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From the Section of Dermatolog y, Medical College o f Georgia,Augusta, a and the Departments of Dermatology, Microbiology/Immunolo gy and Interna l Medicine, University of Texas MedicalBranch,Galveston.b

Reprint requests: Stephen K. Tyring, MD, PhD, Department ofDermatolog y, University of Texas Medical Branch, Galveston, TX77555-1070. E-ma il:t [email protected].

Copyright © 1999 by the American Academy of Dermat ology, Inc.0190-9622/99/$8.00 + 0 16/2/98761

V aricella zoster virus (VZV) is a un ique herpesvirus in that it is capable o f producing tw o dif-ferent synd rom es, varicella (chickenpox) and

herpes zoster (shingles). It belongs to the subfam ilyAlphaherpesvirinae 1 (along w ith herpes sim plexvirus [H SV ] types 1 and 2) and, like these, is a dou-ble-stranded D N A virus. C ontaining the sm allestgenom e of the h erpesviruses, it is an en velopedicosahedral virus app roxim ately 200 nm in diam eter.

HISTORY In 1767, H eberden w as able to clearly distingu ish

chickenpox from sm allpox. 2 It is believed that thew ord “chicken pox”either com es from the O ldEnglish w ord “gican ”m eaning “to itch” 3 or alternate-ly, from the o ld French w ord “chiche-pois”for chick-pea, though t to describe the size of the vesicle. 4 Theassociation betw een chickenpox and shingles w asfirst noticed by vo n B okay in 1888. H e n oted thatchicken pox som etim es developed in susceptiblechildren after exposure to persons w ith acute shin-gles. 5 Th e next developm ent w as m ade w hen

Kundratiz w as able to p rod uce varicella-like lesionsand generalized varicella in children by inoculation

w ith vesicle fluid from patien ts w ith zoster. 6 Thisrelationship w as finally confirm ed in 1952 by W ellerand Stoddard, 7 w ho w ere able to show that identicalviruses w ere recovered from patients w ith chicken -pox and shingles using in vitro studies.

INCIDENCEPrim arily a disease of childhood (90% of cases

occur in children younger than 10 years of age), vari-cella is a disease that has historically touched a largem ajority of the p opulation, w ith 95% of parturien tw om en in N ew York C ity 8 and 95% of H IV-positivem en9 sho w ing serologic eviden ce of infection.Ano ther study show ed a nearly 99% rate of im m un i-ty to varicella. 10 Finally, am ong m ilitary recruits(m ostly from ages 17 to 19 years) the seron egativityrate w as fou nd to be 8.2% . 11 In fact, a study o f preg-nant patien ts w ith negative o r indeterm inant historyof varicella-like illness dem onstrated that 81% w illshow serologic eviden ce o f subclinical infection. 12 Inthe study of m ilitary recruits, how ever, although thepositive predictive value of a h istory of varicella w as

high (> 95% ), alm ost all recruits gave a p ositive his-tory of varicella, even those (< 20% ) lacking the anti-body. 11 Rarely reported recurren ces of varicella areprobably a result of m isdiagnosis (eg, coxsackievirusinfection). 13

Although chickenpox is a disease of children ,shingles o ccurs prim arily in adults older than 50years, although it can occur at any age. By decades,the inciden ce is 2.5/1000 person s affected perannum betw een the ages of 20 and 50 years,5.09/1000 persons per annum for the ages of 51 to 79

CONTINUING MEDICAL EDUCATION

Varicella zoster virus

Monica L. McCrary, MD, a Jessica Severson, MD, b and Stephen K. Tyring, MD, PhD b

Augusta , Georgia , and Ga lv eston , Texa s

Because of its ability to prod uce tw o clinically d istinct disease en tities (chicken pox and shingles), varicellazoster virus (VZV) is an unusual etiologic agent. Although in the p ast viral exanthem s w ere m ostly only ofacadem ic interest to the p ractitioner, the developm en t of antiviral agents and the new ly approved varicella(O KA) vaccine h ave increased the clinical sign ificance. Also, w ith the increasing serop revalen ce o f H IVinfection, m ore patien ts w ill be stricken w ith zoster (at a younger age) and dissem inated varicella. In thisreview , the h istory, inciden ce, pathogenesis, clinical m anifestations, and treatm en t options (of VZV infectionand postherpetic neu ralgia) w ill be d iscussed. (J Am Acad D erm atol 1999;41:1-14.)

Lear n i ng ob jec t ive : At the com pletion of this learning activity, participants sho uld be able to d iscuss thehistory, incidence, pathogenesis, clinical m anifestations, and treatm en t options for bo th VZV infection andP H N .

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(7 m onths). 30 Sim ilarly, 20% to 40% of bo ne m arrowtransplant recipien ts w ill develop herpes zoster inthe first year after their transplan ts. 31-34 A m o ngpatien ts w ith H IV infection, herpes zoster can be thefirst sign of infection, 35,36 and the lesions m ay havean u nusual app earance and m ay recur several

tim es. 37-43 C ontrary to w hat w as previously believed ,shingles is not a reliab le initial indication of anunderlying subclinical m alignancy because a study of590 patien ts w ith zoster had no high er incidence ofcancer than that of the general population. 44 Afterreactivation, VZV undergo es an initial phase o f repli-cation w ithin the affected sensory gan glion andproduces active gan glionitis. The inflam m atoryresponse and neu ronal necrosis that result causesevere neuralgia. This pain intensifies as the virustravels dow n the sensory nerve, producing radicu-loneuritis.

CLINICAL MANIFESTATIONSPrimary varicella

Althou gh occasion ally preceded by a p rod rom e ofsym ptom s such as headache, m yalgia, nau sea,anorexia, and vom iting in older children andadults, 45 in young ch ildren the illness usually beginsabruptly w ith the sim ultaneous on set of rash, low -grade fever, and m alaise. Sm all red m acules appearon the face and trunk and progress rapidly over 12 to14 hours to papules, vesicles, pustules, and finallycrusts. These lesions are u sually m ost abu ndant cen-trally and on the p roxim al upper extrem ities, w ithrelative sparing o f the d istal or low er extrem ities.Alm ost universal is the sym ptom of pruritus associ-ated w ith the skin lesions. Perhaps m ost characteris-tic is the sim ultaneo us presence of lesions in allstages of developm ent. The characteristic vesicle hasbeen liken ed to “a dew drop on a rose petal.”

