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  • Case Study
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A case of macrophage activation syndrome successfully treated with anakinra

Abstract

Background A 13-year-old girl presented with features typical of systemic juvenile idiopathic arthritis, including fever, rash and arthritis. Her past medical history was unremarkable.

Investigations Routine investigations, including CBC, serological tests for urea and electrolyte levels, tests of liver function and clotting, measurement of erythrocyte sedimentation rate, cultures of blood, urine and throat swabs, abdominal ultrasonography, echocardiography, bone marrow aspiration, and determination of laboratory parameters, including presence of anti-streptolysin O antibody and levels of C-reactive protein, lactate dehydrogenase, serum ferritin, D-dimer, fibrinogen and ciclosporin. Specialized investigations included measurement of serum levels of interleukin (IL)-1, IL-6, IL-10, tumor necrosis factor and soluble CD25.

Diagnosis Systemic juvenile idiopathic arthritis complicated by macrophage activation syndrome.

Management The disease remained active following treatment with intravenous steroid, immunoglobulin and ciclosporin. The patient's disease was successfully controlled following the introduction of anakinra.

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References

  1. Kelly A and Ramanan AV (2007) Recognition and management of macrophage activation syndrome in juvenile arthritis. Curr Opin Rheumatol 19: 477–481

    Article  CAS  Google Scholar 

  2. 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 

  3. Stéphan JL et al. (1993) Macrophage activation syndrome and rheumatic disease in childhood: a report of four new cases. Clin Exp Rheumatol 11: 451–456

    PubMed  Google Scholar 

  4. Ravelli A (2002) Macrophage activation syndrome. Curr Opin Rheumatol 14: 548–552

    Article  CAS  Google Scholar 

  5. Bloom BJ et al. (1998) Fibrin D-dimer as a marker of disease activity in systemic onset juvenile rheumatoid arthritis. J Rheumatol 25: 1620–1625

    CAS  PubMed  Google Scholar 

  6. Gallistl S et al. (1998) Activation of the haemostatic system in children with juvenile rheumatoid arthritis correlates with disease activity. Thromb Res 92: 267–272

    Article  CAS  Google Scholar 

  7. Scott JP et al. (1985) Evidence for intravascular coagulation in systemic onset, but not polyarticular, juvenile rheumatoid arthritis. Arthritis Rheum 28: 256–261

    Article  CAS  Google Scholar 

  8. Bleesing J et al. (2007) The diagnostic significance of soluble CD163 and soluble interleukin-2 receptor alpha-chain in macrophage activation syndrome and untreated new-onset systemic juvenile idiopathic arthritis. Arthritis Rheum 56: 965–971

    Article  CAS  Google Scholar 

  9. Gupta A et al. (2008) The role of the initial bone marrow aspirate in the diagnosis of hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 51: 402–404

    Article  Google Scholar 

  10. Henter JI et al. (2007) HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 48: 124–131

    Article  Google Scholar 

  11. 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 

  12. Behrens EM et al. (2007) Occult macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis. J Rheumatol 34: 1133–1138

    PubMed  Google Scholar 

  13. Ramanan AV and Schneider R (2003) Macrophage activation syndrome—what's in a name! J Rheumatol 30: 2513–2516

    PubMed  Google Scholar 

  14. Sawhney SP et al. (2001) Macrophage activation syndrome: a potentially fatal complication of rheumatic disorders. Arch Dis Child 85: 421–426

    Article  CAS  Google Scholar 

  15. Stéphan JL et al. (2001) Reactive haemophagocytic syndrome in children with inflammatory disorders. A retrospective study of 24 patients. Rheumatology (Oxford) 40: 1285–1292

    Article  Google Scholar 

  16. Emmenegger U et al. (2001) Hyperferritinemia as indicator for intravenous immunoglobulin treatment in reactive macrophage activation syndromes. Am J Hematol 68: 4–10

    Article  CAS  Google Scholar 

  17. Emmenegger U et al. (2002) Reactive macrophage activation syndrome: a simple screening strategy and its potential in early treatment initiation. Swiss Med Wkly 132: 230–236

    CAS  PubMed  Google Scholar 

  18. Fishman D et al. (1995) Successful management of reactive haemophagocytic syndrome in systemic- onset juvenile chronic arthritis. Br J Rheumatol 34: 888

    Article  CAS  Google Scholar 

  19. 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 

  20. Verbsky JW and White AJ (2004) Effective use of the recombinant interleukin 1 receptor antagonist anakinra in therapy resistant systemic onset juvenile rheumatoid arthritis. J Rheumatol 31: 2071–2075

    PubMed  Google Scholar 

  21. Quartier P et al. (2003) Efficacy of etanercept for the treatment of juvenile idiopathic arthritis according to the onset type. Arthritis Rheum 48: 1093–1101

    Article  CAS  Google Scholar 

  22. Horneff G et al. (2004) The German etanercept registry for treatment of juvenile idiopathic arthritis. Ann Rheum Dis 63: 1638–1644

    Article  CAS  Google Scholar 

  23. 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 

  24. Prahalad S et al. (2001) Etanercept in the treatment of macrophage activation syndrome. J Rheumatol 28: 2120–2124

    CAS  PubMed  Google Scholar 

  25. Ramanan AV and Schneider R (2003) Macrophage activation syndrome following initiation of etanercept in a child with systemic onset juvenile rheumatoid arthritis. J Rheumatol 30: 401–403

    PubMed  Google Scholar 

  26. Lurati A et al. (2005) Macrophage activation syndrome (MAS) during anti-IL1 receptor therapy (anakinra) in a patient affected by systemic onset juvenile idiopathic arthritis (SoJIA): a report and review of the literature. Pediatr Rheumatol Online J 3: 79–85

    Google Scholar 

  27. Behrens EM et al. (2006) Interleukin 1 receptor antagonist to treat cytophagic histiocytic panniculitis with secondary hemophagocytic lymphohistiocytosis. J Rheumatol 33: 2081–2084

    PubMed  Google Scholar 

Download references

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Correspondence to Athimalaipet V Ramanan.

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Kelly, A., Ramanan, A. A case of macrophage activation syndrome successfully treated with anakinra. Nat Rev Rheumatol 4, 615–620 (2008). https://doi.org/10.1038/ncprheum0919

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