Medication Use and Microscopic Colitis

Robert S. Sandler; Temitope O. Keku; John T. Woosley; Joseph A. Galanko; Anne F. Peery


Aliment Pharmacol Ther. 2021;54(9):1193-1201. 

In This Article

Abstract and Introduction


Background: Microscopic colitis is an increasingly common cause of watery diarrhoea. Several classes of medications have been associated with microscopic colitis in prior studies.

Aims: To determine the association between the use of previously implicated medications and microscopic colitis.

Methods: This was a case-control study of patients referred for elective, outpatient colonoscopy for diarrhoea. Patients were excluded for inflammatory bowel disease, C difficile, or other infectious diarrhoea. Colon biopsies were reviewed by the study pathologist and patients were classified as microscopic colitis cases or non-microscopic colitis controls.

Results: The study population included 110 microscopic colitis cases and 252 controls. The cases were older, better educated and more likely to be female. Cases reported a greater number of loose, watery, or liquid stools, nocturnal stools, more urgency and weight loss compared to controls. There was no association with proton pump inhibitors (PPIs), adjusted OR (aOR) 0.66, 95% CI 0.38–1.13 or nonsteroidal anti-inflammatory drugs, aOR 0.68, 95% CI 0.40–1.17. Cholecystectomy was less common in cases, aOR 0.33, 95% CI 0.17–0.64, but microscopic colitis cases had more frequent bowel movements following cholecystectomy.

Conclusion: Compared to similar patients with diarrhoea, cases with microscopic colitis were not more likely to have taken previously implicated medications. They had more diarrhoea following cholecystectomy, suggesting that bile may play a role in symptoms or aetiology. We conclude that the appropriate choice of controls is crucial to understanding risk factors for microscopic colitis.


Microscopic colitis is currently a common cause of watery diarrhoea in older adults, although it is increasingly recognised in younger individuals.[1] The condition is called "microscopic colitis" because the mucosa appears grossly normal. Under the microscope, however, there may be a thickened collagen band (collagenous colitis) or a lymphocytic infiltration (lymphocytic colitis).[2] Both collagenous and lymphocytic colitis share features of intraepithelial lymphocytes, surface epithelial damage, and increased lamina propria inflammation. Lymphocytic and collagenous colitis, are generally considered to be subtypes of the same disease based on the histologic overlap, parallel increase in incidence, similar clinical presentation and identical response to therapy.[3]

The incidence of microscopic colitis has been increasing and is now thought to be comparable to or exceed inflammatory bowel disease.[4–8] Some of the increased incidence is due to greater recognition of the disease.[9] The aetiology of microscopic colitis is unknown. The disease is widely considered to be an abnormal immune reaction to luminal antigens in predisposed hosts.[10] The concept of a luminal factor is supported by the fact that the disease resolves with diversion of the faecal stream,[11] and recurs when continuity is restored.[11,12] Reported triggers are drugs,[10] smoking[13,14] and autoimmunity.[15]

Published evidence about risk factors for microscopic colitis has been limited by small numbers of cases, retrospective data collection and case series designs. To avoid the limitations of prior research, we conducted a case-control study comparing patients with microscopic colitis to patients with other causes of diarrhoea in order to learn more about associations with medications.