Although usually a m ild self-lim ited illness inim m unocom petent children , varicella can occasion-ally result in significan t m orbidity, w ith 4500 other-w ise h ealthy ch ildren per year hospitalized w ith pri-m ary varicella. H ow ever, varicella infection in adultsis usually m ore severe, w ith m ore skin lesions pre-sent and m ore prom inent and prolon ged fever and

constitutional sym ptom s.M ultiple com plications can result from prim aryvaricella infection; the m ost com m on is bacterialsuperinfection, w ith subsequen t scarring. This canm anifest as im petigo, furuncles, cellulitis, erysipelas,or bu llous skin lesions from the elaboration ofstap hylococcal exfoliative toxin. 46 The m ost com -m on extracutaneous com plication o f VZV infection iscentral nervous system (C N S) involvem en t. Thisincludes Reye’s syndrom e, acu te cereb ral ataxia,en cephalitis, m en ingo encephalitis, polyradicu litis,

years, and 10.1/1000 in those older than 80 years ofage. 14 O verall, each person w ho has a history of vari-cella experiences an ap proxim ately 20% chance ofacquiring shingles in his/her lifetim e. The inciden ceof both of these m anifestations of VZV infectionis likely to change since the Food and D rug

Adm inistration’s (FD A) approval of live atten uated(O KA) varicella vaccine. There is no eviden ce thatherpes zoster can be directly acqu ired through con-tact w ith patients w ith either varicella o r zoster. 14-16

PATHOGENESISPrimary varicella

Acquired by inhalation of respiratory secretionsor contact w ith skin lesions, prim ary varicella initial-ly infects the conjunctiva or the m ucosa in the u pperrespiratory tract. This is follow ed by the first cycle ofviral replication, w hich takes place in the regionallym ph no des on days 2 through 4, and a prim ary

virem ia, w hich occurs betw een days 4 and 6. N ext, asecond rep lication cycle follow s, w hich occurs in theliver, spleen, and other organs. Finally, a secondaryvirem ia occurs, w hich seeds the body w ith viral par-ticles that invade first the capillary endothelial cells,then the cap illaries, and ultim ately the epiderm is onapproxim ately days 14 to 16. 17

Herpes zosterAlthough not fully understood, it is believed that

during the course of prim ary varicella VZV spreadsfrom the skin and m ucosal lesions into the sensorynerve en dings. From there, it travels centripetallyalong these nerve fibers un til it reaches the dorsalganglion cells w here it en ters a laten t state. Then , bym echanism s no t com pletely understood, it is reacti-vated , probably as a result of a decline in VZV-specif-ic cell-m ed iated im m unity (C M I), specifically adecreased T-cell proliferation in response to VZVantigen. 18 O ne p articularly interesting study sho w edthe inciden ce of zoster to be less in ped iatriciansw ith presum ably greater con tact to varicella (andthus increased C M I to VZV) than in psychiatrists orderm atologists. 19 This decline in C M I is seen am ongpersons w ith increased incidence o f herpes zoster,

including the elderly and persons w ith H IV infectionor other im m un ocom prom ising cond ition s such asorgan transplants (w ith im m unosuppression), m alig-nancy necessitating chem otherapy or radiotherapy, 20

or long-term corticosteroid use. 21 Am ong cancerpatien ts, the h ighest risk o f acquiring h erpes zosteris associated w ith patien ts w ith leu kem ia o r lym -phom a; in fact, app roxim ately 20% to 50% ofpatien ts w ith H odgkin’s disease develop herpeszoster, 22-29 and it is usually shortly after the initiationof either chem otherapy (1 m onth) or radiotherapy

2 McCra r y, Sever son , and Tyr in g J A M A C A D D ERMATOL

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and m yelitis (eg, G uillain-B arre syndrom e). 47 Inadult varicella (Fig 1), varicella pneum onia is a fre-quen t com plication, occurring in 1/400 cases. 48 Them ortality rate of adult varicella pneu m onia is high ,w ith death o ccurring in 10% of im m unocom petentand 30% of im m unocom prom ised patients. 49 Rarely,m yocarditis, glom erulonep hritis, appen dicitis, pan-creatitis, hepatitis, H enoch -Sch önlein vasculitis,orch itis, arthritis, optic neuritis, keratitis, or iritis canresult. 45

In pregnancy, m aternal varicella infection cancause a w ide spectrum of congenital disease fromasym ptom atic latency to severe congenital defects oreven fetal w astage. 50 Fetal developm ental com plica-tion s are m ost com m on w hen m aternal infectionoccurs in the first trim ester and include h ypoplasticlim bs, cicatricial skin lesions, co rtical atrophy, ocu larabnorm alities, psycho m otor retardation, and lowbirth w eigh t. After the first 20 w eeks o f pregnancy,the risk of congenital m alform ation changes toapproxim ately 2% .

In im m unocom prom ised children or adu lts, vari-cella can be associated w ith sign ifican t m orbidity andm ortality. They can experien ce a p ersisten t virem ia, aprolonged febrile period, a m ore exten sive rash

(often w ith hem orrhagic and/or purpuric lesions)and are m ore likely to have involvem ent of the lungs,liver, or CN S. 51

Herpes zosterIntense pain in the involved d erm atom e precedes

the rash of herpes zoster in m ore than 90% of cases.This pain typically occurs approxim ately 1 to 3 daysbefore the onset of the rash, but m ay preced e it by aw eek o r m ore. This pain is subject to a w ide arrayof m isdiagn oses, including m yocardial infarction,

pleurisy, cholecystitis, appendicitis, duodenal ulcer,ovarian cyst, herniated interverteb ral disc, throm -bophlebitis, or even biliary or renal colic. In approx-im ately 5% of patients (usually ch ildren), this pain iscom po un ded by other prod rom al sym ptom s offever, m alaise, and headache. O ccasionally, a patien tw ith this derm atom al pain and serologic or virologiceviden ce o f zoster has failed to develop the rashassociated w ith zoster, a condition kn ow n as zostersine herpete (zoster w ithout rash). 52

O nce the characteristic unilateral derm atom alrash appears, the diagnosis is alm ost certain. Thisrash begins as erythem atous m acules and papu les,w hich progress first to vesicles (w ithin 12-24 hours),then the pustules (in 3-4 days), and finally to crusts(in 7-10 days). Scarring can resu lt, particu larly indark-skinned persons (Fig 2). In addition, regionallym phaden opathy is usually presen t. G en erally, therash is located at the site w hich w as m ost severelyaffected by p rim ary varicella. 14 Therefore the m ostcom m on p laces of involvem ent are the facial (V-1)and m idtho racic to up per lum bar derm atom es (T3-L2) (Fig 3), although any derm atom e can be affected(Fig 4).

Sim ilar to chickenpox, the p ain and rash of zoster

are usually m ore severe in im m un ocom prom ised andelderly patients. 51 In contrast, w hen zoster occurs inim m unocom petent children (Fig 5) or young adu lts,the rash tends to evolve m ore rapidly and the n eural-gia usually resolves as the crusts fall off.

Probably the m ost feared and debilitating com pli-cation of zoster is po stherpetic neu ralgia (PH N ).Although various definitions have been used, th isclinical entity exists w hen pain persists either after acertain tim e period or after all crusts have fallen off.U nfortunately, PH N is extrem ely com m on, affecting

McCra r y, Sever son , an d Tyr i n g 3J A M A C A D D ERMATOL

V OLUME 41, N UMBER 1

Fig 1. Prim ary varicella (chicken pox) in an 80-year-oldm an .

Fig 2. H ypertrophic scar from herpes zoster in an H IV-seropositive m an.

