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Because of its distinct clinical and laboratory features, reflecting systemic inflammation, sJIA can be distinguished from other forms of JIA which usually present as a milder phenotype. The exact pathophysiology of sJIA, however, remains unknown. Profound dysregulation of innate pro- and anti-inflammatory cytokines, and rapid clinical response to cytokine blocking strategies in sJIA patients suggest impaired control mechanisms in innate immune cells contributing to sJIA pathogenesis. Endogenous TLR ligands, such as S100 protein complexes, enhance the pro-inflammatory phenotype. Associations with polymorphisms in cytokine genes and their receptors suggest a genetic component. Furthermore, genetic associations that have been reported in familial hemophagocytic lympohistiocytosis also exist in patients with sJIA-associated macrophage activation syndrome, a severe complication of sJIA. Reported mutations in single genes, however, are too weak to confer sJIA, suggesting a multi-factorial mode of inheritance. We provide an overview of current pathophysiological concepts, state-of-the-art treatment regimens, and unanswered questions in sJIA., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Chronic infantile neurological cutaneous and articular (CINCA) syndrome is an autoinflammatory disease, defined by the triad of urticarial rash, neurological manifestations, and arthropathy, accompanied by recurrent fevers and systemic inflammation. Increasing neurological deficits result from aseptic meningitis. Sensorineural hearing loss and progressive loss of vision caused by keratoconjunctivitis or papilloedema may emerge. An autosomal-dominant inheritance is suspected although sporadic cases are reported frequently. Sixty per cent of CINCA patients carry mutations in the cold-induced autoinflammatory syndrome (CIAS1) gene. We report the favourable response of a 23-year-old CINCA patient without CIAS1 mutations to treatment with the recombinant interleukin-1 (IL-1) receptor antagonist anakinra. [ABSTRACT FROM AUTHOR]