Brivudin compared with famciclovir in the treatment of herpes zoster: effects in acute disease and chronic pain in immunocompetent patients. A randomized, double-blind, multinational study

OBJECTIVE: This was a double-blind, randomized multicentre trial comparing efficacy and safety of brivudin (125 mg, once a day) and famciclovir (250 mg, three times a day), both given orally for 7 days, in the treatment of herpes zoster. METHODS: A total of 2027 immunocompetent zoster patients>or=50 years with zoster-related pain at presentation were included. Outcome measures embraced prevalence of postherpetic neuralgia (PHN), defined as at least moderate pain 3 months after treatment initiation, duration of PHN, prevalence and duration of zoster-associated pain (ZAP), duration of vesicle formation and rash healing. RESULTS: The prevalence of PHN at month 3 was 11.3% with brivudin and 9.6% with famciclovir [per-protocol (PP) population]. Equivalence of the two drugs could be demonstrated (P=0.01, PP and intention-to-treat analysis). The median duration of PHN was 46.5 days with brivudin and 58 days with famciclovir (P=0.54, PP analysis). Prevalence and duration of ZAP did not differ significantly between treatment groups. The prevalence of PHN was higher in patients>or=65 years (brivudin: 16.4%, famciclovir: 16.4%), and in patients with severe rash (brivudin: 13.4%, famciclovir: 15.7%), without significant differences between treatment groups. In patients>or=65 years, median duration of PHN was shorter with brivudin than with famciclovir (39.5 vs. 57.5 days), although the difference was not statistically significant. The two drugs had equivalent efficacy in being able to accelerate the stop of vesicle formation, and lesion healing. Adverse events were similar in nature and prevalence among groups. CONCLUSIONS: The study demonstrated equivalent efficacy of brivudin and famciclovir in the treatment of herpes zoster regarding the prevention of chronic pain and the resolution of signs and symptoms of acute herpes zoster. Compared with famciclovir, brivudin provides equivalent efficacy and safety at a more convenient once-daily dose schedule.     

The effects of famciclovir and epidural block in the treatment of herpes zoster.

In our previous study, we concluded that an epidural blockade combined with intravenous acyclovir is very effective in treating the acute pain in herpes zoster and postherpetic neuralgia. We evaluated the efficacy of oral famciclovir and epidural blockade on the pain of herpes zoster, compared to acyclovir administered intravenously and epidural blockade. For this purpose, we examined a new group treated with famciclovir and epidural blockade to compare with the group treated with acyclovir and epidural blockade in our previously study. The changes in the intensity of pain, the number of days required for relief of pain, and the total duration of pain were checked. We compared the days required for relief of pain (DRP) and the total duration of pain (TDP) of this group with those of the previous studied group treated with acyclovir and epidural blockade. DRP was significantly less, but TDP was similar. DRP and TDP were significantly lower, if the patients were treated within 7 days of symptom onset. The patients had a shorter DRP regardless of pain type than the previously studied group treated with acycolvir and epidural blockade. For the severe and moderate pain grades, there was a shorter DRP from 100 to 10. TDP was not significantly different for the groups regardless of pain type or grade. We believe that famciclovir and epidural blockade are very effective in treating the pain of herpes zoster, with a view to shortening the period of acute pain, providing similar effects on the prevention of postherpetic neuralgia, and being convenient to administer, compared to intravenous acyclovir and epidural blockade in our previous study.     

五指疼痛评估法在老年带状疱疹患者疼痛评估中的应用

目的: 评价五指疼痛评分法在老年带状疱疹患者疼痛评估中的效度和首选率。方法: 采用五指疼痛评分法、数字疼痛量表（NRS）和视觉模拟评分法（VAS）对老年带状疱疹患者疼痛进行评价,并对结果进行相关分析,比较三种评估方法所需时间、首选率。结果: 共有60例患者入选,五指疼痛评分法与NRS、VAS在疼痛评估效度上一致,五指疼痛评分法、VAS、NRS评估用时分别为42±12.8s 、67±16.2s和38±9.2s,首选率分别为58%、20%、22%。结论: 五指疼痛评分法在老年带状疱疹患者疼痛评估中简便实用。     

Relationship between prior knowledge about herpes zoster and the period from onset of the eruption to consultation in patients with herpes zoster

