Mycophenolate Mofetil-Induced Non-Healing Gastric and Duodenal Ulcers

Abstract

Mycophenolate mofetil (MMF), also known as Cellcept (Genentech, S. San Francisco, CA), is a commonly used immunosuppressant following solid organ transplantation. It has effectively reduced rates of rejection of transplanted organs, but this medication has been associated with a variety of gastrointestinal (GI) side effects, including abdominal pain, nausea, diarrhea, constipation, vomiting, anorexia, and dyspepsia. Here we present a case of non-healing gastric and duodenal ulcers related to MMF use following liver transplantation. A 36-year-old female with a history of familial intrahepatic cholestasis status-post an orthotopic liver transplant (1986), who was referred with complaints of chronic mid-epigastric and left upper quadrant abdominal pain. She has been maintained on long-term immunosuppressive therapy with MMF and cyclosporine, but unfortunately developed cirrhosis of her transplanted liver for which she has been getting routine variceal screening by esophagogastroduodenoscopies (EGD). Her last EGD in January 2016 revealed 6 moderately-sized esophageal varices, multiple gastric ulcers, and one clean-based duodenal ulcer. Screening for Helicobacter pylori was negative. She was subsequently placed on twice daily proton pump inhibitor (PPI) therapy and follow up EGD was performed in April 2016. This revealed persistent gastric and duodenal ulcers without evidence of healing. On subsequent clinic visit, she continued to endorse unchanged left upper quadrant and mid-epigastric abdominal pain, despite appropriate use of twice daily PPI therapy. Repeat EGD in January 2018 revealed a persistent antral gastric ulcer, as well as numerous white plaques scattered throughout the stomach (Figure 3). Biopsy of these plaques revealed active gastritis with evidence of cellular apoptosis, characteristic of mycophenolate-induced gastropathy. Repeat testing for Helicobacter pylori remained negative. Case Highlights:Mycophenolate mofetil remains a standard of post-transplant immunosuppression but has several known GI side effects. This case describes an instance of a less common side effect, MMF-induced ulcers. GI complications may improve with reduction or cessation of MMF, but this may not always be feasible in cases of transplant immunosuppression. Newer formulations of mycophenolate include an enteric coating which may reduce GI side effects and may be a good alternative for patients who experience more severe symptoms.1917_C Figure 3. Repeat visualization of gastric ulcer during EGD procedure dated January 20181917_A Figure 1. Duodenal ulcer as visualized during January 2016 EGD procedure1917_B Figure 2. Gastric ulcer as visualized during January 2016 EGD procedure