. Median values of age at onset, age at study, and duration of JRA were calculated by considering a logarithmic normal distribution. Age at onset was compared between the 2 groups (with and without ankylosis) by the Student s t-test. Duration of JRA was compared be- Figure 2. Ankylosis between second CMC to trapezium and trapezoid and third CMC to capitate in a 16-year-old male with polyarticular JRA of 14 years duration. tween patient groups by the Tukey s w procedure. Percentages between groups were compared by the Chi-square test. RESULTS Sixteen of the 100 JRA patients with clinical wrist involvement had normal x-rays. Eighty-four patients had abnormal wrist x-rays and were grouped into Figure 3. Diffuse intercarpal and associated second and third CMC ankylosis in a IS-year-old male patient with polyarticular onset JRA since 4 years of age. Figure 4. Fusion of the three wrist segments in a girl with polyarticular JRA since age 4.
CARPAL ANKYLOSIS IN JRA 1253 Figure 5. Isolated radiocarpal joint fusion in a 13-year-old patient with polyarticular onset IRA. those with and without carpal bony ankylosis: 47 (55.9%) patients had different types of carpal fusion, and the remaining 37 (44%) patients had several degrees of radiologic lesions except bone fusion. Carpometacarpal fusion was found in 41 patients; 10 patients had exclusive CMC fusion. The re- maining 3 1 patients had associated intercarpal ankylosis. In 7 of these 31 patients the radiocarpal joint was also fused, thus the three groups of wrist joints were ankylosed. CMC ankylosis was always located between the base of the second and/or third metacarpals and the adjacent trapezoid and capitate. Exclusive ankylosis of single CMC joints was seen in only 5 patients: fusion was present between the second metacarpal and the trapezoid in 4 patients and between the third metacarpal and the capitate in 1 patient (Figure 1). Thirty-six of the 41 patients had associated second and third metacarpal-carpal ankylosis; 18 of these 36 patients also had carpal fusion at the level of the fourth and fifth metacarpal bones (Figure 2). It is noteworthy that in none of the 41 patients with CMC ankylosis was the first metacarpal bone involved and in only 1 patient was the third metacarpal bone involved. Only 5 patients showed intercarpal ankylosis alone. Although capitate, hamate, and lunate were the most frequently affected bones, intercarpal ankylosis was generally diffuse (Figure 3). Besides the 7 patients who had all three wrist compartments involved, there was only one patient with exclusive radiocarpal ankylosis (Figures 4 and 5). Clinical features in the 100 JRA patients are shown in Table 1. No significant differences were found by sex distribution, age at onset, age at study, or type of onset between patients with and without wrist ankylosis. Table 1. findings Clinical features in 100 patients with juvenile rheumatoid arthritis according to radiologic No. of patients Female: male ratio Age at disease onset, years (median) Age at study, years (median) Disease duration, years (median) Type of onset Polyarticular Oligoarticular Systemic Evolution to polyarticulart Rheumatoid factor, positive/ tested Normal 16 1:9 4 8.5 2 8 6 2 14 2/14 No ankylosis Other radiologic lesions 37 28:9 7 13 6 20 13 4 34 9/35 Wrist Total ankylosis Total 53 47 35: 18 31:16 6 6 12 15 4 9* 28 35 19 6 6 6 48 46 11/49 11/42 100 66 34 63 25 12 94 28/9 I Antinuclear antibodies, positive/ tested 1/13 8/35 9/48 10/42 19/90 Cervical spine ankylosis 4/14 4/34 8/48 24/46* 32/94 P > 0.05. t Indicates number of patients who developed polyarticular arthritis. * P < 0.01.
