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

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.