Reactivation of Latent Varicella-Zoster Virus Leading to Meningitis in a Patient With Malignant Pleural Mesothelioma Undergoing Immune Checkpoint Inhibitor Therapy: A Case Report.

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.