Shionoya Risako, Ishiyama Shun, Ono Hirohiko, Sasaki Chihiro, Sugeno Naoto, Saito Takuya, Kikuchi Takashi, Ichikawa Tomohiro, Ebina-Shibuya Risa, Sugiura Hisatoshi
Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, JPN.
Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, JPN.
Cureus. 2025 Jul 24;17(7):e88696. doi: 10.7759/cureus.88696. eCollection 2025 Jul.
Immune checkpoint inhibitor (ICI) therapy represents a significant advancement in cancer treatment through immune system activation. However, ICI presents paradoxical immunotherapy infections due to dysregulated immunity (ITI-DI). Here, we report varicella-zoster virus (VZV) meningitis in a patient with malignant pleural mesothelioma undergoing ICI therapy, characterized by disturbed consciousness and cerebrospinal fluid abnormalities. Although antiviral therapy with acyclovir effectively reduced VZV DNA to undetectable levels, persistent cerebrospinal fluid mononuclear pleocytosis was observed, which is akin to immune reconstitution inflammatory syndrome (IRIS). This case highlights the complex immunological interplay during ICI therapy, where immune activation paradoxically creates vulnerability to certain infections through mechanisms distinct from classic immunosuppression. Our findings underscore the importance of recognizing IRIS and ITI-DI as distinct entities requiring specific clinical consideration. We propose that comprehensive monitoring for atypical infections and implementation of pathogen-specific management strategies are essential components of care for patients receiving ICI therapy, particularly given the unique immunological milieu these treatments create.
免疫检查点抑制剂（ICI）疗法通过激活免疫系统，代表了癌症治疗的重大进展。然而，由于免疫失调（ITI-DI），ICI会引发矛盾的免疫疗法相关感染。在此，我们报告了一名接受ICI治疗的恶性胸膜间皮瘤患者发生水痘-带状疱疹病毒（VZV）脑膜炎，其特征为意识障碍和脑脊液异常。尽管使用阿昔洛韦进行抗病毒治疗有效地将VZV DNA降低到检测不到的水平，但仍观察到持续性脑脊液单核细胞增多，这类似于免疫重建炎症综合征（IRIS）。该病例突出了ICI治疗期间复杂的免疫相互作用，即免疫激活通过不同于经典免疫抑制的机制，反常地导致对某些感染的易感性。我们的研究结果强调了将IRIS和ITI-DI识别为需要特定临床考虑的不同实体的重要性。我们建议，对非典型感染进行全面监测并实施针对病原体的管理策略，是接受ICI治疗患者护理的重要组成部分，特别是考虑到这些治疗所创造的独特免疫环境。
