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AHAGuidelinesonPreventionofRheumaticFeverandDiagnosis
andTreatmentofAcuteStreptococcalPharyngitis
CARRIEARMSTRONG
AmFamPhysician.2010Feb181(3):346359.
Guidelinesource:AmericanHeartAssociation
Literaturesearchdescribed?No
Evidenceratingsystemused?Yes
Publishedsource:Circulation,March24,2009
Availableat:http://circ.ahajournals.org/content/vol119/issue11(http://circ.ahajournals.org/content/vol119/issue11)
AlthoughtheoverallincidenceofacuterheumaticfeverandrheumaticheartdiseaseislowinmostareasoftheUnitedStates,theyaretheleadingcausesof
cardiovasculardeathduringthefirstfivedecadesoflifeindevelopingcountries.Thisdisparityservesasareminderoftheimportanceofcontinuedvigilanceto
preventthesediseases.TheAmericanHeartAssociation(AHA)recentlyupdateditsrecommendationsonthepreventionofrheumaticfever.
PrimaryPreventionofRheumaticFever
GroupAstreptococcus(GAS)infectionsofthepharynxaretheprecipitatingcauseofrheumaticfever.ProperdiagnosisandadequateantibiotictreatmentofGAS
infectionscanpreventacuterheumaticfeverinmostcases.
DIAGNOSISOFSTREPTOCOCCALPHARYNGITIS
Acutepharyngitisiscausedmuchmoreoftenbyvirusesthanbybacteria.However,differentiationofGASpharyngitisfromothercausesofacutepharyngitisis
oftendifficultbecausenoneoftheclinicalfindingssuggestiveofGASinfectionisspecificenoughonitsownfordiagnosis(Table1).Ahistoryofrecentexposureis
helpfulinmakingthediagnosis,asisanawarenessoftheprevalenceofGASinfectionsinthecommunity.
View/PrintTable
Tale1.
GASvs.ViralPharyngitis:ClinicalandEpidemiologicFindings
FeaturessuggestiveofGASinfection
Beefy,swollen,reduvula
Fever
Headache
HistoryofexposuretoGAS
Nausea,vomiting,andabdominalpain
Painwithswallowing
Patient5to15yearsofage
Presentationinwinterorearlyspring(intemperateclimates)
Scarletfeverrash
Softpalatepetechiae(doughnutlesions)
Suddenonsetofsorethroat
Tender,enlargedanteriorcervicalnodes
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IfclinicalandepidemiologicfindingssuggestGASinfection,microbiologicconfirmationwithathroatcultureorrapidantigendetectiontest(RADT)isrequired.The
diagnosisofGASpharyngitisismoreeasilyexcludedthanconfirmed,sotestingusuallyisunnecessaryinpatientswithfindingssuggestiveofaviralorigin.
TreatmentisindicatedforpatientswithacutepharyngitiswhohaveapositivethroatcultureorRADT.However,becauseofthelowsensitivityofmanyRADTs,a
negativetestdoesnotexcludeGASinfection,andathroatcultureusuallyshouldbeperformed.Theexceptionisinadults,inwhomtheincidenceofGAS
pharyngitisandtheriskofacuterheumaticfeverarelow.Inthispopulation,diagnosisofGASpharyngitiscanbemadeonthebasisofanRADTalone,without
confirmationofnegativeresultsbyathroatculture.
Antistreptococcalantibodytitersreflectpastnotpresentimmunologiceventsandthereforecannotbeusedtodeterminewhetherapatientwithpharyngitisand
GASinthepharynxistrulyinfectedormerelyastreptococcalcarrier.Whenpresent,elevatedorincreasingantistreptococcaltiterscanconfirmarecentGAS
infectionandarevaluableinidentifyingaprecedingGASinfectioninapatientsuspectedofhavingrheumaticfever.
TREATMENTOFSTREPTOCOCCALPHARYNGITIS
PrimarypreventionofrheumaticfeverrequiresadequatetherapyforGASpharyngitis.Inselectingatreatmentregimen,physiciansshouldconsiderbacteriologic
andclinicaleffectiveness,easeofadherencetotherecommendedregimen(i.e.,dosingfrequency,durationoftherapy,andpalatability),cost,spectrumofactivity
oftheselectedagent,andpotentialadverseeffects.
