New Current Strategies for Gout and Other Types of Monoarticular … · 2016. 4. 13. · Choose...

4/7/16

1

CurrentStrategiesforGoutandOtherTypesofMonoarticular

Arthritis

Andrew J. Gross, MDRheumatology Clinic Chief

Associate Clinical ProfessorUniversity of California, San Francisco

Disclosures

• None

4/7/16

2

TeachingObjectives

• Beabletodistinguish septicarthritisfromcrystalinduced arthritis

• Befamiliarwithmanagementofacute&chronicgout

• Befamiliarwithdiagnosis andmanagementofcalciumpyrophosphate disease

Case1A75yearoldmanwithahistoryofdiabetes,CKD,andgoutisadmittedwith1dayofacuteswellingandpainintherightankle.Histempis101.4.Theankleiswarmandswollen.Theotherjointsseemunremarkable.ArthrocentesisintheEDdemonstratesnegativelybirefringentcrystals.Cellcount85,000WBC– 91%PMNs.Whatdoyoudonext:A. Holdallopurinol&waitforculturesB. InjectcorticosteroidsintothejointC. Prescribeaprednisone taperD. Prescribenaproxen500mgBIDE. PrescribeIVantibiotics&waitfor

theresultsofthegramstain&Cx

4/7/16

3

75y.o.manwithDM,CKD with1dayacutelyswollen&warmanklewithfever.Synovialfluidshowsnegativelybirefringentcrystals&WBC85,000.

Whatdoyoudonext:

A. Holdallopurinol&waitforGS&Cx

B. InjectcorticosteroidC. Prednisone taperD. Naproxen500mgBIDE. IVantibioticsandwait

forGS&Cx

5

Case1A75yearoldmanwithahistoryofdiabetes,CKD,andgoutisadmittedwith1dayofacuteswellingandpainintherightankle.Histempis101.4.Theankleiswarmandswollen.Theotherjointsseemunremarkable.ArthrocentesisintheEDdemonstratesnegativelybirefringentcrystals.Cellcount85,000WBC– 91%PMNs.Whatdoyoudonext:A. HoldallopurinolandwaitforculturesB. InjectcorticosteroidsintothejointC. Prescribeaprednisone taperD. Prescribenaproxen500mgBIDE. Prescribe IVantibioticsandwaitfor

theresultsofthegramstain&Cx

4/7/16

4

DifferentialDiagnosisofmonoarticulararthritis

• SepticArthritis– GramPositivecocci– GramNegativeRods– Lymedisease– Tb/Fungal

• CrystalArthritis– Gout– Pseudogout

• Spondyloarthritis(e.g.Reactive Arthritis)

• Vasculitis• PalindromicRheumatism

• Trauma• Exacerbationof

Osteoarthritis

1-5%ofpatientswithcrystalarthritiswillalsohavesepticarthritisofthesamejoint(Papanicolas etal,JRheumatol 2012;ShahK,etal,JEmerg Med2007)

Whatcanhelpusdetermineifaninfectionispresentwithoutwaitingforthecultures?

4/7/16

5

Riskfactorsforsepticarthritis

• Recentjointsurgery(Likelihood ratio6.9)Recentarthroplasty(LR3.1)

• Age>80(LR3.5)• Localwound/skininfection(LR2.8)• Diabetes(LR2.7)• Rheumatoidarthritis(LR2.5)

• Immunosuppression(esp.TNFinhibitors)• HIV• IVdruguse

Margaretten ME,etal, JAMA2007,PMID17405973

About50%ofpatientswillhaveafever>101°

SynovialFluidAnalysisisSomewhatHelpfultoIdentifySepticArthritis

• 49culture-positivesynovialfluidaspirates

• 39%hadWBC<50,000/mm3

• 55%hadanegativeGram’sstain– 56%ofthosepatientshadasynovialWBCof<50000/mm3.

