Postherpetic neuralgia

What is 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 episode of shingles or recur in an area previously affected by shingles. See also the separate Shingles article.

How common is postherpetic neuralgia? (Epidemiology)

• There are various definitions for PHN with regard to time of onset and duration of pain. This makes estimates about its prevalence difficult.

• The overall lifetime risk for herpes zoster (shingles) in Europe has been estimated at 23-30%. The risk in people aged 80 years and over is 50%.¹

• Approximately 20% of patients with herpes zoster report some pain at 3 months after the onset of symptoms, and 15% report pain at 2 years.²

• Postherpetic neuralgia is a more common complication of zoster in older people. In one study, 8% of people aged 50-54 had post-herpetic neuralgia at 3 months, rising to 21% of people aged 80-84.³

• It is uncommon in children.

Causes of postherpetic neuralgia (aetiology)

• The virus remains dormant in the nerve cell bodies of the asymptomatic host after an initial infection with varicella-zoster virus.

• It can also become latent in the satellite cells of the dorsal root, cranial nerves or autonomic ganglia.

• Reactivation of the latent herpes virus occurs in around 50% of people. It is more common in older people.

• Pain from acute herpetic neuralgia typically lasts 3-5 weeks.

• The reasons why post-herpetic neuralgia develops in some people are not clearly understood. Acute cytopathic and inflammatory tissue damage during the initial episode of zoster may lead to long-term changes in peripheral and central sensitisation.⁴

Risk factors

Factors that may predispose to PHN include:⁵

• Older age (>50 years).

• Female sex.

• Patients with severe immunosuppression and diabetes mellitus.

• Presence of severe pain during the attack of shingles.

• A more extensive and severe rash from shingles, especially if it extends beyond one dermatome.

• 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).

• The site of the herpes lesion:

  • 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.

Symptoms of postherpetic neuralgia (presentation)

• Herpes zoster presents initially with a painful vesicular eruption in a single dermatome.

• The eruption resolves but in PHN, pain continues.

• PHN is often defined as a chronic neuropathic pain condition that persists three months or more following an outbreak of shingles.⁶

• Pain is intense and may be described as burning, stabbing, shooting or throbbing.

• The affected area may be itchy.

• There may be allodynia: pain is produced by stimuli that are not usually painful - eg, a cold draught or heat, or light touch.

• Hyperalgesia may be present: there is increased sensitivity to painful stimuli.

• Pain can be debilitating. It can interfere with activities of daily living, and can also be so severe that it leads to depression and social isolation.

• Insomnia is very common and occurs more frequently in those with more severe pain.⁷

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.

Diagnosing postherpetic neuralgia (investigations)

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

Management of postherpetic neuralgia

General management

• Explain the nature of the condition to the patient, including expected duration of symptoms and aims of treatment.

• Advise the patient to wear loose clothing and, next to the skin, cotton. This will cause less irritation.

• Cling film or a plastic wound dressing may help to protect sensitive areas.

• Cold packs may help to ease pain (unless there is associated allodynia made worse by cold).

• There is no evidence to support the use of non-steroidal anti-inflammatory drugs (NSAIDs) for patients with PHN.

• Management should consider reducing the impact of pain on quality of sleep as well as overall pain reduction.

Pharmacological management

National Institute for Health and Care Excellence (NICE) guidance suggests the treatment of neuropathic pain should be as follows:⁸

• A choice of amitriptyline, duloxetine, gabapentin or pregabalin should be offered as initial treatment.

• If the initial treatment is not effective or is not tolerated, offer one of the remaining three drugs.

• Consider tramadol only if acute rescue therapy is needed.

• Consider capsaicin cream for people with localised neuropathic pain who wish to avoid, or who cannot tolerate, oral treatments.

Do not start the following in non-specialist settings, unless advised by a specialist to do so:

• Cannabis sativa extract.

• Capsaicin patch.

• Lacosamide.

• Lamotrigine.

• Levetiracetam.

• Morphine.

