Postherpetic Neuralgia

Postherpetic neuralgia (PHN) is the most common complication of herpes zoster (shingles). It produces chronic pain along cutaneous nerves and often some distortion of sensation. The pain can either persist after the acute shingles episode or it can recur in an area previously affected by shingles.

There is a separate articles discussing Shingles (herpes zoster).

• There are various definitions for postherpetic neuralgia with regards to time of onset and duration of the pain. This makes estimates about its prevalence difficult.¹
• The incidence in UK primary care is thought to be about 28 per 100,000 person-years.²
• Another estimate is that about 20% of people will experience post-herpetic neuralgia after the initial rash has cleared.³
• The incidence of post-herpetic neuralgia following an episode of shingles increases with age. It is uncommon in children.

Factors that may predispose to PHN include:

• Older age (>50 years).⁴
• Female sex.⁴
• Presence of severe pain during the attack of shingles.⁴
• A more extensive and severe shingles rash.^5,4
• The presence of a prodrome (48-72 hours of throbbing pain and paraesthesia in the region of the affected sensory nerve before the shingles rash develops).⁴
• It is possible that some psychosocial factors predispose to PHN.⁶
• The site of the herpes lesion:⁵
  • Risk of PHN is low in the jaw, neck, sacral, and lumbar regions.
  • Risk is moderate in the thoracic area.
  • The highest risk is in the trigeminal area, especially the ophthalmic division, and also the brachial plexus.

Research is currently underway looking at biomarkers that can help identify those at risk of developing PHN.⁴

• Herpes zoster presents initially with a painful vesicular eruption in a single dermatome.
• The eruption resolves but in PHN pain continues. Some sources say that pain must continue for at least 3 months to fulfill the definition of PHN.⁵ Others say that PHN is pain persisting more than 30 days after lesions have healed.⁷ Another source says that PHN is pain persisting for more than 4 months after the rash has healed.⁴
• Pain is intense and may be described as burning, stabbing, shooting or throbbing.
• The affected area may be itchy.
• There may be allodynia. This is when pain is produced by stimuli that are not usually painful, e.g. a cold draught or heat or light touch.
• Hyperalgesia may be present. This is where there is increased sensitivity to painful stimuli.
• Pain can be debilitating. It can interfere with sleep, activities of daily living, and can also be so severe that it leads to depression and social isolation.^8,4
• Symptoms may be present for a few months or even years.^9,4

Examination

• The area affected by shingles may show some scarring.
• There may be either hypersensitivity or reduced sensation in affected areas.
• Allodynia may be demonstrated.

The diagnosis is usually clinical and no specific investigations are indicated.

General advice

Clinical Knowledge Summaries suggests the following management.⁹

• Explain the nature of the condition to the patient, including expected duration of symptoms and aims of treatment.
• Advise loose clothing and cotton worn next to the skin. This will cause less irritation.
• Cling film or a plastic wound dressing may help to protect sensitive areas.
• Cold packs may help ease pain (unless there is associated allodynia made worse by cold).

Drug treatment

Clinical Knowledge Summaries suggests the following management.⁹

• Start with paracetamol or a paracetamol/codeine combination.
• If there is severe pain at the outset or if the above measures are not sufficient, add in either a tricyclic antidepressant (off-licence) or gabapentin (licensed) which have been shown to be effective in the treatment of PHN.^4,10
  • Tricyclic antidepressants:
    • Amitriptyline (most widely used), imipramine, or nortriptyline may be used.
    • Care should be taken, especially in the elderly, due to the possibility of anti-cholinergic side effects which can lead to acute confusion or cardiac arrhythmias.⁴
    • Initial dose is 25 mg at night (10 mg if elderly/frail).
    • Increase by weekly increments of 25 mg (10 mg if elderly/frail) until pain is controlled or side effects occur.
    • Maximum dose is 75 mg at night (50 mg if elderly/frail).
  • Gabapentin:
    • Start with 300 mg once daily on day 1, 300 mg twice daily on day 2, and 300 mg three times daily on day 3.
    • Then increase the dose by 300 mg daily every 2-3 days according to the response.
    • Maximum dose is 3600 mg. This dose should be achieved over a minimum period of 3 weeks. Slower titration may be needed for e.g. elderly or frail.
• Capsaicin 0.075% cream can be used topically if other treatments are not appropriate, or at patient request.
• Topical lidocaine 5% patches may be considered if oral or other topical treatment is not suitable or is not tolerated. They are not recommended as first-line treatment. A Cochrane review found limited evidence for their effectiveness.¹¹

Non-drug treatments including acupuncture and transcutaneous electrical nerve stimulation have been reviewed by the American Academy of Neurology and found to be ineffective in the management of PHN.¹²

When to refer to a specialist pain clinic

Clinical Knowledge Summaries suggests referral to a pain clinic or a specialist if:⁹

• The above treatment does not control pain after 4-6 weeks.
• There are adverse effects of medication that are affecting/limiting treatment.
• You are considering the use of strong opioids or carbamazepine.

• Most patients with PHN will experience a slow improvement over a long period of time, particularly when medical management is used.
• There is a small group who fail to show any improvement despite medical treatment.⁵

• No treatment has been shown to prevent PHN completely.⁷
• Antiviral therapy started within 72 hours of onset of the shingles rash may reduce the incidence of PHN.^13,14
• A study showed that amitriptyline initiated within 48 hours of shingles rash onset may reduce pain prevalence at 6 months by up to 50%. Numbers needed to treat were 5.¹⁵
• It is thought that the introduction of a childhood varicella zoster vaccine (as in the USA) can reduce the risk of herpes zoster, and therefore PHN, when this cohort of children become elderly. However, there is concern that reducing the number of children with varicella zoster by introducing a vaccine could lead to a short term increase in herpes zoster in those who are latently infected. This is because cell mediated immunity that suppresses latent infection needs repeated boosting by exposure to 'wild' virus circulating in the community.⁴
• The Shingles Prevention Study looked at giving the varicella zoster vaccine to older people (adults over 60) to boost their waning immunity.¹⁶ It found that the vaccine significantly reduced the morbidity due to herpes zoster and PHN in older adults.¹⁷
• Oral steroids do not seem to prevent PHN.¹⁴
• Epidural steroids repeatedly administered combined with a continuous infusion of anaesthetic for up to 21 days has been shown to reduce the incidence of PHN but the risks and practicalities of this intervention need to be looked into further.¹⁸