Pain Treatment for Herpes zoster

Incidence and Risk of Postherpetic Neuralgia after Varicella Zoster Virus Infection in Hematopoietic Cell Transplantation Recipients: Hokkaido Hematology Study Group

Herpes Zoster Eye Disease: New Ways to Combat an Old Foe?

UK experience of herpes zoster vaccination can inform varicella zoster virus policies

Varicella-zoster virus (VZV) causes chickenpox and then establishes latency in the autonomic ganglia. Reactivation of the virus, known as herpes zoster or shingles, manifests as a unilateral, vesicular rash localized within one dermatome accompanied by pain and pruritus. While the classic rash resolves within three weeks, older or immunocompromised individuals may experience prolonged symptoms, increased vesicle number, and complications such as post-herpetic neuralgia. Although the classic manifestations of VZV are well known, more cases are appearing with an atypical presentation. We highlight eight reports of unusual presentations describing confirmed cases of VZV that become reactivated and note a wide range of ages, with half over 70 years of age and half under 40 years of age, two including children. Unusual presentations include zoster sine herpete, vocal fold paralysis due to vagal nerve involvement, and encephalitis with massive pulmonary emboli in a previously healthy 37-year-old woman. One case features a child who developed shingles from the vaccine strain of VZV. Diagnostic delays occurred in all cases due to the atypical nature of the presentations, often resulting in initial misdiagnoses and inappropriate treatments such as antibiotics or corticosteroids. Despite eventual antiviral therapy, two patients experienced incomplete recovery, suffering from persistent neuropathic pain or muscle atrophy. These cases emphasize the variability in VZV presentations, the importance of timely diagnosis, and the need for greater clinical awareness to prevent delayed treatment and adverse outcomes.

Herpes zoster (HZ) and postherpetic neuralgia (PHN) are common diseases in a pain clinic. In Korea, the rate of clinical visits due to the incidence of herpes zoster was 7.93-12.54/1000 annually [1]. PHN is a painful neuropathy and the most common complication of HZ. A complete recovery from PHN is difficult for doctors despite of proper HZ treatment. In spite of the treatment, some patients suffered from severe PHN for several years. Therefore, the most important aspects are the risk factor of PHN and the method of prevention of PHN. In this issue of the Korean Journal of Pain (KJP), Jung et al. [2] reported the incidence of HZ in Cheonan, Korea. The results show that patients 50 years and older have a higher incidence of HZ, and the most common site of HZ was the thoracic nerve (47.9%), followed by the trigeminal nerve (21.4%). The incidence rate was similar to the affected site of PHN (thoracic area: 52.9%, trigeminal area: 15.6%) in Korea [3]. In patients who suffer from HZ, the risk factors of PHN are old age, presence of a painful prodrome, severe pain of HZ, severe rash, and immuno-compromised status [4,5,6]. In patients with HZ over 60 years, up to 25% progressed to PHN [7]. The proportion of PHN increases steadily from young ages up to 80-84 years [8]. Therefore, patients who are elderly and possess the risk factor with HZ must undergo more intensive treatment. The main treatment of HZ is medication and interventional therapy. Taking antiviral medication beginning within 72 hrs of rash onset is usually recommended [7,9,10]. Two meta-analyses suggest that the antiviral medication can reduce the overall duration of pain and incidence of PHN [11,12]. Epidural injection with a steroid within 2 months of HZ development is also recommended for the prevention of PHN [13]. In the previous survey of Korea, epidural injection was the most commonly performed interventional treatment in PHN patients [3]. Other interventions such as paravertebral block, peripheral block and sympathetic block are clinically effective for the treatment of HZ and PHN. For evidence-based medicine of interventional treatment of HZ and PHN, the investigations of randomized controlled trials regarding the interventions will be necessary. In this issue, Jeon et al. [10] described the prevention and treatment of HZ and PHN. They mention that vaccination against varicella zoster virus (VZV) can be the first line for the prevention of HZ and PHN. A previous review article reported that vaccination of VZV reduced morbidity from HZ and PHN [14]. Vaccination of VZV reduced the occurrence of herpes zoster by approximately 70% in individuals aged 50-59 years old [15]. In persons 60 years or older, the vaccination reduced the burden of illness from HZ by 61.1% and the risk of PHN by 66.5% [16]. Therefore, the vaccination of patients over 50 years old can be effective for the prevention of HZ and PHN. Although PHN is difficult to treat, early and intensive treatment of patients with HZ can reduce the occurrence of PHN. In healthy elderly people, a vaccination of VZV can also decrease the incidence of HZ and PHN.

