sJIA is a systemic autoinflammatory disorder of unknown etiology frequently characterized by quotidian fever, rash, generalized lymphadenopathy, hepatosplenomegaly, pericarditis and arthritis. Transaminitis, defined as elevation of hepatic enzymes (specifically alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) in the absence of other clinical or laboratory evidence of hepatic injury, can be seen in patients with sJIA either in disease flares or due to hepatotoxic therapies like methotrexate [1, 2]. The mechanism by which patients develop sJIA is unknown, but it is felt to involve the interaction of infectious or inflammatory triggers with a genetic predisposition toward an enhanced proinflammatory response. Cytokines, particularly Interleukin-1 (IL-1) and Interleukin-6 (IL-6) have been implicated as important in disease pathogenesis and maintenance of inflammation [1, 2]. MAS is a complication of various rheumatologic and infectious diseases, and is often associated with sJIA. It is clinically characterized by cytopenias, disseminated intravascular coagulation, hemodynamic instability and liver and neurological involvement [3, 4]. Hemophagocytosis by activated macrophages is considered by most authors to be the most specific histopathological feature of MAS [3, 4]. Hemophagocytosis is generally accompanied by a lymphohistiocytic infiltrate including a predominance of CD8+ lymphocytes  although some reports in adults have additionally identified biliary injury and vascular microthrombi as frequent findings . Mortality due to MAS has been estimated at 8-22% [3, 7].
Non-steroidal anti-inflammatory drugs (NSAIDs) and systemic corticosteroids have historically been the mainstays of treatment for sJIA [1, 2]. There is evidence that methotrexate, cyclosporine, and etanercept are less effective in sJIA than in other forms of juvenile arthritis, and some disease-modifying drugs may be associated with development of MAS [1, 2]. IL-1 receptor antagonist (IL1RA) (anakinra) and anti-IL-6 (MRA/tocilizumab) have shown clinical efficacy in small open-label studies in sJIA and adult Still's Disease [8–11]. MAS, which leads to the greatest morbidity and mortality in patients with sJIA, is generally treated with supportive care, high dose intravenous corticosteroids and other immunosuppressive agents. MAS may also be treated with etoposide or cyclosporine in a similar fashion to primary or familial hemophagocytic lymphohistiocytosis (HLH), a genetic disorder related to alterations in cytotoxic granular release that can be triggered by infections and neoplasms . MAS is a form of secondary HLH. There is a single case report of successful treatment of MAS with IL1RA in a patient with sJIA .
As many as 50-100% of patients with sJIA respond to IL1RA [8, 10, 11]. Despite these promising case series, the safety of IL1RA in large numbers of patients with sJIA has not been established. Furthermore, the effects of IL-1 blockade on the inflammatory response of patients with sJIA have not been formally studied. One case report suggests IL1RA as a trigger for MAS in an adolescent with sJIA . In this case series we sought to investigate the extent to which a significant adverse event, acute hepatitis, was related to treatment with IL1RA in three patients with sJIA.