Herpes Zoster (Shingles) Patient-Centered Wound Outcomes: A Literature Review.

GENERAL PURPOSE: To present a comprehensive review of patient-centered outcomes of topical or systemic interventions applied to those with shingles or postherpetic neuralgia to inform clinical practice and identify related research needs. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will be able to:1. Explain the importance of early diagnosis and treatment of herpes zoster (HZ).2. Identify interventions that have resulted in documented improvement of validated patient-centered outcomes in patients with HZ or postherpetic neuralgia.3. Recognize the average per patient medical costs of HZ in the US.

One in three people endure herpes zoster (HZ; also known as shingles) during their lifetime, experiencing pain, secondary infections, postherpetic neuralgia, reduced quality of life, and considerable patient costs. These patient burdens remain to be reviewed. To perform a comprehensive review of patient-centered outcomes of topical or systemic interventions applied to those with shingles or postherpetic neuralgia to inform clinical practice and identify related research needs. The PubMed database was searched with supplementary Google Scholar searches for Medical Subject Headings "shingles" or "post-herpetic neuralgia" to find clinical studies documenting validated patient-centered outcomes: pain, secondary infection, healing, function, depression, social isolation, treatment costs, or quality of life. Six representative case studies were examined. Pertinent original and derivative clinical study references were included. Preclinical studies, reviews, or studies of non-HZ conditions were excluded. Two authors tabulated clinical efficacy evidence for interventions affecting patient-centered outcomes. Evidence supported efficacy for systemic antiviral or topical anesthetic interventions improving pain, healing, sleep, vision, or quality of life for those with HZ or postherpetic neuralgia. Patient cases reported improved pain and/or sleep using occlusive dressings. Treatment costs and secondary infections were reported only in cases or cohort studies. Randomized clinical research focused on medications improving patient pain, healing, sleep, or vision outcomes. Research is needed measuring outcomes of adding occlusive dressings to optimal care and effects on secondary infections and treatment costs.

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.

A cross-sectional study of the knowledge, attitude, and practice of patients aged 50 years or above towards herpes zoster in an out-patient setting.

INTRODUCTION: There has been limited research on the knowledge of and attitudes about herpes zoster in the Hong Kong population. This study aimed to investigate the knowledge, attitude, and practice of patients aged 50 years or above towards herpes zoster and its vaccination. METHODS: This was a cross-sectional study in the format of a structured questionnaire interview carried out in Sai Ying Pun Jockey Club General Outpatient Clinic in Hong Kong. Knowledge of herpes zoster and its vaccination was assessed, and patient attitudes to and concerns about the disease were evaluated. Factors that affected a decision about vaccination against herpes zoster were investigated. RESULTS: A total of 408 Hong Kong citizens aged 50 years or above were interviewed. Multiple regression analysis revealed that number of correct responses regarding knowledge about herpes zoster was positively correlated with educational attainment (B=0.313, P=0.026) and history of herpes zoster (B=0.408, P=0.038), and negatively correlated with age (B= -0.042, P<0.001) and male gender (B= -0.396, P=0.029). Answers to several questions revealed a sizable number of misconceptions about the disease. Among all respondents, 35% stated that they were worried about getting the disease, and 17% would consider vaccination against herpes zoster. CONCLUSIONS: Misconceptions about herpes zoster were notable in this study. More health education is needed to improve the understanding and heighten awareness of herpes zoster among the general public. Although the majority of participants indicated that herpes zoster would have a significant impact on their health, a relatively smaller proportion was actually worried about getting the disease. Further studies on this topic should be encouraged to gauge the awareness and knowledge of herpes zoster among broader age-groups.

WILLINGNESS TO PAY, QUALITY OF LIFE, AND KNOWLEDGE ON HERPES ZOSTER AMONG THAI PATIENTS PRIOR ZOSTER VACCINE ERA.

