Department of Dermatology, Duke University Medical Center, Durham, NC, U.S.A.
Department of Medicine, Duke University Medical Center, Durham, NC, U.S.A.
Br J Dermatol. 2019 Sep;181(3):580-583. doi: 10.1111/bjd.17245. Epub 2018 Dec 10.
Programmed cell death 1 (PD-1) blockade has rapidly emerged as an effective therapy for a wide variety of metastatic malignancies. It has been associated with multiple immune-related adverse effects, including cutaneous eruptions. We describe two patients with clinical and histological findings that were consistent with subacute cutaneous lupus erythematosus (SCLE) after receiving PD-1 inhibitor therapy for metastatic lung cancer. We successfully treated our first patient with systemic and topical steroids, photoprotection and hydroxychloroquine. However, he subsequently developed dermatomyositis after continuing PD-1 inhibitor therapy. Our second patient presented with a protracted course of a cutaneous eruption in spite of discontinuation of anti-PD-1 therapy and treatment with systemic corticosteroids and infliximab. This patient's SCLE resolved after the addition of topical steroids and photoprotection and discontinuation of anti-tumour necrosis factor therapy. She and her oncology team decided to pursue non-PD-1 inhibitor treatment for lung cancer owing to a lack of tumour response. We add SCLE and dermatomyositis to the growing list of autoimmune complications of PD-1 blockade. Our cases raise a number of questions, particularly in relation to the viability of continuing anti-PD-1 therapy after developing SCLE and the role of immunosuppressive therapy in patients with PD-1 inhibitor-associated connective tissue disease. What's already known about this topic? Programmed cell death 1 (PD-1) blockade, which is rapidly emerging as a therapy for a wide variety of metastatic malignancies, has been associated with multiple immune-related adverse effects. These include systemic autoimmune diseases such as colitis and thyroiditis in addition to numerous cutaneous adverse events. Cutaneous side-effects of PD-1 inhibitors most commonly reported in clinical trials include lichenoid reactions, eczematous dermatitis and vitiligo. What does this study add? We report two cases of PD-1 inhibitor-associated subacute cutaneous lupus erythematosus (SCLE), with one patient progressing to dermatomyositis with continued PD-1 inhibitor treatment. In addition to being a novel cutaneous adverse event, we also demonstrate the possibility of development of multiple autoimmune diseases in one patient, which is different from classic drug-related SCLE. We discuss the treatment challenges for patients with autoimmune skin disease receiving PD-1 inhibitor therapy.
程序性细胞死亡蛋白 1 (PD-1) 阻断已迅速成为治疗多种转移性恶性肿瘤的有效方法。它与多种免疫相关的不良反应有关,包括皮肤疹。我们描述了两例接受 PD-1 抑制剂治疗转移性肺癌后出现临床和组织学表现符合亚急性皮肤狼疮 (SCLE) 的患者。我们成功地用全身和局部类固醇、光保护和羟氯喹治疗了我们的第一例患者。然而,他在继续接受 PD-1 抑制剂治疗后随后发展为皮肌炎。我们的第二例患者尽管停止了抗 PD-1 治疗、全身皮质类固醇和英夫利昔单抗治疗,但仍出现了皮肤疹的迁延病程。在添加局部类固醇和光保护并停止抗肿瘤坏死因子治疗后,该患者的 SCLE 得到缓解。由于肿瘤无反应,她和她的肿瘤团队决定为肺癌寻求非 PD-1 抑制剂治疗。我们将 SCLE 和皮肌炎添加到 PD-1 阻断的不断增加的自身免疫并发症列表中。我们的病例提出了一些问题,特别是在发生 SCLE 后继续进行抗 PD-1 治疗的可行性以及免疫抑制治疗在 PD-1 抑制剂相关结缔组织疾病患者中的作用。关于这个话题已经知道些什么?程序性细胞死亡蛋白 1 (PD-1) 阻断作为治疗多种转移性恶性肿瘤的方法正在迅速出现,它与多种免疫相关的不良反应有关。这些包括系统性自身免疫性疾病,如结肠炎和甲状腺炎,以及许多皮肤不良反应。临床试验中最常报告的 PD-1 抑制剂的皮肤副作用包括苔藓样反应、湿疹性皮炎和白癜风。这项研究有何新发现?我们报告了两例 PD-1 抑制剂相关的亚急性皮肤狼疮 (SCLE),其中一例患者在继续 PD-1 抑制剂治疗的情况下进展为皮肌炎。除了是一种新的皮肤不良反应外,我们还在一例患者中证明了发生多种自身免疫性疾病的可能性,这与经典的药物相关的 SCLE 不同。我们讨论了接受 PD-1 抑制剂治疗的自身免疫性皮肤病患者的治疗挑战。