Adult-onset Still's disease: can recent advances in our understanding of its pathogenesis lead to targeted therapy?

Abstract

Adult-onset Still's disease is a rare systemic inflammatory disease of unknown etiology, characterized by daily high, spiking fevers, evanescent rash, and arthritis. There is no single diagnostic test for adult-onset Still's disease; rather, the diagnosis is based on clinical criteria and necessitates the exclusion of infectious, neoplastic, and other 'autoimmune' diseases. Proinflammatory cytokines such as interleukin (IL)-1, IL-6, and IL-18, interferon-gamma, tumor necrosis factor, and macrophage colony-stimulating factor are elevated in patients with adult-onset Still's disease and are thought to have a major role in the pathogenesis of the disease. Treatment consists of nonsteroidal anti-inflammatory drugs, corticosteroids, immunosuppressants (methotrexate, gold, azathioprine, leflunomide, cyclosporin, and cyclophosphamide), intravenous immunoglobulin, and cytokine (tumor necrosis factor, IL-1 and IL-6) inhibitors. Recent advances in basic immunology have enhanced our ability to hinder the pathogenic mechanisms associated with adult-onset Still's disease and have led to a paradigm shift where targeted treatments have an increasingly important role.