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Peer-reviewedCC BYFrontiers in pharmacology

Case Report: Fatal varicella-zoster virus meningoencephalitis with Froin-like cerebrospinal fluid and hydrocephalus following pembrolizumab-containing chemoimmunotherapy.

  • Fangfang Shen1
  • Siyuan Fan2
  • Yanyan Wang3
  • Yan Xu4
  • Wei Guo1
4 affiliations
  1. 1Department of Respiratory Medicine, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China.
  2. 2Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  3. 3Department of Radiology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China.
  4. 4Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
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Abstract

Background

In patients receiving immune checkpoint inhibitors (ICIs), central nervous system (CNS) infections may mimic or coexist with neurological immune-related adverse events (irAEs). ICI-driven immune dysregulation has been proposed to amplify inflammation against latent pathogens ("immunotherapy infections due to dysregulated immunity", ITI-DI), but this remains a hypothesis-generating framework rather than a validated diagnosis.Case presentation

A 54-year-old man with stage IIIC lung adenocarcinoma developed a herpes zoster eruption and lumbosacral pain 7 days after the first infusion of pembrolizumab-containing chemoimmunotherapy, followed by rapidly progressive flaccid paraplegia, urinary incontinence, and declining consciousness. Intravenous acyclovir was not initiated until 20 days after rash onset. The first cerebrospinal fluid (CSF) sample was xanthochromic and coagulated spontaneously in the collection tube (Froin-like CSF), precluding protein measurement. A second lumbar puncture showed mild pleocytosis (8 cells/ μ L; 70% neutrophils) and undetectable glucose; varicella-zoster virus (VZV) DNA was detected in CSF by post-mortem targeted polymerase chain reaction. Spinal Magnetic resonance imaging (MRI) showed diffuse meningeal enhancement; follow-up cranial imaging showed acute hydrocephalus. Despite intravenous acyclovir, corticosteroids, and intravenous immunoglobulin, the patient died 43 days after pembrolizumab initiation.Conclusion

This case highlights VZV CNS infection as an important diagnostic consideration in ICI-treated patients who develop herpes zoster and neurological symptoms, because infection may mimic or coexist with a neurological irAE. The temporal relationship with pembrolizumab raises, but does not establish, the possibility that PD-1 blockade modified the inflammatory response. Prompt virological testing and adequately dosed antiviral therapy are central to management; the role of adjunctive immunomodulation remains uncertain and should be individualized.

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Cite

BibTeXRIS
BibTeX
@article{shen2026case,
  title = {{Case Report: Fatal varicella-zoster virus meningoencephalitis with Froin-like cerebrospinal fluid and hydrocephalus following pembrolizumab-containing chemoimmunotherapy.}},
  author = {Fangfang Shen and Siyuan Fan and Yanyan Wang and Yan Xu and Wei Guo},
  journal = {Frontiers in pharmacology},
  year = {2026},
  month = oct,
  doi = {10.3389/fphar.2026.1937378},
  url = {https://europepmc.org/article/MED/42908576},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Case Report: Fatal varicella-zoster virus meningoencephalitis with Froin-like cerebrospinal fluid and hydrocephalus following pembrolizumab-containing chemoimmunotherapy.
AU  - Fangfang Shen
AU  - Siyuan Fan
AU  - Yanyan Wang
AU  - Yan Xu
AU  - Wei Guo
PY  - 2026
DA  - 2026/10/07
JO  - Frontiers in pharmacology
DO  - 10.3389/fphar.2026.1937378
UR  - https://europepmc.org/article/MED/42908576
AB  - Background  In patients receiving immune checkpoint inhibitors (ICIs), central nervous system (CNS) infections may mimic or coexist with neurological immune-related adverse events (irAEs). ICI-driven immune dysregulation has been proposed to amplify inflammation against latent pathogens ("immunotherapy infections due to dysregulated immunity", ITI-DI), but this remains a hypothesis-generating framework rather than a validated diagnosis.Case presentation  A 54-year-old man with stage IIIC lung adenocarcinoma developed a herpes zoster eruption and lumbosacral pain 7 days after the first infusion of pembrolizumab-containing chemoimmunotherapy, followed by rapidly progressive flaccid paraplegia, urinary incontinence, and declining consciousness. Intravenous acyclovir was not initiated until 20 days after rash onset. The first cerebrospinal fluid (CSF) sample was xanthochromic and coagulated spontaneously in the collection tube (Froin-like CSF), precluding protein measurement. A second lumbar puncture showed mild pleocytosis (8 cells/ μ L; 70% neutrophils) and undetectable glucose; varicella-zoster virus (VZV) DNA was detected in CSF by post-mortem targeted polymerase chain reaction. Spinal Magnetic resonance imaging (MRI) showed diffuse meningeal enhancement; follow-up cranial imaging showed acute hydrocephalus. Despite intravenous acyclovir, corticosteroids, and intravenous immunoglobulin, the patient died 43 days after pembrolizumab initiation.Conclusion  This case highlights VZV CNS infection as an important diagnostic consideration in ICI-treated patients who develop herpes zoster and neurological symptoms, because infection may mimic or coexist with a neurological irAE. The temporal relationship with pembrolizumab raises, but does not establish, the possibility that PD-1 blockade modified the inflammatory response. Prompt virological testing and adequately dosed antiviral therapy are central to management; the role of adjunctive immunomodulation remains uncertain and should be individualized.
SN  - 1663-9812
ER  -