肿瘤患者PD-1治疗后出现大疱性类天疱疮1例

抗肿瘤药物程序性死亡受体1(programmed death-1,PD-1)/程序性死亡配体1(programmed death ligand 1,PD-LI)免疫检查点抑制剂的应用常可引起免疫相关不良反应(immune-related adverse events,irAE).本文报道1例胆管细胞癌患者使用PD-1治...     

二肽基肽酶4抑制剂相关大疱性类天疱疮的研究进展

大疱性类天疱疮（BP）是一种自身免疫性表皮下大疱病，越来越多的研究发现降糖药二肽基肽酶4抑制剂（DPP-4i)）有诱发BP的风险。对新发或是突然加重的BP并发糖尿病患者，应警惕DPP-4i诱发的可能性，该文就二肽基肽酶4抑制剂相关BP的研究进展进行综述。     

PD-1抑制剂致严重皮肤免疫相关不良反应1例

患者女,57岁,全身出现弥漫性红斑、丘疹、斑丘疹、脱屑伴痒20余天。患者患“非霍奇金淋巴瘤”使用程序性死亡蛋白-1(programmed cell death 1,PD-1)抑制剂治疗后全身出现弥漫性红斑、丘疹、斑丘疹伴脱屑,瘙痒明显。在治疗初期,使用糖皮质激素能控制病情,但随着激素剂量减量,皮疹逐渐向非典型脓疱型银屑病样皮损表型转化,后加用甲氨蝶呤及阿维A治疗后病情好转,皮损逐渐消退。     

PD-1/PD-L1抑制剂治疗皮肤恶性肿瘤研究进展

近年来免疫检查点抑制剂程序性细胞死亡蛋白1及其配体1(PD-1/PD-L1)是皮肤恶性肿瘤治疗的重要靶点。本文就PD-1/PD-L1抑制剂在治疗皮肤恶性肿瘤的研究进展作一综述。     

恶性黑素瘤免疫检查点抑制疗法研究进展

【摘要】 免疫检查点抑制剂在过去几年中已成为许多恶性黑素瘤患者的重要治疗选择，其旨在恢复并促进效应T细胞特异性识别和杀伤肿瘤细胞的功能，系统性增强全身的抗肿瘤免疫反应，对于手术切除后具有高复发风险或处于疾病晚期（不可切除或存在转移）的患者都是较好的治疗选择。目前免疫检查点抑制的主要目标是程序性死亡受体 1与细胞毒性T淋巴细胞相关抗原4，它们分别是中枢和外周免疫耐受的两个关键受体。本文主要讨论不同免疫检查点抑制剂的临床效应、可能存在的药物反应性预测标志物与相关不良反应。     

诱导性协同共刺激分子及程序性死亡受体1在大疱性类天疱疮皮损中的表达及意义

【摘要】 目的 通过检测滤泡辅助性T细胞（Tfh）相关分子诱导性共刺激分子（ICOS）及程序性死亡受体1（PD?1）在大疱性类天疱疮（BP）患者皮损中的表达，探讨Tfh在BP发病机制中的作用。方法 收集大连市皮肤病医院2014—2017年间确诊的BP患者石蜡组织标本21份，其中女7例，男14例，平均年龄72.57岁。应用免疫组化SP法检测BP皮损中ICOS与PD?1的表达，以10例正常皮肤组织作为对照组。结果 ICOS、PD?1在BP皮损中均主要表达于表皮基底层、棘细胞层、颗粒层、角质层，以棘细胞层表达最为显著，细胞质、细胞核均见表达，偶见细胞膜表达，真皮层炎症细胞中亦有表达；正常皮肤组织中ICOS、PD?1表达少见。BP组ICOS表达率为85.71%（18/21），PD?1表达率为47.62%（10/21），均高于正常对照组（均为0），差异有统计学意义（P值分别＜0.001、＜0.05）。结论 Tfh细胞相关分子ICOS、PD?1在BP发病机制中可能发挥重要作用。     

英夫利西单抗治疗重度斑块状银屑病的疗效和安全性及其对PD-1、PD-L1表达的影响

目的:探讨英夫利西单抗治疗重度斑块状银屑病的疗效和安全性及其对银屑病皮损组织中程序性死亡蛋白1（PD-1）及程序性死亡蛋白配体1（PD-L1）表达的影响。方法:2019年2-4月收集就诊于上海市皮肤病医院的17例重度斑块状银屑病患者,在第0、2、6、14、22、30、38、46周给予5 mg/kg英夫利西单抗静脉滴注治...     

