Post Herpetic Neuralgia

Post-herpetic neuralgia occurs when the pain associated with shingles becomes chronic. Definitions of post-herpetic neuralgia differ in terms of the time of onset and duration of pain, and this has resulted in difficulty estimating the prevalence of the disease. One source estimates that approximately 20% of people older than 50 years will develop post-herpetic neuralgia, despite antiviral treatment beginning within 72 hours of rash onset.

Risk factors

Increasing age
Presence and severity of prodromal pain
Severity of acute zoster pain

Incidence

Post-herpetic neuralgia is the most common complication of shingles in adults; it is uncommon in children. In UK primary care, the incidence of post-herpetic neuralgia is estimated to be 28 per 100,000 person-years.

Pathophysiology

Varicella zoster virus is a highly contagious double stranded DNA virus of the herpes family. Primary varicella manifests commonly as chickenpox in a non-immune or incompletely immune person. During the primary infection, the virus gains entry into the sensory dorsal root ganglia. Reactivation of the virus occurs following depression of cell-mediated immunity and in advance-aged patients. The reactivated virus replicates and migrates down the sensory nerve leading to the dermatomal distribution of pain. The associated inflammation in the peripheral nerves leads to demyelination, Wallerian degeneration and fibrosis. Thus, as a result, uninhibited and amplified activity in unmyelinated primary afferents leads to pain associated with post-herpetic neuralgia.

Symptoms

The pain of PHN usually follows the typical dermatomal distribution of the rash caused by herpes zoster. Unilateral thoracic dermatomes and the trigeminal nerve, especially the ophthalmic branch, are most frequently affected.

Pain may be either constant or intermittent and is typically burning, stabbing or itching in character and located in the same dermatome distribution as the acute rash. Apart from this, patchy allodynia, hyperesthesia, and hypoesthesia can present to varying degrees in the affected region. Allodynia refers to the precipitation of pain by a non-painful stimulus, such as touch or pressure. It is often a distressing feature of PHN. Sleep disturbance and clinical depression are not uncommon.

General advice to patients

Explanation that symptoms can resolve after a few months, or may persist for longer. Interventions may not completely resolve the pain, but may reduce it.

Wear loose clothing or cotton fabrics, as these will usually cause the least irritation.
Consider protecting sensitive areas by applying a protective layer (such as cling film or a plastic wound dressing such as Opsite®).

Consider frequent application of cold packs, unless this causes pain (allodynia).

Treatment during the acute phase

There is good evidence that prompt antiviral treatment can prevent development of PHN and reduce severity when it does occur. Options include aciclovir and the newer antiviral drugs valaciclovir (now a generic medication) and famciclovir. All three are equally effective though the newer agents appear to be better tolerated and have more evidence to support their use: demonstrated benefits include a reduction in the incidence of PHN at 6 months and a faster resolution of pain symptoms.

The early use of aciclovir has also been shown to reduce the incidence and severity of PHN. The optimum window seems to be within 72 hours of appearance of the rash but observational studies suggest even treatment outside 3 days may be of benefit. This is particularly so for patients at high risk of morbidity such as those affected by herpes zoster ophthalmicus and HIV.

Treatment of established post herpetic neuralgia

Pharmacological agents

Simple analgesics are unlikely to be effective on their own but may contribute to improved overall analgesia. Paracetamol (either alone or in combination with codeine) is recommended by two sets of guidelines but no evidence exists to support this. It is worth trying but do not expect more than modest benefit in isolation. NSAIDs have no evidence to support their use.

Anti neuropathic drugs

These drugs are the main stay of management in post herpetic neuralgia. They include Amitriptyline, Nortriptyline, Gabapentin and Pregabalin. The main limiting factor is the side effect profile of these drugs and hence patient compliance tends to be generally low.

