PDF(Pubmed)
Abstract：
With an increasing number of patients eligible for immune checkpoint inhibitors, the incidence of immune-related adverse events (irAEs) is on the rise. Dermatologic immune-related adverse events (D-irAEs) are the most common and earliest to manifest, often with important downstream consequences for the patient. Current guidelines lack clarity in terms of diagnostic criteria for D-irAEs. The goal of this project is to better define D-irAE for the purposes of identification, diagnosis, and future study of this important group of diseases.The objectives of this project were to develop consensus guidance for an approach to D-irAEs including disease definitions and severity grading. Knowing that consensus among oncologists, dermatologists, and irAE subspecialists would be critical for usability, we formed a Dermatologic irAE Disease Definition Panel. The panel was composed of 34 experts, including oncologists, dermatologists, a rheumatologist, and an allergist/immunologist from 22 institutions across the USA and internationally. A modified Delphi consensus process was used, with two rounds of anonymous ratings by panelists and two virtual meetings to discuss areas of controversy. Panelists rated content for usability, appropriateness, and accuracy on 9-point scales in electronic surveys and provided free text comments. A working group aggregated survey responses and incorporated them into revised definitions. Consensus was based on numeric ratings using the RAND/UCLA Appropriateness Method with prespecified definitions.Following revisions based on panelist feedback, all items received consensus in the second round of ratings. Consensus definitions were achieved for 10 core D-irAE diagnoses: ICI-vitiligo, ICI-lichen planus, ICI-psoriasis, ICI-exanthem, ICI-bullous pemphigoid, ICI-Grover\'s, ICI-eczematous, ICI-eruptive atypical squamous proliferation, ICI-pruritus without rash, and ICI-erosive mucocutaneous. A standard evaluation for D-irAE was also found to reach consensus, with disease-specific exceptions detailed when necessary. Each disorder\'s description includes further details on disease subtypes, symptoms, supportive exam findings, and three levels of diagnostic certainty (definite, probable, and possible).These consensus-driven disease definitions standardize D-irAE classification in a useable framework for multiple disciplines and will be the foundation for future work. Given consensus on their accuracy and usability from a representative panel group, we anticipate that they can be used broadly across clinical and research settings.
摘要：
随着越来越多的患者有资格获得免疫检查点抑制剂，免疫相关不良事件(irAEs)的发生率呈上升趋势.皮肤免疫相关不良事件（D-irAEs）是最常见且最早出现的，通常对患者有重要的下游后果。目前的指南在D-irAE的诊断标准方面缺乏明确性。该项目的目标是更好地定义D-irAE以进行识别，诊断,以及对这一重要疾病组的未来研究。该项目的目标是为D-irAE的方法制定共识指导，包括疾病定义和严重程度分级。知道肿瘤学家之间的共识，皮肤科医生,IRAE专家对可用性至关重要，我们形成了一个皮肤病性IRAE疾病定义小组。该小组由34名专家组成，包括肿瘤学家,皮肤科医生,风湿病学家,来自美国和国际上22个机构的过敏症专家/免疫学家。使用了改进的德尔菲共识过程，由小组成员进行两轮匿名评级，并举行两次虚拟会议讨论争议领域。小组成员对内容的可用性进行了评级，适当性，电子调查中9点量表的准确性，并提供自由文本评论。一个工作组汇总了调查答复，并将其纳入修订的定义。共识是基于数字评分，使用兰德/加州大学洛杉矶分校适当性方法和预先指定的定义。根据小组成员的反馈进行修订后，所有项目在第二轮评级中获得共识。对10种核心D-irAE诊断达成共识定义：ICI-白癜风，ICI-扁平苔藓,ICI-牛皮癣,ICI-exanthem,ICI-大疱性类天疱疮,ICI-Grover's,ICI-湿疹，ICI爆发的非典型鳞状增生，ICI-瘙痒无皮疹,和ICI侵蚀皮肤粘膜。对D-irAE的标准评估也达成了共识，必要时详细说明特定疾病的例外情况。每种疾病的描述包括疾病亚型的进一步细节，症状,支持性考试结果，和三个诊断确定性水平(确定，可能,并且可能）。这些共识驱动的疾病定义在多个学科的可用框架中标准化了D-irAE分类，并将成为未来工作的基础。鉴于代表小组对其准确性和可用性的共识，我们预计它们可以在临床和研究环境中广泛使用.