中国黑素瘤研究进展与新治疗策略

【摘要】 尽管黑素瘤发病率正快速增长,但其在中国所占比例低,肿瘤科医生关注少。黑素瘤患者首诊科室主要是皮肤科,皮肤科医生能综合分析临床诊断、病理诊断、外科治疗和药物治疗,对黑素瘤的诊治具有独特优势。中国学者近年在黑素瘤的细胞死亡调控、表观遗传学修饰、靶向药物耐药、肿瘤微环境和肿瘤免疫调控等方面已获得很大进展。中国独有的一类新药干扰素α-1b不仅可用于Ⅱ、Ⅲ期高危黑素瘤的辅助治疗,对Ⅳ期黑素瘤也有很好的疗效,不良反应远低于干扰素α-2b。与白色人种不同,亚洲人皮肤黑素瘤以肢端型及黏膜型为主。以干扰素α-1b为基础制定联合治疗策略,探索其与程序性死亡受体-配体1抑制剂、靶向药物或血管生成抑制剂等的联合治疗方案,正在为挽救Ⅳ期黑素瘤患者带来希望。     

免疫检查点抑制剂的皮肤并发症及治疗进展

免疫检查点抑制剂包括细胞毒性T淋巴细胞抗原4抑制剂,如易普利姆玛以及程序性死亡受体1/程序性死亡受体-配体1抑制剂nivolumab、派姆单抗和atezolizumab.随着免疫检查点抑制剂在肿瘤治疗领域应用的逐渐增加,免疫疗法相关不良反应已引起重视,其中最常见是皮肤并发症,主要包括以斑丘疹为代表的皮疹以及瘙痒症等疾病.临床上,对不同皮肤并发症早期诊断和制定正确的治疗方案十分重要,对常出现的以斑丘疹为代表的皮疹、瘙痒症等皮肤并发症应根据皮损的严重程度和临床分级进行监控和管理.     

程序性细胞死亡蛋白1及其配体通路在特发性炎症性肌病中的研究进展

【摘要】 程序性细胞死亡蛋白（PD-1）与其配体（PD-L1）特异性结合后，具有共抑制/共刺激的免疫调控作用，可抑制T细胞活化、增殖及细胞因子分泌，参与肿瘤免疫、自身免疫及免疫耐受等。本文综述PD-1/PD-L1信号通路的组成结构、调控机制，以助于理解特发性炎症性肌病合并恶性肿瘤的免疫机制，寻找潜在的治疗靶点和诊断策略。     

药物相关性大疱性类天疱疮研究进展

药物相关性大疱性类天疱疮(drug-associated bullous pemphigoid, DABP)特指应用特定药物诱发的一种特殊类型的类天疱疮,其临床表现、组织学或免疫病理特征与特发性大疱性类天疱疮相同或相近。近年由药物导致大疱性类天疱疮的报道增多,本文就DABP的研究进展进行综述。     

Severe bullous pemphigoid associated with pembrolizumab therapy for metastatic melanoma with complete regression

Bullous pemphigoid (BP) is considered to be a humorally mediated autoimmune disease, but autoreactive T‐cells and T‐regulatory cells (Tregs) have also been implicated in this disease. Tregs and the programmed death‐1 (PD‐1) : programmed death ligand (PD‐L) pathway are both critical in terminating immune response, and elimination of either can result in breakdown of tolerance and development of autoimmunity. We report a patient with metastatic malignant melanoma (MM), who underwent pembrolizumab (anti‐PD‐1) therapy following unsuccessful treatment with ipilimumab [anti‐cytotoxic T‐lymphocyte‐associated protein (CTLA)‐4]. The patient developed BP with increasing serum titres of anti‐BP180 IgG autoantibodies and increasing disease severity during pembrolizumab therapy. High doses of corticosteroids and methotrexate were needed to control the BP. Following the termination of pembrolizumab therapy, imaging showed complete regression of all metastatic sites. This result may indicate a crucial role for T‐cell suppressive activity in controlling and preventing BP.     

