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Background Medication consumption has been suggested as a risk factor for microscopic colitis (MC), but studies of varying design have yielded inconsistent results. Our aim was to evaluate the association between medications and MC. Methods A hybrid cohort of prospectively identified patients undergoing colonoscopy with biopsies for suspicion of MC (N = 144) and patients with MC enrolled within three months of diagnosis into an MC registry (N = 59) were surveyed on medication use. Medication use was compared between patients with and without diagnosis of MC by chi-squared test and binomial logistic regression adjusted for known risk factors of MC: age and gender. Results In total, 80 patients with MC (21 new, 59 registry) were enrolled. Patients with MC were more likely to be older (p = 0.03) and female (p = 0.01) compared to those without MC. Aspirin and other non-steroidal anti-inflammatory drugs were more commonly used among patients who developed MC (p < 0.01). After controlling for age and gender, these medications remained independent predictors of MC with odds ratio for any non-steroidal anti-inflammatory drug use of 3.04 (95% CI: 1.65–5.69). No association between MC and other previously implicated medications including proton pump inhibitors and selective serotonin reuptake inhibitors was found. Conclusions In this cohort of patients with chronic diarrhea, we found use of aspirin and non-steroidal anti-inflammatory drugs, but not other implicated medications to be associated with the development of MC. Whether these drugs trigger colonic inflammation in predisposed hosts or worsen diarrhea in undiagnosed patients is unclear. However, we feel that these findings are sufficient to discuss potential non-steroidal anti-inflammatory drug cessation in patients newly diagnosed with MC.

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