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GoutandPseudogoutTreatment&Management
Author:BruceMRothschild,MDChiefEditor:HerbertSDiamond,MDmore...
Updated:Sep21,2015

ApproachConsiderations
Goutismanagedinthefollowing3stages:
Treatingtheacuteattack
Providingprophylaxistopreventacuteflares
Loweringexcessstoresofuratetopreventflaresofgoutyarthritisandto
preventtissuedepositionofuratecrystals
In2012,theAmericanCollegeofRheumatology(ACR)publishedguidelinesonthe
treatmentandprophylaxisofacutegoutyarthritisandthemanagementof
hyperuricemia. [105,106]
Asageneralrule,asymptomatichyperuricemiashouldnotbetreated,though
ultrasonographicstudieshavedemonstratedthaturatecrystaldepositionintosoft
tissuesoccursinaminorityofpatientswithasymptomatichyperuricemia. [95,97]
Patientswithlevelshigherthan11mg/dLwhooverexcreteuricacidareatriskfor
renalstonesandrenalimpairmenttherefore,renalfunctionshouldbemonitoredin
theseindividuals. [31]
Urateloweringtherapyappearstoreducetheincidenceofkidneydamageingout.
[107]Inaretrospectivestudyof16,186patientswithinitialserumuricacidlevels
above7mg/dL,Levyandcolleaguesfoundthatpatientswithgoutwhoremainedon
urateloweringtherapywerelesslikelytodevelopkidneydamageleadingtochronic
kidneydiseasethanthosewhowereuntreated. [107]Allpatientswerefollowedfor36
monthsfromtheirfirstdocumentedhighserumuricacidlevel.
Patientswhoachievedaserumuricacidlevelbelow6mg/dLhada37%
improvementinrenaloutcomes(P<.0001). [107]Thehazardratioforkidney
damagewas1.08(95%confidenceinterval,0.761.52)inpatientswhoreceived
urateloweringtherapymorethan80%ofthetimeandwas1.27(95%confidence
interval,1.051.55)inthosewhoreceivedurateloweringtherapylessthan80%of
thetime.
Tophishouldnotbesurgicallyremovedunlesstheyareinacriticallocationordrain
chronically.Surgerymaybeindicatedfortophaceouscomplications,including
infection,jointdeformity,compression(eg,caudaequinaorspinalcord
impingement),andintractablepain,aswellasforulcersrelatedtotophaceous
erosions.Delayedhealingisnotedin50%ofpatients.
Treatmentoftheacutephaseofpseudogoutisidenticaltothatofacutegout.In
patientswithidiopathicpseudogout,adeterrentregimenofcolchicinemaybeused.
Ifanunderlyingmetabolicproblemisresponsibleforpseudogout,thearthritismay
becuredwhentheunderlyingproblemisaddressed.

TreatmentofAcuteAttacks
Thetemptationtotreatpatientswithoutaprovendiagnosismustberesisted.Septic
arthritismayclinicallyresemblegoutorpseudogout,andunrecognizedseptic
arthritiscanleadtolossoflifeorlimb.Distinguishingsepticarthritisfromcrystal
inducedarthritisisnotpossiblewithoutanexaminationofjointfluid.
Acutetreatmentofprovencrystalinducedarthritisisdirectedatreliefofthepain
andinflammation.Nonsteroidalantiinflammatorydrugs(NSAIDs),corticosteroids,
colchicine,andadrenocorticotropichormone(ACTH)aretreatmentoptions.The
choiceisbasedprimarilyonwhetherthepatienthasanyconcomitanthealth
problems(eg,renalinsufficiencyorpepticulcerdisease).Colchicine,aclassic
treatment,isnowrarelyindicated.
WhencomorbidconditionslimittheuseofNSAIDsorcolchicine,apreferredoption
maybeanintraarticularsteroidinjection,particularlywhenalarge,easily
accessiblejointisinvolved.Septicarthritismustbereasonablyexcluded.
Therapytocontroltheunderlyinghyperuricemiagenerallyiscontraindicateduntilthe
acuteattackiscontrolled(unlesskidneysareatriskbecauseofanunusuallyheavy
uricacidload).Startingtherapytocontrolhyperuricemiaduringanacuteattackmay
intensifyandprolongtheattack.Ifthepatienthasbeenonaconsistentdosageof
probenecidorallopurinolatthetimeoftheacuteattack,however,thedrugshould
becontinuedatthatdosageduringtheattack.
Furthermore,controlofhyperuricemiagenerallyisnotpursuedforasingleattack.If
attacksarerecurrentorevidenceoftophaceousorrenaldiseaseispresent,therapy
forcontrolofhyperuricemiaisindicated. [108,109,110]

Nonsteroidalantiinflammatorydrugs
NSAIDsarethedrugsofchoiceinmostpatientswithacutegoutwhodonothave
underlyinghealthproblems.AlthoughindomethacinistheNSAIDtraditionally
chosenforacutegout,mostoftheotherNSAIDscanbeusedaswell.Selectan
agentwithaquickonsetofaction.Donotuseaspirin,becauseitcanalteruricacid
levelsandpotentiallyprolongandintensifyanacuteattack.Lowdoseaspirinalters
uricacidlevels,increasingtheriskofgoutattacksandrequiringcloseuricacid

