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The pain from postherpetic neuralgia can be very severe and requires immediate treatment. There is no treatment which modifies the course of the disease and management primarily aims to control symptoms.<ref name="Johnson2014"/>
The pain from postherpetic neuralgia can be very severe and requires immediate treatment. There is no treatment which modifies the course of the disease and management primarily aims to control symptoms.<ref name="Johnson2014"/>


===Topical medications===
===Medications===
====Topical medications====
Medications applied to the skin can be used alone if the pain from PHN is mild or in combination with oral medications if the pain is moderate to severe.<ref name="Johnson2014"/> Topical medications for PHN include low-dose (0.075%) and high-dose (8%) [[capsaicin]] and [[anesthetic]]s such as [[lidocaine]] patches.<ref name="Johnson2014"/> Lidocaine patches (5% concentration) are approved in the United States and Europe to treat PHN though evidence supporting their use is limited.<ref name="Johnson2014"/> A [[meta-analysis]] of multiple small [[placebo]]-controlled [[randomized controlled trial]]s found that for every two people treated with topical lidocaine, one person experienced at least a 50% reduction in their PHN-associated pain ([[number needed to treat]]=2).<ref name="Hempenstall2005">{{cite journal|last1=Hempenstall|first1=K|last2=Nurmikko|first2=TJ|last3=Johnson|first3=RW|last4=A'Hern|first4=RP|last5=Rice|first5=AS|title=Analgesic therapy in postherpetic neuralgia: a quantitative systematic review|journal=PLoS Medicine|date=July 2005|volume=2|issue=7|page=e164|pmid=16013891|type=Systematic Review and Meta-Analysis}}</ref>
Medications applied to the skin can be used alone if the pain from PHN is mild or in combination with oral medications if the pain is moderate to severe.<ref name="Johnson2014"/> Topical medications for PHN include low-dose (0.075%) and high-dose (8%) [[capsaicin]] and [[anesthetic]]s such as [[lidocaine]] patches.<ref name="Johnson2014"/> Lidocaine patches (5% concentration) are approved in the United States and Europe to treat PHN though evidence supporting their use is limited.<ref name="Johnson2014"/> A [[meta-analysis]] of multiple small [[placebo]]-controlled [[randomized controlled trial]]s found that for every two people treated with topical lidocaine, one person experienced at least a 50% reduction in their PHN-associated pain ([[number needed to treat|number needed to treat (NNT)]]=2).<ref name="Hempenstall2005">{{cite journal|last1=Hempenstall|first1=K|last2=Nurmikko|first2=TJ|last3=Johnson|first3=RW|last4=A'Hern|first4=RP|last5=Rice|first5=AS|title=Analgesic therapy in postherpetic neuralgia: a quantitative systematic review|journal=PLoS Medicine|date=July 2005|volume=2|issue=7|page=e164|pmid=16013891|type=Systematic Review and Meta-Analysis}}</ref>


