gout(2)

GOUTGOUT

Dr Bhupesh DhananjayanDr Bhupesh Dhananjayan

MD MPH MD MPH

DefinitionDefinition

Heterogeneous group of diseases involving : Heterogeneous group of diseases involving : An elevated serum urate concentration (hyperuricemia) An elevated serum urate concentration (hyperuricemia) Recurrent attacks of acute arthritis in which monosodium urate Recurrent attacks of acute arthritis in which monosodium urate monohydrate crystals are demonstrable in synovial fluid monohydrate crystals are demonstrable in synovial fluid leukocytes leukocytes Aggregates of sodium urate monohydrate crystals (tophi) Aggregates of sodium urate monohydrate crystals (tophi) deposited chiefly in and around joints, which sometimes lead to deposited chiefly in and around joints, which sometimes lead to deformity and crippling deformity and crippling Renal disease involving glomerular, tubular, and interstitial Renal disease involving glomerular, tubular, and interstitial tissues and blood vessels tissues and blood vessels Uric acid nephrolithiasis Uric acid nephrolithiasis

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

EpidemiologyEpidemiology

Prevalence of hyperuricemiaPrevalence of hyperuricemia 2.3 – 41.4% in various populations. 2.3 – 41.4% in various populations.

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

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

Incidence of GoutIncidence of Gout

Varies depending on population studied – 1.8 /1000 – 3.2/1000Varies depending on population studied – 1.8 /1000 – 3.2/1000

RR for blacks slightly higher (1.3) RR for blacks slightly higher (1.3)

1977 ACR criteria for acute gout 1977 ACR criteria for acute gout The presence of characteristic urate crystals in the joint fluid, or a tophus The presence of characteristic urate crystals in the joint fluid, or a tophus proved to contain urate crystals by chemical means or polarized light proved to contain urate crystals by chemical means or polarized light microscopy, or the presence of 6 of the following 12 clinical, laboratory, and microscopy, or the presence of 6 of the following 12 clinical, laboratory, and radiographic phenomena:radiographic phenomena: 1. More than one attack of acute arthritis 1. More than one attack of acute arthritis 2. Maximum inflammation developed within 1 day 2. Maximum inflammation developed within 1 day 3. Monoarthritis attack 3. Monoarthritis attack 4. Redness observed over joints 4. Redness observed over joints 5. First metatarsophalangeal joint painful or swollen 5. First metatarsophalangeal joint painful or swollen 6. Unilateral first metatarsophalangeal joint attack 6. Unilateral first metatarsophalangeal joint attack 7. Unilateral tarsal joint attack 7. Unilateral tarsal joint attack 8. Tophus (proven or suspected) 8. Tophus (proven or suspected) 9. Hyperuricemia 9. Hyperuricemia 10. Asymmetric swelling within a joint on x ray/exam 10. Asymmetric swelling within a joint on x ray/exam 11. Subcortical cysts without erosions on x ray 11. Subcortical cysts without erosions on x ray 12. Monosodium urate monohydrate microcrystals in joint fluid during attack 12. Monosodium urate monohydrate microcrystals in joint fluid during attack 13. Joint fluid culture negative for organisms during attack 13. Joint fluid culture negative for organisms during attack

Classification of Hyperuricemia and Classification of Hyperuricemia and Gout Gout

Primary Hyperuricemia and Gout with Primary Hyperuricemia and Gout with No Associated Condition No Associated Condition

Uric acid undersecretion(80%–90%) Uric acid undersecretion(80%–90%)

IdiopathicIdiopathic

Urate overproduction (10%–20%)Urate overproduction (10%–20%)

Idiopathic Idiopathic

HGPRT deficiencyHGPRT deficiency

PRPP synthetase overactivityPRPP synthetase overactivity

Secondary Hyperuricemia and Gout Secondary Hyperuricemia and Gout with Identifiable Associated with Identifiable Associated ConditionCondition Uric acid undersecretion Uric acid undersecretion

Renal insufficiency Renal insufficiency Polycystic kidney diseasePolycystic kidney disease Lead nephropathy Lead nephropathy Drugs(Diuretics,Salicylates (low Drugs(Diuretics,Salicylates (low

dose), Pyrazinamide, Ethambutol,Niacidose), Pyrazinamide, Ethambutol,Niacin, Cyclosporine, Didanosine )n, Cyclosporine, Didanosine )Urate overproductionUrate overproduction

