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Kim, Bang, Ahn, Rim, Kim, Uhm, Kim, Jun, Bae, and Yoo: Clinical Features and Course of Systemic Onset Juvenile Rheumatoid Arthritis
Original Article

J Korean Rheum Assoc 2007;14(4):331-339.

Published online: 23 December 2007

DOI: https://doi.org/10.4078/jkra.2007.14.4.331

Clinical Features and Course of Systemic Onset Juvenile Rheumatoid Arthritis

Ji Eun Kim, M.D., So Young Bang, M.D., Sang Bong Ahn, M.D., Keum Nam Rim, M.D., Hyun Soo Kim, M.D., Wan Sik Uhm, MD., Tae Hwan Kim, M.D., Jae Bum Jun, MD., Sang Cheol Bae, M.D., Dae Hyun Yoo, M.D.

Division of Rheumatology, Department of Internal Medicine, The Hospital for Rheumatic Disease, Hanyang University College of Medicine, Seoul, Korea

Received 13 September 200717 October 2007

Copyright © 2007 The Korean Rheumatism Association

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective:

Juvenile rheumatoid arthritis (JRA) is classified as polyarticular, oligoarticular, and systemic onset type by clinical symptoms presented during first six months. This study was performed to investigate the clinical features and course of systemic onset JRA.

Methods:

We performed a retrospective study for patients who were diagnosed as JRA between March 2000 and March 2006 according to the JRA criteria of the International League of Association for Rheumatology (ILAR).

Results:

Of the 216 JRA patients, 33 patients (11 male/ 22 female) were systemic onset type. Because of insufficient data, 6 patients were excluded. Chief complaints at the time of diagnosis were fever (81.5%) and arthralgia (77.7%). During the disease course, all patients manifested fever and arthritis, rash (59.2%) and splenomegaly (22.2%) also occurred. Most patients had symmetric (81.5%) arthritis, and involved more than five joints (59.3%) including knee and wrist. Anemia, leukocytosis, and thrombocytosis were common laboratory abnormalities. Almost all patients had elevated level of C-reactive protein and erythrocyte sediment rate. Some patients had positive results about immunologic marker such as rheumatoid factor (3.8%), antinuclear antibody (57.7%), and antiperinuclear factor (9.5%). Therapeutic regimens included glucocor-ticoids (88.9%), nonsteroidal anti-inflammatory drugs (81.5%), methotrexate (81.5%), and hydroxychloroquine (55.6%). Biologic agents were applied in 5 patients, and 3 showed improvement of disease activity. Combination therapy was introduced in 18.5% of patients, and 63% of patients still required medications.

Conclusion:

In Korea, systemic onset JRA patients had variable clinical manifestations and chronic course of disease, which often extended into adulthood.

