Herpes zoster versus simplex,genital herpes oral verkehr,natural treatment for ovarian cysts and fibroids - Test Out

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Los recortes son una forma practica de recopilar diapositivas importantes para volver a ellas mas tarde. The impact of herpes zoster (HZ) and post-herpetic neuralgia (PHN) on patientsa€™ quality of life (QoL) is currently poorly documented.
Telephone interviews in Germany identified patients a‰?50 years old with painful HZ diagnosed during the previous 5 years. HZ causes substantial pain, which seriously interferes with many aspects of daily life, particularly in patients with PHN. MethodsInterviewsInterviewers from TNS Healthcare Germany contacted randomly selected individuals in private German households between 25 March and 8 May 2008.
Although 97% of patients received treatment for HZ, 41% did not receive treatment within 3 days of rash onset.
High proportions of patients experienced problems in their usual daily activities (75%) and self-care (56%). DiscussionThis scientific survey assessed the impact of HZ and PHN on the QoL and daily life of a German population aged a‰?50 years who had experienced painful HZ during the previous 5 years.
ConclusionsPatients with HZ have high levels of pain, and this affects many areas of their lives, including daily activities, mobility, work, sleep and mood. AcknowledgementsThe authors take full responsibility for the content of this contribution but thank Communigen Ltd., Oxford, UK (supported by Sanofi Pasteur MSD), for their assistance in manuscript preparation. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. Presentations of background materials on zoster and the vaccine were made during ACIP meetings in October 2005 and the three meetings in 2006. VZV is an exclusively human pathogen that infects approximately 98% of the adult population in the United States (5). The triggers for reactivation of VZV have not been identified and probably involve multiple factors. Zoster rash is typically unilateral and does not cross the mid-line, erupting in one or two adjacent dermatomes. A common and potentially debilitating consequence of zoster is PHN, a persistent pain after resolution of the rash.
Regardless of definition, the pain of PHN can last for weeks or months and occasionally persists for many years. An uncommon complication of zoster is Ramsay Hunt syndrome, a peripheral facial nerve palsy accompanied by zoster vesicles on the ear, hard palate, or tongue (42). Occasionally, zoster can cause motor weakness in noncranial nerve distributions, called zoster paresis (44,45).
Rarely, patients will experience acute focal neurologic deficits weeks to months after resolution of the zoster rash, involving the trigeminal distribution contralateral to the initial rash.
Cutaneous dissemination is not life-threatening; however, it is a marker for VZV viremia that can seed the lungs, liver, gut, and brain and cause pneumonia, hepatitis, encephalitis, and disseminated intravascular coagulopathy in 10%–50% of episodes. The risk for neurologic zoster complications is generally increased in immunocompromised persons.
Compared with other immunocompromised persons, the clinical features of zoster are less severe and visceral dissemination less common among persons infected with human immunodeficiency virus (HIV) (56,57). In some cases, particularly in immunosuppressed persons, the location of rash appearance might be atypical, or a neurologic complication might occur well after resolution of the rash. In immunocompromised persons, even when VZV is detected by laboratory methods in lesion specimens, distinguishing chickenpox from disseminated zoster might not be possible by physical examination (72) or serologically (73–75).
Zoster lesions contain high concentrations of VZV that can be spread, presumably by the airborne route (76,77), and cause primary varicella in exposed susceptible persons (77,78–83). Most studies have not documented a seasonal pattern to zoster incidence (13,38,92,95,105,117). Unlike other vaccine-preventable diseases, zoster epidemiology is not directly related to exposure but to the biology underlying the virus-host relation that allows reactivation of latent VZV. The incidence of zoster is increased substantially in persons with hematologic malignancies and solid tumors (120). Zoster is common following hematopoietic stem cell transplantation (HSCT); rates are 13%–55% during the first year (54,128,129). The risk for zoster appears to be elevated in persons with inflammatory diseases; however, for most of these conditions, data are insufficient to determine how much of the risk is attributable to the underlying disease versus its treatment.
Certain studies have evaluated the risk for zoster in persons with other noninflammatory co-morbid conditions, although findings have not been consistent.
VZV can be transmitted from zoster lesions to cause primary varicella in susceptible persons. Although a sufficient number of varicella exposures could reduce the risk for zoster in select populations, it is unclear whether such levels of exposure play an epidemiologically important role in reducing the risk for zoster among the general population of older adults who are at the highest risk for the disease, and, if so, how long such effects would last in the elderly. Trauma or surgery could lead to reactivation of VZV in the affected dorsal root ganglion and increase the risk for zoster rash in that dermatome. Finally, one study indicated that dietary micronutrient intake was protective against zoster. Zoster is not a reportable condition in the United States; therefore, incidence has been inferred from a variety of studies. Despite these limitations, certain analyses of zoster incidence in the United States have been conducted. Certain studies provide evidence of increasing age-specific zoster incidence in the United States (38,62,165,166), although other studies have shown no such trend (104). In a community-based study in Olmsted County, Minnesota, approximately 3% of patients with zoster were hospitalized for the illness (62).
Drawing conclusions from studies on the risk for PHN is difficult because definitions for PHN vary and results are influenced by many factors, including the source and age of the study population.
The treatment of acute zoster, the prevention of PHN development among patients with acute zoster, and the treatment of patients with current PHN are complex clinical problems with ongoing uncertainties and active research (31).
Two clinical trials have assessed the role of corticosteroids in combination with acyclovir for treatment of zoster and prevention of subsequent PHN (179,180).
