2/11/2015 Candidavulvovaginitis

OfficialreprintfromUpToDate
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Candidavulvovaginitis

Author SectionEditors DeputyEditor

JackDSobel,MD RobertLBarbieri,MD KristenEckler,MD,FACOG
CarolAKauffman,MD

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Sep2015.|Thistopiclastupdated:Jun05,2015.
INTRODUCTIONVulvovaginalcandidiasisreferstoadisordercharacterizedbysignsandsymptomsof
vulvovaginalinflammationinthepresenceofCandidaspecies.Itisthesecondmostcommoncauseofvaginitis
symptoms(afterbacterialvaginosis)andaccountsforapproximatelyonethirdofvaginitiscases[1].Incontrastto
oropharyngealcandidiasis,itisgenerallynotconsideredanopportunisticinfection,and,unliketrichomonas
vaginitis,itisnotconsideredasexuallytransmitteddisease.

PREVALENCECandidaspeciescanbeidentifiedinthelowergenitaltractin10to20percentofhealthy
womeninthereproductiveagegroup,6to7percentofmenopausalwomen,and3to6percentofprepubertalgirls
[2,3].However,identificationofvulvovaginalCandidaisnotnecessarilyindicativeofcandidaldisease,asthe
diagnosisofvulvovaginitisrequiresthepresenceofvulvovaginalinflammation.

Theprevalenceofvulvovaginalcandidiasisisdifficulttodeterminebecausetheclinicaldiagnosisisoftenbased
onsymptomsandnotconfirmedbymicroscopicexaminationorculture(asmanyasonehalfofclinically
diagnosedwomenmayhaveanothercondition[4]).Inaddition,thewidespreaduseofoverthecounterantimycotic
drugsmakesepidemiologicstudiesdifficulttoperformandculturewithoutclinicalcorrelationislikelyto
overestimatetheprevalenceofdisease.

Insurveys,theprevalenceofvulvovaginalcandidiasisishighestamongwomenintheirreproductiveyears:55
percentoffemaleuniversitystudentsreporthavinghadatleastonehealthcareproviderdiagnosedepisodebyage
25years,29to49percentofpremenopausalwomenreporthavinghadatleastonelifetimeepisode,and9percent
ofwomenreporthavinghadfourormoreinfectionsina12monthperiod(ie,recurrentvulvovaginalcandidiasis
[RVVC])[5,6].Inwomenwithaninitialinfection,theprobabilityofRVVCwas10percentbyage25years,and25
percentbyage50years[6].

TheprevalenceincreaseswithageuptomenopauseandishigherinAfricanAmericanwomenthaninotherethnic
groups.Thedisorderisuncommoninpostmenopausalwomen,unlesstheyaretakingestrogentherapy.Itisalso
uncommoninprepubertalgirls,inwhomitisfrequentlyoverdiagnosed.

MICROBIOLOGYCandidaalbicansisresponsiblefor80to92percentofepisodesofvulvovaginalcandidiasis
[7]andC.glabrataaccountsforalmostalloftheremainder[8].Some,butnotall,investigatorshavereportedan
increasingfrequencyofnonalbicansspecies,particularlyC.glabrata[9,10],possiblyduetowidespreaduseof
overthecounterdrugs,longtermuseofsuppressiveazoles,andtheuseofshortcoursesofantifungaldrugs.

AllCandidaspeciesproducesimilarvulvovaginalsymptoms,althoughtheseverityofsymptomsismilderwithC.
glabrataandC.parapsilosis.

Incontrasttobacterialvaginosis,vulvovaginalcandidiasisisnotassociatedwithareductioninvaginallactobacilli
[1114].

PATHOGENESISCandidaorganismsprobablyaccessthevaginaviamigrationfromtherectumacrossthe
perianalarea[15]culturesofthegastrointestinaltractandvaginaoftenshowidenticalCandidaspecies.Less
commonly,thesourceofinfectionissexualorrelapsefromavaginalreservoir.

Symptomaticdiseaseisassociatedwithanovergrowthoftheorganismandpenetrationofsuperficialepithelial

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cells[1618].ThemechanismbywhichCandidaspeciestransformfromasymptomaticcolonizationtoaninvasive
formcausingsymptomaticvulvovaginaldiseaseiscomplex,involvinghostinflammatoryresponsesandyeast
virulencefactors.(See"BiologyofCandidainfections".)

RecurrentvulvovaginalcandidiasisRecurrentvulvovaginalcandidiasisisdefinedasfourormoreepisodesof
symptomaticinfectionwithinoneyear[16].LongitudinalDNAtypingstudiessuggestthat,inmostwomen,
recurrentdiseaseisduetorelapsefromapersistentvaginalreservoiroforganismsorendogenousreinfectionwith
theidenticalstrainofsusceptibleC.albicans[19,20].Rarely,infectionisduetoadifferentCandidaspecies.

Recurrentvulvovaginalcandidiasishasbeenassociatedwithdecreasedinvivoconcentrationofmannosebinding
lectin(MBL)andincreasedconcentrationofinterleukin4.Twospecificgenepolymorphisms,variantsintheMBL
andinterleukin4alleles,canaccountforthisfindinginsomewomen.TheprevalenceofavariantMLBgeneis
higherinwomenwithrecurrentvulvovaginalcandidiasisthanincontrolswithoutcandidiasis[21,22].Sincethe
directinteractionofMBLwithC.albicansisanimportantcomponentofthehost'sabilitytoresistcandidiasis,
impairmentofthisinteractioninMBLdeficientindividuals,suchasthosewithcertainMBLpolymorphisms,
appearstopredisposethesewomentorecurrentvulvovaginalcandidalinfection[21,2326].Thesewomenmounta
stronginflammatoryresponsewhenexposedtosmallamountsofCandida,whereasnormalwomenmaynot
mountanyinflammatoryresponseandremainasymptomatic.Interleukin4blockstheantiCandidaresponse
mediatedbymacrophages,thuselevatedIL4levelsresultininhibitionoflocaldefensemechanisms.

RISKFACTORSSporadicattacksofvulvovaginalcandidiasisusuallyoccurwithoutanidentifiableprecipitating
factor.Nevertheless,anumberoffactorspredisposetosymptomaticinfection[27,28]:

DiabetesmellitusWomenwithdiabetesmellituswhohavepoorglycemiccontrolaremoreproneto
vulvovaginalcandidiasisthaneuglycemicwomen[29,30].Inparticular,womenwithType2diabetesappear
pronetononalbicansCandidaspecies[31].

AntibioticuseUseofbroadspectrumantibioticssignificantlyincreasestheriskofdeveloping
vulvovaginalcandidiasis[32].Asmanyasonequartertoonethirdofwomendevelopthedisorderduringor
aftertakingtheseantibioticsbecauseinhibitionofnormalbacterialflorafavorsgrowthofpotentialfungal
pathogens,suchasCandida.Administrationoflactobacillus(oralorvaginal)duringandforfourdaysafter
antibiotictherapydoesnotpreventpostantibioticvulvovaginitis[33].

IncreasedestrogenlevelsVulvovaginalcandidiasisappearstooccurmoreofteninthesettingof
increasedestrogenlevels,suchasoralcontraceptiveuse(especiallywhenestrogendoseishigh),
pregnancy,andestrogentherapy.

ImmunosuppressionCandidalinfectionsaremorecommoninimmunosuppressedpatients,suchas
thosetakingglucocorticoidsorotherimmunosuppressivedrugs,orwithhumanimmunodeficiencyvirus(HIV)
infection[34].