Herpes zoster (HZ) is a common internal infection caused by latent varicella zoster virus. Emergence of antiviral chemotherapy has changed the treatment of HZ dramatically, but the effects of such therapy are documented only in patients who started treatment within 72 h of HZ onset of the eruption. There have been few studies addressing the question of factors that determine early attendance of patients at a clinic. We questioned 256 patients with acute HZ about: (i) date from onset of the eruption to first clinic visit; and (ii) their prior knowledge of HZ. We found a tendency that patients who already knew about HZ had consulted dermatology clinics earlier (P < 0.05). People most commonly obtained information about the disease from friends and family members who had previously had HZ, but not from the Internet or other mass media. Our results indicate that patient education is important for early attendance at dermatology clinics, which in turn, should result in the improved outcome of antiviral chemotherapy and prevention of postherpetic neuralgia.     

Incidence of serum antibody titers against varicella zoster virus in Japanese patients with herpes zoster

Herpes zoster is an internal reactivation of varicella zoster virus following establishment of latent infection in the dorsal root ganglia during primary infection, which presents as chickenpox. Therefore, serologically, herpes zoster patients already have anti‐varicella zoster virus immunoglobulin G at the onset of disease. Hence, positive serum antibody does not confirm the diagnosis of herpes zoster. We retrospectively investigated the incidence of varicella zoster virus‐specific complement fixation in 865 zoster patients at initial presentation to a dermatology clinic. As a result, 66% of patients showed negative complement fixation, with patient numbers decreasing as titer increased. Paired complement fixation tests conducted within a short period showed a marked elevation in titer, and complement fixation titer gradually decreased after a year. Furthermore, incidence showed no correlation with patient age. These observations indicate that the complement fixation titer at first visit is mainly influenced by the duration from onset to presentation at clinic. Our findings indicate that a positive complement fixation result by single‐point testing confirms at least recent onset of herpes zoster, while paired tests can confirm disease when primary tests are negative.     

Factors influencing pain outcome in herpes zoster: an observational study with valaciclovir

AIM OF THE STUDY: An observational study with valaciclovir was conducted to assess clinical outcome in herpes zoster, especially pain and associated neurological signs and symptoms in relation to a series of demographic and disease characteristics discernible at presentation. The safety and acceptability of valaciclovir for treatment of zoster was assessed in a wide variety of primary care and clinic referral settings. METHODS: In total, 1897 immunocompetent adults with clinically diagnosed, localized acute herpes zoster were enrolled in this international, open-label study of valaciclovir. All subjects received treatment with oral valaciclovir (1000 mg three times daily) for 7 days from entry to the study and were asked to record the presence of zoster-associated pain and abnormal sensations throughout treatment and 6 months' follow-up. They were seen frequently in clinic to verify subjective assessments and for evaluation of rash healing. Safety and tolerability were assessed by adverse event monitoring. RESULTS: Overall, 1191 subjects (63%) were aged > or = 50 years, and 203 (11%) had ophthalmic zoster. Cessation of zoster-associated pain was significantly faster in the younger age group; median times to loss of zoster-associated pain were 23 days and 9 days in the > or = 50 and < 50 years age groups, respectively. Similarly, abnormal sensations resolved significantly more rapidly in the younger subjects; the median duration of abnormal sensations was 31 days in the > or = 50 year olds and 16 days in those aged < 50 years. In cases of ophthalmic zoster, the rate of pain resolution was not different from those with zoster in other dermatomes (median duration of pain 18 vs. 16 days). However, abnormal sensations persisted significantly longer in subjects with ophthalmic zoster than in those with zoster at other sites (47 vs. 22 days). In addition to advancing age, subjects suffering moderate to severe prodromal pain or acute pain during the rash phase were at significantly greater risk of zoster-associated pain and abnormal sensations persisting for longer. Subjects with concomitant neurological disorders were also more likely to develop prolonged abnormal sensations. Valaciclovir treatment was well tolerated, and adverse events were rare and generally mild. CONCLUSION: This study confirmed the prognostic importance of advancing age and the intensity of prodromal or acute pain as risk factors for prolonged zoster-associated pain and persisting abnormal sensations in the affected dermatome. Ophthalmic zoster and pre-existing neurological disorders are also identified as highly significant risk factors for prolonged abnormal sensations in herpes zoster.     

