Adult-onset Still's disease

Abstract

First described in 1971, adult-onset Still's disease (AOSD) is a rare multisystemic disorder considered as a complex (multigenic) autoinflammatory syndrome. A genetic background would confer susceptibility to the development of autoinflammatory reactions to environmental triggers. Macrophage and neutrophil activation is a hallmark of AOSD which can lead to a reactive hemophagocytic lymphohistiocytosis. As in the latter disease, the cytotoxic function of natural killer cells is decreased in patients with active AOSD. IL-18 and IL-1β, two proinflammatory cytokines processed through the inflammasome machinery, are key factors in the pathogenesis of AOSD; they cause IL-6 and Th1 cytokine secretion as well as NK cell dysregulation leading to macrophage activation. The clinico-biological picture of AOSD usually includes high spiking fever with joint symptoms, evanescent skin rash, sore throat, striking neutrophilic leukocytosis, hyperferritinemia with collapsed glycosylated ferritin (<20%), and abnormal liver function tests. According to the clinical presentation of the disease at diagnosis, two AOSD phenotypes may be distinguished: i) a highly symptomatic, systemic and feverish one, which would evolve into a systemic (mono- or polycyclic) pattern; ii) a more indolent one with arthritis in the foreground and poor systemic symptomatology, which would evolve into a chronic articular pattern. Steroid- and methotrexate-refractory AOSD cases benefit now from recent insights into autoinflammatory disorders: anakinra seems to be an efficient, well tolerated, steroid-sparing treatment in systemic patterns; tocilizumab seems efficient in AOSD with active arthritis and systemic symptoms while TNFα-blockers could be interesting in chronic polyarticular refractory AOSD.

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

“…Recent studies have shown that inflammatory cytokines, including interleukin (IL)-1, IL-6, IL-18, interferon (IFN)-γ, and tissue necrosis factor (TNF)-α play pathogenic roles in the disease processes of both s-JIA and AOSD [12,13]. Furthermore, biological therapies intended to block these cytokines yield dramatic effects in patients with s-JIA and AOSD [14,15].…”

Extremely high serum ferritin level in a patient with Hemophagocytic Syndrome and Adult-Onset Still's disease

“…Adult-onset Still's disease (AOSD) generally affects children or young adults, and also was described up to 83 years (1). The etiology of AOSD remains unknown.…”

“…and environmental factors such as infections (Epstein-Barr virus, hepatitis B and C virus, human immunodeficiency virus, yersinia enterocolitica etc.) have been suspected in the pathogenesis (1). Hemophagocytic syndrome (HS) is also a rare disorder.…”

“…It may be primary, or secondary to infections, malignancies, juvenile idiopathic arthritis and AOSD (1). Serum ferritin may be useful marker for AOSD disease activity, but has limited value for the diagnosis of AOSD (1,2). Although elevated serum ferritin levels are associated with leukaemia, lymphomas, haemochromatosis; levels up to 10.000 μg/L was described in patients with multiple blood transfusion and hemophagocytic syndrome (2,3).…”

“…Hemophagocytic syndrome (HS) is also a rare disorder. It may be primary, or secondary to infections, malignancies, juvenile idiopathic arthritis and AOSD (1). Serum ferritin may be useful marker for AOSD disease activity, but has limited value for the diagnosis of AOSD (1,2).…”