Systemic juvenile idiopathic arthritis (sJIA) represents up to 10–20% of all JIA categories and is characterized by chronic arthritis, intermittently high, spiking temperatures up to 40 °C, maculopapular rash, hepatosplenomegaly, lymphadenopathy, serositis and a marked increase in the level of acute-phase reactants such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). The age at onset of disease is not limited to a specific period of childhood, but in a large cohort was found to accumulate within the first 6 years with a median age of disease onset of 4.7 years. Girls and boys are affected in the same proportion. Arthritis can be presented as mono-articular, oligo-articular or polyarticular predominantly affecting the cervical spine, hips, wrists and ankles but affecting smaller joints as well. One of the leading problems of sJIA is the potential joint destruction with luxation, ankyloses, and synostosis especially within polyarticular disease. Extra-articular manifestations are frequent with macrophage activation syndrome (MAS), a dreaded potentially life threatening complication still responsible for fatalities. Laboratory workup except, for elevated CRP and ESR, frequently shows distinct anaemia, leucocytosis and thrombocytosis, whereas mostly antibodies or rheumatic factors are not detected. At present, as the most severe JIA subtype, sJIA remains a challenge for prognosis and treatment.
Established therapies for treatment of JIA have been systemic glucocorticoids and nonsteroidal anti-inflammatory drugs (NSAIDs), which are associated with many side effects if given for years in this disease. In contrast to their efficacy for treatment of arthritis, there is a poor clinical response to established JIA treatments such as methotrexate (MTX) or TNF-inhibitors of the systemic disease.
Studies have revealed that myeloid-related protein 8 (MRP-8 (S100A8)) and MRP-14 (S100A9), two calcium-binding S-100 proteins expressed and released by phagocytes, are highly elevated in active disease and may be used for diagnosis and for management of sJIA.[5,6] The clinical characteristics of sJIA suggest that it is distinct from other forms of JIA, leading to the contention by some that sJIA should be separated from other forms of JIA and labelled as an autoinflammatory disease.
Thus, sJIA is regarded as an autoinflammatory disease due to the good response to inhibition of interleukin (IL)-1ß or IL-6.[8,9] Inhibition of the biologic activity of IL-6 by therapy with the monoclonal IL-6 receptor antibody tocilizumab (TOC) and inhibition of IL-1β with anti–IL-1 therapies such as canakinumab recently became approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for systemic JIA, and both have demonstrated remarkable benefit in randomized controlled trials.[8–10] In addition, anakinra, an IL-1 receptor antagonist has been used successfully in case series and in a randomized short-term pilot trial. The improvement in therapeutic options prompted the Childhood Arthritis and Rheumatology Research Alliance (CARRA) to develop standardized consensus treatment plans for new-onset systemic JIA, including the use of biologic agents towards IL-1 or IL-6. In Germany, biologic therapy for JIA is monitored prospectively by the established Biologics register (BiKeR - Biologika in der Kinderrheumatologie). This enabled us to analyse the experience with several biologic treatments in patients with sJIA in clinical practice.
Arthritis Res Ther. 2017;19(256) © 2017 BioMed Central, Ltd.
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