Elsevier

Joint Bone Spine

Volume 74, Issue 5, October 2007, Pages 500-503
Joint Bone Spine

Case report
Efficacy of thalidomide in systemic onset juvenile rheumatoid arthritis

https://doi.org/10.1016/j.jbspin.2006.12.004Get rights and content

Abstract

Thalidomide is an immunomodulating agent which reverses many of the cytokine disturbances seen in systemic onset juvenile idiopathic arthritis (SoJIA) with inadequate response to other treatments. We report 3 cases of recalcitrant SoJIA which improved dramatically after treatment with thalidomide.

Patients

Three children aged 9, 8, and 6 years diagnosed with SoJIA treated with conventional therapy including NSAIDs, corticosteroids, methotrexate and etanercept failed to respond fully and their condition worsened. Thalidomide was begun based on two previous reports showing its efficacy in recalcitrant SoJIA.

Results

Thalidomide produced successful remission of the disease in all 3 patients according to the preliminary criteria for inactive disease and clinical remission of JIA.

Conclusion

Thalidomide may be a viable, alternative corticoid-sparing therapy in patients with recalcitrant, multidrug-resistant SoJIA.

Introduction

Systemic onset juvenile idiopathic arthritis (SoJIA) is a severe, debilitating inflammatory condition characterized by fever, rash and arthritis with many laboratory abnormalities including leukocytosis, thromobocytosis, anaemia, dramatically elevated erythrocyte sedimentation rate (ESR), elevated C-reactive protein (CRP), and elevated ferritin with a specific pattern of cytokine abnormalities [1]. The current definition of Juvenile idiopathic arthritis (JIA) is arthritis of unknown aetiology that begins before the 16th birthday and persists for at least 6 weeks [2]. It has recently been suggested that SoJIA is a distinct entity from JIA, and that the aetiology, pathogenesis, and therapy of children with SoJIA should be considered separately from those with other forms of JIA [3]. Approximately one-third of children with SoJIA are dependent on corticosteroids to control the systemic manifestations of the disease and are at high-risk for steroid-associated morbidity. The permanent physiologic and psychological sequelae associated with long-term steroid use are well documented and should be avoided [1], [4]. Current non-steroidal therapies available for the treatment of SoJIA alone or in combination include: anakina, autologous stem cell transplantation, azathioprine, cyclophosphamide, cyclosporine, etanercept, infliximab, intravenous gamma-globulin, methotrexate, sulfasalazine, and tocilizumab [3]. None has proven to be consistently successful. Thalidomide is a unique anti-inflammatory agent that reduces the production of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) and suppresses angiogenesis and cell adhesion molecule expression [5], [6].

Section snippets

Patient 1

A 9-year-old girl who fulfilled the criteria for SoJIA was seen in our center. She was started on prednisone 0.2 mg/kg/day, methotrexate 10 mg/m2/week p.o. and non-steroidal anti-inflammatory drugs (NSAID) (aspirin 80 mg/kg/day). The dose of methotrexate was raised to 15 mg/m2/week but marked active synovitis and constitutional symptoms persisted. It was decided to initiate etanercept at a dose of 0.4 mg/kg SC twice weekly due to the inadequate therapeutic response to conventional treatment. Before

Discussion

It is known that, in children with active SoJIA, TNF-α is significantly overproduced while interferon gamma levels are markedly decreased [8], [9]. Polymorphisms in the 5′-flanking promoter/enhancer region of TNF-α in patients with SoJIA have been reported compared with other types of JIA and healthy controls [10]. Levels of interleukin-6, interleukin-8 and monocyte chemo-attractant protein-1 are also altered. Interleukin-6 levels increase in SoJIA patients with active disease and decrease with

Acknowledgment

The authors thank David Buss for his editorial assistance.

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