Drug Exposure and the Risk of Microscopic Colitis: A Critical Update

Abstract

A variety of luminal antigens, including a wide range of drugs, have been associated with the still little-known pathophysiology of microscopic colitis (MC), with variable evidence suggesting causality. This article aims to review the aspects related to drugs as potential triggers of MC; to discuss the most commonly identified associations between drugs and MC; and to analyze the limitations of the studies currently available. A literature search was performed in PubMed combining the search terms ‘drug exposure’, ‘drug consumption’, and ‘risk factors’ with ‘microscopic colitis’, ‘lymphocytic colitis’, and ‘collagenous colitis’, with no language restrictions. Reference lists of retrieved documents were also reviewed. A handful of case–control studies have demonstrated significant associations between some commonly used drugs and a higher risk of developing MC. No universally accepted criteria for establishing cause–effect relationships in adverse reactions to drugs are available, but several methods that can be applied to MC, can provide degrees of the likelihood of an association. A high probability imputation in the development of MC as a drug adverse effect has only been demonstrated for individual cases by applying chronological (challenge, de-challenge, and relapse with re-challenge) and semiological criteria. Several case–control studies have shown significant associations between exposure to drugs and MC, but the variability in their design, the reference populations used, and the definitions for drug exposure considered require specific analyses. It can be concluded that drug exposure and MC as a likely cause–effect relationship has only been described for a handful of drugs and in individual cases.

Decreased risk for microscopic colitis and inflammatory bowel disease among patients with reflux disease

“…Previous investigators have described positive associations between antisecretory medication and microscopic colitis [9][10][11], as well as inflammatory bowel disease [6][7][8]. How could these positive associations be reconciled with the inverse (negative) associations of the present analysis?…”

“…Similarly, epidemiological studies have suggested that gastric acid suppression using histamine‐2 receptor antagonists (H2RAs) or PPIs is associated with an increased risk for flares and adverse outcomes, such as hospitalization and surgery, among patients with Crohn's disease and ulcerative colitis . Several potential mechanisms have been suggested to explain these associations . Experimental studies have shown that PPIs induce relaxation of intestinal smooth muscle, which in turn may affect the tight junctions between colonocytes and lead to increased paracellular permeability.…”

A case of collagenous colitis with cryptogenic organizing pneumonia

“…Finally, this case was diagnosed as having lansoprazole induced collagenous colitis. Already there are many reports about relevance between PPI and collagenous colitis [5,[7][8][9]. This case had a past history of administration of rabeprazole against peptic ulcer, and there was no diarrhea during administration.…”

Modulation of the immune response by helminths: a role for serotonin?

“…For instance, EC cells from patients with Crohn’s disease exhibit elevated 5-HT production [ 90 ], while patients with ulcerative colitis have reduced SERT expression [ 91 ]. Use of selective serotonin reuptake inhibitors has been associated with the development of microscopic colitis [ 92 ]. Mice engineered to lack components of the serotonergic system have revealed 5-HTs participation in gut disease: TPH1 −/− mice exhibited reduced severity of chemical-induced colitis and an accompanying reduction in IL-1β, IL-6, and TNF-α [ 93 ].…”