Individuals with a history of post-traumatic stress disorder (PTSD) had twice the risk of subsequently developing lupus, an analysis of a large diverse group of Medicaid enrollees found. The prevalence of PTSD was 10.74 (95% CI 9.37-12.31) per 1,000 among patients who were later diagnosed with systemic lupus erythematosus (SLE) compared with 7.83 (95% CI 7.42-8.27) per 1,000 among controls, according to Siobhan Case, MD, of Brigham and Women's Hospital in Boston, and colleagues. After adjustment for multiple factors including age, sex, race, income, region of residence, obesity, smoking, and use of oral contraceptives, the odds ratio for SLE among patients with PTSD was 2.0 (95% CI 1.64-2.46, P<0.001), the researchers reported online in Arthritis Care & Research. Exposure to trauma has been linked with multiple hormonal and metabolic changes. "These alterations can in turn affect the immune system and inflammatory responses through many potential pathways, such as cytokine production, immune cell signaling, endocannabinoids, and epigenetic modifications," they explained. PTSD is more common among women and Black people, which is also the case for SLE. A previous report from the Nurses' Health Study II found that symptomatic PTSD was associated with an almost threefold increased risk of SLE (HR 2.94, 95% CI 1.19-7.26), but that study was limited by its homogeneous population who were largely women and white. To assess the risk in a more diverse group of individuals, Case and colleagues analyzed data for Medicaid enrollees residing in the 29 most populous states during the years 2007 to 2010. They identified 10,942 incident cases of SLE, who were matched according to age, sex, and race/ethnicity with 109,420 controls. Participants' mean age was 41, and more than 90% were women; 40% were Black, 38% were white, 17% were Hispanic, and small numbers were Native American or "other." Rates of smoking and obesity were low and similar among cases and controls. The median time between the first diagnostic code for PTSD and first code for SLE was 432 days, with a range of 1 to 1,356 days. In a matched but unadjusted logistic regression analysis, the odds ratio for SLE among those with PTSD was 1.96 (95% CI 1.66-2.33, P<0.001), rising to 2.0 after multiple adjustments for potentially influential covariates. A sensitivity analysis that included only patients who had been enrolled in Medicaid for at least 2 years before having a diagnostic code for SLE (to increase the likelihood of incident SLE) was also conducted. In this analysis, which included 4,504 cases of SLE and 45,040 matched controls, the prevalence of PTSD was 15.74 (95% CI 12.71-19.49) per 1,000 for patients with SLE compared with 9.97 (95% CI 9.09-10.93) per 1,000 for controls. The incidence of PTSD among SLE cases was 7.95 (95% CI 5.88-10.76) per 1,000 and 6.51 (95% CI 5.81-7.30) per 1,000 among controls. The odds ratio on conditional logistic regression analysis for SLE was 2.64 (95% CI 2.07-3.4, P<0.0001), increasing to 3.62 (95% CI 2.35-5.56, P<0.0001) on multivariate analysis. The results of this study differ from a previous study of U.S. military members, which found increased levels of autoimmune diseases in general among those with PTSD, though not SLE specifically. However, that study population was predominantly male and included few cases of SLE. Biologic changes associated with trauma exposure can help explain the relationship with autoimmunity. "Widespread DNA methylation epigenetic changes and shorter telomere length have both been identified in patients with PTSD. Inflammatory markers such as C-reactive protein and interleukin-6 are also increased in populations of patients with PTSD compared to those without, which could lead to downstream effects in inflammation and immune cell function," the researchers observed. Further investigations will be needed, however, to determine the specific mechanisms and pathways involved in loss of self-tolerance, development of autoantibodies, and immune dysfunction, and also to identify potential interventions that could modify the risk of SLE and other autoimmune diseases among individuals already diagnosed with PTSD. Limitations to the study included its case-control design and relatively short follow-up. Source