A variety of approaches have been used with varying degrees of success for control of acute zoster pain, including acetaminophen, nonsteroidal anti-inflammatory agents, tricyclic antidepressants, opiates, anticonvulsants, capsaisin, and topical anesthetics (31). Patients with uncomplicated zoster should be advised to keep the rash clean and dry, to avoid topical antibiotics, and, if possible, to keep the rash covered. Some health-care institutions might exclude personnel with zoster from work until their lesions dry and crust (85). Zoster vaccine, when reconstituted as directed in the package label using the supplied diluent, is a sterile preparation for subcutaneous administration. The efficacy of zoster vaccine was evaluated in a phase 3 vaccine trial termed the Shingles Prevention Study, a double-blind randomized, placebo-controlled trial involving 38,546 healthy adults aged >60 years who had a history of varicella or at least 30 years of residence in the continental United States (as a marker of previous infection).
In general, with increasing age at vaccination, the vaccine retained efficacy against severity of zoster better than against zoster itself. Twelve clinical lots of zoster vaccine were used in the Shingles Prevention Study, nine of which were heat treated to accelerate aging of the vaccine. A substudy of the Shingles Prevention Study was conducted among 1,395 persons to assess VZV-specific immunity at baseline and 6 weeks following administration of zoster vaccine or placebo.
No clear dose response for increases in GMTs was observed; similar increases were achieved in vaccine recipients throughout the dosage range used in the Shingles Prevention Study (189). Vaccine efficacy for zoster prevention declined during the first year following vaccination, but remained stable through the remaining 3 years of follow up (Figure 4).
Adverse events were monitored in the Shingles Prevention Study population, with more comprehensive ascertainment in a safety substudy comprising 6,616 persons (3,345 vaccine recipients and 3,271 placebo recipients) (Table 4). The safety and tolerability of zoster vaccine was evaluated in a separate study among persons aged 50–59 years, including 62 persons who received the standard potency (approximately 58,000 PFUs) and 123 persons who received high potency (approximately 207,000 PFUs) (195).
Varicella-like rashes, including injection site varicella-like lesions, generalized varicella-like rashes, and zoster-like rashes, were evaluated in the Shingles Prevention Study during the first 42 days of observation (Table 4).
The economic burden of zoster in the elderly is substantial and includes direct costs attributed to health-care use and indirect costs attributed to losses in productivity from temporary or more permanent disability. Five studies have estimated the cost-effectiveness of a 1-dose routine vaccination program of immunocompetent persons aged >60 years (196,197,199,202,203) (Table 5). Patients with PHN had a greater prevalence of these problems than those with HZ: usual daily activities (91% versus 73%) and self-care (75% versus 54%). This retrospective approach enabled information to be captured on the full course of HZ episodes, from rash onset to pain resolution.
Results of this survey clearly showed that the development of PHN is consistently associated with worse outcomes than HZ. Weinke has received honoraria or consulting fees from GlaxoSmithKline, Novartis Vaccines and Sanofi Pasteur MSD. Following vaccine licensure on May 25, 2006, recommendation options were presented to ACIP in June 2006, and final options were presented at the October 2006 meeting. However, specific components of cell-mediated immunity (CMI) have an important role in controlling the development of zoster by preventing reactivation within the neuron or the full clinical expression of reactivated VZV as zoster. The frequency of zoster occurrence in different dermatomes has been evaluated in certain studies. Pathologic observations thought to distinguish PHN from uncomplicated zoster include axonal and cell body degeneration, atrophy of the spinal cord dorsal horn, scarring of the dorsal root ganglion, and loss of epidermal innervation of the affected area.
The nature of PHN pain varies from mild to excruciating in severity, constant, intermittent, or triggered by trivial stimuli. Among persons with zoster, 10%–25% have eye involvement, called herpes zoster ophthalmicus (HZO) (38,39) (Figure 2). The pathophysiology of this complication involves reactivation of VZV in the geniculate ganglion of the facial nerve. This ischemic stroke syndrome, termed granulomatous angiitis, is believed to be caused by direct extension of VZV from the trigeminal ganglion to the internal carotid artery or its branches, resulting in inflammation (30).
Visceral dissemination with no skin involvement can occur in profoundly immunocompromised persons. These complications, which can be aggressive and even fatal, include myelitis, chronic encephalitis, ventriculitis, meningoencephalitis, and cranial palsies (30). Some zoster presentations that are unique to persons infected with HIV include atypical skin eruptions (58,59) and an aggressive variant of acute retinal necrosis that generally results in blindness (60).
Patients with localized pain or altered skin sensations might undergo evaluation for kidney stones, gallstones, or coronary artery disease until the zoster rash appears and the correct diagnosis is made (62).
In these instances, a history of VZV exposure, a history that the rash began with a dermatomal pattern, and results of VZV antibody testing at or before the time of rash onset might help guide the diagnosis. Because zoster reflects reactivation of latent VZV, the primary risk factor and a necessary precondition for zoster is previous VZV infection.
Persons acquiring an intrauterine or early childhood infection with VZV are at increased risk for pediatric zoster (91–93). Loss of specific immunity allows VZV to complete the process of reactivation and spread to the epidermis to produce the fully expressed clinical illness (12).
