Systemic juvenile idiopathic arthritis (sJIA), formerly called Still's disease, is officially classified as a subset of juvenile idiopathic arthritis (JIA). Beside arthritis, it is characterized by prominent systemic features and a marked inflammatory response. Even if it is still included in the group of juvenile arthritides, sJIA is set apart from all the other forms of JIA. This disorder has markedly distinct clinical and laboratory features suggesting a different pathogenesis. sJIA does not show any association with HLA genes or with autoantibodies and is characterised by an uncontrolled activation of phagocytes with hypersecretion of IL-1 and IL-6. Based on clinical and laboratory features, as well as on new acquisitions on the pathogenesis, it seems evident that sJIA is an autoinflammatory disease related to abnormality in innate immune system. The new insights on the pathogenesis of sJIA have therefore dramatically changed the approach to treatment, with the development of targeted treatments (anti-IL-1 and anti-IL-6 agents) more effective and safer than earlier medications. 1. Introduction Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood. It is a heterogeneous disease of unknown aetiology encompassing different forms of arthritis, which begins before the age of 16 years and persists for more than 6 weeks. JIA classification [1] is based on the number of joints involved during the first 6 months of disease and on the extra-articular involvement. Most JIA subsets are characterized by female predominance, prominent arthritis, various degrees of biological inflammation, a strong susceptibility associated with some HLA class II antigens, and an overt or suspected autoimmunity, for example, antinuclear antibodies (ANA) rheumatoid factor (RF) and anticyclic-citrullinated peptide (anti-CCP) antibodies. Dramatic response to anti-TNFα treatments [2] is an important feature, which supports the role of the adaptative immunity in generating chronic inflammation. 2. Still’s Disease as a Subset of Juvenile Idiopathic Arthritis sJIA was officially classified as a subset of JIA, and the presence of at least one active synovitis was mandatory to support the diagnosis, even if some patients do not present arthritis at disease onset [3]. Moreover, sJIA can have a highly variable outcome, and a monocyclic course with minimal or absent articular complications was reported in about 50% of 56 cases [4]. Other differences with the other subtypes of JIA include an equal sex ratio, marked systemic features with spiking fever, a
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