ContraceptivedevicesVaginalsponges,diaphragms,andintrauterinedeviceshavebeenassociatedwith
vulvovaginalcandidiasis,butnotconsistently.SpermicidesarenotassociatedwithCandidainfection.

BehavioralfactorsVulvovaginalcandidiasisisnottraditionallyconsideredasexuallytransmitteddisease
(STD)sinceitoccursincelibatewomenandsinceCandidaspeciesareconsideredpartofthenormalvaginal
flora.ThisdoesnotmeanthatsexualtransmissionofCandidadoesnotoccurorthatvulvovaginal
candidiasisisnotassociatedwithsexualactivity.Forexample,anincreasedfrequencyofvulvovaginal
candidiasishasbeenreportedatthetimemostwomenbeginregularsexualactivity[5,27,35].Inaddition,
partnersofinfectedwomenarefourtimesmorelikelytobecolonizedthanpartnersofuninfectedwomen,
andcolonizationisoftenthesamestraininbothpartners.However,thenumberofepisodesofvulvovaginal
candidiasisawomanhasdoesnotappeartoberelatedtoherlifetimenumberofsexualpartnersorthe
frequencyofcoitus[27,36,37].

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Thetypeofsexmaybeafactor.Infectionmaybelinkedtoorogenitaland,lesscommonly,anogenitalsex.
Evidenceofalinkbetweenvulvovaginalcandidiasisandhygienichabits(eg,douching,useof
tampons/menstrualpads)orwearingtightorsyntheticclothingisweakandconflicting[27,3845].

RecurrentvulvovaginalcandidiasisTheriskfactorsdescribedaboveareapparentinonlyaminorityof
womenwithrecurrentdisease(see'Riskfactors'above).Intheremainder,factorsthatpredisposetorecurrent
infectionlikelyinvolveabnormalitiesinlocalvaginalmucosalimmunity[46]andgeneticsusceptibility(see
'Recurrentvulvovaginalcandidiasis'above).

Theroleofsexualtransmissioninrecurrentinfectionremainsunresolved,butdoesnotappeartobeamajorfactor
asthebulkofevidencefromrandomizedtrialsdoesnotsupporttreatmentofsexualpartners[4750].

CLINICALFEATURESVulvarpruritusisthedominantfeatureofvulvovaginalcandidiasis[8,17,5153].Vulvar
burning,soreness,andirritationarealsocommon,andcanbeaccompaniedbydysuria(typicallyperceivedtobe
externalorvulvarratherthanurethral)ordyspareunia.Symptomsareoftenworseduringtheweekpriortomenses
[53].Theintensityofsignsandsymptomsvariesfrommildtosevere,exceptamongwomenwithC.glabrataorC.
parapsilosisinfection,whotendtohavemildorminimalclinicalfindings[54].

Physicalexaminationoftheexternalgenitalia,vagina,andcervixoftenrevealserythemaofthevulvaandvaginal
mucosaandvulvaredema.Vulvarexcoriationandfissuresarepresentinaboutonequarterofpatients.Therecan
belittleornodischargewhenpresent,itisclassicallywhite,thick,adherent,andclumpy(curdlikeorcottage
cheeselike)withnoorminimalodor.However,thedischargemaybethinandloose,watery,homogeneous,and
indistinguishablefromthatinothertypesofvaginitis.Thecervixusuallyappearsnormal.

DIAGNOSISThegeneraldiagnosticapproachtowomenwithvaginalcomplaintsisreviewedseparately.(See
"Approachtowomenwithsymptomsofvaginitis".)

ThediagnosisofvulvovaginalcandidiasisisbasedonthepresenceofCandidaonwetmount,Gramsstain,or
cultureofvaginaldischargeinawomanwithcharacteristicclinicalfindings(eg,vulvovaginalpruritus,burning,
erythema,edema,and/orcurdlikedischargeattachedtothevaginalsidewall)andnootherpathogenstoaccount
forhersymptoms.(See'Clinicalfeatures'above.)Becausenoneoftheclinicalmanifestationsofvulvovaginal
candidiasisispathognomonic,suspectedclinicaldiagnosisshouldalwaysbeconfirmedbylaboratorymethods.
Importantly,althoughvulvarpruritusisacardinalsymptomofthedisorder,lessthan50percentofwomenwith
genitalpruritushavevulvovaginitiscandidiasis[55].

OfficediagnosisThevaginalpHinwomenwithCandidainfectionistypicallynormal(4to4.5),which
distinguishescandidiasisfromtrichomoniasisorbacterialvaginosis(table1).Candidaspeciescanbeseenona
wetmountofthedischargeadding10percentpotassiumhydroxidedestroysthecellularelementsandfacilitates
recognitionofbuddingyeast,pseudohyphae,andhyphae(picture1andpicture2andpicture3andpicture4and
picture5andpicture6)[56].UseofSwartzLamkinsfungalstain(potassiumhydroxide,asurfactant,andbluedye)
mayfacilitatediagnosisbystainingtheCandidaorganismsbluesotheyareeasiertoidentify[57].However,
microscopyisnegativeinupto50percentofpatientswithcultureconfirmedvulvovaginalcandidiasis[16].

Microscopyisalsoimportantforlookingforcluecellsormotiletrichomonads,whichindicatebacterialvaginosis
andtrichomoniasis,respectively,asalternativediagnoses,coinfection,ormixedvaginitis[58].

RoleofcultureWerecommendnotculturingallpatientsbecausecultureisnotnecessaryfordiagnosisif
microscopyshowsyeast,anditiscostly,delaysthetimetodiagnosisbyseveraldays,andmaybepositivedue
tocolonizationratherthaninfection.

Weobtainaculturein:

Womenwithclinicalfeaturesofvulvovaginalcandidiasis,normalvaginalpH,andnopathogens(yeast,clue
cells,trichomonads)visibleonmicroscopy.Apositivecultureinthesepatientsconfirmsthediagnosisand
revealsthespeciesofCandida,thusavoidingempiric,unindicatedorincorrecttherapy.

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Womenwithpersistentorrecurrentsymptomsbecausemanyofthesewomenhavenonalbicansinfection
resistanttoazoles(see'Diagnosisofrecurrentvulvovaginalcandidiasis'below).

Toperformaculture,avaginalsampleisobtainedfromthelateralwallusingacottontippedswabandinoculated
ontoSabouraudagar,Nickerson'smedium,orMicrostixcandidamediumthesemediaperformequallywell[8].
CultureforCandidadoesnotrequirequantificationofinvitrocolonycount.SpeciationofCandidaisnotessential
forprimarydiagnostictestingasmostisolatesareCandidaalbicanshowever,speciesidentificationisessentialin
refractoryandrecurrentdisease.LaboratorytechniquesforidentificationofmultipleCandidaspeciesarereviewed
separately.(See"BiologyofCandidainfections",sectionon'Detectioninthemicrobiologylaboratory'.)

OthertestsTherearenoreliablepointofcaretestsforCandidaavailableintheUnitedStates[5964].A
DNAprobetestperformedinacentralizedlaboratoryoffersresultscomparabletoculturewithresultsavailablein
severalhours,butnospeciation(AffirmVPIII).

Polymerasechainreaction(PCR)methodshavehighsensitivityandspecificityandashorterturnaroundtime
thanculture[6568],butarecostlyandoffernoprovenbenefitovercultureinsymptomaticwomen[65].

