gout. case a 45y/o obese male with h/o painfull ankle associated with hottness and redness since 2...

GOUTGOUT

Case Case

A 45y/o obese male with h/o painfull A 45y/o obese male with h/o painfull ankle associated with hottness and ankle associated with hottness and redness since 2 days agoredness since 2 days ago

PMH: HTN, DMPMH: HTN, DMP/E: Signs of severe ankle arthritisP/E: Signs of severe ankle arthritis

GoutGout(monosodium urate crystal (monosodium urate crystal

deposition disease)deposition disease) is characterized biochemically by is characterized biochemically by

extracellular urate supersaturation extracellular urate supersaturation

GoutGoutRecurrent attacks of acute Recurrent attacks of acute

inflammatory arthritis inflammatory arthritis Accumulation of urate crystals in the Accumulation of urate crystals in the

form of tophaceous deposits form of tophaceous deposits Uric acid nephrolithiasis Uric acid nephrolithiasis NephropathyNephropathy

EpidemiologyEpidemiology incidence = 0.2-0.35/1000 incidence = 0.2-0.35/1000 Prevalence = 1.6-13.6/1000Prevalence = 1.6-13.6/1000Prevalance increased with age and Prevalance increased with age and

uric acid leveluric acid levelThe incidence rate of gout is 4.9% for The incidence rate of gout is 4.9% for

urate greater than 9mg/dl and 0.5% urate greater than 9mg/dl and 0.5% for 7-8.9 and 0.1% for less than for 7-8.9 and 0.1% for less than 7mg/dl7mg/dl

Familial incidence range from 11-Familial incidence range from 11-80%80%

hyperuricemiahyperuricemia

Hyperurecemia: Overproduction or underexcretion of uric acid,the byproduct of purine metabolism in humans can result in hyperurecemia

The upper limit = at 7 mg/dl in men and 6 mg/dl in women

Decreased efficiency of renal uric Decreased efficiency of renal uric acid excretion is responsible for acid excretion is responsible for about 85 to 90 percent of primary or about 85 to 90 percent of primary or secondary hyperuricemia .secondary hyperuricemia .

Supersaturated concentration of urate (> or= 6/8mg/dl)

cause crystalization and deposition in joints and other connective tissues

DNADNARNARNA

PyrimidinesPurines

Uric acid Energy

PRPP.Syn

IMP.DXMP

GTP & ATP &

AMP.SAS.S

5’NAMP. D

GuanaseXantine oxidase

Xantine oxidase

Aden.PRT

Ribose-5 phosphate + ATP

PRPP + AMP

PRPP Synthetases

IMPUric Acid

Uric acid productionUric acid production

SalvageSalvageSometime free purine base are Sometime free purine base are

salvaged and reused instead of salvaged and reused instead of degrading them all the way to uric degrading them all the way to uric acid.acid.

Salvage of purine BasesSalvage of purine Bases

AdenineAdenineGuanine Guanine HypoxanthineHypoxanthine

PhosphoribosylationPrimary nuclotides

Hyperuricemia cascadeHyperuricemia cascade

Hyperuricemia

UnderexcretionOverproduction

Endogenous purinesynthesis

Dietary purines

Tissuenucleicacids

Uric acid overproductionUric acid overproduction

• Primary hyperurecimiaPrimary hyperurecimia

•Secondary hyperuricemia Secondary hyperuricemia

·IdiopathicIdiopathic·HGPRT deficiencyHGPRT deficiency·PRPP synthetase superactivityPRPP synthetase superactivity

·Excessive dietary purine intakeExcessive dietary purine intake·Increased nucleotide turnoverIncreased nucleotide turnover myelo & lymphoproliferative dis. ,multiple myelomamyelo & lymphoproliferative dis. ,multiple myeloma secondary polycytemia,pernicious anemia,hemoglobinopathysecondary polycytemia,pernicious anemia,hemoglobinopathy hemolysis,infectious mononucleosis hemolysis,infectious mononucleosis ·Accelerated ATP degradation Accelerated ATP degradation Glycogen storage dis( type3,5,7) ,G6PDGlycogen storage dis( type3,5,7) ,G6PD Fruoctose intolerance(F1P.aldolase)Fruoctose intolerance(F1P.aldolase) Hypoxemia & tissue underperfusionHypoxemia & tissue underperfusion Sever muscle exertion ,acutly ill patient,MI, epilepsySever muscle exertion ,acutly ill patient,MI, epilepsy

