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Relapsing polychondritis: clinical updates and new differential diagnoses

Nature Reviews Rheumatology (2024)Cite this article

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Abstract

Relapsing polychondritis is a rare inflammatory disease characterized by recurrent inflammation of cartilaginous structures, mainly of the ears, nose and respiratory tract, with a broad spectrum of accompanying systemic features. Despite its rarity, prompt recognition and accurate diagnosis of relapsing polychondritis is crucial for appropriate management and optimal outcomes. Our understanding of relapsing polychondritis has changed markedly in the past couple of years with the identification of three distinct patient clusters that have different clinical manifestations and prognostic outcomes. With the progress of pangenomic sequencing and the discovery of new somatic and monogenic autoinflammatory diseases, new differential diagnoses have emerged, notably the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome, autoinflammatory diseases and immune checkpoint inhibitor-related adverse events. In this Review, we present a detailed update of the newly identified clusters and highlight red flags that should raise suspicion of these alternative diagnoses. The identification of these different clusters and mimickers has a direct impact on the management, follow-up and prognosis of patients with relapsing polychondritis and autoinflammatory syndromes.

Key points

  • Studies in the past few years have allowed improved clustering of relapsing polychondritis phenotypes, with relevant clinical and prognostic implications.

  • Somatic mutations in UBA1 have been linked to the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome, as well as to a specific relapsing polychondritis phenotype.

  • Screening for UBA1 mutations is indicated in patients with a compatible clinical presentation, regardless of age and sex.

  • In patients with cancer, immune-checkpoint inhibitors can induce relapsing polychondritis features and require specific management.

  • Other autoinflammatory conditions can mimic relapsing polychondritis, thus warranting consideration of genetic testing, particularly in paediatric-onset cases.

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Fig. 1: Main differences between idiopathic relapsing polychondritis and VEXAS syndrome–relapsing polychondritis.

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Acknowledgements

The authors wish to thank K. Baumgaertner for her invaluable assistance in the preparation of the manuscript.

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Authors and Affiliations

  1. Department of Rheumatology, National Reference Center for Rare Autoimmune Diseases (RESO), INSERM UMR-S 1109, Hôpitaux Universitaires de Strasbourg, Strasbourg, France

    Philippe Mertz & Laurent Arnaud

  2. National Referral Centre for Rare Autoimmune and Systemic Diseases, Department of Internal Medicine, Hôpital Cochin, AP-HP Centre, Université Paris Cité, Paris, France

    Nathalie Costedoat-Chalumeau

  3. National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA

    Marcela A. Ferrada & Peter C. Grayson

  4. Department of Internal Medicine, Toulouse University Hospital, Toulouse, France

    Guillaume Moulis

  5. Service de Médecine Interne, DHUi2B, Hôpital Saint-Antoine, Paris, France

    Arsène Mekinian

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Contributions

L.A. and P.M. researched data for the article and wrote the article. All authors contributed substantially to discussion of the content and reviewed and/or edited the manuscript before submission.

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Correspondence to Laurent Arnaud.

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Competing interests

G.M. has received research grants from Amgen, Grifols, Novartis and Sanofi, and is on the advisory board for Amgen, Argenx, Grifols, Novartis, Sanofi and Sobi. The other authors declare no competing interests.

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Nature Reviews Rheumatology thanks David D’Cruz, who co-reviewed with Kathryn Biddle, Jun Shimizu and Manuel Ugarte-Gil for their contribution to the peer review of this work.

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Mertz, P., Costedoat-Chalumeau, N., Ferrada, M.A. et al. Relapsing polychondritis: clinical updates and new differential diagnoses. Nat Rev Rheumatol (2024). https://doi.org/10.1038/s41584-024-01113-9

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