690  American Family Physician www.aafp.org/afp Volume 84, Number 6 ◆ September 15, 2011

Painthatoccursafterresolutionofacuteher­peszosterinfectioncanbesevere.Itmaybeaccompaniedbyitchingandfollowsthedis­tributionoftheoriginalinfection.Alldefini­tions of postherpetic neuralgia are arbitraryand include development from one to sixmonthsaftertherash.Forclinicaltrials,neu­ralgiaof threemonthsormorehasbecomethe most common definition, because reso­lutionofneuralgiaafterthreemonthsisslow.

• The main risk factor for postherpeticneuralgia is increasingage.Thecondition isuncommoninpersonsyoungerthan50years.However,amongpersonswhohavehadacuteherpes zoster, it develops in 20 percent ofthose60to65yearsofageandingreaterthan30percentofthoseolderthan80years.

• Up to 2 percent of persons with acuteherpes zoster may continue to have post­herpeticpainforfiveyearsormore.

Oral antiviral agents (acyclovir, famci­clovir, valacyclovir, and netivudine), takenduring acute herpes zoster infection, mayreducethedurationofpostherpeticneural­giacomparedwithplacebo.

• We do not know whether topical anti­viraldrugs,tricyclicantidepressants,orcor­ticosteroids taken during an acute attackreducetherisksofpostherpeticneuralgia,aswefoundfewgood­qualitystudies.

• Corticosteroids may cause dissemina­tionofherpeszosterinfection.

• We do not know whether the use ofdressings, oral opioids, or gabapentin dur­inganacuteattackreducestheriskofpost­herpeticneuralgia,aswefoundnostudies.

• There is limited evidence that gaba­pentinandoxycodonemayreducetheacutepainofherpeszoster.

• Gabapentin, tricyclic antidepressants(amitriptyline, nortriptyline), and someopioids(oxycodone,morphine,methadone)may reduce pain at up to eight weeks in

persons with established postherpetic neu­ralgiacomparedwithplacebo.

• Topical lidocaine may be more effec­tive than placebo in treating postherpeticneuralgia.

• Adverse effects of tricyclic antidepres­sants are dose­related and may be less fre­quent in postherpetic neuralgia comparedwithdepression,aslowerdosesaregenerallyused.

• Opioid analgesic drugs are likely to beeffective in reducing pain associated withpostherpetic neuralgia, but they can causesedation and other well­known adverseeffects.

• Wedonotknowwhetherdextromethor­phan is effective at reducing postherpeticneuralgia.

• We do not know whether topicalcounterirritants such as capsaicin reducepostherpeticneuralgia.

• The herpes zoster vaccine should beused for the primary prevention of herpeszosterandpostherpeticneuralgiainpersonsolderthan60years.

• We do not know whether serotonin­norepinephrine reuptake inhibitors (dulox­etine, venlafaxine) or selective serotoninreuptakeinhibitorsareeffectiveatreducingpostherpeticneuralgia.

DefinitionPostherpeticneuralgiaispainthatoftenfol­lowsresolutionofacuteherpeszosterinfec­tion and healing of the zoster rash. Herpeszoster is caused by reactivation of latentvaricellazostervirus(humanherpesvirus3)inpersonswhohavebeenrenderedpartiallyimmune by a previous case of chickenpox.Herpeszosterinfectsthesensorygangliaandtheirareasofinnervation.Itischaracterizedby pain in the distribution of the affectednerve, and crops of clustered vesicles over

Postherpetic NeuralgiaPETERWATSON,University of Toronto, Toronto, Canada

This is one in a series of chapters excerpted from the Clinical Evidence Handbook, published by the BMJ Publishing Group, London, U.K. The medical information contained herein is the most accurate available at the date of publication. More updated and comprehensive infor-mation on this topic may be available in future print editions of the Clinical Evidence Handbook, as well as online at http://www.clinicalevidence.bmj.com (subscription required). Those who receive a complimentary print copy of the Clinical Evidence Handbook from United Health Foundation can gain complimentary online access by register-ing on the Web site using the ISBN number of their book.

This clinical content con-forms to AAFP criteria for evidence-based continuing medical education (EB CME). See CME Quiz on page 621.

A collection of Clinical Evidence Handbook pub-lished in AFP is available at http://www.aafp.org/afp/bmj.

Clinical Evidence HandbookA Publication of BMJ Publishing Group

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Clinical Evidence Handbook

September 15, 2011 ◆ Volume 84, Number 6 www.aafp.org/afp American Family Physician  691

the area. Pain may occur days before rashonset,ortherashmaybeabsent(zostersineherpete),makingthediagnosisdifficult.

