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
Oevrproduction Underexcretion

Hyperuricemia ________________________________________ Silent Gout Tissue Deposition Renal manifestations Associated CV events & 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 Dont 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

Wont 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 ?
Allopurinol
Issue in renal disease Drug interactions Potentially fatal hypersensitivity syndrome Risk of nephrolithiasis Mutiple daily dosing X X X X X

Uricosuric
X 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 : Cant 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: 51 & 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 : 62 & 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. Doesnt have gout

B. ASX. Hyperuricemia
C. Interflare period D. Advanced Gout

WOULD YOU CHANGE MDS 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