1254 MALDONADO-COCCO ET AL Median duration of disease was longer in the patients with wrist ankylosis (9 years) as compared with patients without ankylosis (4 years) (P < 0.05). As expected, patients without radiologic lesions had the shortest duration of disease (median 2 years) (P < 0.05). Polyarticular arthritis was the most common type of onset in all groups: 8 of 16 (50%) patients with normal x-rays, 20 of 37 (54%) patients without ankylosis, and 35 of 47 (74%) patients with ankylosis. Evolution of the disease was also polyarticular in about 90% of all patients. Prominent systemic features of JRA were not frequently observed during followup and were equally distributed among the patients with or without wrist ankylosis. Twenty-eight of 9 1 patients tested were positive for RF: 17 of 42 (40%) patients with ankylosis and 11 of 49 (22%) of the remaining patients (P > 0.05). The frequency of ANA was similar in both groups. Cervical apophyseal joint ankylosis was far more frequent in patients with carpal fusion: 24 of 46 (52%) patients with wrist ankylosis also had cervical apophyseal ankylosis, whereas only 8 of 48 (16.6%) patients without carpal fusion had cervical ankylosis. This difference is statistically significant (P < 0.0 1). In the group of 100 patients with adult onset RA, wrist ankylosis was observed in 15 patients, 11 patients had CMC fusion, and 4 other patients had IC ankylosis. Duration of disease in the adult patients was comparable to that of the juveniles (Table 2). DISCUSSION Bony ankylosis in the extremities of JRA patients is commonly regarded as a frequent finding (1,2,10). Fusion between the carpal bones has been mentioned as one of the most frequent findings by several authors (1-3). However, the real incidence of this complication has been scarcely reported (3). In Laaksonen s study it becomes apparent that at least 30% of 5 17 radiographed JRA patients showed carpometacarpal fu- sion; radiocarpal fusion was observed in 58 patients, or 11.2%. In another study (2) 13 of 15 patients with bony ankylosis had carpal bone fusion. Medsger and Christy (4) described CMC fusion in 7 of 13 adult onset JRA patients; they suggested that these roentgenographic changes may be a valuable clue to the diagnosis of this type of disease, regardless of the age at onset. However, only 19 juvenile RA patients were studied. In our total group of JRA patients about twothirds had wrist involvement. Carpal ankylosis, especially CMC, was a frequent finding in our JRA population regardless of the type of onset and the age at the study; the majority of patients showing this abnormality had polyarticular onset. No relation with systemic onset or systemic features during followup was found. Our results show that 47 of 100 radiographed JRA patients had different types of wrist ankylosis, the CMC being the most frequently involved (41 of 47). As in Laaksonen s series (3), the second and third CMCs were far more commonly affected than the others. Ankylosis of the fourth and fifth CMC was always observed associated with second and third CMC ankylosis. The first CMC segment was never found to be involved. Local steroid injections or rest splinting of the wrist were not different in patients with or without ankylosis. Since our institution is a referral center, our patient population probably represents the more severe cases in the community. However, in a similarly referred adult population with RA, carpal ankylosis was observed in only 15% of the patients. The difference between juvenile and adult patients regarding this complication is statistically significant (P < 0.01). None of the adult patients had features of adult onset systemic RA. In our experience, carpal ankylosis has not been observed in patients without clinical wrist involvement. Although seropositivity was slightly more frequent in the group of JRA patients with wrist ankylosis, many of them were seronegative. An interesting observation was the finding of a Table 2. Comparison between juvenile and adult rheumatoid arthritis patients with and without wrist ankylosis JRA Adult-onset RA No No Ankylosis ankylosis Ankylosis ankylosis No. of patients 47 53 15 85 Female : male ratio 31:16 35: 18 14: 1 69: 16 Age at onset, years (median) 6 6 36 41 Disease duration, years (median) 9 4 13 4
CARPAL ANKYLOSIS IN JRA 1255 frequent association between carpal and cervical zygapophyseal joint fusion. Of the 94 patients for whom neck x-rays were available, 32 had zygapophyseal joint fusion, and 24 of them (75%) had associated carpal ankylosis. Our findings demonstrate the frequent occurrence of carpal joint ankylosis in JRA and its lack of relationship to any particular type of disease onset; it was related to longer duration of disease. The significant coexistence of wrist and cervical apophyseal joint ankylosis suggests an increased tendency to the development of ankylosis in a particular portion of the JRA population. 1. 2. REFERENCES Sairanen E: On rheumatoid arthritis in children. Acta Rheumatol Scand (suppl) 2:l-79, 1958 Martel W, Holt JF, Cassidy JT: Roentgenologic manifestations of juvenile rheumatoid arthritis. Am J Roentgen01 Radium Ther Nucl Med 88:400-423, 1962 3. 4. 5. 6. 7. 8. 9. 10. Laaksonen AL: A prognostic study of juvenile rheumatoid arthritis. Acta Paediatr Scand (suppl) 166:l-163, 1966 Medsger TA, Christy WC: Carpal arthritis with ankylosis in late onset Still's disease. Arthritis Rheum 19:232-242, 1976 Ansell BM, Bywaters EGL: Prognosis in Still's disease. Bull Rheum Dis 9:189-192, 1959 Ropes MW, Bennett GH, Cobb S, Jacox RF, Jessar RA: Revision of diagnostic criteria for rheumatoid arthritis. Bull Rheum Dis 9:175-176, 1958 Singer JM, Plotz CM: The latex fixation test. I. Application to the serological diagnosis of rheumatoid arthritis. Am J Med 21:888-898, 1956 Roitt IM, Doniach D: Sheep cell agglutination test (SCAT) for the detection of rheumatoid factors. WHO Manual of Autoimmune Serology, May 1969, pp 27-28 Hammard M, Cannat A, Seligmann M: La recherche d'anticorps antinucleaires par Immunofluorescence. Etude de 1430 Serums. Rev fr Et Clin et Biol 9:716-728, 1964 Cassidy JT, Martel W: Juvenile rheumatoid arthritis: clinicoradiologic correlations. Arthritis Rheum 20:207-2 1 1, 1977