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monitoringwhenaspirinisaddedtoauricacid/gouttreatmentregimen. [111]
Cyclooxygenase2(COX2)inhibitorshavebeenusedwithsuccess,butpatients
mayrequirehigherdosagesthanaretypicallyused. [112]
AvoidNSAIDsinpatientswithahistoryofpepticulcerdiseaseorgastrointestinal
(GI)bleeding,thosewithrenalinsufficiencyorabnormalhepaticfunction,those
takingwarfarin(aselectiveCOX2inhibitorcanbeused),andthoseintheintensive
careunit(ICU)whoarepredisposedtogastritis.LimitNSAIDuseinelderly
patients,becauseofthepotentialforadversecentralnervoussystem(CNS)effects.
UseNSAIDscautiouslyinpatientswithdiabetesandthosewhoarereceiving
concomitantangiotensinconvertingenzyme(ACE)inhibitors.
Tocontroltheacuteattack,NSAIDsareprescribedatfulldosagefor25days.
Oncetheacuteattackiscontrolled.thedosageisreducedtoapproximatelyonehalf
toonefourthofthatamount.Taperthedosageoverapproximately2weeks.Gout
symptomsshouldbeabsentforatleast2daysbeforetheNSAIDisdiscontinued.

Colchicine
Althoughcolchicinewasoncethetreatmentofchoiceforacutegout,itisnowless
commonlyusedthanNSAIDsbecauseofitsnarrowtherapeuticwindowandriskof
toxicity. [113,114]Tobeeffective,colchicinetherapyisideallyinitiatedwithin36
hoursofonsetoftheacuteattack.Whenusedforacutegoutinclassichourly
dosingregimens(nolongerrecommended),colchicinecausesadverseGIeffects,
particularlydiarrheaandvomiting,in80%ofpatients.
Dosingrecommendationsforcolchicineinthetreatmentofacutegouthave
undergonemodificationsasawarenessofitstoxicitieshasincreased.Newer
recommendationstrendtowardlowereddailyandcumulativedoses. [113,115]
Theregimencurrentlyfavoredconsistsof1.2mgofcolchicine,followedby0.6mg
1hourlatertoinitiatetreatmentoftheearlygoutflare.Inamulticenter,
randomized,doubleblind,placebocontrolled,parallelgroupstudy,Terkaltaubetal
foundthatthisregimenyieldedbothmaximumplasmaconcentrationandearlygout
flareefficacycomparablewiththoseofhighdosecolchicine(4.8mgtotalover6
hours),withasafetyprofileindistinguishablefromthatofplacebo. [116]
Datafrom7separatedrugtodruginteraction(DDI)studiessuggestscolchicine
dosereductionsof3366%fortreatmentofacutegoutand5075%forprophylaxis
whencolchicineisgivenincombinationwiththeextendedreleasecalciumchannel
blockersverapamilanddiltiazemorwiththenumerousPgpand/orCYP3A4
inhibitors(eg,clarithromycinandcyclosporine)inaddition,patientsshouldavoid
grapefruitjuice.Dosagesofcolchicinedidnothavetobeadjustedwhenthedrug
wasusedincombinationwithazithromycin. [117]
Colchicineshouldgenerallybeavoidediftheglomerularfiltrationrate(GFR)is
lowerthan10mL/min,andthedoseshouldbedecreasedbyatleasthalfifthe
GFRislowerthan50mL/min.Colchicineshouldalsobeavoidedinpatientswith
hepaticdysfunction,biliaryobstruction,oraninabilitytotoleratediarrhea.
Aclinicalresponsetocolchicineisnotpathognomonicforgout.Responsesmay
alsooccurinpatientswithpseudogout,sarcoidarthropathy,psoriaticarthritis,or
calcifictendonitis.
InFebruary2008,theUSFoodandDrugAdministration(FDA)ruledthat
intravenous(IV)colchicinecannolongerbeproducedorshippedintheUnited
States,becauseofitstoxicities.Consequently,IVcolchicineisnolongeradvocated
forthetreatmentofacutegoutintheUnitedStates. [118]

Corticosteroids
CorticosteroidscanbegiventopatientswithgoutwhocannotuseNSAIDsor
colchicine.Steroidscanbegivenorally,IV,intramuscularly(IM),orintraarticularly.
Usingparenteralcorticosteroidsconfersnoadvantageunlessthepatientcannot
takeoralmedications.
Prednisonecanbegivenatadoseofapproximately40mgfor13days,whichis
thentaperedoverapproximately2weeks(taperingmorerapidlycanresultina
reboundflare).Monitorcloselyforcorticosteroideffects.Iftreatmentcontinuesfor
morethan2weeks,considermeasurestopreventosteoporosis.
Intraarticularlongacting(depot)corticosteroidsareparticularlyusefulinpatients
withamonoarticularflaretohelpreducethesystemiceffectsoforalsteroids.
Ensuringthatthejointisnotinfectedbeforeinjectingintraarticularcorticosteroidsis
particularlyimportant.
AnalternativetocorticosteroidadministrationistogiveACTH(40IU
subcutaneously,withrepeatdosingasneeded)toinduceproductionof
corticosteroidbythepatientsownadrenalglands.Sucharegimendoesnotdepend
onthepatientforpropertaperingofprednisone.