Low-dose capsaicin may be useful for reducing PHN-associated pain but is limited by side effects ([[erythema|redness]] and a burning or stinging sensation with application) and the need to apply it four times daily.<ref name="Johnson2014"/> Approximately three people must be treated with low-dose capsaicin cream for one person to experience significant pain relief (number needed to treat =3.3).<ref name="Johnson2014"/><ref name="Hempenstall2005"/> A single topical application of a high-dose capsaicin patch over the affected area after [[Anesthesia|numbing the area]] with a topical anesthetic has also been found to relieve PHN-associated pain.<ref name="Johnson2014"/> For every eleven people treated with a high-dose capsaicin patch for up to 12 weeks, one person experienced a significant improvement in their pain. (number needed to treat=11).<ref name="Derry2017">{{cite journal|last1=Derry|first1=S|last2=Rice|first2=AS|last3=Cole|first3=P|last4=Tan|first4=T|last5=Moore|first5=RA|title=Topical capsaicin (high concentration) for chronic neuropathic pain in adults|journal=Cochrane Database of Systematic Reviews|date=January 2017|volume=1|page=CD007393|doi=10.1002/14651858.CD007393.pub4|pmid=28085183|type=Systematic Review and Meta-Analysis}}</ref> Due to the need for topical anesthesia before application of the high-dose capsaicin patch, referral to a pain specialist is generally recommended if this approach is being considered.<ref name="Johnson2014"/>
Low-dose capsaicin may be useful for reducing PHN-associated pain but is limited by side effects ([[erythema|redness]] and a burning or stinging sensation with application) and the need to apply it four times daily.<ref name="Johnson2014"/> Approximately three people must be treated with low-dose capsaicin cream for one person to experience significant pain relief (number needed to treat =3.3).<ref name="Johnson2014"/><ref name="Hempenstall2005"/> A single topical application of a high-dose capsaicin patch over the affected area after [[Anesthesia|numbing the area]] with a topical anesthetic has also been found to relieve PHN-associated pain.<ref name="Johnson2014"/> For every eleven people treated with a high-dose capsaicin patch for up to 12 weeks, one person experienced a significant improvement in their pain. (number needed to treat=11).<ref name="Derry2017">{{cite journal|last1=Derry|first1=S|last2=Rice|first2=AS|last3=Cole|first3=P|last4=Tan|first4=T|last5=Moore|first5=RA|title=Topical capsaicin (high concentration) for chronic neuropathic pain in adults|journal=Cochrane Database of Systematic Reviews|date=January 2017|volume=1|page=CD007393|doi=10.1002/14651858.CD007393.pub4|pmid=28085183|type=Systematic Review and Meta-Analysis}}</ref> Due to the need for topical anesthesia before application of the high-dose capsaicin patch, referral to a pain specialist is generally recommended if this approach is being considered.<ref name="Johnson2014"/>

====Oral medications====
Multiple oral medications have demonstrated efficacy in relieving postherpetic neuralgia pain. [[Tricyclic antidepressant]]s (TCAs) (e.g., [[nortriptyline]] or [[desipramine]]) are effective in reducing postherpetic neuralgia pain but are limited by their numerous side effects. For every three people treated with a tricyclic antidepressant, one person is expected to have a clinically significant reduction in their pain (NNT=3).<ref name="Johnson2014"/> Additionally, of every sixteen people treated with a TCA, one person is expected to stop the medication due to a bothersome side effect, such as [[xerostomia|dry mouth]], [[constipation]], or [[urinary retention]] ([[number needed to harm]]=16).<ref name="Johnson2014"/> The [[anticonvulsant]] medications [[pregabalin]] and [[gabapentin]] also effectively relieve postherpetic neuralgia pain. Treatment with pregabalin leads to a reduction in pain intensity of 50% or more in one person out of every 4-5 people treated (NNT=4-5).<ref name="Wiffen2013">{{cite journal|last1=Wiffen|first1=PJ|last2=Derry|first2=S|last3=Moore|first3=RA|last4=Aldington|first4=D|last5=Cole|first5=P|title=Antiepileptic drugs for neuropathic pain and fibromyalgia - an overview of Cochrane reviews|journal=Cochrane Database of Systematic Reviews|date=November 2013|volume=11|issue=CD010567|doi=10.1002/14651858.CD010567.pub2|pmid=24217986|type=Systematic Review and Meta-Analysis}}</ref> Similarly, treatment with gabapentin also leads to a 50% reduction in pain intensity in one person out of every 7-8 people treated (NNT=7.5).<ref name="Wiffen2013"/>


==Prognosis==
==Prognosis==

Revision as of 00:28, 4 January 2018

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Postherpetic neuralgia
SpecialtyNeurology Edit this on Wikidata

Postherpetic neuralgia (PHN) is a nerve pain which occurs due to damage to a peripheral nerve caused by the reactivation of the varicella zoster virus (Herpes Zoster). Typically, the nerve pain (neuralgia) is confined to an area of skin innervated by a single sensory nerve, which is known as a dermatome. PHN is defined as dermatomal nerve pain that persists for more than 90 days after an outbreak of herpes zoster affecting the same dermatome.[1] Multiple types of pain may occur with PHN include continuous burning pain, episodes of severe shooting or electric-like pain, and a heightened sensitivity to gentle touch which would not otherwise cause pain (mechanical allodynia) or to painful stimuli (hyperalgesia).[1] Abnormal sensations and itching may also occur.[1]

PHN follows an outbreak of herpes zoster (commonly known as shingles) in that same dermatome. The nerve pain typically begins when the herpes zoster vesicles have crusted over and begun to heal, but can begin in the absence of herpes zoster—a condition called zoster sine herpete.

