Ingen-Housz-Oro Saskia, Milpied Brigitte, Bensaid Benoit, Elshot Yannick, Brüggen Marie Charlotte, Starace Michela, Kaffenberger Benjamin H, Carrera Cristina, Pham-Ledard Anne, Freites-Martinez Azael, Sanchez-Pena Paola, Lebrun-Vignes Bénédicte, French Lars E, Sibaud Vincent
Dermatology Department, AP-HP, Henri Mondor Hospital.
Reference Center for Toxic Bullous Diseases and Severe Drug Reactions TOXIBUL, Créteil.
Melanoma Res. 2023 Apr 1;33(2):155-158. doi: 10.1097/CMR.0000000000000877. Epub 2023 Feb 6.
Among dermatologic adverse events induced by immune checkpoint inhibitors (ICI), drug reactions with eosinophilia and systemic symptoms (DRESS) have been very rarely reported. The objective of this study is to better define the clinical and histologic features, treatment and prognosis of ICI-related DRESS. This retrospective case series was conducted between 01 January 2015 and 31 December 2021 by the dermatology departments of five international networks involved in drug reactions. Inclusion criteria were age ≥18 years old, DRESS with Regiscar score ≥4 (probable or certain) and ICI as a suspect drug. Clinical, biologic and follow-up data were extracted from the medical charts. Thirteen patients were included. The median time to onset was 22 days (3-11). No patients had a high-risk drug introduced in the past 3 months. A majority of patients presented fever (92%), diffuse exanthema (77%) and facial edema (69%). Biologic features included hypereosinophilia in eight patients (61.5%), hyperlymphocytosis in 3 (23%), elevated liver function tests in 11 (85%, grade 1 or 2 in most cases) and renal involvement in 5 (38%). Two patients (15%) had lung involvement. PCR evidence of viral replication was detected in five patients (38.5%). Treatment involved discontinuation of the suspect ICI and systemic steroids with variable dose and duration regimens. Among the four patients in which ipilimumab + nivolumab combination therapy was initially suspected, one was rechallenged with nivolumab monotherapy with good tolerance. Five patients were switched to another anti-PD-1 plus low-dose systemic steroids, with good tolerance in four cases. No patient died because of DRESS. DRESS induced by ICI are rare and of moderate severity. A consensus for management is still pending.
在免疫检查点抑制剂（ICI）引起的皮肤不良事件中，药物性嗜酸性粒细胞增多和系统症状（DRESS）的报道非常罕见。本研究的目的是更好地界定与ICI相关的DRESS的临床和组织学特征、治疗及预后。本回顾性病例系列研究由五个参与药物不良反应的国际网络的皮肤科在2015年1月1日至2021年12月31日期间开展。纳入标准为年龄≥18岁、Regiscar评分≥4（可能或肯定）的DRESS且ICI为可疑药物。从病历中提取临床、生物学和随访数据。共纳入13例患者。发病的中位时间为22天（3 - 11天）。在过去3个月内没有患者引入高风险药物。大多数患者出现发热（92%）、弥漫性皮疹（77%）和面部水肿（69%）。生物学特征包括8例患者（61.5%）嗜酸性粒细胞增多、3例（23%）淋巴细胞增多、11例（85%，大多数情况下为1级或2级）肝功能检查升高以及5例（38%）肾脏受累。2例患者（15%）有肺部受累。5例患者（38.5%）检测到病毒复制的PCR证据。治疗包括停用可疑的ICI以及使用不同剂量和疗程方案的全身性类固醇。在最初怀疑为伊匹木单抗 + 纳武单抗联合治疗的4例患者中，1例患者再次接受纳武单抗单药治疗且耐受性良好。5例患者换用另一种抗PD - 1加低剂量全身性类固醇，4例患者耐受性良好。没有患者因DRESS死亡。ICI引起的DRESS罕见且严重程度中等。管理方面的共识仍有待达成。