泛昔洛韦与阿昔洛韦治疗带状疱疹临床对比观察

目的 评价泛昔洛韦治疗带状疱疹的疗效和安全性。方法 将60例带状疱疹患者随机分为治疗组泛昔洛韦250mg一日三次和对照组阿昔洛韦200mg一日五次。治疗后第1,3,5,7,8天观察记录。结果 治疗组与对照组在水疱干涸时间和疱疹缓解开始时间比较有显著性差异（P＜0．01）,在水疱停止出现时间和完全结痂时间比较无显著性差异（P＞0．05）。两组病例不良反应相似且轻微。结论 泛昔洛韦是治疗带状疱疹的安全有效药物。     

Annual pattern and clinical characteristics of herpes zoster in immunocompetent children in a rural area

This study aims to investigate the clinical signs, symptoms, complications and seasonal distribution of herpes zoster for otherwise healthy children and to demonstrate the outcome of varicella vaccinations on the herpes zoster incidence in a pediatric population. A retrospective study was conducted by using the data of the pediatric patients who were referred to two rural cities of Turkey, clinically diagnosed as Herpes Zoster (HZ). All participants were evaluated for clinical‐epidemiological factors, signs, symptoms, complications and varicella vaccination status for HZ. This study was comprised of 69 pediatric patients (29 [42%] female and 40 [58%] male) who were diagnosed with HZ. The mean age was 10.57 (6 months‐17) years old. The rash of HZ mostly appeared on the thoracic dermatome as seen in 29 patients. The findings revealed that among 56 unvaccinated patients of all, 25 (44.6%) had a painful rash, in comparison among vaccinated patients none reported pain as the characterization of shingles (P = .001). Annual distribution of cases showed two peaks (March and September), whereas in August no cases were detected. Of all participants, one patient had postherpetic neuralgia, who also had ophthalmic dermatomal involvement, and this was the only complication observed in this study cohort. In immunocompetent children, the most common involvement site was the thoracic dermatome. Our findings show that varicella vaccination has a protective role in the herpes zoster clinic, both by decreasing the prevalence and by making the infection course less severe.     

Identification and characterization of 20 immunocompetent patients with simultaneous varicella zoster and herpes simplex virus infection

Background It has been shown that varicella zoster virus (VZV) and herpes simplex virus (HSV) can co‐localize to the same sensory ganglion. However, only a few case reports on VZV/HSV co‐infections exist. Objective To identify and characterize patients with concurrent VZV and HSV infection at the same body site. Subjects/Methods In 1718 patients, the presence of VZV and HSV in suspicious skin lesions was investigated by polymerase chain reaction analysis. Clinical characteristics of co‐infected patients were compared with matched control patients infected with either VZV or HSV. The data are discussed in the context of an extensive review of the literature. Results Twenty (1.2%) of 1718 patients were infected with both VZV and HSV at the same body site. The mean age was 54 years (range, 2–83). The clinical diagnosis was zoster in 65%, herpes simplex in 20%, varicella in 10% and erythema multiforme in 5% of cases. The trigeminus region was affected in 60% and the trunk in 25%. Involvement of the head was most commonly associated with a severe course of disease and with older age. Conclusion Simultaneous VZV/HSV infection is rare but can occur in immunocompetent patients, which is often overlooked. The majority of cases is localized to the trigeminus region and affects elderly people.     

Close correlation of herpes zoster‐induced voiding dysfunction with severity of zoster‐related pain: A single faculty retrospective study

Herpes zoster (HZ), a common vesiculo‐erythematous skin disease associated with reactivation of varicella zoster virus in the cranial nerve, dorsal root, and autonomic ganglia, is accompanied by several related symptoms represented by postherpetic neuralgia. Among them, involvement of vesicorectal dysfunction is relatively rare. The vesicorectal symptom can usually be recovered in transient course, but is quite important in terms of impaired quality of life. Male individuals affected with HZ and skin lesions on sacral dermatome have been reported as independent risk factors of zoster‐related voiding dysfunction. In this study, urinary symptoms were focused upon and six patients with zoster‐related voiding dysfunction at a single faculty of dermatology in Japan from 2009 to 2014 were retrospectively analyzed. All patients showed HZ lesions on the sacral area and the urinary symptom recovered in approximately 2 months (14 days to 7 months). The term of treatment for zoster‐associated urinary dysfunction was positively correlated with that for zoster‐related pain without significance (r = 0.661, P = 0.153). Average treatment term for pain relief of sacral HZ accompanied by voiding dysfunction (91.3 ± 76.44 days) was significantly longer than that of sacral HZ without urinary symptom (18.9 ± 20.42 days) (P = 0.032). These results suggested that zoster‐related voiding dysfunction would mainly be involved in sacral HZ and closely associated with severity of zoster‐related pain. Dermatologists should be aware that severe zoster‐related pain accompanied by sacral HZ, which is related to prolonged treatment of pain relief, can be a predictive factor of voiding dysfunction.     

