Update on Postherpetic Neuralgia

Approximately 1 million cases of herpes zoster, or shingles, occur each year in the United States. Lifetime risk of this common condition is estimated to be close to 30% or higher, with age-adjusted, sex-specific rates higher in women than in men (3.9 vs. 3.2 per 1000 person-years, respectively).1

Pain is the most common symptom associated with herpes zoster, occurring in 90% of cases, often preceding the development of a unilateral rash which most frequently follows a pattern of thoracic and cranial dermatomal distribution. In uncomplicated cases, the rash usually resolves within 2-4 weeks of the outbreak. However, a significant subset of patients (27-68%) develops persistent pain after the resolution of the rash, a serious condition known as postherpetic neuralgia (PHN). Although there is lack of consensus as to when pain associated with an acute attack becomes PHN, it is generally considered to be present when pain persists more than a month after the eruption of the acute zoster rash2. Since many patients experience resolution of the pain over the following 1-2 months, PHN is considered to be chronic in nature when the pain persists for 3 to 6 months after onset.

Considered by many to be the prototypical example of a neuropathic pain condition (due to its adherence to dermatomal distribution of the affected nerves), the pathogenesis of PHN is not completely understood. The theory has been proposed that it is caused by virus-induced damage of peripheral afferent neurons, and resulting changes from viral replication and immune responses in central afferent neurons and efferent pain-modulating neurons.

Well established epidemiologic studies indicate that the likelihood of developing PHN following acute zoster in an immunocompetent individual is strongly linked to age, with older patients at much greater risk than younger individuals3. Yawn et al.1 recently reported that the percentage of patients studied with an episode of herpes zoster who developed PHN strongly correlated with advanced age:

  • – 5% in those younger than 60 years
  • – 10% in those aged 60 to 69 years
  • – 20% in those aged 80 years or older

In addition to the direct correlation of age and occurrence, the severity and duration of a PHN attack seem to be related to age as well. When it occurs, PHN-related pain can be quite severe, with most patients reporting:

  • – Spontaneous constant pain that is aching or burning in nature
  • – Intermittent “shock-like” radiating pain
  • – Usual stimuli, such as clothing or bed sheets cause excruciating pain (allodynia)
  • – Exaggerated pain (lasting for hours) often occurring after a relatively mild painful stimulus (hyperpathia)

Pain from PHN can last for months or sometimes even years. One study of patients 65 years or older measured the mean duration of pain associated with PHN as 3.3 years, ranging from 3 months to more than 10 years4.

PHN can have dramatic clinically significant physical, psychological, and social consequences for patients and their caregivers. Katz et al. reported that a studied sample of patients ranked pain from PHN worse than post-surgical or labor pain5. From a physical perspective, normal daily function can be brought to a standstill. Additionally, signs and symptoms that decrease overall quality of life may occur, such as insomnia, fatigue, anorexia, and weight loss. In some cases, the physical effects can be so debilitating that some elderly patients may permanently lose their independence after an episode of PHN.

From a psychological perspective, the most common consequence of PHN is depression, which can be severe and sometimes lead to suicide. In fact, PHN is one of the most common causes of pain-related suicide in the elderly patient population6. Socially, sufferers may withdraw completely from normal social interactions, especially those that involve leaving home to do things such as shop, travel, go to work, or attend social activities.

Like other neuropathic pain conditions, effective treatment can be challenging and options include several classes of pharmacologic agents2, for example:

  • – Tricyclic antidepressants (e.g., Amitriptyline, Desipramine, Nortriptyline)
  • – Other antidepressants (e.g., Selective serotonin reuptake inhibitors)
  • – Anticonvulsants (e.g., Gabapentin)
  • – Topical agents
  • – Lidocaine Patch 5%
  • – Capsaicin
  • – Opioids
  • – Interventional therapies

Psychological and behavioral interventions may also be employed at any time in the course of treatment for PHN as part of a multidisciplinary plan.

Antiviral agents (e.g., acyclovir) have been shown to be effective in decreasing the severity of an attack of herpes zoster if promptly administered within 1 to 2 weeks of rash onset. This may also reduce the risk of developing PHN, and its duration7.

The most important way to treat PHN is from a prevention perspective – by decreasing the incidence of a herpes zoster attack altogether. The herpes zoster vaccine has been associated with reduced risk of developing an attack of acute herpes zoster, and significantly reducing the severity of an attack if it should occur8. A recent study by Tseng et al. of almost 76,000 vaccinated people and 227,283 unvaccinated people matched for age showed that herpes zoster vaccine administration was associated with a 55% reduction in incidence of an attack of herpes zoster across all age groups9 leading the authors to postulate that “Our results support recommendations to offer herpes zoster vaccine to eligible patients of all ages including the oldest population. Not only might these patients experience a reduction in their relative risk of herpes zoster, but for the oldest group, this could translate into a very large absolute reduction in disease because they bear the greatest burden of herpes zoster and postherpetic neuralgia and are also especially vulnerable to these disabling conditions.”

Unfortunately, these authors identify that despite the beneficial evidence of vaccination, “to date, herpes zoster vaccine uptake has been poor due to weaknesses in the adult vaccine infrastructure and also due to serious barriers to the vaccine among clinicians and patients”. These barriers may include:

  • – The relatively recent approval and recommendations for vaccination
  • – Supply deficits
  • – Lack of awareness by patients and healthcare providers
  • – Difficulty in storage (needs to be stored frozen until use)
  • – Cost (about $200 and not covered by all insurance plans)

Considering the fact that anyone who has had the chickenpox (more than 95% of Americans) is susceptible to an attack of herpes zoster, and the potential devastation of PHN on overall quality of life, it would seem clear that everything possible should be done to aggressively treat an attack when it occurs, and prevent or minimize the likelihood of PHN if at all possible.

References

  1. 1. Yawn BP, Saddier P, Wollan PC, et al. A population-based study of the incidence and complication rates of herpes zoster before zoster vaccine introduction. Mayo Clin Proc. 2007;82(11):1341-1349
  2. 2. Argoff CE, Katz N, Backonja M. Treatment of postherpetic neuralgia: a review of therapeutic options. J Pain Symptom Manage. 2004; 28(4):396-411.
  3. 3. Hope-Simpson RE. Postherpetic neuralgia. J R Coll Gen Pract. 1975;25:571–575.
  4. Oster G, Harding G, Dukes E, Edelsberg J, Cleary PD. Pain, medication use, and health-related quality of life in older persons with postherpetic neuralgia: results from a population-based survey. J Pain. 2005;6:356–363.
  5. 4. Katz J, Melzack R. Measurement of pain. Surg Clin North Am. 1999; 79:231–252.
  6. Schamder K. Postherpetic neuralgia in immunocompetent elderly people. Vaccine. 1998;16:1768-1770.
  7. 5. Wood MJ, Kay R, Dworkin RH, et al. Oral acyclovir therapy accelerates pain resolution in patients with herpes zoster: a meta-analysis of placebo controlled trials. Clin Infect Dis. 1996;22:341–347.
  8. 6. Oxman MN, Levin MJ, Johnson GR, et al. Shingles Prevention Study Group. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005;352(22):2271-2284.
  9. 7. Tseng HF, Smith N, Harpaz R, Bialek SR, Sy LS, Jacobsen SJ. Herpes zoster vaccine in older adults and the risk of subsequent herpes zoster disease. JAMA. 2011 Jan 12;305(2):160-6.

A corresponding version of this article that is appropriate for your patients, titled “Postherpetic neuralgia: Shingles pain that doesn’t stop” is now available at www.painaction.com.