Table 1_Risk factors for cutaneous immune-related adverse events: a systematic scoping review.docx

ObjectiveTo comprehensively summarize risk factors and explore potential mechanisms associated with cutaneous immune-related adverse events (cirAEs) in cancer patients treated with immune checkpoint inhibitors (ICIs).
MethodConducted in accordance with the PRISMA-ScR guidelines, this review included studies published in English and Chinese that investigated cirAEs risk factors in cancer patients receiving ICIs. A scoping review with systematic search criteria was conducted using PubMed, Embase, Cochrane, Web of Science, ProQuest, CINAHL, CNKI, Wanfang Data, VIP, and SinoMed from database inception to December to December 31, 2023.
Results4905 studies were identified and 50 studies were included in this review, encompassing 198,514 participants. Among these, 12.5% experienced at least one cirAEs, with maculopapular rash, pruritus, and unspecified rash being the most common subtypes. A total of 68 distinct risk factors were identified from these studies, categorized into three primary risk domains: demographic factors, clinical characteristics, and biomarkers, including age, gender, BMI, smoking history, specific treatment regimens (e.g., camrelizumab), tumor type (e.g., melanoma), eosinophil count, and cytokine levels, among others. The odds ratios (OR) for reported risk factors demonstrated significant associations with specific cirAEs subtypes, with melanoma patients exhibiting higher risk for multiple cirAEs subtypes. However, there was significant variability in the quality of reporting for these risk factors, emphasizing the need for improved consistency and accuracy in data reporting.
ConclusionsA variety of demographic, clinical, and biomarker-related factors contribute to the development of cirAEs. Characterizing these risk factors can address clinical needs for cirAE identification, while further mechanistic studies are needed to enhance management strategies. However, there is a limited amount of high-quality prospective evidence on these risk factors, and the quality of reporting on immunotherapy-related adverse events is inconsistent. Future research should focus on validating clinically valuable risk factors and interrogating mechanisms underlying cirAEs emergence.

**研究目的**：全面总结接受免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）治疗的癌症患者皮肤免疫相关不良事件（cutaneous immune-related adverse events, cirAEs）的相关危险因素，并探讨其潜在发病机制。
**研究方法**：本综述遵循PRISMA范围综述扩展指南（PRISMA-ScR）开展，纳入了已发表的探讨接受免疫检查点抑制剂治疗的癌症患者皮肤免疫相关不良事件危险因素的中英文文献。本研究采用系统检索策略开展范围综述，检索时限为各数据库建库至2023年12月31日，检索数据库包括PubMed、Embase、Cochrane图书馆、Web of Science、ProQuest、CINAHL、中国知网（CNKI）、万方数据、维普资讯（VIP）及中国生物医学文献服务系统（SinoMed）。
**研究结果**：本综述共检索到4905篇文献，最终纳入50项符合要求的研究，涉及198514名受试者。其中12.5%的患者发生过至少1次皮肤免疫相关不良事件，最常见的亚型为斑丘疹、瘙痒及未特指皮疹。本研究从纳入文献中共识别出68种不同的危险因素，可归为三大类风险领域：人口统计学特征、临床特征及生物标志物，具体包括年龄、性别、体重指数（Body Mass Index, BMI）、吸烟史、特定治疗方案（如卡瑞利珠单抗）、肿瘤类型（如黑色素瘤）、嗜酸性粒细胞计数及细胞因子水平等。已报道的危险因素的比值比（odds ratios, OR）显示其与特定皮肤免疫相关不良事件亚型存在显著关联，其中黑色素瘤患者发生多种皮肤免疫相关不良事件亚型的风险更高。但现有研究对这些危险因素的报告质量存在显著异质性，提示亟需提升数据报告的一致性与准确性。
**研究结论**：多种人口统计学、临床及生物标志物相关因素均可影响皮肤免疫相关不良事件的发生。明确此类危险因素可满足皮肤免疫相关不良事件临床识别的实际需求，但仍需开展进一步机制研究以优化其管理策略。然而，目前关于此类危险因素的高质量前瞻性证据较为匮乏，且免疫治疗相关不良事件的报告质量参差不齐。未来研究应聚焦于验证具有临床价值的危险因素，并深入解析皮肤免疫相关不良事件的发病机制。