Combinationtherapy
Ifthepatientdoesnothaveanadequateresponsetoinitialtherapywithasingle
drug,ACRguidelinesadvisesthataddingasecondappropriateagentisacceptable.
Usingcombinationtherapyfromthestartisappropriateforanacute,severegout
attack,particularlyiftheattackinvolvesmultiplelargejointsorispolyarticular.
Acceptableregimensincludeanyofthefollowing,infullorprophylacticdosesas
appropriate[106]:
ColchicineplusNSAIDs
Oralcorticosteroidspluscolchicine
IntraarticularsteroidspluscolchicineorNSAIDs

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TreatmentofChronicGout
Whenapatientexperiencesafirstattackofgout,anymedicationregimensthat
mayhavecontributedtothegoutattackmustbealtered,andanypredisposing
medicalconditionsorhabitsmustbeaddressed. [119]Patientsshouldbeinstructed
togoonadietifobese,tostopdrinkingbeer,andtoavoidpurinerichfoods.
Inmanycases,patientswhohaveafirstattackofgoutshouldundergotherapywith
agentsthatloweruricacid,giventhehighriskforfurtherinflammatoryattacksand
thepotentialfordestructivetophaceousdepositioninthebone,synovium,and
kidney,evenwithoutepisodesofacuteinflammation.Ifthefirstattackisnot
severe,however,somerheumatologistsadvocatewaitingforasecondattackbefore
initiatingsuchtherapynotallpatientsexperienceasecondattack,andsome
patientsmayrequireconvincingthattheyneedlifelongtherapy.
Theriskofasecondattackofgoutafterthefirstattackis62%after1year,78%
after2years,and93%after10years.Thedecisiontobegintherapydependspartly
onthebaselineserumuricacidlevels(>9mg/dLdenotesahigherriskforrecurrent
goutyarthritisandtophi).
ACRguidelinesrecommendpharmacologicurateloweringtherapyforpatientswith
goutwhohave1ormoretophionclinicalexaminationorimagingstudyorhave
frequentattacksofacutegoutyarthritis(2attacksperyear).Lessrobustevidence
supportspharmacologictherapyforpatientswithchronickidneydiseaseofstage2
orworseorapasthistoryofurolithiasis. [105]
Longtermmanagementofgoutisfocusedonloweringuricacidlevels.Thegoalof
therapyistoreduceserumuricacidlevelstobelow6mg/dL,atminimum.Inmany
cases,loweringuricacidlevelstolessthan5mg/dLisnecessarytoimprovethe
signsandsymptomsofgout.ACRguidelinesrecommendthatoncepalpabletophi
andallacuteandchronicgoutsymptomshaveresolved,serumuricacidlevels
shouldbemaintainedbelow6mg/dLindefinitely. [105]
Incontrast,PerezRuizetalhaveproposedthatoncedissolutionofexistingurate
crystalshasbeenachieved,lessstringentcontrolmaysufficetopreventformation
ofnewcrystals. [120]Intheirprospectivecohortstudyof211patientsfromwhom
urateloweringtherapywaswithdrawneitherafter5yearsifnotophuswaspresent
atbaselineor5yearsafterresolutionofthelasttophus,nopatientwhomaintained
anaverageserumuratelevellowerthan7mg/dLdevelopedacrystalproven
recurrenceofgout.
Avoidingtheuseofmedicationsthatelevateuricacidinpatientswithgoutis
prudent.Thus,inpatientswithhypertension,otheragentsarepreferabletoa
thiazidediuretic,providedthatbloodpressurecanbemanagedeasilywithasingle
drug.Lowdoseaspirinisalsouricosuric.Theangiotensinreceptorblocker(ARB)
losartanshouldbeconsidered,becauseitisuricosuricat50mg/day.However,
medicationsthatelevateuricacidcanstillbeused,ifrequired,bymaking
appropriateadjustmentsofallopurinolorprobeneciddoses.
Urinaryexcretionamountingtolessthan800mgper24hourperiodonan
unrestricteddietisconsideredunderexcretion.Underexcretingpatientsare
candidatesforuricosurictherapywithprobenecid.Thedosageisincreasedat
monthlyintervalsuntiltheuricacidlevelisloweredtotarget.Urinaryalkalization
(eg,withpotassiumcitrate)andingestionofcopiousamountsoffluidareadjunctive
recommendations.
Inpatientswithgoutwhohaverenaldisease,ACRguidelinesrecommendxanthine
oxidaseinhibitortherapywitheitherallopurinolorfebuxostatasthefirstline
pharmacologicapproach.Probenecidcanbeusedinpatientswhohave
contraindicationstoorareintolerantofatleast1ofthosefirstlineagents,oritmay
becombinedwithaxanthineoxidaseinhibitoriftheinhibitordoesnotloweruric
acidsufficiently. [105]Probenecidcouldalsobeusedforthosepatientswhoconsider
therisksofxanthineoxidaseinhibitorstobetoohigh.
TheACRadvises,however,thatmonotherapywithprobenecidisnotafirstline
choiceinpatientswithacreatinineclearanceoflessthan50mL/min. [105]In
addition,druginteractionsmayoccurwithprobenecid(seeMedication).