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A particularly high com plication rate is seen w ith

ophthalm ic zoster. Affecting 7% of all cases ofzoster, 49 ophthalm ic zoster is com plicated by oculardisease in 20% to 70% of patients. 53 Associated cica-tricial lid retraction, paralytic ptosis, (acute epithe-lial) keratitis, scleritis, uveitis, secondary glaucom a,oculom otor palsies, chorioretinitis, optic n eu ritis, orpanophthalm itis are seen, all w ith poten tial for visu-al im pairm ent or even blindness. O f particular con-cern is involvem en t of the nasociliary division of theophthalm ic nerve. This can be recognized by vesiclespresent on the side an d the top of the n ose, alsokn ow n as H utchinson ’s sign (Fig 6). 55

O ther nervous system com plications are seenoccasionally w ith zoster. The R am say H unt syn-drom e is caused by involvem ent of the facial or audi-tory nerves and consists of ipsilateral facial palsy incom bination w ith lesions of the external ear, tym -panic m em brane, or anterior tw o thirds of thetongue. It can result in tinnitus, vertigo , deafness,otalgia, or loss of taste. In addition, m en ingo en -cep halitis and m yelitis have been rep orted in 0.2% to0.5% of patients and are associated w ith headache,fever, photophobia, m en ingeal irritation, vom iting,nerve p alsies, or altered m en tation. 47,56-60 Rarely,zoster involvem en t of the vagus nerve o r its ganglia

can result in dysphagia, nausea, vom iting, gastricupset, or cardiac irregularities. M otor paralysis fromdirect extension from the sensory gan glion to anteri-or horn cells occu rs in 1% to 5% of patien ts w ithzoster. 61-64 This paralysis usually o ccu rs in the first 2to 3 w eeks after rash onset and can persist for sever-al w eeks. Localized m otor deficiencies are found inup to 20% of patien ts w ith zoster involving the facialnerve or the nerves of the extrem ities. 47 A delayedC N S com plication of ophthalm ic zoster is granu lo-m atous cerebral angiitis w ith sym ptom s often occur-

10% to 15% of all paten ts w ith zoster 53 and at least50% of patien ts older than 60 years of age. U sually,patients experien ce a sign ifican t reduction of painw ithin 6 m onths, although this is variable. 54 O therabnorm al sensations can p ersist after healing of skinlesions has occu rred and include p ruritus, paresthe-sia, dysesthesia, or anesthesia.


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Fig 3. H erpes zoster in the L-1 derm atom e. Fig 5. H erpes zoster in a 2-year-old girl.

Fig 4. H erpes zoster in distribution of sacral nerves 1 and2.

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ring w eeks to m onths after the attack. This has beenassociated w ith a rather high m ortality rate (15% )and m ay presen t as transien t ischem ic attacks,stroke-in-evolution, or isolated or m ultiple cerebralinfarctions. H ow ever, the m ost frequent C N S findingis asym ptom atic cerebrospinal fluid abnorm alitiessuch as a lym phocytotic p leo cytosis and elevatedprotein.

Although uncom m on in im m unocom petentpatien ts, zoster has a high risk of dissem ination (upto 40% ) 49 in im m un ocom prom ised person s (Figs 7and 8). D efined as m ore than 20 vesicles outside theprim ary and im m ediately adjacent derm atom es,cutaneo us dissem ination is follow ed by visceral(lungs, liver, brain) involvem en t in 10% of thesehigh-risk p atients. O ccasionally, a few vesicles can befound rem ote from the p rim arily affected der-m atom e in im m un ocom petent patients (17% -35% ),65 w hich p robably results from hem atogenousspread of the virus. In addition, H IV patien ts w ithzoster show ed increased neu rologic (eg, asepticm eningitis, radicu litis, and m yelitis) 66 and ophthal-m ologic com plications, particularly peripheral outerretinal necrosis. 66-68

DERMATOPATHOLOGY The initial test of choice is usually a Tzanck sm ear

perform ed by scraping the base of an early lesionand then staining w ith hem atoxylin-and-eo sin,G iem sa, W righ t’s, toluidine blue, or Pap anicolaou.W ith herpes sim plex o r herpes zoster infections,m ultinucleated giant cells and epithelial cells con-taining acidophilic intranuclear inclusions can beseen. H ow ever, VZV cannot be differentiated fromH SV infection using a Tzanck sm ear.

LABORATORY FINDINGSM ultiple tests can be used to differen tiate VZV

from H SV including cu lture, serology, directim m uno fluorescence, and m olecular techniqu es.C ulture, although specific, is not alw ays easily



Fig 6. H erpes zoster in first branch of trigem inal nerve(ie, ophthalm ic zoster) w ith lesions on bridge of the n ose(ie, H utch inson’s sign) as w ell as contralateral eyelidedem a.

Fig 7. Prim ary derm atom e (ie, thoracic) affected by her-pes zo ster in a p atien t receiving radiation therapy for car-cinom a of the larynx.

Fig 8. D issem inated vesicles of herpes zoster in patien tseen in Fig 7.

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bodies, or Tzanck sm ears m ay be perform ed to con-

firm the clinical im pression.

TREATMENT/PROPHYLAXIS OFCHICKENPOX

In the past, otherw ise healthy children w ith prim a-ry varicella have been treated only sym ptom aticallyw ith calam ine lotion, tep id baths, cool com presses,and antipyretics (excluding aspirin seco ndary to itsassociation w ith Reye’s synd rom e). 77,78 Although acy-clovir (20 m g/kg 4 tim es a day for 5 days) w as show nto decrease both the d uration and severity of chicken -pox,79 this has not received w idespread acceptancebecau se o f the h igh cost of treatm en t, difficu lty inrapid institution of therapy, and concern of develop-m ent of acyclovir-resistant strains of VZV. In addition,the u sually benign course of the d isease an d low rateof com plications in this population w eakens the m oti-vation to start antiviral therapy. By allow ing the child toreturn to school 1 to 2 d ays earlier, how ever, antiviraltherapy m ay be considered cost-effective if it allow sthe paren t(s) or guardian(s) to return to w ork earlier.

In co ntrast, acyclovir is m uch m ore com m onlyused to treat prim ary varicella in im m unocom pro-m ised patien ts. 80,81 Although vidarabine and par-enteral hum an interferon alfa have also been proven

to be efficacious in the treatm ent of varicella in thispopulation, 82-86 the presence of significan t toxicities(neurotoxicity w ith vidarabine and fever and m yal-gias w ith interferon alfa) have lim ited their use.Therefore acyclovir (intraven ous dosing of 500m g/m 2 every 8 h ours for 7-10 days) 87 continues to bethe d rug o f ch oice for treatm en t of varicella inim m unocom prom ised patients.

N aturally, the prevention of varicella w ould bepreferable to treatm en t of an existing infection.Varicella-zoster im m une globulin (VZIG ) has been

obtained because VZV is a labile virus that is cultured

m uch less readily than H SV. 69-71 Although lim ited bycross-reactivity w ith H SV, serologic tests such ascom plem ent fixation can be u sed to retrospectivelydiagnose VZV infection. 72 C urren tly, the m ost usefultest to diagnose VZV infection is direct im m unofluo-rescence o f cellular m aterial from skin lesions.H ow ever, m olecu lar tech niques w ith high sensitivitysuch as dot-blot hybridization and polym erase chainreaction have been used recently to detect VZV inthe skin lesions, peripheral blood m ononuclearcells, and other tissues of patients w ith VZV infec-tion, and m ay be the d iagn ostic tests of choice in thefuture. 70,73,74

DIFFERENTIAL DIAGNOSISThe varicella rash associated w ith chickenpox can

som etim es be confused w ith other viral exanthem s,insect bites, scabies, erythem a m ultiform e, papularurticaria, drug eruptions, or other vesicu lar der-m atoses such as derm atitis herpetiform is. In con-trast, zoster is prim arily confused w ith derm atom alH SV infections, particularly an ogenital herpes (Figs 9and 10). H ow ever, “shingles”that recurs in the sacralarea is alm ost alw ays herpes sim plex virus 2. O therconditions occasionally confused w ith zoster include

contact derm atitis, burns, arthrop od reactions, local-ized bacterial or viral skin infections, or even vacciniaautoinoculation.

