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Objectives: Psychosis is a rare but severe neuropsychiatric manifestation of systemic lupus erythematosus (SLE). Its prevalence, clinical predictors, and immunopathogenesis remain incompletely understood. This study aimed to estimate the prevalence of psychosis in adult SLE patients and identify associated clinical and immunological risk factors.

Methods: This systematic review and meta-analysis was conducted following PRISMA guidelines. A comprehensive search of PubMed, Embase, and the Cochrane Library was conducted to identify all relevant studies with ≥10 adults through November 2024. Case-series, case reports, narrative reviews and conference abstracts were excluded. Quality assessment employed the Cochrane Risk of Bias Tool for randomized controlled trials and the Newcastle-Ottawa Scale for observational studies. Statistical analysis was performed using the random-effects model, with heterogeneity assessed via I2 statistics.

Results: A total of 65 studies, comprising 31,495 SLE patients, were included. The pooled prevalence of psychosis in SLE patients was 4.5% (95% CI: 3.6%–5.5%) and 20.5% (95% CI: 10.0%–37.6%) among neuropsychiatric SLE (NPSLE) patients. Psychosis frequently occurred within 2 years of SLE onset and was strongly associated with higher SLE disease activity, positive anti-ribosomal P antibodies, antiphospholipid antibodies, and complement consumption. Delusions and hallucinations predominated among clinical presentations. Heterogeneity among studies was substantial.

Conclusion: Observational studies have reported that psychosis in SLE is strongly associated with increased disease activity and immune dysregulation. Anti-ribosomal P antibodies demonstrate a high negative predictive value, offering a valuable diagnostic adjunct. Recognition of psychosis may prompt closer clinical evaluation and, where appropriate, consideration of immunosuppressive treatment.