Exploring the Potential Stimuli and Deterrents of Varicella-Zoster Viral Reactivation: A Scoping Review

The varicella-zoster virus (VZV) causes a pruritic rash known as chickenpox during primary infection, which can become latent in neural tissue and reactivate as a painful rash called herpes zoster (HZ, also called shingles), often resulting from an age-related decline in cell-mediated immunity. A common complication following HZ is postherpetic neuralgia (PHN), a severe and often chronic neuropathic pain within the site of the initial HZ outbreak. The recombinant Shingrix and live attenuated Zostavax vaccines were created to provide immunity against viral reactivation. The objective of this scoping review is to evaluate the literature to understand the additional factors that contribute to VZV reactivation and can result in HZ and PHN. This review also aims to understand the vaccine efficacy (VE) of Shingrix and Zostavax in reducing VZV reactivation and PHN compared to non-vaccinated individuals. This study used the PubMed database to identify studies. Search terms included chickenpox, postherpetic neuralgia, reactivation stimuli, Shingrix, shingles, varicella zoster, "varicella zoster viral reactivation", and Zostavax. The exclusion criteria were literature reviews, meta-analyses, case reports, and gray literature. Only studies published in English between January 1, 2018, and April 1, 2023, were included. There were 17 studies extracted that focused on VZV reactivation stimuli, which indicated that comorbidities/disease stress, unrelated medical interventions, lifestyle/environmental assault, and depression were potential inciting factors of viral reactivation. There were two studies regarding the effect of body mass index (BMI) on HZ risk with conflicting results; one found a higher correlation of HZ with an overweight BMI, while the other found no correlation with a higher BMI and instead reported a higher HZ incidence in those with a normal BMI. There were 15 studies covering VE for HZ prevention and seven studies for VE against PHN, with some overlapping studies measuring both data values. Overall, the findings revealed that vaccinated individuals had consistently lower incidence rates of HZ and PHN compared to their non-vaccinated counterparts, as well as a consistently superior VE in Shingrix and a notable decline in VE with age. Three articles with data regarding PHN pathophysiology suggested that it is more likely caused by neurological damage with some genetic influence rather than further viral reactivation. While further investigation into the relationship between viral reactivation and risk factors is warranted based on this analysis, the results suggest that immunosuppression that has been previously linked to or correlated with these variables likely also contributes to VZV reactivation and PHN.