Investigating the association between proton pump inhibitors and the risk of lupus: A retrospective cohort study of systemic and cutaneous manifestations

Summary: Abstract Body: Proton pump inhibitors (PPIs) are among the most prescribed medications in the United States. While short-term use of PPIs is related to mild adverse effects, their use has also been implicated in the development of autoimmune diseases, including systemic (SLE) and cutaneous lupus erythematosus (CLE). However, population-level analyses are limited. A retrospective cohort study was conducted using the TriNetX US Network to evaluate patients in the exposed cohort who were prescribed PPIs, identified by the ATC code classification A02BC. Patients with prior use of comparable treatment modalities, including histamine receptor agonists were excluded. The control cohort consisted of patients who had not been treated with PPIs. Propensity score matching (1:1) was performed based on baseline demographics, including age at index, biological sex, and ethnicity. Stratified analyses were conducted across distinct age groups (0-19, 20-50, 51-70, and 71+) for both male and female populations to assess potential age- and sex- specific variations in associations. The cohorts were then analyzed for incidence of SLE and CLE. The results revealed a statistically significant association between PPI use and the development of SLE in females aged 20-50 (p<0.001), 51-70 (p<0.001), and 71+ (p<0.001), as well as in males aged 20-50 (p=0.041) and 51-70 (p<0.001). However, no significant association was observed between PPI use and CLE in either group, although there was a limited number of CLE cases in each cohort. These findings suggest that PPI use is associated with an increased risk of SLE in females across multiple age groups (20-50, 51-70, and 71+) and in males aged 20-50 and 51-70. While PPIs showed no association with the development of CLE, larger population-based studies should be performed. As dermatologists are responsible for the management of lupus erythematosus, it is imperative to recognize this potential link between a widely prescribed medication and a life-threatening dermatosis. Antonio Jimenez¹, Luke Hamilton¹, Elise Weisert¹, Michael G. Wilkerson¹ 1. Dermatology, The University of Texas Medical Branch at Galveston, Galveston, TX, United States. Clinical Research: Epidemiology and Observational Research