Herpes zoster is a devastating condition affecting patients' wellbeing. Policy on zoster vaccine in developing countries needs more data on the disease burden. This study was designed to assess willingness to pay, quality of life, and the patients' knowledge on herpes zoster disease. All of the patients were asked to complete questionnaires about the willingness to pay for zoster treatment using the Dermatology Life Quality Index (DLQI) questionnaires in Thai version and basic knowledge about herpes zoster. The demographic and clinical data were all recorded. Eighty-two from one hundred and eighteen patients in this study were female (69.5%), and the mean (SD) age was 57.6 (14.9) years. The median of their willingness to pay for zoster treatment was THB500 (range of THB50-10,000) or only 4.2% of median income per month. The mean of total DLQI score (SD) was 10.7 (6.2), which indicated moderate to severe impact on quality of life. From multiple linear regression analysis, three factors were related to inferior patients' quality of life including facial involvement (regression coefficients, b=4.789, p=0.001), presence of zoster complications (b=5.018, p=0.001) and advanced pain score (b=0.883, p<0.001). Moreover, more than half of them still had mistaken knowledge about the disease.

Functional decline and herpes zoster in older people: an interplay of multiple factors.

Herpes zoster is a frequent painful infectious disease whose incidence and severity increase with age. In older people, there is a strong bidirectional link between herpes zoster and functional decline, which refers to a decrement in ability to perform activities of daily living due to ageing and disabilities. However, the exact nature of such link remains poorly established. Based on the opinion from a multidisciplinary group of experts, we here propose a new model to account for the interplay between infection, somatic/psychiatric comorbidity, coping skills, polypharmacy, and age, which may account for the functional decline related to herpes zoster in older patients. This model integrates the risk of decompensation of underlying disease; the risk of pain becoming chronic (e.g. postherpetic neuralgia); the risk of herpes zoster non-pain complications; the detrimental impact of herpes zoster on quality of life, functioning, and mood; the therapeutic difficulties due to multimorbidity, polypharmacy, and ageing; and the role of stressful life events in the infection itself and comorbid depression. This model underlines the importance of early treatment, strengthening coping, and vaccine prevention.

The societal impact of herpes zoster and postherpetic neuralgia on patients, life partners, and children of patients in Germany.

The aim of this study was to assess the impact of herpes zoster (HZ) and postherpetic neuralgia (PHN) on the daily activities of patients and family members who care for them. Some former patients and family members participated in face-to-face interviews or in a T-group meeting (qualitative phase) and some participated in telephone interviews (quantitative phase). They all expressed feelings of helplessness and frustration mixed with depression, sadness, or rage. Many of the former patients said their lives stopped, in contrast to family members who said that their lives were busy and stressful. Family members caring for patients with PHN were more psychologically stressed than those caring for patients with HZ. Although former patients appreciated the psychological and emotional support given by their family members, they underestimated the impact that their disease had on them. Former patients and their family never forgot this illness and its considerable impact on their lives, particularly when PHN occurred. We need to raise the awareness of the general public about the real life impact of HZ and PHN and their often severe, debilitating consequences and the potential benefits from vaccination.

Quality of pain in herpes zoster patients.

Pain typically accompanies acute herpes zoster and persists well beyond rash healing. Different types of pain are reported by patients with herpes zoster. Current studies show that these types of pain vary with respect to their presence, location, duration, intensity and quality, hence pain needs to be analyzed more thoroughly. The aim of the study was to assess different components of pain in patients with herpes zoster. The study subjects were 46 patients diagnosed with herpes zoster and selected out of 493 patients treated at the Pain Therapy Clinic, the outpatient facility of Zagreb Clinic for Traumatology, in 2010. Measures used to assess pain and daily activities were the following: SF McGill Pain Questionnaire, Visual Analogue Scale, Self-Assessment of Life Satisfaction, Health Satisfaction and Enjoyment in Life. Analgesic treatment together with demographic and clinical characteristics of patients were also taken into account. The results have shown that the patients report about spontaneous pain mostly in terms of the following qualities of high level pain intensity: throbbing, aching, hot-burning and sharp. The results also demonstrate that herpes zoster pain significantly affects the patients' everyday living quality and their emotional health. Comprehensive assessment of pain is necessary for clinical research about the epidemiology, natural history, pathophysiologic mechanisms, treatment, and prevention of pain in herpes zoster.

Effect of hyperbaric oxygen therapy on patients with herpes zoster.

