Use of Proton Pump Inhibitors Is Not an Independent Risk Factor for Microscopic Colitis: A Large Retrospective Case Controlled Study

Abstract

Introduction: Microscopic Colitis (MC) is a chronic inflammatory disease of the colon that presents with chronic, watery, non-bloody diarrhea and is diagnosed with colonoscopy (CSPY). Recent literature has been mixed on the association of proton pump inhibitor (PPI) use with the development of MC. We investigated the possible association of PPI’s with MC among patients with clinically significant diarrhea. Methods: We performed a retrospective case-control study of all patients whom underwent CSPY to rule out MC in the setting of clinically significant chronic diarrhea from 1/2012-12/2016 at a tertiary care academic medical center. 127 patients diagnosed with MC were propensity score matched to 127 patients with normal biopsies on pathology based on age and gender. Patients were excluded if they were <18 years old, inpatients, or had FMT. The primary outcome was history of PPI use. The secondary outcome included use of NSAIDs or anti-depressants. An OR was calculated for the primary outcome and binomial logistic regression modeling was used to control for other medication use. Statistical analysis and propensity score matching were performed in R using the MatchIt Package. Results: 50/127 patients diagnosed with MC and 44/127 patients with normal biopsies used PPI’s (OR 1.2; 95% interval 0.751-2.078). No significant differences were observed among the case and control groups with respect to age, gender, celiac disease, or antidepressants. In addition, no statistical difference was seen in the lymphocytic (LC) vs. collagenous colitis (CC) subtypes among MC patients with PPI use. More patients with celiac disease had LC than CC but this difference is not significant and further studies may elucidate this association. Logistic regression revealed that compared with controls, only NSAID use was a predictor of the development of MC. Anti-depressant use was not a predictor of the development of MC. Conclusion: In this study, a history of PPI use was not associated with and does not predict a pathologic diagnosis of MC in an at risk population. Despite the effect of PPI’s on the microbiome; in this series, PPI’s were not an independent risk factor for MC. Further studies may prove beneficial in relating the development of MC in patients with long-term PPI use and their influence on the microbiome; however, our case-control study shows no such association. Based on this data, the diagnosis of LC or CC does not warrant discontinuing PPI’s if they are otherwise indicated.196_A Figure 1. Demographics196_B Figure 2. Results of Drug Regression196_C Figure 3. MC Subtype Demographics