Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Systemic juvenile idiopathic arthritis: diagnosis, management, and outcome

Abstract

Systemic juvenile idiopathic arthritis is a heterogeneous form of arthritis in childhood and represents 10–20% of all juvenile idiopathic arthritides in the Caucasian populations of Northern America and Europe. Up to 30% of patients will still have active disease after 10 years, and morbidity within this group is high. Secondary complications (e.g. growth failure, osteoporosis, deformities, and loss of function) and amyloidosis are the medical sequelae, but there are also serious developmental and social consequences. The medical treatment of patients who are at the more severe end of the disease spectrum is unsatisfactory; however, new therapies that might improve prognosis, such as autologous stem-cell transplantation and approaches for blocking interleukin-6 signaling, are currently being assessed in clinical trials.

Key Points

  • Systemic juvenile idiopathic arthritis (sJIA) can be long-lasting

  • If untreated, sJIA can lead to serious complications, such as hemophagocytic lymphohistiocytosis, growth failure, osteoporosis, and amyloidosis

  • Current medical treatment for severe sJIA is still unsatisfactory

  • Research into the pathogenesis of the disease will help with the development of more appropriate treatments

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Typical quotidian fever of systemic juvenile idiopathic arthritis, which is resistant to high-dose oral prednisone (>1mg/kg).
Figure 2
Figure 3: Treatment algorithm for systemic juvenile idiopathic arthritis in the unit at Great Ormond Street Hospital for Sick Children in London, UK.
Figure 4: Osteoporosis in juvenile idiopathic arthritis.
Figure 5: Comparison of height between twins.

Similar content being viewed by others

References

  1. Petty RE et al. (2004) International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision; Edmonton, 2001. J Rheumatol 31: 390–392

    PubMed  Google Scholar 

  2. Symmons DP et al. (1996) Pediatric rheumatology in the United Kingdom: data from the British Pediatric Rheumatology Group National Diagnostic Register. J Rheumatol 23: 1975–1980

    CAS  PubMed  Google Scholar 

  3. Fishman D et al. (1998) The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest 102: 1369–1376

    Article  CAS  Google Scholar 

  4. Peterson LS et al. (1996) Juvenile rheumatoid arthritis in Rochester, Minnesota 1960–1993. Is the epidemiology changing? Arthritis Rheum 39: 1385–1390

    Article  CAS  Google Scholar 

  5. Gare BA and Fasth A (1992) Epidemiology of juvenile chronic arthritis in southwestern Sweden: a 5-year prospective population study. Pediatrics 90: 950–958

    CAS  PubMed  Google Scholar 

  6. Fujikawa S and Okuni M (1997) Clinical analysis of 570 cases with juvenile rheumatoid arthritis: results of a nationwide retrospective survey in Japan. Acta Paediatr Jpn 39: 245–249

    Article  CAS  Google Scholar 

  7. Seth V et al. (1996) Clinico -immunological profile in juvenile rheumatoid arthritis—an Indian experience. Indian J Pediatr 63: 293–300

    Article  CAS  Google Scholar 

  8. Moroldo MB et al. (2004) Juvenile rheumatoid arthritis affected sibpairs: extent of clinical phenotype concordance. Arthritis Rheum 50: 1928–1934

    Article  Google Scholar 

  9. Thomson W et al. (2002) Juvenile idiopathic arthritis classified by the ILAR criteria: HLA associations in UK patients. Rheumatology (Oxford) 41: 1183–1189

    Article  CAS  Google Scholar 

  10. Donn R et al. (2004) A functional promoter haplotype of macrophage migration inhibitory factor is linked and associated with juvenile idiopathic arthritis. Arthritis Rheum 50: 1604–1610

    Article  Google Scholar 

  11. De Benedetti F et al. (2003) Functional and prognostic relevance of the -173 polymorphism of the macrophage migration inhibitory factor gene in systemic-onset juvenile idiopathic arthritis. Arthritis Rheum 48: 1398–1407

    Article  CAS  Google Scholar 

  12. Ogilvie EM et al. (2003) The -174G allele of the interleukin-6 gene confers susceptibility to systemic arthritis in children: a multicenter study using simplex and multiplex juvenile idiopathic arthritis families. Arthritis Rheum 48: 3202–3206

    Article  CAS  Google Scholar 

  13. Pascual V et al. (2005) 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 201: 1479–1486

    Article  CAS  Google Scholar 

  14. Yokota S et al. (2005) Therapeutic efficacy of humanized recombinant anti-interleukin-6 receptor antibody in children with systemic-onset juvenile idiopathic arthritis. Arthritis Rheum 52: 818–825

    Article  CAS  Google Scholar 

  15. Woo P et al. (2005) 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 7: R1281–R1288

    Article  CAS  Google Scholar 

  16. Wulffraat NM et al. (2005) Treatment of refractory autoimmune diseases with autologous stem cell transplantation: focus on juvenile idiopathic arthritis. Bone Marrow Transplant 35 (Suppl 1): S27–S29

    Article  Google Scholar 

  17. Villanueva J et al. (2005) Natural killer cell dysfunction is a distinguishing feature of systemic onset juvenile rheumatoid arthritis and macrophage activation syndrome. Arthritis Res Ther 7: R30–R37

    Article  CAS  Google Scholar 

  18. Grom AA (2004) Natural killer cell dysfunction: a common pathway in systemic-onset juvenile rheumatoid arthritis, macrophage activation syndrome, and hemophagocytic lymphohistiocytosis? Arthritis Rheum 50: 689–698

