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  • Review Article
  • Published:

Mechanisms, biomarkers and targets for adult-onset Still’s disease

Nature Reviews Rheumatology volume 14, pages 603–618 (2018)Cite this article

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Abstract

Adult-onset Still’s disease (AoSD) is a rare but clinically well-known, polygenic, systemic autoinflammatory disease. Owing to its sporadic appearance in all adult age groups with potentially severe inflammatory onset accompanied by a broad spectrum of disease manifestation and complications, AoSD is an unsolved challenge for clinicians with limited therapeutic options. This Review provides a comprehensive insight into the complex and heterogeneous nature of AoSD, describing biomarkers of the disease and its progression and the cytokine signalling pathways that contribute to disease. The efficacy and safety of biologic therapeutic options are also discussed, and guidance for treatment decisions is provided. Improving the approach to AoSD in the future will require much closer cooperation between paediatric and adult rheumatologists to establish common diagnostic strategies, treatment targets and goals.

Key points

  • Similar to systemic-onset juvenile idiopathic arthritis, adult-onset Still’s disease (AoSD) is a rare systemic autoinflammatory disease with potentially severe inflammatory onset accompanied by a broad spectrum of disease manifestation and complications.

  • AoSD should be considered in patients with persistent fever, and the diagnosis is based on the combination of clinical and laboratory findings as well as the exclusion of other inflammatory conditions.

  • Central to the pathogenesis of AoSD is the intense activation of innate immune cells and overproduction of several pro-inflammatory cytokines including IL-1, IL-6 and IL-18.

  • Two IL-1 antagonists have been approved for treatment of AoSD, and growing evidence suggests that other biologic agents are therapeutic options, such as anti-IL-6 and anti-IL-18 therapeutics.

  • As a reliable prediction of response and outcome is not possible, therapeutic decisions have to be made on the basis of clinical, biological or imaging characteristics of disease.

  • A close cooperation between paediatric and adult rheumatologists is required to establish common diagnostic strategies, treatment targets and goals.

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Fig. 1: Pathogenic pathways in AoSD.
Fig. 2: Signs of AoSD.
Fig. 3: Managing patients with AoSD.

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Acknowledgments

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Nature Reviews Rheumatology thanks M. McDermott, M. Gonzalez-Gay and Y. Shoenfeld for their contribution to the peer review of this work.

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Authors and Affiliations

  1. Department of Rheumatology and Clinical Immunology, Charité- Universitätsmedizin, Berlin, Germany

    Eugen Feist

  2. Department of Rheumatology, AP-HP, Pitié-Salpêtrière Hospital, AP-HP, Paris, France

    Stéphane Mitrovic & Bruno Fautrel

  3. Department of Internal Medicine, Institut Mutualiste Montsouris, Paris, France

    Stéphane Mitrovic

  4. Sorbonne Université, GRC 08, Pierre Louis Institute of Epidemiology and Public Health, Paris, France

    Bruno Fautrel

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E.F. has received consultant fees from AbbVie, Biogen, BMS, Celgene, Janssen, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Roche, Sanofi-Aventis, Swedish Orphan Biovitrum and UCB, as well as research grants from BMS, Lilly, Novartis, Pfizer and Roche. S.M. has received consultant fees from BMS and Pfizer. B.F. has received consultant fees from AbbVie, Biogen, BMS, Celgene, Janssen, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Roche, Sanofi-Aventis, Swedish Orphan Biovitrum and UCB, as well as research grants from AbbVie, MSD and Pfizer.

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Feist, E., Mitrovic, S. & Fautrel, B. Mechanisms, biomarkers and targets for adult-onset Still’s disease. Nat Rev Rheumatol 14, 603–618 (2018). https://doi.org/10.1038/s41584-018-0081-x

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