S5006 Exacerbation of Microscopic Colitis Following Pancreatic Enzyme Replacement Therapy: A Case of Severe Diarrhea Leading to Hospitalization

Introduction: Microscopic colitis (MC) is an inflammatory condition of the colonic mucosa characterized by chronic, watery, non-bloody diarrhea. It is classified as either collagenous or lymphocytic colitis. Known triggers for MC include nonsteroidal anti-inflammatory drugs, SSRIs, proton pump inhibitors, and dietary changes. Pancreatic enzyme replacement therapy (PERT) is widely used in the treatment of exocrine pancreatic insufficiency and is considered safe and well tolerated. However, mild gastrointestinal side effects such as abdominal pain, vomiting, and diarrhea may occur, often due to incorrect dosing, inappropriate dietary modifications, or coexisting gastrointestinal disorders. This is a case of worsening diarrhea that led to hospitalization in a patient with MC shortly after the initiation of PERT. Case Description/Methods: A 60-year-old woman with a history of hypertension and colonic polyps presented to her primary care provider with several weeks of chronic diarrhea, and unintentional weight loss. Notably, she reported steatorrhea. Work-up revealed a fecal pancreatic elastase level of 99 μg/g, and she was empirically started on PERT. Within 3 days of initiating PERT, patient experienced a marked worsening of diarrhea along with intensified cramping. Symptoms were refractory to loperamide and diphenoxylate-atropine. She was subsequently hospitalized after a syncopal episode and was found to be volume depleted, hypotensive, and tachycardic. Infectious and inflammatory etiologies were ruled out with a negative GI pathogen panel, C. diff assay, and negative celiac serology. Serum gastrin was normal. Abdominal imaging was unremarkable. Stool studies were consistent with secretory diarrhea. Colonoscopy with colonic biopsies demonstrated MC (lymphocytic). She was treated with intravenous fluids and electrolyte repletion. Started on Budesonide 9 mg daily. Repeat fecal elastase testing was deferred until stool consistency normalized, given the potential for falsely low results in watery diarrhea. Discussion: MC is a common cause of chronic diarrhea, often requires biopsy for diagnosis. While several medications have been implicated, PERT has not previously been associated with MC flares. In this case, symptom worsening shortly after PERT initiation suggests a potential triggering or unmasking effect. Clinicians should consider MC in patients who develop worsening diarrhea after starting PERT and pursue colonoscopy with biopsies when appropriate. This case highlights the importance of a broad differential and cautious interpretation of fecal pancreatic testing.