Postherpetic neuralgia (PHN) is the most common complication of herpes zoster (HZ), characterized by persistent neuropathic pain that significantly impairs quality of life. Despite the availability of multiple treatment options, PHN remains under-recognized and undertreated, with wide variation in management practices across Europe. This Delphi consensus aimed to: (1) identify key challenges and unmet needs in PHN diagnosis and management; (2) determine the optimal use and positioning of topical treatments, such as lidocaine-medicated plasters; and (3) develop best-practice recommendations to support clinical decision-making and improve patient outcomes. A modified Delphi methodology was followed. An international steering group (SG) comprising seven healthcare professionals (HCPs) experienced in PHN management met online and developed 42 consensus statements for inclusion in an HCP survey; 16 statements were adapted for inclusion in a patient survey. Each statement was presented with a four-point Likert scale to assess agreement, and the surveys were distributed online by a third party to 640 HCPs and 205 patients located in France, Germany, Ireland, Italy, and the UK. Consensus was defined a priori as ≥ 75% agreement. The SG reviewed the results at a second meeting, identified key findings, and formulated best-practice recommendations. A total of 205 HCPs experienced in managing PHN and 26 patients with PHN completed the surveys. Consensus was achieved on 41 of 42 statements in the HCP survey and on all 16 statements in the patient survey. The SG reviewed and discussed the consensus results and formulated eight key recommendations addressing HZ prevention, PHN diagnosis, and optimization of management, including the appropriate positioning of topical therapies and multidisciplinary care. The results of this consensus highlight the unmet needs in PHN care. Implementation of the recommendations into clinical practice is hoped to support more consistent, patient-centered management and improved outcomes for individuals with PHN across Europe.

Delayed Apical Pathology during Trigeminal Postherpetic Neuralgia Managed with Antiviral-Antibiotic Therapy: A Case Report.

Evaluation of Varicella Zoster Prophylaxis after Allogeneic Hematopoietic Cell Transplantation Using Valacyclovir Followed By Vaccination