Prophylaxis
Becauseallopurinol,febuxostat,andprobenecidchangeserumandtissueuricacid
levels,theymayprecipitateacuteattacksofgout.Toreducethisundesiredeffect,
colchicineorlowdoseNSAIDtreatmentisprovidedforatleast6months.In
patientswhocannottakecolchicineorNSAIDs,lowdosesofprednisonecanbe
considered.Whenusedprophylactically,colchicinecanreducesuchflaresby85%.
[121]Patientswithgoutmaybeabletoabortanattackbytakingasinglecolchicine
tabletatthefirsttwingeofanattack.
Thestandarddosageofcolchicineforprophylaxisis0.6mgtwicedaily,butlower
dosageshavealsobeensuggested.Significantdosagereductioniscriticalfor
patientswhoarealsotakingcalciumchannelblockers(eg,verapamilordiltiazem)
andanyofthelargenumberofPgporCYP3A4inhibitors(eg,clarithromycinor
cyclosporine).Inpatientswithrenalinsufficiency,thedosingfrequencymayhaveto
bedecreasedtooncedailyoreveryotherday.
AdverseGIeffectsareuncommonwiththisdosage,occurringinonly4%of
patients.Thisstandsincontrasttothe80%riskofadverseGIeffectswiththe
classichourlycolchicineregimenforthetreatmentofacutegout.
Eveninprophylacticdoses,however,longtermuseofcolchicinecanleadto
marrowtoxicityandtoneuromyopathy,withelevatedlevelsofcreatinekinaseand
resultingmuscleweakness.Colchicineinducedneuromyopathyisaparticularriskin
patientswithrenalinsufficiency. [122]
Ifthepatientdevelopsagoutflareafterbeginningtherapywithauricacidlowering
agent,theagentshouldnotbediscontinued,becausediscontinuancewillonly

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causeanotherfluxintheuricacidlevel,whichmayprolongandintensifytheattack.

Allopurinol
Allopurinolblocksxanthineoxidaseandthusreducesthegenerationofuricacid.
Approximately310%ofpatientstakingallopurinoldevelopsymptomsof
intolerance,suchasdyspepsia,headache,diarrhea,orpruriticmaculopapularrash.
Lessfrequently(1%ofcases),patientstakingallopurinolcandevelopsevere
allopurinolhypersensitivitysyndrome,whichcarriesamortalityof2030%. [123]
Featuresofthissyndromeincludefever,toxicepidermalnecrolysis,bonemarrow
suppression,eosinophilia,leukocytosis,renalfailure,hepaticfailure,andvasculitis.
Corticosteroidsareoftenusedtotreatsevereallopurinolhypersensitivitysyndrome.
Severeallopurinolhypersensitivitysyndromeismorelikelytooccurinpatientswith
renalinsufficiency,thosewhoaretakingathiazidediuretic,andthosestartedon
allopurinolatadosageof300mg/day. [124]Inaddition,strongassociationshave
beenfoundbetweensevereallopurinolhypersensitivityreactionsandcarriageofthe
HLAB*5801allele. [125]
ACRguidelinesrecommendconsideringscreeningforHLAB*5801carriage,using
apolymerasechainreactionbasedtest,inselectedhighriskpatientsbefore
startingallopurinol.Patientsatparticularlyhighriskareknowntoincludethoseof
HanChineseorThaidescentKoreansarealsoatrisk,iftheyhavestage3or
worsechronickidneydisease. [105]Itisunclearwhethersuchprecautionsare
necessarywitha100mgstartingdoseofallopurinol.Additionally,availabilityofthis
testmaybeanissue.
SevereallopurinolhypersensitivitysyndromemaypresentasStevensJohnson
syndromeorasdrugrashwitheosinophiliaandsystemicsymptoms(DRESS)
syndrome.DRESSsyndromeaffectstheliver,kidney,andskin.Itisadelayed
hypersensitivityresponseoccurring68weeksafterinitiationofallopurinol.The
underlyingmechanismisthoughttobeacellmediatedimmunereactionto
allopurinolanditsmetabolites.Althoughthefrequencyisonlyis0.4%,therateof
organfailureanddeathishigh.TreatmentiswithIVNacetylcysteineandsteroids.
Allopurinolshouldimmediatelybediscontinuedinpatientswhodeveloppruritusora
rashconsistentwithallopurinolhypersensitivity.
Inmostpatients,startallopurinolat100mg/day(50mg/dayinpatientswithrenal
insufficiency).Stampetalhaveproposedthattheriskofallopurinolhypersensitivity
maybereducedbystartingallopurinolatadoseof1.5mgperunitofestimated
GFR. [126]
Adjustthedosageupwardevery25weeksaccordingtotheuricacidleveluntilthe
goalofauricacidlevelof6mg/dLorlessisachieved.Oncethetargeturicacid
levelhasbeenachievedandmaintainedfor6months,discontinuecolchicine
prophylaxis,unlessthepatienthas1ormoretophionclinicalexam.
Previously,adjustingtheallopurinolmaintenancedosagetothecreatinineclearance
ratewasrecommendedforpatientswithrenalinsufficiency.However,Vzquez
Melladoetalfoundnoincreaseintheprevalenceofadversereactionstoallopurinol
inpatientswhowerestartedatanadjusteddosagebutsubsequentlyhadtheir
dosageraisedtomeettherapeutictargets. [127]
ACRguidelinesadvisethatthedosageofallopurinolcanberaisedabove300
mg/day,eveninpatientswithrenalimpairment,providedthatthepatientreceives
adequateeducationandmonitoringfordrugtoxicity(includingmeasurementof
transaminaselevels).ThemaximumdosageofallopurinolapprovedbytheUSFood
andDrugAdministration(FDA)is800mg/day, [105]butthemaximumdosageshould
belowerinpatientswithchronickidneydisease.
Bewareofdruginteractions.Forexample,allopurinolprolongsthehalflifeof
azathioprineand6mercaptopurine.Itenhancesthebonemarrowtoxicityof
cyclophosphamide.Patientstakingconcomitantampicillinareatanincreasedriskof
rash.
Allopurinolcanbeusedincombinationwithprobenecid.However,notethat
probenecidincreasestheexcretionofallopurinol.
Inaretrospective24monthstudyofgoutpatientswhohadbeenprescribed
allopurinol,Riedeletalfoundthatonly18%ofthemfilledalltheirprescriptions
throughouttheentirefollowupperiodandthuswerepresumablycompliant10.4%
filledonlyasingleprescription. [128]Incontrast,Reesetalreportedthatwhen
patientsreceivingurateloweringtherapyweregivenapredominantlynurse
deliveredinterventionthatincludededucationandindividualizedlifestyleadvice,
92%achievedtargetserumuricacidlevelsat1year. [129]

