Pathogenesis Of Herpes Zoster Research Articles

A study on the causal relationship between the gut microbiome and herpes zoster using Mendelian randomization.

The relationship between herpes zoster recurrence and the gut microbiome was not studied. We analyzed data on the gut microbiome and herpes zoster from the Large-Scale Genome-Wide Association Study (GWAS) database using bidirectional Mendelian randomization. For the first time, we identified a potentially bidirectional causal relationship between the gut microbiome and herpes zoster (HZ). These findings are groundbreaking and hold promise for new directions in the treatment of HZ, a global disease. HZ had a high global incidence, characterized by shingled blisters, blood blisters, and neuropathic pain, and could develop in various parts of the body, including the ear and throat. It was believed its onset was closely related to old age and infirmity. Some studies reported that the incidence of herpes zoster in patients with inflammatory intestinal diseases (such as Crohn's disease and ulcerative colitis) was higher than in the general population. Existing studies attributed this to the reactivation of varicella-zoster virus (VZV) due to autoinflammatory attacks and immunosuppressive drugs. This provided a basis for exploring the new pathogenesis of HZ and investigating whether there was a relationship between intestinal auto-flora and the development of HZ. This study aimed to examine this potential relationship using bidirectional Mendelian analyses. GWAS data on HZ and gut microbiota were obtained from FinnGen, the Mibiogen consortium, and HZ meta-analysis data from the IEU Open GWAS Project. These data were subjected to two-sample Mendelian randomization (MR) analysis to determine if there is a causal relationship between gut microbiota and HZ. Additionally, bidirectional Mendelian analyses were conducted to identify the direction of causality and to clarify any potential interactions. In our Mendelian Randomization (MR) analysis, we identified, for the first time, two gut microbes that might be associated with HZ reactivation. In the reverse MR analysis, four gut microbiota showed a potential association between the genetic susceptibility of gut microbiota and HZ reactivation. We found that genus Tyzzerella3 (OR: 1.42, 95% CI: 1.17-1.72, FDR < 0.1) may be strongly correlated with an increased probability of HZ (ICD-10: B02.901) reactivation. Additionally, phylum Cyanobacteria was identified as a potential risk factor for the onset of HZ rekindling (OR: 1.42, 95% CI: 1.09-1.87). Analyzing the results of the reverse MR, we also identified a potential inhibitory effect (OR: 0.91, 95% CI: 0.84-0.99) of HZ onset on the genus Eubacteriumhallii group in the gut, suggesting that HZ might reduce its abundance. However, genus Escherichia/Shigella (OR: 1.11, 95% CI: 1.01-1.22), genus Veillonella (OR: 1.16, 95% CI: 1.04-1.30), and phylum Proteobacteria (OR: 1.09, 95% CI: 1.01-1.18) appeared to act as potential protective factors, indicating that the relative abundance and viability of these three bacteria increased in the HZ state. We identified the influence of gut flora as a new causative factor for HZ reactivation. Additionally, we found that individuals suffering from HZ might potentially impact their gut flora. Specific bacterial taxa that could influence the onset and progression of HZ were identified, potentially providing new directions for HZ treatment.

Kako prepoznati i lečiti herpes zoster infekciju?

Herpes zoster (HZ) is a common, infectious vesicular dermatosis caused by the reactivation of the varicella-zoster virus (VZV). It is a common clinical problem, especially in people over 50 and immunocompromised patients. Treatment of HZ consists of antiviral drugs, analgesics in the control of acute pain and adequate topical therapy that prevents the occurrence of secondary infection and promotes healing process. This paper presents the most important information related to the etiology and pathogenesis of HZ, epidemiological data and so far known risk factors, the spectrum of clinical manifestations and methods used in the diagnosis of this disease. Therapeutic modalities used in the treatment of HZ and accompanying complications are especially presented, and the need for the timely introduction of antiviral therapy is emphasized, as well as the importance of preventive vaccination of older age groups. Herpes zoster, due to its frequency and associated complications, is a significant public health problem. Due to the global increase in the number of people with compromised immune systems, whether due to age, disease or immunosuppressive therapy, there has been a significant increase in population risk for HZ and postherpetic neuralgia as the most common complication of this disease. For that reason, as well as due to the possible role of HZ in the development of vasculopathy, strokes and heart attacks, experts strongly recommend prevention of HZ by comprehensive vaccination of the elderly.