Consumption of pain medication by hospitalized patients with acute herpes zoster

Background The effect of acyclovir on inpatients with acute herpetic pain has been examined in only few studies. Aim To examine the effect of acyclovir on intensity and course of herpes zoster-associated neuralgia in hospitalized patients. Method Two groups of patients (50 each) hospitalized for acute herpes zoster in 1983/84 (before acyclovir was available) and in 1989/90 (when acyclovir was given for at least 5 days intravenously) were evaluated for pain and consumption of pain medication. Results The score for pain intensity did not differ significantly in acyclovir-related patients compared to patients who did not receive the drug. Conclusion This study fails to demonstrate a beneficial effect of acyclovir on acute herpetic neuralgia.     

系统性红斑狼疮合并带状疱疹临床分析

目的：分析SLE患者的带状疱疹临床特点，以及探讨SLE患者的病情活动和治疗对发生带状疱疹的影响。方法：临床回顾1991－2000年住院合并有带状疱疹的SLE患者临床特点，对带状疱疹发生的一些可能的相关因素行分析比较和χ^2检验。结果：这一组患者中，带状疱疹的发生率为9．80％，高于同期全部住院患者带状疱疹的发生率，临床症状相对较重；带状疱疹的发生率在病情活动、应用糖皮质激素及环磷酰胺治疗时较高。结论：SLE容易合并带状疱疹；病情相对较重；病情活动、应用糖皮质激素及环磷酰胺治疗时带状疱疹的发生率较高。     

头面部带状疱疹患者的临床与肌电图分析

目的 :　探讨头面部带状疱疹患者的临床表现与不同年龄组肌电图特征。方法 :　对门诊确诊的 6 8例头面部带状疱疹患者按不同年龄段的临床表现与肌电图特征进行分析。结果 :　患者发病前诱因以发热、感冒、过度劳累为多 (6 4 % ) ;发病以先有神经痛而后发疹者为最多见 (72 % ) ;在肌电图检测中 ,瞬目反射异常阳性率最高 (5 9% ) ,其次为异常自发活动 (37% )、混合肌肉动作电位 (CMAP)异常 (2 1% )、MCV异常 (12 % ) ;在上述四项检测中 ,除CMAP异常中各年龄组均无显著性差异 (P >0 .0 5 )外 ,其余三项中均以 >6 0岁年龄组最高 ,4 1～ 6 0岁组次之 ,≤ 4 0岁组最低 ,其间的差异均有显著性意义 (P <0 .0 1)。结论 :　肌电图是检查头面部带状疱疹神经肌肉是否受累的主要手段 ,其中以瞬目反射异常的阳性率最高。     

Famciclovir vs. aciclovir in immunocompetent patients with recurrent genital herpes infections: a parallel-groups, randomized, double-blind clinical trial