Antiviral drugs decrease the pain and enhance the resolution of acute herpes zoster lesions in immunocompetent patients [1-6]. However, the effect of antiviral therapy on postherpetic neuralgia (PHN) remains controversial. Whereas some studies reported a lower incidence of prolonged pain with antiviral therapy [4], others found no benefit with respect to prolonged pain [5]. In an attempt to improve patient comfort and long-term outcome with respect to PHN, combinations of different drugs have also been evaluated [5-7]. Anecdotal reports have suggested that electroacupuncture may be helpful in the management of herpes-related pain [8,9]. Clinical experience with a novel form of electroanalgesia known as percutaneous electrical nerve stimulation (PENS) in the treatment of patients with acute herpes zoster suggested that it is effective in decreasing herpes-related pain and is associated with rapid resolution of the cutaneous lesions (Craig WF, Taylor SM, Fort Worth Center for Pain Management, personal communication, 1997). Therefore, we designed this clinical study to compare PENS therapy with a standard antiviral regimen with respect to the severity of the associated pain, impact on the patient's physical activity and quality of sleep, resolution of the herpes lesions, and incidence and severity of PHN. Methods After obtaining institutional review board approval and written, informed consent, 50 adult patients (27 female and 23 male) with the recent acute onset (<72 h) of herpes zoster lesions were administered one of two different treatment modalities according to a randomized, single-blind study design. Exclusionary criteria included known hypersensitivity to the antiviral drugs, preexisting neurological impairment, women who were pregnant or nursing, any previous experience with acupuncture-like therapies, the presence of the zoster rash for >72 h, or secondary complications from the viral infection. The patients were randomly assigned using a computer-based program to either the control group (which received famciclovir 500 mg three times a day for 1 wk) or the experimental group (which received PENS therapy for 30 min three times a week for 2 wk). The PENS therapy consisted of the placement of 32-gauge stainless steel acupuncture-like needle probes into the soft tissue to a depth of 1-2 cm at dermatomes one level above and below the cutaneous lesions (Figure 1 and Figure 2). The needle probes were connected to a low-output (5 mAmp) electrical generator and stimulated at frequencies ranging from 4 to 100 Hz. Patients in both treatment groups were evaluated daily by a physician (HEA) not involved in either the famciclovir or PENS treatments. The patients were instructed not to use any topical medications or systemic treatments during the 2-wk study period.Figure 1: The "arc" montage was applied initially when the lesions were wet during the first week of therapy, consisting of bipolar leads connected to needle probes placed in the soft tissues at one dermatomal level above and below the acute lesions. Each lead was connected to a pair of needles, alternating the positive (+) and the negative (-) electrode positions as shown.Figure 2: The "vertical" montage was applied after the lesions became crusted during the second week of therapy, consisting of bipolar leads stimulating across the dermatomal region from C4 to C7. Each lead was connected to a pair of needles, alternating the positive (+) and the negative (-) positions as shown.Before receiving the study treatments, all patients were asked to assess their baseline degree of pain, level of physical activity, and quality of sleep using three separate 100-mm visual analog scales (VAS), with 0 = minimal (lowest) to 100 = maximal (highest). All patients were instructed to return to the medical center daily during the 2-wk study period to assess the appearance of their cutaneous lesions and to complete the pain, physical activity, and quality of sleep VASs. At the end of the study period, all patients were asked to complete a global assessment questionnaire to evaluate the change in pain, physical activity, and quality of sleep using the VASs. The assessment of the cutaneous lesions was performed by a blind observer and included: 1) location of the rash; 2) severity of the rash (i.e., number of the lesions in the involved dermatomes) using the following classification system: mild (<25), moderate (25-50), or severe (> 50); 3) the last day that new lesions appeared; 4) the first day without any new lesions; 5) the first day with full crusting of the lesions; and 6) the time to complete healing of the lesions. All patients were contacted at 3-, 6-, and 9-mo intervals to inquire about the presence of pain in a dermatomal pattern corresponding to the level of the acute lesions (i.e., PHN). The severity of the PHN pain was quantified using the 100-mm pain VAS. Changes in the VAS scores were analyzed by using analysis of variance, with t-tests used to determine intergroup differences and Bonferroni's adjustment for multiple comparisons. Analysis of discrete data was performed using the chi squared test, with P values <0.05 considered statistically significant. Results The two treatment groups were similar with respect to demographic characteristics, including the location and severity of the herpetic lesions (Table 1). The PENS group experienced more rapid resolution of the vesicles and complete healing of the lesions (Table 2). The VAS pain scores were consistently lower in the PENS group during the 2-wk observation period (Table 3). On the global assessment questionnaire, the percent decrease in the VAS pain score was 67% in the PENS group compared with 45% in the control group (P < 0.05). The percent improvement in the VAS physical activity and quality of sleep scores (78% vs 60% and 55% vs 37%, respectively) was also greater in the PENS- versus famciclovir-treated patients at the end of the second week. The older patients (>or=to50 yr) were more likely to develop PHN symptoms, and PENS therapy was associated with a decrease in the severity of pain at 3 and 6 mo in this subpopulation (Table 2). However, no differences in PHN symptoms were apparent at the 9-mo follow-up assessment period.Table 1: Demographic Characteristics of Patients with Acute Herpes Zoster Receiving Antiviral Drug (Control) or PENS TherapyTable 2: Effect of Antiviral Drug (Control) or PENS Therapy on Resolution of Acute Herpes Zoster Lesions and the Incidence and Severity of Postherpetic NeuralgiaTable 3: Effect of Antiviral Drug (Control) or PENS Therapy on Pain Scores, Physical Activity, and Quality of Sleep in Patients with Acute Herpes ZosterDiscussion This comparative study suggests that PENS, a novel, nonpharmacologic analgesia technique, may be a viable alternative to antiviral drugs for the treatment of acute herpes zoster lesions. The use of PENS therapy provided pain relief, increased physical activity, and an improved quality of sleep that compared favorably with a standard antiviral therapy. In this preliminary study, PENS therapy was also more effective than famciclovir in preventing PHN-related pain symptoms 3 and 6 mo after resolution of the cutaneous lesions. Although this study can be criticized because it did not include a placebo (or sham) group, the benefits of antiviral therapy have been firmly established during the acute phase of the illness, and other investigators [4] have suggested that it would be unethical to include a placebo treatment group. The outcome assessments were blinded because the physician making the assessment was unaware of the treatment that the patients were receiving. Furthermore, the small cutaneous needle puncture sites (0.2 mm) produced by the PENS probes were not apparent to the individual performing the clinical assessments. Nevertheless, future studies should include a sham PENS group that receives the antiviral therapy in combination with the needle probes but without electrical stimulation. Unfortunately, the inclusion of a sham PENS group would not blind the patients because it does not mimic the sensation provided by the electrical stimulation associated with PENS therapy. The improved physical activity and quality of sleep during the second week of treatment in the PENS group may be secondary to the decrease in the intensity of pain. Although the mechanism of PENS-induced analgesia is not known, it may be related to both neural modulation produced by the electrical stimulus [10] and an increase in endogenous morphine-like substances (e.g., dynorphins, endorphins, enkephalins) within the central nervous system [11]. Using a rat model for studying electroacupuncture, Chen et al. [12] reported that an alternating 2-Hz and 15-Hz pattern of electrical stimulation was more effective than a fixed frequency of stimulation at either 2 Hz or 100 Hz in producing experimental analgesia. In a clinical study, Han et al. [11] reported that low-and high-frequency electrical stimulation resulted in increased cerebrospinal fluid levels of met-enkephalin and dynorphin, respectively. Further studies are clearly needed to determine the precise central nervous system mechanism(s) of PENS-induced analgesia. Because herpes zoster is caused by a reactivation of the varicella virus residing in the sensory ganglia and spinal cord after the primary viral infection, the beneficial effects of PENS therapy may also be related to electrical stimulation of the involved peripheral sensory nerves. The electrical current can produce localized vasodilation and may stimulate the release of antiinflammatory mediators at the site of injury. Further studies evaluating the efficacy of PENS therapy in immunosuppressed patients would be helpful in understanding the basis for its apparent analgesic and antiinflammatory activity. However, PENS therapy should be evaluated as a supplement to antiviral therapy in this high-risk patient population. In conclusion, PENS therapy is a unique nonpharmacologic approach to treating immunocompetent patients with acute herpes zoster that compared favorably with standard antiviral drug therapy in this preliminary study.

