MYCOPHENOLATE MOFETIL-INDUCED COLONIC ULCERATIONS IN RENAL TRANSPLANT PATIENTS

Abstract

Introduction: Mycophenolate mofetil (MMF) is a common immunosuppressive agent used to prevent rejection in renal transplant patients. We report two cases of colonic ulcers associated with MMF in renal transplant recipients. Case Reports: Case #1: A 48-year-old Caucasian man who received a renal transplant in December 2002. His maintenance immunosuppression regimen included prednisone, sirolimus and mycophenolate mofetil (2 gm/day). After 8 months of immunosuppressive therapy he presented with melena and anemia. Patient denied use of aspirin and other non-steroidal anti-inflammatory medications. Colonoscopy with biopsy was performed which revealed a large solitary ulcer in the ascending colon. Pathology revealed necrotic debris and was negative for malignancy. Immunochemical stains and serology for cy-tomegalovirus (CMV) and herpes simplex virus (HSV) were also negative. The anemia resolved after discontinuation of MMF. Repeat colonoscopy two months later revealed complete resolution of the colonic ulcer. Case #2: A 51-year-old African American man who underwent renal transplant in 2002. His immunosuppressive regimen included tacrolimus, sirolimus, prednisone and MMF (2 gm/day). Two years later patient underwent colonoscopy for anemia and weight loss. Patient did not report overt symptoms of gastrointestinal bleeding. Colonoscopy revealed a medium sized ulcer in the cecum. Pathology showed acute ulceration with inflammation and no evidence of malignancy or viral infection. MMF dose was reduced to 1 gm/day with improvement of patient's anemia. Discussion: MMF is associated with various gastrointestinal (GI) side effects including nausea, vomiting and diarrhea. Gastro duodenal ulceration with bleeding has also been reported with the use of MMF, however development of colonic ulcers is rare and limited to case reports. The actual mechanism of MMF induced colonic ulcer is unknown. It has been hypothesized that colonic ulcers develop due to high levels of active MMF metabolites in the colon in patients with renal transplant. While infection, especially CMV colitis, remains the more common cause of colonic ulceration and lower GI bleeding in immunosuppressed renal transplant patients, MMF-induced colonic ulceration should be included in the differential diagnosis. Healing of the ulcer can occur with dose-reduction or discontinuation of the drug.