Apalutamide-induced life-threatening dermatologic toxicity: Clinical histopathological correlations and salvage therapies in four cases: Case report series

阿帕鲁胺诱发的危及生命的皮肤毒性:四例临床组织病理学相关性及挽救治疗:病例报告系列

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Abstract

RATIONALE: Apalutamide is a novel next-generation oral antiandrogen receptor targeting agent for castration-resistant prostate cancer. However, it is associated with skin adverse events (AEs), which have been reported in clinical trials but are not fully understood due to limited clinical data. This case report explored the clinical presentation and management of apalutamide-associated skin events through 4 representative cases. PATIENT CONCERNS: Four male patients with prostate cancer developed various skin rashes after taking apalutamide. The rashes were characterized by different manifestations, including erythema, itching, flaking, swelling, and even mucosal erosion, which significantly affected the patients' quality of life and required prompt intervention. DIAGNOSES: Based on the clinical presentation and histopathological examination of the skin, the diagnoses included eczema and severe drug rashes such as toxic epidermal necrolysis and Stevens-Johnson syndrome. The incubation periods of the rashes ranged from 1 week to 2 months, and some patients also exhibited other symptoms like elevated white blood cell count, eosinophilia, increased C-reactive protein and lactate dehydrogenase levels, lymph node enlargement, fever, liver damage, and nail dystrophy. INTERVENTIONS: All patients discontinued the use of apalutamide. They were treated with oral antihistamines and topical glucocorticoid ointment. Three cases received systemic glucocorticoid therapy, and 1 case was administered Duplizumab. The treatment strategies were adjusted according to the severity and progression of the rashes. OUTCOMES: The rashes gradually improved after the discontinuation of apalutamide and the initiation of appropriate treatment. In one case, the rash reappeared after the patient self-administered apalutamide again, but it subsided on its own after discontinuation of the drug. The symptoms of the other patients were well controlled, and no significant complications were observed during the follow-up period. LESSONS: This case report highlights the importance of recognizing and managing apalutamide-associated skin AEs. The development of these AEs appears to be dose-dependent, and early discontinuation or dose reduction of the drug is crucial for controlling the symptoms. A multidisciplinary approach involving oncologists and dermatologists is recommended to optimize the treatment strategy and maintain the patients' quality of life.

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