DIAGNOSISU sually diagnosed clinically, varicella is often diag-

nosed easily w hen there is the characteristic rash incom bination w ith a history of exp osure w ithin thepreceding 2 to 3 w eeks. 61,75,76 As m entioned previ-ously, w hile the d iagnosis of zoster is also usuallym ade clinically, viral cu ltures, direct fluorescent an ti-


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Fig 9. Perianal herpes zoster in an H IV-seropositive m an. Fig 10. Zosteriform herpes sim plex virus type 2.

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used in the past to treat im m un ocom prom isedpatien ts w ho have received sign ificant exp osure tovaricella (recom m ended do se is 125 U /10 kg).U nfortunately, one third to one half of these patien tsstill develop clinical infection. 88 Therefore therecently app roved live attenuated VZV vaccine (O KA

strain) has been received w ith m uch interest. Thisvaccine ap pears to be both high ly efficacious (96%seroconversion in healthy children in one study) 89

and very safe, w ith only such m ild side effects asslight varicelliform rash, fever, an d infection-sitereactions rep orted . 90,91 In addition, the incidence o fzoster occurring after vaccination seem s to bedecreased com pared w ith that after natural infec-tion. 92 A recen t study 93 found that varicella occurredin 14% of vaccinated children in a child care cen terversus 88% of unvaccinated children . In addition, thevaccinated children had less severe d isease andfew er days of absence from school than the unvacci-

nated ch ildren . Finally, the large so cietal savings intim e off from w ork to care for sick ch ildren and thehigh cost of caring for varicella-related com plicationsm ake the vaccine appear to be cost-effective. In fact,one study estim ated that an effective varicella vacci-nation program w ould be expected to have a net sav-ings of $384 m illion per year in the U nited States indiscou nted costs from the social perspective. 94

TREATMENT OF ZOSTER (ACUTEINFECTION)

Although no antiviral treatm ent has been show nto totally preven t PH N , early therapy h as been foundto reduce its duration. C urrently, acyclovir, idoxuri-dine, fam ciclovir, vidarabine, foscarnet, valacyclovir,and interferon alfa have all been show n to be effica-cious in treating VZV infections. Idoxuridine w as thefirst antiviral agen t to be evaluated for the treatm en tof zoster. 95 It is an antim etabolite of thym idine andacts to inhibit D N A synthesis after being intracellu-larly phosphorylated to idoxuridine triphosphate.H ow ever, because viral and host cell D N A are equ al-ly affected, it is too toxic for system ic u se but insteadw as used topically in a dim ethylsulfoxide base. A 40%solution applied every 4 to 6 h ours had ben eficial

effects on rash healing, acute p ain, and the p reven-tion of PH N . 95 H ow ever, other studies 96,97 show edno effect on PH N . Therefore, because of the lack ofeffect on PH N in com bination w ith a high potentialfor toxicity, idoxuridine is no longer used routinely inthe treatm en t of acute zoster.

Vidarabine w as the first system ic antiviral agentto be app roved by the FD A. It acts as an analogue o fthe nucleoside adenosine and interferes w ith D N Asynthesis. W hen vidarabine w as given intravenouslyto im m unocom prom ised patients (10 m g/kg every

12 hours for 5 days), viral shed ding, tim e to cessa-tion of pain and new vesicle form ation, total heal-ing tim e, cutaneo us dissem ination, visceral com pli-cations, and the d uration of PH N w ere allreduced. 51,98 H ow ever, later studies com paringvidarabine w ith acyclovir found that the rates o f

cutaneo us healing, resolution of acute pain, andincidence of PH N did not differ betw een the tw oagents in the treatm en t of patien ts w ith dissem inat-ed zoster. 99 In addition, the d ifficulty of adm inistra-tion and significan t side effects of vidarabine (neu-rotoxicity, m yelosup pression) have m ade acyclovirm uch m ore com m only used.

Acyclovir has (until recently) been the d rug ofchoice in the treatm en t of herpes zoster. An ana-logue of the nucleoside guanosine, it is ph osph ory-lated (first by viral thym idine kinase, then by cellu-lar kinases) into acyclovir triphosphate. It theninhibits viral D N A polym erase by acting as a com -

petitive inhibitor of gu anosine triphosphate. 100

Available in topical, intraven ous, and oral form ula-tions, only the intravenous and oral form s have anyrole in the treatm en t of VZV. W hen given toim m unocom petent and im m unocom prom isedpatien ts, intravenous acyclovir (500 m g/m 2/day for5-7 days) w as found to reduce acute pain and speedcutaneous healing. 101-104 The o ral form is lim ited bya poor availability (15% -20% ). H ow ever, w hen it w asgiven at a dose of 800 m g 5 tim es daily (curren tlyrecom m ended regim en: 7 days) accelerated rashhealing w as seen and pain w as reduced. 105-110

H ow ever, several trials have sho w n no benefit in theuse of acyclovir in red ucing the d uration ofP H N .101-103 Adverse effects seen w ith acyclovir arerare but include h eadaches, nausea, diarrhea, andrenal toxicity (in ren al patien ts w ho thus sho uldhave their doses red uced). Rarely, C N S toxicity canoccur w ith sym ptom s of disorien tation, delirium ,seizures, trem or, or slurred speech. 111

Valacyclovir is a p rod rug of acyclovir (the L-valylester of acyclovir) w ith the advan tage o f greatlyincreased oral bioavailability (65% ). 112,113 It w asapproved by the FD A for the treatm ent of shingles inJune 1995. In one trial com paring valacyclovir 1 g 3

tim es daily (currently recom m ended cou rse: 7 d ays)to acyclovir 800 m g 5 tim es daily, valacyclovir w asfound to be as effective in decreasing the appearanceof new lesions, tim e to crusting, and tim e to 50%healing. 114 In addition, valacyclovir reduced them edian duration of pain from 60 days after healing(w ith acyclovir) to 40 days. Six m onths after healing,only 19% of patien ts taking valacyclovir had paincom pared w ith 26% of patien ts taking acyclovir. 115

Finally, valacyclovir appears to have a sim ilar safetyprofile to acyclovir, w ith som e n ausea, vom iting,



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clovir, or fam ciclovir. Alm ost all published studieshave defined im m ediate treatm ent as that w hichbegins w ithin 72 hours of the first vesicle. B ecausepatien ts frequen tly present after 72 hours of vesicles,the question often arises as to the effectiveness ofinitiating therapy after this tim e. Although the

answ er to this qu estion is un clear, it appears reason-able to use an tiviral therapy in the patien t presentingafter 72 hours of the appearance of vesicles if thelesions are n ot com pletely crusted and she/he isolder than 50 years of age, im m un ocom prom ised,and/or has trigem inal zoster. Although no antiviralagen t has dem onstrated any efficacy in the treatm entof PH N , a variety of m odalities including analgesics,narcotics, cu taneo us stim ulation, tricyclic an tide-pressants, capsaicin, biofeedback, and nerve b lockshave been rep orted to be effective in relieving painin som e p atien ts. N arcotics and analgesics are n otgenerally effective in the treatm ent of PH N , and the

poten tial for dep en den cy w ith long-term use dis-courages the u se of narcotics. Anticonvulsants suchas carbam azepine h ave been found to have efficacyin painful conditions such as trigem inal neu ralgia inw hich lancinating p ain is a prom inen t part of theircondition. 136,137 H ow ever, since this type o f pain isnot a com m on feature of PH N , little benefit has beenshow n w ith their use. 138,139 In addition, one half ofthe p atien ts treated by Killian and From m 138 experi-en ced significant side effects w ith their use. In con-trast, gabapen tin, a structural analogue of gam m a-am inobutyric acid w hich is m arketed as an anticon-vulsant, w as recently d em onstrated to be effective inthe treatm ent of PH N . 140 G abapen tin w as statistical-ly sign ifican tly better than placebo in reducing theaverage daily pain score and dem onstrated benefitsin restoring norm al sleep patterns. Although adverseevents w ere m ore com m on in the gabapentin recip-ien ts, w ithdraw als from the study w ere com parablew ith the placebo group.

