Abstract
Background: Cutaneous viral infections, defined as viral pathogens that either primarily affect the skin (e.g., herpesviruses, enteroviruses) or frequently produce dermatologic manifestations despite systemic tropism (e.g., HIV, SARS-CoV-2), can trigger systemic inflammatory and neurotropic responses that extend their impact to the nervous system. A growing body of evidence suggests that viruses with dermatologic manifestations may play a significant role in the pathogenesis of neurologic disorders. Summary: Although individual viruses have been studied in isolation, the skin-brain axis in viral infections remains incompletely characterized. This review synthesizes existing knowledge and highlights gaps in understanding the mechanisms linking cutaneous viral infections to neurologic disease. We explore the principal mechanisms linking viral skin infections to central and peripheral nervous system damage, including direct neuroinvasion, immune-mediated injury, and vascular or endothelial dysfunction. Particular attention is given to herpesviruses, retroviruses, enteroviruses, and respiratory viruses, which have been associated with conditions such as dementia, multiple sclerosis, myelopathies, Guillain-Barré syndrome, and the post-acute neurologic sequelae of COVID-19. Furthermore, we discuss the role of neuroinflammation in viral-associated neurodegeneration and highlight emerging evidence supporting the recombinant zoster vaccine (Shingrix) as a potential modulator of neuroinflammatory processes and a protective factor against dementia. Conclusions: Cutaneous viral infections extend beyond local skin pathology, contributing to a broad spectrum of neurologic complications through intertwined infectious and inflammatory mechanisms. A clearer understanding of how peripheral viral activity shapes central nervous system vulnerability remains a major unmet need. A multidisciplinary approach integrating dermatologic and neurologic perspectives is essential for early recognition and prevention. While observational studies suggest that zoster vaccination may reduce viral reactivation and modulate neuroinflammatory pathways, definitive evidence of neuroprotection is still lacking. Future studies should clarify causal relationships, test mechanistic hypotheses regarding skin-brain immune crosstalk, and explore vaccine-mediated neuroprotection as a novel therapeutic strategy.