Bullous pemphigoid associated with anti-programmed cell death protein 1 and anti-programmed cell death ligand 1 therapy: A case series of 13 patients

We present a case series of 13 patients, the first Australian single-centre study of bullous pemphigoid (BP) associated with immune checkpoint inhibitors (ICI): cytotoxic T-lymphocyte antigen (CTLA4) and programmed cell death receptor (PD1) inhibitors. All our patients achieved adequate control of BP with a combination of treatments including oral prednisolone, intravenous immunoglobulin, rituximab and omalizumab. The majority of patients ceased or interrupted immunotherapy treatment upon diagnosis of BP and greater tumour progression was seen in the cohort who ceased immunotherapy.     

Bullous Pemphigoid in a Renal Transplant Recipient

Bullous pemphigoid (BP) is an autoimmune disease with chronic, recurrent bullous eruptions. BP has been reported to be associated with drugs, physical stimuli, malignancies, and immune abnormalities. Its association with renal transplant is rare and only four cases have been reported. We present a case of BP in a 52-year-old man with chronic hepatitis B and C infection who underwent a cadaveric renal transplant 13 years earlier. His graft was still functioning well when BP appeared. The occurrence of BP in our patient might be a result of drugs (furosemide or tacrolimus), viruses, or renal allograft. As the patient was receiving regular T-cell immunosuppressant therapy, his BP lesions were recalcitrant to corticosteroid treatment. We discuss the pathogenesis and treatment of such patients.     

Incidence and mortality of bullous pemphigoid in France

A major increase in the incidence of BP has been recently reported in the United Kingdom. In addition, there are some controversies about the over-mortality of BP patients. The primary objective was to reevaluate the incidence of BP in France as compared with that we estimated 15 years ago. The secondary objective was to assess mortality of BP patients. BP incidence was retrospectively estimated from all BP cases diagnosed between January 2000 and December 2005 in three French regions with a total population of 3.858 million inhabitants. BP mortality was assessed from a prospective cohort accrued during the same time period. A total of 502 incident BP patients (mean age: 82.6±8.8 years) were identified. Overall estimated incidence was 21.7 cases per million persons per year (95%CI:19.8-23.7 cases per million persons per year), which is about 3-fold higher than the incidence that we estimated 15 years ago. In the population aged 70 years or above, BP incidence was 162 cases per million per year (95%CI:147-177 cases per million per year). The overall 1-year survival rate was 62% (95% CI: 56-67%). The risk of death for BP patients was more than six times greater than that for the general population (SMR:6.60; 95%CI:5.47-7.90). The incidence of BP in France has increased 3-fold in the last 15 years. BP is associated with high mortality.     

Inmunoterapia en cáncer cutáneo no melanoma

Immunotherapy is emerging as a new and promising treatment for a great variety of tumors, including nonmelanoma skin cancer. Checkpoint inhibitors —antibodies that block proteins that regulate the immune system— mainly target the surface protein CTLA-4 (cytotoxic T-lymphocyte-associated antigen 4) and the PD-1/PD-L1 (programmed cell death protein 1/PD-ligand 1) axis. We review the CTLA-4 and PD-1/PD-L1 pathways and current evidence supporting checkpoint inhibitor therapy in the main types of nonmelanoma skin cancer.     

The life-threatening eruptions of immune checkpoint inhibitor therapy

Immune checkpoint inhibitors (ICPi) have emerged as a new frontier of cancer therapy. Although monoclonal antibodies to cytotoxic T-lymphocyte associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1) have revolutionized oncologic management, these agents may result in a spectrum of immune-related adverse events (irAE) of which dermatologic toxicities are among the most frequent. Prompt recognition and management of irAE is essential for dermatologists caring for the expanding population of cancer patients exposed to these drugs. Cutaneous toxicities range from mild cases to severe and life-threatening presentations that may cause significant morbidity and mortality. This review provides an overview of severe cutaneous adverse reactions (SCARs) that may develop during ICPi therapy, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). In addition, immunobullous disorders, erythroderma, neutrophilic dermatoses, and cutaneous eruptions associated with systemic manifestations are discussed.