Febuxostat
Febuxostat,anonpurineselectiveinhibitorofxanthineoxidase,isapotential
alternativetoallopurinolinpatientswithgout. [130,131]Febuxostatisadministered
orallyandismetabolizedmainlyintheliver.Incontrast,allopurinolandits
metabolitesareexcretedprimarilybythekidney.Therefore,febuxostatcanbeused
inpatientswithrenalimpairmentwithnodosageadjustment. [132]Itismore
expensivethanallopurinol.
TheCONFIRMStrialdemonstratedtheefficacyandsafetyoffebuxostatinlowering
hyperuricemia.By6months,theprimaryendpointaserumuricacidlevelofless
than6.0mg/dLwasachievedin45%ofsubjectsonfebuxostat40mg/day,67%
onfebuxostat80mg/day,and42%onallopurinol.Insubjectswithrenal
impairment,theprimaryendpointwasachievedin50%ofsubjectsonfebuxostat40
mg/day,72%onfebuxostat80mg/day,and42%onallopurinol.Adverseevent
rateswerelowandsimilarinallgroups. [133]
Inpatientsaged65yearsorolder,theprimaryendpointwasachievedin62%on

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febuxostat40mg/day,82%onfebuxostat80mg/day,and47%onallopurinol.
Thesefiguresremainedessentiallyunchangedinsubjectswithmildtomoderate
renalimpairment. [134]
InAfricanAmericansubjects,theprimaryendpointwasreachedin47%on
febuxostat40mg/day,68%onfebuxostat80mg/day,and43%onallopurinol.
Similarrateswereseeninsubjectswithrenalimpairment. [135]Adverseeventrates
inbothsubgroupswerecomparablewiththoseintheoveralltrial.
Theefficacyandsafetyoffebuxostatinwomenwasdemonstratedinthe
CONFIRMStrialandin2othertrialscomparingfebuxostatandallopurinol:FACT
(FebuxostatVersusAllopurinolControlledTrial)andAPEX(Allopurinoland
PlaceboControlled,EfficacyStudyofFebuxostat).Achievementofauricacidlevel
below6.0mg/dLrosewithincreasingdailydosesoffebuxostatdoses,from54.3%
inpatientsreceiving40mgto100%inthosereceiving240mg,comparedwith
45.9%withallopurinol.Resultsweresimilarinsubjectswithrenalimpairment. [136]

Uricase
Nonrecombinanturateoxidase(uricase)isusedinEuropetopreventsevere
hyperuricemiainducedbychemotherapyinpatientswithmalignancies,aswellasin
selectedpatientswithtreatmentrefractorygout.Shorttermuseofsuchagentsin
patientswithseveretophaceousgoutcoulddebulkthetotalbodyurateload,
allowingmaintenancewithprobenecidorallopurinol.
In2009,theFDAapprovedrecombinanturicase(rasburicase)forthepreventionof
tumorlysissyndrome.However,itishighlyimmunogenicandmaycause
anaphylaxis. [137]
In2010,apolyethyleneglycolconjugateduricase(pegloticase)wasapprovedby
theFDAforgout.Pegloticase,whichenzymaticallycatalyzestheoxidationofuric
acidtoallantoin,isanIVbiologicagenttobeconsideredwhenadjustmentof
contributingmedications(eg,diuretics)andtreatmentwithallopurinol,febuxostat,
anduricosuricagentsareinsufficienttoachieveappropriatereductionofserumuric
acidlevels. [105]
TheEuropeanMedicinesAgency(EMA)isnowweighingapprovalofpegloticasein
Europe.Approvalwasrecommendedbyanexpertadvisorycommittee. [138]
Adverseeffectsofpegloticaseincludeanaphylaxis,infusionreactions,goutflares,
andexacerbationofcongestiveheartfailure.Atpresent,substantialexpense
compromisesitscosteffectivenessasaninitialapproach. [139]TheACRguidelines
donotrecommendpegloticaseasafirstlineapproach.