Topical treatments

Capsaicin 0.075%

This topical treatment is licensed for the symptomatic relief of PHN after lesions have healed. Two studies have demonstrated benefit over placebo in PHN. The preparation should be applied four times a day. Benefit may be delayed for up to 4 weeks. The commonest side-effect is a burning sensation; patients should be advised that this decreases with continued use, but if it remains problematical, lidocaine 5% ointment applied 10 minutes beforehand can alleviate this. Mixing the capsaicin with GTN paste or EMLA cream has proved useful.

5% Lidocaine plasters

These plasters have to be applied over the painful area, and are used in a 12 hours on, 12 hours off regimen. If tolerated, clinical experience has found that some patients benefit from wearing the plasters 36 hours out of 48, reducing any pain associated with its application/removal. The plasters can be used as 1st line treatment where allodynia is prominent and distressing or where patients are particularly sensitive to side effects of systemic pharmacotherapy. In a study on pain resulting from PHN and diabetic neuropathy, the 5% lidocaine plaster had an incidence of drug related adverse events of under 6% (half were skin reactions) versus 42% for pregabalin.

Qutenza treatment

Qutenza is a high-potency capsaicin (8%) topical patch available for treating pain associated with postherpetic neuralgia. The efficacy of a single 60-minute application to the affected locations has been shown in controlled clinical trials conducted in patients with PHN. Pain reduction was observed as early as week one and was maintained throughout the 12-week study period. Qutenza decreases pain sensation by reducing transient receptor potential vanilloid 1 (TRPV1) expression and decreasing the density of epidermal nerve fibers in the application area. Qutenza must be administered by a nurse or a physician or under the close supervision of a physician. It is not available for self-use.

The most common adverse drug reactions occurring with capsaicin 8% are application site erythema (63%) and application site pain (42%). Some patients experienced transient increases in blood pressure during Qutenza application.

Interventional treatments for post herpetic neuralgia

Interventional treatments should be considered in  patients with refactory pain, where the quality of life is significantly affected by the severity of pain.

Intercostal nerve block

Intercostal nerve block should be considered in patients who do not respond to conservative management. The procedure is done on an outpatient basis. The procedure is performed under ultrasound guidance to ensure accuracy of needle placement. Generally a mixture of local anaesthetic and steroid is injected. The local anaesthetic is probably responsible for immediate pain relief, whereas steroids are believed to be responsible for pain relief 2–6 days after their administration.

Intercostal nerve ablation

Patients who get temporary relief from intercostal nerve block may be suitable for intercostal nerve ablation (pulsed radiofrequency treatment). This is likely to provide longer-term pain relief.

Dorsal root ganglion block and pulsed radiofrequency treatment

Lesioning of the dorsal root ganglion (DRG) using pulsed radiofrequency (PRF) has shown pain reduction in patients with severe post-herpetic neuralgia. In an open, nonrandomized study, 49 patients with PHN, refractory to conservative therapy, were subject to PRF, performed thrice, adjacent to the DRG of the corresponding levels at 42°C for 120 seconds, under the fluoroscopy. There was excellent pain relief (about 55%) at four weeks, with the effect lasting till the 12-week follow-up. (Kim YH, Lee CJ, Lee SC, Huh J, Nahm FS, Kim HZ, et al)

Summary

Post-herpetic neuralgia occurs when the pain associated with shingles becomes chronic. Symptoms may include constant or intermittent stabbing or burning pain, allodynia (pain induced by a non-painful stimulus), hyperalgesia (severe pain from a mildly painful stimulus), and intense itching. The risk of post-herpetic neuralgia increases with age, presence and severity of prodromal pain, and severity of acute shingles pain. Approximately 20% of people will continue to experience pain after the shingles rash heals. Symptoms can resolve after a few months, or may persist for longer. Interventions may not completely resolve the pain, but may reduce it. Initial treatment with paracetamol should be offered, either alone or in combination with codeine. Referral to a specialist pain clinician is recommended in patients with severe pain.

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