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14/10/2015 PracticeGuidelines:AHAGuidelinesonPreventionofRheumaticFeverandDiagnosisandTreatmentofAcuteStreptococcalPharyngitisAmeric

PracticeGuidelines(http://www.aafp.org/afp/viewRelatedDepartmentsByDepartment.htm?departmentId=99&page=0)

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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