title: 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.
authors.affiliation: Hospices Civils de Lyon, Hôpital Universitaire de la Croix-Rousse, Service de médecine interne, F-69004 Lyon, France; Université Lyon I, F-69100 Villeurbanne, France; Université de Lyon, F-69000 Lyon, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Gerfaud-Valentin
authors.affiliation: Hospices Civils de Lyon, Hôpital Universitaire de la Croix-Rousse, Service de médecine interne, F-69004 Lyon, France; Inserm U1111, Centre International de Recherche en Infectiologie, F-69365 Lyon, France; Département de Biochimie, Université de Lausanne, 1006 Epalinges, Switzerland.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Jamilloux
authors.affiliation: Université Lyon I, F-69100 Villeurbanne, France; Université de Lyon, F-69000 Lyon, France; Hospices Civils de Lyon, Service de Biostatistique, F-69000 Lyon, France; CNRS UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique Santé, F-69310 Pierre-Bénite, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Iwaz
authors.affiliation: Hospices Civils de Lyon, Hôpital Universitaire de la Croix-Rousse, Service de médecine interne, F-69004 Lyon, France; Université Lyon I, F-69100 Villeurbanne, France; Université de Lyon, F-69000 Lyon, France. Electronic address: pascal.seve@chu-lyon.fr.
authors.forename: Pascal
authors.initials: P
authors.lastname: Sève
mesh_terms: D056704:Adaptive Immunity; D000328:Adult; D020022:Genetic Predisposition to Disease; D006801:Humans; D007113:Immunity, Innate; D011379:Prognosis; D016706:Still's Disease, Adult-Onset / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*
keywords: Adult-onset Still's disease; Anakinra; Autoinflammatory disorder; Hemophagocytic lymphohistiocytosis; Hyperferritinemia; Macrophage activation syndrome