·Excessive dietary purine intakeExcessive dietary purine intake·Increased nucleotide turnoverIncreased nucleotide turnover myelo & lymphoproliferative dis. ,multiple myelomamyelo & lymphoproliferative dis. ,multiple myeloma secondary polycytemia,pernicious anemia,hemoglobinopathysecondary polycytemia,pernicious anemia,hemoglobinopathy hemolysis,infectious mononucleosis hemolysis,infectious mononucleosis

·Accelerated ATP degradationAccelerated ATP degradation Glycogen storage dis( type3,5,7) ,G6PDGlycogen storage dis( type3,5,7) ,G6PD Fruoctose intolerance(F1P.aldolase)Fruoctose intolerance(F1P.aldolase) Hypoxemia & tissue underperfusionHypoxemia & tissue underperfusion Sever muscle exertion ,acutly ill patient,MI, epilepsySever muscle exertion ,acutly ill patient,MI, epilepsy

·Accelerated ATP degradation Accelerated ATP degradation Glycogen storage dis( type3,5,7) ,G6PDGlycogen storage dis( type3,5,7) ,G6PD Fruoctose intolerance(F1P.aldolase)Fruoctose intolerance(F1P.aldolase) Hypoxemia & tissue underperfusionHypoxemia & tissue underperfusion Sever muscle exertion ,acutly ill patient,MI, epilepsySever muscle exertion ,acutly ill patient,MI, epilepsy

·Excessive dietary purine intakeExcessive dietary purine intake·Increased nucleotide turnoverIncreased nucleotide turnover myelo & lymphoproliferative dis. ,multiple myelomamyelo & lymphoproliferative dis. ,multiple myeloma secondary polycytemia,pernicious secondary polycytemia,pernicious anemia,hemoglobinopathyanemia,hemoglobinopathy hemolysis,infectious mononucleosis hemolysis,infectious mononucleosis ·Accelerated ATP degradation Accelerated ATP degradation Glycogen storage dis( type3,5,7) ,G6PDGlycogen storage dis( type3,5,7) ,G6PD Fruoctose intolerance(F1P.aldolase)Fruoctose intolerance(F1P.aldolase) Hypoxemia & tissue underperfusionHypoxemia & tissue underperfusion Sever muscle exertion ,acutly ill patient,MI, epilepsySever muscle exertion ,acutly ill patient,MI, epilepsy

·Accelerated ATP degradationAccelerated ATP degradation Glycogen storage dis( type3,5,7) ,G6PDGlycogen storage dis( type3,5,7) ,G6PD Fruoctose intolerance(F1P.aldolase)Fruoctose intolerance(F1P.aldolase) Hypoxemia & tissue underperfusionHypoxemia & tissue underperfusion Sever muscle exertion ,acutly ill patient,MI, epilepsySever muscle exertion ,acutly ill patient,MI, epilepsy

Uric acid UnderexcretionUric acid Underexcretion Primary hyperurecimiaPrimary hyperurecimia

Secondary hyperuricemiaSecondary hyperuricemia•IdiopathicIdiopathic

•Diminished renal function ( GFR)Diminished renal function ( GFR)• Inhibition of tubular urate secretionInhibition of tubular urate secretion•Enhanced tubular urate reabsorptionEnhanced tubular urate reabsorption•Mechanism incompletely definedMechanism incompletely defined

•Diminished renal function ( GFR)Diminished renal function ( GFR)• Inhibition of tubular urate secretionInhibition of tubular urate secretion Competitive anions ( keto & lactic acidosis ) Competitive anions ( keto & lactic acidosis ) Polycyctic kidney, Lead nephropathy?Polycyctic kidney, Lead nephropathy?

