Case reportEfficacy of thalidomide in systemic onset juvenile rheumatoid arthritis
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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