BACKGROUND: The purpose of this study was to observe the effect of hyperbaric oxygen (HBO2) therapy on patients with herpes zoster. METHODS: A total of 68 cases with herpes zoster were randomly divided into HBO2 and control groups. The patients in the control group were treated with drugs, while the patients in the HBO2 group were treated with both drugs and HBO2. Parameters of therapeutic efficacy including period of blister resolution, scar formation time and percentage of patients developing post-herpetic neuralgia (PHN) were determined for the patients in both groups. Numeric Pain Rating Scale (NPRS) and Hamilton Depression Rating Scale (HAMD) were also scored for the patients before and after treatment. RESULTS: The therapeutic efficacy in the control group was 81.25%, which was significantly lower than that (97.22%) in the HBO2 group (p < 0.05). The percentage of patients developing PHN, scar formation time and NPRS score in the HBO2 groups were significantly lower than those in the control group (p < 0.05). HAMD score in the HBO2 group was significantly lower than that in the control group (p < 0.05). CONCLUSION: HBO2 can significantly enhance therapeutic efficacy, relieve pain, accelerate herpes blister healing and lesion resolution, reduce the percentage of patients developing PHN and improve depression in patients with herpes zoster.

Major depressive disorder and immunity to varicella-zoster virus in the elderly.

Major depressive disorder has been associated with activation of inflammatory processes as well as with reductions in innate, adaptive and non-specific immune responses. The objective of this study was to evaluate the association between major depression and a disease-relevant immunologic response, namely varicella-zoster virus (VZV)-specific immunity, in elderly adults. A cross-sectional cohort study was conducted in 104 elderly community dwelling adults ≥ 60years of age who were enrolled in the depression substudy of the shingles prevention study, a double blind, placebo-controlled vaccine efficacy trial. Fifty-two subjects had a current major depressive disorder, and 52 age- and sex-matched controls had no history of depression or any mental illness. VZV-specific cell-mediated immunity (VZV-CMI) was measured by VZV responder cell frequency (VZV-RCF) and interferon-γ enzyme-linked immunospot (ELISPOT) assays, and antibody to VZV was measured by an enzyme-linked immunosorbent assay against affinity-purified VZV glycoproteins (gpELISA). VZV-CMI, measured by VZV-RCF, was significantly lower in the depressed group than in the controls (p<0.001), and VZV-RCF was inversely correlated with the severity of depressive symptoms in the depressed patients. In addition, an age-related reduction in VZV-RCF was observed in the depressed patients, but not in the controls. Furthermore, there was a trend for depressive symptom severity to be associated with lower ELISPOT counts. Finally, VZV-RCF was higher in depressed patients treated with antidepressant medications as compared to untreated depressed patients. Since lower levels of VZV-RCF appear to explain the increased risk and severity of herpes zoster observed in older adults, these findings suggest that, in addition to increasing age, depression may increase the risk and severity of herpes zoster.

Perceptions of herpes zoster and attitudes towards zoster vaccination among 50-65-year-old Danes.

INTRODUCTION: Herpes zoster (HZ or shingles) and its complication post-herpetic neuralgia (PHN) are common in persons above 50 years of age. A vaccine that decreases the incidence and morbidity associated with HZ was licensed for use in 2006 and will be marketed in Denmark as from 2013. This study aimed to explore the relations between illness perceptions of shingles and attitudes towards zoster vaccination. MATERIAL AND METHODS: Three qualitative focus group interviews were conducted with 22 patients, relatives and individuals with no personal experiences with HZ. Semi-structured interview guides were applied including questions identified in a literature study. The data were analysed using a medical anthropological approach. RESULTS: The study showed that HZ and PHN, in particular, have severe impacts on patients' quality of life (QoL) and often affect their relatives' daily lives as well. Nevertheless, people who have no experience with HZ underrate both its prevalence and its QoL impacts. Such misperceptions often result in delayed treatment and may lead to a low uptake of zoster vaccination. CONCLUSION: Individual attitudes towards zoster vaccination are closely related to subjective perceptions of HZ and views on vaccination in general. Vaccination recommendations to target groups are necessary, but individual choice is determined by knowledge about the disease, personal risk assessment and the recommendations of the general practitioner. FUNDING: The study was funded by a research grant from Sanofi Pasteur MSD. TRIAL REGISTRATION: not relevant.

Herpes zoster pain, postherpetic neuralgia, and quality of life in the elderly.