•Diminished renal function ( GFR)Diminished renal function ( GFR)• Inhibition of tubular urate secretionInhibition of tubular urate secretion•Enhanced tubular urate reabsorptionEnhanced tubular urate reabsorption Dehydration : diuretics,adrenal insufficency, Dehydration : diuretics,adrenal insufficency, nephrogenic DInephrogenic DI Insulin resistance SyndromeInsulin resistance Syndrome

•Diminished renal function ( GFR)Diminished renal function ( GFR)• Inhibition of tubular urate secretionInhibition of tubular urate secretion•Enhanced tubular urate reabsorptionEnhanced tubular urate reabsorption•Mechanism incompletely definedMechanism incompletely defined Hypertension,Hyperparathyroidism,hypoparathyroidismHypertension,Hyperparathyroidism,hypoparathyroidism

.hypothyroidism, Drugs (cyclosporine, pyrazinamide , .hypothyroidism, Drugs (cyclosporine, pyrazinamide , ethambutol , salicylate, nicotinic acid) , ethambutol , salicylate, nicotinic acid) , Chronic lead nephropathyChronic lead nephropathy

Classification of hyperuricemiaClassification of hyperuricemia3- Combined Overproduction & Underexcretion3- Combined Overproduction & Underexcretion

• Alcohol consumptionAlcohol consumption• Inborn errors of metabolismInborn errors of metabolism

Glucose - 6 - phosphatase deficiencyGlucose - 6 - phosphatase deficiencyFructose -1- phosphate aldolase deficienccyFructose -1- phosphate aldolase deficienccy

Conditions influencing the Conditions influencing the deposition deposition of urate crystalsof urate crystals

Decreased solubility of urate Decreased solubility of urate Low temperatureLow temperature Low PHLow PH

Disturbance to the joint or soft tissueDisturbance to the joint or soft tissue Trauma or tissue injury or altered connective Trauma or tissue injury or altered connective

tissue matrixtissue matrix

Reabsorbtion of water resulting in Reabsorbtion of water resulting in supersaturation supersaturation

Lack of joint activity during sleepLack of joint activity during sleep

OthersOthers Gammaglobulin, insoluble collagen, proteoglycansGammaglobulin, insoluble collagen, proteoglycans

Urate crystal phagocytosis leads to Urate crystal phagocytosis leads to an inflammatory cascade and acute an inflammatory cascade and acute gouty arthritisgouty arthritis

Pathogenesis of acute gouty Pathogenesis of acute gouty inflammationinflammationHyperurecimia

Urate crystals

Activation of mast cellsActivation of endothelium

Chemotactic factor

SynovitisNeutrophil influx

Amplification of synovitis by neutrophil activation

Synovial liningCell activation

Complementactivation

Extracellular urateExtracellular urate

Urate-cell contactUrate-cell contact

Entrance of uric acidEntrance of uric acid

Phagocytosis of uratePhagocytosis of urate

Late phagocytosisLate phagocytosis

Intracellular urateIntracellular urate

CLINICAL SYNDROMESCLINICAL SYNDROMES

1- Asymptomatic 1- Asymptomatic hyperurecemiahyperurecemia

2- Acute flare2- Acute flare

3- Intercritical segments3- Intercritical segments

4- Advanced gout4- Advanced gout

Silent hyperurecemiaSilent hyperurecemia

Silent deposition of urate crystalsSilent deposition of urate crystalsElevated serum urate with no clinical Elevated serum urate with no clinical

manifestation of goutmanifestation of gout

Acute flareAcute flare

Acute inflammation in the joint caused Acute inflammation in the joint caused by urate crystallization ,often at nightby urate crystallization ,often at night

erythema. Swelling ,warmth in a jointerythema. Swelling ,warmth in a jointFever , chills and malaise may occureFever , chills and malaise may occureUntreated initial attach subside over Untreated initial attach subside over

3-10 days3-10 days90% first attack monoarticular( 50% 90% first attack monoarticular( 50%

podagra)podagra)

Acute arthritisAcute arthritis

initial or early attacksinitial or early attacks

Lower extremity and distal joint Lower extremity and distal joint involvement usually predominatesinvolvement usually predominates

however, the shoulders, hips, however, the shoulders, hips, sternoclavicular joints, and even the sternoclavicular joints, and even the spine and sacroiliac joints may spine and sacroiliac joints may become inflamed and cause become inflamed and cause diagnostic confusion. diagnostic confusion.