BACKGROUND: Twice-daily therapy with famciclovir (FCV) was shown to be effective for episodic therapy for recurrent genital herpes in a large placebo-controlled trial. However, no study has been published to date comparing FCV and aciclovir (ACV). OBJECTIVES: We have evaluated the effectiveness of FCV vs. ACV in the treatment of recurrent genital herpes infection. METHODS: A multicentre, double-blind, double-placebo, randomized, parallel-design study, assessed for equivalence, was conducted. As the analysis was based on confidence intervals, a difference of lesion healing time between ACV and FCV (Delta) of 1.05 days with a standard deviation of 2.30 days was chosen. Two hundred and four outpatients were included. Patients self-initiated oral therapy with 125 mg of FCV twice daily or ACV 200 mg five times daily for 5 days. The principal end-point of the study was the complete healing of lesions. Duration of the complete resolution of all symptoms, and safety were also considered. RESULTS: The mean healing time was 5.1 days and 5.4 days for FCV and ACV, respectively, with a crude value of Delta = 0.25 days (CI 95%: -0.32; 0.82) in the intent-to-treat population. Therefore, the confidence interval for the difference between the two treatments lies entirely within the equivalence range (-1.05-1.05). The value of Delta in the per-protocol population [0.35 day (CI 95%: -0.24; 0.93)] was comparable between the two groups. No differences were detected in the proportion of patients having complete healing at the different days of evaluation as well as in the duration until the complete resolution of all the symptoms. The frequency, nature and severity of adverse events did not differ among the two treatment groups. CONCLUSIONS: Twice-daily FCV was as effective and safe in the treatment of recurrent genital herpes simplex virus infection as five times daily ACV.     

Efficacy of low dose gabapentin in acute herpes zoster for preventing postherpetic neuralgia: a prospective controlled study

Postherpetic neuralgia (PHN) is a sequela of herpes zoster that adversely affects quality of life seriously. The risk factors for PHN are well known but the effective interventions that reduce the incidence of PHN are less studied. The objective of this study is to evaluate the efficacy of treatment with gabapentin in patients with acute herpes zoster for preventing PHN. We performed a prospective randomized controlled study of 120 participants diagnosed with acute herpes zoster, aged 50 and over and complaining moderate to severe pain. All patients were treated with valacyclovir and acetaminophen. Half of the participants were assigned to the gabapentin group and received gabapentin 300 mg three times a day additionally. The intensity of pain at every visit and the incidence of PHN in both groups were measured. Total 52 and 49 patients in the gabapentin group and the control group, respectively, had completed 12 weeks of follow‐up period. Although the incidence of PHN was higher in the control group, the difference was not statistically significant (6.1% vs. 3.8%, p = 0.67). Our results indicate that the use of low‐dose gabapentin in acute herpes zoster seems not effective in the prevention of PHN.     

Thermography as a predictor of postherpetic neuralgia in acute herpes zoster patients: a preliminary study

Background/purpose: Infrared thermal images in patients suffering from herpes zoster (HZ) may exhibit thermal asymmetry due to the unilateral distribution of HZ lesions. This study examined the usefulness of infrared thermography in acute HZ as a predictor for the development of postherpetic neuralgia (PHN). Methods: The authors collected demographic and clinical data including age, sex, onset of skin lesion, pain intensity by a visual analogue scale (VAS) and the development of PHN from a total of 55 patients diagnosed with HZ. We evaluated the body surface thermographic parameters between the lesion and contralateral normal skin: maximal difference in the temperature (ΔT) and the size of the body surface area (BSA) showing thermal asymmetry. Results: Temperatures of the lesions were found to be warmer than the control side in most patients with acute HZ. We compared the patient group who developed PHN with those who did not. In univariate analysis, patients with PHN were older (P=0.004), had a higher VAS score for pain (P<0.001), higher ΔT (P<0.001) and larger BSA (P=0.001). In logistic regression analysis to identify independent risk factors of PHN, older age (>60 years old) and ΔT more than 0.5 °C were found to be statistically significant.     

带状疱疹患者外周血T细胞及NK细胞检测

目的:评价机体免疫功能与带状疱疹的相关性。方法:选取25例带状疱疹患者和30名对照者,流式细胞术检测CD4~+T细胞、CD3~+T细胞、CD8~+T细胞、CD4/CD8及NK细胞。结果:与对照组相比较,患病组CD4~+T细胞、CD3~+T细胞降低,NK细胞升高。差异有统计学意义(P0.05)。结论:带状疱疹存在免疫功能异常。     

Abdominal distention and constipation followed by herpes zoster infection in a 2‐month‐old female infant

Gastrointestinal symptoms of herpes zoster in infants are rarely reported. A 2‐month‐old female infant presented with herpes zoster and additional complication of abdominal distention and constipation. While rashes resolved, abdominal distention and constipation improved soon. To our knowledge, this is the first report of gastrointestinal complication of herpes zoster in infants. Physicians should be aware of the potential for motor involvement of herpes zoster in such infants. Herpes zoster should be considered during the diagnosis in the event of infants presenting with constipation.