P098 Worsening Colitis and Congestive Heart Failure Related to Mesalamine Use

Abstract

BACKGROUND: Five-amino salicylic acid derivatives are generally well-tolerated agents commonly used to treat ulcerative colitis. Serious reactions are rare. We present a case of paradoxical worsening of ulcerative colitis and acute heart failure in a young woman on mesalamine therapy. CASE: A 37-year old white female with a history of sleeve gastrectomy and recently diagnosed mild to moderate extensive ulcerative colitis (UC) had been on oral mesalamine for 1 month. She endorsed worsening symptoms, with 10-12 watery bowel movements daily along with 3-4 episodes of hematochezia and generalized abdominal cramps. Lack of response to prednisone prompted admission. She was found to be severely dehydrated, hyponatremic with a sodium of 132 mEq/L, and anemic with a hemoglobin of 10.2 g/dL (from normal three months earlier). Albumin was decreased at 3.1 g/dL and C-reactive protein (CRP) was elevated at 4.2 mg/dL. Stool tests for Clostridioides difficile, other bacteria, and viruses, were negative. Flexible sigmoidoscopy showed Mayo 3 colitis despite 3 days of IV methylprednisolone. Her hospital course was complicated by acute heart failure presenting as leg edema and shortness of breath. Brain natruretic peptide level was elevated at 550 pg/mL. Echocardiogram revealed global hypokinesis of the left ventricle and an estimated ejection fraction of 30-35%. Given this contraindication to anti-tumor necrosis factor agents, she was started on tofacitinib 10 mg thrice daily. Surgical consultation was also obtained. After three doses her abdominal pain improved, diarrhea decreased to 5 bowel movements daily, and CRP decreased to 1.9 mg/dL. After three days, the dose was decreased to 10 mg twice daily. On clinic follow-up 3 weeks later, she was pain-free and bowel movements were back to baseline with no blood and no diarrhea. CRP and albumin normalized. Her shortness of breath and leg edema had also resolved. Multigated acquisition scan 3 months after discharge showed resolution of left ventricle wall motion abnormalities, and a normal ejection fraction of 61%. DISCUSSION: Five-amino salicylic acids (5-ASA) are relatively safe medications. Serious reactions including pancreatitis, interstitial nephritis, blood dyscrasias, pneumonitis, and Stevens Johnson syndrome, are rare. Infrequently, paradoxical worsening of colitis is seen. This phenomenon is not well understood and there is no consistency in the presence of inflammatory markers. Confirmation requires a mesalamine challenge, which is not often feasible. Acute cardiac side effects from mesalamine are extremely uncommon, potentially serious, and appear dose-independent. The exact mechanism by which it might induce myocardial inflammation and heart failure is unclear. Existing hypotheses include: a hypersensitivity reaction due to inhibition of COX enzyme and subsequent acceleration in metabolism of arachidonic acid to lipoxygenases, humoral-mediated hypersensitivity wherein antibodies against mesalamine cross-react with the myocardium, cell-mediated hypersensitivity, and immunoglobulin E-mediated allergic reaction. Symptoms usually manifest within 2-4 weeks of starting the drug. CONCLUSION: The temporal relationship between our patient’s symptom onset and initiation of mesalamine indicates a causal relationship. Mesalamine should remain on the differential of worsening UC, and acute heart failure, after evaluating for more common causes.