S4958 First Reported Case of Upadacitinib-Induced Cytomegalovirus Viremia and Pneumonitis in Ulcerative Colitis

Introduction: Upadacitinib is an immunosuppressant that selectively inhibits Janus Kinase 1. It may elevate the risk of opportunistic infections and viral reactivations. To date, no instances of upadacitinib-induced cytomegalovirus (CMV) viremia or pneumonitis in the presence of inflammatory bowel disease (IBD) have been reported in the literature. Case Description/Methods: The patient is a 59-year-old man with a medical history of ulcerative colitis managed with upadacitinib (on his fourth week of treatment), primary sclerosing cholangitis, polymyalgia rheumatica managed with a stable, chronic dose of Prednisone and prostate cancer status post-brachytherapy, who presented with a 9-day history of persistent fever, chills, night sweats, shortness of breath, and a nonproductive cough. A computed tomography angiogram of the chest revealed bilateral pneumatoceles, pulmonary densities, and a right-sided posterior subpleural density. A magnetic resonance cholangiopancreatography demonstrated diffuse irregular intrahepatic bile ducts, more prominent in the left lobe than the right, consistent with primary sclerosing cholagitis. Additionally, there was colonic wall thickening, most prominent in the ascending colon, hepatic flexure, and proximal transverse colon, consistent with ulcerative colitis. A white blood cell scan revealed an atypical infection in the bilateral lung bases. Subsequent complete blood count with differential revealed 59% lymphocytes, suggesting a viral etiology. Inflammatory markers included an erythrocyte sedimentation rate of 40 mm/hr, C-reactive protein of 4.8 mg/dL, and stool calprotectin of 734 µg/g. CMV DNA polymerase chain reaction was markedly elevated at 119,000 IU/mL, confirming CMV viremia. Valganciclovir was initiated. A Fiberoptic bronchoscopy with bronchoalveolar lavage was performed. Bronchoalveolar lavage cytology from the right lower lobe showed rare cells with cytopathic changes suggestive of CMV, consistent with CMV pneumonitis. The patient’s symptoms continued to improve on valganciclovir. Discussion: CMV viremia and pneumonitis are recognized complications of upadacitinib therapy; however, these conditions are exceedingly rare in the context of IBD. The current literature on upadacitinib-induced CMV infections in IBD remains limited. As this case represents a novel presentation, further epidemiologic studies are warranted to assess the incidence, risk factors, and mechanisms of upadacitinib-induced CMV reactivation in IBD patients.