• WBC<10,000/mm3 hasaverystrongnegativepredictivevalueforsepticarthritis

• WBC>100,000/mm3 hasastrongpositivepredictivevalue

• Gramstainis40-60%sensitive

• Culturesare90%sensitive

McGillicuddy DC,etal,AmJEmerg Med,2007 Margaretten ME,etal, JAMA2007

4/7/16

6

Anasideaboutsepticarthritis

Allofthefollowingtestsshouldbeconsideredina30yearoldwomanwithsubacutedevelopmentofawarmswollenkneewithsynovialfluid50,000WBCs/mm3 EXCEPT:a) Bloodculturesb) LymediseaseELISAonserumc) SynovialfluidLDHandglucosed) Vaginalswabforgonococcus&

chlamydia(bynucleicacidamplificationtesting)

e) PPD&synovialbiopsyforAFBstain&mycobacterialculture

Allofthefollowingtestsshouldbeconsideredina30y.o.womanwithsubacutekneeswelling&synovialfluidwith50,000WBCs/mm3 EXCEPT:

a) Bloodculturesb) LymediseaseELISAc) Synovial fluidLDHand

glucosed) VaginalswabforGC&

chlamydiae) PPD&synovial biopsy

forAFB

5

4/7/16

7

Allofthefollowingtestsshouldbeconsideredina30yearoldwomanwithsubacutedevelopmentofawarmswollenkneewithsynovialfluid50,000WBCs/mm3 EXCEPT:a) Bloodculturesb) LymediseaseELISAonserumc) SynovialfluidLDHandglucosed) Vaginalswabforgonococcus&

chlamydia(bynucleicacidamplificationtesting)

e) PPD&synovialbiopsyforAFBstain&mycobacterialculture

García-AriasM,etal,BestPract ResClin Rheumatol,2011

Anasideaboutsepticarthritis

• Bloodculturesarereportedtobepositivein50–70%ofpts

• Routeofinfection:– Hematogenousseeding– infectedcontiguous fociorneighboringsoft-tissuesepsis

– directinoculationduetotrauma• Organisms

– Staphaureus(~50%)– Streptococcus species(~20%)– GramNegativeRods(20%)

• Septicjointsshould bedrained(repeatedaspirationorarthroscopically)

García-AriasM,etal,BestPract ResClin Rheumatol,2011

SepticArthritis

4/7/16

8

Cantini Fetal,AnnRheumDis,2007,PMID17768172

SubacuteArthritisoftheKnee

ReactiveArthritisIBDassoc ArthritisAnkylosingSpondylitis

NoLymeDisease?…ItalianStudy

H

Backtoourquestion:Whatcanhelpusdetermineifaninfectionispresentwithoutwaitingforthecultures?

4/7/16

9

AcuteGoutyArthritis

• Provocation: trauma,ethanol,exercise,newmedication

• FirstAttack:– fourth tosixthdecadeoflife– 90%Monoarticular– 50%Podagra

• Sites:– 1stMTP– Instep,mid-foot, ankle,knee– wrist, fingers,elbow

http://images.rheumatology.org/image_dir/album75676/md_99-14-0009.tif. jpg

SepticArthritismostcommonlyaffectslargejoints

TheValueofaCarefulJointExam

http://www.eorthopo d.co m/pu blic/pati en t_ed ucati on/65 88/gou t.h tml

Tip:Inapatientwithahistoryofmanyattacksofgout,attackstendtobeoligoarticular orpolyarticular.Thiscanbeappreciatedbydoingaverycarefuljointexamination.

4/7/16

10

Case3

A53yearoldmanwithHTN&nephrolithiasiscomestoseeyou forrecurrentfootpain.Hisfirstattackofjointpaincameinhis1st toeabout2 yearsagowithasuddenonsetofintensepainthatgraduallyimprovedover2weeks.Sincethenhehashad2moreattacksaffectingjointsinboth feet.Themostrecentattackstarted3daysagoinhis1st toeandinstep.Onexaminationthereismarkedswelling,erythemaandtendernessover the1st MTPbursaaswellasthe1st metatarsal-tarsaljoint.

