Drug-induced microscopic colitis: a systematic review of implicated agents and case-level causality

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.