Medication Use and Microscopic Colitis

A Multicentre Retrospective Cohort Study

Haley M. Zylberberg; Amrit K. Kamboj; Nicole De Cuir; Conor M. Lane; Sahil Khanna; Darrell S. Pardi; Benjamin Lebwohl


Aliment Pharmacol Ther. 2021;53(11):1209-1215. 

In This Article

Abstract and Introduction


Background: Medication use has been implicated in the development of microscopic colitis (MC). However, studies have demonstrated inconsistent findings and there exist variations in design.

Aim: To measure the association between medication use and MC.

Methods: Patients who underwent a colonoscopy over a 10-year period at two academic medical centres (Columbia University Medical Centre and Mayo Clinic) were identified. Cases were patients with biopsy-proven MC and controls were patients who underwent colonoscopy for evaluation of diarrhoea with biopsies negative for MC. Cases were matched by age, gender and calendar period with up to two controls. Demographics, medication use, smoking history and coeliac disease status were collected. Conditional logistic regression was used with and without adjustment for smoking.

Results: A total of 344 patients with MC were matched to 668 controls. After adjusting for smoking, there was an inverse association between MC and use of proton pump inhibitors (PPIs) (OR 0.64; 95% CI 0.47–0.87), H2 blockers (OR 0.46; 95% CI 0.24–0.88) and oral diabetes medications (OR 0.47; 95% CI 0.27–0.81). There was a positive association with nonsteroidal anti-inflammatory drug (NSAID) use and MC (OR 1.63; 95% CI 1.12–2.38).

Conclusions: NSAID use was associated with MC, while use of PPIs, H2 blockers and oral diabetes medications were inversely related to MC. Our use of a control group with diarrhoea, as opposed to healthy controls, may have contributed to these inverse associations. Future studies of drug-induced microscopic colitis should include control groups with diarrhoea, and not only healthy controls.


Microscopic colitis (MC) is an inflammatory disorder of the colon that causes chronic watery diarrhoea and is characterised by the presence of intraepithelial lymphocytes on colonic histology.[1,2] There are two subtypes of MC, lymphocytic colitis (LC) and collagenous colitis (CC), which are clinically similar, but are distinguished by the presence of a thickened subepithelial collagen band seen only in the collagenous subtype.[1,2]

While inflammation underlies the MC disease process, the exact pathogenesis has not been well-defined.[1,2] It has been suggested that the colonic inflammation in MC is triggered by an intraluminal antigen.[1,2] Given the high prevalence of MC in patients with coeliac disease,[3] it has been hypothesised that gluten exposure or autoimmunity may play a role in the development of MC.[1] Other luminal antigens, such as certain medications, have also been suggested to play a role.[1,2]

Studies have examined the association between MC and several classes of medications, including proton pump inhibitors (PPIs),[4–15] nonsteroidal anti-inflammatory drugs (NSAIDs),[4–15] selective serotonin reuptake inhibitors (SSRIs),[4–7,11,12,14] statins,[4,6,7,11,12,14] beta blockers (B-blockers),[6,7,12] bisphosphonates[6,7] and H2 receptor blockers (H2 blockers),[7,14] among others. However, there is currently no consensus on which medications are implicated and to what degree.[16–18] While a majority of studies from Europe have demonstrated a positive association between MC and PPIs[4,6,10,12,14,15] and NSAIDs,[4–6,12,14,15,19] the only two studies performed in the United States (US) failed to corroborate the association with PPIs.[5,13] Aside from the paucity of US data, the literature on this topic is further limited by small samples of patients with MC[5–11,13,19] and failure to include multiple medication classes among the larger studies.[4,14,15]

The primary aim of this two-centre US study was to investigate the association between MC and medication use compared to patients without MC who underwent colonoscopy for evaluation of chronic diarrhoea.