IntramuscularpenicillinGbenzathine,oralpenicillinVpotassium,andoralamoxicillinaretherecommendedantimicrobialagentsforthetreatmentofGAS
pharyngitisinpersonswithoutpenicillinallergy(Table2).GASresistancetopenicillinhasneverbeendocumented,andpenicillinpreventsprimaryattacksof
rheumaticfeverevenwhenstartedninedaysafterillnessonset.Patientsarenolongerconsideredcontagiousafter24hoursofantibiotictherapy.
View/PrintTable
Tale2.
PrimaryPreventionofRheumaticFever
AGENT
DOSAGE
EVIDENCE
RATING*
Penicillins
Amoxicillin
50mgperkg(maximum,1g)orallyoncedailyfor10days
1B
PenicillinGbenzathine
Patientsweighing27kg(60lb)orless:600,000unitsIMonce
1B
Patientsweighingmorethan27kg:1,200,000unitsIMonce
PenicillinVpotassium
Patientsweighing27kgorless:250mgorally2or3timesdailyfor10days
1B
Patientsweighingmorethan27kg:500mgorally2or3timesdailyfor10days
Forpatientsallergictopenicillin
Narrowspectrumcephalosporin(cephalexin[Keflex],cefadroxil
[formerlyDuricef])
Varies
1B
Azithromycin(Zithromax)
12mgperkg(maximum,500mg)orallyoncedailyfor5days
2aB
Clarithromycin(Biaxin)
15mgperkgorallyperday,dividedinto2doses(maximum,250mgtwice
daily),for10days
2aB
Clindamycin(Cleocin)
20mgperkgorallyperday(maximum,1.8gperday),dividedinto3doses,for
10days
2aB
PenicillinVpotassiumispreferredoverpenicillinGbenzathinebecauseitismoreresistanttogastricacid.However,penicillinGbenzathineshouldbeconsideredin
patientswhoareunlikelytocompletea10daycourseoforaltherapy,inthosewithpersonalorfamilyhistoriesofrheumaticfeverorrheumaticheartfailure,andin
thosewithenvironmentalfactorsthatputthematriskforrheumaticfever(e.g.,crowdedlivingconditions,lowsocioeconomicstatus).
OTHERRECOMMENDATIONS
BecausemostpatientswithGASpharyngitisrespondwelltoantimicrobialtherapy,posttreatmentthroatculturesareindicatedonlyinthosewhoremain
symptomatic,whohaverecurrentsymptoms,orwhohavehadrheumaticfeverpreviously.
Withtheexceptionofpersonswhohavehadorwhosefamilymembershavehadrheumaticfever,repeatedcoursesofantibioticsaretypicallynotindicatedin
asymptomaticpersonswhocontinuetoharborGASafterappropriatetherapy.
AlthoughacuteinfectionswithgroupBandCbetahemolyticstreptococcicanappearsimilartoGASpharyngitis,rheumaticfeverhasnotbeendocumentedasa
complicationoftheseinfections.
SecondaryPreventionofRheumaticFever
Recurrentrheumaticfeverisassociatedwithworseningordevelopmentofrheumaticheartdisease.PreventionofrecurrentGASpharyngitisisthemosteffective
methodofpreventingsevererheumaticheartdisease.However,aGASinfectiondoesnothavetobesymptomatictotriggerarecurrence,andrheumaticfevercan
recurevenwhenasymptomaticinfectionistreatedoptimally.Therefore,preventionofrecurrentrheumaticfeverrequirescontinuousantimicrobialprophylaxis
ratherthanrecognitionandtreatmentofacuteepisodesofGASpharyngitis.
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SECONDARYPROPHYLAXIS
Continuousprophylaxisisrecommendedinpatientswithwelldocumentedhistoriesofrheumaticfeverandinthosewithevidenceofrheumaticheartdisease
(Tables3and4).Prophylaxisshouldbeinitiatedassoonasacuterheumaticfeverorrheumaticheartdiseaseisdiagnosed.ToeradicateresidualGAS,afull
courseofpenicillinshouldbegiventopatientswithacuterheumaticfever,evenifathroatcultureisnegative.
