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Objectives: Emerging evidence suggests that post-traumatic stress disorder (PTSD) may increase susceptibility to autoimmune diseases, including SLE. PTSD-related immune dysregulation is hypothesized to heighten vulnerability to autoimmunity. This systematic review sought to evaluate the relationship between PTSD and the risk of developing SLE, as well as explore potential shared genetic predispositions.

Methods: Following Preferred Reporting Items for Systematic reviews and Meta-Analysis statement (PRISMA) guidelines, a systematic review of PubMed and Scopus databases was conducted up to 1 January 2025. Search terms included 'post-traumatic stress disorder' AND 'SLE' OR 'systemic lupus erythematosus'. Included were full-text original articles assessing the PTSD-SLE relationship, while systematic and narrative reviews, case reports and studies with fewer than 10 patients were excluded. Genetic overlap between PTSD and SLE was analysed using genes identified by genome-wide association study.

Results: From 24 identified studies, 7 met the inclusion criteria, comprising 5 prospective cohort studies, 1 retrospective cohort and 1 case-control study. Across 11 614 SLE patients, 1325 (11.4%) had comorbid PTSD, predominantly females in USA-based studies. All studies demonstrated a positive association between PTSD and SLE, with three reporting at least a 2-fold increased risk of SLE in PTSD patients. Depression and anxiety were common comorbidities in PTSD-SLE patients (n = 2 studies). Genetic analysis did not reveal significant common genetic variants between the two conditions.

Conclusion: PTSD is strongly associated with an increased risk of developing SLE. These findings underscore the need for further investigation into PTSD-induced immune dysregulation and its role in autoimmunity. Early PTSD intervention may mitigate the risk of developing SLE.