The association of family history of herpes zoster and the risk of incident herpes zoster: the SHEZ Study.

BACKGROUND: We investigated whether family histories of herpes zoster (HZ) are associated with the risk of incident HZ in a Japanese population. METHODS: A total of 12,522 Japanese residents aged ≥50 years in Shozu County participated in the baseline survey between December 2008 and November 2009 (the participation rate = 72.3%). They were interviewed at baseline by research physicians regarding the registrants' history of HZ. A self-administered questionnaire survey was conducted to evaluate the potential confounding factors. 10,530 participants without a history of HZ were followed up to ascertain the incidence of HZ during 3-years follow-up until the end of November 2012 with Japanese nationals. We estimated hazard ratios (HRs) of incident HZ according to first-degree family histories using the Cox proportional hazard regression after adjusting for age, sex, and other potential confounding factors. RESULTS: Compared to no HZ history of each family member, a history of brother or sister was associated with a higher risk of incident HZ while histories of father and mother were not. The multivariable HR (95%CI) of incident HZ for a history of brother or sister was 1.67 (1.04-2.69). When comparing to no family histories of all first-degree relatives, the multivariable HRs (95%CIs) were 1.34 (0.77-2.34) for a history of brother or sister alone, but 4.81 (1.78-13.00) for a history of mother plus brother or sister. As for the number of family histories, the multivariable HRs (95%CIs) were 1.08 (0.76-1.54) for one relative (father, mother, or brother or sister) and 2.75 (1.13-6.70) for two or more relatives. CONCLUSION: Family histories of mother plus brother or sister and two or more first-degree relatives were associated with a higher risk of incident HZ.

Risk of Herpes Zoster in Relation to Body Mass Index Among Residents Aged ≥50 Years: The Shozu Herpes Zoster Study.

BACKGROUND: The impact of body mass index on incidence of herpes zoster is unclear. This study investigated whether body mass index was associated with a history of herpes zoster and incidence during a 3-year follow-up, using data from a prospective cohort study in Japan. METHODS: In total, 12,311 individuals were included in the cross-sectional analysis at baseline, of whom 1,818 with a history of herpes zoster were excluded from the incidence analysis, leaving 10,493 individuals. Body mass index (kg/m2) was classified into three categories (underweight: <18.5; normal: 18.5 to <25; and overweight: ≥25). To evaluate the risk of herpes zoster, we used a logistic regression model for prevalence and a Cox proportional hazard regression model for incidence. RESULTS: Being overweight or underweight was not associated with herpes zoster prevalence at baseline. The multivariate hazard ratios of herpes zoster incidence for overweight versus normal-weight groups were 0.67 (95% confidence interval, 0.51-0.90) in all participants, and 0.57 (95% confidence interval, 0.39-0.83) in women, with no significant difference for men. CONCLUSION: Being overweight was associated with a lower incidence of herpes zoster than being normal weight in older Japanese women.

Associations of Perceived Mental Stress, Sense of Purpose in Life, and Negative Life Events With the Risk of Incident Herpes Zoster and Postherpetic Neuralgia: The SHEZ Study.

In the present population-based prospective study, we examined the associations of psychosocial factors with the incidence of herpes zoster (HZ) and postherpetic neuralgia (PHN). Data were collected from 12,359 participants (≥50 years of age) who answered a self-completed health questionnaire in the Shozu County of Kagawa Prefecture in Japan. During a 3-year follow-up between December 2008 and November 2012, HZ and PHN were diagnosed in 400 and 79 subjects, respectively. We used Cox regression analysis to estimate hazard ratios of incident HZ and PHN according to psychosocial factors, adjusting for age, sex, histories of HZ, cancer, and diabetes, smoking and drinking habits, and time from disease onset to treatment. Men with high levels of mental stress were twice as likely to be at risk for incident HZ. The risk of incident HZ was approximately 60% lower among men and women who reported a high sense of purpose in life. Women who experienced negative life events-particularly changes in their work, living environment, and relationships-had a 2- to 3-fold higher risk of incident PHN. Psychosocial factors such as perceived mental stress, sense of purpose in life, and negative life events may contribute to the development of HZ and PHN in the general population.

Incidences of Herpes Zoster and Postherpetic Neuralgia in Japanese Adults Aged 50 Years and Older From a Community-based Prospective Cohort Study: The SHEZ Study.