In the literature, 7% of all cases of herpes zoster present as herpes zoster ophthalmicus (HZO). Of these cases, 20 to 79% have orbital involvement [1]. Nearly all orbital tissues, including extra-ocular muscles, can be affected by the varicella zoster virus. Orbital involvement may present as keratitis, uveitis, scleritis, optic neuritis, ocular motor palsy, or postherpetic neuralgia (PHN) [2]. HZO is often suspected when symptoms and signs follow characteristic skin rashes and edema. Here, we report an unusual case where orbital myositis preceded vesicular skin eruptions. A 66 year-old man, who had diabetes for 15 years and hypertension for 10 years, was hospitalized due to a 4-day history of left orbital shooting pain. Cranial nerve examination was nearly normal except for mild ptosis and hyperemic conjunctiva on the left side. examination revealed normal intraocular pressure and normal eyeground. There were no specific findings in other physical examinations. Orbital CT revealed left orbital myositis involving superior, inferior, medial, and lateral rectus muscles compared with the right orbit (Fig. 1A). We treated him with intra-venous mannitol, 60 mg/day per-oral prednisolone (nisolone®, Kukje, Seongnam, Korea), levofloxin eye-drops (Cravit®, Santen, Shiga, Japan), dorzolamide HCl 2% with timolol 0.5% (Cosopt®, MSD, Seoul, Korea), and latamoprost (Xalost®, Taejoon, Seoul, Korea). Fig. 1 (A) Orbital computed tomography (CT) image with contrast, coronal view. CT shows relatively moderately enhanced and enlarged left superior, inferior, medial, and lateral rectus muscles compared with right orbit. (B) 2 weeks later, a follow-up orbital ... After 3-days, he developed vesicular skin rashes at the distribution of the branch of the left trigeminal nerve and along the nasal ridge (Hutchinson's sign) (Fig. 1C). He complained of severe pain in his left forehead and nose. The pattern of the pain included lancinating, shooting, and itching sensations. The pain measured by the visual analogue scale (VAS) was approximately 90/100 mm. Laboratory data, including routine biochemical and hematological examinations, were normal except for glucose (423 mg/dl) and hemoglobin A1c (10.6%). The erythrocyte sedimentation rate (ESR) was 30 mm/hr and C-reactive protein (CRP) was 0.74 mg/dl. Immunologic studies, including IgA, IgM, C3, C4, antimitochondrial antibody (AMIA), anti-nuclear antibody (ANA), and anti-double stranded DNA, were all within normal limits. Thyroid function test was normal and the VDRL/TPHA test was negative. Immediately, we treated him with 7-day intra-venous (IV) acyclovir, IV dexamethasone, and per-oral (PO) gabapentin. At the same time, we performed supraorbital and supratrochlear nerve blocks. After the nerve block, the headache and allodynia were improved. The eyelid swelling and orbital pain gradually lessened by the time he was discharged. The patient returned to our clinic with persistent left orbital pain and paroxysmal and lancinating pain along the nose ridge and forehead. We performed supraorbital and supratrochlear nerve blocks then and again in two weeks, for a total of three times. The pain was reduced to VAS 10-20/100 mm. A follow-up orbital CT revealed resolved myositis in the rectus muscles (Fig. 1B). The patient was undergoing oral administration of gabapentin (600 mg/day). He revisited the hospital 5 months later without particular exacerbation of the pain or any other inconvenience in his daily tasks. Ophthalmic complications following HZO result directly from inflammatory changes or nerve damage, or indirectly from tissue scarring. These complications vary from mild, which may pass unnoticed, to severe, which may threaten life or sight. Except for diplopia, our patient developed characteristic symptoms of orbital myositis, such as orbital pain worsening with eye movements, proptosis, swollen eyelid, and hyperemic conjunctiva. He had Hutchinson's sign, which is typical for HZO [1]. Normal immunologic and serologic surveys excluded other etiologies of orbital myositis, for example, thyroid disease, syphilis, and auto-immune diseases. His ocular symptoms improved after antiviral therapy and the follow-up orbital MRI four months later revealed total recovery of orbital myositis. Typically, complications of HZO occur between 5 days and 14 days following cutaneous lesions. Our case is unusual in that the orbital myositis preceded vesicular rashes. Two similar patients have been reported previously [3,4]. Both patients came to the hospital for retrobulbar pain with diplopia. Volpe et al. demonstrated orbital myositis on computed tomographic (CT) scans in their patient one day before the development of skin vesicles [3]. As reported by Kawasaki et al., MRI demonstrated orbital myositis three days prior to appearance of typical skin eruptions in their patient [4]. In these two patients and ours, their extraocular myositis had excellent recovery. However, our patient suffered from PHN, which did not occur in the previously reported patients. Although Marsh and Cooper had proposed extraocular myositis as a possible cause of ophthalmoplegia in HZO [2], it was not well documented until these case reports. To date, there is no histopathologic study of orbital myositis in HZO [4]. Orbital myositis preceding vesicular skin eruptions is a diagnostic challenge in HZO. Since zoster rashes may develop one week or more after dermatomal pain [1], serological and immunological tests may be helpful for early diagnosis in extraocular myositis preceding zoster rashes. In 1958, Lewis reported a syndrome of ophthalmic zoster sine herpete [5], in which orbital pain, extraocular palsy, and periorbital skin swelling occurred without skin rashes. Ophthalmic zoster sine herpete further confounds the diagnosis of HZO. We emphasize that, even without vesicular skin rashes, a diagnosis of extraocular myositis case as idiopathic should not be given before the availability of negative serological and immunological results for herpes zoster. In conclusion, orbital myositis can be the presenting sign of HZO. In these patients, recovery of extraocular myositis is excellent and serological and immunological studies may be helpful for early diagnosis. HZO should be listed as a cause of acute orbital myositis even without skin eruptions. Therefore, early diagnosis of acute orbital myositis and anti-viral therapy will prevent PHN. And, if zoster skin rashes are found, we should control pain aggressively by nerve blocks to prevent the development to PHN.

