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