Relation between TNFα and S100B in patients with herpes zoster and postherpetic neuralgia

One of the most important components in the pathogenesis of herpes zoster and postherpetic neuralgia is presented by disturbed neuroimmune interaction, characterized by development of chronic inflammation in the nervous system structures. Normally existing interaction between immune and nervous systems is altered and results in development of pathological system. Altered level of TNFα and S100B proteins may characterize the features of neuroimmune inflammation during herpes zoster infection. Objective: to assess a relationship between TNFα and S100B level in patients with herpes zoster and postherpetic neuralgia. We examined 106 patients with herpes zoster within the framework of our study. Based on assessing intensity of pain syndrome and its three-month follow-up data after primary treatment patients were subdivided into 3 main groups: group I – weak or moderate pain syndrome; group II – severe pain syndrome; group III – postherpetic neuralgia. The control group contained 30 age-matched apparently healthy volunteers. Venous blood sampling was performed twice: on day 1 and day 10 after disease onset. Biological material in control group was collected once. Level of blood serum TNFα and S100B was measured by using solid-phase enzyme immunoassay (ELISA) on analyzer “Multiscan”. While assessing TNFα level in all three main groups, its lowered level was detected (p 0.05) on day 1, without finding inter-group differences. On day 10 after disease onset, level of TNFα did not differ from the control values found in groups I and II, while in group III it remained lowered, not being significantly differed from those found on day 1. Level of S100B in the blood serum in patients vs. control group was equivalently increased (p 0.05), showing no inter-group differences. On day 10, the level of S100B in the blood serum from patients of groups I and II tended to stabilize, by decreasing almost by 2-fold to reference intervals in group I, without reaching control values, in group II. Patients from group III were found to have serum level of S100B remained elevated compared to control group without dynamic changes between 1 and 10 days. A correlation analysis for TNFα and s100b protein revealed significant feedback relation between them (p 0.05) in group III.

Herpes zoster vaccine live: A 10 year review of post-marketing safety experience

BackgroundZoster vaccine is a single dose live, attenuated vaccine (ZVL) indicated for individuals ≥50 years-old for the prevention of herpes zoster (HZ). Safety data from clinical trials and post-licensure studies provided reassurance that ZVL is generally safe and well tolerated. The objective of this review was to provide worldwide post-marketing safety information following 10 years of use and >34 million doses distributed. MethodsAll post-marketing adverse experience (AE) reports received worldwide between 02-May-2006 and 01-May-2016 from healthcare professionals following vaccination with ZVL and submitted to the MSD AE global safety database, were analyzed. ResultsA total of 23,556 AE reports, 93% non-serious, were reported. Local injection site reactions (ISRs), with a median time-to-onset of 2 days, were the most frequently reported AEs followed by HZ. The majority of HZ reports were reported within 2 weeks of vaccination and considered, based on time-to-onset, pathogenesis of HZ, and data from clinical trials, to be caused by wild-type varicella-zoster virus (VZV). HZ confirmed by PCR analysis to be VZV Oka/Merck vaccine-strain was identified in an immunocompetent individual 8 months postvaccination and in 4 immunocompromised individuals. Disseminated HZ was reported very rarely (<1%) with 38% occurring in immunocompromised individuals. All reports of disseminated HZ confirmed by PCR as VZV Oka/Merck vaccine-strain were in individuals with immunosuppressive conditions and/or therapy at the time of vaccination. ConclusionsThe safety profile of ZVL, following 10 years of post-marketing use, was favorable and consistent with that observed in clinical trials and post-licensure studies.

Multisegmental Herpes Zoster in a Healthy Girl

Children infrequently are afflicted with herpes zoster (HZ). Activation of latent varicella-zoster virus (VZV) in a partially immune host results in HZ. Herpes zoster in children can be benign or with varied severity, especially in cases associated with malignancy. Because of its rarity, we report widespread multisegmental HZ primarily presenting on the right side of the body and right flank in a 11 years old immunocompetent girl. The Authors have previously described a similar observation in a 6 years old female immunocompetent girl Children infrequently are afflicted with herpes zoster (HZ). Activation of latent varicella-zoster virus (VZV) in a partially immune host results in HZ. Herpes zoster in children can be benign or with varied severity, especially in cases associated with malignancy. Defects in normal immunity and cellular immunity have been postulated as important factors in the pathogenesis of HZ. Disseminated HZ is typical HZ associated with widespread cutaneous lesions simulating chicken pox and it may be associated with immunosuppression [1].

Study on the T-helper cell 1/2 cytokine profile in blister fluid of patients with herpes zoster and its clinical significance

Herpes zoster (HZ) is a Varicella zoster virus infection disease. Previous studies have presumed the connection between development of HZ and involvement of cellular immunity in peripheral blood. However, whether cellular immunity plays a role in the local skin lesion has not been addressed. To explore the levels of T-helper cell (Th)1/Th2 type cytokine profiles in the blister fluid of the skin lesions from the patients with HZ and its role in pathogenesis, we used the cytometric bead array kit to compare the levels of cytokines (interleukin [IL]-2, tumor necrosis factor [TNF]-α, IL-10 and IL-4) in blister fluid from 46 patients with those from the suction blister fluids from 20 volunteers without any infectious disease (the control group). The results indicated that the levels of Th1 cytokines, IL-2 and TNF-α in the blister fluid from the patients' skin lesions were significantly lower than those from the control group, whereas the levels of Th2 cytokines IL-10 and IL-4 were significantly higher than those in the control group. Moreover, significant variation of the levels of Th1/Th2 cytokines (IL-2, TNF-α, IL-10 and IL-4) in the blister fluid from the HZ patients' lesions was also observed among different stages of the disease. It is concluded that a cytokine imbalance was present in the local lesions of patients with HZ during disease development. Our data suggested that the Th immunity was associated with disease activity, which may play an important role in the pathogenesis of HZ.

