Beyond the bowel: three rare complications of upadacitinib therapy in inflammatory bowel disease

Upadacitinib, a selective Janus kinase (JAK) 1 inhibitor, is approved for the treatment of moderate-to-severe inflammatory bowel disease (IBD). Although clinical trials and real-world studies support its efficacy and overall safety profile, rare high-acuity adverse events are emerging with broader use. We describe three complications temporally associated with therapy: invasive hypopharyngeal squamous cell carcinoma (SCC), severe anemia requiring transfusion in the setting of refractory pouchitis with acute pulmonary embolism, and pulmonary blastomycosis. Although causality cannot be established, these cases highlight the need for vigilance for malignancy, hematologic abnormalities, and opportunistic infections, and emphasize careful risk stratification, individualized monitoring, and prompt evaluation of atypical symptoms.