View/PrintTable
Tale3.
DurationofSecondaryProphylaxisforRheumaticFever
TYPE
DURATIONAFTERLASTATTACK
EVIDENCE
RATING*
Rheumaticfeverwithcarditisandresidualheartdisease(persistent
valvulardisease)
10yearsoruntilage40years(whicheverislonger)lifetimeprophylaxis
maybeneeded
1C
Rheumaticfeverwithcarditisbutnoresidualheartdisease(novalvular
disease)
10yearsoruntilage21years(whicheverislonger)
1C
Rheumaticfeverwithoutcarditis
5yearsoruntilage21years(whicheverislonger)
1C
*AmericanHeartAssociationevidenceratings:1C=casestudies,standardofcare,orconsensusopinionthataprocedureortreatmentisbeneficial,useful,andeffective.
Clinicalorechocardiographicevidence.
AdaptedfromGerberMA,BaltimoreRS,EatonCB,etal.PreventionofrheumaticfeveranddiagnosisandtreatmentofacuteStreptococcalpharyngitis:ascientificstatementfromthe
AmericanHeartAssociationRheumaticFever,Endocarditis,andKawasakiDiseaseCommitteeoftheCouncilonCardiovascularDiseaseintheYoung,theInterdisciplinaryCouncilon
FunctionalGenomicsandTranslationalBiology,andtheInterdisciplinaryCouncilonQualityofCareandOutcomesResearch:endorsedbytheAmericanAcademyofPediatrics.
Circulation.2009119(11):1547.
View/PrintTable
Tale4.
SecondaryPreventionofRheumaticFever
AGENT
PenicillinGbenzathine
DOSAGE
Patientsweighing27kg(60lb)orless:600,000unitsIMevery4
weeks
EVIDENCE
RATING*
1A
Patientsweighingmorethan27kg:1,200,000unitsIMevery4
weeks
PenicillinVpotassium
250mgorallytwicedaily
1B
Sulfadiazine
Patientsweighing27kgorless:0.5gorallyoncedaily
1B
Patientsweighingmorethan27kg:1gorallyoncedaily
Macrolideorazalideantibiotic(forpatientsallergictopenicillinand
sulfadiazine)
Varies
1C
IM=intramuscularly.
*AmericanHeartAssociationevidenceratings:1A=evidencefrommultiplerandomizedtrialsormetaanalysesthataprocedureortreatmentisbeneficial,useful,andeffective1B=
evidencefromasinglerandomizedtrialornonrandomizedstudiesthataprocedureortreatmentisbeneficial,useful,andeffective1C=casestudies,standardofcare,orconsensus
opinionthataprocedureortreatmentisbeneficial,useful,andeffective.
Administrationevery3weeksisrecommendedincertainhighrisksituations.
MacrolideantibioticsshouldnotbeusedinpersonstakingothermedicationsthatinhibitcytochromeP4503A,suchasazoleantifungalagents,humanimmunodeficiencyvirus
proteaseinhibitors,andsomeselectiveserotoninreuptakeinhibitors.
AdaptedfromGerberMA,BaltimoreRS,EatonCB,etal.PreventionofrheumaticfeveranddiagnosisandtreatmentofacuteStreptococcalpharyngitis:ascientificstatementfromthe
Continuousantimicrobialprophylaxisprovidesthemosteffectiveprotectionfromrecurrencesofrheumaticfever.Becausetheriskofrecurrencedependsonmany
factors,physiciansshoulddeterminetheappropriatedurationofprophylaxisonacasebycasebasiswhilealsoconsideringthepresenceofrheumaticheart
disease.Patientswhohavehadrheumaticcarditis,withorwithoutvalvulardisease,areathighriskofrecurrencesandarelikelytohaveincreasinglyseverecardiac
involvementwitheachepisode.Thesepatientsshouldreceivelongtermantibioticprophylaxiswellintoadulthood,andperhapsforlife.Patientswithpersistent
valvulardiseaseshouldreceiveprophylaxisfor10yearsafterthelastepisodeofacuterheumaticfeveroruntil40yearsofage,whicheverislonger.Atthattime,
theseverityofvalvulardiseaseandthepotentialforexposuretoGASshouldbedetermined,andcontinuedprophylaxis(possiblylifelong)shouldbeconsideredin
highriskpatients.
