Herpes Zoster (Shingles)

Herpes zoster (HZ) infection, commonly called shingles, is the reactivation of a latent varicella zoster virus (VZV) that caused an earlier episode of chicken pox. Patients experience HZ as a painful or pruritic, usually unilateral, blistering rash similar to the original VZV infection. It occurs over the dermatome innervated by the ganglion, where the VZV resides for life until stress, immunosuppression, or some other condition allows it to travel to the skin served by the affected nerve. Those at increased risk of developing HZ include females, Caucasians, those with advanced age or a family history of HZ, autoimmune disorders, asthma, diabetes mellitus, or chronic obstructive pulmonary disease.^1,2 It is estimated that HZ occurs in 30% of those originally infected with VZV.¹ Systemic antiviral agents are most commonly prescribed as treatment, with mixed clinical outcomes. Covering the rash as early as possible with a moisture-retentive dressing can limit early pain or itching and prevent drying or secondary bacterial infection due to patients scratching affected skin.³ Vaccination prevents primary varicella and subsequent HZ, which is complicated by serious nerve pain, called post herpetic neuralgia (PHN), after about 15% of HZ cases.⁴ This nerve pain can be severe and intractable, often with less than 50% pain relief for more than 4 months.⁴ Other serious complications of HZ include meningoencephalitis, myelitis, cranial palsy, gastrointestinal disorders, stroke, or cardiovascular events.¹

Emerging science is improving varicella and HZ outcomes. Childhood vaccination with live Oka VZV strain-based attenuated virus began in the United States in 1995. This was replaced by a 2-dose formula in 2006, reducing the incidence of both varicella and its related mortality by 90% in vaccines.^1,5 Childhood vaccinees still developed shingles, but at a significantly lower rate than similar children with a history of chicken pox. The more potent, live vaccine of 2006 reduced healthy adult HZ infection rates from 2 to 3 per 1000 patient-years in naturally infected, same-age individuals to 0.9 per 1000 patient-years in vaccines.¹ Fears that vaccinating a broader population may increase  the likelihood of HZ in unvaccinated individuals have proved baseless. Like many chronic wounds, preventing and managing HZ requires a multidisciplinary approach, with reliable, valid diagnostic techniques and outcome measures and groups matched at baseline on known HZ risk factors. Reported herein are a recently validated algorithm for assessing HZ epidemiology⁶ and a randomized controlled trial (RCT) exploring the effects of radiofrequency dorsal root ganglion stimulation to reduce PHN.⁷

Reference: Schmidt SAJ, Vestergaard M, Baggesen LM, Pedersen L, Schønheyder HC, Sørensen HT.  Prevaccination epidemiology of herpes zoster in Denmark: quantification of occurrence and risk factors [published online ahead of print September 2, 2017]. Vaccine. 2017;35(42):5589–5596.

Rationale: While HZ is a vaccine- preventable disease, its burden is poorly understood and addressed since most countries do not record HZ cases in the general population. 

Objective: Develop and validate an algorithm using routinely collected registry data to identify and quantify HZ occurrence and risk factors in Denmark prior to marketing of the HZ vaccine.

Methods: Patients in the Danish nationwide health registries from 1997 to 2013 were included if they were at least 40 years of age and received a first-time systemic acyclovir, valacyclovir, or famciclovir prescription or a hospital-based HZ diagnosis. A validation substudy (n = 176) computed the percent of those diagnosed with HZ who redeemed antiviral prescriptions. In a cohort of 45 297 258 person-years, age-specific incidence of HZ was calculated. A case-controlled study then computed odds ratios (ORs) for common chronic diseases and immunosuppressive factors among HZ cases (n = 189 025) as compared to matched population controls (n = 945 111). Statistical significance of ORs was set at α < 0.05 or likelihood outside the 95% confidence interval.

Results: Herpes zoster was confirmed in 87% of those at least 40 years of age who filled antiviral prescriptions at doses recommended for HZ. Incidence of HZ was highest in women and increased from 2.15 per 1000 person-years in 40-year-olds to 9.45 per 1000 person-years in 95-year-olds. In 3.5% of cases, HZ was diagnosed during hospitalization. Those with severe immunosuppressive conditions had the highest ORs of HZ (1.82–4.12). Individuals with various autoimmune diseases, asthma, or chronic kidney disease or users of inhaled glucocorticoids also had high ORs of experiencing HZ (1.06–1.64).