Among persons experiencing zoster, the primary risk factor for the development of PHN is age. In North Carolina, reported lifetime zoster occurrences and reported incidence were lower in blacks by 65% and 75%, respectively, compared with whites after controlling for relevant confounders (115,116). Because CMI plays a key role in controlling both development of zoster and the features of its clinical expression, deficiencies in CMI, regardless of their etiology, are risk factors for both zoster and its severe manifestations. Rates are increased following solid organ transplants (renal, cardiac, liver, and lung) (5%– 17%).
Zoster has been associated with systemic lupus erythematosus (SLE), with rates of 15–91 per 1000 person years (138–143). Although some experts have suggested that zoster can be caused directly by exposure to VZV from varicella or from other cases of zoster (72,153,154), in general, zoster is not associated with epidemics of varicella. Protection might be partially maintained by exposure to varicella circulating in the population and the resulting exogenous boosting of VZV-specific immunity (15,117,155). Women are at greater risk for zoster (13,102,103,110,111) despite the fact that women probably have more exposure to young children who experience varicella. However, only two rigorous evaluations of the role of psychological stress on zoster have been conducted.
Such a development would seem to be specific and easily ascertained, and certain reports and case series describe such events (158–161).
Observed rates have varied substantially on the basis of methods for case ascertainment, access to health care, and case definitions. The observed increases cannot be solely attributed to changes in the epidemiology of varicella, because documentation of increases predated licensure of varicella vaccine in the United States in 1995 (38) and because age-specific increases over time also are being reported in certain international settings, including in the absence of varicella vaccination programs (105,167,168). Although data are limited, certain studies suggest a recurrence rate that is comparable to the rate of initial episodes (13,38,114). Conclusions about hospitalization for zoster should be interpreted carefully if they are derived from administrative data. A crude rate of 16.1 per 100,000 population was identified in an analysis of Connecticut-wide hospitalization data that included all zoster episodes, not just primary discharge diagnosis (172).
Although values differ substantially, all studies indicate that zoster hospitalization rates increase with age (170,172–174).
On the basis of clinical experience and in the absence of zoster-related deaths in cohort studies, certain experts believe that zoster mortality appears to be uncommon, particularly among healthy persons (176).
Among zoster patients treated with a placebo in clinical trials of antiviral drugs, approximately one third still had pain after 3 months and approximately one fourth had pain at 6 months (177,178). Acyclovir, famciclovir, and valacyclovir are approved by the FDA for treatment of zoster in immunocompetent patients. In more severe instances of pain, referral to a pain specialist, or even hospitalization and administration of epidural analgesics, is often considered. They should alert their physician if the rash worsens or they have fever, which could indicate bacterial superinfection (31). Persons with localized zoster should avoid contact with susceptible persons at high risk for severe varicella in household and occupational settings until lesions are crusted. The Oka strain was isolated in Japan (184) in the early 1970s from vesicular fluid from a healthy child who had varicella; the strain was attenuated through sequential propagation in cultures of human embryonic lung cells, embryonic guinea-pig cells, and human diploid cells (WI-38). The vaccine should not be injected intravascularly or intramuscularly and should only be reconstituted and injected using a sterile syringe free of preservatives, antiseptics, and detergents, which can inactivate the vaccine virus.
Active case ascertainment was conducted through monthly telephone contact supplemented by a close-out interview.
Efficacy analyses were performed with the use of a follow-up interval that excluded the first 30 days after vaccination and the modified intention-to-treat population, which excluded persons who withdrew or in whom a confirmed case of herpes zoster developed, within the first 30 days after vaccination.
Thus, efficacy for the prevention of zoster was highest among persons aged 60–69 years and declined with increasing age (Table 2). Peak CMI responses were present 1–3 weeks following vaccination (187,190,191), as would be expected for anamnestic responses that would occur in persons with previous VZV infection. Vaccine efficacy for PHN prevention had a similar pattern, with an initial decline and subsequent stabilization. In the Shingles Prevention Study population, the number and types of serious adverse events (4) during the 42 days after receipt of vaccine or placebo were similar (1.4%). Otherwise, percentages are rates weighted in proportion to the number of persons with safety follow-up in each age group.


In addition, much of the economic burden of zoster is borne by individual patients as reduced quality of life because of pain and suffering. Among patients with acute episodes of zoster, average expenditures ranged from $112–$287 per episode of out patient care, $73–$180 per antiviral treatment, and  $3,221–$7,206 per hospitalization (2006 dollars). Consulta nuestras Condiciones de uso y nuestra Politica de privacidad para mas informacion. Consulta nuestra Politica de privacidad y nuestras Condiciones de uso para mas informacion.
It is based on the a€?Infratest-Telephon Master Sample,a€™ which was developed specifically for telephone surveys and leads to bias-free, representative samples. Eight patients could not be classified as having HZ or PHN, so results are presented for 280 patients.
In contrast, patients with PHN had statistically significantly worse outcomes on every pain and QoL measure than patients with HZ.Patient-reported pain and treatmentIn 60% of patients, HZ pain was spontaneous, with some patients reporting spontaneous pain that increased with friction (30%), pressing (28%) or contact with a cold object (6%). Patient-reported outcomes clearly showed that HZ causes substantial pain that seriously interferes with many aspects of patientsa€™ daily life, particularly sleep, mood and work. This survey will contribute to an increased awareness of the significant burden that patients with HZ and PHN suffer.
