GOUT

Wayne Blount, MD, MPHProfessor,Emory Univ. S.O.M.

OBJECTIVESIdentify diagnostic criteria for gout

Identify 3 treatment goals for gout

Name the agents used to treat the acute flares of gout and the chronic disease of gout

Why Worry About Gout ?Prevalence increasingMay be signal for unrecognized comorbidities : ( Not to point of searching)

Obesity (Duh!)Metabolic syndromeDMHTNCV diseaseRenal disease

URATE, HYPERURICEMIA & GOUT

Urate: end product of purine metabolism

Hyperuricemia: serum urate > urate solubility (> 6.8 mg/dl)

Gout: deposition of monosodium urate crystals in tissues

HYPERURICEMIA & GOUT

Hyperuricemia caused byOverproductionUnderexcretion

No Gout w/o crystal deposition

THE GOUT CASCADE UrateOevrproductionUnderexcretion

Hyperuricemia

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SilentGoutRenalAssociatedTissue manifestationsCV events &Deposition mortality

GOUT: A Chronic Disease of 4 stages

Asymptomatic hyperuricemia

Acute Flares of crystallization

Intervals between flares

Advanced Gout & Complications

ACUTE GOUTY FLARESAbrupt onset of severe joint inflammation, often nocturnal;Warmth, swelling, erythema, & pain;Possibly feverUntreated? Resolves in 3-10 days90% 1st attacks are monoarticular50% are podagra

SITES OF ACUTE FLARES90% of gout patients eventually have podagra : 1st MTP joint

SitesCan occur in other joints, bursa & tendons

INTERVALS SANS FLARESAsymptomatic

If untreated, may advance

Intervals may shortenCrystals in asx jointsBody urate stores increase

FLARE INTERVALSSilent tissue deposition & Hidden Damage

ADVANCED GOUTChronic Arthritis

X-ray Changes

Tophi Develop

Acute Flares continue

ADVANCED GOUTChronic ArthritisPolyarticular acute flares with upper extremities more involved

TOPHISolid urate deposits in tissues

TOPHIIrregular & destructive

TOPHI RISK FACTORS

Long duration of hyperuricemia

Higher serum urate

Long periods of active, untreated gout

RADIOLOGIC SIGNS

X-RAYS

X-RAYS

DIAGNOSING GOUT

Hx & P.E.

Synovial fluid analysis

Not Serum Urate

SERUM URATE LEVELSNot reliable

May be normal with flares

May be high with joint Sx from other causes

GOUT RISK FACTORSMalePostmenopausal femaleOlderHypertensionPharmaceuticals:Diuretics, ASA, cyclosporine

GOUT RISK FACTORSTransplantAlcohol intakeHighest with beerNot increased with wineHigh BMI (obesity)Diet high in meat & seafood

SYNOVIAL FLUID ANALYSIS (Polarized Light Microscopy)The Gold standard

Crystals intracellular during attacks

Needle & rod shapes

Strong negative birefringence

SYNOVIAL FLUID

DIFFERENTIAL DIAGNOSIS

Pseudogout: Chondrocalcinosis, CPPDPsoriatic ArthritisOsteoarthritisRheumatoid arthritisSeptic arthritisCellulitis

Gout vs. CPPD

Similar Acute attacks

Different crystals under Micro;Rhomboid, irregular in CPPD

Gout vs CPPD

RA vs Gout

Both have polyarticular, symmetric arthritis

Tophi can be mistaken for RA nodules

RA vs Gout

REDNECK MEDICAL TERMS

BENIGN : WHAT YOU BE AFTER YOU BE EIGHT

TREATMENT GOALS

Rapidly end acute flaresProtect against future flaresReduce chance of crystal inflammation

Prevent disease progressionLower serum urate to deplete total body urate poolCorrect metabolic cause

ENDING ACUTE FLARESControl inflammation & pain & resolve the flareNot a cureCrystals remain in jointsDont try to lower serum urate during a flareChoice of med not as critical as alacrity & duration EBM

Acute Flare Med Choices

NSAIDS

Colchicine

Corticosteroids

MED ConsiderationsNSAIDS : Interaction with warfarinContraindicated in:Renal diseasePUDGI bleedersASA-induced RAD

MED ConsiderationsColchicine :Not as effective late in flareDrug interaction : Statins, Macrolides, CyclosporineContraindicated in dialysis pt.sCautious use in : renal or liver dysfunction; active infection, age > 70

