Pathogenesis and Management of Adult-Onset Still’s Disease

Abstract

To review recent literature regarding the pathogenesis and treatment of adult-onset Still's disease (AOSD). We searched MEDLINE and PUBMED from 1971 to present using the following terms: adult-onset Still's disease, AOSD, or adult Still's disease. In addition we manually retrieved relevant abstracts from recent American College of Rheumatology and European League Against Rheumatism meetings. The etiology of AOSD, a rare, immune-mediated, multisystem inflammatory disorder characterized by quotidian spiking fevers, evanescent rash, and arthritis, remains unknown. An infectious etiology has been postulated, although a definitive agent has yet to be identified. Cytokines, such as interleukin (IL)-1, IL-6, interferon (IFN)-gamma, and tumor necrosis factor-alpha, are elevated in patients with AOSD. IL-18 and macrophage-colony stimulating factor also seem to play a role. Treatment historically consisted of nonsteroidal antiinflammatory drugs, often in combination with low-dose corticosteroids. Immunosuppressants (mainly methotrexate, but also intramuscular gold, azathioprine, cyclosporine A, leflunomide, and cyclophosphamide) and intravenous gamma-globulin are efficacious and have been used as steroid-sparing drugs. The recently reported use of anticytokine (anti-TNF-alpha, anti-IL-1, and anti-IL-6) agents in refractory cases has opened new horizons in the treatment of AOSD and provided important clues for its pathophysiology. Advances in immunology have enhanced our understanding of the role of cytokines in AOSD pathogenesis. Early, promising studies of anticytokine agents in AOSD may provide further insight into the pathogenetic mechanisms of this complex disease.