Antipsychotics such as chlorprothixene, flu-phen azine, and haloperidol have also been tried(often in com bination w ith antidep ressants) butw hen used alone in a p lacebo-controlled trial, chlor-prothixene w as found to be of m arginal efficacy. 141

Local treatm en ts such as the local injection of bupi-vacaine, cryoanalgesia, and sym pathetic b lockad ehave been reported to provide relief in som epatients. 142-145 In addition, such topical treatm en tsas topical lidocaine, eu tectic m ixture of local anes-thetics (EM LA) cream , or transcutaneous electricalstim ulation have been u sed w ith som e success. 146-149

O ne top ical treatm en t that has had sign ificant suc-cess is capsaicin, w hich acts by enhancing the releaseor inhibiting the reaccum ulation of substance P fromcell bodies and nerve term inals. In one study by

Bernstein et al, 150 alm ost 80% of the patien ts treatedexp erien ced som e pain relief. So m e p atien ts areunable to tolerate the burning associated w ith cap-saicin, but som e au thors have advocated applyingEM LA or topical lignocaine before its use. 151 Patientssho uld be cautioned not to apply capsaicin to the

unhealed skin lesions of acu te zo ster. Su rgicalm easures have b een m ostly disapp ointing, 152,153

although som e success w as initially found byFriedm an and H asho ld 154 w ith the use of the dorsalroot en try zon e lesion procedure. This neu rode-structive tech nique involves m aking radiofrequencylesions at m ultiple levels of the sen sory nerve roo ten try zones that are involved in the pain, but it is nolon ger recom m ended for the treatm ent of PH N . O fgreatest efficacy, perhaps, is the use of tricyclic anti-depressants. They are though t to act in a m ann erindep en den t of their antidep ressant actions (sincerelief of PH N occurs at less than antidep ressant

dosages). In fact, som e authors 155 recom m end start-ing am itriptyline at low doses (10-25 m g) and gradu-ally increasing this to doses of 50 to 75 m g over 2 to3 w eeks in all patien ts older than 60 years of age assoo n as shingles is diagn osed. They report this regi-m en to d ecrease the incidence of PH N by 50% .Am itriptyline, m aprotiline, and desipram ine have allbeen show n to be effective, 156-158 bu t desipram inem igh t be p referable becau se of its low anticholiner-gic and sedative effects. These drugs probably act byblockad e of norep inep hrine reuptake. In co ntrast,seroton in reu ptake inhibitors such as zim elidinehave not been show n to be effective. 159

PROPHYLAXIS OF HERPES ZOSTERA live attenuated vaccine (O KA varicella vaccine)

against VZV received FD A app roval in M arch 1995.This vaccine w as show n to be 100% efficacious inpreventing varicella in one clinical trial. 160 In addi-tion, am ong ch ildren w ith leukem ia w ho receivedthe vaccine, the inciden ce of zoster w as decreasedcom pared w ith children w ith leukem ia w ho hadexperienced n atural varicella infections. 161 H ow ever,w hile it w as initially hoped zoster w ould not occur invaccinated patien ts at all, som e p atien ts have had

herpes zoster caused by vaccine-type virus.162

Finally, it is believed that the vaccine w ill be cost-effective in term s of m edical and w ork-loss costs. 94

Stud ies are no w under w ay to see w hether theim m unization of healthy adu lts w ith O KA vaccinew ill preven t shingles. In one study of adults olderthan 50 years of age w ith a history of prim ary zoster,an increase of VZV-specific T lym phocytes and VZVim m un ity w as seen. 163 H ow ever, in another study ofadults older than 55 years of age, anti-VZV antibodylevels w ere enhanced for only 1 year after im m u-



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11. Strueiving JP,Hyams KC,Tuellar JE,Gray GC.The risk of m easles,mumps,a nd varicella among young a dults:a serosurvey of USNavy and Marine Corps recruits. Am J Public Health1993;83:1717-20.

12. McGrego r JA, Mark S, Crawford GP, Levin MJ. Varicella zosterantibody testing in the care of pregnant wom en exposed tovaricella. Am J Obstet Gyneco l 1987;157:281-4.

13. Junker AK, Angus E, Thoma s EE. Recurrent varicella-zosterinfections in apparently immunoco mpetent children. PediatrInfect Dis J 1991;10:569-75.

14. Hope-Simpson RE. The nat ure of herpes zoster: a long -termstudy a nd a new hypo thesis.Proc R Soc Lond B 1965;58:9-20.

15. Seiler HE. A study o f herpes zoster pa rticularly in its relation-ship to chickenpox. J Hyg (Camb ) 1949;47:253.

16. Straus SE. Shingles: sorrows, salves, and solutions. JAMA1993;269:1836-9.

17. Grose C.Variation on a theme by Fenner:the pathogenesis ofchickenpox. Pedia trics 1981;68:735-7.

18. Arvin AM. Cell-mediat ed immunity to varicella-zoster virus. JInfect Dis 1992;166(suppl 1):S35-S41.

19. Solomon BA, Kapo ris AG, Glass AT, Simon SI, Baldwin HE.Lasting immunity to varicella in do cto rs study (L.I.V.I.D.stud y).

J Am Acad Dermatol 1998;38:763-5.20. Ruckdeschel JC, Schimpff SC, Smyth AC, Mardiney MR Jr.

Herpes zoster and impaired cell-associated immunity to thevaricella zoster virus in patien ts w ith Hodg kin’s disease. Am JMed 1977;62:77-85.

21. Arvin AM. Immune responses to varicella-zoster virus. InfectDis Clin North Am 1996;10:529-70.

22. Dolin R, Reichman RC, Mazur MH, Whitley RJ. Herpes zoster-varicella infection in immunosuppressed p atients. Ann InternMed 1978;89:375-88.

23. Juel-Hensen BE, MacCallum FO. Herpes simplex, varicella andzoster.Philadelphia: JB Lippincott ; 1972;p. 72-7.

24. Sokal JE, Firat D.Varicella-zoste r infection in Hodg kin’s disease.Am J Med 1965;39:452-63.

25. Schimpff S, Serpick A, Stoler B,Rumack B, Mellin H, Joseph JM,

et al. Varicella-zoster infection in patients with ca ncer. AnnIntern Med 1972;76:241-54.26. Feldma n S, Hughes WT, Kim HY. Herpes zoster in children w ith

cancer.Am J Dis Child 1973;126:178-84.27. Goffinet DR, Glatstein EJ, Merigan TC. Herpes zoster-varicella

and lympho ma . Ann Intern Med 1972;76:235-40.28. Good man R, Jaffe N, Filler R. Herpes zoster in children with

sta ge I-III Hodgkin’s disease . Radio log y 1976;118:429-31.29. Rebo ul F, Donaldson SS,Kaplan HS.Herpes zoster and varicel-

la infections in children w ith Hodgkin’s disease: an analysis ofcontributing factors.Cancer 1978;41:95-9.