There is no treatment which modifies the disease course of PHN; therefore, controlling the affected person's symptoms is the main goal of treatment. Medications applied to the skin such as capsaicin or topical anesthetics (e.g., lidocaine are used for mild pain and can be used in combination with oral medications for moderate to severe pain.[1] Oral anticonvulsant medications such as gabapentin and pregabalin are also approved for treatment of PHN.[1] Tricyclic antidepressants are also useful for improving pain but their use is limited by side effects.[1] Opioid medications are not generally recommended for treatment except in specific circumstances and under the care of a pain specialist due to mixed evidence of efficacy and concerns about potential for abuse and addiction.[1]

PHN is the most common long-term complication of herpes zoster.[1] The incidence and prevalence of PHN are uncertain due to varying definitions. Approximately 20% of people affected by herpes zoster report pain in the affected area three months after the initial episode of herpes zoster and 15% of people similarly report this pain two years after the herpes zoster rash.[1] Since herpes zoster occurs due to reactivation of the varicella zoster virus, which is more likely to occur with a weakened immune system, both herpes zoster and PHN occur more often in the elderly and in people with diabetes mellitus.[1] Risk factors for PHN include older age, a severe herpes-zoster rash, and pain during the herpes zoster episode.[1] PHN is often very painful and can be quite debilitating. Affected individuals often experience a decrease in their quality of life.[1]

Signs and symptoms

Symptoms:

  • With resolution of the herpes zoster eruption, pain that continues for three months or more is defined as postherpetic neuralgia.
  • Pain is variable, from discomfort to very severe, and may be described as burning, stabbing, or gnawing.

Signs:

  • Area of previous herpes zoster may show evidence of cutaneous scarring.
  • Sensation may be altered over the areas involved, in the form of either hypersensitivity or decreased sensation.
  • In rare cases, the patient might also experience muscle weakness, tremor, or paralysis if the nerves involved also control muscle movement.

Pathophysiology

Postherpetic neuralgia is thought to be due to nerve damage caused by herpes zoster. The damage causes nerves in the affected dermatomic area of the skin to send abnormal electrical signals to the brain. These signals may convey excruciating pain, and may persist or recur for months, years, or for life.[2]

A key factor in the neural plasticity underlying neuropathic pain is altered gene expression in sensory dorsal root ganglia neurons. Injury to sensory nerves induces neurochemical, physiological and anatomical modifications to afferent and central neurons, such as afferent terminal sprouting and inhibitory interneuron loss.[2] Following nerve damage, NaCl channel accumulation causes hyperexcitability, and downregulation of the TTX-resistant Nav1.8 (sensory neuron specific, SNS1) channel and upregulation of TTX-sensitive Nav1.3 (brain type III) and TRPV1 channels. These changes contribute to increased NMDA glutamate receptor-dependent excitability of spinal dorsal horn neurons and are restricted to the ipsilateral (injured) side. A combination of these factors could contribute to the neuropathic pain state of postherpetic neuralgia.

Frequency

In the United States each year approximately 1,000,000 individuals develop herpes zoster.[3] Of those individuals approximately 10-18% develop postherpetic neuralgia.[4]

Less than 10 percent of people younger than 60 develop postherpetic neuralgia after a bout of herpes zoster, while about 40 percent of people older than 60 do.

Diagnosis

Lab Studies:

  • No laboratory work is usually necessary.
  • Results of cerebrospinal fluid evaluation are abnormal in 61%.
    • Pleocytosis is observed in 46%, elevated protein in 26%, and VZV DNA in 22%.
  • These findings are not predictive of the clinical course of postherpetic neuralgia.
  • Viral culture or immunofluorescence staining may be used to differentiate herpes simplex from herpes zoster in cases that are difficult to distinguish clinically.
  • Antibodies to herpes zoster can be measured. A 4-fold increase has been used to support the diagnosis of subclinical herpes zoster (zoster sine herpete). However, a rising titer secondary to viral exposure rather than reactivation cannot be ruled out.

