Tehran University of Medical Sciences Case Reports in Clinical Practice 2538-2683 11 3 2026 09 28 111 115 Sina Salari Hematology and Oncology Department, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Alireza Rezvani Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Maryam Salimi Hematology and Oncology Department, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Ehsan Beyramzadeh Hematology and Oncology Department, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Farid Javandoust Gharehbagh Imam Reza Hospital, Iranian Social Security Organization (ISSO), Urmia University of Medical Sciences, Urmia, Iran. 2026 05 05 2026 07 27 Enfortumab vedotin (EV), an antibody–drug conjugate targeting Nectin-4, has become an important therapeutic option for patients with advanced urothelial carcinoma. Although cutaneous adverse events are frequently observed with EV, severe cutaneous toxicity is rare and may be associated with mortality. We describe a 77-year-old woman with metastatic urothelial carcinoma who developed a severe cutaneous adverse reaction after initiation of EV in combination with pembrolizumab for platinum-refractory disease. Within the first treatment cycle, following the initial doses of EV, she developed progressive dermatologic symptoms beginning with pruritus and erythema and rapidly evolving into widespread painful erosive and desquamative skin lesions with epidermal detachment and oral mucosal involvement. The cutaneous involvement affected approximately 70% of the total body surface area (TBSA), predominantly involving the trunk and extremities. No evidence of ocular involvement or genital mucosal lesions was identified. EV was discontinued, and the patient received systemic corticosteroids. Her clinical course was complicated by secondary infection and sepsis, and she died due to sepsis-related complications. This case highlights the diagnostic and therapeutic challenges of severe EV-associated cutaneous toxicity, particularly given its clinical overlap with other severe cutaneous adverse reactions and the frequent limitations encountered in critically ill oncology patients. Early recognition of evolving skin toxicity and prompt interruption of treatment are essential to reduce the risk of severe complications. https://crcp.tums.ac.ir/index.php/crcp/article/view/1185 https://crcp.tums.ac.ir/index.php/crcp/article/download/1185/790