30. Rusthoven JJ, Ahlgren P,Elhakim T, Pinfold P, Reid J, Stewart L,et a l.Varicella-zoster infection in adult ca ncer patients: a po p-ulat ion study. Arch Inte rn Med 1988;148:1561-6.

31. Arvin AM. Cell-mediated immunity to varicella zoster virus. J

Infect Dis 1992;166:S35-S41.32. Ljungman P,Lonnqvist B,Ga hrton G, Ringden O, Sundqvist VA,Wahren B. Clinical and subclinical react ivations o f varicella-zoster in immunocompromised pa tients. J Infect Dis 1986;153:840-7.

33. Meyers JD, Flournoy N,Thom as ED.Cell-med iated immunity tovaricella-zoster virus after allog enic marrow transplant. JInfect Dis 1980;141:479-87.

34. Locksley RM,Flourno y N,Sullivan KM,Meyers JD.Infection w ithvaricella-zoster virus after bon e marrow transplanta tion. JInfect Dis 1985;152:1172-81.

35. Colebunders R, Mann JM,Francis H,Bila K, Izaley L,Ilwa ya M, etal. Herpes zoster in African pa tients: a clinical predictor of

nization, although VZV-responding T cells rem ainedelevated . In addition, im m unity failed to increase in10% to 15% of vaccinees regardless of dose. 164 Incon trast, ano ther study show ed cell-m ediated im m u-nity w as still detected at 5 years after im m unizationin 87% of children and 94% of adu lts. 165 Acyclovir has

been tried in suppressive doses to try and preven tzoster in groups at high risk because of im m uno-com prom ise. Althou gh som e benefit has been fou ndw hen used in the peritransplant period of bo ne m ar-row transplant recipien ts, 166 long-term use in H IV-positive p atien ts has been associated w ith thedevelopm en t of acyclovir-resistan t strains ofVZV.37,39,42,167,168

CONCLUSIONInfection w ith VZV is un ique b ecau se of its tw o

clinical m anifestations. Although the increasing use o fO KA vaccine m ay decrease the incidences of bo th pri-

m ary varicella and zoster for the next several decades,w e w ill continue to see zoster as a consequ ence ofprevious varicella infection. Therefore the n eed forthe developm ent and evaluation of new antivirals, asw ell as m ore effective treatm ent of PH N w ill continue.In addition, the rise in inciden ce of H IV infection w illalso continue to m ake safe an d effective treatm ents ofim m un ocom prom ised ho sts w ith chickenpo x andzoster infections necessary, particularly as rates of acy-clovir-resistant VZV strains increase.

W e extend special thanks to M rs M ichelle H arden andM iss Am y Shaabani for their help in preparing this m anu -script.

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79. Dunkel LM, Arvin AM, Whitley RJ, Rot ba rt HA, Fede r HM, Jr,Feldman S, et a l.A controlled trial of acyclovir for chickenpoxin no rmal children. N Eng l J Med 1983;309:133-9.

80. Probe r CG, Kirk LE,Keene y RE. Acyclovir therap y of chickenpoxin immunosuppressed children: a collaborative study. JPediatr 1982;101:622-5.

81. Nyerges G, Meszner Z, Gyarmati E, Kerpel-Fronius S. Acyclovirprevents dissemination of varicella in immunocomprom isedchildren. J Infect Dis 1988;157:309-13.

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83. Arvin AM, Kushner JH, Feldman S, Baehner RL, Hammond D,Merigan TC. Human leukocyte interferon in the t reatment ofvaricella in ch ildren w ith ca ncer.N Engl J Med 1982;306:761-5.

84. Whitley RJ, Gnann JW. Acyclovir: a d ecade later.N Engl J Med1992;327:782-9.

85. Nyerges G, Meszner Z.Treatment of chickenpox in immuno-supp ressed children. Am J Med 1988;85(supp l 2A):94-5.

86. McGregor RS, Zitelli BJ, Urbach AH, Malata ck JJ, Gartner JC Jr.Varicella in ped iatric ortho to pic liver transplan t recipients.Pediatrics 1989;83:256-61.

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90. Gershon AA.Viral vaccines of the fut ure.Pediat r Clin North Am1990;37:689-707.

91. Gershon AA. Live attenua ted varicella va ccine.Annu Rev Med1987;38:41-50.

92. Guess HA, Broughton DD, Melton LJ III, Kurland LT.Epidemiology of he rpes zoster in children and ad olescents: apopulation-based study.Pediatrics 1985;76:512-7.

93. Izurieta HS, Strebel PM, Blake PA. Post licensure effectivenessof varicella vaccine d uring an o utbreak in a child care center.JAMA 1997;278:1495-9.

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95. Juel-Hensen BE, MacCallum FO, Mackenzie AM, Pike MC.Treat ment o f zoster with ido xuridine dimet hyl sulfoxide: resultsof t wo do uble-blind cont rolled trials. BMJ 1970;4:776-80.

96. Wildenho ff KE, Ipsen J, Esmann V, Ingem ann-Jensen J, PoulsenJH. Treatment of herpes zoster w ith idoxuridine ointme ntincluding a multivariate analysis of signs and symptoms.

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Schonheyder H. Treatment of trigeminal and thoracic zosterwith ido xuridine.Scand J Infect Dis 1981;13:257-62.

98. Whitley RJ, Chien LT, Dolin R, Galasso GJ, Alford CA, Jr.Adenosine arabinoside therapy of herpes zoster in theimmuno suppressed. N Eng l J Med 1976;294:1193-9.

99. Whitley RJ, Gnann JW Jr,Hinthorn D,Liu C,Po llard RB, HaydenF, et a l. Disseminated herpes zoster in the immunocompro-mised host: a compa rative trial of acyclovir and vidarabine. JInfect Dis 1992;165:450-5.

100. Derse D,Che ng YC,Furman PA, St Clair MH, Elion GB.Inhibitionof p urified huma n a nd herpes simplex virus-induced DNA


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121. Tyring SK, Ring J , Lasson de M, Martel A,Van Slycken S, Crann R,et al. Famciclovir for the treatment o f ophtha lmic herpeszoster.Presented at the 38th Annual Interscience Conferenceon Antimicrobial Agent s and Chemo therapy, San Diego, Calif,Sept 24-27, 1998.

122. Machida H. Comparison of susceptibilities of varicella-zostervirus and herpes simplex viruses to nucleoside analogs.Antimicrob Agents Chemo the r 1986;29:524-6.

123. Bodsworth N J, Boag F, Burdge D, Genereux M, Borleffs JCC,Evans BA, et a l.Evaluat ion o f sorivudine (BV-araU) versus acy-clovir in the treatment of acute localized herpes zoster inhuma n immunode ficiency virus-infected ad ults. J Infect Dis1997;176:103-11.

