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OBJECTIVE: Ultraviolet radiation (UV) exposure is associated with photosensitivity, rashes, and flares in systemic lupus erythematosus (SLE). However, it is not known whether UV exposure increases risk of developing SLE. We examined UV exposure and SLE risk in a large prospective cohort. METHODS: The Nurses’ Health Study (NHS) enrolled 121,700 U.S. female nurses in 1976; in 1989, 116,429 were enrolled in NHSII. Biennial questionnaires collected lifestyle and medical data. Self-reported incident SLE by American College of Rheumatology classification criteria was confirmed by medical record review. Ambient UV exposure was estimated by linking geocoded residential addresses with a spatiotemporal UV exposure model. Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) across tertiles of time-varying cumulative average UV. We examined SLE risk overall and stratified by anti-Ro/La antibodies and by cutaneous manifestations from 1976 through 2014 (NHS)/2015 (NHSII), adjusting for confounders. RESULTS: With 6,054,665 person-years of exposure, we identified 297 incident SLE cases; mean age at diagnosis was 49.8 (10.6) years. At diagnosis, 16.8% of women had +anti-Ro/La, and 80% had either +anti-Ro/La or ≥1 cutaneous manifestation. Compared to the lowest UV exposure tertile, risk of overall SLE was increased, but not significantly (HR 1.28 [95%CI 0.96–1.70]). Women in the highest tertile had increased risk of malar rash (HR 1.62 [95% CI 1.04–2.52]). CONCLUSION: Cumulative UV exposure was not associated with SLE risk. Higher UV exposure, however, was associated with increased risk of malar rash at presentation. UV exposure may trigger SLE onset with malar rash among susceptible women.

OBJECTIVE To investigate the association of depression with subsequent risk of rheumatoid arthritis (RA) by serologic phenotype. METHODS We performed a cohort study using pooled data from the Nurses' Health Study (NHS; 1992-2014) and the NHSII (1993-2015). Depression was defined according to the following composite definition: diagnosis by clinician, regular antidepressant use, or a 5-question Mental Health Inventory score of

Objective To investigate whether menopausal factors are associated with the development of serologic rheumatoid arthritis (RA) phenotypes. Methods Data were analyzed from the Nurses’ Health Studies (NHS; 1976–2010 and NHSII 1989–2011). A total of 120,700 female nurses ages 30–55 years in the NHS, and a total of 116,430 female nurses ages 25–42 years in the NHSII, were followed via biennial questionnaires on lifestyle and disease outcomes. In total, 1,096 incident RA cases were confirmed by questionnaire and chart review. Seropositive RA was defined as rheumatoid factor positive (RF) or antibodies to citrullinated protein antigen (ACPA) positive, and seronegative RA was defined as RF negative and ACPA negative. We used Cox proportional hazards models to obtain multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) of seropositive/seronegative RA associated with menopausal status, age at menopause, type of menopause, ovulatory years, and postmenopausal hormone therapy (PMH) use. Results Postmenopausal women had a 2-fold increased risk of seronegative RA, compared with premenopausal women (NHS: HR 1.8 [95% CI 1.1–3.0], NHSII: HR 2.4 [95% CI 1.4–3.9], and pooled HR 2.1 [95% CI 1.4–3.0]). Natural menopause at early age (≤44 years) was associated with an increased risk of seronegative RA (pooled HR 2.4 [95% CI 1.5–4.0]). None of the menopausal factors was significantly associated with seropositive RA. We observed no association between PMH use and the risk of seronegative or seropositive RA, except that PMH use of ≥8 years was associated with increased risk of seropositive RA (pooled HR 1.4 [95% CI 1.1–1.9]). Conclusion Postmenopause and natural menopause at an early age were strongly associated with seronegative RA, but only marginally with seropositive RA, suggesting potential differences in the etiology of RA subtypes.