Case Presentation: A 72 year-old male patient with recent deceased donor renal transplant was on combined immune suppression with prednisone, tacrolimus and MMF. He Had multiple comorbidities but no previous history of IBD or autoimmune disease. He presented with normocytic anemia (hemoglobin 6.5 g/dL), weakness, anorexia and diarrhea. He was found to have ulcerated hemorrhoids which was thought to be the culprit of his anemia despite no clinical or gross evidence of bleed on flex sigmoidoscopy. Despite surgical treatment of his hemorrhoids (hospital day 7), hematochezia persisted prompting endoscopic evaluation. Colonoscopy (hospital day 14) revealed congested, erythematous, ulcerated mucosa with exudates of the distal ileum, decreased vascular pattern, and discontinuous ulcerations in the remaining colon. Biopsy of the colon showed scattered apoptotic crypt abscesses and increased apoptosis suggestive of MMF toxicity. Terminal ileum biopsies showed acute ileitis with ulceration. MMF was discontinued with histology and clinical picture of drug induced colitis. Bleeding persisted with hemodynamic instability. Tagged RBC scan showing blush in the right abdomen consistent with the distal ileum/right colon. Urgent hemicolectomy with end ileostomy resulting in hemostasis and improved anemia.

Discussion: MMF induced diarrhea is reported in 24-53% of those using the medication. MMF inhibits inosine monophosphate in the de novo purine synthesis pathway preventing DNA and RNA production. Lymphocytes depend on this pathway preventing DNA and RNA production. Lymphocytes depend on this pathway, as do enterocytes. Colitis with hemodynamically significant hemorrhage requiring hemicolectomy is rare. Endoscopic control of bleeding is difficult due to multifocal/serpiginous lesions and associated ischemia. Early recognition of MMF colitis is essential to remove the offending agent, prevent significant bleeding and prevent the need for surgical intervention. This case likely resulted in delayed diagnosis as the patient was thought to have anemia from hemorrhoids. Treatment includes removal of offending agent, IV glucocorticoids, and infliximab if indicated. Surgical intervention is not common. Colitis is unlikely to recur if MMF is reduced or eliminated.

Conclusions: Mycophenolate mofetil can cause colitis resulting in life threatening bleeding. Life threatening bleeding from hemorrhoids is extremely rare, and never reported before surgical intervention. All causes of lower gastrointestinal bleeding should be excluded before life threatening bleeding due to hemorrhoids is diagnosed.