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Introduction: Severe hypoalbuminemia (, 1gm/dL) is a rare complication of ulcerative colitis and may be both debilitating and refractory to therapy. Literature reports indicate that colectomy is curative and imply that it is the treatment of choice. We successfully treated such a patient medically. Case Description/Methods: This 40-year-old female was diagnosed with proctosigmoiditis in 2017, initially treated with oral mesalamine, then lost to care from 2018 through 2021. She presented in November 2021 with a disease flare and was shown to have pan-colitis. She was started on corticosteroids and began therapy with infliximab with initial symptomatic improvement. However, diarrhea continued, she developed increased symptoms plus anasarca during the steroid taper and was admitted. Serum albumin was 0.5 mg/dL. Inflammatory markers were elevated: C-reactive protein 103.8 mg/L and fecal calprotectin 1,126 ug/g. After infection was ruled out, colonoscopy was performed and showed extensive pseudopolyposis. Non-intestinal causes of protein loss were ruled out. Fecal alpha-1 antitrypsin levels were elevated before but not after an infliximab infusion (0.850 vs 0.110 mg/g, respectively). Despite receiving 10 mg/kg of infliximab every 6 weeks, her trough levels were undetectable and low levels of antibodies were detected. Intravenous albumin and diuretics provided some relief, but serum albumin concentration plateaued around 2.5 gm/dL. Mesalamine then was added to the regimen and the patient improved rapidly, with complete cessation of diarrhea, a rise in serum albumin concentration to 3.5 g/dL over 4 weeks, and clearance of the patient's edema. Discussion: Severe hypoalbuminemia as a result of ulcerative colitis has previously been described and may lead to treatment failure and colectomy, even during treatment with biologic agents. Some cases are not due to intestinal protein losses such as in co-existing Menetriere's disease or nephrotic syndrome. Elevated clearance rates of the biologic agents lead to subtherapeutic serum levels and antibody formation, promoting treatment failure. This case suggests that there may a role for adjunctive 5-ASA therapy. As part of the medications' anti-inflammatory effects, they decrease enteric loss of infliximab and elevate its serum levels.

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