Postherpeticneuralgiaisthoughttoarisefollowing nerve damage caused by herpeszoster.Postherpeticneuralgiacanbesevere,accompanied by itching, and it follows thedistribution of the original infection. Alldefinitions of postherpetic neuralgia arearbitraryandincludedevelopmentfromoneto six months after the rash. Neuralgia ofthreemonthsormorehasbecomethemostcommondefinitioninclinicaltrialsbecauseresolutionofneuralgiaafterthreemonthsisslow.Thus,thenumberofpersonsrequiredfor parallel and crossover trial designs islimited, and there is less risk of a periodeffectinacrossovertrial.

Incidence and PrevalenceIn a U.K. general practice survey of 3,600to 3,800 persons (321 cases of acute herpeszoster),theannualincidenceofherpeszosterwas3.4outof1,000;however,theincidencevariedwithage.Herpeszosterwasrelatively

uncommoninpersonsyoungerthan50years(less than two out of 1,000 per year), butrose tobetween fiveand sevenoutof1,000peryearinpersons50to79yearsofage,and11outof1,000inpersons80yearsandolder.Apopulation­basedstudyintheNetherlandsreportedasimilarincidence(3.4outof1,000peryear)andasimilarincreaseofincidencewithage(threeto10outof1,000peryearinpersonsolderthan50years).

Prevalence of postherpetic neuralgiadependsonwhenit ismeasuredafteracuteinfection. There is no agreed upon timeperiodfordiagnosis.About10percentofallageshavepostherpeticneuralgiaonemonthafter the rash, but because there is a directrelationship to age, about 50 percent willcontinuetobeaffectedat60yearsofage.

Etiology and Risk FactorsThe main risk factor for postherpetic neu­ralgia is increasing age. In the U.K. generalpractice study there was little risk in thoseyoungerthan50years,butpostherpeticneu­ralgia developed in greater than 20 percent

Clinical Questions

What are the effects of interventions aimed at preventing herpes zoster and subsequent postherpetic neuralgia?

Beneficial Herpes zoster vaccines

What are the effects of interventions during an acute attack of herpes zoster aimed  at preventing postherpetic neuralgia?

Unknown effectiveness Antiviral agents (oral acyclovir, famciclovir, valacyclovir, netivudine)

Antiviral agents (topical idoxuridine)

Dressings

Gabapentin

Opioid analgesic drugs (oral)

Tricyclic antidepressants (amitriptyline)

Likely to be ineffective or harmful Corticosteroids

What are the effects of interventions to relieve established postherpetic neuralgia  after the rash has healed?

Beneficial Gabapentin

Tricyclic antidepressants

Likely to be beneficial Lidocaine (topical)

Oral opioid analgesic drugs (oxycodone, morphine, methadone, tramadol)

Unknown effectiveness

Capsaicin (topical)

Dextromethorphan

Selective serotonin reuptake inhibitors

Serotonin-norepinephrine reuptake inhibitors

Clinical Evidence Handbook

of persons 60 to 65 years of age who had had acuteherpes zoster, and in 34 percent of those older than80years.Nootherriskfactorhasbeenfoundtocon­sistentlypredictwhichpersonswithherpeszosterwillexperiencecontinuedpain.InageneralpracticestudyinIceland(421personsfollowedforuptosevenyearsafter an initial episode of herpes zoster), the risk ofpostherpetic neuralgia was 1.8 percent (95% confi­denceinterval,0.6to4.2percent)forpersonsyoungerthan 60 years, and the pain was mild in all persons.Theriskofseverepainafterthreemonthsinpersonsolderthan60yearswas1.7percent(95%confidenceinterval,0to6.2percent).

Other risk factors for postherpetic neuralgia areseverepainwithherpeszoster,greater rashseverity,increased neurologic abnormalities in the affecteddermatome (sensory loss), the presence of a pro­drome, a more pronounced immune response, andpsychosocialfactors.

PrognosisAbout2percentofpersonswithacuteherpeszosterintheU.K.generalpracticesurveyhadpainforgreaterthan five years. Prevalence of pain decreases as timeelapses after the initial episode. Among 183 personsolderthan60yearsintheplaceboarmofaU.K.trial,theprevalenceofpainwas61percentatonemonth,24 percent at three months, and 13 percent at sixmonthsafteracuteinfection.Inonerandomizedcon­trolledtrial,theprevalenceofpostherpeticpainintheplaceboarmatsixmonthswas35percentin72per­sonsolderthan60years.Afterpostherpeticneuralgiahaspersistedformorethanoneyear,about50percentofpersonswillhave significantpain, and50percentwillrecoverorhavepaincontrolwithmedicationatamedianoftwoyearsoffollow­up.

EDITOR’S NOTE: Idoxuridine and netivudine are not available in the United States.

SEARCH DATE: December 2009.

Author disclosure: Peter Watson has received funding to attend an infectious disease conference from Pfizer, the manufacturer of gabapentin.

Adapted with permission from Watson P. Postherpetic neuralgia. Clin Evid Handbook. June 2011:301-303. Please visit http://www.clinical-evidence.bmj.com for full text and references. ■