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Sex- and gender-related differences in psoriatic arthritis

Abstract

Psoriatic arthritis (PsA) is an inflammatory musculoskeletal disease with a chronic, progressive course. Various aspects of PsA, including its clinical features, disease course and response to treatment, are influenced by sociodemographic characteristics of the patient. This includes patient sex, the biological attributes associated with being male or female, and gender, a sociocultural construct that comprises attitudes, traits and behaviours associated with being a man or a woman. An understanding of sex- and gender-related differences in PsA, as well as their underlying mechanisms, is therefore important for individualized care. In this narrative review, the influence of sex and gender on PsA manifestation and course, patient function and quality of life, and their association with comorbidities are described. Sex- and gender-related disparities in response to advanced therapies and their potential underlying mechanisms are delineated. Differences in pathophysiological mechanisms between male and female patients including genetics, immune and hormonal mechanisms are discussed. Finally, fertility and pregnancy outcomes in PsA are outlined. By adopting sex and gender lenses, this review is aimed at highlighting key differences between male and female patients with PsA and uncovering mechanisms underlying these differences, ultimately promoting individualized care of men and women with PsA and informing future research in this area.

Key points

  • The majority of studies show that peripheral arthritis is more common in female patients with PsA, whereas axial disease and severe psoriasis are more common in male patients, emphasizing the need for specific sex-gender considerations in diagnosis and treatment selection.

  • Female patients with PsA are less likely to develop radiographic damage in axial and peripheral joints than male patients, and therefore require more sensitive imaging modalities (such as MRI and ultrasound) for diagnosis.

  • Higher levels of pain, fatigue, poor functional status and worse quality of life in female patients with PsA have been reported compared with male patients. Women with PsA might require psycho-social support, occupational modification and targeted pain management.

  • Female patients with PsA are at a higher risk of discontinuing or switching advanced therapy than male patients, thereby necessitating closer monitoring after drug initiation.

  • Parameters of PsA disease activity improve during pregnancy and flare up during the postpartum period, emphasizing the need for close monitoring after pregnancy.

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Fig. 1: Sex- and gender-related mechanisms and disease outcomes in PsA.

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Acknowledgements

Y.-Y.L. has been supported by National Medical Research Council, Singapore (NMRC/CSA-Inv/0022/2017). S.R.J. has been awarded a Canadian Institutes of Health Research New Investigator Award. J.W. receives support from the Arthritis Society Stars Career Development Award (STAR-19-0610). P.R. holds the RTOERO Chair in Geriatric Medicine at the University of Toronto. L.E. has been awarded the Early Researcher Award from the Ontario Ministry of Research, Innovation and Science and Canada Research Chair (Tier 2) in Inflammatory Rheumatic Diseases.

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All authors contributed to the conception of the manuscript and approved the final version for submission. S.T., Y.-Y.L. and L.E. researched data for the article. S.T. and L.E. wrote the manuscript. All authors reviewed and edited the article. All authors approved the final version for submission.

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Correspondence to Lihi Eder.

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Y.-Y.L. received an honorarium from AbbVie, DKSH, Janssen, Novartis and Pfizer. V.S. has received consultation fees from AbbVie, Amgen Corporation, Arena, Aria, AstraZeneca, BMS, Boehringer Ingelheim, Celltrion, Galapagos, Genentech/Roche, Gilead, GSK, Horizon, Ichnos, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Rheos, Samsung, Sandoz, Sanofi, Sorrento, Sun Pharma, and UCB. L.E. received educational and research grants and consultation fees from AbbVie, UCB, Eli Lily, Novartis, Sandoz and Pfizer. S.R.J., J.W., S.T. and P.R. declare no competing interests.

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Tarannum, S., Leung, YY., Johnson, S.R. et al. Sex- and gender-related differences in psoriatic arthritis. Nat Rev Rheumatol (2022). https://doi.org/10.1038/s41584-022-00810-7

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