Papsmearispositivein25percentofpatientswithculturepositive,symptomaticvulvovaginalcandidiasis[8].It
isinsensitivebecausethecellsarederivedfromthecervix,whichisnotaffectedbyCandidavaginitis.Treatment
ofCandidaonaPapsmearofanasymptomaticwomanisnotindicated(see'Treatment'below).

SelfdiagnosisSelfdiagnosisofvulvovaginalcandidiasisisfrequentlyinaccurateandshouldbediscouraged
[69,70].Inastudythatadministeredaquestionnaireto600womentoassesstheirknowledgeofthesymptoms
andsignsofvulvovaginalcandidiasis(andotherinfections)afterreadingclassiccasescenarios,only11percent
ofwomenwithoutapreviousdiagnosisofvulvovaginalcandidiasiscorrectlydiagnosedthisinfection[69].Women
whohadhadapriorepisodeweremoreoftencorrect(35percent),butwerelikelytouseoverthecounterdrugs
inappropriatelytotreatother,potentiallymoreserious,gynecologicdisorders.

Inanotherreport,theactualdiagnosesin95womenwhoselfdiagnosedvulvovaginalcandidiasiswere:
vulvovaginalcandidiasis(34percent),bacterialvaginosis(19percent),mixedvaginitis(21percent),normalflora
(14percent),trichomonasvaginitis(2percent),andother(11percent)[70].Womenwithapreviousepisodeof
vulvovaginalcandidiasisandthosewhoreadthepackageinsertfortheiroverthecountermedicationwerenot
moreaccurateinmakingadiagnosisthanotherwomen.

Someconsequencesofmisdiagnosisandinappropriatetherapyincludeadelayincorrectdiagnosisandtreatment,
wastedmonetaryexpenditure,andprecipitationofvulvardermatitis.

DiagnosisofrecurrentvulvovaginalcandidiasisRecurrentvulvovaginalcandidiasisisdefinedasfouror
moreepisodesofsymptomaticinfectionwithinoneyear[16].Vaginalculturesshouldalwaysbeobtainedto
confirmthediagnosisandidentifylesscommonCandidaspecies,ifpresent.Asdiscussedabove,recurrent
diseaseisusuallyduetorelapsefromapersistentvaginalreservoiroforganismsorendogenousreinfectionwith
identicalstrainsofsusceptibleC.albicans[19]however,rarely,anewstrainofCandidaisresponsibleforthe
infection.

TestingforHIVinfectionVulvovaginalcandidiasisoccursmorefrequentlyandhasgreaterpersistence,but
notgreaterseverity,inhumanimmunodeficiencyvirus(HIV)infectedwomenwithverylowCD4countsandhigh
viralloadhowever,thispopulationislikelytomanifestotheracquiredimmunedeficiencysyndrome(AIDS)related
sentinelconditions[34].HIVtestingofwomenonlyfortheindicationofrecurrentvulvovaginalcandidiasisisnot
justified,giventhatrecurrentCandidavaginitisisacommonconditioninwomenwithoutHIVinfectionandthe
majorityofcasesoccurinuninfectedwomen.ThemicrobiologyofvulvovaginalcandidiasisinHIVinfectedwomen
issimilartothatinHIVnegativewomen[8].

WomenwithriskfactorsforacquisitionofHIVshouldbecounseledandofferedscreening.Theseriskfactorsare
describedindetailseparately.(See"Screeningforsexuallytransmittedinfections".)

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DifferentialdiagnosisOtherconditionstobeconsideredinthedifferentialdiagnosisofvulvovaginitiswith
normalvaginalpHincludehypersensitivityreactions,allergicorchemicalreactions,andcontactdermatitis.These
conditionsarediscussedindetailelsewhere.Recognizinglocaladversereactionstotopicalagentsisimportant
otherwise,additionaltopicalagents,includinghighpotencycorticosteroids,areoftenprescribedempiricallyand
furtheraggravatesymptoms.(See"Dermatitisofthevulva".)Mechanicalirritationduetoinsufficientlubrication
duringcoituscanalsoresultinvaginaldiscomfort.

IfvaginalpHexceeds4.5orexcesswhitecellsarepresent,mixedinfectionwithbacterialvaginosisor
trichomoniasismaybepresent.Mixedinfection(2pathogensandallaresymptomatic)isestimatedtooccurin<5
percentofpatientscoinfection(2pathogensbutsomearenotsymptomatic)ismorecommon:20to30percent
ofwomenwithbacterialvaginosisarecoinfectedwithCandidaspecies[58].(See"Bacterialvaginosis"and
"Trichomoniasis".)

TREATMENTTreatmentisindicatedforreliefofsymptoms.Tento20percentofreproductiveagewomenwho
harborCandidaspeciesareasymptomaticthesewomendonotrequiretherapy[56].

Thetreatmentregimenisbasedonwhetherthewomanhasanuncomplicatedinfection(90percentofpatients)or
complicatedinfection(10percentofpatients).Criteriaarelistedinthetable(table2).Uncomplicatedinfections
usuallyrespondtotreatmentwithinacoupleofdays.Complicatedinfectionsrequirealongercourseoftherapy
andmaytaketwoweekstofullyresolve.

Treatmentofsexualpartnersisunnecessary.Thereisnomedicalcontraindicationtosexualintercourseduring
treatment,butitmaybeuncomfortableuntilinflammationimproves.

UncomplicatedinfectionCriteriaforuncomplicatedinfectionincludeallofthefollowing[17]:

Sporadic,infrequentepisodes(3episodes/year)
Mildtomoderatesigns/symptoms
ProbableinfectionwithCandidaalbicans
Healthy,nonpregnantwoman

Avarietyoforalandtopicalpreparations,manyavailableoverthecounterandinsingledoseregimens,isavailable
forthetreatmentofuncomplicatedvulvovaginalcandidiasis(table3)[71].Inrandomizedtrials,oralandtopical
antimycoticdrugsachievedcomparableclinicalcurerates,whichareinexcessof90percentshortterm
mycologiccureisslightlylower(70to80percent)[7275].Studiesthathaveassessedpatientpreference
consistentlyreportedapreferencefortheconvenienceoforaltreatment[73].However,topicaltreatmentshave
fewersideeffects(eg,possiblelocalburningorirritation),whileoralmedicationmaycausegastrointestinal
intolerance,headache,rash,andtransientliverfunctionabnormalities.Inaddition,oralmedicationstakeadayor
twolongerthantopicaltherapytorelievesymptoms.Theabsenceofsuperiorityofanyformulation,agent,orroute
ofadministrationsuggeststhatcost,patientpreference,andcontraindicationsarethemajorconsiderationsinthe
decisiontoprescribeanantifungalfororalortopicaladministration[75].

Wesuggestuseoforalfluconazole,giventhatmostwomenconsideroraldrugsmoreconvenientthanthose
appliedintravaginally.Fluconazolemaintainstherapeuticconcentrationsinvaginalsecretionsforatleast72hours
aftertheingestionofasingle150mgtablet[76].Sideeffectsofsingledosefluconazole(150mg)tendtobemild
andinfrequent.However,fluconazoleinteractswithmultipledrugstherefore,thepotentialfordruginteractions
shouldbeaddressedwhenprescribingthisagent.Sincefluconazoleisnowavailableinagenericform,asingle
doseregimenoffluconazoleislessexpensivethanoverthecountertopicalantifungals.