Keywords: Juvenile rheumatoid arthritis, Systemic onset

REFERENCES

1). Mason TG., Reed AM. Update in juvenile rheumatoid arthritis. Arthritis Rheum. 2005. 53:796–9.
crossref
2). Brewer EJ Jr., Bass J., Baum J., Cassidy JT., Fink C., Jacobs J, et al. Current proposed revision of JRA Criteria. JRA Criteria Subcommittee of the Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Section of The Arthritis Foundation. Arthritis Rheum. 1977. 20:195–9.
3). Cassidy JT., Levinson JE., Bass JC., Baum J., Brewer EJ Jr., Fink CW, et al. A study of classification criteria for a diagnosis of juvenile rheumatoid arthritis. Arthritis Rheum. 1986. 29:274–81.
crossref
4). Harris ED., Budd RC., Firestein GS., Genovese MC., Sergent JS., Ruddy S, et al. Kelley's textbook of rheumatology. 7th ed.p. 1579. Philadelphia, W.B. Saunders;2004.
5). Woo P., Wedderburn LR. Juvenile chronic arthritis. Lancet. 1998. 351:969–73.
crossref
6). Yilmaz M., Kendirli SG., Altintas D., Bingol G., Antmen B. Cytokine levels in serum of patients with juvenile rheumatoid arthritis. Clin Rheumatol. 2001. 20:30–5.
7). Pascual V., Allantaz F., Arce E., Punaro M., Banchereau J. Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade. J Exp Med. 2005. 201:1479–86.
crossref
8). Schneider R., Passo MH. Juvenile rheumatoid arthritis. Rheum Dis Clin North Am. 2002. 28:503–30.
crossref
9). Manners PJ., Bower C. Worldwide prevalence of juvenile arthritis why does it vary so much? J Rheumatol. 2002. 29:1520–30.
10). Danner S., Sordet C., Terzic J., Donato L., Velten M., Fischbach M, et al. Epidemiology of juvenile idiopathic arthritis in Alsace, France. J Rheumatol. 2006. 33:1377–81.
11). Hanova P., Pavelka K., Dostal C., Holcatova I., Pikhart H. Epidemiology of rheumatoid arthritis, juvenile idiopathic arthritis and gout in two regions of the Czech Republic in a descriptive population-based survey in 2002-2003. Clin Exp Rheumatol. 2006. 24:499–507.
12). 김중곤: 정주영: 윤보영: 한윤수. 연소성류마티스관절염에대한임상적고찰(I. 전신형). 대한류마티스학회지. 1994. 1:175–82.
13). Baksiene D., Kasparaviciene J., Zebiene M., Puteliene B. Juvenile idiopathic systemic arthritis. Medicina (Kaunas). 2003. 39:751–5.
14). Spiegel LR., Schneider R., Lang BA., Birdi N., Silverman ED., Laxer RM, et al. Early predictors of poor functional outcome in systemic-onset juvenile rheumatoid arthritis: a multicenter cohort study. Arthritis Rheum. 2000. 43:2402–9.
crossref
15). Ramanan AV., Schneider R., Batthish M., Achonu C., Ota S., McLimont M, et al. Developing a disease activity tool for systemic-onset juvenile idiopathic arthritis by international consensus using the Delphi approach. Rheumatology (Oxford). 2005. 44:1574–8.
crossref
16). Cunha BA. Fever of unknown origin caused by adult juvenile rheumatoid arthritis: the diagnostic significance of double quotidian fevers and elevated serum ferritin levels. Heart Lung. 2004. 33:417–21.
crossref
17). Woo P., Wilkinson N., Prieur AM., Southwood T., Leone V., Livermore P, et al. Open label phase II trial of single, ascending doses of MRA in Caucasian children with severe systemic juvenile idiopathic arthritis: proof of principle of the efficacy of IL-6 receptor blockade in this type of arthritis and demonstration of prolonged clinical improvement. Arthritis Res Ther. 2005. 7:R1281–8.
18). Hur M., Kim YC., Lee KM., Kim KN. Macrophage activation syndrome in a child with systemic juvenile rheumatoid arthritis. J Korean Med Sci. 2005. 20:695–8.
crossref
19). Kim TY., Chang CS., Kim SY. A new substrate (ΓΓ-1) for the antinuclear antibody (ANA) test. Arthritis Rheum. 1994. 37(Suppl):s317.
20). Kim TY., Chang CS., Kim SY. New autoantibodies (anti-MTOC) detected by macrophage cell line (IT-1) in rheumatoid arthritis. Arthritis Rheum. 1995. 38(Suppl):s255.
21). el-Gamal Y., Hossny E., Mabrouk R., el-Gamasey T. Antiperinuclear factor in the diagnosis of juvenile rheumatoid arthritis. Pediatr Allergy Immunol. 1995. 6:165–9.
crossref
22). 김신규: 오지하: 서일혜: 김덕언: 장성렬: 유대현등. 류마티스관절염의새로운표지자항체Antiperinuclear factor (APF)에관한연구. 대한면역학회. 1994. 16:109–13.
23). Nesher G., Moore TL., Grisanti MW., el-Najdawi E., ᄋsborn TG. Antiperinuclear factor in juvenile rheumatoid arthritis. Ann Rheum Dis. 1992. 51:350–2.
crossref
24). Brooks CD. Sulfasalazine for the management of juvenile rheumatoid arthritis. J Rheumatol. 2001. 28:845–53.
25). Lurati A., Pontikaki I., Teruzzi B., Desiati F., Gerloni V., Gattinara M, et al. A comparison of response criteria to evaluate therapeutic response in patients with juvenile idiopathic arthritis treated with methotrexate and/or anti-tumor necrosis factor alpha agents. Arthritis Rheum. 2006. 54:1602–7.
26). Iesaka K., Kubiak EN., Bong MR., Su ET., Di Cesare PE. Orthopedic surgical management of hip and knee involvement in patients with juvenile rheumatoid arthritis. Am J ᄋrthop. 2006. 35:67–73.
27). ᄋen K., Malleson PN., Cabral DA., Rosenberg AM., Petty RE., Cheang M. Disease course and outcome of juvenile rheumatoid arthritis in a multicenter cohort. J Rheumatol. 2002. 29:1989–99.
28). Wallace CA., Levinson JE. Juvenile rheumatoid arthritis: outcome and treatment for the 1990s. Rheum Dis Clin North Am. 1991. 17:891–905.
crossref
29). Minden K., Kiessling U., Listing J., Niewerth M., Doring E., Meincke J, et al. Prognosis of patients with juvenile chronic arthritis and juvenile spondyloarthropathy. J Rheumatol. 2000. 27:2256–63.
30). Lomater C., Gerloni V., Gattinara M., Mazzotti J., Cimaz R., Fantini F. Systemic onset juvenile idiopathic arthritis: a retrospective study of 80 consecutive patients followed for 10 years. J Rheumatol. 2000. 27:491–6.
31). Zak M., Pedersen FK. Juvenile chronic arthritis into adulthood: a long-term follow-up study. Rheumatology (Oxford). 2000. 39:198–204.
crossref

