Adult onset Still's disease (AOSD) is a rare inflammatory disorder characterized by hectic spiking
fever, evanescent
rash and joint involvement. Prognosis is highly variable upon disease course and specific involvements, ranging from benign and limited outcome to chronic destructive
polyarthritis and/or life-threatening events in case of visceral complications or reactive
hemophagocytic lymphohistiocytosis (RHL). AOSD remains a debatable entity at the frontiers of
autoimmune diseases and autoinflammatory disorders. The pivotal role of macrophage cell activation leading to a typical Th1
cytokine storm is now well established in AOSD, and confirmed by the benefits using treatments targeting TNF-α, IL-1β or
IL-6 in refractory patients. However, it remains difficult to determine predictive factors of outcome and to draw guidelines for patient management. Herein, reviewing literature and relying on our experience in a series of 8 refractory AOSD patients, we question nosology and postulate that different
cytokine patterns could underlie contrasting clinical expressions, as well as responses to targeted
therapies. We therefore propose to dichotomize AOSD according to its clinical presentation. On the one hand, 'systemic AOSD' patients, exhibiting the highest
inflammation process driven by excessive
IL-18, IL-1β and
IL-6 production, would be at risk of life-threatening complications (such as multivisceral involvements and RHL), and would preferentially respond to IL-1β and
IL-6 antagonists. On the other hand, 'rheumatic AOSD' patients, exhibiting pre-eminence of joint involvement driven by
IL-8 and IFN-γ production, would be at risk of articular destructions, and would preferentially respond to TNF-α blockers.