Polyarticular gouty arthritisPolyarticular gouty arthritis

(less than 20 percent of instances), (less than 20 percent of instances), uncommon as an initial manifestation), uncommon as an initial manifestation),

may be more frequent in patients with may be more frequent in patients with secondary to a secondary to a myeloproliferativemyeloproliferative or or lymphoproliferativelymphoproliferative disorder, or in organ disorder, or in organ transplant recipients who are receiving transplant recipients who are receiving cyclosporine Acyclosporine A. “. “

. Polyarticular symptoms are particularly . Polyarticular symptoms are particularly common late in the course of common late in the course of untreated untreated goutgout, when multiple recurrences, short or , when multiple recurrences, short or absent symptom free intervals, and absent symptom free intervals, and tophaceous deposits are common. tophaceous deposits are common.

Acute arthritisAcute arthritis

Precipitating factors in acute Precipitating factors in acute flareflare

Local traumaLocal traumaBinges of alcoholBinges of alcoholOvereating or fastingOvereating or fastingConcurrent acute medical or surgical Concurrent acute medical or surgical

illnessillnessMarked rise or fall in serum uric acidMarked rise or fall in serum uric acidSeasonal factorsSeasonal factors

Gouty handGouty hand

Gouty burcitisGouty burcitis

Diagnosing GoutDiagnosing Gout

Serum urate( may be normal)Serum urate( may be normal)History and physical examHistory and physical examSynovial fluid analysisSynovial fluid analysisDiff is very importantDiff is very important

Fluid analysisFluid analysis

microscope with crossed microscope with crossed polarizing filterspolarizing filters

Birefringence phenomenon Birefringence phenomenon

when light enters a non-equivalent when light enters a non-equivalent axis, it is refracted into two rays, axis, it is refracted into two rays, each polarized with the vibration each polarized with the vibration directions oriented at perpendicular directions oriented at perpendicular to one another and traveling at to one another and traveling at different velocities. different velocities.

Birefringent CrystalsBirefringent Crystals

Crystals bend light and become visible in Crystals bend light and become visible in joint fluid when viewed through a joint fluid when viewed through a microscope with crossed microscope with crossed polarizing filterspolarizing filters

When a compensator plate is used on the When a compensator plate is used on the microscope’,monosodium urate crystals microscope’,monosodium urate crystals parallel to the axis of the compensator parallel to the axis of the compensator appear yellow (appear yellow (negatively birefringentnegatively birefringent) and ) and calcium pyrophosphate dihydrate crystals calcium pyrophosphate dihydrate crystals parallel to the axis of the compensator parallel to the axis of the compensator appear blue (positively birefringent appear blue (positively birefringent

Birefringent CrystalsBirefringent Crystals

negative birefringent negative birefringent CrystalsCrystals

Positive birefringent Positive birefringent CrystalsCrystals

Criteria for clinical Criteria for clinical diagnosisdiagnosis

A classic history of one or more episodes of A classic history of one or more episodes of monoarticular arthritis followed by intercritical monoarticular arthritis followed by intercritical periods completely free of symptoms periods completely free of symptoms

Maximum inflammation within 24 hours Maximum inflammation within 24 hours Rapid resolution of synovitis after colchicine Rapid resolution of synovitis after colchicine

therapy therapy Unilateral first metatarsophalangeal joint attack Unilateral first metatarsophalangeal joint attack Hyperuricemia Hyperuricemia Subcortical bone cysts apparent on plain Subcortical bone cysts apparent on plain

radiograph radiograph Sterile joint fluid obtained from an affected joint Sterile joint fluid obtained from an affected joint

during an attack during an attack identify urate crystals, or in the presence of a identify urate crystals, or in the presence of a

negative polarized light microscopic studynegative polarized light microscopic study

DIFFERENTIAL DIAGNOSISDIFFERENTIAL DIAGNOSIS

PseudogoutPseudogoutSeptic arthritisSeptic arthritisHydroxyapatite calcific tendinitisHydroxyapatite calcific tendinitisSarcoid arthritisSarcoid arthritisErythema nodusumErythema nodusumRheumatoid arthritisRheumatoid arthritisFamilial mediterranian feverFamilial mediterranian fever