AzoleresistancehasonlybeenreportedinonecaseofvaginitiscausedbyC.albicans[77].Thus,invitro
susceptibilitytestsarerarelyindicatedunlesscompliantpatientswithacultureprovendiagnosishavenoresponse
toadequatetherapy.

ComplicatedinfectionsCharacteristicsofcomplicatedinfectionsincludeoneormoreofthefollowingcriteria
[17]:
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Severesigns/symptoms
CandidaspeciesotherthanC.albicans,particularlyC.glabrata
Pregnancy,poorlycontrolleddiabetes,immunosuppression,debilitation
Historyofrecurrent(4/year)cultureverifiedvulvovaginalcandidiasis

Thetreatmentofcomplicatedinfectionissummarizedinthetableanddescribedinmoredetailbelow(table4).

SeveresymptomsorcompromisedhostWomenwithsevereinflammationorhostfactorssuggestiveof
complicatedinfectionneedlongercoursesoforalortopicalantimycoticdrugs.Itisunknownwhetheronerouteis
moreeffectivethantheother,ascomparativetrialsoftopicalversusoraltreatmentofcomplicatedinfectionhave
notbeenperformed.

Giventheconvenienceoforaltherapy,wesuggestfluconazole(150mgorally)fortwotothreesequentialdoses
72hoursapartfortreatmentofcomplicatedinfections,dependingontheseverityoftheinfection(table4)[75].The
efficacyofthisapproachwassupportedbyatrialthatrandomlyassigned556womenwithsevereorrecurrent
candidiasistotherapywithasingledoseoffluconazole(150mg)ortwosequentialdosesgiventhreedaysapart
[78].Severityofdiseasewasbaseduponascoringsysteminvolvingdegreeofpruritusandphysicalsigns
(erythema,edema,excoriation/fissureformation).Thetwodoseregimenresultedinsignificantlyhigherclinical
cure/improvementratesatevaluationonday14(94versus85percent)andday35(80versus67percent)in
womenwithsevere,butnotrecurrent,disease.However,theresponsetotherapywaslowerinthe8percentof
womeninfectedwithnonalbicansCandida.

Ifthepatientpreferstopicaltherapy,observationalseriesreportthatcomplicatedpatientsrequire7to14daysof
topicalazoletherapy(eg,clotrimazole,miconazole,terconazole)ratherthanaonetothreedaycourse[75,79].

ForsevereCandidavulvarinflammation(vulvitis),lowpotencytopicalcorticosteroidscanbeappliedtothevulva
for48hoursuntiltheantifungalsexerttheireffect.

C.glabrataC.glabratahaslowvaginalvirulenceandrarelycausessymptoms,evenwhenidentifiedby
culture.EveryeffortshouldbemadetoexcludeothercoexistentcausesofsymptomsandonlythentreatforC.
glabratavaginitis.Treatmentfailurewithazolesiscommon(around50percent)inpatientswithC.glabrata
vaginitis[54].Moderatesuccess(65to70percent)inwomeninfectedwiththisorganismcanbeachievedwith
intravaginalboricacid(600mgcapsuleoncedailyatnightfortwoweeks)[54,80].Betterresults(>90percentcure)
havebeenachievedwithintravaginalflucytosinecream(5gnightlyfortwoweeks)[80].Neitherboricacid
capsulesnorflucytosinecreamisavailablecommerciallyandmustbemadebyacompoundingpharmacy.Boric
acidcapsulescanbefatalifswallowed.

TherearenogooddataregardinguseoforalvoriconazoleforC.glabratavaginitis.Anecdotalreportssuggestpoor
responseandrarecures,andthepotentialfortoxicity.

Therearealsonogooddataontheefficacyofnystatin,whichisavailableasapessaryinsomepartsoftheworld.
Oneortwopessariesof100,000unitsnystatinareinsertedintothevaginanightlyfor14days[81].Alternatively,a
suppositorycanbepreparedbyacompoundingpharmacy.Potentialsideeffectsincludeburning,redness,and
irritation.

C.kruseiCandidakruseiisusuallyresistanttofluconazole,butishighlysusceptibletotopicalazole
creamsandsuppositories,suchasclotrimazole,miconazole,andterconazole.Wetreatfor7to14days.Itisalso
likelytorespondtooralitraconazoleorketoconazole,buttheseoralagentshavevariabletoxicitysotopical
therapyisadvisedforfirstlinetherapy.Idiosyncratichepatotoxicitysecondarytoketoconazoletherapyisa
concern,butrareinthissetting.Invitrosusceptibilitytestingisindicatedincompliantpatientswithcultureproven
diagnosisofC.kruseiandnoresponsetoaconventionalcourseofoneofthesenonfluconazoletherapies.

PregnancyTreatmentofpregnantwomenisprimarilyindicatedforreliefofsymptoms.Vaginalcandidiasis
isnotassociatedwithadversepregnancyoutcomes[82].Wesuggestapplicationofatopicalimidazole
(clotrimazoleormiconazole)vaginallyforsevendays[79,83].Thereislessinformationaboutthepregnancysafety
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profileofterconazole,atriazole,thanforimidazoles.Vaginalnystatinisanotheroption.Asdiscussedabove,a
pessaryisavailableinsomepartsoftheworld.Oneortwopessariesof100,000unitsnystatinareinsertedinto
thevaginanightlyfor14days[81].Alternatively,asuppositorycanbepreparedbyacompoundingpharmacy.
Potentialsideeffectsincludeburning,redness,andirritation.

Administrationoforalazolesduringthefirsttrimesterisnotrecommended,ascasereportshavedescribeda
patternofbirthdefects(abnormalitiesofcranium,face,bones,andheart)afterfirsttrimesterexposuretohighdose
therapy(400to800mg/day)[84,85].Themagnitudeoftheteratogenicriskisunknown.Firsttrimesteruseofa
single,lowdoseoffluconazole150mgtotreatvaginalyeastinfectionhasnotbeenassociatedwithanincreased
riskofbirthdefectsoverallinonelargeepidemiologicstudy(7352pregnancies)[86]andinseveralsmaller
epidemiologicstudies[8792].Inthelargenationwidecohortstudy,therewasnooverallriskofembryopathy
associatedwithexposuretocumulativefluconazoledosesof150,300,or350to6000mgduringthefirsttrimester
norwithexposuretooralitraconazoleorketoconazole[86].Althoughthesedataarereassuringforwomenwho
tookfluconazolebeforerealizingthattheywerepregnant,anincreasedriskofspecificanomaliescannotbe
definitivelyexcluded.Sincevaginaladministrationisaneffectivealternativetooraladministration,thevaginal
routeispreferabletotheoralrouteinpregnancy,especiallythefirsttrimester,untilmoredataareavailable
supportingthesafetyoflowdoseoraladministration.

AlthoughtreatmentofvaginalCandidacolonizationinhealthypregnantwomenisunnecessary,inGermany
treatmentisrecommendedinthethirdtrimesterbecausetherateoforalthrushanddiaperdermatitisinmature
healthynewbornsissignificantlyreducedbymaternaltreatment[55].

