A case of toxic epidermal necrolysis associated with apalutamide administration

Dear Editor, Apalutamide, a novel nonsteroidal antiandrogen agent, is used for the treatment of castration-resistant prostate cancer. Although skin rash is a common side effect of apalutamide, toxic epidermal necrolysis (TEN) has not been reported yet. Here, we report a case of apalutamide-associated TEN. A 77-year-old male patient received apalutamide (240 mg/day) for the treatment of prostate cancer, metastasized to bladder and rectum. Two weeks after initiating apalutamide, he experienced fatigue and erythema on his trunk. He continued apalutamide and visited our hospital 12 days after the onset of rash. Physical examination revealed high fever and erythema, with atypical target lesions on trunk and skin detachment over 30% of the body surface area. Hemorrhagic erosions on the lips, oral mucosa, and genital region were also observed. Nikolsky's sign was positive. Ophthalmological examination showed severe dry eyes. No leukocytosis or eosinophilia was observed. Laboratory testing revealed liver and renal dysfunction and high anti-SS-A antibody titer (1810 U/mL), in the absence of elevated antinuclear and anti-SS-B antibody titers. Histological examination showed full-thickness necrosis of the epidermis and mononuclear cell infiltration of the upper dermis (Figure 1A,B). Thus, we diagnosed TEN and all medications including apalutamide, lubiprostone, magnesium oxide, irbesartan, febuxostat, linagliptin, vonoprazan fumarate, and apixaban were discontinued. The patient's severity-of-illness score for TEN (SCORTEN)1 was 6. He was placed on mechanical ventilation for unstable hemodynamics in