Mycophenolate mofetil-related gastrointestinal mucosal injury in multivisceral transplantation

Mycophenolate mofetil (MMF) has become an important and commonly used drug for maintenance immunosuppression therapy in recipients of all types of organ transplants. The drug is an antimetabolite that blocks the de novo pathway of purine synthesis. Although it selectively inhibits B- and T-lymphocyte proliferation, enterocytes are partially susceptible to MMF. One of the main limitations of this drug is gastrointestinal toxicity, with diarrhea the most frequently reported adverse effect. Most studies of MMF-associated gastrointestinal toxicity have been performed in patients with solid-organ transplants, although no data on changes related to MMF toxicity in bowel allografts have been published in the English literature. We evaluated mucosal intestinal biopsy tissue from patients with multivisceral transplants receiving MMF therapy. Our objective was to find morphologic changes that might be attributed to MMF toxicity, as well as changes that could differentiate MMF toxicity from acute rejection. Examination of the surface epithelium, lamina propria, and crypts in this small group of patients showed no specific changes that could be associated with MMF toxicity. Changes such as graft-vs-host disease or inflammatory bowel disease described in previous studies of solid-organ transplantation were not observed. Larger studies and the use of special stains and new markers might be necessary to characterize possible patterns of MMF toxicity and their differences from acute rejection.