Rossi Agnese, Brancorsini Donatella, Gioacchini Helena, Campanati Anna
Dermatology Department, Polytechnic University of Marche, Ancona, Marche, Italy.
Department of Biomedical Sciences, Polytechnic University of Marche, Ancona, Italy.
Skin Health Dis. 2025 Feb 14;5(1):70-74. doi: 10.1093/skinhd/vzae023. eCollection 2025 Feb.
Immune checkpoint inhibitors are a class of drugs used in cancer treatment that promote the immune system's response by blocking the inhibitor signals from tumour cells, such as programmed cell death protein 1/programmed death ligand 1 and cytotoxic T-lymphocyte associated protein 4. Despite their clinical benefit, these monoclonal antibodies unspecifically activate the immune system and can lead to the development of 'immune-related adverse events'. Cutaneous toxicities are the most frequent immune-related adverse events, reported in approximately 30-50% of patients treated with immunotherapy; the most common dermatological toxicities are represented by rash, vitiligo, pruritus and lichenoid reactions. Usually, these reactions are mild and it is not necessary to suspend immunotherapy. Potentially life-threatening skin toxicities, such as immunobullous eruption, are rare and may appear in approximately 1% of patients. In this report we describe a case of bullous pemphigoid, the most frequent bullous disease, that developed after treatment with pembrolizumab for a metastatic melanoma. The diagnosis, first suspected by the referring clinic, was confirmed by performing serology and biopsy with direct immunofluorescence. The patient was first treated with high doses of systemic corticosteroids, without suspending the immunotherapy treatment. Subsequently, due to the continuous relapses, we decided to suspend pembrolizumab and systemic corticosteroid and to begin off-label treatment with dupilumab. The following case gives cause for reflection about the management of a drug-induced disease in an immunocompromised patient, while exploring the therapeutic options.
免疫检查点抑制剂是一类用于癌症治疗的药物,通过阻断肿瘤细胞的抑制信号(如程序性细胞死亡蛋白1/程序性死亡配体1和细胞毒性T淋巴细胞相关蛋白4)来促进免疫系统的反应。尽管它们具有临床益处,但这些单克隆抗体非特异性地激活免疫系统,可能导致“免疫相关不良事件”的发生。皮肤毒性是最常见的免疫相关不良事件,在接受免疫治疗的患者中约有30%-50%会出现;最常见的皮肤毒性表现为皮疹、白癜风、瘙痒和苔藓样反应。通常,这些反应较轻,无需暂停免疫治疗。潜在危及生命的皮肤毒性,如免疫性大疱性皮疹,较为罕见,约1%的患者可能出现。在本报告中,我们描述了一例在用派姆单抗治疗转移性黑色素瘤后发生的大疱性类天疱疮病例,这是最常见的大疱性疾病。转诊诊所最初怀疑的诊断通过血清学检查和直接免疫荧光活检得以证实。患者首先接受了高剂量的全身性糖皮质激素治疗,并未暂停免疫治疗。随后,由于病情持续复发,我们决定暂停派姆单抗和全身性糖皮质激素治疗,并开始使用度普利尤单抗进行超说明书用药治疗。以下病例引发了我们对免疫功能低下患者药物性疾病管理的思考,同时也探讨了治疗选择。