GOUT
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GOUT. Wayne Blount, MD, MPH Professor, Emory Univ. S.O.M. OBJECTIVES. Identify 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 increasing

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GOUT

Wayne Blount, MD, MPH

Professor,

Emory Univ. S.O.M.


OBJECTIVES

  • Identify 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 increasing

  • May be signal for unrecognized comorbidities : ( Not to point of searching)

    Obesity (Duh!)

    Metabolic syndrome

    DM

    HTN

    CV disease

    Renal 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 by

    Overproduction

    Underexcretion

  • No Gout w/o crystal deposition


THE GOUT CASCADE

  • Urate

  • OevrproductionUnderexcretion

  • Hyperuricemia

  • ________________________________________

  • SilentGoutRenalAssociated

  • Tissue 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 FLARES

  • Abrupt onset of severe joint inflammation, often nocturnal;

    Warmth, swelling, erythema, & pain;

    Possibly fever

  • Untreated? Resolves in 3-10 days

  • 90% 1st attacks are monoarticular

  • 50% are podagra


SITES OF ACUTE FLARES

  • 90% of gout patients eventually have podagra : 1st MTP joint


Sites

  • Can occur in other joints, bursa & tendons


INTERVALS SANS FLARES

  • Asymptomatic

  • If untreated, may advance

  • Intervals may shorten

  • Crystals in asx joints

  • Body urate stores increase


FLARE INTERVALS

  • Silent tissue deposition & Hidden Damage


ADVANCED GOUT

  • Chronic Arthritis

  • X-ray Changes

  • Tophi Develop

  • Acute Flares continue


ADVANCED GOUT

  • Chronic Arthritis

  • Polyarticular acute flares with upper extremities more involved


TOPHI

  • Solid urate deposits in tissues


TOPHI

  • Irregular & 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 LEVELS

  • Not reliable

  • May be normal with flares

  • May be high with joint Sx from other causes


GOUT RISK FACTORS

  • Male

  • Postmenopausal female

  • Older

  • Hypertension

  • Pharmaceuticals:

    Diuretics, ASA, cyclosporine


GOUT RISK FACTORS

  • Transplant

  • Alcohol intake

    Highest with beer

    Not increased with wine

  • High 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, CPPD

  • Psoriatic Arthritis

  • Osteoarthritis

  • Rheumatoid arthritis

  • Septic arthritis

  • Cellulitis


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 flares

    Protect against future flares

    Reduce chance of crystal inflammation

  • Prevent disease progression

    Lower serum urate to deplete total body urate pool

    Correct metabolic cause


ENDING ACUTE FLARES

  • Control inflammation & pain & resolve the flare

  • Not a cure

  • Crystals remain in joints

  • Don’t try to lower serum urate during a flare

  • Choice of med not as critical as alacrity & duration EBM


Acute Flare Med Choices

  • NSAIDS

  • Colchicine

  • Corticosteroids


MED Considerations

  • NSAIDS :

    Interaction with warfarin

    Contraindicated in:

    Renal disease

    PUD

    GI bleeders

    ASA-induced RAD


MED Considerations

  • Colchicine :

    Not as effective “late” in flare

    Drug interaction : Statins, Macrolides, Cyclosporine

    Contraindicated in dialysis pt.s

    Cautious use in : renal or liver dysfunction; active infection, age > 70


MED Considerations

  • Corticosteroids :