Etiology ofEtiology of spontaneous resolutionspontaneous resolution

TNF induced PMN apoptosisTNF induced PMN apoptosisMembranolysis due to crystal ingestionMembranolysis due to crystal ingestion Increased crystal coated by Increased crystal coated by

apolipoprotein apolipoprotein Production of IL1 antagonist Production of IL1 antagonist Increased tempreture and solubilityIncreased tempreture and solubilityACTH secretionACTH secretion Increased circulation and moved crystalIncreased circulation and moved crystal

ASSOSIATED CONDITIONASSOSIATED CONDITION

ObesityObesity Diabetes mellitusDiabetes mellitus HypertriglyceridemiaHypertriglyceridemia HypertentionHypertention Athrosclerosis Athrosclerosis HypothyroidismHypothyroidism Ethanol consumptionEthanol consumption PregnancyPregnancy Syndrome XSyndrome X

NEGATIVE NEGATIVE ASSOCIATION CONDITIONASSOCIATION CONDITION

Rheumatoid arthritisRheumatoid arthritisSystemic lupus erythmatosisSystemic lupus erythmatosisAnkylosing spondylitisAnkylosing spondylitisLong-term use of NSAIDLong-term use of NSAID

Intercritical SegmentsIntercritical SegmentsClinically silent gout without crystal Clinically silent gout without crystal

deposition and potential hidden deposition and potential hidden damagedamage

The intervals between acute flaresThe intervals between acute flaresThe patient hasn’t any symptom but The patient hasn’t any symptom but

Joint fluid revealed crystal in 12.5-Joint fluid revealed crystal in 12.5-58% with mild leukocytosis58% with mild leukocytosis

In 78% , second attack occur within In 78% , second attack occur within 6month to 2years6month to 2years

Synovial analysis during Synovial analysis during intercritical period intercritical period

extracellular urate crystals are extracellular urate crystals are identifiable in synovial fluid from identifiable in synovial fluid from previously affected joints in virtually previously affected joints in virtually all untreated gouty patients all untreated gouty patients

CHRONIC TOPHACEOUS GOUTCHRONIC TOPHACEOUS GOUT

collections of solid urate in connective collections of solid urate in connective tissues (which may be calcified). tissues (which may be calcified).

a a chronic granulomatouschronic granulomatous inflammatory inflammatory response is identifiable on histological response is identifiable on histological examination of the lesions, and, on examination of the lesions, and, on occasion, acute inflammation occasion, acute inflammation mimicking that of gouty arthritis occurs mimicking that of gouty arthritis occurs in one or several tophiin one or several tophi

CHRONIC ARTHRITISCHRONIC ARTHRITIS

The average interval between the first The average interval between the first attack and chronic arthritis is 11.6 yattack and chronic arthritis is 11.6 y

2% gouty patients has crippling disease2% gouty patients has crippling diseaseMay polyarticularMay polyarticular History of intermittent attacks, additive& ascendingHistory of intermittent attacks, additive& ascending

Chronic taphusChronic taphus

Chronic goutChronic gout

Advanced goutAdvanced gout

Erosion in both Erosion in both destructive and destructive and hypertrophic leads to hypertrophic leads to overhanging edgeoverhanging edge

Joint space is often Joint space is often preserved untile very preserved untile very late in the disease late in the disease processprocess

TaphousTaphous

Over hangingOver hanging

TaphousTaphous

Crystal precipitate in joint and Crystal precipitate in joint and soft tissuessoft tissues

RENAL COMPLICATIONS OF RENAL COMPLICATIONS OF CHRONIC HYPERURICEMIACHRONIC HYPERURICEMIA

nephrolithiasisnephrolithiasis;(only5 to 10 percent ;(only5 to 10 percent of all urinary tract stones in the of all urinary tract stones in the United States and Europe)United States and Europe)

chronic urate nephropathychronic urate nephropathy

three major risk factors for uric three major risk factors for uric acid nephrolithiasis acid nephrolithiasis

Increased uric acid excretion Increased uric acid excretion Reduced urine volume Reduced urine volume Low urine pH, a setting in which most Low urine pH, a setting in which most

of the uric acid exists as the intact of the uric acid exists as the intact insoluble acid. insoluble acid.

Uric acid stoneUric acid stone

Chronic urate Chronic urate nephropathynephropathy

urate may deposit in the renal urate may deposit in the renal medullary interstitium.medullary interstitium.

