Pathogenesis of adult-onset Still’s disease: new insights from the juvenile counterpart

Abstract

Adult-onset Still's disease (AOSD) is a rare inflammatory disease characterized by the classical triad of daily fever, arthritis, and typical salmon-colored rash. Recent accumulation of knowledge, mostly arising from hereditary autoinflammatory diseases and from the systemic-onset juvenile idiopathic arthritis (sJIA), has given raise to new hypotheses on the pathophysiology of AOSD. In this review, we first discuss on the continuum between AOSD and sJIA. Then, we summarize current hypotheses on the underlying pathogenesis: (1) an infectious hypothesis; (2) an autoinflammatory hypothesis; (3) a lymphohistiocytic hypothesis; and (4) a hyperferritinemic hypothesis. Finally, we present the recent data suggesting that patients with AOSD fall into two distinct subgroups with different courses, one with prominent systemic features and one with chronic arthritis.

Presentation and diagnosis of adult-onset Still’s disease: the implications of current and emerging markers in overcoming the diagnostic challenge

“…These patients can be included in the definition of AOSD and, as proposed by Martini [88], should be incorporated in the sJIA disease category with a possible new name that might be Still's disease. This idea is in agreement with other reports suggesting that, given the almost indistinguishable disease course of sJIA and AOSD, these conditions may represent a continuum of a single disease entity [89,90] sJIA is considered a polygenic autoinflammatory condition characterized by abnormalities in the innate immune response. Several polymorphisms in the promoter elements and genes encoding TNF, IL-6, IL-10, MIF and the IL-1 family (IL-1A, IL-1RN, IL-1R2 and possibly IL-1F10) have been found to be associated with the disease [91].…”

Cytokine profile in adult-onset Still's disease: Comparison with systemic juvenile idiopathic arthritis

“…Macrophage activation syndrome (MAS) is a severe, potentially life-threatening complication of both s-JIA and AOSD [7][8][9]. MAS occurs in 7%-10% of patients with s-JIA and 12%-17% of patients with AOSD [9].…”

“…MAS occurs in 7%-10% of patients with s-JIA and 12%-17% of patients with AOSD [9]. The hallmark of MAS is an uncontrolled and dysfunctional immune response involving the continual activation and expansion of T lymphocytes and macrophages, leading to marked hypercytokinemia [10].…”

Occurrence of Ulcerative Colitis in a Patient With Adult-Onset Still's Disease: Coincidence or Correlated

“…In addition, recent studies suggest that AOSD has two distinct subsets: one with prominent systemic features and the other with chronic arthritis associated with TNF-a. 9 In light of this, AOSD, as a subtype of JIA or arthritis, could exhibit IBD as an extra-articular manifestation. This may be the supporting evidence for the unusual cases of coexistence of AOSD and IBD.…”