Subacute cutaneous lupus erythematosus and dermatomyositis associated with anti-programmed cell death 1 therapy
Subacute cutaneous lupus erythematosus and dermatomyositis associated with anti-programmed cell death 1 therapy
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DOI：
10.1111/bjd.17245
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发表时间：
2019-09-01
影响因子：
10.3
通讯作者：
Cardones, A. R.
中科院分区：
文献类型：
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作者：
Marano, A. L.;Clarke, J. M.;Cardones, A. R.
程序性细胞死亡1 （PD-1）阻断已迅速成为各种转移性恶性肿瘤的有效治疗方法。它与多种免疫相关的不良反应有关，包括皮肤皮疹。我们描述了两例患者在接受PD-1抑制剂治疗转移性肺癌后，其临床和组织学表现与亚急性皮肤红斑狼疮（SCLE）一致。我们成功地用全身和局部类固醇、光保护和羟氯喹治疗了第一位患者。然而，在继续PD-1抑制剂治疗后，他随后出现皮肌炎。尽管停止了抗pd -1治疗和全身皮质类固醇和英夫利昔单抗治疗，我们的第二例患者仍然出现了长期的皮肤皮疹。该患者的SCLE在添加局部类固醇和光保护以及停止抗肿瘤坏死因子治疗后消退。由于缺乏肿瘤反应，她和她的肿瘤团队决定寻求非pd -1抑制剂治疗肺癌。我们将SCLE和皮肌炎添加到PD-1阻断的自身免疫性并发症的不断增长的列表中。我们的病例提出了许多问题，特别是在发生SCLE后继续抗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。关于这个话题我们已经知道了什么？程序性细胞死亡1 （PD-1）阻断正在迅速成为一种治疗多种转移性恶性肿瘤的方法，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，以及许多皮肤不良事件。临床试验中最常报道的PD-1抑制剂的皮肤副作用包括类地衣反应、湿疹性皮炎和白癜风。这项研究补充了什么？我们报告了两例PD-1抑制剂相关的亚急性皮肤红斑狼疮（SCLE），其中一名患者在持续PD-1抑制剂治疗后进展为皮肌炎。除了作为一种新的皮肤不良事件外，我们还证明了在一名患者中发生多种自身免疫性疾病的可能性，这与经典的药物相关SCLE不同。我们讨论了自身免疫性皮肤病患者接受PD-1抑制剂治疗的治疗挑战。
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.