Herpes zoster, also referred to as Shingles, is a relatively common disease; the estimated incidence of acute herpes infection in the European population varies from 1.2 to 5.2 per 1000 people per year. There is a correlation between the incidence of the disease and age. People younger than 50 years have a low risk of developing herpes zoster which equals approximately 2%. The incidence sharply rises in adults above 50 years; the risk makes up to at least 20% and continues to increase further reaching 35% in people above 80 years. The recent upswing in chickenpox infection and varicella-zoster virus (HZ) in the community has increased the risk of developing post-herpetic neuralgia (PHN).  

Professor Dominic Hegarty (Clinical Director Pain Relief Ireland) writing in a recent medical article in Rheumatology & Pain section of the Medical Independent (Vol 6, June 2023) said “PHN is an extremely painful condition, that can persist for many years making life miserable for the unfortunate patient. Early recognition is very important and can offset chronicity”.  

“PHN is an extremely painful condition, that can persist for many years making life miserable for the unfortunate patient. Early recognition is very important and can offset chronicity”.  

Complicating the situation now is the relationship between COVID 19 infection and incidence of  PHN. In a retrospective cohort study of over 2 million people it was highlighted that adults over 50 years of age who had mild COVID-19 are 15% more likely to develop HZ within 6 months compared to those who have not been infected by coronavirus. The risk was 21% greater in older people who were hospitalized by with COVID19. (Bhavsar et al. Open forum Infectious Diseases).

How do we diagnose PHN?

The diagnosis of postherpetic neuralgia is relatively straightforward and not one of exclusion. And include:

1. An episode of herpes zoster is a prerequisite for PHN. Therefore, a history of rash with blisters in a dermatomal pattern would be expected. Rarely the characteristic rash will not be found.
2. Persistent (more than or equal to 3 months) lancinating/burning pain, allodynia, paraesthesia’s, pruritus, dysesthesias, and/or hyperalgesia at or near the area of the rash is characteristic of PHN.
3. Herpes zoster can reactivate sub clinically with no rash. This condition is called zoster sine herpete and is more complicated. It affects the central nervous system at multiple levels and causes cranial neuropathies, myelitis, polyneuritis, or aseptic meningitis.
4. Physical examination of a patient with postherpetic neuralgia may reveal the following:
   • Evidence of cutaneous scarring on an area of previous herpes zoster
   • Altered sensation in the affected areas, either hypersensitivity or hypoesthesia
   • Pain is produced by non-noxious stimuli, such as a light touch, known as allodynia.
   • Autonomic dysfunction, such as excessive sweating over the involved area.

“...quite simply if an individual who has shingles continue to have daily pain in the affected area 3 months after the onset, they really should discuss the matter with their GP or pain physician.”

Professor Hegarty says that “quite simply if an individual who has shingles continue to have daily pain in the affected area 3 months after the onset, they really should discuss the matter with their GP or pain physician”. There are a variety options as Professor Hegarty outlined in his recent educational review and in summary these include:

1. Prevention.
   This focuses on identifying populations at risk for contracting HZ and administering a vaccine. At present there are two licenced HZ vaccines in Ireland ( MIMS May 2023) – Shingrix and Zostavax. This should be considered in those over 50 years and in those in the higher risk groups. It is not necessary to determine whether patients have a history of varicella or zoster prior to vaccination because weaning antibodies in those previously exposed may lead to negative results despite past infection. Unfortunately, these vaccines are not part of the national immunisation program so patients need to discuss this option with their GP and self-fund the vaccine.
    
2. Early Recognition.
   Early recognition and treatment of an acute HZ infection, may reduce the chance of developing PHN. The benefit of rapid treatment has been shown to be very useful. If a combination of agents can be commenced with 72 hours of first symptoms this will lower the chance of compilations.
    

   Table 1 Suggested Agents to consider in the early management plan
   Antivirals	Acyclovir (Sitavig, Zovirax) Famciclovir (Famvir) Valacyclovir (Valtrex)
   Simple Analgesics	Acetaminophen Ibuprofen Naproxen
   Neuropathic Pain Management	Pregabalin Gabapentin Amitriptyline
   Topical	Lidocaine patches Capsaicin cream Ice packs

    

3. PHN management.
   In the situation where PHN develops the symptom management of PHN is best considered using multimodal medication regimens and interventional procedures. The evidence regarding the efficacy of these methods is mixed but rapidly evolving, and certain approaches appear to be more successful than others. There is no one superior treatment regimen; however, expert consensus suggests that multimodal therapy is likely the best approach. Lastly, many of the advocated approaches treat chronic neuropathic pain in general and are not specific to PHN.

