To highlight an unusual case of disseminated Varicella-zoster virus (VZV) with encephalitis in an immunocompetent adult, emphasizing diagnostic localization and differential considerations

Varicella-zoster virus (VZV) can cause meningoencephalitis and vasculopathy, particularly in immunocompromised individuals. Disseminated VZV infection with central nervous system involvement is exceedingly rare in immunocompetent adults and may present diagnostic challenges especially when the rash is absent or missed. 

A 48-year-old man presented after a generalized tonic–clonic seizure followed by significant deterioration in mental status. On arrival, he was found to be comatose and was intubated. Physical examination was remarkable for a diffuse pustular and vesicular rash involving the trunk, face, palms, and soles in a non-dermatomal distribution, as well as mucosal involvement. Acyclovir was initiated promptly, followed by laboratory and imaging workup, including EEG, lumbar puncture with CSF PCR testing, and PCR testing of the vesiculopustular rash.

EEG revealed triphasic waves with diffuse slowing. However, the patient was treated with anti-seizure medication based on clinical suspicion. CSF analysis demonstrated lymphocytic pleocytosis. Varicella PCR from both CSF and vesiculopustular rash was positive, confirming the diagnosis of disseminated varicella with encephalitis. The patient was treated with intravenous acyclovir, resulting in gradual neurological recovery.

Although uncommon in immunocompetent hosts, the presence of a generalized, non-dermatomal rash with rapid neurological deterioration is a hallmark feature of disseminated VZV. This case highlights that disseminated VZV with encephalitis can occur and should be considered among the differential diagnoses even in immunocompetent adults, particularly following transient physiologic stress. As demonstrated in this case, early recognition of the characteristic rash and prompt initiation of acyclovir are critical for favorable outcomes. Recognition of this entity is important to avoid diagnostic delays.