Myeloproliferative/ Lymphoproliferative Myeloproliferative/ Lymphoproliferative diseases / Hemolytic diseases / Hemolytic anemias/ Polycythemia vera/Other anemias/ Polycythemia vera/Other malignanciesmalignancies

Psoriasis/Glycogen storage disease Psoriasis/Glycogen storage disease Dual mechanism Dual mechanism

Obesity, ETOH,Hypoxemia and Obesity, ETOH,Hypoxemia and hypoperfusionhypoperfusion

Outcomes in Gout Outcomes in Gout Clinical outcomesClinical outcomes

60% of untreated gout have attacks within 1 yr , 78% have 60% of untreated gout have attacks within 1 yr , 78% have recurrence in 2 yrs, only 7% have no attacks in 10 yrs.recurrence in 2 yrs, only 7% have no attacks in 10 yrs.

Chronic tophaceous gout develops after 10 -20 yrs of untreated Chronic tophaceous gout develops after 10 -20 yrs of untreated gout.gout.

Incidence decreased from 14% in 1949 –> 3% in 1972.(Oduffy Incidence decreased from 14% in 1949 –> 3% in 1972.(Oduffy et al)------’colchicine’ effect’et al)------’colchicine’ effect’

Hyperuricemia control superior to self medication alone. Hyperuricemia control superior to self medication alone.

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

study)study)

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

lowering drugs is $487 to $983 compared with a cost of $5070 to lowering drugs is $487 to $983 compared with a cost of $5070 to $6571 for those not using these agents.$6571 for those not using these agents.

Diagnosis Diagnosis ClinicalClinical : :

In men , initial attack monoarticular – 1In men , initial attack monoarticular – 1stst MTP joint(50% of cases) MTP joint(50% of cases) Other jts involved – instep/knees/wrists/ olecranon bursa. Often Other jts involved – instep/knees/wrists/ olecranon bursa. Often

begins at night. Usually abrupt , severely painful. begins at night. Usually abrupt , severely painful. Later attacks – polyarticular , assoc with systemic signs., most often Later attacks – polyarticular , assoc with systemic signs., most often

initial presenting complaint in women. (hands/tarsal jts/knees)initial presenting complaint in women. (hands/tarsal jts/knees) Precipitants – Minor trauma , ETOH, diuretic Rx, Surgery, severe Precipitants – Minor trauma , ETOH, diuretic Rx, Surgery, severe

medical illness, hypouricemic Rx.medical illness, hypouricemic Rx. Tophi – Classically , helix/ antihelix ,but rare ; more common , hands, Tophi – Classically , helix/ antihelix ,but rare ; more common , hands,

feet, olecranon bursa. Complications : ulceration/infection.feet, olecranon bursa. Complications : ulceration/infection.LaboratoryLaboratory:- GOLD STANDARD:- GOLD STANDARD

SF Analysis – WBC ct – 2000-100 000/ml SF Analysis – WBC ct – 2000-100 000/ml MSU crystals- needle shaped , negatively birefringent.MSU crystals- needle shaped , negatively birefringent. Serum Uric acid level – important in monitoring treatment .(42% - Serum Uric acid level – important in monitoring treatment .(42% -

normal levels)normal levels) 24 hr uric acid collection –useful in young pts with gout/ + fam h/o24 hr uric acid collection –useful in young pts with gout/ + fam h/o

DiagnosisDiagnosis

RadiologicRadiologic X RAYX RAY : :

Punched out erosions – Punched out erosions – only 45% of pts have only 45% of pts have them, takes 6 yrs to them, takes 6 yrs to developdevelop

Martel’s signMartel’s sign CT/MRI/US/Bone scanCT/MRI/US/Bone scan

Sensitive , non specificSensitive , non specific

Treatment Treatment

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

Endpoints – improvement in jt symptoms/ GI symptoms/ 10 doses taken.Endpoints – improvement in jt symptoms/ GI symptoms/ 10 doses taken. NSAIDs if diagnosis confirmed. Any NSAID can be used . NSAIDs if diagnosis confirmed. Any NSAID can be used .

