S3974 Sigmoid Ulceration With Cholestyramine Use: Medication-Associated Colitis?

Introduction: Medication-associated mucosal injury is an underrecognized but important cause of colitis. Bile-acid salt sequestrant (BAS) resins, such as cholestyramine, have been identified in the colon, with histologic findings ranging from nonspecific inflammation to erosions and ulceration. Although these occurrences are rare, their clinical implications warrant attention. We present a case of cholestyramine-associated colitis manifesting as a significant sigmoid ulceration. Case Description/Methods: A 64-year-old man with a history of a cholecystectomy and urothelial carcinoma status post chemoradiation and cystectomy presented with chronic diarrhea. Stool studies were unremarkable. Colonoscopy revealed diverticulosis throughout the colon and mild mucosal congestion in the rectosigmoid colon; however, biopsies showed no significant pathologic alteration. He was empirically started on cholestyramine for presumed bile acid diarrhea, with partial symptomatic improvement. However, a few months later, he presented to the emergency department with worsening diarrhea along with anorexia and fatigue. Computed tomography with rectal contrast demonstrated minimal sigmoid colon wall thickening with trace pericolonic stranding and a large colonic stool burden. He was treated with an aggressive bowel regimen for management of stercoral colitis with clinical improvement and he was discharged. Despite symptomatic relief, his diarrhea persisted. Laboratory evaluation showed an elevated fecal calprotectin of 1074 µg/g. Given recent pembrolizumab therapy, his oncologist initiated a prednisone taper for presumed checkpoint inhibitor (CPI) colitis with initial improvement, but he experienced symptom relapse upon tapering. Repeat colonoscopy was performed to rule out CPI colitis. It demonstrated a solitary, large ulcer involving over 50% of the luminal circumference in the sigmoid colon. The remainder of the colonoscopy was unremarkable. Histopathology of the ulcer base revealed scattered crystal-like material consistent with cholestyramine crystals along with associated mucosal injury. Discussion: While BAS resins are typically regarded as pharmacologically inert within the gastrointestinal tract, they can rarely induce mucosal injury. In this case, the temporal relationship between cholestyramine initiation and the development of ulceration, in conjunction with histologic evidence of cholestyramine crystals, supports a possible causative role. This case highlights the potential for BAS agents to cause clinically significant ulceration.