RecurrentinfectionThetreatmentofwomenwithrecurrentinfectionscanbedifficultandfrustrating[93].
Recurrentvulvovaginalcandidiasisisdefinedasfourormoreepisodesofsymptomaticcandidalvaginitisina12
monthperiod[79,93].Attemptsshouldbemadetoeliminateorreduceriskfactorsforinfectionifpresent(eg,
improveglycemiccontrol,switchtolowerestrogendoseoralcontraceptive).Althoughnotbasedupondatafrom
randomizedtrials,implementingachangeinoneormorebehavioralfactors(eg,avoidanceofpantyliners,
pantyhose,cranberryjuice,sexuallubricants)toseeifthereisimprovementmaybebeneficialinrarewomen[38].
Managementofsexualdysfunctionandthemaritaldiscordthatfrequentlyaccompanychronicvaginitisshouldalso
beaddressed.

DecreasinggastrointestinalCandidacolonizationbyoraladministrationofnystatindoesnotpreventrecurrent
symptomaticvaginalinfection[16].

AzolesRandomizedtrialscomparingdifferenttherapeuticregimenshavenotbeenperformed.Basedon
thedatacitedbelowandpersonalexperience,webelievethattheoptimaltherapyforrecurrentvulvovaginal
candidiasisinnonpregnantwomenconsistsofinitialinductiontherapywithfluconazole150mgevery72hoursfor
threedoses,followedbymaintenancefluconazoletherapyonceperweekforsixmonths[94].Therapyisthen
discontinued,atwhichpointsomepatientsachieveaprolongedremission,whileothersrelapse.Ashortterm
relapse,withcultureconfirmationofthediagnosis,meritsreinductiontherapywiththreedosesoffluconazole,
followedbyrepeatweeklymaintenancefluconazoletherapy,thistimeforoneyear.Aminorityofwomenpersistin
relapsingassoonasfluconazolemaintenanceiswithdrawn(fluconazoledependentrecurrentvulvovaginal
candidiasis).Symptomsinthesepatientscanbecontrolledbymonthsoryearsofweeklyfluconazole.

Giventhesafetyprofileoflowdosefluconazole,mostexpertsdonotsuggestanylaboratorymonitoringhowever,
ifotheroralimidazoles(ketoconazole,itraconazole)areused,particularlyiftakendaily,thenmonitoringliver
functiontestsisrecommended.Idiosyncratichepatotoxicitysecondarytoketoconazoletherapyisaconcern,but
rareinthissetting.

Althoughdruginteractionsarereportedwithfluconazoleandseveraloralagents(eg,warfarin,rifampin),such
interactionsareextremelyunlikelywithmaintenancefluconazoleduetothelowplasmaconcentrations
accompanyingtheonceweekly150mgdosingregimen.Accordingly,noadditionaltestingneeded.

Alternativeapproachesthathavebeensuggestedinclude:

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Treateachrecurrentepisodeasanepisodeofuncomplicatedinfection(table3)[79]

Treateachrecurrentepisodewithlongerdurationoftherapy(eg,topicalazolefor7to14daysorfluconazole
150mgorallyonday1,day4,andday7)[79]

TheInfectiousDiseasesSocietyofAmerica(IDSA)recommends10to14daysofinductiontherapywitha
topicalororalazole,followedbyfluconazole150mgonceperweekforsixmonths(clotrimazole200mg
vaginalcreamtwiceweeklyisanonoralalternative)[75].

EvidenceforsuppressivetherapyMultipleobservationalstudiesofnonpregnantwomenwith
recurrentvulvovaginalcandidiasishaveshownthatantifungalmaintenancesuppressivetherapytakenforsix
monthsafteraninitialinductionregimenresultedinnegativecultures[72,95].Thebestavailableoptionin
nonpregnantwomenisfluconazole150mgorallyonceperweekforsixmonths[75].However,maintenance
therapyisonlyeffectiveforpreventingrecurrentinfectionaslongasthemedicationisbeingtaken.Thiswas
illustratedinatrialof387womenwithrecurrentvulvovaginalcandidiasistreatedwithopenlabelfluconazole(150
mgorallyat72hourintervalsforthreedoses)andthenrandomlyassignedtoweeklydosesoffluconazole(150
mg)orplaceboforsixmonths[94].Themaintenancetherapyphasewasbeguntwoweeksafterinitiationof
treatmentinpatientswhowereclinicallycured.Studydrugswerediscontinuedinpatientsdiagnosedwithrecurrent
candidalinfectionduringfollowupvisits.

Theproportionofwomenwhoremaineddiseasefreewassignificantlyhigherinthefluconazolegroup(91
versus36percentat6months,73versus28percentat9months,and43versus22percentat12months).

Themeantimetorecurrenceinthefluconazoleandplacebogroupswas10.2and4.0months,respectively.

ResistantisolatesofC.albicansorsuperinfectionwithC.glabratawerenotobserved.

Althoughthisregimenofmaintenancefluconazolewasconvenient,safe,andaseffectiveasothertherapies,long
termcureofrecurrentvulvovaginalcandidiasiswasnotachievedinonehalfofthewomenstudied.Episodesof
recurrentcandidiasisresumedwhenmaintenancetherapywasdiscontinued.

FluconazoleresistanceInwomenwithrecurrentvulvovaginalcandidiasis,thereissomeevidence
thatfrequentandprolongeduseoffluconazolecaninfrequentlyselectforfluconazoleresistanceinC.albicans
strainspreviouslysusceptibletofluconazole,whichlimitstheoptionsavailablefortreatingthesewomen.Ina
studyof25womenwithrefractoryCandidavaginitisandaC.albicansisolatewithfluconazoleminimuminhibitory
concentration(MIC)2micrograms/mL,thosewithfluconazoleMICvaluesof2or4micrograms/mLweretreated
successfullybyincreasingfluconazoledosageto200mgtwiceweekly[96].Intheauthorsexperience,ahigher
doseoffluconazolewasnoteffectiveforwomenwithMIC8micrograms/mL.Thesewomenshouldbeevaluated
forcrossresistancetoitraconazoleandketoconazole,assomepatientscanbetreatedeffectivelywithlongterm
maintenancedailyimidazoletherapy.However,useofitraconazoleorketoconazolerequiresintermittenthepatic
functiontesting.Idiosyncratichepatotoxicitysecondarytoketoconazoletherapyisaconcern,butrareinthis
setting.

Womenwithsevererecurrentvulvovaginalcandidiasisinfectionandhighlevelpanazoleresistancedonothave
optionsotherthantopicalboricacid(see'Boricacid'below)ornystatinsuppositories[97].

InwomenwithrefractoryvulvovaginalcandidiasiswithpersistentlypositiveC.albicanscultures,MICstovarious
antifungalscanbetestedbyusingthebrothmicrodilutionmethodconductedinaccordancewithClinicaland
LaboratoryStandardsInstitution(CLSI)criteriaandbreakpoints[98].(See"Antifungalsusceptibilitytesting".)

ProbioticsThereisnoevidencethatwomenwithrecurrentvulvovaginalcandidiasishavevaginalflora
deficientinlactobacilli,andthereforewedonotrecommenduseofprobioticlactobacilli[11,12].Althoughthereisa
popularbeliefthatingestionorvaginaladministrationofyogurtorotheragentscontaininglivelactobacillidecreases
therateofcandidalcolonizationandsymptomaticrelapse,thefewstudiesinthisareahaveanumberof
methodologicflaws(eg,nocontrolgroup,shortfollowup)andsmallnumbersofsubjects[99103].Thevalueof

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administeringlivelactobacillitowomenwithrecurrentinfectionhasbeenrefutedinotherstudies[38,104]andthis
approachshouldbeconsideredunproven.ThequalityofprobioticsvariesworldwideintheUnitedStatesthese
productsarenotstandardizedandoftenofpoorquality.TheUSFoodandDrugAdministrationhascautioned
againstusingprobioticswithbacteriaoryeastinimmunocompromisedpatients[105].