These results were published in June 2005 (4) and presented at the ACIP meeting later that month. During review by CDC and external partners, modifications were made to the proposed recommendations to update and clarify wording in the document. During its viremic phase, cell-associated VZV gains access to epidermal cells, causing the typical varicella rash. The effectiveness of these protective components of CMI is well maintained in immunocompetent persons during childhood and early adulthood. In general, thoracic, cervical, and ophthalmic involvement are most common (Figure 1) (26–28). Certain experts believe this neuronal damage might be caused by ongoing viral replication (30,31). Approximately half of patients with zoster or PHN describe their pain as “horrible” or “excruciating”, ranging in duration from a few minutes to constant on a daily or almost daily basis (32).
HZO can occur when reactivation involves the nasociliary branch of the trigeminal nerve, sometimes preceded by the presence of zoster vesicles on the nose (Hutchinson sign). Additional signs and symptoms of Ramsey Hunt syndrome can include pain, vertigo, hearing loss, sensitivity to sound, tinnitus, and loss of taste.
The weakness develops abruptly within 2–3 weeks after onset of the rash and can involve upper or lower extremities. One specific risk for persons with some immunosuppressive conditions is dissemination of the zoster rash.
Even with antiviral treatment, the case fatality rate from visceral dissemination is 5%–15%, with most deaths attributable to pneumonia (49,54,55). However, the risk for PHN is not appreciably increased among immunocompromised persons who develop zoster (30). In its classical manifestation, the signs and symptoms of zoster are usually distinctive enough to make an accurate clinical diagnosis once the rash has appeared (63). Tzanck smears are inexpensive and can be used at the bedside to detect multinucleated giant cells in lesion specimens, but they do not distinguish between infections with VZV and HSV.
When VZV infections occur before age 2 months, the risk for zoster occurring by the age of 12 years is increased >35-fold compared with the risk for VZV infections occurring after infancy (92).
Virtually all studies conducted in numerous settings and with various study designs have indicated an association between age and increasing zoster incidence, extending to the oldest cohorts (4,62,95,102–104). Although precise correlates of protection against zoster have not been identified, certain CMI responses to VZV antigen decline with age (21,22,107,108).
Several studies have indicated that the risk for PHN among persons with zoster increases with age, particularly for persons aged >50 years (13,35,62,109,110) (Figure 3).
Other studies (13,102–104,112) using a variety of methods also demonstrated an age-standardized excess of zoster among women. A study in the United Kingdom indicated that zoster risk in patients was 54% lower among blacks after adjusting for age, sex, country of birth, or household childhood contacts (95).
This pattern might be related to ultraviolet irradiation that peaks during summer months and might serve as a trigger for zoster (28,118,119).
Although the magnitude of zoster risk can be extremely high among immunocompromised persons, the overall population attributable risk is modest because immunosuppression is uncommon (62,103,114). The magnitude of risk depends on both the nature of the underlying cancer and the type of treatment (121). Incidence is highest during the months immediately following the procedure, and the majority of zoster cases occur within a year of transplantation (130–132). For HIV-infected children, the risk is even higher (467 per 1000 person years), especially among children who acquire VZV infection when they are profoundly immunosuppressed (137).
In addition, zoster does not have a seasonal pattern to suggest it is spread directly from varicella (13,28,38,92,105,117).
A Japanese study indicated that the risk for zoster in children was not diminished by repeated varicella exposures (92). A case-control study documented a significant association with number of stressful life events within 6 months of reported zoster (p = 0.012) (157). The age distribution in the population being studied also is an important consideration when comparing these studies because zoster can vary dramatically across study sites. Because the basis for this increase remains unclear, predicting whether the age-specific risk for zoster will continue to increase in the future is difficult.
A community-based study of clinician-diagnosed zoster was conducted in Olmsted County, Minnesota. Hospital administrative data often do not distinguish zoster episodes that were reasons for hospitalizations from those episodes that were incidental to the hospitalization or that occurred during prolonged hospital stay. Vital records might not distinguish deaths attributed to zoster from incidental deaths occurring merely in the presence of zoster, and they might not capture information on the immunologic status among those deaths. However, these trials might include a population of patients with more severe zoster pain, thereby introducing a detection bias that could inflate estimated risks for PHN. All three are nucleoside analogs that inhibit replication of human herpes viruses, including VZV. A 3-week tapering course of corticosteroids diminished acute zoster pain and decreased the time to cutaneous healing, cessation of analgesic therapy, and return of uninterrupted sleep and normal daily activities.
Many of these same modalities are used with varying degrees of success for control of chronic PHN pain (26,181,182).
Further passage of the virus was performed at Merck Research Laboratories in human diploid cell cultures (MRC-5). Zoster cases were confirmed by PCR testing (93%), viral culture (1%), or evaluation by a panel of five physicians with expertise in zoster diagnosis (6%). Declines in efficacy of preventing zoster were observed with each 5-year increase in age throughout the age range of participants (187).
Anamnestic antibody response was evaluated using gpELISA to measure increases in VZV antibody levels after vaccination.
After conclusion of the Shingles Prevention Study, approximately 7,500 vaccine recipients will be followed to extend observation to 10 years.
Certain studies provide a range of estimates for health-care use among persons aged >60 years for treatment of zoster and PHN. All five studies used a Markov cohort model (105), followed a cost-utility analytic approach that included a societal perspective (204,205), and used quality-adjusted life-year (QALY) scores to assess the incremental impact of the vaccine program on quality of life. Many patients with PHN (91%) and HZ (73%) experienced problems with daily activities, including work, studies, housework, family and leisure activities. The impact of walking ability on QoL rating was not significant according to multiple regression analysis. In September 2005, ACIP’s measles-mumps-rubella and varicella workgroup expanded its membership to include experts in adult medicine and in zoster and began review of relevant data on zoster and the investigational vaccine.
