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Post-herpetic neuralgia

Author: Arcana Luo, Medical Student, University of Auckland, New Zealand; Chief Editor: Dr Amanda Oakley, Dermatologist, Hamilton, New Zealand, March 2014.


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What is post-herpetic neuralgia?

Post-herpetic neuralgia describes chronic skin pain in an area previously affected by herpes zoster (shingles).

Herpes zoster is a localised painful blistering rash caused by reactivation of herpes varicella-zoster virus sometime after the primary generalised infection with varicella (chickenpox).

How is post-herpetic neuralgia diagnosed?

Because post-herpetic neuralgia is defined as pain after and caused by, re-activation of the herpes zoster virus, evidence of herpes zoster infection is critical for diagnosis.

Usually, the diagnosis of herpes zoster is easily made when a painful blistering rash arises that has dermatomal distribution (ie, along the pathway of a cutaneous nerve).

However, not all patients with post-herpetic neuralgia have a history of rash or acute symptoms. In these cases, a rise in antibody levels on serial blood tests may confirm the previous infection by herpes zoster virus.

Post-herpetic neuralgia is often used to describe any pain that persists after herpes zoster blisters have cleared up. Some experts prefer to reserve the term only for pain that lasts for more than 28 days or more than 120 days. 'Acute' and 'sub-acute' herpetic neuralgia may be used to describe earlier pain associated with herpes zoster infection.

What are the clinical features of post-herpetic neuralgia?

Features of post-herpetic neuralgia include:

  • Dermatomal distribution: pain limited to 1–3 dermatomes and usually confined to one side of the body. Rarely, pain can be disseminated or affect both sides of the body.
  • Post-herpetic neuralgia is usually a chronic neuropathic pain with a burning character, but some patients experience sharp stabbing pains.
  • Pain may be constant or intermittent.
  • Other symptoms and sensory changes may be present in the same dermatome/nerve distribution as the pain:
    • Itch
    • Anaesthesia (numbness)
    • Hyperaesthesia (sensitivity to touch)
    • Allodynia (pain from a light touch)
    • Other sensory change such as reaction to temperature.
  • Motor dysfunction (this is rare):
    • Autonomic dysfunction (eg sweating)
    • Organ damage (eg blindness if there is ophthalmic involvement)

Chronic pain can lead to insomnia, anxiety and depression.

What are the risk factors for the development of post-herpetic neuralgia?

The main risk factors for post-herpetic neuralgia are:

  • Older age
    • Post-herpetic neuralgia is rare in people younger than 40
    • About 50% of herpes zoster patients aged 70 years or older will develop post-herpetic neuralgia
  • Immunosuppression
  • Severe infection
    • Pain beginning before the blisters appear
    • Severe pain in the acute phase of infection
    • Severe and prolonged blistering, ulceration and necrosis

Some other possible risk factors include:

  • Being female
  • Having other sensory abnormalities
  • Infection of the ophthalmic nerve (leading to eye infection)

What causes post-herpetic neuralgia?

Acute herpes zoster pain is due to direct damage of peripheral nerves by the herpes zoster virus. Ongoing post-herpetic neuralgia is due to slow recovery and the involvement of the central nervous system.

Research has shown that the nerves or neurones affected by post-herpetic neuralgia are damaged. Microscopic changes include:

  • Atrophy and deafferentation (loss of connections) of dorsal horns of affected dermatomes
  • Pathological changes in spinal cord sensory ganglions (nerve cell bodies)
  • Markedly reduced number and density of sensory nerves in affected skin

It has been suggested that these damaged nerves send fewer signals from the skin to central nervous structures, which leads to neuron hyperexcitability and the constant perception of pain. However, the exact pathways are unknown.

It is likely that acute and sub-acute pain, and sensory changes such as allodynia, arise from slightly different mechanisms.

How is post-herpetic neuralgia prevented?

Herpes zoster pain and post-herpetic neuralgia are common and very debilitating conditions. But they can be prevented to a large extent by vaccination of at-risk individuals and by prompt antiviral treatment during the acute phase of herpes zoster infection.

Herpes zoster vaccines

  • Herpes zoster vaccines have been shown to reduce the incidence of reactivation of herpes varicella-zoster virus.
  • Vaccinated patients that develop herpes zoster have less severe acute symptoms and are less likely to develop post-herpetic neuralgia.
  • Post-herpetic neuralgia is less severe and lasts a shorter time in vaccinated patients.
  • Herpes zoster vaccines are less effective in older and immunocompromised people.
  • In New Zealand, the Zostavax® vaccine is available and approved for people 50 years old and above. It is a live attenuated virus (ie a virus that is much less virulent than the original strain) and is unsuitable for patients with immunodeficiency or immunosuppression.

