Adult-onset Still's disease: pathogenesis, clinical manifestations and therapeutic advances

Abstract

Adult-onset Still's disease (AOSD) is a rare, systemic inflammatory disease of unknown aetiology, characterized by daily high spiking fevers, evanescent rash and arthritis. Our objective was to review the most recent medical literature regarding advances in the understanding of disease pathogenesis, diagnosis and treatment. There is no single diagnostic test for AOSD, and diagnosis is based on clinical criteria and usually necessitates the exclusion of infectious, neoplastic and autoimmune diseases. Laboratory tests are nonspecific and reflect heightened immunological activity with leukocytosis, elevated acute phase reactants and, in particular, extremely elevated serum ferritin levels. Abnormal serum liver function tests are common, while rheumatoid factor and antinuclear antibodies are usually absent. Recent studies of the pathogenesis of the disease have suggested an important role for cytokines. Interleukin (IL)-1, IL-6 and IL-18, macrophage colony-stimulating factor, interferon-gamma and tumour necrosis factor (TNF)-alpha are all elevated in patients with AOSD. Prognosis depends on the course of the disease and tends to be more favourable when systemic symptoms predominate. Treatment includes the use of corticosteroids, often in combination with immunosuppressants (e.g. methotrexate, gold, azathioprine, leflunomide, tacrolimus, ciclosporin and cyclophosphamide) and intravenous immunoglobulin. Biological agents (e.g. anti-TNFalpha, anti-IL-1 and anti-IL-6) have been successfully used in refractory cases. Further progress has been hampered by the rarity and heterogeneity of the disease, which has not permitted the execution of randomized controlled studies.