As new information on the epidemiology and prevention of zoster becomes available, it will be reviewed by ACIP and recommendations will be updated as needed. The virus then enters sensory nerves in mucocutaneous sites and travels through retrograde axonal transport to the sensory dorsal root ganglia adjacent to the spinal cord where the virus establishes permanent latency in neuronal cell bodies (6–7).
These CMI components are believed to be partially or substantially maintained by periodic immunologic boosting. In addition, consensus is lacking regarding criteria needed to distinguish the quality, duration, or underlying pathophysiology of pain occurring with zoster versus PHN. The pain can disrupt sleep, mood, work, and activities of daily living, adversely impacting the quality of life and leading to social withdrawal and depression (Table 1) (31–33). Keratitis occurs in approximately two thirds of patients with HZO (40), often causing corneal ulceration.
Other rare neurologic complications of zoster include myelitis, aseptic meningitis, and meningoencephalitis. True cutaneous dissemination generally occurs only among immunocompromised patients, occurring in up to 37% of zoster cases in the absence of antiviral treatment (49–54). Occasionally, zoster might be confused with impetigo, contact dermatitis, folliculitis, scabies, insect bites, papular urticaria, candidal infection, dermatitis herpetiformis, or drug eruptions.
VZV obtained from lesions can be identified using tissue culture, but this can take several days and false negative results occur because viable virus is difficult to recover from cutaneous lesions. In one study of VZV transmission from zoster, varicella occurred among 15.5% of susceptible household contacts (78). Other case series suggest that the risk for pediatric zoster also might be increased in children who experienced varicella at older ages (94). In one study, the risk for experiencing at least 2 months of pain from PHN increased 27.4-fold among patients aged >50 years compared with those aged 50 years (62).
Patients with Wegener’s granulomatosis have a reported incidence of 45 zoster cases per 1000 person years (146), and recurrences in these patients are common. Another study documented an increased risk for zoster in persons who subsequently had multiple sclerosis diagnosed (152). Theoretically, reactivation of latent VZV might be triggered by exposure to exogenous VZV (123,153); however, no evidence suggests that such episodes occur more frequently than would be expected to occur by chance. A prospective cohort study indicated a nonsignificant association (p = 0.078) between zoster risk and negative life events. Conclusions cannot be drawn from cross-study comparisons without adjusting for age or comparing age-specific rates directly. An Australian study using administrative data indicated that 1% of patients hospitalized with a primary zoster diagnosis died; the number of deaths directly attributable to zoster was not validated (174).
Clinical trials have indicated that these agents, taken orally, reduce the duration of viral shedding and lesion formation, reduce the time to rash healing, and decrease the severity and duration of acute pain from zoster and the risk for progression to PHN. Elderly persons, who already have reduced physiologic reserve and typically take multiple medications for pre-existing chronic conditions, might be unable to tolerate psychotropic and other medications for management of their acute zoster or chronic PHN pain (31,33). The cells, virus seeds, virus bulks, and bovine serum used in the manufacturing are all tested to provide assurance that the final product is free of adventitious agents.
However, its minimum potency is at least 14-times the potency of VARIVAX®, which contains a minimum of 1,350 (approximately 3.13 log10) PFU. Patients with confirmed zoster were followed for at least 182 days to assess the outcome of the condition, including presence and severity of pain. However, no significant differences were observed among persons aged 60–69 years versus those aged >70 years in vaccine efficacy at reducing BOI or PHN, probably because the independent effect of reducing PHN among patients who developed zoster was greatest among persons aged 70–79 years (Table 2). Because placebo recipients were offered zoster vaccine at the conclusion of the Shingles Prevention Study, zoster rates in these 7,500 persons will be compared with historic controls.
Nonetheless, no temporal or clinical patterns of adverse events were observed in vaccine recipients to suggest a causal relation (4,186). Three persons who had withdrawn from the study because of worsening health and subsequently died were included in the safety analysis.† Confidence interval. The estimates vary widely because of differing assumptions regarding the risk for PHN and of complications resulting from zoster. Among the subset of patients with PHN persisting from 30 days to 12 months, annualized health-care costs, including costs of the acute episode, ranged from $2,159 to $5,387 (200,201). HZ is characterized by a vesicular skin rash, which is often preceded or accompanied by acute pain or itching.
Initially, only patients with HZ diagnosed during the previous 12 months were included, but this criterion was changed to obtain the required sample size in a shorter timeframe (na€‰=a€‰280).
High levels of pain (score 8a€“10) on average and at worst were reported by greater proportions of patients with PHN than with HZ (Table 2A). High proportions of patients experienced problems with mobility (63% overall), particularly those with PHN (78% versus 61% of those with HZ). Shortly thereafter, this workgroup reformed as the ACIP shingles workgroup and, during subsequent months, held 19 conference calls to review and discuss scientific evidence related to herpes zoster and zoster vaccine, including the epidemiology and natural history of zoster and its sequelae, and the safety, immunogenicity, efficacy, financing, storage, and handling of the zoster vaccine. The rash is initially erythematous and maculopapular but progresses to form coalescing clusters of clear vesicles containing high concentrations of VZV (Figure 1). Therefore, the duration of pain used to define PHN has been inconsistent, ranging from any duration after resolution of the rash to periods from >30 days to >6 months after rash onset. Anecdotes of suicide among patients suffering from PHN have been reported (34; Peter Richards, MD, personal communication, 2007). Other complications include conjunctivitis, uveitis, episcleritis and scleritis, retinitis, choroiditis, optic neuritis, lid retraction, ptosis, and glaucoma.