Herpes zoster pain and postherpetic neuralgia (PHN) particularly affect older persons. This literature review presents how quality of life is evaluated and the consequences of shingles and PHN on the quality of life of older persons. Although more than 150 articles have been published on herpes zoster and its consequences, specific studies focusing on the older population are needed, in several domains like epidemiology, preventive medicine, neuropsychology, and pharmacology.

Impact of Reactogenicity After Two Doses of Recombinant Zoster Vaccine Upon Physical Functioning and Quality of Life: An Open Phase III Trial in Older Adults.

BACKGROUND: Herpes zoster may significantly impact quality of life (QoL) in older adults. The recombinant zoster vaccine (RZV) is efficacious in adults aged ≥50 and older and is associated with increased reactogenicity compared to placebo. We report here on the impact of reactogenicity of the second RZV dose on the QoL and physical functioning (PF) of vaccine recipients, and summarize findings following both doses. METHOD: In this single-arm study, 401 adults aged ≥50 and older were enrolled to receive two RZV doses 2 months apart. Change in mean Short Form Survey-36 (SF-36) PF and EuroQol-5 Dimension (EQ-5D) scores, reactogenicity, safety, productivity loss, and healthcare resource utilization were evaluated. RESULTS: In total, 391 (97.5%) participants received dose 2. Post-dose 2, the most common solicited local symptoms were injection site pain (75.1%), erythema (22.4%), and swelling (13.9%), and the most common systemic symptoms were fatigue (46.3%), headache (37.5%), and myalgia (32.9%). Grade 3 solicited (local and systemic) adverse events were reported by 61 (15.6%) participants and were associated with a transient clinically significant decrease in SF-36 PF score on Days 1-2 post-dose 2 that recovered by Day 3. Overall, no clinically important reduction in mean SF-36 PF scores was observed from baseline to post-dose 2 (mean change -0.4), and no quality-adjusted-life-year loss was recorded. CONCLUSIONS: Overall, QoL and PF of RZV vaccinees were not affected by vaccine-related reactogenicity. A transient reduction was observed in the first 2 days after RZV vaccination in individuals with Grade 3 adverse events. No safety concerns were identified.

The impact of herpes zoster and post-herpetic neuralgia on quality-of-life.

BACKGROUND: The potentially serious nature of herpes zoster (HZ) and the long-term complication post-herpetic neuralgia (PHN) are often underestimated. One in four people will contract herpes zoster in their lifetime, with this risk rising markedly after the age of 50 years, and affecting one in two in elderly individuals. Pain is the predominant symptom in all phases of HZ disease, being reported by up to 90% of patients. In the acute phase, pain is usually moderate or severe, with patients ranking HZ pain as more intense than post-surgical or labour pains. Up to 20% of patients with HZ develop PHN, which is moderate-to-severe chronic pain persisting for months or years after the acute phase. We review the available data on the effect of HZ and PHN on patients' quality-of-life. DISCUSSION: Findings show that HZ, and particularly PHN, have a major impact on patients' lives across all four health domains--physical, psychological, functional and social. There is a clear correlation between increasing severity of pain and greater interference with daily activities. Non-pain complications such as HZ ophthalmicus can increase the risk of permanent physical impairment. Some elderly individuals may experience a permanent loss of independence after an acute episode of HZ. Current challenges in the management of HZ and PHN are highlighted, including the difficulty in administering antiviral agents before pain becomes established and the limited efficacy of pain treatments in many patients. We discuss the clinical rationale for the HZ vaccine and evidence demonstrating that the vaccine reduces the burden of the disease. The Shingles Prevention Study, conducted among >38,000 people aged >or=60 years old, showed that the HZ vaccine significantly reduces the burden of illness and the incidence of both HZ and PHN. In the entire study population, zoster vaccination reduced the severity of interference of HZ and PHN with activities of daily living by two-thirds, as measured by two questionnaires specific to HZ. SUMMARY: A vaccination scheme may positively impact the incidence and course of HZ disease, thereby improving patients' quality-of-life.

Public awareness and knowledge of herpes zoster: results of a global survey.