Background: Herpes zoster affects millions of people worldwide each year and many go on to suffer long-term pain, called postherpetic neuralgia (PHN). As zoster is common and PHN is difficult to treat, preventing zoster through vaccination is important. This thesis aims to better understand risk factors for zoster and PHN, in order to inform vaccination policy. Methods: Three large observational studies were carried out using primary care data from the UK Clinical Practice Research Datalink and linked secondary care data from the Hospital Episodes Statistics. First, a matched case-control study quantified the effects of possible risk factors for zoster and explored whether their effects differed by age group. Second, a descriptive study looked at antiviral prescription patterns and patient characteristics associated with antiviral receipt after zoster diagnosis. Third, a cohort study assessed risk factors for PHN and investigated whether their effects were modified by antiviral use. Results: The case-control study of zoster risk factors included 144,959 zoster patients and 549,336 controls and found an increased risk of zoster among patients with rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, chronic obstructive pulmonary disease, asthma, chronic kidney disease, depression and type 1 diabetes; odds ratios ranged from 1.14 to 1.72. In general, the relative effects of these risk factors on zoster decreased with increasing age. In the descriptive study of antiviral use, of 142,216 zoster cases, only 58.1% received an antiviral prescription at zoster diagnosis. Antivirals were even under-prescribed among the immunosuppressed and older individuals, for whom guidelines recommend routine treatment. The cohort study of PHN risk factors identified 119,413 zoster patients, 5.8% of whom developed PHN. An increased risk of PHN was found among patients with rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, chronic obstructive pulmonary disease, asthma, depression, type 2 diabetes, lower socioeconomic status, smoking and under- or overweight; odds ratios ranged from 1.13-1.82. Antiviral use was not associated with PHN risk overall. The zoster case-control and PHN cohort study showed that patients with severely immunosuppressive conditions were at greatest risk of both zoster and PHN. Conclusions: A number of patient characteristics and comorbidities were associated with increased zoster and PHN risks. Patients at highest risk of zoster and PHN are those of older age and those with immunosuppression; currently, patients with immunosuppression are not eligible for vaccination, highlighting a need for alternative risk reduction strategies in this group. Low antiviral use at zoster diagnosis suggests treatment guidelines be revised to encourage greater use, especially among the immunosuppressed and older individuals who are recommended, but not routinely given, antivirals. Research on the cost-effectiveness of vaccinating patients with specific risk factors is needed.