Idiopathic facial palsy (Bell’s palsy) might be caused by inapparent VZV reactivation (42,43).
The prognosis for these conditions is good, although encephalomyelitis can be life threatening.
Dissemination usually begins with a dermatomal rash; however, the rash sometimes begins with no primary dermatomal involvement (54).
More frequently, zoster is confused with the rash of herpes simplex virus (HSV), including eczema herpeticum (4,31,64–66). Direct fluorescent antibody (DFA) staining of VZV-infected cells in a scraping of cells from the base of the lesion is rapid and sensitive. In contrast, following household exposure to varicella, a more recent study demonstrated VZV transmission among 71.5% of susceptible contacts (84).
Varicella vaccine is effective at preventing initial wild-type VZV infection in persons not previously infected. Conversely, the risk for zoster might be diminished in persons born in countries (95) or living in communities (96) where varicella infection tends to occur at later ages. Women with zoster might also be at increased age-specific risk for developing PHN compared with men (35,62). The basis by which these stimuli provoke zoster is unclear, but they suggest that nonimmunologic factors can play important roles in the pathophysiology of zoster. Differences in the prevalence of immunosuppression or in racial makeup also can influence population-wide zoster incidence. On the basis of these data, an estimated 32% of persons in the United States will experience zoster during their lifetime (CDC unpublished data, 2007).
Of 1,669 persons that experienced an episode of zoster during that period, 24 experienced a second episode, suggesting a high incidence of zoster recurrence and providing no evidence that an episode of zoster protects against recurrence (62). In addition, underlying immunosuppressive conditions might not be available or might not be collected from administrative data. Certain analyses have indicated that almost all zoster deaths occur in the elderly, with a rate >10-fold higher among persons aged >65 years (171,173,174).


Results from the trial might not reflect risks for progression to PHN in community settings because ascertainment, diagnosis, and antiviral treatment of zoster were standardized and thorough. Because all three antiviral agents are safe and well tolerated, many experts recommend that treatment should be considered for all eligible patients with zoster, and specifically recommend treatment for persons aged >50 years who have moderate or severe pain, moderate or severe rash, or involvement of nontruncal dermatomes (31). Theoretically, corticosteroids should be equally effective in combination with valacyclovir or famciclovir; however, combinations of these agents have not been studied in clinical trials. For persons aged >80 years, efficacy against zoster was 18% (Table 2), but efficacy against PHN (39%) was better retained (186). ELISPOT responses were greater in persons aged 60–69 years than in persons aged >70 years (p60 years (193). Increases in RCF and IFN-γ ELISPOT responses persisted for 3–6 years following vaccination (192,194). The incidence of death and hospitalizations was similar in the two treatment groups throughout the observation time (4,186). Although indirect costs from death can occur with zoster, these costs result mostly from losses in work time caused by temporary or more permanent disability. Although virtually all adults are infected with VZV (5), specific immunologic parameters have not been identified to distinguish who will develop zoster.
These symptoms can precede the zoster rash by days to weeks (25) and rarely might be the only clinical manifestation of VZV reactivation (termed zoster sine herpete) (7). The vesicles form over several days and then evolve through pustular, ulcer, and crust stages. Among persons experiencing zoster, predictors of PHN include the occurrence and severity of pain both before and after onset of the rash, the extent of the rash, trigeminal or ophthalmic distribution (35,36), and the occurrence of viremia (37).
Zoster also can result in autonomic dysfunction, causing urinary retention and colon pseudo-obstruction. The accuracy of diagnosis is lower for children and younger adults in whom zoster incidence is lower and its symptoms less often classic.
DFA and other antigen-detection methods also can be used on biopsy material, and eosinophilic nuclear inclusions (Cowdry type A) are observed on histopathology. In hospital settings, transmission has been documented between patients or from patients to health-care personnel, but transmission from health-care personnel to patients has not been documented. These observations suggest that changes in the epidemiology of varicella caused by varicella vaccination or by other factors can alter the epidemiology of zoster, particularly pediatric zoster. In addition, the incidence of zoster appears to have been increasing over recent decades, even after adjusting for other factors, although this increase has not been observed consistently. These factors preclude determination of the portion of hospitalizations that could be prevented by a live-attenuated vaccine that is contraindicated for immunosuppressed persons. However, in a community-based study in Olmsted County, Minnesota, in which almost all medical events were captured, the risk for PHN in patients with zoster was 18%, 13%, and 10% when defining PHN as at least 30, 60, and 90 days of pain, respectively (62). In clinical trials, treatment has been initiated within 72 hours of rash onset, a biologically arbitrary time point that often is not feasible in clinical practice.
No evidence indicates that topical antiviral therapy or corticosteroids without systemic antiviral therapy have a role in treatment of zoster. Outcomes evaluated included incidence of zoster, incidence of PHN (defined as pain level of three or more [on a numerical rating scale of 0-10] persisting at least 90 days after rash onset), and burden of illness (BOI), measured using a mean value of severity-by-duration index for each treatment group, thus incorporating the incidence, severity, and duration of pain and discomfort from zoster). No significant differences by sex were observed in the efficacy of the vaccine at reducing BOI, PHN, or zoster (4). With all three assays, VZV-specific immunity measured 6 weeks after vaccination increased following receipt of vaccine but not placebo.
