Fever of Unknown Origin as an Isolated Manifestation of Ulcerative Colitis Despite Clinical and Radiographic Remission: A Case Report

Fever is a recognized manifestation of active ulcerative colitis (UC); however, isolated fever in the absence of GI symptoms or objective evidence of active colonic inflammation is exceedingly uncommon. The diagnostic challenge is amplified in immunocompromised patients receiving biologic therapy, in whom occult infection must be rigorously excluded. We present a 68-year-old woman with a history of well-controlled HIV infection and recently diagnosed UC who was initiated on vedolizumab, mesalamine, and a prednisone taper in the outpatient setting. She presented with persistent daily fevers and initial concern for an infectious etiology of pyrexia. Ulcerative colitis appeared to be well treated, with outpatient CT demonstrating resolution of colitis, and the patient denied diarrhea, abdominal pain, hematochezia, or other symptoms suggestive of active disease. An extensive infectious workup, including blood cultures, viral studies, fungal biomarkers, Lyme disease testing, tick-borne testing, and autoimmune serologies, was negative. During the laboratory evaluation, thrombocytopenia, markedly elevated inflammatory markers, and elevated D-dimer levels were noted. Despite a comprehensive multidisciplinary evaluation, no infectious, malignant, thrombotic, or rheumatologic etiology was identified. Throughout her hospital course, the patient developed sequelae of a severe inflammatory response, including atrial fibrillation. The patient's fevers were ultimately attributed to an atypical systemic inflammatory manifestation of UC. This case highlights a rare presentation of UC manifesting predominantly as fever of unknown origin (FUO) despite apparent clinical and radiographic remission. Clinicians should recognize that significant systemic inflammation may occur even in the absence of overt GI disease activity after exclusion of alternative causes.