Othertherapeuticoptions
Benzbromaroneisaneffectiveuricosuricagentavailableonarestrictedbasisonly
outsidetheUnitedStates.However,ithasbeenwithdrawnbecauseitcauses
fulminanthepatotoxicity.
VitaminC,withitsuricosuriceffect,mayreducetheserumconcentrationofuric
acid.Inonestudy,500mg/dayfor2monthsreduceduricacidbyameanof0.5
mg/dLinpatientswithoutgout. [140]However,goutpatientsappeartobeless
responsivetosuchalowdoseofascorbate.VitaminCtreatmentshouldbeavoided
inpatientswithnephrolithiasis,uratenephropathy,orcystinuria.
Inanopenlabelpilotstudyof10patientswithrefractoryacutegouttreatedwiththe
interleukin(IL)1antagonistanakinra,painwassubstantiallyreducedinallpatients
within2days,withoutsideeffects.Clinicalsignsofinflammationhaddisappeared
in9of10patientsbyday3oftreatment. [141]
Thelipidloweringdrugfenofibrate,afibricacidderivative,lowersserumuricacid
levelswhilereducingverylowdensitylipoprotein(VLDL),totalcholesterol,and
triglyceridelevels. [142]However,thecreatininelevelincreases,andalleffectsare
negatedoncethedrughasbeendiscontinued. [137]

Canakinumab
In2010,an8week,singleblind,doubledummy,doserangingstudyshowedthat
theselectiveIL1antibodycanakinumabyieldedfastandlastingreliefofpainin
patientswithacutegoutyarthritisflaresrefractorytotreatmentwithNSAIDsor
colchicine. [143]However,inJune2011,canakinumabwasdeniedapprovalbythe
FDA. [144](SeeFDAPanelSaysNotoCanakinumabforGoutAttacks.)

DietandActivity
Becauseuricacidisabreakdownproductofpurine,highpurinefoodsshouldbe
eitheravoidedorconsumedonlyinmoderation.Foodsveryhighinpurinesinclude
organmeatssuchassweetbreads(eg,pancreasandthymus),smelt,sardines,and
mussels.Foodsmoderatelyhighinpurinesincludeanchovies,trout,haddock,
scallops,mutton,veal,liver,bacon,salmon,kidneys,andturkey.
Purinesarefoundinallproteinfoods.Allsourcesofpurinescannotandshouldnot
beeliminated.
Overall,purinerestrictiongenerallyreducesserumuricacidlevelsbynomorethan
1mg/mL,withmodestimpact,anddietswithverylowpurinecontentarenot
palatable.Dietmodificationsalonearerarelyabletoloweruricacidlevels
sufficientlytopreventaccumulationofurate,buttheymayhelplessenthetriggers
ofacutegoutattacks.
Patientswithgoutshouldavoidexcessingestionofalcoholicdrinks,particularly
beer,becausealcoholuseelevatesuricacidlevelsandthuscanprecipitateattacks
ofgout.Indeed,heavydrinkersaremuchmorelikelytohaverecurrentgoutattacks,

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evenwithallopurinoltherapy.Moderatewineintakeisnotassociatedwithincreased
developmentofincidentgout, [1]butexcessesofanyformofalcoholingoutpatients
areassociatedwithacutegoutflares.
Patientsshouldavoidsodasandotherbeveragesorfoodssweetenedwithhigh
fructosecornsyrup.Theyshouldalsolimittheiruseofnaturallysweetfruitjuices,
tablesugar,andsweetenedbeveragesanddesserts,aswellastablesalt. [105]
Patientstakingcolchicineshouldavoidgrapefruitandgrapefruitjuice.
Maintainingahighlevelofhydrationwithwater(atleast8glassesofliquidsper
day)maybehelpfulinavoidingattacksofgout.Inviewoftheassociationofgout
withatherosclerosis,thediagnosisofgoutmayaffordaparticularlygoodopportunity
forthecliniciantoadvisealowcholesterol,lowfatdietifsuchadietisotherwise
appropriateforthepatient.Althoughadietofthistypemayhelpuricacidlevels,
suchadviceshouldbegivenprimarilytohelppreventatherosclerosis.
Weightreductioninpatientswhoareobesecanimprovehyperuricemia.Ketosis
inducingdiets(eg,fasting)shouldbeavoided,however.
Becauseacuteattacksarealreadysufficientlylimitingofactivity,additional
limitationsofactivityarenotnecessary.Thepatientshouldavoidtraumatothe
affectedjointotherwise,theyshouldbeactive.