Otherwise, the differences in risk and 95% CIs are based on an asymptotic method for the difference of two binomial proportions where the proportions are weighted according to the number of persons with safety follow-up in each age group. Approximately 1%–4% of zoster episodes result in hospitalization, with a mean duration of 4.8 days. Patients with zoster (including those progressing to PHN) lose an average of >129 hours of work per episode (197,198), including losses of 12 or more hours of work time and 69 hours of leisure time during the first 30 days (196). Model assumptions varied regarding duration of vaccine protection, the efficacy of the vaccine for preventing PHN among vaccine recipients who developed zoster, costs associated with vaccine adverse events, and costs attributed to losses in work productivity. There is no standard definition of PHN, but it is commonly defined as pain that persists for at least 3 months after the onset of HZ rash (Oxman et al. This was mainly due to pain (60%), discomfort (60%), inability to concentrate (48%) and health care visits (48%). Lukas are employees of Sanofi Pasteur MSD, a provider of a herpes zoster vaccine approved in the European Union.
Workgroup members participated in 10 additional conference calls to develop and discuss recommendation options for preventing zoster. Prolonged or permanent sequelae of HZO include pain, facial scarring, and loss of vision (41). Polymerase chain reaction (PCR) techniques performed in an experienced laboratory also can be used to detect VZV DNA rapidly and sensitively in properly-collected lesion material, although VZV PCR testing is not available in all settings.
Persons with localized zoster are less likely to transmit VZV to susceptible persons in household or occupational settings if their lesions are covered (85). For all these conditions, zoster is generally not life-threatening, although cutaneous dissemination is more common, and deaths have been reported in such patients (138,141,142). In the Shingles Prevention Study, two of approximately 20,000 vaccine placebo recipients had two episodes of zoster within 3 years of the initial episode. A total of 957 confirmed cases of zoster occurred among study participants: 315 among vaccine recipients and 642 among placebo recipients. Negative values for the difference in risk result when the rate in the placebo group is larger than that in the vaccine group.¶ Events classified as possibly related to vaccination were assessed by a blinded investigator at each site. Data on the national economic impacts of zoster and its complications on quality of life have not been reported. Patients also rated pain level on a scale from 0 (a€?no paina€™) to 10 (a€?pain as bad as you can imaginea€™).
When scientific evidence was lacking, recommendations incorporated expert opinions of the workgroup members.
Parameters that have been monitored and correlate with such protection include anamnestic boost in anti-VZV antibodies in vivo in response to VZV-based vaccination, and the presence of and boost in memory CD4 T cells as measured in vitro by proliferation of peripheral blood mononuclear cells (PBMC), by frequency of proliferating PBMC, or by frequency of interferon-? Altered sensitivity to touch, pain provoked by trivial stimuli, and unbearable itching are all frequently reported. These cases provide the first laboratory-confirmed evidence that zoster can recur in immunocompetent persons, even soon after the initial episode (4). If treatment cannot be initiated within 72 hours of rash onset, experts recommend that it should be initiated as soon as possible, particularly in the presence of new vesicle formation or of complications. However, for all three assays, no threshold level of immunity that predicted complete protection from zoster was observed. Health-care use for zoster and PHN increases substantially with the age of patients (196–198). Receipt of treatments or medications and the pain relief that they provided were also assessed.Further questions assessed the impact of HZ and PHN on QoL.
At a vaccine cost of $150 per dose, the societal costs of routinely vaccinating immunocompetent persons aged >60 years range from $27,000 to $112,000 per QALY gained. Overall, 65% of patients did not have sufficient sleep most of the time (HZ, 63%; PHN, 78%).
In the sensitivity analyses, variables with the strongest influence on outcomes include vaccine costs, duration of vaccine efficacy, risks for PHN as a complication, and costs and QALY scores for zoster and its complications. 2008).In Western countries, the estimated incidence of acute HZ in the general population is 3a€“5 per 1,000 person-years (annual events per 1,000 population)(Gauthier et al. Limitations in the activities of daily living were also assessed (including moderate physical efforts and climbing flights of stairs) and consequences for family members and the social circle of the patient. These latter two parameters are generally assessed using a responder cell frequency (RCF) assay and an IFN-? Patients rated interference of pain from 0 (a€?does not interferea€™) to 10 (a€?completely interferesa€™) in the following seven areas: general activity, mood, walking ability, normal work, social relations, sleep and enjoyment of life. 252 La semejanza en las lesiones clinicas de la erisipela facial y el herpes zoster bilateral, y la ausencia de pruebas diagnosticas especificas en Atencion Primaria hacen necesaria la valoracion de la respuesta al tratamiento como metodo de confirmacion diagnostica.
Patients were asked about the impact of HZ and PHN on work and sleep, as well as feelings of stress and enjoyment.
In one study, acute HZ pain affected all domains of patientsa€™ activities of daily living (Lydick et al.
VZV-specific class I-restricted and unrestricted cytotoxicities also have been monitored using target cell lysis (23). Mujer de 80 anos que hace una semana presenta vesiculas agrupadas en mejilla izquierda que han progresado bilateralmente hasta ambos pabellones auriculares, con calor y picor. Eighty percent of patients experienced stress during the time they had HZ pain, particularly those with PHN (91% versus 78% of those with HZ) (Table 2C).
Although CMI is necessary for the control of zoster, other nonimmunologic factors also might be involved (24).