• Oxcarbazepine.

• Topiramate.

• Long-term tramadol.

• Venlafaxine.

• Sodium valproate.

Tricyclic antidepressants

Amitriptyline is the most widely used, or nortriptyline as an alternative.⁹

• Care should be taken, especially in the elderly, due to the possibility of anticholinergic side-effects which can lead to acute confusion or cardiac arrhythmias.

• Initial dose of amitriptyline is 25 mg at night (10 mg if elderly/frail) and 10 mg of nortriptyline.

• Increase by weekly increments of 25 mg (10 mg if elderly/frail) for amitriptyline and 10 mg for nortriptyline until pain is controlled or side-effects occur.

• Maximum dose is 75 mg at night (50 mg if elderly/frail) for amitriptyline and 100 mg for nortriptyline.

• Use of tricyclic antidepressants is often limited by their side-effects.

Anticonvulsant treatments

Gabapentin and pregabalin have been shown to reduce pain and improve sleep patterns in patients with PHN.¹⁰

• Gabapentin can be started with 300 mg once daily on day one, 300 mg twice daily on day two, and 300 mg three times daily on day three.

• Then increase the dose by 300 mg daily every two to three days according to the response. Maximum dose is 3600 mg.

• This dose should be achieved over a minimum period of three weeks.

• Slower titration may be needed for patients such as the elderly or frail.

• A single bedtime dose of 100 mg can be given to elderly frail patients.

• Pregabalin 75 mg bd can be given (to a maximum of 300 mg bd) if there are side-effects, such as sedation or ataxia, with gabapentin.

Capsaicin

Topical capsaicin (8%) patch can be used topically if other treatments have not worked, are not appropriate or at a patient's request.¹¹

• The skin needs to have healed completely.

• There can sometimes be a four-week delay before benefit is felt.

• If patients experience a burning sensation with topical capsaicin then the cream can be mixed with either glyceryl trinitrate (GTN) paste or Emla® cream.

Lidocaine patch

Topical lidocaine 5% patches can be considered if oral or other topical treatment is not suitable or is not tolerated.

• They are not recommended as first-line treatment.

• They should be applied for 12 hours and then removed for 12 hours.

• The 5% lidocaine medicated plaster has been shown to be as effective as systemic pregabalin in PHN but with an improved tolerability profile.¹²

• It also provides benefits beyond pain relief such as improving quality of sleep.¹³

There is an increasing body of evidence that botulinum toxin treatment is also effective in managing PHN.¹⁴

When to refer to a specialist pain clinic⁸

• If the above treatment does not control pain after four to six weeks.

• Patients with severe pain.

• Patients whose quality of life is being affected.

• There are adverse effects of medication that are affecting/limiting treatment.

Prognosis

• The duration of PHN is highly variable, with up to 50% of people experiencing pain for more than one year.¹

• A small number of people fail to show any improvement despite medical treatment.

Prevention of postherpetic neuralgia

• No treatment has been shown to prevent PHN completely.

• Placebo-controlled trials of antiviral drugs for acute herpes zoster have shown that they reduce the severity of acute pain and rash, hasten rash resolution and reduce the duration of pain.²

• However, there is high-quality evidence that oral antiviral treatments do not reduce the incidence of PHN above placebo.¹⁵

• There is no evidence that prescribing oral steroids, either alone or with antivirals, actually reduces the risk of developing PHN.¹⁶

• The only well-documented means of preventing PHN is the prevention of herpes zoster.²

• Vaccination is the most effective way to prevent the occurrence of herpes zoster complications in the elderly, in particular PHN.¹⁷ See the separate Shingles article.

• A universal vaccination programme for those aged 70-79 was introduced in the UK from September 2013, and is expanding to eventually include people from age 60 and above.

• In 2023, Shingrix®, a recombinant varicella zoster vaccine, replaced Zostavax® in the UK's routine immunisation programme. Two doses of Shingrix® have approximately 76% effectiveness against postherpetic neuralgia.¹⁸