Oral Herpes

Risk of herpes zoster and family history: A Meta-analysis of case–control studies Lai YC, Yew YW

Little is known about reactivation of latent varicella zoster virus as herpes zoster in individuals with no underlying immunosuppression. Although cognitive and behavioral disturbances following herpes encephalitis are often severe, improvement can occur over an extended period, and chronic residual sequelae may be relatively mild. Primary varicella infection (chickenpox) was not reliably distinguished from smallpox until the end of the 19th century. Aims and Objectives: We aimed to conduct a meta-analysis to evaluate the association between HZ infection and family history. The patients with post-herpetic neuralgia were enrolled at the Pain Clinic of the Policlinico Tor Vergata in Rome, Italy, within 1 year from the onset of acute zoster. Materials and Methods: Observational studies were searched from MEDLINE, EMBASE, and Cochrane Central Register from inception to April 15, 2015. Subsequent laboratory studies of the virus led to the development of a live attenuated varicella vaccine in Japan in the 1970s.

To estimate the pooled odds ratio, random-effects model of DerSimonian and Laird was used. Further and larger prospective cohort studies are needed to ascertain whether a family history of herpes zoster is really an independent predictor of zoster in different geographical settings. A dose-response meta-analysis with studies that reported appropriate data were done using the generalized least squares for trend method. Like other herpesviruses, VZV has the capacity to persist in the body after the primary (first) infection as a latent infection. Cases with HZ were 3.03 (95% confidence interval [CI]: 1.86–4.94, P < 0.001) and 3.27 (95% CI: 1.75–6.10, P < 0.001) times more likely to report the first-degree relatives and total relatives with a history of HZ, respectively. 82:1007–1011, 2010. Conclusions: This meta-analysis demonstrated that family history is a significant risk factor for HZ infection. The virus is believed to have a short survival time in the environment. The Meta-analysis of Observational Studies in Epidemiology guidelines were followed in conducting this study.[9] A systematic and quantitative synthesis of all studies that evaluated the relationship between HZ infection and family history of HZ was planned a priori. A comprehensive database search was performed independently by using MEDLINE, EMBASE, and Cochrane Central Register. The following search criteria were used: “Herpes zoster” [MeSH] and “family history” [MeSH]. Further replication occurs in the viscera, followed by a secondary viremia, with viral infection of the skin. All abstracts were evaluated based on the inclusion criteria to determine eligibility for meta-analysis. Additional studies were identified from manual searches of references in retrieved articles. The following inclusion criteria were used to select original studies for the analysis: Cohort, case–control, or cross-sectional study design; analysis of the association between HZ infection and family history of HZ (i.e., presence of relatives with a history of HZ); availability of cases and controls, and description of exposure (i.e., presence and numbers of first-degree/total relatives with HZ). The incubation period may be prolonged in immunocompromised patients and those who have received postexposure treatment with a varicella antibody–containing product. Where such information was not readily available, crude data with the number of cases in the exposed and unexposed groups should be reported. Two reviewers independently reviewed the titles and abstracts of these articles. Based on the inclusion criteria and information from abstract, articles were identified for full-text review. The rash usually appears first on the head, then on the trunk, and then the extremities; the highest concentration of lesions is on the trunk. Any disagreements were resolved by consensus. Reviewers independently extracted the data with a standardized data extraction form. Relevant information extracted included the study year, country of study, study design, exposure (i.e., number of relatives with a history of HZ infection) in cases versus control group, OR and their respective 95% CIs when available, and confounding factors adjusted. Vesicles may rupture or become purulent before they dry and crust. No study was identified from the Cochrane Central Register. There were 33 duplicates, which were removed from further evaluation. Of the 61 articles (after removing duplicate studies) initially identified, nine studies were selected based on the prescribed inclusion criteria. Breakthrough varicella is defined as a case of varicella due to infection with wild-type VZV occurring more than 42 days after varicella vaccination.