Antiviral agents

  • Antiviral agents such as aciclovir reduce the severity and duration of acute symptoms of herpes zoster.
  • Even with optimum antiviral therapy, 20–30% of herpes zoster patients develop post-herpetic neuralgia.
  • Treatment with antivirals is most effective if it is started within 72 hours of the onset of herpes zoster rash; however, antivirals may still be effective when started later.
  • Most experts recommend antiviral treatment for all older people with herpes zoster and whenever there is ophthalmic nerve involvement.
  • As antiviral agents are very safe, some experts recommend treating everyone that has acute herpes zoster infection.

Tricyclic antidepressants

  • Amitriptyline is the most commonly prescribed tricyclic agent to treat pain due to acute zoster or post-herpetic neuralgia. Nortriptyline and desipramine are alternatives.
  • Early use of a tricyclic agent may reduce the risk of post-herpetic neuralgia.

Other agents

The following have not been shown to prevent post-herpetic neuralgia:

What is the treatment for post-herpetic neuralgia?

Multiple treatments are often required to control post-herpetic neuralgia.

Topical medications

Oral medications

  • Tricyclic antidepressants
    • Amitriptyline
    • Nortriptyline
    • Desipramine
  • Non-steroidal anti-inflammatory drugs
    • Ibuprofen
    • Indomethacin
    • Diclofenac
  • Anticonvulsants
    • Gabapentinoids (gabapentin, pregabalin)
    • Valproic acid
  • Opioids
    • Oxycodone
    • Tramadol, tapentadol
    • Morphine

Invasive methods

  • Sympathetic nerve blocks
  • Subcutaneous injection of botulinum toxin A or triamcinolone acetonide
  • Neuraxial blocks
  • Peripheral nerve blocks
  • Spinal cord stimulation
  • Pulsed radiofrequency
  • Light cryotherapy of affected skin or direct freezing of the sensory neurone

Other treatments

  • Support, psychotherapy and biofeedback techniques may help patients manage their pain.
  • A transcutaneous electrical nerve stimulation (TENS) machine may help some patients

What is the outlook for post-herpetic neuralgia?

The duration of post-herpetic neuralgia is variable.

  • In the majority of people, symptoms resolve within 6 months to 1 year.
  • In untreated patients, about half have no pain at 6 months.
  • Some people have pain lasting for many years, sometimes several decades.
  • The duration and severity of neuralgia increase with age.

 

References

  • Bruxelle J, Pinchinat S. Effectiveness of antiviral treatment on acute phase of herpes zoster and development of post herpetic neuralgia: review of international publications. Med Mal Infect. 2012 Feb;42(2):53–8. doi: 10.1016/j.medmal.2011.11.001. PubMed
  • Serpell M, Gater A, Carroll S, Abetz-Webb L, Mannan A, Johnson R. Burden of post-herpetic neuralgia in a sample of UK residents aged 50 years or older: findings from the Zoster Quality of Life (ZQOL) study. Health Qual Life Outcomes. 2014 Jun 11;12:92. PubMed
  • Derry S, Sven-Rice A, Cole P, Tan T, Moore RA. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2013 Feb 28;2:CD007393. PubMed
  • Levin MJ, et al. Prevention strategies for herpes zoster and post-herpetic neuralgia. J Clin Virol. 2010 May;48 Suppl 1:S14–9. doi: 10.1016/S1386-6532(10)70004-4. PubMed
  • Opstelten W, et al. The impact of varicella zoster virus: chronic pain. J Clin Virol. 2010 May;48 Suppl 1:S8–13. doi: 10.1016/S1386-6532(10)70003-2. PubMed
  • Philip A, et al. Post herpetic neuralgia. J Palliat Med. 2011 Jun;14(6):765–73. doi: 10.1089/jpm.2011.9685. PubMed
  • Watson CP, et al. Post-herpetic neuralgia: 208 cases. Pain. 1988 Dec;35(3):289–97. PubMed
  • Whitley RJ, et al. Management of herpes zoster and post-herpetic neuralgia now and in the future. J Clin Virol. 2010 May;48 Suppl 1:S20-8. doi: 10.1016/S1386-6532(10)70005-6. PubMed
  • Wolff RF, et al. 5% lidocaine-medicated plaster vs other relevant interventions and placebo for post-herpetic neuralgia (PHN): a systematic review. Acta Neurol Scand. 2011 May;123(5):295–309. doi: 10.1111/j.1600-0404.2010.01433.x. PubMed
  • New Zealand Data sheet. Zostavax. Merck Sharp and Dohme Corp. 2011. Retrieved 5/3/2014. Medsafe
  • Watson CP, et al. The prognosis with post-herpetic neuralgia. Pain 1991 Aug;46(2):195–9. PubMed
  • Dworkin RH, et al. Diagnosis and assessment of pain associated with herpes zoster and post-herpetic neuralgia. J Pain. 2008 Jan;9(1 Suppl 1):S37-44. doi: 10.1016/j.jpain.2007.10.008. PubMed

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