   • Oral and topical medications
     Traditional non-invasive treatments include oral and topical medications. The American Academy of Neurology (AAN), Special Interest Group on Neuropathic Pain (NeuPSIG), and European Federation of Neurological Societies (EFNS) all recommend an oral tricyclic antidepressant (TCA), pregabalin, and the lidocaine 5% patch as first-line therapies. The anticholinergic, antihistaminergic, and alpha receptor-blocking side effects of TCAs must be considered, as the elderly are more susceptible. As a result, it is commonplace to initially prescribe and titrate a gabapentinoid, keeping in mind that patients with reduced renal function should be started at a lower dose and up-titrated more slowly.

   • Opioids
     The use of opioids to combat PHN is controversial because of the changing landscape regarding what constitutes appropriate use and also renewed governmental interest in their administration given the epidemic of abuse, addiction, and mortality. The above three medical societies recommend opioids as either first or second-line treatments, which underscores the pain-reducing capability of this medication class.

   • Lidocaine Patches
     Multiple studies have confirmed the short and long-term efficacy of the lidocaine 5% patch. This patch also has the additional benefit of a small side effect profile that is mostly limited to application site reactions. Application is required for 12 hours at a time and should be used over prolonged period (4-8 weeks initially)

   • Capsaicin
     Capsaicin preparations in the patch and cream formulations are also available but not as well-studied as the lidocaine patch. The leading cause of discontinuing capsaicin treatment is pain and irritation at the application site, suffered by almost all users in proportion to the capsaicin concentration. The cream has a low concentration of capsaicin, requiring multiple applications to achieve a therapeutic effect throughout the day. Conversely, the capsaicin patch is available in an 8% formulation, delivering a therapeutic dose in just one application. The higher concentration patch should only be provided by those trained in the application and monitoring of outcome. Nevertheless, encouraging case reports and other literature suggest the intervention warrants consideration and further study.

   • Non-TCA antidepressants and NMDA antagonists.
     There is limited evidence to supports their usefulness. For example, larger studies involving SNRIs (serotonin-norepinephrine reuptake inhibitors) and SSRIs (selective serotonin reuptake inhibitors) have not shown better outcomes than TCAs, and both classes possess concerning side effect profile, though typically less severe than TCAs.

   • Invasive Therapies
     If the pain persists in a specific dermatomal or nerve distribution then a simple effective option is to use a peripheral nerve block or pulsed denervation the dorsal root ganglion  Pulsed radiofrequency (PRF) is a minimally invasive technique that applies pulsed current (300–500 kHz) to the target nerve. The current is delivered in a pulse of 20 ms (45 V’ voltage) followed by a silent period of 480 ms to avoid heat lesions. Recent studies have confirmed the beneficial effects of PRF against post-operative pain, peripheral neuropathic pain, and postherpetic neuralgia. The thoracic nerves (T1-12) are the most commonly affected by PHN with an incidence of up to 50% cases. Studies have shown that both DRG and intercoastal nerve treated with PRF treatments are effective in the treatment of thoracic postherpetic neuralgia. Targeting the dorsal root ganglion gas shown to have a better outcome in pain intensity and other quality of life domains (SF-36).

     Other invasive therapies include botulinum toxin injections, sympathetic blockade with local anaesthetics, and epidural/intrathecal injections have a limited side effect profile. However, more studies need to be conducted to evaluate their efficacy. The other invasive therapies mentioned carry the potential for significant peri-procedural risk and/or side effects.

   • Future therapy options
     Neuromodulation offers the possibility of long-term drug-free pain therapy inn a wide range of neuropathic pain conditions. The development of the dorsal root ganglion stimulator to treat focal dermatomal neuropathic pain conditions is theoretically promising for PHN. Traditional spinal cord stimulation programming option can now target painful area with greater accuracy. We need to extend studies to consider the role of technology to advance our options.

      

Long-term Enhancement of Healthcare Team Outcomes

In Professor Hegarty’s opinion “Considering that postherpetic neuralgia is difficult to treat and outcomes are variable, prevention is of paramount importance”. Therefore, primary care physicians and geriatricians are tasked with administering vaccinations to at-risk populations. The ever-growing aging population means that demands on this service will continue to increase. Inclusion of the vaccines on the national immunisation program by the Department of Health needs to be considered as a priority if we are to protect our venerable senior citizens. When preventative measures fail or are never instituted, experts in the field of pain management who have experience with the condition and multimodal treatment techniques should be consulted. Interventional pain management can offer solutions. An interprofessional approach to managing patients with postherpetic neuralgia is the best way forward.

As Prof. Hegarty quite rightly highlighted the fact is that “PHN is painful but preventable”.

“PHN is painful but preventable”.

If you feel you may be suffering post-herpetic neurlgia and would like to see if there is a treatment option for you contact Pain Relief Ireland and arrange a clinical review or discuss the issue with your GP.

Article in Rheumatology & Pain section of the Medical Independent (Vol 6, June 2023)
https://www.medicalindependent.ie/clinical-news/update-journal/update-rheumatology-pain-june-2023/