TestYourKnowledge…

AllofthefollowingarereasonabletreatmentsforacutegoutEXCEPT:

a) NSAIDS(naproxen500mgBID,indomethacin 50mgTID)

b) Prednisone: 40-60mg/d,taperedover6-18daysc) Intra-muscularcorticosteroidinjection.(Triamcinalone 60-

80mgIM;mayneedtorepeatinacoupleofdays)d) Intra-articular steroidinjection(Triamcinalone 20-40mg)e) Colchicine0.6mgevery30minutesuntilresolutionor GI

upset

4/7/16

11


A. NSAIDSB. Prednisone TaperC. IMTriamcinoloneD. Intra-Articular

TriamcinoloneE. Colchicine q30min

5

TestYourKnowledge…


a) NSAIDS(naproxen500mgBID,indomethacin 50mgTID)

b) Prednisone: 40-60mg/d,taperedover6-18daysc) Intra-muscularcorticosteroidinjection.(Triamcinalone 60-

80mgIM;mayneedtorepeatinacoupleofdays)d) Intra-articular steroidinjection(Triamcinalone 20-40mg)e) Colchicine0.6mgevery30minutes 1.2mgthen0.6mg1

hour later. Donotrepeatfor2weeksifPt hasCKD.

4/7/16

12

EfficacyofOralColchicineforAcuteGout

Terkeltaub RA,etal,ArthritisRheum2010,PMID20131255

“high-dose”colchicine(1.2mgfollowedby0.6mgeveryhourfor6hours[4.8mgtotal])

“low-dose”colchicine(1.2mgfollowedby0.6mgin1hour[1.8mgtotal])

Diarrhea26%,0%77%,19%

% o

f pat

ient

s im

prov

ed

% improvement

any, severe

EfficacyofNSAIDs&Corticosteroids forAcuteGout

• NSAIDS(naproxen 500mgBID,indocin 50mgTID,diclofenac 50mgBID)

• Prednisone: 60mgqd, taperover6-18days

Janssens H, et al, Lancet 2008, PMID 18514729also see Rainer TH, et al, Ann Intern Med 2016, PMID 26903390

Prednisone

Naproxen

4/7/16

13

TreatmentofAcuteGout

NSAIDsareproblematicinpatientswithCKD

Withdrawal of NSAIDs for 1 year (along with control of hyperuricemia) resulted in improved renal function in patients.

Perez-Ruiz F, et al, Nephron 2000, PMID 11096285

Henry D, et al, Br J Pharmacol 1997,

NSAIDsusewasassociatedwithincreased riskofCKDinpatientswithhyperuricemia orgout(matchedcase-control study)

[RiskofCKD]

MechanismofInflammation inGout

Neogi T, NEJM 2011, PMID 21288096

4/7/16

14

IL-1antagonismingout

• Allpatientsreceivedanakinra (IL-1receptorantagonist)• Treatedwith100mgSQinjectiondailyfor3days ($50-100/injection)• All10patientswithacutegoutrespondedrapidlytoanakinra.• 9/10hadcompleteresolutionofgoutsymptomsin3days• Noadverse effectswereobserved.• SimilarResultsreportedbyChenKetal,Semin ArthritisRheum2010

Case3(continued)

Thesame53yearoldmanwithHTNandnephrolithiasisreturns9monthslatercomplainingofanotherflareofjointpaininhisfeet(now4totalin3years). HismedicationsincludeASA,HCTZ,lisinopril,andibuprofenforthejointpain. Heaskswhatcanbedonetoprevent futureattacks.Choose themostcorrectanswer:A. ModifyhisdiettoavoidallfoodswithhighpurinecontentB. StopthethiazideC. StoptheACEinhibitorD. TreatedwithprobenecidE. Treatwithcolchicine

4/7/16

15

53y.o manwithHTNandnephrolithiasiswith4goutattacksover3yearsaskswhatcanbedonetoprevent

futureattacks.Choosemostcorrectanswer:

A. Avoidallhighpurinefoods

B. StopthiazideC. StopACEinhibitorD. TreatwithprobenecidE. Treatwithcolchicine

5

Case3(continued)

Thesame53yearoldmanwithHTNandnephrolithiasisreturns9monthslatercomplainingofanotherflareofjointpaininhisfeet(now4totalin3years). HismedicationsincludeASA,HCTZ,lisinopril,andibuprofenforthejointpain. Heaskswhatcanbedonetoprevent futureattacks.Choose themostcorrectanswer:A. ModifyhisdiettoavoidallfoodswithhighpurinecontentB. Stopthe thiazideC. StoptheACEinhibitorD. TreatedwithprobenecidE. Treatwithcolchicine

4/7/16

16

Non-PharmacologicTreatmentofGout

TreatmentApproaches:• ReduceIntake• ReduceProduction• (IncreaseMetabolism)• IncreaseExcretion

DietandRiskofGoutinMen

Adapted from Choi HK, et al, New Engl J Med 2004, PMID 15014182

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

TotalMeat Seafood Purine-richVegetables

TotalDairy

RelativeRiskofD

evelop

ingGou

t

Meninthetopquintileofintakecomparedwiththoseinthelowestquintile(multivariateanalysis)

4/7/16

17

TreatingGout:Diet&Meds

FoodsModeratelytoVeryHighinPurines

• Hearts, sweetbreads,liver,Kidney,Herring, smelt,sardines, mussels,anchovies,Yeast

• Grouse, Turkey,Partridge,Goose, Pheasant,Mutton,Veal,Bacon

• Salmon,Trout, Haddock,Scallops

Medicationsthatinhibituricacidsecretion

• Thiazide diuretics• Loopdiuretics• Aspirin(<1gm/d)

JohnsHopkins:DietandGouthttp://www.johnshopkinshealthalerts.com/reports/arthritis/460-1.html

Beveragesassociatedwithhyperuricemia

• Beer• Highfructosedrinks

ReasonstoStartUricAcidLoweringTherapy(ULT):

AllofthefollowingareindicationsforstartingUricAcidLoweringTherapyinpatientswithanestablisheddiagnosis ofgoutyarthritisEXCEPT:

a. TophaceousGoutb. Recurrentattacksofgout(≥2attacks/year)c. Historyoferosions onx-rayscharacteristicofgoutd. Serumuricacid≥8.0e. PresenceofCKDclassIIorgreater

4/7/16

18

AllofthefollowingareindicationsforstartingUricAcidLoweringTherapyinpatientswithanestablisheddiagnosisofgoutyarthritisEXCEPT:

a. Tophaceous goutb. ≥2goutattacks/yrc. Erosions onx-raysd. Uricacid≥8.0e. CKDclass≥II

5

ReasonstoStartUricAcidLoweringTherapy(ULT):

AllofthefollowingareindicationsforstartingUricAcidLoweringTherapyinpatientswithanestablisheddiagnosis ofgoutyarthritisEXCEPT:

a. TophaceousGoutb. Recurrentattacksofgout(≥2attacks/year)c. Historyoferosions onx-rayscharacteristicofgoutd. Serumuricacid≥8.0e. PresenceofCKDclassIIorgreater

4/7/16

19

IncidenceofGoutamongMen

SerumUrateLevel: <6 6-6.9 7-7.9 8-8.9 9-9.9 >105-yearcumulative 0.5% 0.6% 2.0% 4.1% 9.8% 30%Incidence

Campion E,etal,Asymptomatichyperuricemia.Am.J.Med.82:421,1987.

Recurrenceofacutegoutarthritisfollowing initialattack:<1year62%1-2 years 16%2-5years 11%Never 7%Gutman AB,Gout,Beeson&McDermott(ed):Textbook ofMedicine,12thEd.,1958

ChronicManagementinpatientswithrecurrentattacksofgout

UricAcidLoweringTherapytoPrevent&TreatTophi!

4/7/16

20

ImprovedOutcomesinGoutPatientswhoachieveUricAcidReductionstoLevels≤6.0mg/dl

Reducedfrequencyofattacks(Li-YuJetal.JRheumatol 28:577-580,2001;ShojiAetal.ArthritisRheum51:321-325,2004;BeckerMAetal.NEngl JMed353:2540-2461,2005)

Reducedtophussize(Perez-RuizFetal.JClin Rheumatol 5:49-55,1999;BeckerMAetalNEngl JMed353:2540-2461,2005)

Depletecrystalstoresinsynovial fluid(Li-YuJetal.JRheumatol 28:577-580,2001)

ImprovedrenalfunctionwithreductionofNSAIDuse(Perez-RuizFetal.Nephron856:287-291,2000)

Slowsprogressionofexistingrenaldisease(Siu Y-Petal.AmJKidneyDis47:51-59,2006)

Perez-RuizFandLiote F.Loweringserumuricacidlevels:whatistheoptimaltargetforimprovingclinicaloutcomesingout?ArthritisRheum57:1324-1328,2007

4/7/16

21

PharmacologicUricAcidLoweringTherapy

TreatmentApproaches:• ReduceIntake• ReduceProduction• (IncreaseMetabolism)• IncreaseExcretion


• Uricosurics (probenecid) arerecommendedforpatientswithnormalkidneyfunction&withouturatenephrolithiasis whoare“underexcretors”(24hr urinecollection:<700mg/d ofuricacid)

• Themajorityofpatientswithrecurrentgoutwillhavechronickidney diseaseandshould betreatedwithxanthineoxidase inhibitors(allopurinol, febuxostat).

2012AmericanCollegeofRheumatologyguidelinesformanagementofgoutKhanna D,etal,ArthritisRheum2012,PMID23024028

4/7/16

22


ManypatientsarestartedonAllopurinol300mg/danddonotachieveUricAcid<6.0

Roddy E,etal,AnnRhueum Dis2007AmericanCollegeofRheumatologyGuidelines

Khanna D,etal,ArthritisCare&Res2012

SowhatistheconcernaboutallopurinolinpatientswithCKD?

4/7/16

23

Allopurinol warnings

• 2%develop arash– MuchhigherinpatientswithHLA–B*5801.HighfrequenciesseeninHanChinese&Thaipopulations

• 0.1%develophypersensitivity reaction(DRESS)

• CutaneousRash92%• Fever87%• RenalDysfunction85%• Eosinophilia73%• Hepatitis68%• Leukocytosis39%• Death21%

Hande etal,AmJMed76:47,1984

RecommendedmaintenancedoseofallopurinolbasedontheGFR

GFR(ml/min) Dose(mg/d)100 30080 25060 20040 15020 10010 50

AdaptedfromKelley,TextbookofRheumatology, 1997

4/7/16

24

DoseAdjustment ofAllopurinolAccordingtoCreatinineClearanceDoesNotProvideAdequateControlofHyperuricemiainPatientswithGout

Dalbeth Netal.JRheumatol 2006

Renally-DosedAllopurinol :SafetyandEfficacy

Adherence topublishedallopurinoldosingguidelinesledtosuboptimalcontrolofhyperuricemiaanddidnotpreventhypersensitivityreactions.Dalbeth Netal.JRheumatol, 2006

Severehypersensitivityreactionsarenotdosedependent.Puig JGetal.J.Rheumatol,1989

Noincreaseinadversereactionstoallopurinolinpatientsreceivinghigherthanrecommendedcreatinine clearance-adjusteddoses.Vazquez-Mellado Jetal.AnnRheumDis,2001

Starting allopurinolatadoseof1.5mgperunitofestimatedGFRisassociatedwithareducedriskofallopurinolhypersensitivity. StampLK,etal,Arthritis Rheum2012

4/7/16

25

Whynotjustprescribefebuxostat?

19230

59

706

162

1944

0

500

1000

1500

2000

1-month 12-month

USDollars

AllopurinolProbenecidFebuxostat

CourtesyofGabriela

SchmajukUCSF

Costs ofurate-loweringtherapies

Useoffebuxostat as2nd linetherapyafterallopurinoliscosteffectiveBeardSM,etal,Eur JHealthEcon2014

TreatwithColchicinewheninitiatinguricacidreducingagent

• >60%ofpatientswillhaveagoutflareafterstartingtreatment withfebuxostatorallopurinol.(BeckerMA,etal,NEJM2005)

• Colchicine0.6mg/dprophylactictherapyhelpspreventattacks

• Avoidcontinuingcolchicine formorethan6months

• Colchicinetoxicity: (especiallyinrenalinsufficiency)– Myopathy– Neuropathy– Bonemarrowsuppression– GIupset

2012AmericanCollegeofRheumatologyguidelinesformanagementofgoutKhanna D,etal,ArthritisRheum2012,PMID23024028

4/7/16

26

“TreatmentFailureGout”

• Inthemajorityofpatientswithgout,thereisinadequatecontrolofhyperuricemiaorgoutsymptoms

• Usuallythisisdueto:– Inadequatemanagementbythephysician– Poorcompliance bythepatientwith medicaltherapy