124. Yan J, Tyring SK,McCrary ML, Lee PC,Hawo rth S,Raymond R, etal.The effect of sorivudine on dihydropyrimidine dehydrog e-nase activity in patients with acute herpes zoster. ClinPha rmacol Ther 1997;61:563-73.

125. Gna nn JW, Crumpacker CS, Laleza ri JP, Smith JA, Tyring SK,Baum KF, et al. Sorivudine versus acyclovir for treatme nt ofdermato mal herpes zoster in human immuno deficiency virus-infected patients: results from a randomized, controlled clini-cal t rial.Antimicrob Age nts Chemo the r 1998;42:1139-45.

126. Gnann JW. New antivirals with a ctivity a ga inst varicella-zostervirus. Ann Neurol 1994;35(suppl):S69-72.

127. Söltz-Szöt s J, Tyring S, Ande rson PL, Lucht F, McKendrick MW,Dial Perez JL,e t al. A random ized controlled trial of acyclovirversus netivudine for treat ment of herpes zo ster.J AntimicrobChemother 1998;41:549-56.

128. Wills RJ, Dennis S,Spieg el HE, Gibson DM, Nadler PI.Interfe ronkinetics and ad verse reactions a fter intravenous,intramuscu-lar, and subcutaneo us injection. Clin Pharmaco l Ther 1984;35:722-7.

129. Eag lstein WH, Katy R, Brow n JA.The e ffects of early corticos-teroid therapy on the skin eruption and p ain of herpes zoster.JAMA 1970;211:1681-3.

130. Post B, Philbrick JT. Do corticosteroids prevent postherpet icneuralgia? A review of the e vidence. J Am Acad Derma tol1988;18:605-10.

131. Wood MJ, Joh nson RW, McKendrick MW, Taylor J , Manda l BK,Crooks J. A random ized trial of acyclovir for 7 days o r 21 dayswith and without prednisolone for treatment of acute herpeszos ter. N Eng l J Med 1994;330:896-900.

132. Whitley RJ,Weiss H,Gnann JW,Tyring S, Mertz GJ, Papp as PG, etal.Acyclovir with and w ithout prednisone for the treatment o fherpes zost er.Ann Intern Med 1996;125:376-83.

133. Safrin S, Assaykeen T, Follansbee S, Mills J. Foscarnet therapyfor acyclovir-resistant mucocutaneous herpes simplex virusinfection in 26 AIDS patients: preliminary da ta. J Infect Dis1990;161:1078-84.

134. Wahren B, Oberg B. Reversible inhibition of cytom ega lovirusreplication by phosphonoformate.Intervirology 1980;14:7-15.

135. Tyring SK. Adva nces in antiviral therap y and p rophylaxis indermatology. Presented at the 56th Annual Meeting,

American Acade my of Dermato logy, Orlando, Fla, Feb 27-March 4, 1998.

136. Swerdlow M. Anticonvulsant drugs and chronic pain. ClinNeuropharmacol 1982;7:51-82.

137. Swerdlow M.The treatment o f shooting pa in.Postgrad Med J1980;56:159-61.

138. Killian JM,Fromm GH.Carba mazepine in the treatm ent o f neu-ralg ia. Arch Neurol 1968;19:129-36.

139. Row bot ham M,Harden N,Stacey B, Bernstein P, Magnus-MillerL. Gab apentin for the treatmen t of postherpetic neuralgia.JAMA 1998;280:1837-42.

140. Taylor JC. Trigemina l neuralgia trea ted w ith G.32883. J NeurolNeurosurg Psychiatry 1963;26:553-4.

141. Nathan PW. Chlorproth ixene (Tarac tan) in post-herpetic neu-ralgia and o the r severe chronic pain. Pain 1978;5:367-71.

142. Tenicela R, Lovasik D, Eag lstein W. Treatm ent o f herpes zost erwith sympa the tic blocks. Clin J Pa in 1985;1:63-7.

143. Suzuki H,Ogaw a S,Nakagaw a H,Kanaya ma T,Tai K,Saitoh H,etal. Cryocautery of sensitized skin areas for the relief of paindue to posth erpetic neuralg ia. Pain 1980;9:355-62.

144. Colding A. The effect of sympa thetic b locks on herpes zoster.Acta Anaesthesiol Scand 1969;13:133-41.

145. Colding A.Treatment o f pain: organ ization of a pain clinic;treat ment o f acute herpe s zoster. Proc R Soc Med 1973;66:541-3.

146. Row bot ham MC, Fields HL. Topical lidocaine reduces pa in inpost -herpet ic neura lgia. Pain 1989;38:297-301.

147. Kissin J, McDanal J, Xavier AV. Topica l lido caine for relief ofsuperficial pain in po stherpetic neuralgia. Neurology1989;39:1132-3.

148. Stow PJ, Glynn CJ, Minor B. EMLA cream in the treatment ofpost-herpetic neuralgia: efficacy and pharmaco kinetic profile.Pain 1989;39:301-5.

149. Natha n PW, Wall PD. Treatment of po st-herpetic neuralgia b yprolonged electric stimulation.Br Med J 1974;3:645-7.

150. Bernstein JE, Korma n NJ, Bickers DR, Dah l MV, Millikan LE.Topical capsa icin t reatment of ch ronic postherpetic neuralgia.J Am Acad Dermatol 1989;21:265-70.

151. Watson CPN, Evans RJ, Watt VR. Postherpetic neuralgia andtop ical ca psaicin. Pain 1988;33:333-40.

152. Tindall GT, Odam GL, Vieth RG. Surgical t reatment of posther-petic neuralgia: results o f skin und ermining and excision in 14pa tien ts. Arch Neuro l 1962;7:423-6.

153. Weidman MJ. Surgical relief of post-herpetic pa in by excisionof sca rred skin. Med J Aust 1976;63:472-3.

154. Friedma n AH,Nashold BS. DREZ lesions for po stherpetic neu-ralgia. Neurosurgery 1984;15:969-70.

155. Bowsher D. The mana gement of postherpetic neuralgia.Postg rad Med J 1996;73:623-9.

156. Wat son CP, Evans RJ, Reed K,Merskey H, Goldsm ith L, Warsh J.Amitriptyline versus placebo in postherpetic neuralgia.

Neurology 1982;32:671-3.157. Watson CP, Chipman M, Reed K, Evans RJ, Birkett N.

Amitriptyline versus maprotiline in po stherpetic neuralgia: arandomized, do uble-blind, crossover trial. Pain 1992;48:29-36.

158. Kishore-Kumar R, Max MB,Scha fer SC, Gaughan AM, Smoller B,Gracely RH,et al.Desipramine relieves po stherpetic neuralgia.Clin Pharmaco l Ther 1990;47:305-12.

159. Watson CP, Evans RJ. A comparat ive trial of a mitriptyline andzimelidine in post herpet ic neuralg ia. Pain 1985;23:387-94.

160. Takahachi M.Current status and prospects o f live varicella vac-cine. Vaccine 1992;10:1007-14.

161. Hardy I, Gershon AA, Steinbe rg SP, LaRussa P. The incidence o fzoster after immunization with live attenuated varicella vac-cine. N Eng l J Med 1991;325:1545-50.

162. Liang MG, Heidelberg KA, Jaco bson RM, McEvoy MT. Herpes

zoster after varicella immunization. J Am Acad Derma tol1998;38:761-3.