GentianvioletTopicalgentianvioletwaswidelyusedpriortotheavailabilityofthetopicalazole
intravaginalantifungalcreamsandsuppositories.Useofthisagenthaslargelybeenabandonedbecauseazole
antimycoticsaremoreeffective(potent)andbecauseitismessyandinconvenient(eg,itpermanentlystains
clothes).However,itisusefulasavulvarantipruriticandforoccasionalrefractorycasesofvulvovaginal
candidiasis,especiallythosedemonstratingazoleresistance[106].Thedrugisappliedtoaffectedareasofthe
vulvaandvaginadailyfor10to14days.

BoricacidWebelieveboricacidhasnoroleintreatmentofrecurrentvulvovaginitisduetoC.albicans,
unlessazoleresistanceisdemonstratedbyinvitrotests[107].Therearenosafetydataonlongtermuseofboric
acid,whichcausessignificantlocalirritationandhasthepotentialfortoxicity(includingdeath)ifingestedby
accident.Acourseofboricacid(600mgintravaginalboricacidvaginalsuppositoriesdailyfortwoweeks)should
beconsideredonlyincasesofprovenazoleresistantinfectionthesecasesarerare.

ImmunotherapyLocalvaginalhypersensitivitytoC.albicanshasbeenproposedasthecauseof
recurrentinfectioninsomewomen[108].Immunotherapyofcandidalvaginitisforbothpreventionandtreatmentis
atherapeuticapproachunderinvestigation[109].Aprophylacticvaccinewouldneedtoinduceahostimmune
responseagainstfungalvirulencetraitswithoutalteringthetolerance/inflammationbalanceofthevaginal
environment,whereasatherapeuticvaccineindicatedforwomenwithrecurrentvulvovaginalcandidiasiscould
enhanceorrectifytolerance/inflammationimbalanceinthevagina[110].Twovaccinesareindevelopment.

AllergytofluconazoleTheincidenceoffluconazoleallergyinwomenwithacuteCandidavaginitisis
unknown,butuncommon.Theauthorhasseenpatientswithallergicsymptoms,varyingfromrashto,
occasionally,angioedema.Itisimportanttorecognizethatfluconazoleisonememberoftheazoleclassofdrugs
anditisdifficulttodistinguishbetweenpatientswithallergytofluconazolealoneversusthosewithallergytothe
entireazoleclass.Therefore,otheroralazolessuchasketoconazole(Nizoral)oritraconazole(Sporanox)should
notbeprescribedtopatientswithtruefluconazoleallergy.However,patientswithfluconazoleallergycanreceive
topicalazoles,suchasmiconazoleorclotrimazole.Forthosepatientswithfluconazoleallergymanifestedby
angioedemaorsevererash,theauthorhasresortedtouseoftopicalagentsinsteadofweeklyfluconazole150mg.
Bothmiconazoleandclotrimazolecanbeprescribedonaonceweeklyhighdoseregimen,500to1500mg,
dependingonthedosecommerciallyavailablelocally.Otheroptionsincludenystatinpervagina100,000unitsdaily
for7daysforacutevaginitisorboricacidpervaginafor7days.Discussionwithanallergistisrecommended.
Therearenodataontheefficacyoffluconazoledesensitization,whichistheoreticallypossible.

TreatmentofpartnersAlthoughsexualtransmissionofCandidaspeciescanoccur,mostexpertsdonot
recommendtreatmentofsexualpartnerssincesexualactivityisnotasignificantcauseofinfectionorreinfection.
Althoughthebulkofevidencefromrandomizedtrialsdoesnotsupporttreatmentofsexualpartners[4750],in
womanwithrecurrentvulvovaginitis,thisissueremainscontroversial.

Treatmentofsymptomaticmenisreviewedseparately.(See"Balanitisandbalanoposthitisinadults".)

BreastfeedingwomenNystatindoesnotenterbreastmilkandiscompatiblewithbreastfeeding.Fluconazole
isexcretedinhumanmilk,buttheAmericanAcademyofPediatrics(AAP)considerstheuseoffluconazole
compatiblewithbreastfeeding[111],asnoadverseeffectshavebeenreportedinbreastfedinfantsorinfants
treatedwithparenteralfluconazole[112].Thereisnoinformationontheeffectofmiconazole,butoconazole,
clotrimazole,tioconazole,orterconazoleonnursinginfants,butsystemicabsorptionaftermaternalvaginal
administrationisminimal,hencetopicaluseinnursingmothersisreasonable.

PostcoitalhypersensitivityreactioninmalepartnerInavariantsyndrome,malepartnersofwomenwith
vaginalCandidacolonizationdevelopimmediatepostcoitalitchingandburningwithrednessandarashofthe

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penis.ThispostcoitalsyndromeprobablyrepresentsanacutehypersensitivityreactiontoCandidaorganismsor
antigensinthepartner'svagina,evenintheabsenceofsymptomaticvulvovaginitis.

Maleswithrecurrentpostcoitalsymptomsdonotbenefitfromtopicalantimycotictherapysincethekeyto
eradicatingsymptomsliesineliminatingCandidaorganismsfromthelowergenitaltractofthefemalesexual
partner.Thisoftenrequiresthefemalepartnertofollowalongtermmaintenanceantimycoticregimen.

Apostcoitalshowerandapplicationofatopicallowpotencycorticosteroidtothepenismayprovidesymptomatic
reliefwithin12to24hours.PenileculturesmayremainpositiveforCandidadespitenormalphysicalfindings.

PREVENTIONAsdiscussedabove,oralnystatindoesnotpreventvaginalcandidiasisandlactobacillus(oralor
vaginal)doesnotpreventpostantibioticvulvovaginitis.Inwomensusceptibletosymptomaticyeastinfections
whentakingantibiotictherapy,adoseoffluconazole(150mgorally)atthestartandendofantibiotictherapymay
preventpostantibioticvulvovaginitis[8].

COMPLEMENTARYANDALTERNATIVEMEDICINEThereisnoevidencefromrandomizedtrialsthat
garlic,teatreeoil,yogurt(orotherproductscontainingliveLactobacillusspecies),ordouchingiseffectivefor
treatmentorpreventionofvulvovaginalcandidiasisduetoCandidaalbicans[113].

INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,TheBasicsand
BeyondtheBasics.TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6thgrade
readinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.These
articlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.Beyond
theBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewritten
atthe10thto12thgradereadinglevelandarebestforpatientswhowantindepthinformationandarecomfortable
withsomemedicaljargon.

Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthese
topicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingon
patientinfoandthekeyword(s)ofinterest.)

Basicstopics(see"Patientinformation:Vulvovaginalyeastinfection(TheBasics)"and"Patientinformation:
Vulvaritching(TheBasics)")

BeyondtheBasicstopics(see"Patientinformation:Vaginalyeastinfection(BeyondtheBasics)")

SUMMARYANDRECOMMENDATIONS

Candidaisconsideredpartofthenormalvaginalflora,butovergrowthoftheorganismandpenetrationof
superficialepithelialcellscanresultinvulvovaginitis.Candidaalbicansaccountsfor80to92percentof
episodesofvulvovaginalcandidiasisCandidaglabrataisthenextmostcommonspecies.(See'Prevalence'
aboveand'Microbiology'aboveand'Pathogenesis'above.)