Consultations
Rheumatologistsshouldbeinvolvedinthecareofpatientswithdifficultgout,as
advisedintheACRguidelines.Theycanestablishthediagnosiswitharthrocentesis
andsynovialfluidanalysisforcrystals.Theyalsoareskilledinthemanagementof
thisdisorder,andconsultationmaybehelpfulforpatientswithanacutegoutattack
thatdoesnotrespondtoNSAIDswithin2daysortocolchicinewithin1day,aswell
asforpatientswithrefractoryhyperuricemia.
Rheumatologyororthopedicconsultationisindicatedforanypatientwithseptic
arthritisorforanypatientinwhomasepticarthritiscannotberuledout.

LongTermMonitoring
Afterdiagnosisandtreatmentofanacutegoutyarthritisepisode,thepatientshould
returnforafollowupvisitinapproximately1monthtobeevaluatedfortherapyto
lowerserumuricacidlevels.
Ifuricacidloweringtherapyisbegun,patientsshouldbeseenwithin2weeksto
ensurethatnountowardtoxicityhasdevelopedandthenevery12monthswhile
medicationdosagesareadjustedtoachievethetargeturicacidlevelof56mg/dL.
Oncethislevelisachievedandmaintained,patientscanbeseenevery612months
andtheirserumuricacidmonitoredtohelpassessefficacyandadherence.
Medication

ContributorInformationandDisclosures
Author
BruceMRothschild,MDProfessorofMedicine,NortheastOhioMedicalUniversityAdjunctProfessor,
DepartmentofBiomedicalEngineering,UniversityofAkronResearchAssociate,UniversityofKansasMuseum
ofNaturalHistoryResearchAssociate,CarnegieMuseum
BruceMRothschild,MDisamemberofthefollowingmedicalsocieties:AmericanAssociationforthe
AdvancementofScience,AmericanCollegeofRheumatology,InternationalSkeletalSociety,NewYork
AcademyofSciences,SigmaXi,SocietyofSkeletalRadiology
Disclosure:Nothingtodisclose.
Coauthor(s)
MarkLFrancis,MDProfessorofMedicalEducation,DepartmentofMedicalEducation,PaulLFosterSchoolof
Medicine,TexasTechUniversityHealthSciencesCenter
MarkLFrancis,MDisamemberofthefollowingmedicalsocieties:AmericanCollegeofPhysicians,PhiBeta
Kappa
Disclosure:Nothingtodisclose.
AnneVMiller,MDChief,RheumatologyDivisionAssistantProfessorofInternalMedicine,Departmentof
Medicine,DivisionofRheumatology,SouthernIllinoisUniversitySchoolofMedicine
AnneVMiller,MDisamemberofthefollowingmedicalsocieties:AlphaOmegaAlpha,AmericanCollegeof
Physicians,AmericanCollegeofRheumatology,InternationalSocietyforClinicalDensitometry
Disclosure:Nothingtodisclose.
ChiefEditor
HerbertSDiamond,MDVisitingProfessorofMedicine,DivisionofRheumatology,StateUniversityofNewYork
DownstateMedicalCenterChairmanEmeritus,DepartmentofInternalMedicine,WesternPennsylvaniaHospital
HerbertSDiamond,MDisamemberofthefollowingmedicalsocieties:AlphaOmegaAlpha,AmericanCollege
ofPhysicians,AmericanCollegeofRheumatology,AmericanMedicalAssociation,PhiBetaKappa
Disclosure:Nothingtodisclose.
Acknowledgements
RichardWAllinson,MDAssociateProfessor,DepartmentofOphthalmology,TexasA&MUniversityHealth
ScienceCenterSeniorStaffOphthalmologist,ScottandWhiteClinic
RichardWAllinson,MD,isamemberofthefollowingmedicalsocieties:AmericanAcademyofOphthalmology,
AmericanMedicalAssociation,andTexasMedicalAssociation
Disclosure:Nothingtodisclose.