    Article  Google Scholar 

  19. Ravelli A et al. (2005) Preliminary diagnostic guidelines for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. J Pediatr 146: 598–604

    Article  Google Scholar 

  20. Woo P (2002) Cytokines and juvenile idiopathic arthritis. Curr Rheumatol Rep 4: 452–457

    Article  Google Scholar 

  21. Mangge H et al. (1999) Long-term follow-up of cytokines and soluble cytokine receptors in peripheral blood of patients with juvenile rheumatoid arthritis. J Interferon Cytokine Res 19: 1005–1010

    Article  CAS  Google Scholar 

  22. de Jager W et al. (2004) Simultaneous detection of 30 soluble mediators in plasma and synovial fluid of patients with JIA [abstract]. Clin Exp Rheumatol 22(4): 538

    Google Scholar 

  23. Silverman ED et al. (1990) Intravenous gamma globulin therapy in systemic juvenile rheumatoid arthritis. Arthritis Rheum 33: 1015–1022

    Article  CAS  Google Scholar 

  24. Laxer RM and Schneider R (2004) Systemic-onset juvenile chronic arthritis. In Oxford Textbook of Rheumatology, 798–810 (Eds Isenberg DA et al.) Oxford: Oxford University Press

    Google Scholar 

  25. Woo P et al. (2000) Randomized, placebo-controlled, crossover trial of low-dose oral methotrexate in children with extended oligoarticular or systemic arthritis. Arthritis Rheum 43: 1849–1857

    Article  CAS  Google Scholar 

  26. Kimura Y et al. (2005) Etanercept treatment in patients with refractory systemic onset juvenile rheumatoid arthritis. J Rheumatol 32: 935–942

    CAS  PubMed  Google Scholar 

  27. Wulffraat NM et al. (2003) Long-term follow-up of autologous stem cell transplantation for refractory juvenile idiopathic arthritis. Bone Marrow Transplant 32 (Suppl 1): S61–S64

    Article  CAS  Google Scholar 

  28. Davies UM et al. (1994) Treatment of growth retardation in juvenile chronic arthritis with recombinant human growth hormone. J Rheumatol 21: 153–158

    CAS  PubMed  Google Scholar 

  29. Fernandes JL et al. (2004) Biphosphonate-induced radiographic changes in two pediatric patients with rheumatic diseases. Skeletal Radiol 33: 732–736

    Article  Google Scholar 

  30. White PH (2002) Transition: a future promise for children and adolescents with special health care needs and disabilities. Rheum Dis Clin North Am 28: 687–703

    Article  Google Scholar 

  31. McDonagh JE et al. (2004) Unmet education and training needs of rheumatology health professionals in adolescent health and transitional care. Rheumatology (Oxford) 43: 737–743

    Article  CAS  Google Scholar 

  32. Baum J et al. (1980) Juvenile rheumatoid arthritis. A comparison of patients from the USSR and USA. Arthritis Rheum 23: 977–984

    Article  CAS  Google Scholar 

  33. Prieur AM et al. (1984) Prognosis of the systemic forms of juvenile chronic arthritis. Apropos of 100 cases. Arch Fr Pediatr 41: 91–97

    CAS  PubMed  Google Scholar 

  34. Hafner R and Truckenbrodt H (1986) Course and prognosis of systemic juvenile chronic arthritis—retrospective study of 187 patients. Klin Padiatr 198: 401–407

    Article  CAS  Google Scholar 

  35. Spiegel LR et al. (2000) Early predictors of poor functional outcome in systemic-onset juvenile rheumatoid arthritis: a multicenter cohort study. Arthritis Rheum 43: 2402–2409

    Article  CAS  Google Scholar 

  36. Modesto C et al. (2001) Systemic onset juvenile chronic arthritis, polyarticular pattern and hip involvement as markers for a bad prognosis. Clin Exp Rheumatol 19: 211–217

    CAS  PubMed  Google Scholar 

  37. Duffy CM (2004) Health outcomes in pediatric rheumatic diseases. Curr Opin Rheumatol 16: 102–108

    Article  Google Scholar 

  38. Ansell BM and Hall MA (1976) Rheumatic disorders in childhood (1). Rep Rheum Dis 59: 1–2

    Google Scholar 

  39. Lomater C et al. (2000) Systemic onset juvenile idiopathic arthritis: a retrospective study of 80 consecutive patients followed for 10 years. J Rheumatol 27: 491–496

    CAS  PubMed  Google Scholar 

  40. David J et al. (1994) The functional and psychological outcomes of juvenile chronic arthritis in young adulthood. Br J Rheumatol 33: 876–881

    Article  CAS  Google Scholar 

  41. Packham JC and Hall MA (2002) Long-term follow-up of 246 adults with juvenile idiopathic arthritis: education and employment. Rheumatology (Oxford) 41: 1436–1439

    Article  CAS  Google Scholar 

  42. Packham JC and Hall MA (2002) Long-term follow-up of 246 adults with juvenile idiopathic arthritis: social function, relationships and sexual activity. Rheumatology (Oxford) 41: 1440–1443

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Patricia Woo.

Ethics declarations

Competing interests

The author declares no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Woo, P. Systemic juvenile idiopathic arthritis: diagnosis, management, and outcome. Nat Rev Rheumatol 2, 28–34 (2006). https://doi.org/10.1038/ncprheum0084

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncprheum0084

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing