GOUTYARTHRITIS:CURRENTTREATMENTS&NEWDEVELOPMENTS

JenniferBettschen
BSPCandidate2010
INTRODUCTION
Goutyarthritis,morecommonlyreferredtoasgout,isoneofthebestunderstoodand
mostmanageablerheumaticdiseases(9).Itisapainfulconditioncausedbydepositsofurate
crystalsinajoint,mostcommonlythebig toe(1,2,5).Effectivetreatmentsareavailableforgout
andothersarebeinginvestigatedallthetime.
Uricacidisabyproductofpurinemetabolisminthebody(1).Purinescomefromfoods
suchasredmeat,herring,asparagusandmushrooms.Uricacidhasnobiologicalfunctionin
humans(2).Itisdissolvedintheblood,passesintothekidneys,andexcretedintheurine.An
attackofgoutoccurswhentheuratecrystallizesintomonosodiumurate(MSU)crystals,and
depositsinajoint,orjoints,somewhereinthebody.Thebuildupofthesharp,needlelike
crystalscausespainandinflammation.Hyperuricemiaiscausedbyincreasedproductionor
decreasedexcretionofurateinthebody(1,2,5,6).Itisimportanttonotethatgoutand
hyperuricemiaarenotthesamecondition.Aswell,apersoncanhaveanattackofgoutwithout
thepresenceofhyperuricemia,andviceversa.
Goutismoreprevalentinmenthaninwomen(1,6).Itisusuallyfirstseenbetweenthe
agesof40and50inmen,andinpostmenopausalwomen.Premenopausalwomenareless
likelytodevelopgoutbecauseestrogencausesincreasedurateclearance.
Attacksofgoutdonottendtohaveprecipitatingevents(2).However,certainconditions
cancontributetothedevelopmentofgout,suchas obesity,insulinresistance,hypertension,
andhyperlipidemia(1,8).Crashdieting,adietofrichfoodsandtotalparenteralnutritionmay
alsocontribute.Excessivealcoholconsumptioncanpredisposetogout(1,5,9).Excessivealcohol
intakeisdefined asmorethan2drinksperdayformenandmorethanonedrinkperdayfor
women.Itisimportanttonote,however,thatmoderatewineconsumptiondoesnotcontribute
tothedevelopmentofgout.

Potentialsecondarycausesofgoutincludeinfection,traumaandsurgery,suchasa
renalallograft(2,5).Drugsthatcompeteforrenalexcretionmayalsocontribute.Theseinclude
drugssuchasloopandthiazidediuretics,lowdoseAspirin,andcyclosporine.Cyclosproineis
particularlyproblematicinallograftpatients;upto80%ofallograftpatientsoncyclosporinewill
develophyperuricemia(9).
Somepatientswhoexperienceanattackofgoutwillneverhaveanotheroneintheirlife
(2,5).However,manypatientsexperiencerecurrentattacks,soitisimportanttomonitor
patientsandtoprovidebothacuteandpossiblyprophylactictreatment.

SIGNS&SYMPTOMS
Anattackofgoutusuallyoccursatnight,suddenlyandwithoutwarning(1,2,5).Painis
moderateatfirstandbuildsoverseveralhoursuntilitbecomes almostunbearable.Initial
attacksofgoutaremonoarticular(affectingonlyonejoint)andareusuallysomewhereinthe
lowerextremities.Themostcommonmanifestationofgoutiscalledpodagra(2).Thisiswhen
thelargejointofthebigtoeisaffected.Theaffectedjointbecomesswollen,tenderandred
(1,2,5).Thismayalsobeaccompaniedbyfeverandchills.Thepainisnotsharp,butratheran
intensepressure,likebeingsqueezedinavice.
Goutcanalsooccurinthefeet,ankles,knees,wristsandhands(1,2,5).Thehips,
shouldersandspinearerarelyaffected,likelyduetotheseareasbeingofaslightlyhigher
temperaturethatisnotconducivetocrystallization(8).Recurrentattacksofgoutbecome
polyarticular(affectingmultiplejoints)andwillinvolvetheascendingextremities(2).
Prophylactictreatmentofgoutcanbeusedinpatientsexperiencingrecurrentattacks.

DIAGNOSIS
Goutissuspectedifapatientcallstheirphysiciancomplainingofjointpainandfever,
thoughajointfluid testisneededtomaketheofficialdiagnosis(1,2).Synovialfluidisdrawn
fromtheinflamedjointandlookedatunderamicroscopeforthepresenceofMSUcrystals.The
crystalsarelongandneedleshaped.Serumuratelevelsarenotusuallyusedasan indicatorof
goutbecause,ashasalreadybeenstated,hyperuricemiaisnotdiagnosticofgout(6).An

increasedserumuratelevelfavourscrystalformation,butevenduringanacuteattackofgout
theserumlevelsmayappearnormal.

TREATMENT
Acute
Episodesofgoutareselflimitingandwillresolvewithin7to10dayswithouttreatment
(6).However,treatmentcanprovidepainreliefandspeedtherecoveryprocess.Themain
reasonfortreatmentfailureispatientnoncompliance,thoughthiscanbepreventedwith
properpatientcounselling.Treatmentshouldbestartedassoonaspossibleafterthediagnosis;
thesoonerthetreatmentisstarted,thequickertheresponse.

NSAIDs
Nonsteroidalantiinflammatories(NSAIDs)areusedtorelievepainandinflammation,
whichistheimmediategoalofantigouttherapy(1,2).NSAIDsincludeindomethacin,
ibuprofen,naproxenanddicolfenac(4).NSAIDsarethedrugsofchoiceforthetreatmentof
goutbecausetheyareoflongdurationandhaveabettersideeffectprofilethanotheranti
goutdrugs,suchascolchicine.Thesedrugsaregenerallywelltoleratedandthesideeffectsare
mildduetotheshortdurationoftherapy.
ThechoiceofNSAIDuseddependsonthepatient(6).Whenimprovementinsymptoms
begins tooccuritisrecommenedtotaperthedosetodecreasethepotentialfor
gastrointestinal(GI)toxicity.NSAIDsarecontraindicatedforpatientswithheartfailure,GI
disease,renalinsufficiencyandthosepatientsonanticoagulanttherapy(4,5,6).Luckilythere
areothertherapeuticoptionsavailableforthesepatients.

Colchicine
AlthoughNSAIDsarethepreferreddrugsforthetreatmentofacutegout,colchicine
offerssomethingNSAIDsdonot:specificity.Colchicineisspecificforgout(4).Patientswhodo
notwanttoundergoapainfuljointaspirationcanbegivencolchicine.Ifthesymptomsclearup,
itisassumedthatthepatienthadanattackofgout.

ColchicineisanantimitoticthatpreventsMSUcrystalsfrombecomingdepositedin
joints(7).ItalsopreventsphagocytosisofdepositedMSUcrystals,theprocessthatcontributes
toinflammation.Colchicineismosteffectivewithin10to12hoursofanattack,andwillresolve
anattackofgoutwithin2to3days(4).ThemajorflawofcolchicineisthatitcausesGIdistress,
resultinginnauseaandvomitingordiarrhea(1,4).Theappearanceofthesesideeffects
coincideswithimprovementinjointsymptoms.Patientsareadvisedtotakethedruguntilpain
isrelievedoradverseGIeffectsoccur(2,3).OftenGIdistressoccursbeforepainrelief,and
patientsareadvisedtostoptakingthedrugoncetheyoccur(6).Again,NSAIDsaregenerally
preferredover colchicineitsbecauseofitsadverseGIeffects.

Corticosteroids
Corticosteroidssuchasprednisonecanbeusedasalastresortforgouttherapy,when
neitherNSAIDsnorcolchicinecanbeused(1,9).Aswell,intraarticularsteroidscanbeuseful
whenmediumtolargejointsareaffected(9).Steroidsareusedtocontrolpainand
inflammation.Normallypatientstakingcorticosteroidsaregiventapereddoseswhencoming
offoftreatment(2,3).However,taperingisnotusuallynecessaryforgoutpatientsbecauseof
theshortdurationoftherapy.

Prophylaxis
Prophylactictreatmentofgoutinvolvesdecreasinguricacidproductionorincreasing
uricacidsecretion(1,3,5).Atthetimeofanacuteattack,thesedrugscanactuallyworsenthe
problem;byrapidlydecreasingserumurateconcentration,uratestoreswillmobilizeand
prolongtheattack(2).Itisrecommendedtostartprophylaxis3to4weeksaftertheresolution
ofanacuteepisode(2,6).Starttherapyatalowdoseandgraduallyincreaseover several
weeks.Itisalsorecommendedtousecolchicineprophylacticallyforonemonth,atasmalldaily
doseof0.5to0.6milligrams(5).

Uricosurics
Uricosuricslikeprobenecidandsulfinpyrazoneincreaserenalexcretionofuricacidby
inhibitingtubularreabsorptioninthekidneys(1,3).Itisimportanttostartatlowdosesbecause
largeamountsofuricacidpassingthroughthekidneyswillincreasetheriskofforminguricacid
stones(2).Theantihypertensivedruglosartanhasbeenshownto haveauricosuriceffect,but
thiseffectdecreasesdrasticallyoncethedrughasreachsteadystate(9).Itcanalsoworsenpre
existingrenalimpairment.Uricosuricdrugsarecontraindicatedforpatientswithkidneystones
andrenalinsufficiency(7,9). Thosepatientsshoulduseadrugthatwillfunctionindependently
ofkidneyfunction.

Allopurinol
Allopurinolisaxanthineoxidaseinhibitorandworkstoblocktheproductionofuricacid
(1,2).Allopurinolworksindependentlyofrenalfunction,soitisidealforpatientswithrenal
insufficiency(5).Serumuratelevelsbegintofallwithin1to2daysofbeginningtherapy,and
willreachmaximalsuppressionwithin7to10days.
Allopurinolisgenerallywelltolerated,buthypersensitivityreactionscanbeaproblem
(2,9).Rashisthemostcommonadverseeffectandpatientsareadvisedtodiscontinuetaking
thedrugifarashappears(3).Thereisanincreasedriskofhypersensitivityreactionsinpatients
concurrentlytakingangiotensinconverting enzymeinhibitorsandthiazidediuretics.

Diet&AlcoholIntake
Dietaryintervention,weightmanagementanddecreasedalcoholconsumptioncan
reducehyperuricemiaingoutpatients(9).Purinerestricteddietsarenotverypalatableand
rarelymaintained,soresearchersarelookingintotailored,lowcarbohydrateandcalorie
restricteddiets.Itisrecommendedtoincreaseproteinandunsaturatedfatintake,andtoavoid
crashdietsandfasting(6,9).Aswasstatedearlier,excessivealcoholconsumptionisassociated
withanincreasedriskofdevelopinggout.Goutpatientsshouldbediscouragedtoavoidalcohol
intakeandtodrinklotsfluids(3,9).Dairyconsumptionhasbeenassociatedwithdecreasedrisk

ofgout,possiblyduetoauricosuriceffectofmilkproteins(12).Thisassociationhasnotbeen
entirelyestablishedyetandisstillbeingresearched.

Fenofibrate
Fenofibrateisemergingasanewpossibleprophylactictreatmentforgout.Thedrugis
normallyusedtotreathyperlipidemiabydecreasing triglyceridelevelsandincreasingHDL
cholesterollevels(8).Thedrughasalsobeenshowntolowerserumuratelevels.Longterm
administrationoffenofibratehasbeenassociatedwithsubstantialandsustaineddecreasein
serumurate.Ithasalsobeenassociatedwithadecreaseinacutegoutattacks.
OnecasereportexplainshowaTypeIIdiabetesmellituspatient,withahistoryof
severalgoutattacksperyear,hashadnoattackssincestartingfenofibratetherapy(8).The
patienthasalsohadnoneedforprophylaxis.Anothercasereportshowsapatientwitha
historyofgoutrespondingwelltofenofibratetherapywhenotherprophylactictreatments
havefailed.
Fenofibrateincreasesrenalclearanceofuricacid,aneffectnotseenwithotherfibrates
(8).Althoughfenofibratesurateloweringeffectisnotasgoodastraditionaluricosuricssuchas
probenecid,researchersaresuggestingitmaybeusedincombinationwithotherantigout
drugs.Fenofibratelookstobeapromisingadjuncttoantigout therapy.

CONCLUSION
Goutyarthritisisapainfulbutreadilytreatableconditionexperiencedbymanyadults.
The prevalenceofgoutinWesterncountriesisontherise,mostlikelyduetolifestylechoices.
Hypertension,highalcoholintake,diureticuse(specifically,thiazidesandloopdiuretics)and
obesitycontributebothindependentlyandadditivelytothedevelopmentofgoutin
hyperuricemicpatients(9).Prevalenceisalsorisinginelderlypatients,possiblyduetohigh
ratesofdiureticuseandthedeclininguseofestrogenreplacementtherapy.Thisisproblematic
becausetraditionaltreatmentsforgoutsuch ascolchicineandNSAIDshaveahigherriskof
toxicityinelderlypatients.

Researchshowshyperuricemiatobeagoodpredictorofischemiccardiovascular
diseasesandpooroutcomesrelatedtothesediseases(9).Althoughasymptomatic
hyperuricemiaisnotanindicationfortherapy(3,9),researcherssuggestthattreating
asymptomatichyperuricemiamayimprovemanagementofcardiovasculardisease(9).
Thoughthetreatmentofgouthaslongbeenestablished,researchersarestillfinding
potentialnewtreatments,suchasfenofibrate,andpotentialimplicationsfortreatment,suchas
outcomesincardiovasculardisease.Goutresearchremainsanimportantendeavour.

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