Newer agents – Etoricoxcib 120 OD comparable to indomethacin 50 TID.Newer agents – Etoricoxcib 120 OD comparable to indomethacin 50 TID. In c/o renal failure /PUD - IM ACTH , oral /iv prednisone.In c/o renal failure /PUD - IM ACTH , oral /iv prednisone. Avoid adjusting dosage of urate lowering agents.Avoid adjusting dosage of urate lowering agents.

ProphylaxisProphylaxis : : Only indicated if patient is started on urate lowering Rx.Only indicated if patient is started on urate lowering Rx. Colchicine( 1-3 pills a day)/ NSAID( in colchicine intolerant).Colchicine( 1-3 pills a day)/ NSAID( in colchicine intolerant). Does not alter crystal deposition and development of tophi.Does not alter crystal deposition and development of tophi. Continue till serum urate levels stabilize and no attacks for 3 – 6 mths.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. If long term prophylactic colchicine given, check CBC ,CK every 6 mths.

Treatment (contd) Treatment (contd)

Control of hyperuricemiaControl of hyperuricemia Differing opinions regarding initiation esp. around 1Differing opinions regarding initiation esp. around 1stst

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

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

initiation.initiation. Choice of agents : Choice of agents :

Xanthine oxidase inhibitor Xanthine oxidase inhibitor Uricosuric agents. Uricosuric agents. Equal efficacy in pts with normal renal function and Equal efficacy in pts with normal renal function and who excrete < 800 mg/day of uric acid. who excrete < 800 mg/day of uric acid.


Xanthine oxidase inhibitorsXanthine oxidase inhibitors Allopurinol- only prescription drug available. Allopurinol- only prescription drug available. Renally excreted, therefore adjust dose if s.creat > 2mg% or CrCl <50Renally excreted, therefore adjust dose if s.creat > 2mg% or CrCl <50 Usually DOC in most patients.Usually DOC in most patients. S/E – GI / rash / sarcoid like reaction/Allopurinol hypersensitivity S/E – GI / rash / sarcoid like reaction/Allopurinol hypersensitivity

syndrome syndrome Drug interaction – esp. with 6 MP/azathioprine/ warfarin/theophylline.Drug interaction – esp. with 6 MP/azathioprine/ warfarin/theophylline. Desensitization protocols exist. Desensitization protocols exist. Oxypurinol – possible optionOxypurinol – possible option

Uricosuric agentsUricosuric agents Indications – no h/o renal calculi , pts <60 yrs, U.A excretion < 800 mg/dIndications – no h/o renal calculi , pts <60 yrs, U.A excretion < 800 mg/d CI - + nephrolithiasis, renal insufficiency CI - + nephrolithiasis, renal insufficiency Limit ASA to 81 mg/dayLimit ASA to 81 mg/day Probenecid/ BenzbromaroneProbenecid/ Benzbromarone


Adjuvant RxAdjuvant Rx Control obesity ,ETOH intake, hyperlipidemia ,HTN Control obesity ,ETOH intake, hyperlipidemia ,HTN Losartan / fenofibrate – weakly uricosuricLosartan / fenofibrate – weakly uricosuric Diet – moderation in purine intake. Makes a difference of up to Diet – moderation in purine intake. Makes a difference of up to

1mg % in s. uric acid.1mg % in s. uric acid. Beer, other alcoholic beverages. Beer, other alcoholic beverages. Anchovies, sardines in oil, fish roes, herring. Anchovies, sardines in oil, fish roes, herring. Yeast. Yeast. Organ meat (liver, kidneys, sweetbreads) Organ meat (liver, kidneys, sweetbreads) Legumes (dried beans, peas) Legumes (dried beans, peas) Meat extracts, consommé, gravies. Meat extracts, consommé, gravies. Mushrooms, spinach, asparagus, cauliflower Mushrooms, spinach, asparagus, cauliflower

Treatment (contd)Treatment (contd)

Newer agentsNewer agents PEG- uricase PEG- uricase FebuxostatFebuxostat

Asymptomatic hyperuricemia Asymptomatic hyperuricemia Investigate cause Investigate cause No recommendations for Rx.No recommendations for Rx.

THANK YOU THANK YOU

gout(2)

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