Mycophenolate-Induced Colitis

Abstract

Mycophenolate mofetil (MMF) is an immunosuppressive drug used in various autoimmune diseases, bone marrow and solid organ transplants. Gastrointestinal side effects occur in 45% of patients with diarrhea being the most common symptom (64-92%). Colitis is seen in around 9% of patients on MMF. Discontinuing MMF leads to resolution of diarrhea 98% of the time. We report a case of MMF-induced colitis diagnosed by colonoscopy and histopathology. This case illustrates challenges that were faced while managing refractory MMF-induced colitis. A 68-year-old man with a history of single lung transplant on MMF presented with 6-8 episodes of bloody diarrhea daily for the past 8 weeks. Physical exam: ill-appearing man with tenderness in the right lower quadrant and maroon colored stool on digital rectal exam. Laboratory studies revealed iron deficiency anemia with hemoglobin of 9.4 g/dL (baseline 11 g/dL). Cytomegalovirus, stool ova & parasites, tuberculosis, and clostridium difficile were negative. Magnetic resonance enterography of the abdomen showed small bowel wall thickening, 10 cm peri-enteric stranding of the distal terminal ileum extending to the ileo-colonic anastomosis (Fig 1). An EGD was normal, while colonoscopy revealed numerous ulcers in the ascending colon, ileo-colonic anastomosis, and in the distal 15 cm of the neo-terminal ileum (Fig 2). Histology of ulcer revealed mild crypt architectural distortion and crypt cell apoptosis (Fig 3). Three days after discontinuation of MMF, the patient continued to have bloody diarrhea requiring RBC transfusions. Intravenous (IV) Solumedrol 60 mg daily was initiated. After 5 days of IV Solumedrol, a repeat colonoscopy showed healing of numerous ulcerations and improvement in the appearance of the large ulcerations suggestive of overall endoscopic improvement. The patient was transitioned to oral steroids and steadily experienced clinical improvement. Since the advent of immunosuppression therapy, MMF-induced colitis is an uncommon however debilitating complication with only a few case reports to date and no current guidelines in the literature. There continues to be unanswered questions as to why some patients have refractory colitis, the benefits of oral or IV steroids, or biologic therapy (i.e. Infliximab), and the need for endoscopic reassessment for mucosal healing. With more cases being reported, we can better understand the natural course of the disease and formulate guidelines to manage refractory colitis1546_A Figure 1. Magnetic resonance enterography depicting small bowel wall thickening, mural hyper enhancement and peri-enteric stranding involving 10-cm segment of the distal terminal ileum.1546_B Figure 2. Colonoscopy revealing several deep punched out ulcers with heaped up edges in the ascending colon, ileo-colonic anastomosis, and terminal ileum.1546_C Figure 3. Hematoxylin and eosin photomicrograph of an ulcer biopsy demonstrating increased crypt cell apoptosis with mild architectural distortion. There is no evidence of active inflammation or viral cytopathic effect.