Authors’ Conclusions: This algorithm served as a valid tool for identifying episodes of HZ using routinely collected health care data. It showed HZ to be common in Denmark, especially in high-risk patients with certain chronic conditions who may benefit from prioritized vaccination against HZ.

Reference: Kim K, Jo D, Kim E. Pulsed radiofrequency to the dorsal root ganglion in acute herpes zoster and postherpetic neuralgia. Pain Physician. 2017;20(3):E411–E418.

Rationale: Pulsed radiofrequency stimulation (PRF) of the dorsal root ganglion (DRG) has alleviated other types of pain but has not been applied to the neuropathic pain of PHN, which often originates from reactivation of latent VZV from the DRG.

Objective: Conduct a retrospective comparative study of safety and efficacy of PRF stimulation of the DRG in reducing the pain associated with either HZ episodes or related PHN.

Methods: The authors conducted a retrospective chart review of 58 patients with moderate to severe HZ-related pain attending a university hospital pain center in Korea. Each patient underwent an epidural foraminal block preparatory to PRF stimulation through a 10-cm needle electrode with a 1-cm active tip inserted with fluoroscopic guidance into the DRG sufficiently to generate a tingling sensation in the involved dermatome in response to a brief 50 Hz pulse of < 0.5 V. Pulsed radiofrequency stimulation was delivered in 20 millisecond pulses of 45 V amplitude with impedance < 500 Ω for a total of 360 seconds at 42°C. Early treatment of HZ-related pain was defined as during the first 90 days after the onset of HZ (n = 29). Identical late PRF treatment occurred more than 90 days after onset of the HZ episode to treat PHN (n = 29). The primary outcome was patient-rated pain intensity reported on a 0 to 10 scale before PRF stimulation and at 1, 4, 8, or 12 weeks after PRF stimulation. Baseline demographics, affected dermatome, and risk factors for PHN were reported as well as pain medication use at each time when pain was reported. Statistical significance (P < .05) was tested using the Student’s t or Mann-Whitney U test for continuous variables or chi-square test for categorical variables.

Results: Pain ratings decreased significantly in the first week after PRF DRG stimulation for all patients, from an average rating of about 6 before PRF DRG stimulation to about 4.3 for the > 90-day group or about 3.5 for those stimulated before day 90 after HZ onset. Reported pain and pain medication use remained stable and significantly lowered from week 1 through week 12 after the PRF DRG stimulation compared with those receiving later PRF. More patients in the early PRF DRG group discontinued their pain medications. 

Authors’ Conclusions: Despite the small sample size in this single-center, retrospective chart review, these results suggest the merit of using PRF of the DRG to alleviate pain associated with HZ and the subsequent intractable pain of PHN.

Incidence of HZ is widely under- reported.⁶ It has been increasing since the mid-20th century, long before development of effective vaccines. Clinicians are only beginning to understand its complex links to gender, stress, immunology, cardiovascular, cerebrovascular, and other conditions. Measuring PHN complications has opened minds to new directions of inquiry. Is the increased risk of stroke after HZ infection directly caused by the virus, or does it result from hypertension induced by the often severe intractable pain of PHN? Availability of effective HZ and VZV vaccinations may help prevent HZ and PHN but only if routine vaccination is practiced. 

Epidemiologic research before and after introducing VZV and HZ vaccination is replacing fears with facts. Many countries still refrain from using these vaccines based on unfounded concerns that widely practiced vaccination would increase incidence of VZV and/or HZ infection in unvaccinated individuals.¹ Consistent monitoring of HZ⁶ has shown how fast the HZ epidemic has grown and the greatness of its clinical and patient burdens, setting the stage to test hypotheses about effects of both VZV and HZ vaccinations. Decreases in shingles-related pain resulting from PRF DRG stimulation during the first 90 to 180 days after HZ onset have exceeded those achieved by epidural nerve blocks,⁸ with maximum efficacy achieved during the first 90 days after onset of HZ infection, before onset of what is considered the PHN period.⁷ Efficacy and safety of PRF DRG stimulation remains to be tested in blind evaluated RCTs and compared to the effects of intrathecal steroid injections or spinal cord electrical stimulation, also shown to reduce HZ-induced pain.

Emerging evidence is improving knowledge of HZ epidemiology, prevention, and treatment options that could help multidisciplinary teams optimize HZ patients’ pain, healing, immunologic, neural, vascular, and dermatologic outcomes. Consistently monitoring risk factors and outcomes of HZ management is helping researchers remove the cloak of superstition about the VZV and HZ epidemic and providing important insights for serving those affected by HZ.

This article was not subject to the WOUNDS peer-review process.