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.