S4928 Flare, Infection, or Hypersensitivity? Recognizing Mesalamine Hypersensitivity in Ulcerative Colitis With C. difficile

Introduction: Mesalamine (5-ASA) is a first-line treatment for mild ulcerative colitis (UC), but hypersensitivity reactions occur in up to 11% of patients, with increasing reports since 2007. These reactions often mimic UC flares, presenting with symptoms such as fever, worsening diarrhea, hematochezia, chest pain, palpitations, and arthralgia. We report a case of mesalamine-induced hypersensitivity initially mistaken for recurrent UC flare and C. difficile colitis. Case Description/Methods: A 27-year-old woman was initially diagnosed with suspected UC vs Crohn’s disease at an outside facility and started on prednisone and mesalamine. She presented to the emergency department with severe bloody stools, chest pain, palpitations, flushing, weakness, and a ground-level fall. She had recently tested positive for C. difficile, untreated. On arrival, she was hypotensive and transferred to the ICU for suspected hypovolemic or septic shock. Computed tomography angiography showed colitis; troponin was elevated to 1.072 ng/mL, fecal calprotectin was 1609, and electrocardiogram showed no ischemic changes. Colonoscopy revealed pancolitis with Mayo 3 severity; esophagogastroduodenoscopy was normal. She was treated with oral vancomycin and intravenous steroids for presumed severe C. difficile colitis on UC flare. She improved, transitioned to oral prednisone, and restarted mesalamine 4.8 g daily with plans for outpatient Anti-TNF therapy. Two days post-discharge, she returned with recurrent bloody diarrhea, weakness, and chest pain, requiring ICU admission for pressor support. Troponin remained intermittently elevated (0.055–1.027 ng/mL); repeat electrocardiogram, echocardiogram, cardiac magnetic resonance imaging, and chest computed tomography angiography were unremarkable. Given her symptoms, troponin elevation, flushing, and timing, mesalamine hypersensitivity was suspected rather than myocarditis or pericarditis, both ruled out. Mesalamine was discontinued, prednisone tapered, and infliximab initiated (10 mg/kg) due to low albumin and elevated C-reactive protein. At 2 months, she was clinically well, fecal calprotectin normalized, and remained on infliximab maintenance. Discussion: Mesalamine hypersensitivity should be suspected in patients with worsening symptoms soon after therapy initiation, especially when chest pain and troponin elevation occur without evidence of cardiac disease. Recognizing this reaction early is crucial to avoid unnecessary treatments for presumed UC flare or cardiac conditions. Discontinuation of mesalamine leads to symptom resolution and allows initiation of appropriate therapy.