Suspected upadacitinib-associated drug hypersensitivity mimicking disease exacerbation in ulcerative colitis

A woman in her 40s with a 4-year history of pancolitis-type ulcerative colitis (UC) was admitted with acute severe colitis unresponsive to intravenous corticosteroids. Remission was achieved with infliximab, but maintenance therapy was switched to high-dose 5-aminosalicylic acid (5-ASA) because of infliximab-induced alopecia. Two months later, she experienced a moderate relapse while on 5-ASA, and filgotinib was administered. However, her symptoms worsened, necessitating a switch to upadacitinib. Despite treatment, diarrhea and increased C-reactive protein levels persisted. Contrast-enhanced computed tomography revealed diffuse colonic inflammation, and the withdrawal of 5-ASA failed to improve her condition. With upadacitinib deemed ineffective, she was hospitalized for tacrolimus induction. Upon admission, colonoscopy demonstrated active mucosal inflammation, and stool studies excluded infection. Tacrolimus induced rapid clinical remission within 10 days. A drug-induced lymphocyte stimulation test (DLST) revealed a stimulation index of 230% for upadacitinib. Considering the clinical deterioration during upadacitinib therapy, improvement after its discontinuation, and DLST positivity, the clinical course was compatible with a suspected drug hypersensitivity to upadacitinib. This case suggests that suspected drug hypersensitivity to Janus kinase inhibitors may mimic apparent disease exacerbation in UC and should be considered when clinical deterioration persists during therapy.