163. Haywa rd A, Villaneuba E, Cosyns M, Levin M. Varicella-zostervirus (VZV) specific cytotoxicity after immunization of nonim-mune a dults w ith OKA strain at tenuat ed VZV vaccine. J InfectDis 1992;166:260-4.

164. Levin MJ, Murray M, Zerbe GO,White CJ, Haywa rd AR. Immuneresponses of e lderly persons 4 yea rs after receiving a liveat tenuate d va ricella vaccine. J Infect Dis 1994;170:522-6.

165. Zerboni L, Nad er S, Aoki K, Arvin AM. Analysis of the persis-tence of h umoral and cellular immunity in children and adultsimmunized w ith varicella va ccine. J Infect Dis 1998;177:1701-4.

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168. Safrin S, Berger TG, Gilson I, Wolfe PR, Wofsy CB, Mills J, et al.Foscarnet therapy in five patients with AIDS and acyclovir-resistant varicella zoster virus infection. Ann Intern Med1991;115:19-21.

166. Perren TJ, Powles RL, Easton D,Stolle K, Selby RJ. Prevention ofherpes zoster in patients b y long -term oral a cyclovir after allo-geneic bone ma rrow transplantation. Am J Med 1988;85(supp l 2A):99-101.

167. Pahw a S, Biron K, Lim W, Swenson P, Kaplan MH, Sadick N.Continuous varicella-zoster infection associated with acy-clovir resist ance in a child w ith AIDS. JAMA 1988;260:2879-82.


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1.c2.c3.b4.a5.b

6.b7.b8.a9.a

10.a11.b12.b13.b14.a15.b16.a

17.b18.c19.a20.e21.d

22.a23.c24.e25.d26.b27.c28.a29.b30.d31.a, c, e

Answers to CME examination

Iden tification N o. 899-106

Jun e 1999 issue of the Journal of the Am erican Academ y of D erm atology

Q uestions 1-31, Landau M , K rafchik B R. J Am Acad D erm atol 1999;40:877-90.

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15

Di r ection s for qu esti on s 1-20: Give si ngle best r espon se.

1. The incidence of shingles in a person w ith a history ofvaricella infection isa. 10%b. 20%c. 30%

d. 40%e. 50%

2. At w hat point in tim e does the secondary virem ia ofvaricella infection infect the epiderm is?a. 2 to 4 daysb. 4 to 6 daysc. 6 to 8 daysd. 10 to 14 dayse. 14 to 16 days

3. The h ighest incidence of herpes zoster is seen am on gcancer patien ts w itha. lun g cancerb. breast cancer

c. colon cancerd. H odgkin’s diseasee. prostate cancer

4. Th e m ost com m on extracutaneous com plication ofvaricella zoster virus (VZV) infection isa. central nervous systemb. cardiovascularc. gen itourinaryd. m usculoskeletale. lym ph oreticular

5. The p ain preced ing the onset of shingles typicallyoccurs how m any days before the onset of the rash?a. 1 to 3

b. 3 to 5c. 5 to 7d. 7 to 10e. 10 to 14

6. Each of the follow ing is com m on ly seen w ith m aternalinfection w ith VZV in the first trim ester except a. cicatricial skin lesionsb. hypo plastic lim bsc. hypertelorismd. cortical atrophye. low birth w eight

7. The percen tage of patients w ith h erpes zoster w hoexperience pain in the involved derm atom e beforethe developm ent of the rash isa. 50%b. 60%c. 70%d. 80%

e. 90%8. Postherpetic neu ralgia affects w hat percentage o f

patien ts w ith herpes zoster w ho are o lder than 60years of age?a. 10% to 15%b. 20%c. 30%d. 40%e. 50%

9. Ram say H un t syndrom e can be associated w ith her-pes zoster and each of the follow ing except a. ipsilateral facial palsyb. vesicles on the external ear

c. chorioretinitisd. tinnituse. deafness

10. O phthalm ic zoster is com plicated by o cular disease inw hat percentage o f patien ts?a. 1%b. 10% to 20%c. 20% to 70%d. 30% to 50%e. M ore than 90%

11. O cular m anifestation s of herpes zoster com m onlyinclude each of the follow ing except a. keratitisb. cataractsc. uveitisd. scleritise. secondary glaucom a

12. M otor paralysis occurs in w hat percentage o f patientsw ith h erpes zoster?a. 1% to 5%b. 5% to 10%c. 10% to 15%d. 15% to 20%e. 20% to 30%

CME examination

Iden tification N o. 899-107

Instructions for Category I CM E cred it appear in the front advertising section. See last page of C onten ts for page num ber.

Q uestions 1-30: M cCrary M L, Severson J, Tyring SK. J Am Acad D erm atol 1999;41:1-14.

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20. The m odality that is probably of greatest ben efit inthe treatm en t of postherpetic neu ralgia isa. EM LA creamb. anticon vulsantsc. narcoticsd. tricyclic antidep ressantse. serotonin reuptake inhibitors

Di r ection s for qu esti on s 21-30: For each nu mber ed item,choose the appr opr i ate letter ed item.

a. Trueb. False

21. H erpes is an RN A virus.

22. Shingles can be acquired by direct contact w ith vari-cella lesions.

23. Im m un ocom prom ised p atients w ith V ZV infection arem ost likely to have lung, liver, and cen tral nervous sys-tem involvem ent.

24. H erpes zoster can be d iagno sed in the absence of arash.

25. The rash of herpes zoster is m ost likely to be in thearea that w as m ost severely affected by varicella.

26. VZV can be distinguished from herpes sim plex virusby a Tzanck sm ear.

27. Acyclovir has been show n to d ecrease the durationand severity of varicella.

28. Both valacyclovir and fam ciclovir have been show n tored uce the d uration of acute p ain associated w ithzoster.

29. Acyclovir m ust first be phosph orylated by cellular

thym idine kinase.

30. Acyclovir is useful in the p revention of postherpeticneu ralgia.

13. The m ost com m on cen tral nervou s system find ingw ith herpes zoster isa. facial paralysisb. m otor p aralysisc. granu lom atous cerebral angiitisd. cerebrospinal fluid abnorm alitiese. m eningitis

14. A few vesicles can be fou nd rem ote from the prim ari-ly affected derm atom e in app roxim ately w hat per-centage of im m un ocom petent patients?a. 5% to 10%b. 10% to 20%c. 20% to 40%d. 40% to 60%e. 60% to 70%

15. Th e risk of dissem ination in im m un ocom prom isedpatients w ith herpes zoster can b e estim ated at w hatpercentage?a. 10%b. 20%

c. 40%d. 60%e. 80%

16. Each of the follow ing can be used as a stain for aTzanck sm ear except a. hem atoxylin-and-eosinb. G iem sac. W rightd. periodic acid–Sch iffe. Papanicolaou

17. The efficacy of the VZV vaccine (in term s of serocon -version) is estim ated to be m ore than w hat percent-age?a. 50%b. 60%c. 70%d. 80%e. 90%

18. M yelosuppression occurs if sorivud ine is given in con-junction w itha. cytoxanb. 5-fluorouracilc. cyclospo rined. im urane. m etho trexate

19. For strains of herpes sim plex or herpes zoster foundto be resistant to acyclovir, the m ost approp riate ther-apy isa. foscarnetb. valaciclovirc. fam ciclovird. vidarabinee. ido xuridine

16 CME exam in ati on J A M A C A D D ERMATOL

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