ACUTE HERPES ZOSTER AND POSTHERPETIC NEURALGIA

Herpes zoster (HZ) is a localized disease characterized by unilateral radicular pain and a vesicular cutaneous eruption that is generally limited to the dermatome innervated by a single spinal or cranial sensory ganglion. It results from reactivation of an endogenous varicella-zoster virus (VZV) infection that has persisted in latent form within the sensory ganglia following an earlier attack of varicella. 109,180,212 Pain is a major symptom of HZ. It often precedes and generally accompanies the characteristic rash, and it frequently persists after the rash has healed—a complication known as postherpetic neuralgia (PHN). Pain during the acute phase of HZ and PHN has a severe impact on quality of life and accounts for much of the morbidity of HZ. Many treatments have been employed to reduce the severity of HZ, prevent the development of PHN, and relieve the pain and suffering caused by the complication of PHN. Few have proven beneficial, however, and there is a dearth of well-designed and well-controlled studies evaluating treatment outcomes in HZ and PHN. This article reviews the natural history and pathogenesis of HZ and PHN and critically evaluates approaches to treatment and prevention. This discussion is limited to HZ and PHN in immunocompetent patients. The management of HZ and its complications in immunosuppressed patients is not addressed.

Immunization to reduce the frequency and severity of herpes zoster and its complications

Herpes zoster (HZ) is a localized disease that results from reactivation of an endogenous varicella-zoster virus (VZV) infection that has persisted in latent form within sensory ganglia following an earlier attack of varicella. The incidence and the severity of HZ and its complications increase with advancing age, and this is temporally associated with an age-related decline in cell-mediated immunity (CMI) to VZV. Information on the cellular site and mechanism of VZV latency and on the events that follow reactivation appears to explain many of the clinical features of HZ and to provide a pathophysiologic basis for the presumption that immunity to VZV plays a critical role in limiting the frequency and consequences of VZV reactivation. The close temporal correlation between the decline in VZV-specific CMI and the increased frequency and severity of HZ and its complications in older individuals suggests that HZ may actually develop because VZV-specific CMI falls below some critical threshold. The development of a live attenuated varicella vaccine provides a means of stimulating VZV-specific CMI and thus of determining its role in the pathogenesis of HZ. Levin and his colleagues have demonstrated that waning VZV-specific CMI in elderly persons can be stimulated by varicella vaccine to levels typical of those observed in younger persons, in whom the incidence and severity of HZ are much reduced. Thus the stage is set for a large placebo-controlled clinical trial that will test directly the hypothesis that restoration of waning CMI to VZV will reduce the frequency and severity of HZ and its complications in the elderly.

Maxillary osteomyelitis and spontaneous tooth exfoliation after herpes zoster

Reports of spontaneous tooth exfoliation and osteonecrosis trigeminal herpes zoster are extremely rare and have been sporadic. This article reports a pertinent case of a 50-year-old man who exhibited prodromal odontalgia before the appeatance of vesicular mucocutaneous lesions, together with severe destruction of the maxillary bone and exfoliation of multiple teeth. This patient was successfully treated using a unique closed nasal-vestibular drainage system for the ultimate control of maxillary bone viability. A review and analysis of the clinical aspects and the pathogenesis of herpes zoster and bone necrosis are discussed.

Varicella-Zoster virus infection of human astrocytes, Schwann cells, and neurons

Human fetal cell cultures enriched for astrocytes, Schwann cells, or dorsal root ganglia neurons were infected with cell-free varicella-zoster virus (VZV), and the course of these infections was compared with that in fetal fibroblasts. Virus replication was detected in each neural cell type as early as 10–16 hr postinfection. Permissiveness of each cell type was confirmed by electron microscopy. However, the kinetics of virus spread varied between the neural cell types. Moreover, the accumulation, progression, and localization of VZV putative immediate early (IE), early (E), and late proteins was neural cell-type specific. VZV replication was slower in Schwann cells and neurons than in astrocytes. In Schwann cells and neurons VZV E proteins could be detected before IE proteins, a reversal of the order of accumulation noted with astrocytes and fibroblasts. There was also relatively more VZV IE protein in the perinuclear cytoplasm of Schwann cells and neurons, suggesting a delay in the transport of this antigen to its nuclear site. The permissiveness of non-neuronal cell types suggests that they could play a role in the pathogenesis of herpes zoster.