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Drug-induced microscopic colitis: a systematic review of implicated agents and case-level causality
Muhanad Alzahrani1, Abdullah Alabbasi2, Ziyad Alzahrani3
1Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA. mohandsaleh50@gmail.com.
Abstract:
Microscopic colitis (MC), including collagenous colitis (CC), lymphocytic colitis (LC) and incomplete MC, is a common cause of chronic watery diarrhoea. Drugs are reported triggers, but observational studies cannot establish individual causality. We reviewed case-level evidence and graded causality using dechallenge/rechallenge criteria. We included published biopsy-confirmed MC case reports and series in which drug exposure preceded symptoms and dechallenge was documented. Data were extracted at the patient level without language or date restriction. Cases were graded as Tier 1 for positive rechallenge or Tier 2 for dechallenge without rechallenge. Quality was assessed using the Murad tool. Twenty-four studies including 69 patients met criteria. Proton-pump inhibitors were most frequent (29/69, 42%), and acid suppressants plus NSAIDs accounted for 36/69 cases (52%). Other agents included ticlopidine, dopaminergic anti-Parkinson drugs, etifoxine, a venotonic, ACE inhibitors and antidepressants. CC and LC were both common. All cases were dechallenge-positive; 11 (16%) had positive rechallenge. Median reported latency was 12 days (range, 5-112). Histology normalised in 22/26 re-biopsied cases. Case-level evidence supports drug-related MC, especially with acid suppressants and NSAIDs. Drug withdrawal remains the key diagnostic and therapeutic step.
Insights
Drug-induced microscopic colitis (MC) is a significant cause of chronic diarrhea. Case reviews confirm causality, especially with acid suppressants and NSAIDs, highlighting drug withdrawal as crucial for diagnosis and treatment.
Area of Science:
- Gastroenterology
- Pharmacology
- Pathology
Background:
- Microscopic colitis (MC), encompassing collagenous colitis (CC) and lymphocytic colitis (LC), is a frequent cause of chronic watery diarrhea.
- While drugs are suspected triggers, establishing individual causality requires rigorous evidence beyond observational studies.
Purpose of the Study:
- To review case-level evidence and grade the causality of drug-induced microscopic colitis using dechallenge and rechallenge criteria.
- To identify specific drug classes associated with microscopic colitis.
Main Methods:
- Systematic review of published biopsy-confirmed MC case reports and series with documented drug exposure and dechallenge.
- Causality grading based on dechallenge (Tier 2) and positive rechallenge (Tier 1) using the Murad tool for quality assessment.
- Data extraction from 24 studies involving 69 patients.
Main Results:
- Proton-pump inhibitors (42%) and NSAIDs (52%, often with acid suppressants) were the most frequently implicated drug classes.
- Other implicated drugs included ticlopidine, dopaminergic agents, etifoxine, venotonics, ACE inhibitors, and antidepressants.
- All cases showed dechallenge-positive results, with 16% demonstrating positive rechallenge; histology normalized in most re-biopsied cases.
Conclusions:
- Case-level evidence strongly supports a causal link between certain medications and microscopic colitis.
- Acid suppressants and NSAIDs are particularly implicated in drug-induced MC.
- Discontinuation of the offending drug is the primary diagnostic and therapeutic intervention for microscopic colitis.
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