Antiviral treatment of herpes zoster is controversial because of uncertain benefits and relatively high costs. Most studies show that antiviral therapy lessens acute herpes zoster symptoms and postherpetic neuralgia (PHN). Current clinical recommendations support antiviral treatment of severely symptomatic herpes zoster in all adults, and mild herpes zoster in those 50 or 60 years of age or older. However, it is unclear if these recommended strategies are cost effective. Published studies of herpes zoster costs and the effect of antiviral therapy on costs and quality of life have significant variation in study design and results, as well as many shortcomings in the data. Thus, definitive economic recommendations cannot be made based on the present data. Another approach, which we have used, is to develop a 'reference case' analysis using decision-analysis techniques and the available data to estimate the incremental cost effectiveness of antiviral treatment in patients of differing age and herpes zoster severity. In the baseline analysis, parameter values and assumptions were consistently slightly biased against antiviral use. Effectiveness was measured in quality-adjusted life years (QALYs). We assumed that antiviral treatment did not change PHN risk, but decreased PHN duration in patients older than 50 years. PHN risk increased with age and with acute herpes zoster severity as seen in published data. Mild acute herpes zoster was assumed to have a utility value of 0.9 and severe acute herpes zoster a value of 0.7 on a scale where 0 = death and 1 = perfect health. Treating mildly symptomatic acute herpes zoster cost $US89,200/QALY gained in 40-year-olds, $US47,700/QALY in 60-year-olds and $US40,700/QALY in 70-year-olds (1995 values). Results were most sensitive to variation of antiviral costs (baseline $US134), but changes in acute symptom relief, PHN risk, duration, costs and utility, and antiviral effect on PHN duration increased costs/QALY above $US50,000 in 60- and 70-year-olds in extremes of parameter ranges. However, no variation resulted in treatment of mild illness in 40-year-olds to fall below $US50,000/QALY gained. Treatment of severe acute herpes zoster cost $US29,700, $US18,000 and $US16,500/QALY gained in 40-, 60- and 70-year-olds, respectively. Results were sensitive to variation of antiviral costs (> $US225) and acute symptom relief (< 21%) in 40-year-olds. Based on this analysis, antiviral therapy of herpes zoster seems economically justifiable for mildly symptomatic acute herpes zoster in patients aged 50 years and older, and for severely symptomatic acute herpes zoster in all adults.

The History and Mystery of VZV in Saliva

Patient characteristics and analgesic efficacy of antiviral therapy in postherpetic neuralgia

Herpes zoster guideline of the German Dermatology Society (DDG).