MED Considerations

Corticosteroids :Worse glycemic controlMay need to use mod-high doses

TREATMENT GOALSRapidly end acute flaresProtect against future flaresReduce chance of crystal inflammation

Prevent disease progressionLower serum urate to deplete total body urate poolCorrect metabolic cause

PROTECTION VS. FUTURE FLARESColchicine : 0.5-1.0 mg/dayLow-dose NSAIDS

Both decrease freq & severity of flaresPrevent flares with start of urate-lowering RX Best with 6 mos of concommitant RXEBM

Wont stop destructive aspects of gout

TREATMENT GOALSRapidly end acute flaresProtect against future flaresReduce chance of crystal inflammation

Prevent disease progressionLower serum urate to deplete total body urate poolCorrect metabolic cause

PREVENT DISEASE PROGRESSIONLower urate to < 6 mg/dl : DepletesTotal body urate poolDeposited crystals EBM

RX is lifelong & continuousMED choices :Uricosuric agentsXanthine oxidase inhibitor

PREVENT THIS

URICOSURIC AGENTSProbenecid, (Losartan & fenofibrate for mild disease)

Increased secretion of urate into urine

Reverses most common physiologic abnormality in gout ( 90% pt.s are underexcretors)

XANTHINE OXIDASE INHIBITORAllopurinol :Blocks conversion of hypoxanthine to uric acidEffective in overproducersMay be effective in underexcretorsCan work in pt.s with renal insufficiency

WHICH AGENT ?AllopurinolUricosuricIssue in renal disease X XDrug interactions X XPotentially fatal hypersen- sitivity syndrome XRisk of nephrolithiasis XMutiple daily dosing X

WHICH AGENTBase choice on above considerations & whether pt is an overproducer or underexcretor : Need to get a 24-hr. urine for urate excretion:< 700 --- underexcretor (uricosuric)> 700 --- overproducer (allopurinol)

NEW AGENTSRX gaps : Cant always get urate < 6AllergiesDrug interactionsAllopurinol intoleranceWorse Renal disease

URICASE ENZYMES (Stay Tuned)

Catabolize urate to allantoin:More soluble, excretable form

Currently approved for hypoeruricemia in tumor lysis syndrome

Some concerns: fatal immunogenicity & unknown long-term effects

CASE STUDIES

CASE J.F.80 YO W F c/o acute overnight pain & swelling in R kneePE: 51 & 180 lbsR knee swollen, warm & erythematousPMH : HTN x 5 yrsMeds: HCTZ (25 QD) & ASASH : 20 PY smoker; 5 wine drinks/wk

WHAT ARE J.F.s RISK FACTORS FOR GOUT ?A. HTNB. SMOKERC. HCTZD. ASAWINE CONSUMPTIONOBESITYAGEPOSTMENOPAUSAL

HOW WOULD YOU DX GOUT ?

A. HX & PE COMPATIBLEB. CHECK SERUM URATE LEVELASSESS SYNOVIAL FLUIDTRIAL OF COLCHICINECHECK X-RAYS

IF YOU DX GOUT, WHAT RX TODAY? (& Why?)

A. MOTRINB. INDOCINC. PREDNISONED. ALLOPURINOLE. PROBENECIDF. COLCHICINE

NEXT STEP FOR J.F. ?

A. Modify risk factorsB. Give refills to rx next flareC. Start colchicine to prevent flaresD. Check serum urate levelE. Start allopurinolF. Start probenecid

CASE M.B.

56 YO W M c/o hand stiffness & growthsPE : 62 & 205 lbsMultiple tophi; chronic arthritisPMH : DM x 8 yrs; gout x4 yrs, but no flares x 3 yrs, lost 20# on Atkins dietMeds: Glyburide; colchicine (0.6 mg TID)Labs: Creat.= 2.0; Urate = 11.4

IN WHAT STAGE OF GOUT IS M.B. ?

A. Doesnt have gout

B. ASX. Hyperuricemia

C. Interflare period

D. Advanced Gout

WOULD YOU CHANGE MDS RX ?

No Not goutNo No flare x 3 yrs.Yes - Increase colchicineYes Add allopurinolYes Add benemid

WHAT OTHER ISSUES WOULD YOU CONSIDER ?

Renal dysfunctionWeightDMGlyburideDiet

CONCLUSIONSGout is chronic with 4 stagesUncontrolled gout can lead to severe diseaseSeparate RX for flares & preventing advancementMany meds for flaresTreating the disease requires lowering urateGet a 24-hr urine for urate excretion

QUESTIONS