Vulvarpruritusisthedominantsymptom.Vulvarburning,soreness,andirritationarecommonandmayresult
indysuriaanddyspareunia.Thevulvaandvaginaappearerythematous,andvulvarexcoriationandfissures
maybepresent.Thereisoftenlittleornodischargewhenpresent,itisclassicallywhite,thick,adherent,
andclumpy(curdlikeorcottagecheeselike)withnoorminimalodor.(See'Clinicalfeatures'above.)

ThediagnosisofvulvovaginalcandidiasisisbasedonthepresenceofCandidaonwetmount,Gramsstain,
orcultureofvaginaldischargeinawomanwithcharacteristicclinicalfindings.(See'Officediagnosis'above.)

Cultureisnotnecessaryfordiagnosisifmicroscopyshowsyeast,butshouldbeobtainedin(see'Roleof
culture'above):

Womenwithclinicalfeaturesofvulvovaginalcandidiasis,normalvaginalpH,andnegativemicroscopy.

Womenwithpersistentorrecurrentsymptomsbecausemanyofthesewomenhavenonalbicans

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infectionresistanttoazoles.

Treatment

Treatmentisindicatedtorelievesymptoms.Asymptomaticwomenandsexualpartnersdonotrequire
treatment.(See'Treatment'aboveand'Treatmentofpartners'above.)

Thetreatmentregimenisbasedonwhetherthewomanhasanuncomplicatedinfection(90percentof
patients)orcomplicatedinfection(10percentofpatients).Criteriaarelistedinthetable(table2).(See
'Treatment'above.)

UncomplicatedinfectionsOralandtopicalantimycoticdrugsachievecomparableclinicalcurerates,which
areinexcessof80percentinuncomplicatedinfection(table3).(See'Uncomplicatedinfection'above.)

Wesuggestasingledoseoforalfluconazole(150mg)fortreatmentofuncomplicatedinfectionsratherthan
multidoseandtopicalregimens(Grade2C).(See'Uncomplicatedinfection'above.)

ComplicatedinfectionsWomenwithcomplicatedinfectionrequirelongercoursesoftherapythanwomen
withuncomplicatedinfection.(See'Complicatedinfections'above.)

Forwomenwithseveresymptoms,wesuggestfluconazole(150mg)intwosequentialdosesgiventhree
daysapartratherthantopicalantimycoticagents(Grade2C).(See'Severesymptomsorcompromisedhost'
above.)

FortreatmentofC.glabrata,wesuggestintravaginalboricacid(600mgcapsuleoncedailyatnightfortwo
weeks)ratherthananazole,boricacid,orflucytosinecream(Grade2C).(See'C.glabrata'above.)

Forpregnantwomen,wesuggestatopicalimidazole(clotrimazole,miconazole)vaginallyforsevendays
ratherthananystatinpessaryoranoralazole(Grade2C).Casereportshavedescribedapatternofbirth
defects(abnormalitiesofcranium,face,bones,andheart)afterfirsttrimesterexposuretohighdoseoral
azoletherapy(400to800mg/day).(See'Pregnancy'above.)

Forwomenwithrecurrentvulvovaginitis(4episodes/year),wesuggestsuppressivemaintenancetherapy
ratherthantreatmentofindividualepisodes(Grade2B).Weprescribeinitialinductiontherapywith
fluconazole150mgevery72hoursforthreedoses,thenmaintenancefluconazole150mgonceperweekfor
sixmonths.Womenwithrecurrentinfectionshouldtrytoeliminateorreduceriskfactorsforinfection.(See
'Recurrentinfection'above.)

UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.

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2/11/2015 Candidavulvovaginitis

GRAPHICS

Clinicalfindingsinwomenwithvaginitis

Normal Vulovaginal Bacterial

Parameter Trichomoniasis
findings candidiasis vaginosis
Symptoms Noneormild, Pruritus, Malodorous Malodorous
transient soreness, discharge,no discharge,burning,
dyspareunia dyspareunia postcoitalbleeding,
dyspareunia,dysuria

Signs Normalvaginal Vulvarerythema Offwhite/gray Thingreenyellow

discharge and/oredema. thindischarge discharge,
consistsof1to Dischargemay thatcoatsthe vulvovaginal
4mLfluid(per bewhiteand vagina erythema
24hours), clumpyandmay
whichiswhite ormaynot
ortransparent, adheretovagina.
thinorthick,
andmostly
odorless

VaginalpH 4.0to4.5 4.0to4.5 >4.5 5.0to6.0

Aminetest Negative Negative Positive(in70 Oftenpositive

80percentof
patients)

Saline PMN:ECratio PMN:ECratio PMN:EC<1loss PMN++++mixed

microscopy <1rods <1rods ofrods floramotile
dominate dominate increased trichomonads
squames+++ squames+++ coccobacilliclue (presentinabout60
pseudohyphae cellscompriseat percentofpatients)
(presentinabout least20percent
40percentof ofepithelialcells
patients) (presentin>90
buddingyeastfor percentof
nonalbicans patients)
Candida

10percent Negative Pseudohyphae Negative Negative

potassium (inabout70
hydroxide percentof
microscopy patients)

Othertests Ifmicroscopy Quantitative Ifmicroscopy

nondiagnostic: Gramstain(eg, nondiagnostic:
Culture Nugentcriteria, Culture(eg,InPouch
Hay/Ison TVculturesystem)
DNA
criteria)
hybridization Rapidantigentest
probe(eg,Affirm DNA (eg,OSOM
VPIII) Hybridization TrichomonasRapid
probe(eg,Affirm
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2/11/2015 Candidavulvovaginitis

VPIII) Test)
Cultureofno Nucleicacid
value amplificationtest
(eg,APTIMA
Trichomonas
vaginalistest)

DNAHybridization
probe(eg,AffirmVP
III)

Differential Physiologic Contactirritant ElevatedpHin Purulentvaginitis,

diagnosis leukorrhea orallergicvulvar trichomoniasis, desquamative
dermatitis, atrophic inflammatory
chemical vaginitis,and vaginitis,atrophic
irritation,focal desquamative vaginitis,erosive
vulvitis inflammatory lichenplanus
(vulvodynia) vaginitis

PMN:polymorphonuclearleukocytesEC:vaginalepithelialcells.

Graphic68759Version10.0

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2/11/2015 Candidavulvovaginitis

Candidaalbicansvaginitis

Lowpowermicrographofhyphalelementsseenon10percentKOH
examinationofapatientwithC.albicansvaginitis.

CourtesyofJackDSobel,MD.

Graphic59030Version3.0

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2/11/2015 Candidavulvovaginitis

Buddingyeast

BuddingyeastrepresentingC.glabrata.

Graphic61326Version2.0

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2/11/2015 Candidavulvovaginitis

BuddingcellsofCandidaspecies

Candidaalbicans,C.krusei,C.parapsilosisandC.tropicalisallform
ellipticalbuddingcellsthattypicallyarelargerinsizethanthoseofC.
glabrata.Elaboratemulticellularfilaments,particularlywhenin
contactwithasolidsubstratesuchasmucosalmembranesoragar
culturemedia.

CourtesyofWileySchell,MS.