Case4

An82yearoldmanwithahistoryofdiabetes,CKD,andosteoarthritisisbrought toseeyou foragitation.Onexamhistempis101.1°Fandheissomewhatdisoriented.Theexamisonlynotableforwarmth&swellingoftherightknee.Inadditiontoobtainingbloodandurine tests&cultures,youaspiratethekneetoevaluatefor:A. SepticArthritisB. GoutC. Pseudogout(acuteCPPD)D. Alloftheabove

4/7/16

27

82y.o.manwithfever,delerium andkneeswelling.Youaspiratethekneetoevaluatefor:

A. SepticArthritisB. GoutC. PseudogoutD. Alloftheabove

5

Case4

An82yearoldmanwithahistoryofdiabetes,CKD,andosteoarthritisisbrought toseeyou foragitation.Onexamhistempis101.1°Fandheissomewhatdisoriented.Theexamisonlynotableforwarmth&swellingoftherightknee.Inadditiontoobtainingbloodandurine tests&cultures,youaspiratethekneetoevaluatefor:A. SepticArthritisB. GoutC. Pseudogout(acuteCPPD)D. Alloftheabove

4/7/16

28

TipsforKneeAspirationwatchNEJMvideo:DOI10.1056/NEJMvcm051914

• Ifsendingcultures,– Acheive sterileenvironmentwithbetadine orhibiclens.

– Usesterilegloves• Anesthetizewith1%lidocaine(butcandissolve crystals)

• Usea20-22Gneedleand10ccsyringe

Don’t:• Aspiratethroughcellulitis

• Aspirateafteracuteinjury andfractureisaconcern

• Aspirateaprostheticjoint

• (patientisanti-coagulated)

AcuteCPPDisanexcellentmimickerofsepticarthritis

• SystemicSymptoms arecommon, especially intheelderly– 25%ofpatientspresentwithfever38-39°C– 10%ofpatientshavementalstatuschanges

• Preferentiallyaffectslargerjoints(wrists, elbows,shoulders, hips, knees, ankles)

• CPPDcancoexistswithsepticarthritis(just likegout)

MasudaI&KIshikawa,Clin Orthop Relat Res,1988,PMID3349673Papanicolas LE,etal, JRheumatol 2012

4/7/16

29

http://courses .washington.e du/hu bio5 53/ im ages/crystal. jpg

http:/ /aaaamom.blogspo t.co m/2008/0 3/crystal -qu een. html

http:/ /www.rad.washingto n.ed u/static pix/mskb ook/CP P DAPW ris t. jpg

Chondrocalcinosis

4/7/16

30

Calciumpyrophosphate(CPP)crystalmediateddisease(CPPD)

RosenthalAK&RyanLM,NatRevRheumatol 2011

Calciumpyrophosphate(CPP)crystalmediateddisease(CPPD)

Abhishek A&DohertyM,NatRevRheumatol 2011

4/7/16

31

SecondarycausesofCPPD

• Hyperparathyroidism• Hypophosphatasia• Hypomagnesemia

– Barttersyndrome(hypomagnesemia,hypokalemia,metabolicalkalosis)

– Gitelman syndrome(hypomagnesemia,tubularhypokalemia,hypocalciuria)

• Hemochromatosis

TreatmentofPseudogout

• JointAspiration• CorticosteroidInjection

• NSAIDS(naproxen500mgBID,indocin 50mgTID,voltaren)

• Prednisone: 30-60mgqd,taperover6-18days• Colchicine 0.6mgqD - BID

4/7/16

32

Summary

• In patients presenting with monoarticular arthritis, infection is the primary concern

• Recognize signs of acute gout • Gout can cause severe arthritis but can easily be

managed (although often it is not).• Acute calcium pyrophosphate disease (CPPD) is

a strong mimicker of septic arthritis in the elderly.

Thanks!

4/7/16

33

AdditionalReading

• 2012AmericanCollegeofRheumatologyguidelinesformanagement ofgout.Part1&2,ArthritisCare&Res2012,PMID23024028&23024029

• Doesthisadultpatienthaveseptic arthritis?MargarettenME,etal,JAMA2007,PMID17405973

• EULARrecommendationsforcalciumpyrophosphatedeposition.PartI&II;AnnRheumDis,2011

New Current Strategies for Gout and Other Types of Monoarticular … · 2016. 4. 13. · Choose...

Documents

Transcript of New Current Strategies for Gout and Other Types of Monoarticular … · 2016. 4. 13. · Choose...