Qin Wei, Wu Xiaoying, Xu Qiongyuan, Deng Min, Lin Xiangling, Cai Nan, Chen Wei, Zhuo Chenya, Liu Li, Wang Li, Qian Xingyu, Tian Huan, Peng Songlin
Department of General Surgery, the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China.
Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China.
Clin Immunol. 2025 Sep;278:110534. doi: 10.1016/j.clim.2025.110534. Epub 2025 May 28.
Immune-related adverse events (irAEs) include a rare, idiosyncratic but potentially life-threatening drug reaction with eosinophilia and systemic symptoms (DRESS), characterized by exanthem, fever, as well as hematologic and visceral organ involvement.
We describe a 54-year-old man under the novel sequential treatment including all-trans retinoic acid (ATRA) and programmed death protein 1(PD-1) antibody (Tislelizumab) for advanced intrahepatic cholangiocarcinoma (iCCA). He was found to have Tislelizumab-induced DRESS syndrome during adjuvant therapy, and also showed the evidence of IgG4-related lymphadenopathy (IgG4-RLAD) as well as Epstein-Barr virus (EBV) infection in the absence of hemophagocytic lymphohistiocytosis (HLH) and T cell lymphoma. The patient's clinical status was successfully ameliorated through the administration of corticosteroids, intravenous immunoglobulin (IVIG), and antiviral agents, demonstrating a positive response to the treatment protocol. He was the first-ever case report of Tislelizumab-induced DRESS syndrome in the context of IgG4-RLAD with an exploration of potential mechanisms. Furthermore, we found that a somatic fibroblast growth factor receptor (FGFR) 3 p.P774L mutation at the frequency of 1.96 % was detected in his iCCA tissue.
These findings indicated that this novel therapy, based on ARTA and PD-1 antibody, is more effective and could guide the clinical application of PD-1 antibody in the iCCA patients with elevated IgG4. Human leukocyte antigen (HLA) typing assay might help to screen the potential susceptible individuals to avoid immune checkpoint inhibitors (ICIs)-induced DRESS syndrome.
免疫相关不良事件（irAEs）包括一种罕见的、特异质性但可能危及生命的伴有嗜酸性粒细胞增多和全身症状的药物反应（DRESS），其特征为皮疹、发热以及血液学和内脏器官受累。
我们描述了一名54岁男性，正在接受包括全反式维甲酸（ATRA）和程序性死亡蛋白1（PD-1）抗体（替雷利珠单抗）的新型序贯治疗，用于晚期肝内胆管癌（iCCA）。他在辅助治疗期间被发现患有替雷利珠单抗诱导的DRESS综合征，并且在没有噬血细胞性淋巴组织细胞增生症（HLH）和T细胞淋巴瘤的情况下，还表现出IgG4相关淋巴结病（IgG4-RLAD）以及爱泼斯坦-巴尔病毒（EBV）感染的证据。通过给予皮质类固醇、静脉注射免疫球蛋白（IVIG）和抗病毒药物，患者的临床状况得到成功改善，表明对治疗方案有积极反应。这是在IgG4-RLAD背景下替雷利珠单抗诱导的DRESS综合征的首例病例报告，并对潜在机制进行了探索。此外，我们发现他的iCCA组织中检测到体细胞成纤维细胞生长因子受体（FGFR）3 p.P774L突变，频率为1.96%。
这些发现表明，这种基于ARTA和PD-1抗体的新型疗法更有效，可指导PD-1抗体在IgG4升高的iCCA患者中的临床应用。人类白细胞抗原（HLA）分型检测可能有助于筛查潜在的易感个体，以避免免疫检查点抑制剂（ICIs）诱导的DRESS综合征。
