New insights in systemic juvenile idiopathic arthritis--from pathophysiology to treatment

Systemic juvenile idiopathic arthritis (SJIA) is characterized by the clinical features of remitting fever, a typical skin rash and arthritis. Many patients show frequent flares or persistent disease activity with significant morbidity and serious complications. Recent investigations in the pathophysiology of SJIA have focused on mediators of the innate immune system. Especially IL-1beta, IL-6 and IL-18 as well as phagocyte-specific S100-proteins (S100A8, S100A9 and S100A12) are correlated with disease activity and secondary complications. Beside IL-6 all these molecules are secreted by a so-called alternative pathway. A loss of control of the alternative secretory pathway seems to be involved in release of pro-inflammatory proteins leading to the inflammatory process of SJIA. These insights lead to new promising treatment approaches, like application of recombinant anti-IL-1 receptor antagonist or anti-IL-6 receptor antibodies in patients resistant to conventional anti-inflammatory treatment. First case studies show improvement and remission on therapy in a substantial portion of these patients. In this review, we summarize the current knowledge of pathophysiology and experiences in the treatment of SJIA.