BACKGROUND: Many cross-sectional studies have examined the incidences of herpes zoster (HZ) and postherpetic neuralgia (PHN), but prospective studies in Japanese older adults are lacking. Therefore, we conducted a community-based prospective cohort study to determine the incidence in Japanese adults aged ≥50 years. METHODS: We recruited 12 522 participants from Shozu County, Kagawa Prefecture, between December 2008 and November 2009 and followed participants for 3 years. When a subject presented with symptoms suggestive of HZ, they were examined at collaborating medical institutions and cooperated with onset and recovery surveys (eg, measurement of varicella zoster virus-specific immunity and a pain survey). The hazard ratios (HRs) of HZ and PHN according to sex and age were analyzed by Cox regression analysis with a significance level of 5%. RESULTS: The incidence of HZ was 10.9/1000 person-years (men: 8.5/1000 person-years; women: 12.8/1000 person-years) and was significantly higher in women than in men (HR 1.5; 95% confidence interval, 1.2-1.8). The incidence of PHN was 2.1/1000 person-years (men: 1.7/1000 person-years; women: 2.4/1000 person-years), with no significant sex differences. A total of 19% of HZ cases progressed to PHN; no sex-specific difference in the proportion of PHN cases was observed. CONCLUSIONS: We clarified the accurate incidences of HZ and PHN in a population of Japanese older adults. These incidences increased with age. HZ incidence was higher in women than in men, while PHN incidence did not differ markedly between the sexes.

VZV skin-test reaction, but not antibody, is an important predictive factor for postherpetic neuralgia.

BACKGROUND: The decline of cell-mediated immunity (CMI) is thought to be related to the risk of postherpetic neuralgia (PHN) as well as herpes zoster (HZ). However, the relationship between immunological condition and the incidence of PHN is still unclear. OBJECTIVE: We conducted a large-scale prospective cohort study to clarify the relationship between immunological factors for varicella-zoster virus (VZV) and the incidence of PHN. 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 follow-up period of 3 years, with a focus on the relationship between cell-mediated and humoral immunity and the incidence of PHN. A total of 12,522 people over the age of 50 were enrolled in this study, and 401 registrants were diagnosed with HZ, including 79 PHN cases. We evaluated anatomical location and severity of skin lesion, acute pain severity, presence or absence of abnormal sensations, CMI assessed by VZV skin test, and VZV-specific antibody titer measured by serological tests. RESULTS: The incidence of PHN was significantly associated with a weak response to the VZV skin test, as well as facial or lumbosacral localization of skin rash, severe skin lesion, severe acute pain, and presence of abnormal sensations, but not related to VZV-specific antibody titer. CONCLUSION: The incidence of PHN is significantly associated with the decline of VZV-specific CMI, but not related to VZV-specific humoral immunity.

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.

The Shozu Herpes Zoster (SHEZ) study: rationale, design, and description of a prospective cohort study.

BACKGROUND: The incidence and risk factors for herpes zoster have been studied in cross-sectional and cohort studies, although most such studies have been conducted in Western countries. Evidence from Asian populations is limited, and no cohort study has been conducted in Asia. We are conducting a 3-year prospective cohort study in Shozu County in Kagawa Prefecture, Japan to determine the incidence and predictive and immunologic factors for herpes zoster among Japanese. METHODS: The participants are followed for 3 years, and a telephone survey is conducted every 4 weeks. The participants were assigned to 1 of 3 studies. Participants in study A gave information on past history of herpes zoster and completed health questionnaires. Study B participants additionally underwent varicella-zoster virus (VZV) skin testing, and study C participants additionally underwent blood testing. If the participants develop herpes zoster, we evaluate clinical symptoms, measure cell-mediated immunity and humoral immunity using venous blood sampling, photograph skin areas with rash, conduct virus identification testing by polymerase chain reaction (PCR) and virus isolation from crust sampling, and evaluate postherpetic pain. RESULTS: We recruited 12 522 participants aged 50 years or older in Shozu County from December 2009 through November 2010. The participation rate was 65.7% of the target population. CONCLUSIONS: The present study is likely to provide valuable data on the incidence and predictive and immunologic factors for herpes zoster in a defined community-based population of Japanese.