Imaging studies:

  • Magnetic resonance imaging lesions attributable to herpes zoster were seen in the brain stem and cervical cord in 56% (9/16) of patients.
  • At three months after onset of herpes zoster, 56% (5/9) of patients with an abnormal magnetic resonance image had developed postherpetic neuralgia.
  • Of the seven patients who had no herpes-zoster-related lesions on the magnetic resonance image, none had residual pain.

Prevention

Primary prevention

In 1995, the Food and Drug Administration (FDA) approved the Varicella vaccine to prevent chickenpox. Its effect on postherpetic neuralgia is still unknown. The vaccine—made from a weakened form of the varicella-zoster virus—may keep chickenpox from occurring in nonimmune children and adults, or at least lessen the risk of the chickenpox virus lying dormant in the body and reactivating later as shingles. If shingles could be prevented, postherpetic neuralgia could be completely avoided.

In May 2006 the Advisory Committee on Immunization Practices approved a new vaccine by Merck (Zostavax) against shingles. This vaccine is a more potent version of the chickenpox vaccine, and evidence shows that it reduces the incidence of postherpetic neuralgia.[5] The CDC recommends use of this vaccine in all persons over 60 years old.[6]

Secondary prevention

An April 2013 Cochrane Collaboration meta-analysis of 6 randomized controlled trials (RCTs) investigating oral antiviral medications given within 72 hours after the onset of herpes zoster rash in immunocompetent people for preventing postherpetic neuralgia (PHN) found no significant difference between placebo and acyclovir. Combining four RCTs, 44.1% of the acyclovir treatment group developed herpetic neuralgia whereas 53.3% of the placebo group developed herpetic neuralgia. Heterogeneity between the four RCTs was moderate: Chi2 =3.36, df = 2 (P=0.19); I2 = 40%. Additionally, there was no significant difference in preventing the incidence of PHN found in the one RCT included in the meta-analysis that compared placebo to PO famciclovir treatment within 72 hours of HZ rash onset. Studies using valaciclovir treatment were not included in the meta-analysis. PHN was defined as pain at the site of the dermatomic rash at 120 days after the onset of rash, and incidence was evaluated at 1, 4, and 6 months after rash onset. There was a slight reduction in the incidence of pain at 4 weeks after the onset of rash in the aciclovir group (153 study participants with pain out of 347 study participants in the aciclovir group) versus the placebo group (184 study participants with pain out of 345 study participants in the placebo group). Patients who are prescribed PO antiviral agents after the onset of rash should be informed that their chances of developing PHN are no different than those not taking PO antiviral agents.[7]

A randomized controlled trial found that amitriptyline 25 mg per night for 90 days starting within two days of onset of rash can reduce the incidence of postherpetic neuralgia from 35% to 16% (number needed to treat is 6).[8]

Treatment

The pain from postherpetic neuralgia can be very severe and requires immediate treatment. There is no treatment which modifies the course of the disease and management primarily aims to control symptoms.[1]

Medications

Topical medications

Medications applied to the skin can be used alone if the pain from PHN is mild or in combination with oral medications if the pain is moderate to severe.[1] Topical medications for PHN include low-dose (0.075%) and high-dose (8%) capsaicin and anesthetics such as lidocaine patches.[1] Lidocaine patches (5% concentration) are approved in the United States and Europe to treat PHN though evidence supporting their use is limited.[1] A meta-analysis of multiple small placebo-controlled randomized controlled trials found that for every two people treated with topical lidocaine, one person experienced at least a 50% reduction in their PHN-associated pain (number needed to treat (NNT)=2).[9]

Low-dose capsaicin may be useful for reducing PHN-associated pain but is limited by side effects (redness and a burning or stinging sensation with application) and the need to apply it four times daily.[1] Approximately three people must be treated with low-dose capsaicin cream for one person to experience significant pain relief (number needed to treat =3.3).[1][9] A single topical application of a high-dose capsaicin patch over the affected area after numbing the area with a topical anesthetic has also been found to relieve PHN-associated pain.[1] For every eleven people treated with a high-dose capsaicin patch for up to 12 weeks, one person experienced a significant improvement in their pain. (number needed to treat=11).[10] Due to the need for topical anesthesia before application of the high-dose capsaicin patch, referral to a pain specialist is generally recommended if this approach is being considered.[1]

