Histological Patterns of Mycophenolate Mofetil-Induced Gastrointestinal Mucosal Injury in Renal Transplant Recipients

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BACKGROUND: Mycophenolate mofetil (MMF) is widely used in renal transplant recipients but is commonly associated with gastrointestinal (GI) toxicity, often presenting as chronic watery diarrhoea. Its histological injury patterns may mimic other pathological conditions, creating diagnostic challenges. The present study aimed to evaluate the spectrum of histopathological changes in GI biopsies of renal transplant recipients with MMF-associated watery diarrhoea. MATERIALS AND METHODS: This retrospective observational study (2011-2020), conducted at a tertiary care centre, included 103 GI biopsies from 84 renal transplant recipients. Infective causes and de novo inflammatory bowel disease were excluded. Histological features in upper and lower GI biopsies were analysed and correlated with clinical findings. RESULTS: A total of 103 biopsies (51 colorectal, 42 small intestinal, 6 gastric, and 4 oesophageal) were evaluated. Chronic diarrhoea was the most common symptom (60/84, 71.4%). Colorectal mucosa showed crypt architectural disarray in all biopsies (51/51, 100%), with moderate-to-severe changes in approximately two-thirds of biopsies (39/51, 76.4%). Increased apoptosis (29/51, 56.8%), lamina propria oedema (27/51, 52.9%), and active colitis in the form of cryptitis and crypt abscesses (22/51, 43.1%) were frequent findings. Dilated damaged crypts, a defining lesion of drug-induced colitis, were seen in a small proportion of colorectal mucosa biopsies (7/51, 13.7%). In small intestinal biopsies, apoptosis was the predominant finding (25/42, 59.5%), followed by intraepithelial lymphocytosis (10/42, 23.8%) and villous blunting (7/42, 16.6%). All six gastric biopsies showed reactive gastropathy, while all four oesophageal biopsies revealed ulcerative oesophagitis. CONCLUSION: MMF-induced GI injury shows a wide histological spectrum, with crypt distortion and apoptosis as key diagnostic features. Recognition of these patterns aids in differentiating MMF toxicity from its histological mimics and guides appropriate management.

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