Sex- and gender-related differences in systemic lupus erythematosus: a scoping review

A scoping review was conducted to compile evidence on sex-specific differences in systemic lupus erythematosus (SLE) with focus on autoantibodies, organ manifestation, damage, treatment and patient-reported outcomes (PROs). Systematic searches in PubMed and Cochrane were performed including meta-analyses, observational studies and clinical trials from 01/2015 to 11/2024. Studies of adults with SLE reporting outcomes by sex were eligible. The research protocol is registered in the Registry for Scoping Reviews (OSF, https://osf.io/gfbs9 ). From 373 screened articles, 81 publications were included. Studies comprised differences in autoantibodies (n = 13), damage (n = 40), organ involvement (n = 27), treatment (n = 14), and PROs (n = 6). Twenty studies compared proportions of outcomes by sex with patient numbers ranging from 98 to 11,943. The female/male ratio was between 4:1 and 11:1. The review found a higher age at onset in men and a higher proportion of positive lupus anticoagulant, nephritis, serositis, antiphospholipid syndrome, greater renal and cardiovascular damage and severe infections. SLE in women more often presented with Ro/SSA autoantibodies, alopecia, photosensitivity, Raynaud, and osteoporosis. Some studies showed more frequent cyclophosphamide and less frequent antimalarials in men. Little evidence indicated more frequent non-adherence with azathioprine and mycophenolate in women. Limited evidence was available for PROs. This review confirms significant sex differences in SLE, with men showing later onset, more severe organ damage, and distinct autoantibody and treatment patterns, while women more often present with Ro/SSA autoantibodies, photosensitivity, and osteoporosis. Evidence on patient-reported outcomes remains limited, highlighting the need for further research to guide sex-specific management.