After these exclusions, five studies, yielding a total of 4169 subjects, were included in the meta-analysis. There were considerable heterogeneity between studies for meta-analyses involving the first-degree relatives (I2 = 86.1%, P < 0.001) and total relatives (I2 = 93.2%, P < 0.001). To account for study heterogeneity, the random-effects model of meta-analysis was employed. Breakthrough varicella has been reported in both one- and two-dose vaccine recipients. Publication bias cannot be ruled out by visual inspections of the funnel plots [Figure 4]. Both funnel plots showed a lack of small size studies with negative association. Formal testing with Egger's test, however, failed to provide any evidence for small study effect in meta-analyses of the first-degree relatives (P = 0.557) and total relatives (P = 0.513). Children with lymphoma and leukemia may develop a severe progressive form of varicella characterized by high fever, extensive vesicular eruption, and high complication rates. By analyzing data from five studies involving 2247 cases of HZ infection and 1922 controls, we found that those who had HZ were 3 times more likely to report a family history of HZ. This relationship was statistically significant and corroborated by sensitivity analysis. The dose-response analysis of three studies with appropriate data demonstrated that an individual's risk of having HZ infection increased as he/she reported a greater numbers of first-degree/total relatives with a history of HZ. As with other viral diseases, reexposure to natural (wild) varicella may lead to reinfection that boosts antibody titers without causing clinical illness or detectable viremia. Various studies have explored genetic susceptibility to HZ by evaluating the risk of infection in certain families with no known history of immunosuppression. An allelic expression of ATA haplotype at the promoter region of interleukin 10 (IL-10) genes has been reported in a significant proportion of HZ patients.[7] This genetic polymorphism may affect the immune functions of this cytokine and, therefore, predisposes an individual to HZ infection. Similarly, another genetic study of the Korean population demonstrated that polymorphism in IL-10 promoter region, especially the GCC haplotype, was associated with susceptibility to HZ.[8] Another study reported the relationship of human leukocyte antigen (HLA) Class I alleles with an individual's immune response to the virus and the risk of postherpetic neuralgia.[19] While genetic susceptibility is associated with an increased risk of HZ infection, other risk factors also tend to cluster within the family. In immunocompromised persons, zoster may disseminate, causing generalized skin lesions and central nervous system, pulmonary, and hepatic involvement. It is interesting to note that there appeared to be a gender predilection in HZ infection, with women more likely to be affected than men. A female predominance was observed in four of the five included studies, with females accounting for 53.5–59.5% of the HZ cases.[14],[16],[17],[18] The study by Gatti et al., on the other hand, demonstrated that men represented 58.4% of the cases with postherpetic neuralgia.[15] This is in contrast with the results of other epidemiological studies, which showed postherpetic neuralgia as being more prevalent in female than male HZ patients.[22],[23] More research is needed to explore the association of gender with the prevalence of HZ infection and its sequelae. This meta-analysis demonstrated that a positive family history significantly increased the risk of occurrence of HZ. There are few systemic symptoms. While a significant family history may provide an indirect evidence for certain genetic susceptibility, more genome-wide association studies are required to get a better understanding of the mechanism underlying such genetic predisposition for HZ infection. Currently, zoster vaccine (Zostavax ®) is recommended for healthy individuals ≥60 years old to reduce the incidence of HZ.[24] Earlier prophylactic vaccination with Zostavax ® can be considered in selected individuals with a positive family history, before the age of 60, to lower the likelihood of VZV reactivation and prevent the development of postherpetic neuralgia. Awn BP, Saddier P, Wollan PC, St Sauver JL, Kurland MJ, Sy LS. Pneumonia following varicella is usually viral but may be bacterial. Mayo Clin Proc 2007;82:1341-9. Gershon AA, Gershon MD, Breuer J, Levin MJ, Oaklander AL, Griffiths PD. Advances in the understanding of the pathogenesis and epidemiology of herpes zoster. Encephalitis is an infrequent complication of varicella (estimated 1.8 per 10,000 cases) and may lead to seizures and coma. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: A proposal for reporting. Meta-analysis of Observational Studies in Epidemiology (MOOSE) group. There has been a dramatic decrease in the incidence of Reye syndrome, presumably related to decreased use of aspirin by children. Gatti A, Pica F, Boccia MT, De Antoni F, Sabato AF, Volpi A. No evidence of family history as a risk factor for herpes zoster in patients with post-herpetic neuralgia. J Med Virol 2010;82:1007-11. From 1990 through 1996, an average of 103 deaths from varicella were reported each year. Herpes zoster vaccine effectiveness against incident herpes zoster and post-herpetic neuralgia in an older US population: A cohort study. PLoS Med 2013;10:e1001420.