IntheUnitedStates,aninjectionofpenicillinGbenzathineeveryfourweeksistherecommendedprophylacticregimenforsecondarypreventioninmost
circumstances.Incertainpopulations,administrationeverythreeweeksisjustifiedbecauseserumdruglevelsmayfallbelowaprotectivelevelbeforefourweeks
aftertheinitialdose.Athreeweekdosingregimenisrecommendedonlyforpatientswhohaverecurrentacuterheumaticfeverdespiteadherencetoafourweek
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regimen.TheadvantagesofpenicillinGbenzathineshouldbeweighedagainsttheinconveniencetothepatientandthepainofinjection,whichcausessome
patientstodiscontinueprophylaxis.
Successfuloralprophylaxisdependsonpatientadherencetotheprescribedregimen.Patientsshouldbegivencareful,repeatedinstructionsabouttheimportance
ofcompliancetothedosingregimen.Evenwithoptimalpatientcompliance,theriskofrecurrenceishigherinpatientsreceivingoralprophylaxisthaninthose
receivinginjectionsofpenicillinGbenzathine.Therefore,oralregimensaremoreappropriateforpatientsatlowerriskofrecurrentrheumaticfever.
BacterialEndocarditis
TheAHAnolongerrecommendsprophylaxisforinfectiveendocarditisinmostpatientswithrheumaticheartdisease.Theexceptionsarepatientswithprosthetic
valvesorvalvesrepairedwithprostheticmaterial,patientswithpreviousendocarditisorspecificformsofcongenitalheartdisease,andcardiactransplantrecipients
whodevelopcardiacvalvulopathy.Inthesepatients,anagentotherthanpenicillinshouldbeusedtopreventinfectiveendocarditis,becausealphahemolytic
streptococcihavelikelydevelopedresistancetopenicillin.
PoststreptococcalReactiveArthritis
Poststreptococcalreactivearthritis(PSRA)mayoccurafteranepisodeofGASpharyngitisinpatientswhodonothaveanyothermajorcriteriaofacuterheumatic
fever.PSRAgenerallyfollowsasymptomfreeintervalofabout10daysaftertheGASpharyngitis,iscumulativeandpersistent,involvesthelargeandsmalljoints
andtheaxialskeleton,anddoesnotrespondtoaspirintherapy.Incontrast,arthritisassociatedwithrheumaticfeveroccurstwotothreeweeksafteranepisodeof
GASpharyngitis,ismigratoryandtransient,involvesonlythelargejoints,andrespondsrapidlytoaspirintherapy.
AlthoughallpatientswithPSRAhaveserologicevidenceofarecentGASinfection,GASisisolatedinnomorethanonehalfofthesepatientswhohaveathroat
culture.BecausevalvularheartdiseasecandevelopinpatientswithPSRA,secondaryprophylaxisshouldbeadministeredforuptooneyearaftersymptomonset,
andthesepatientsshouldbeobservedforseveralmonthsforclinicalevidenceofcarditis.Ifsuchevidenceisnotobserved,prophylaxiscanbediscontinued.
However,ifvalvulardiseaseisdetected,thepatientshouldbeclassifiedashavinghadacuterheumaticfever,andsecondaryprophylaxisshouldbecontinued.
PANDAS
Ithasbeenproposedthatanautoimmuneresponseafterastreptococcalinfectionmayresultinobsessivecompulsivedisorderorticsinsomechildren.This
concept,knownasPANDAS(pediatricautoimmuneneuropsychiatricdisordersassociatedwithstreptococcalinfections),iscontroversial,andthecurrentevidence
suggeststhatitshouldbeconsideredayetunprovenhypothesis.UntilacausalrelationshiphasbeenestablishedbetweenPANDASandGASinfections,routine
laboratorytestingforGASisnotrecommendedtodiagnosethisdisorder,andlongtermprophylaxisorimmunoregulatorytherapyisnotrecommended.
CoverageofguidelinesfromothersourcesdoesnotimplyendorsementbyAFPortheAAFP.
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