An Inverse Correlation of VZV Skin-test Reaction, but Not Antibody, with Severity of Herpes Zoster Skin Symptoms and Zoster-associated Pain

Background: Cell-mediated immunity (CMI) has been considered to be related to the development of herpes zoster (HZ). However, there have been no large-scale prospective studies on the relationship between VZV-specific CMI and severity of HZ.

Objective: We carried out a large-scale prospective cohort study to clarify the relationship between immunological factors for varicella-zoster virus (VZV) and the clinical severity of HZ.

Methods: We carried out a cohort study on VZV immunity in a population living on an island cluster, Shozu County in Japan, and examined the people who developed HZ during a median follow-up period of 2 years, with a focus on the relationship between cell-mediated and humoral immunity and the severity of skin lesions and zoster-associated pain. A total of 12,522 people over the age of 50 were enrolled in this study, and 258 registrants were diagnosed as HZ. CMI was measured by VZV skin test, and humoral immunity was assessed with serological tests (neutralization test, immunoadherence hemagglutination test, and gpELISA test) for VZV-specific antibodies.

Results: CMI to VZV assessed by VZV skin test showed a significant inverse relationship to the severity of HZ skin lesions, and also to the severity of acute and subacute pain. Furthermore, weak response to the VZV skin test was associated with a high risk of post-herpetic neuralgia. In contrast, VZV-specific antibody titer was not associated with the severity of skin lesions and zoster-associated pain.

Conclusion: VZV-specific CMI, but not humoral immunity, may play a key role in controlling the severity of HZ skin lesions and zoster-associated pain.