BACKGROUND: Herpes zoster (HZ), the reactivation of varicella zoster virus, occurs in 1 in 5 people worldwide and may result in a variety of complications, including postherpetic neuralgia (PHN). Treatment of patients with HZ represents a considerable challenge, especially among the elderly who are prone to get a more severe form of the disease and its complications. Since May 2006, a vaccine was approved for the prevention of HZ or PHN among individuals aged 50 or 60 years and older. OBJECTIVE: Since the success of any new vaccine initiative depends on public awareness of the disease, we conducted the HZ Global Awareness Survey to gauge existing levels of awareness and knowledge of HZ. METHODS: The survey was conducted by telephone or face-to-face among 8,688 adults >OR=50 years of age in 22 countries between December 2006 and January 2007 and addressed awareness, knowledge, symptoms, and treatment of HZ. RESULTS: Wide variation in HZ awareness was noted among countries. In some countries (New Zealand, Brazil, and Malaysia) nearly all individuals surveyed (97-100%) over the age of 50 years had heard of HZ. In contrast, less than 20% of individuals surveyed were aware of HZ in Turkey, India and Chile. The survey revealed almost universally poor knowledge of the causes and symptoms of HZ. Only 3% of respondents mentioned chicken pox as the cause of the disease. The majority of respondents were unaware of their risk of HZ, with 71% considering themselves unlikely or very unlikely to develop HZ. The survey also revealed that those respondents with prior HZ experience were much more likely to consider pain as the worst symptom of the disease than those without prior HZ experience. The misconception of HZ-related morbidity among individuals with no first-hand experience of the disease highlights the global educational need to raise awareness of the seriousness of HZ and its potential long-term complications. CONCLUSIONS: This survey suggests a population-wide effort to improve global awareness of HZ would be required for a successful vaccine initiative. Further studies would be required to understand regional differences in the understanding of HZ.

Somatosensory profiles in acute herpes zoster and predictors of postherpetic neuralgia.

This prospective cohort study aimed to characterize the sensory profile during acute herpes zoster (AHZ) and to explore sensory signs as well as physical and psychosocial health as predictors for postherpetic neuralgia (PHN). Results of quantitative sensory testing of 74 patients with AHZ at the affected site and at the distant contralateral control site were compared to a healthy control group. Pain characteristics (Neuropathic Pain and Symptom Inventory and SES), physical functioning, and psychosocial health aspects (Pain Disability Index, SF-36, and STAI) were assessed by questionnaires. Patients with PHN (n = 13) at 6-month follow-up were compared to those without PHN (n = 45). Sensory signs at the affected site were thermal and vibratory hypesthesia, dynamic mechanical allodynia (DMA), pressure hyperalgesia, and high wind-up (18%-29%), as well as paradoxical heat sensations and pinprick hypalgesia (13.5%). The unaffected control site exhibited thermal and vibratory hypesthesia, DMA, and pressure hyperalgesia. Dynamic mechanical allodynia and pinprick hypalgesia were mutually exclusive. Postherpetic neuralgia was associated with DMA (38.5% vs 6.7%; P = 0.010) and vibratory hypesthesia (38.5% vs 11.1%; P = 0.036) at the control site, with mechanical gain and/or loss combined with normal thermal detection (affected site: 69.2% vs 31.1%; P = 0.023; control site: 53.8% vs 15.5%; P = 0.009). Pain Disability Index (P = 0.036) and SES affective pain perception scores (P = 0.031) were over 50% higher, and 6 of 8 SF-36 subscores were over 50% lower (P < 0.045) in PHN. Sensory profiles in AHZ indicate deafferentation and central but not peripheral sensitization. Sensory signs at distant body sites, strong affective pain perception, as well as reduced quality of life and physical functioning in the acute phase may reflect risk factors for the transition to PHN.

Impact of Herpes Zoster and Post-Herpetic Neuralgia on Health-Related Quality of Life in Japanese Adults Aged 60 Years or Older: Results from a Prospective, Observational Cohort Study.

