Systemic juvenile idiopathic arthritis (sJIA) constitutes a small part of juvenile idiopathic arthritis (JIA), yet has a disproportionally higher rate of mortality. Despite being grouped under JIA, it is considered to be a multifactorial autoinflammatory disease. The objective of this paper is to review the epidemiology, pathogenesis, genetics, clinical manifestations, complications, therapy, prognosis, and outcome of sJIA. The presentation and clinical manifestations of sJIA have not changed much in the past several decades, but the collective understanding of the pathogenesis and the development of new targeted therapies (particularly the biologic agents) have transformed and improved the disease outcome for children with sJIA. 1. Introduction In 1897, Sir George Fredrick Still described 22 children, 12 of whom had a unique constellation of symptoms that included chronic arthritis, adenopathy, splenomegaly, and fevers [1]. Initially bearing his name, and later known by other names (systemic juvenile rheumatoid arthritis, systemic juvenile chronic arthritis), this entity is now known as systemic arthritis [2]. To allow for improved identification and research the International League of Associations of Rheumatology (ILAR) proposed a classification for JIA [2, 3]. To fulfill the criteria for systemic juvenile idiopathic arthritis (sJIA) a child must be under 16 years of age and have “arthritis in one or more joints with or preceded by fever of at least 2 weeks’ duration that is documented to be daily (“quotidian”) for at least 3 days and accompanied by one or more of the following: (1) evanescent (nonfixed) erythematous rash, (2) generalized lymph node enlargement, (3) hepatomegaly and/or splenomegaly, (4) serositis” [3]. Exclusions include “(a) psoriasis or a history of psoriasis in the patient or a first-degree relative, (b) arthritis in an HLA-B27 positive male beginning after the 6th birthday, (c) ankylosing spondylitis, enthesitis-related arthritis, sacroiliitis with inflammatory bowel disease, Reiter’s syndrome, or acute anterior uveitis, or a history of one of these disorders in a first-degree relative, (d) the presence of IgM rheumatoid factor on at least 2 occasions at least 3 months apart” [3]. Despite being included under the inclusive umbrella of juvenile idiopathic arthritis (JIA), it is likely that sJIA is a different disease, for it appears to be unlike the other forms of JIA both in clinical presentation and its pathogenesis [4] (refer to section under pathogenesis). In the following sections we will review the epidemiology,
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