Do medications really cause microscopic colitis?

Review by Prof. Eamonn Quigley (USA)

Study Summary 

Microscopic colitis (encompassing both lymphocytic and collagenous colitis) is a relatively common cause of painless diarrhea in middle-aged to elderly females, predominantly. The etiology of the disorder is unknown but several medications, such as proton pump inhibitors (PPIs) and NSAIDs, have been so strongly linked to an increased risk of the disorder that their cessation has become a standard recommendation in treatment guidelines. A large study based on data from the entire population of Sweden 65 years of age or older now questions this dogma. No association was noted for risk of onset of microscopic colitis (MC) with angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, NSAIDs, PPIs or statins over one or two years, with the overall risk for MC being less than 0.5%.  Interestingly, the initiation of these medications was associated with a small increase in the likelihood of having a colonoscopy with colonic biopsies, suggesting that being on these medications may have biased the clinician towards seeking a diagnosis of MC. Selective serotonin receptor inhibitors (SSRIs) were associated with a small increase in risk for MC but the clinical implications of this finding were uncertain.

Commentary 

This is a very important study which should change our approach to a common problem. When MC is diagnosed there is little (or nothing) to be gained by adjusting the patient’s pre-diagnosis medication list and attention should be paid instead to uncovering associated diseases such as celiac disease. While the study did not find an increase in risk for MC with angiotensin-receptor blockers, it would be interesting to see data for individual agents within this class, as olmesartan has been linked to an enteropathy similar to celiac disease and, in some cases, to MC.

Citation

Khalili H, McGee EE, Challa PK, et al. Medications and risk for microscopic colitis: a nationwide study of older adults in Sweden. Ann Intern Med 2025;178:1106-15.

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