BACKGROUND AND OBJECTIVES: Herpes zoster (HZ) and its most frequent complication, post-herpetic neuralgia (PHN), have been shown to considerably impact quality of life (QoL). This has not yet been demonstrated in Japan. METHODS: QoL in HZ and PHN patients was evaluated using the Zoster Brief Pain Inventory (ZBPI), EuroQoL-5 Dimension (EQ-5D), Short-Form 12 version 2.0, and short-form McGill Pain Questionnaire up to 270 days after rash onset as part of a prospective, observational, cohort study conducted in Kushiro, Hokkaido, Japan. RESULTS: This study involved 412 adults ≥ 60 years of age diagnosed with HZ, 38 of whom developed PHN. QoL in daily activity performance and emotional and physical functioning was impaired at Day 0 (rash onset) and almost resolved by Day 90. Although the mean ZBPI worst pain score for HZ patients without PHN improved from 4.1 at Day 0 to 0.1 at Day 90, the score for HZ patients with PHN at Day 90 was comparable to that for HZ patients without PHN at Day 0. While the EQ-5D score in HZ without PHN improved, on average, from 0.755 to 0.949, the score for HZ with PHN was dependent on PHN duration and did not improve until PHN disappearance. CONCLUSIONS: HZ impaired QoL in daily activity performance and emotional and physical functioning. The negative impact on QoL was more prevalent in patients with a longer PHN duration compared with HZ without PHN. ClinicalTrials.gov identifier: NCT01873365.

Evaluating Physician Attitudes and Practices Regarding Herpes Zoster Vaccination.

PURPOSE: To investigate the knowledge, attitudes, and practice patterns of primary care physicians regarding administration of the herpes zoster (HZ) vaccine at NYU Langone Health (NYULH). METHODS: A cross-sectional online survey was distributed from January to March 2017 to all physicians in the Division of General Internal Medicine and Clinical Innovation at NYULH across 5 different practice settings. RESULTS: The response rate was 26% (138 of 530). Of the surveyed physicians, 76% (100/132) agreed that the HZ vaccine was an important clinical priority, compared with 93% and 94% for influenza and pneumococcal vaccination, respectively (P < 0.001). Only 35% (47/132) strongly agreed that it was important, compared with 68% (90/132) and 74% (98/132) who strongly agreed that pneumococcal and influenza vaccines, respectively, were important. Respondents estimated that 43% of their immunocompetent patients aged 60 or older received the HZ vaccine, whereas only 11% of patients aged 50 to 59 received the HZ vaccine (P < 0.001). The rate of HZ vaccination was lower in public hospitals (26%) than in the NYULH faculty group practice (46%) (P = 0.007). A greater percent (67% and 72%) of their patients have received influenza and pneumococcal vaccines, respectively (P < 0.001). Almost all doctors (99%, 131/132) consider the Centers for Disease Control and Prevention recommendations important in determining vaccination practices. CONCLUSIONS: HZ vaccination rates remain relatively low compared with rates of influenza and pneumonia vaccination. The recommendation for vaccination against zoster by the Centers for Disease Control and Prevention for individuals aged 50 years and older and stronger recommendations by primary care physicians for administration of zoster vaccines are needed to increase HZ vaccination rates.

Reduced NK cell IFN-γ secretion and psychological stress are independently associated with herpes zoster.

The pathogenesis of herpes zoster is closely linked to reduced varicella-zoster virus-specific cell-mediated immunity. However, little is known about the interplay between natural killer cells and psychological stress in the pathogenesis of herpes zoster. This study aimed to investigate possible associations among natural killer cells, T cells and psychological stress in herpes zoster. Interferon-gamma secretion from natural killer cell, psychological stress events, stress cognition scale scores and cytomegalovirus-specific cell-mediated immunity were compared between 44 patients with herpes zoster and 44 age- and gender-matched control subjects. A significantly lower median level of interferon-gamma secreted by natural killer cells was observed in patients with a recent diagnosis of herpes zoster than in control subjects (582.7 pg/ml vs. 1783 pg/ml; P = 0.004), whereas cytomegalovirus-specific cell-mediated immunity was not associated with herpes zoster. Psychological stress events and high stress cognition scale scores were significantly associated in patients with herpes zoster (P<0.001 and P = 0.037, respectively). However, reduced interferon-gamma secretion from natural killer cell and psychological stress were not associated. In conclusion, patients with a recent diagnosis of herpes zoster display reduced interferon-gamma secretion from natural killer cells and frequent previous psychological stress events compared with controls. However, reduced natural killer cell activity is not an immunological mediator between psychological stress and herpes zoster.