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

Our plain-English summary of Reactivation of Latent Varicella-Zoster Virus Leading to Meningitis in a Patient With Malignant Pleural Mesothelioma Undergoing Immune Checkpoint Inhibitor Therapy: A Case Report, by R. Shionoya, S. Ishiyama, H. Ono, et al (Curēus, 2025).

The study

• Authors: R. Shionoya, S. Ishiyama, H. Ono, C. Sasaki, N. Sugeno, T. Saito, T. Kikuchi, T. Ichikawa, R. Ebina-Shibuya, H. Sugiura
• Journal: Curēus
• Published: 2025;17(7):e88696
• Type of article: Case report
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

Copyright © 2025, Shionoya et al.

In plain English

This was a case report from Tohoku University in Sendai, Japan, describing one patient. A 73-year-old man with epithelial malignant pleural mesothelioma had received three courses of ipilimumab and nivolumab, a combination of immune checkpoint inhibitor drugs. Six days after his last nivolumab dose he developed disturbed consciousness, unsteady gait, headache and fever. He had no skin rash at first. His spinal fluid tested positive for varicella-zoster virus DNA, and doctors diagnosed varicella-zoster virus meningitis. He was treated with intravenous acyclovir. A shingles rash appeared on day two, and his neurological symptoms had improved by day nine. Spinal fluid tested negative for the virus on days 16 and 23, but its cell count stayed raised: 102 cells per microliter on day 23 and 67 on day 30, against a normal range of 0 to 5. Mesothelioma treatment was stopped, and he stayed relapse-free for over a year. The authors concluded that the lasting inflammation raised the possibility that immune dysregulation (which they call ITI-DI or IRIS-like mechanisms) contributed to the illness. The article does not discuss asbestos exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: case report (single patient)
• Who was studied: One 73-year-old man with epithelial malignant pleural mesothelioma, treated at Tohoku University (Sendai, Japan). He was not using steroids or immunosuppressive drugs, had no history of diabetes, HIV or apparent shingles, and had not had a shingles vaccination.
• Exposure: Immune checkpoint inhibitor therapy: three courses of ipilimumab and nivolumab combination therapy. The article reports no asbestos or fiber exposure.
• Main results:
  • In the patient, the cerebrospinal fluid tested positive for varicella-zoster virus DNA, confirming VZV meningitis. The fluid also showed elevated opening pressure (over 300 mmH2O), pleocytosis with mononuclear predominance, and raised protein.
  • On the second day of hospitalization, after intravenous acyclovir was started, a typical herpes zoster rash appeared on the patient's lower jaw area, neck and right thigh.
  • By day nine the patient's skin lesions had crusted and his neurological symptoms had improved significantly.
  • The patient's spinal fluid was negative for VZV DNA on days 16 and 23, but pleocytosis (raised cell count) persisted. Cell counts per microliter were 37 on day 1, 94 on day 16 and 102 on day 23. After antiviral therapy stopped, the count decreased to 67 on day 30, which was still above the reference range of 0 to 5.
  • The patient's mesothelioma treatment was stopped after meningitis began. He remained relapse-free and under observation for over one year.
• The authors' conclusion: The authors concluded that the persistent spinal fluid pleocytosis and unusual clinical course raised the possibility that ITI-DI (immunotherapy infections due to dysregulated immunity) or IRIS-like (immune reconstitution inflammatory syndrome-like) mechanisms contributed to the disease. They called for early diagnostic testing, including PCR for viral pathogens, in patients treated with immune checkpoint inhibitors who develop neurological symptoms.
• Limitations the authors state:
  • The authors state that more cases are needed to clarify whether the risk of infection, including VZV, differs between immune checkpoint inhibitor monotherapy and combination therapy.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, checkpoint inhibitors, Immunotherapy.

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