Oral medications

Multiple oral medications have demonstrated efficacy in relieving postherpetic neuralgia pain. Tricyclic antidepressants (TCAs) (e.g., nortriptyline or desipramine) are effective in reducing postherpetic neuralgia pain but are limited by their numerous side effects. For every three people treated with a tricyclic antidepressant, one person is expected to have a clinically significant reduction in their pain (NNT=3).[1] Additionally, of every sixteen people treated with a TCA, one person is expected to stop the medication due to a bothersome side effect, such as dry mouth, constipation, or urinary retention (number needed to harm=16).[1] The anticonvulsant medications pregabalin and gabapentin also effectively relieve postherpetic neuralgia pain. Treatment with pregabalin leads to a reduction in pain intensity of 50% or more in one person out of every 4-5 people treated (NNT=4-5).[11] Similarly, treatment with gabapentin also leads to a 50% reduction in pain intensity in one person out of every 7-8 people treated (NNT=7.5).[11]

Prognosis

The natural history of postherpetic neuralgia involves slow resolution of the pain syndrome. A subgroup of affected individuals may develop severe, long-lasting pain that does not respond to medical therapy.

References

  1. ^ a b c d e f g h i j k l m n o p q r s t u v Johnson, RW; Rice, AS (October 2014). "Clinical practice. Postherpetic neuralgia". New England Journal of Medicine (Review). 371 (16): 1526-33. doi:10.1056/NEJMcp1403062. PMID 25317872.
  2. ^ a b Gharibo, Christopher; Kim, Carolyn (December 2011). "Neuropathic Pain of Postherpetic Neuralgia" (PDF). Pain Medicine News. McMahon Publishing. Retrieved 6 October 2014.
  3. ^ Brian J. Hall; John C. Hall. "Infectious diseases in the skin". Sauer's Manual of Skin Diseases. Lippincott Williams & Wilkins, 2010. p. 232.
  4. ^ Weaver, B A (2009). "Herpes zoster overview: natural history and incidence" (PDF). J Am Osteopath Assoc. 109 (6 (Suppl 2)): S2-6. PMID 19553632. Retrieved 6 October 2014.
  5. ^ Chen N, Li Q, Zhang Y, Zhou M, Zhou D, He L (2011). He L (ed.). "Vaccination for preventing postherpetic neuralgia". Cochrane Database Syst Rev (3): CD007795. doi:10.1002/14651858.CD007795.pub2. PMID 21412911.
  6. ^ https://www.cdc.gov/vaccines/vpd-vac/shingles/default.htm
  7. ^ Chen N, Li Q, Yang J, et al. (2014). He L (ed.). "Antiviral treatment for preventing postherpetic neuralgia". Cochrane Database Syst Rev. 2 (2): CD006866. doi:10.1002/14651858.CD006866.pub3. PMID 24500927.
  8. ^ Bowsher D (1997). "The effects of pre-emptive treatment of postherpetic neuralgia with amitriptyline: a randomized, double-blind, placebo-controlled trial". Journal of Pain and Symptom Management. 13 (6): 327–31. doi:10.1016/S0885-3924(97)00077-8. PMID 9204652.
  9. ^ a b Hempenstall, K; Nurmikko, TJ; Johnson, RW; A'Hern, RP; Rice, AS (July 2005). "Analgesic therapy in postherpetic neuralgia: a quantitative systematic review". PLoS Medicine (Systematic Review and Meta-Analysis). 2 (7): e164. PMID 16013891.
  10. ^ Derry, S; Rice, AS; Cole, P; Tan, T; Moore, RA (January 2017). "Topical capsaicin (high concentration) for chronic neuropathic pain in adults". Cochrane Database of Systematic Reviews (Systematic Review and Meta-Analysis). 1: CD007393. doi:10.1002/14651858.CD007393.pub4. PMID 28085183.
  11. ^ a b Wiffen, PJ; Derry, S; Moore, RA; Aldington, D; Cole, P (November 2013). "Antiepileptic drugs for neuropathic pain and fibromyalgia - an overview of Cochrane reviews". Cochrane Database of Systematic Reviews (Systematic Review and Meta-Analysis). 11 (CD010567). doi:10.1002/14651858.CD010567.pub2. PMID 24217986.

External links

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