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LawrenceHBrent,MDAssociateProfessorofMedicine,JeffersonMedicalCollegeofThomasJefferson
UniversityChair,ProgramDirector,DepartmentofMedicine,DivisionofRheumatology,AlbertEinsteinMedical
Center
LawrenceHBrent,MDisamemberofthefollowingmedicalsocieties:AmericanAssociationforthe
AdvancementofScience,AmericanAssociationofImmunologists,AmericanCollegeofPhysicians,and
AmericanCollegeofRheumatology
Disclosure:AbbottHonorariaSpeakingandteachingCentocorConsultingfeeConsultingGenentech
Grant/researchfundsOtherHGS/GSKHonorariaSpeakingandteachingOmnicareConsultingfeeConsulting
PfizerHonorariaSpeakingandteachingRocheSpeakingandteachingSavientHonorariaSpeakingand
teachingUCBHonorariaSpeakingandteaching
AndrewADahl,MDDirectorofOphthalmologyTeaching,MidHudsonFamilyPracticeInstitute,TheInstitute
forFamilyHealthAssistantProfessorofSurgery(Ophthalmology),NewYorkCollegeofMedicine
AndrewADahl,MDisamemberofthefollowingmedicalsocieties:AlphaOmegaAlpha,AmericanAcademyof
Ophthalmology,AmericanCollegeofSurgeons,AmericanMedicalAssociation,AmericanSocietyofCataract
andRefractiveSurgery,andWildernessMedicalSociety
Disclosure:Nothingtodisclose.
PaulEDiCesare,MD,FACSProfessorandChair,DepartmentofOrthopedicSugery,UniversityofCalifornia,
Davis,SchoolofMedicine
PaulEDiCesare,MD,FACSisamemberofthefollowingmedicalsocieties:AmericanAcademyofOrthopaedic
Surgeons,AmericanCollegeofSurgeons,andSigmaXi
Disclosure:StrykerConsultingfeeConsulting
StevenCDronen,MD,FAAEMChair,DepartmentofEmergencyMedicine,LeConteMedicalCenter
StevenCDronen,MD,FAAEMisamemberofthefollowingmedicalsocieties:AmericanAcademyof
EmergencyMedicineandSocietyforAcademicEmergencyMedicine
Disclosure:Nothingtodisclose.
GinoAFarina,MD,FACEP,FAAEMAssociateProfessorofClinicalEmergencyMedicine,AlbertEinstein
CollegeofMedicineProgramDirector,DepartmentofEmergencyMedicine,LongIslandJewishMedicalCenter
GinoAFarina,MD,FACEP,FAAEMisamemberofthefollowingmedicalsocieties:AmericanAcademyof
EmergencyMedicine,AmericanCollegeofEmergencyPhysicians,andSocietyforAcademicEmergency
Medicine
Disclosure:Nothingtodisclose.
HarrisGellman,MDConsultingSurgeon,BrowardHandCenterVoluntaryClinicalProfessorofOrthopedic
SurgeryandPlasticSurgery,DepartmentsofOrthopedicSurgeryandSurgery,UniversityofMiami,LeonardM
MillerSchoolofMedicine
HarrisGellman,MDisamemberofthefollowingmedicalsocieties:AmericanAcademyofMedicalAcupuncture,
AmericanAcademyofOrthopaedicSurgeons,AmericanOrthopaedicAssociation,AmericanSocietyforSurgery
oftheHand,andArkansasMedicalSociety
Disclosure:Nothingtodisclose.
JosephKaplan,MD,MS,FACEPAttendingPhysician,DepartmentofEmergencyMedicine,MartinArmy
CommunityHospital,FortBenning
JosephKaplan,MD,MS,FACEPisamemberofthefollowingmedicalsocieties:AmericanCollegeof
EmergencyPhysicians
Disclosure:Nothingtodisclose.
JeganKrishnan,MBBS,FRACS,PhDProfessor,Chair,DepartmentofOrthopedicSurgery,FlindersUniversity
ofSouthAustraliaSeniorClinicalDirectorofOrthopedicSurgery,RepatriationGeneralHospitalPrivate
Practice,OrthopaedicsSA,FlindersPrivateHospital
JeganKrishnan,MBBS,FRACS,PhD,isamemberofthefollowingmedicalsocieties:AustralianMedical
Association,AustralianOrthopaedicAssociation,andRoyalAustralasianCollegeofSurgeons
Disclosure:Nothingtodisclose.
EdwardAMichelson,MDAssociateProfessor,ProgramDirector,DepartmentofEmergencyMedicine,
UniversityHospitalHealthSystemsofCleveland
EdwardAMichelson,MDisamemberofthefollowingmedicalsocieties:AmericanCollegeofEmergency
Physicians,NationalAssociationofEMSPhysicians,andSocietyforAcademicEmergencyMedicine
Disclosure:Nothingtodisclose.
SriyaKMRanatunga,MD,MPHAssociateProfessor,DepartmentofClinicalMedicine,SouthernIllinois
UniversitySchoolofMedicine
Disclosure:Nothingtodisclose.
HamptonRoySr,MDAssociateClinicalProfessor,DepartmentofOphthalmology,UniversityofArkansasfor
MedicalSciences
HamptonRoySr,MDisamemberofthefollowingmedicalsocieties:AmericanAcademyofOphthalmology,
AmericanCollegeofSurgeons,andPanAmericanAssociationofOphthalmology
Disclosure:Nothingtodisclose.
FranciscoTalavera,PharmD,PhDAdjunctAssistantProfessor,UniversityofNebraskaMedicalCenterCollege
ofPharmacyEditorinChief,MedscapeDrugReference
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RChristopherWalton,MDProfessor,DirectorofUveitisandOcularInflammatoryDiseaseService,Department
ofOphthalmology,AssistantDeanforGraduateMedicalEducation,UniversityofTennesseeCollegeof

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MedicineConsultingStaff,RegionalMedicalCenter,MemphisVeteransAffairsMedicalCenter,StJude
Children'sResearchHospital
RChristopherWalton,MDisamemberofthefollowingmedicalsocieties:AmericanAcademyof
Ophthalmology,AmericanCollegeofHealthcareExecutives,AmericanUveitisSociety,AssociationforResearch
inVisionandOphthalmology,andRetinaSociety
Disclosure:Nothingtodisclose.

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