There was a clear correlation between increased intensity of pain and greater interference with activities. La falta de respuesta al Valaciclovir indicado inicialmente y la mejoria con Levofloxacino determino el diagnostico. The devastating effects of HZ pain on patientsa€™ QoL were comparable to the effects of myocardial infarction and clinical depression. HZ incidence increases with age because of a decline in specific immunity against latent VZV (Arvin 2005).
Two observational studies that employed various QoL questionnaires demonstrated a substantial pain burden of HZ in the first 30 days after rash onset, with moderate and severe levels of pain commonly experienced (Schmader et al.
MA?nster, Waxmann, pp 46a€“58Hope-Simpson RE (1965) The nature of herpes zoster: a long-term study and a new hypothesis. Pain interfered with all activities of daily living, particularly enjoyment of life, sleep, general activities, leisure activities, leaving the house and going shopping. The risk of patients developing complications such as PHN increases with age (Gauthier et al. Regression analysis showed that significant independent contributions were made by sensory pain burden to poorer physical functioning, overall pain burden to poorer role and social functioning, and affective pain burden to depression.Greater levels of acute pain may contribute to the development and severity of PHN. Psychosocial variables such as measures of role functioning, personality disorder symptoms and disease conviction may be additional risk factors for PHN (Katz et al.
1- La lesion es una placa eritematoedematosa, indurada , dolorosa y caliente con bordes bien definidos. This chronic complication remains refractory to pharmacological treatments and prevention strategies (Johnson and McElhaney 2009).
PHN is thought to be associated with numerous constitutional symptoms (chronic fatigue, anorexia, weight loss, physical inactivity, insomnia) and psychological symptoms (depression, difficulty concentrating). Results from a postal survey in the USA that used pain and QoL questionnaires showed that patients commonly reported moderate and severe levels of pain despite receiving analgesic agents (Oster et al.
3- Si no hay respuesta rapida al tratamiento valorar complicaciones, mas frecuentes en pacientes con enfermedad de base , o diagnostico incorrecto. 4-El Herpes zoster bilateral tiene baja incidencia y su presencia obliga a descartar un compromiso en el estado inmunitario. PHN burden was substantial and multidimensional, with all domains of daily functioning and health status negatively affected.
ESTRATEGIA PRACTICA DE ACTUACION JUICIO CLINICO: Erisipela facial BIBLIOGRAFIA - Mensa J, Gatell JM, Martinez JA, Soriano A, Vidal F, Serrano R, et al. There was a positive correlation between increasing pain severity and the extent of the negative QoL impact. An observational study that used patient questionnaires showed that the mean pain level in patients with PHN was moderate (score 4.2) (van Seventer et al. Pain interference was reported on all seven domains of health status, particularly mood, sleep and general activity.
QoL seems to be a particular problem in patients whose pain persists as PHN (Chidiac et al.
The prevalence of HZ and PHN is expected to increase with the rising mean age of the population (Brisson et al.
Increased awareness of the burden of HZ and PHN on QoL may lead to improved strategies for prevention and management. 2001).This retrospective survey has shown that pain levels in patients with HZ were unacceptably high, particularly in those who developed PHN. The aim of this survey was to assess the impact of HZ and PHN on the QoL of a German population aged a‰?50 years who had experienced painful HZ during the previous 5 years. HZ treatment using antiviral agents may reduce acute pain if given within 72 h of rash onset (Christo et al. 2007; Breuer and Whitley 2007), but probably will not ameliorate subsequent PHN (Johnson and McElhaney 2009).
Many patients in the present survey did not receive treatment within this time window, nearly half of patients needed more than one pain medication and patients with PHN experienced significantly less pain relief than patients with HZ, despite receiving more medications.
Multiple regression analysis revealed that general activity, sleep, mood, enjoyment of life and relations with others all had a significant impact on QoL rating. Patients with PHN had considerably worse outcomes on every QoL measure compared with patients with HZ.
Pain and QoL data from patients diagnosed in the previous 12 months were consistent with data from all patients. This demonstrated that patientsa€™ recollection of the impact of disease was not affected by time.The high burden of HZ and PHN demonstrated in the present study is similar to the findings from the observational studies discussed above (van Seventer et al.
The present survey proved to be a useful tool for assessing patient-reported outcomes in HZ and PHN. Therefore, the questionnaire has been translated and adapted for use in six other countries.
In lieu of prospective studies, retrospective studies can provide information more rapidly and with a larger sample size, and may give important leads for the design of a prospective study on the impact of HZ and PHN on patientsa€™ QoL.This study had certain limitations.
First, there was a relatively high proportion of patients diagnosed with HZ in the previous 12 months versus the total number of patients diagnosed in the last 5 years. This was because the screening criterion regarding length of time since diagnosis was changed after initial interviews to obtain the required sample size in a shorter timeframe.
Second, we evaluated the full course of HZ episodes, and thus were not able to use currently available validated questionnaires to evaluate pain and QoL, which only evaluate current pain.
However, this approach allowed a better view of the patienta€™s global experience of their illness and follows the approach taken in the pivotal SPS study that assessed the HZ burden of illness using a severity-by-duration measure (Oxman et al. Third, patients were required to recall information about their HZ disease from up to 5 years before the interviews. However, data clearly showed that patientsa€™ recollection of pain associated with HZ and PHN and the impact of disease on QoL were not affected by time. In the present telephone survey, many more women than men aged a‰?50 years may have been willing to discuss their health.



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