Fig. 1.
Age distribution of systemic onset JRA at onset.
jkra-14-331f1.tif
Table 1.
The changes of clinical manifestations in systemic onset juvenile rheumatoid arthritis during follow up period
Clinical manifestations At diagnosis During follow up
Intermittent high fever 22 (81.5%) 27 (100%)
Arthritis 21 (77.7%) 27 (100%)
Rash 7 (25.9%) 16 (59.2%)
Lymphadenopathy 4 (14.8%)
Hepatomegaly 4 (14.8%)
Splenomegaly 6 (22.2%)
Myalgia 2 (7.4%) 4 (14.8%)
Table 2.
Characteristics of arthritis in systemic onset juvenile rheumatoid arthritis
Patients (%)
Pattern
Symmetric 22 (81.5%)
Asymmetric 5 (18.5%)
Number of affected joints
Less than 5 11 (40.7%)
More than 5 16 (59.3%)
Involved sites
Finger 12 (44.4%)
Wrist 15 (55.6%)
Elbow 12 (44.4%)
Shoulder 6 (22.2%)
Spine 1 (3.7%)
Toe 4 (14.8%)
Ankle 14 (51.9%)
Knee 15 (55.6%)
Hip 8 (29.6%)
Table 3.
Laboratory findings of systemic onset juvenile rheumatoid arthritis at diagnosis
Patients (%)
Hemoglobin Below 12 years old
(g/dL) <7 0
7-9 4 (44.4%)
9-11 2 (22.2%)
>11 3 (33.3%)
Above 12 years old
<8 3 (16.7%)
8-10 6 (33.3%)
10-12 5 (27.8%)
>12 4 (22.2%)
White blood cell Below 12 years old
(10x3/mm3) 4,500-13,500 5 (55.6%)
13,500-20,000 2 (22.2%)
20,000 - 40,000 2 (22.2%)
Above 12 years old
5,000-10,000 6 (33.3%)
10,000 - 20,000 8 (44.4%)
20,000 - 40,000 4 (22.2%)
Platelet 150,000-450,000 14 (51.9%)
(10x3/mm3) > 450,000 13 (48.1%)
AST (U/L) > 40 2 (8.0%)
<40 23 (92.0.1%)
ALT (U/L) > 45 3 (12.0%)
< 45 22 (88.0%)
LDH (U/L) > 200 6 (33.3%)
60 - 200 12 (66.7%)
Creatine kinase >165 0 (0%)
(U/L) 30-165 17 (100%)
ESR (mm/hr) > 20 23 (92.0%)
< 20 2 (8.0%)
CRP (mg/dL) >0.3 24 (92.3%)
<0.3 2 (7.7%)
Ferritin (ng/mL) >150 13 (61.9%)
<150 8 (38.1%)

ALT: alanine aminotransferase, AST: aspartate aminotransferase, CRP: C-reactive protein, ESR: erythrocyte sediment rate, LDH: lactate dehydrogenase

Table 4.
The changes of medications in systemic onset juvenile rheumatoid arthritis during follow up
Initial medication (n=27) Follow up medication (n=17)
NSAIDs 22 (81.5%) 13 (76.5%)
Glucocorticoid 24 (88.9%) 10 (58.8%)
Methotrexate 22 (81.5%) 9 (52.9%)
Hydroxychloroquine 15 (55.6%) 2 (11.8%)
Cyclosporine 11 (40.7%) 6 (35.3%)
Bucillamine 3 (11.1%) 2 (11.8%)
Leflunomide 5 (18.5%) 3 (17.6%)
Infliximab 3 (11.1%) 2 (11.8%)
Sulfasalazine 7 (25.9%)
Azathioprine 3 (11.1%) 1 (5.9%)
Etanercept 4 (14.8%) 4 (23.5%)
Surgery 3 (11.1%)

NSAIDs: nonsteroidal anti-inflammatory drugs

Table 5.
Frequent patterns of combined medication in systemic onset juvenile rheumatoid arthritis
Basic combination Combined medication Patients (%)
MTX+glucocorticoid 19 (70.4%)
NSAIDs 16 (59.3%)
Cyclosporine 9 (33.3%)
Hydroxychloroquine 9 (33.3%)
Leflunomide 3 (11.1%)
Bucillamine 3 (11.1%)
Etanercept 3 (11.1%)
Infliximab 2 (7.4%)

MTX: methotrexate, NSAIDs: non-steroidal anti-inflammatory drugs

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