    Worse glycemic control

    May need to use mod-high doses


TREATMENT GOALS

  • Rapidly end acute flares

    Protect against future flares

    Reduce chance of crystal inflammation

  • Prevent disease progression

    Lower serum urate to deplete total body urate pool

    Correct metabolic cause


PROTECTION VS. FUTURE FLARES

  • Colchicine : 0.5-1.0 mg/day

  • Low-dose NSAIDS

  • Both decrease freq & severity of flares

  • Prevent flares with start of urate-lowering RX

    Best with 6 mos of concommitant RX

    EBM

  • Won’t stop destructive aspects of gout


TREATMENT GOALS

  • Rapidly end acute flares

    Protect against future flares

    Reduce chance of crystal inflammation

  • Prevent disease progression

    Lower serum urate to deplete total body urate pool

    Correct metabolic cause


PREVENT DISEASE PROGRESSION

  • Lower urate to < 6 mg/dl : Depletes

    Total body urate pool

    Deposited crystals EBM

  • RX is lifelong & continuous

  • MED choices :

    Uricosuric agents

    Xanthine oxidase inhibitor


PREVENT THIS


URICOSURIC AGENTS

  • Probenecid, (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 INHIBITOR

  • Allopurinol :

  • Blocks conversion of hypoxanthine to uric acid

  • Effective in overproducers

  • May be effective in underexcretors

  • Can work in pt.s with renal insufficiency


WHICH AGENT ?

AllopurinolUricosuric

Issue in renal disease X X

Drug interactions X X

Potentially fatal hypersen-

sitivity syndrome X

Risk of nephrolithiasis X

Mutiple daily dosing X


WHICH AGENT

  • Base 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 AGENTS

  • RX gaps :

  • Can’t always get urate < 6

  • Allergies

  • Drug interactions

  • Allopurinol intolerance

  • Worse 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 knee

  • PE: 5’1’’ & 180 lbs

    R knee swollen, warm & erythematous

  • PMH : HTN x 5 yrs

  • Meds: HCTZ (25 QD) & ASA

  • SH : 20 PY smoker; 5 wine drinks/wk


WHAT ARE J.F.’s RISK FACTORS FOR GOUT ?

  • A. HTN

  • B. SMOKER

  • C. HCTZ

  • D. ASA

  • WINE CONSUMPTION

  • OBESITY

  • AGE

  • POSTMENOPAUSAL


HOW WOULD YOU DX GOUT ?

  • A. HX & PE COMPATIBLE

  • B. CHECK SERUM URATE LEVEL

  • ASSESS SYNOVIAL FLUID

  • TRIAL OF COLCHICINE

  • CHECK X-RAYS


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

  • A. MOTRIN

  • B. INDOCIN

  • C. PREDNISONE

  • D. ALLOPURINOL

  • E. PROBENECID

  • F. COLCHICINE


NEXT STEP FOR J.F. ?

  • A. Modify risk factors

  • B. Give refills to rx next flare

  • C. Start colchicine to prevent flares

  • D. Check serum urate level

  • E. Start allopurinol

  • F. Start probenecid


CASE M.B.

  • 56 YO W M c/o hand stiffness & growths

  • PE : 6’2’’ & 205 lbs

    Multiple tophi; chronic arthritis

  • PMH : DM x 8 yrs; gout x4 yrs, but no flares x 3 yrs, lost 20# on Atkins diet

  • Meds: Glyburide; colchicine (0.6 mg TID)

  • Labs: Creat.= 2.0; Urate = 11.4


IN WHAT STAGE OF GOUT IS M.B. ?

  • A. Doesn’t have gout

  • B. ASX. Hyperuricemia

  • C. Interflare period

  • D. Advanced Gout


WOULD YOU CHANGE MD’S RX ?

  • No – Not gout

  • No – No flare x 3 yrs.

  • Yes - Increase colchicine

  • Yes – Add allopurinol

  • Yes – Add benemid


WHAT OTHER ISSUES WOULD YOU CONSIDER ?

  • Renal dysfunction

  • Weight

  • DM

  • Glyburide

  • Diet


CONCLUSIONS

  • Gout is chronic with 4 stages

  • Uncontrolled gout can lead to severe disease

  • Separate RX for flares & preventing advancement

  • Many meds for flares

  • Treating the disease requires lowering urate

  • Get a 24-hr urine for urate excretion


QUESTIONS


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