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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-γ, 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, ciclosporin, 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.

Key Points

  • Adult-onset Still's disease is a rare systemic inflammatory disease manifested by quotidian fever, salmon-colored perifebrile rash, and, occasionally, destructive arthritis

  • The pathogenesis of adult-onset Still's disease is poorly understood and probably involves both genetic and environmental factors

  • Recent advances in immunology indicate that proinflammatory cytokines such as interleukins 1, 6, and 18, interferon-γ, tumor necrosis factor, and monocyte chemoattractant protein 1 have a major role in the pathogenesis of adult-onset Still's disease

  • Standard treatment involves low-dose corticosteroids, with or without traditional disease-modifying antirheumatic drugs—mainly methotrexate

  • Recently, off-label use of biologic agents that inhibit proinflammatory cytokines, such as tumor necrosis factor and interleukins 1 and 6, has been successful in treatment-refractory cases; however, these findings await validation in controlled studies

  • The preliminary benefits observed with biologic agents, together with the recently acquired knowledge on cytokine biology, emphasize the need for continuing research that may lead to improved, targeted therapy for adult-onset Still's disease

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Correspondence to Petros Efthimiou.

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Efthimiou, P., Kontzias, A., Ward, C. et al. Adult-onset Still's disease: can recent advances in our understanding of its pathogenesis lead to targeted therapy?. Nat Rev Rheumatol 3, 328–335 (2007). https://doi.org/10.1038/ncprheum0510

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  • DOI: https://doi.org/10.1038/ncprheum0510

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