Stress exposure prior to diagnosis and clinical characteristics in systemic lupus erythematosus: a cross-sectional study

Abstract Psychological stress has been linked to the onset and course of autoimmune diseases. However, limited data exist regarding the relationship between pre-diagnosis stress exposure and subsequent disease course in systemic lupus erythematosus (SLE). We evaluated the association between psychological stress prior to SLE diagnosis and subsequent disease characteristics. We conducted a cross-sectional study of adults with SLE treated at a tertiary hospital between November 2019 and December 2022. Stress exposure during the two years preceding SLE diagnosis was assessed using the Holmes-Rahe Social Readjustment Rating Scale (life change units, LCU), and categorized as low (< 150), intermediate (150–299), or high (≥ 300). Data on clinical manifestations, comorbidities, disease activity patterns, patient-reported outcomes, and organ damage were collected. Associations between stress levels and outcomes were analyzed using logistic regression models. A total of 140 patients were included (90.7% female; median age at diagnosis 35.5 years). Moderate-to-high stress exposure (LCU ≥ 150) was reported by 46% of patients. Compared with low stress exposure (< 150 LCU), high stress exposure (≥ 300 LCU) was associated with significantly higher rates of depression (62.5% vs. 28.0%; p = 0.002), hypertension (54.2% vs. 24.0%, p = 0.006), and obesity (12.5% vs. 0.0%, p = 0.013), as well as greater fatigue burden (median 68.7 vs. 46.9, p = 0.005). High stress exposure was associated with antiphospholipid syndrome (OR 6.3, 95% CI 1.4–28.8), depression (OR 4.3, 95% CI 1.6–11.3), and a lower likelihood of long quiescent disease course (OR 0.22, 95% CI 0.07–0.7). Patients with higher stress exposure more frequently believed that stress contributed to both disease onset (100% vs. 71.7%, p = 0.006) and flares (100% vs. 69%, p = 0.006). Elevated stress levels preceding SLE diagnosis are associated with comorbidities and less favorable disease patterns. These findings underscore the clinical relevance of psychological stress in SLE and support the need for prospective studies examining its relationship with disease course.