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GOUT

Dr Bhupesh Dhananjayan

MD MPH

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Definition

Heterogeneous group of diseases involving :An elevated serum urate concentration (hyperuricemia)Recurrent attacks of acute arthritis in which monosodium uratemonohydrate crystals are demonstrable in synovial fluidleukocytes

Aggregates of sodium urate monohydrate crystals (tophi)deposited chiefly in and around joints, which sometimes lead todeformity and cripplingRenal disease involving glomerular, tubular, and interstitial tissuesand blood vesselsUric acid nephrolithiasis

Hyperuricemia : serum uric acid >7mg% (males) and >6mg% (females)

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Epidemiology

Prevalence of hyperuricemia

2.3 41.4% in various populations.

Corresponds with serum creatinine /BUN levels, body weight,height, age, blood pressure, and alcohol intake. (Taiwan)

Body bulk (as estimated by body weight, surface area, or body massindex) has proved to be one of the most important predictors ofhyperuricemia in people of widely differing races and cultures.

Incidence of Gout

Varies depending on population studied 1.8 /1000 3.2/1000RR for blacks slightly higher (1.3)

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1977 ACR criteria for acute gout

The presence of characteristic urate crystals in the joint fluid, or a tophusproved to contain urate crystals by chemical means or polarized lightmicroscopy, or the presence of 6 of the following 12 clinical, laboratory, andradiographic phenomena:1. More than one attack of acute arthritis2. Maximum inflammation developed within 1 day3. Monoarthritis attack

4. Redness observed over joints5. First metatarsophalangeal joint painful or swollen6. Unilateral first metatarsophalangeal joint attack7. Unilateral tarsal joint attack8. Tophus (proven or suspected)9. Hyperuricemia

10. Asymmetric swelling within a joint on x ray/exam11. Subcortical cysts without erosions on x ray12. Monosodium urate monohydrate microcrystals in joint fluid during attack13. Joint fluid culture negative for organisms during attack

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Classification of Hyperuricemia andGout

Primary Hyperuricemia and Gout withNo Associated Condition

Uric acid undersecretion(80%90%)

Idiopathic

Urate overproduction (10%20%)

Idiopathic

HGPRT deficiency

PRPP synthetase overactivity

Secondary Hyperuricemia and Goutwith Identifiable AssociatedCondition

Uric acid undersecretionRenal insufficiencyPolycystic kidney diseaseLead nephropathyDrugs(Diuretics,Salicylates (low

dose), Pyrazinamide, Ethambutol,Niacin, Cyclosporine, Didanosine )Urate overproductionMyeloproliferative/ Lymphoproliferativediseases / Hemolyticanemias/ Polycythemia vera/Other

malignanciesPsoriasis/Glycogen storage diseaseDual mechanismObesity, ETOH,Hypoxemia andhypoperfusion

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Outcomes in Gout

Clinical outcomes 60% of untreated gout have attacks within 1 yr , 78% have

recurrence in 2 yrs, only 7% have no attacks in 10 yrs. Chronic tophaceous gout develops after 10 -20 yrs of untreated

gout.Incidence decreased from 14% in 1949> 3% in 1972.(Oduffy

et al)------colchicine effect Hyperuricemia control superior to self medication alone.

Humanistic outcomes Treatment outcomes decrease QOL in pts with gout. Adherence to allopurinol only 56%. (Riedel et al , managed care

study)

Economic outcomes Direct burden annually is 27.4 million USD. (men only) Patients with acute gout miss 3-5 days of work annually. Average cost-effectiveness ratio for patients using urate-lowering

drugs is $487 to $983 compared with a cost of $5070 to $6571

for those not using these agents.

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Diagnosis

Clinical : In men , initial attack monoarticular 1st MTP joint(50% of cases)

Other jts involved instep/knees/wrists/ olecranon bursa. Oftenbegins at night. Usually abrupt , severely painful.

Later attacks polyarticular , assoc with systemic signs., most ofteninitial presenting complaint in women. (hands/tarsal jts/knees)

Precipitants Minor trauma , ETOH, diuretic Rx, Surgery, severemedical illness, hypouricemic Rx.

Tophi Classically , helix/ antihelix ,but rare ; more common , hands,feet, olecranon bursa. Complications : ulceration/infection.

Laboratory:- GOLD STANDARD SF Analysis WBC ct 2000-100 000/ml

MSU crystals- needle shaped , negatively birefringent. Serum Uric acid level important in monitoring treatment .(42% -

normal levels) 24 hr uric acid collectionuseful in young pts with gout/ + fam h/o

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Diagnosis

Radiologic

X RAY :

Punched out erosionsonly 45% of pts have

them, takes 6 yrs todevelop

Martels sign

CT/MRI/US/Bone scan

Sensitive , non specific

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Treatment

Acute gouty arthritis: Anti- inflammatory drugs ( if s.creat < 2mg/dl, no PUD) Colchicine preferred in pts without confirmed diagnosis of gout.

Endpoints improvement in jt symptoms/ GI symptoms/ 10 doses taken.

NSAIDs if diagnosis confirmed. Any NSAID can be used .Newer agents Etoricoxcib 120 OD comparable to indomethacin 50 TID.

In c/o renal failure /PUD - IM ACTH , oral /iv prednisone. Avoid adjusting dosage of urate lowering agents.

Prophylaxis : Only indicated if patient is started on urate lowering Rx. Colchicine( 1-3 pills a day)/ NSAID( in colchicine intolerant).

Does not alter crystal deposition and development of tophi. Continue till serum urate levels stabilize and no attacks for 3 6 mths. If long term prophylactic colchicine given, check CBC ,CK every 6 mths.

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Treatment (contd)

Control of hyperuricemia Differing opinions regarding initiation esp. around 1st

attack. Clear evidence if erosions + on X-ray / chronic

tophaceous gout/ >2 gout attacks per year. Goal : s. urate levels < 6 mg%. Serial s. uric acid at least once every 6 mths upon

initiation. Choice of agents :

Xanthine oxidase inhibitorUricosuric agents.Equal efficacy in pts with normal renal function andwho excrete < 800 mg/day of uric acid.

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Treatment (contd)

Xanthine oxidase inhibitors Allopurinol- only prescription drug available. Renally excreted, therefore adjust dose if s.creat > 2mg% or CrCl

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Treatment (contd)

Adjuvant Rx Control obesity ,ETOH intake, hyperlipidemia ,HTN

Losartan / fenofibrate weakly uricosuric

Diet moderation in purine intake. Makes a difference of up to1mg % in s. uric acid.

Beer, other alcoholic beverages.

Anchovies, sardines in oil, fish roes, herring.

Yeast.

Organ meat (liver, kidneys, sweetbreads)

Legumes (dried beans, peas)

Meat extracts, consomm, gravies.

Mushrooms, spinach, asparagus, cauliflower

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Treatment (contd)

Newer agents

PEG- uricase

Febuxostat

Asymptomatic hyperuricemia Investigate cause

No recommendations for Rx.

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