Risk Factors for Microscopic Colitis: A Systematic Review and Meta-Analysis.

Background: Microscopic colitis (MC) is still an underdiagnosed disease due to its primarily histological appearance. We aimed to address the scarcity and inconsistency of data on MC risk factors.

Methods: Our protocol was prospectively registered in PROSPERO (CRD42022286624). We systematically searched PubMed, Embase, and Cochrane from inception to January 6, 2025. Cohort, case-control, and cross-sectional studies were included. Controls were distinguished with or without a histopathological examination. We used the random-effect model to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs).

Results: The systematic search yielded 6493 articles, of which 45 were meta-analyzed. We found increased odds for MC in the case of nonsteroidal anti-inflammatory drug (NSAID) and statin use compared to histological (OR = 2.57, CI: 1.45-4.53; OR = 2.15, CI: 1.14-4.05) and random (OR = 2.56, CI: 1.13-5.79; OR = 1.84, CI: 0.58-5.80) controls. Our results did not show an association between proton pump inhibitors (PPIs) and MC, compared to histological controls (OR = 1.81, CI: 0.75-4.35), except in the case of random controls (OR = 4.31, CI: 1.66-11.20). Neither current (OR = 1.35, CI: 0.88-2.06) nor previous smoking (OR = 1.26, CI: 0.67-2.39) increased the odds of MC compared to histological controls. In contrast, the odds doubled for current smoking and slightly changed for past smoking when MC patients were compared to random controls (OR = 2.40, CI: 1.64-3.50; OR = 1.11, CI: 0.93-1.31).

Conclusions: NSAID and statin treatment were associated with an increased risk for MC compared to histological controls. PPIs and smoking showed only an association with MC when random controls were used.