Graphic53369Version3.0

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2/11/2015 Candidavulvovaginitis

Candidapseudohyphae

Pseudohyphae(asopposedtotruehyphae)areformedwhenbuds
elongatewithdifferentialratesofwallsynthesisatvariouspoints
alongthecellwall.Elongationthenstops,andthecellproducesanew
apicalbudwhichelongates.Thisrepeatedprocessofbuddingand
elongationcanresultinextensivefilamentation.Sidebranches
initiateasbudsanddevelopinthesamemanner.Inmostcases,a
constrictionremainsandcanbeseenattheoriginofeachbud.

CourtesyofWileySchell,MS.

Graphic80723Version2.0

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2/11/2015 Candidavulvovaginitis

TruehyphaeofCandidaalbicans

Truehyphae(asopposedtopseudohyphae)elongatethrougha
processofapicalsynthesisthatdoesnotinvolvebudding.Sincebuds
arenotpresentatthehyphaltips,thehyphaedonotexibitperiodic
constrictionsassociatedwiththebuddingprocess.

CourtesyofWileySchell,MS.

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2/11/2015 Candidavulvovaginitis

Candidaglabrata

Candidaglabratagrowsasasmall,elliptical,budding,unicellular
yeast.Budsrarelyadheretooneanotherinrudimentarychains,but
filamentousgrowthdoesnotoccur.

CourtesyofWileySchell,MS.

Graphic61641Version3.0

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2/11/2015 Candidavulvovaginitis

Classificationofcandidalvaginitis

Uncomplicated
Variable Complicateddisease
disease*
Symptomseverity Mildormoderate Severe

Frequency Sporadic Recurrent

Organism Candidaalbicans Nonalbicansspecies

Host Normal Abnormal(eg,uncontrolleddiabetesmellitus,

recurrentinfections,immunosuppression)

*PatientsmusthaveALLofthesefeatures.
PatientsmayhaveANYofthesefeatures.

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2/11/2015 Candidavulvovaginitis

Treatmentofuncomplicatedvaginalcandidiasis

Requiresa
Drugandtrade Intravaginal*
prescriptionin Preparation
name(s) doseforadult
US

Clotrimazole

GyneLotrimin No 1percentcream 1applicatorful(~5g)

dailyfor7days

GyneLotrimin3 No 2percentcream 1applicatorful(~5g)

dailyfor3days

GyneLotrimin Notapplicable(not 100mgvaginal Insert1vaginaltablet

availableinUS) tablet dailyfor7daysor2
tabletsdailyfor3days

Miconazole

Monistat7 No 2percentcream 1applicatorful(~5g)

dailyfor7days
(combinationkitmay
include2percent
miconazolecreamfor
externaluse)

Monistat3 No 4percentcream 1applicatorful(~5g)

dailyfor3days

Monistat7 No 100mgvaginal 1suppositorydailyfor

suppository 7days

Monistat3 , No(combinationkit) 200mgvaginal 1suppositorydailyfor

Vagistat3 suppository 3days
Yes(generic
(combinationkitmay
suppository)
include2percent
miconazolecreamfor
externaluse)

Monistat1 No 1200mgvaginal 1suppositoryfor1day

suppository
(combinationkitmay
include2percent
miconazolecreamfor
externaluse)

Nystatin

Nystatinvaginal Notapplicable(not 100,000unitvaginal Insert1vaginaltablet

(formerUStrade availableinUS) tablet dailyfor14days
nameMycostatin)

Terconazole

Terazole7,Zazole Yes 0.4percentcream 1applicatorful(~5g)

dailyatbedtimefor7
days

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2/11/2015 Candidavulvovaginitis

Terazole3,Zazole Yes 0.8percentcream 1applicatorful(~5g)

dailyatbedtimefor3
days

Terazole3,Zazole Yes 80mgvaginal 1suppositorydailyat

suppository bedtimefor3days

Tioconazole

Vagistat1,1Day No 6.5percentointment 1applicatorful(~5g)

(fromMonistat) atbedtimeasasingle
dose

Butoconazole

Gynazole1 Yes 2percentcream 1applicatorful(~5g)

asasingledose

FluconazoleORALADMINISTRATION

Diflucan Yes 150mgoraltablet Singledosebymouth

Therearenosignificantdifferencesinefficacyamongtopicalandsystemicazoles(curerates
>80percentforuncomplicatedvulvovaginalcandidiasis).

g:grams.
*Exceptfluconazole(oraladministration).
Genericequivalentpreparation(s)areavailableinUS.
NotavailableinUS.
Cureratewithnystatinis70to80percent.
Itraconazoleisanotheroralantifungalthatappearstobeeffective.PitsouniE,etal.AmJObstet
Gynecol2008198:153.
Rarecasesofanaphylaxisandtoxicepidermalnecrolysishavebeenreportedduringterconazole
therapy.

Datafrom:LexicompOnline.Copyright19782015Lexicomp,Inc.AllRightsReserved.

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2/11/2015 Candidavulvovaginitis

Treatmentofcomplicatedvaginalcandidiasis

Severevaginitissymptoms
Oralfluconazole150mgevery72hoursfor2or3doses(dependingonseverity)

OR

Topicalazoleantifungaltherapydailyfor7to14days.Alowpotencytopicalcorticosteroidcanbe
appliedtothevulvafor48hourstorelievesymptomsuntiltheantifungaldrugexertsitseffect.

Recurrentvulvovaginalcandidiasis
Inductionwithfluconazole150mgevery72hoursfor3doses,followedbymaintenance
fluconazole150mgonceperweekfor6months.

Iffluconazoleisnotfeasible,optionsinclude10to14daysofatopicalazoleoralternateoralazole
(eg,itraconazole)followedbytopicalmaintenancetherapyfor6months(eg,clotrimazole200mg
[eg,10gramsof2percent]vaginalcreamtwiceweeklyor500mgvaginalsuppositoryonce
weekly).

NonalbicansCandidavaginitis
Therapydependsuponspeciesidentified:

C.glabrata:Intravaginalboricacid*600mgdailyfor14days

Iffailureoccurs:17percenttopicalflucytosinecream,5gramsnightlyfor14days

C.krusei:Intravaginalclotrimazole,miconazole,orterconazolefor7to14days

Allotherspecies:Conventionaldosefluconazole

Compromisedhost(eg,poorlycontrolleddiabetes,immunosuppression,
debilitation)andCandidaisolatesusceptibletoazoles
Oralortopicaltherapyfor7to14days

Pregnancy
Topicalclotrimazoleormiconazolefor7days

Boricacidcapsulesandflucytosinecreamarenotcommerciallyavailable,butcanbemadeby
acompoundingpharmacy.

*Boricacidcapsulescanbefatalifswallowed.

Reference:
1. PappasPG,KauffmanCA,AndesD,etal.Clinicalpracticeguidelinesforthemanagementof
candidiasis:2009updatebytheInfectiousDiseasesSocityofAmerica.ClinInfectDis2009
48:503.

Graphic50932Version8.0

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2/11/2015 Candidavulvovaginitis

Disclosures
Disclosures:JackDSobel,MDNothingtodisclose.RobertLBarbieri,MDNothingtodisclose.CarolAKauffman,MDNothingto
disclose.KristenEckler,MD,FACOGNothingtodisclose.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseareaddressedbyvettingthrougha
multilevelreviewprocess,andthroughrequirementsforreferencestobeprovidedtosupportthecontent.Appropriatelyreferenced
contentisrequiredofallauthorsandmustconformtoUpToDatestandardsofevidence.
Conflictofinterestpolicy

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