Deposition in this area induces a Deposition in this area induces a modest chronic inflammatory modest chronic inflammatory ((tophaceoustophaceous) reaction, and varying ) reaction, and varying degrees of degrees of fibrosis fibrosis

Treatment of GoutTreatment of Gout

• The therapeutic aim in gout :The therapeutic aim in gout :1- To terminate the acute attack1- To terminate the acute attack2- To prevent recurrence of acute gouty 2- To prevent recurrence of acute gouty arthritisarthritis3- To prevent or reverse complications of 3- To prevent or reverse complications of the diseasesthe diseases4 - To prevent or reverse associated feature 4 - To prevent or reverse associated feature ( Obesity , hypertriglyceridemia and( Obesity , hypertriglyceridemia and hypertension ) hypertension )

TreatmentTreatment

Anti-inflammatory therapy — prompt Anti-inflammatory therapy — prompt and safe termination of the acute and safe termination of the acute arthritic attack arthritic attack

Prophylaxis — prevention of Prophylaxis — prevention of recurrences of acute gouty arthritis recurrences of acute gouty arthritis

Antihyperuricemic therapy Antihyperuricemic therapy

Treatment of GoutTreatment of Gout

• Acute Gouty arthritisAcute Gouty arthritis

• ProphyProphyllaxisaxis

• ControControl l of hyperuricemia of hyperuricemia

· ColchicineColchicine· NSAIDNSAID· CorticosteroidCorticosteroid

· ·ColchicineColchicine· NSAIDNSAID

· AAllllopurinoopurinoll · Uricosuric agents ( Probenecid, suUricosuric agents ( Probenecid, sullfinpyrazone )finpyrazone )

The recommended duration of The recommended duration of prophylactic colchicine or NSAIDs prophylactic colchicine or NSAIDs during the initiation of during the initiation of uric acid uric acid

lowering therapylowering therapy

In patients without evident tophi, In patients without evident tophi, prophylaxis can be safely prophylaxis can be safely discontinued 6 months after normal discontinued 6 months after normal serum urate values have been serum urate values have been obtained. obtained.

The optimal duration of prophylactic The optimal duration of prophylactic therapy for patients with tophi is therapy for patients with tophi is uncertain. uncertain.

COMORBID RISK COMORBID RISK REDUCTIONREDUCTION

Nutritional strategies (eg, Nutritional strategies (eg, achievement of ideal body weight, achievement of ideal body weight, reduction of dietary protein intake, reduction of dietary protein intake, and limitation of ethanol and limitation of ethanol consumption) can treat both the consumption) can treat both the associated conditions and associated conditions and hyperuricemia hyperuricemia

general goal of general goal of antihyperuricemic therapy antihyperuricemic therapy

is a serum urate concentration of 5 is a serum urate concentration of 5 to 6 mg/dL [297 to 357 µmol/L], a to 6 mg/dL [297 to 357 µmol/L], a level substantially below that at level substantially below that at which monosodium urate is which monosodium urate is saturating in extracellular fluids.saturating in extracellular fluids.

Indication of Indication of antihyperurecemic therapyantihyperurecemic therapy

Frequent and disabling Frequent and disabling attacksattacks of gouty of gouty arthritis (three or more per year) arthritis (three or more per year)

Clinical or radiographic signs of chronic Clinical or radiographic signs of chronic gouty gouty jointjoint disease disease

TophaceousTophaceous deposits in soft tissues or deposits in soft tissues or subchondral bone subchondral bone

Gout with Gout with renal insufficiencyrenal insufficiency Recurrent Recurrent nephrolithiasisnephrolithiasis Urinary uric acid excretion exceeding Urinary uric acid excretion exceeding 11001100

mg/day (when determined in men < 30 mg/day (when determined in men < 30 years of age and premenopausal women) years of age and premenopausal women)

Xanthine oxidase Xanthine oxidase inhibitorsinhibitors

xanthine oxidase inhibitors are likely xanthine oxidase inhibitors are likely to be effective in virtually all to be effective in virtually all circumstances warranting therapy for circumstances warranting therapy for gout ( gout ( AllopurionlAllopurionl))

Uricase (urate oxidase) Uricase (urate oxidase)

Uricase, an enzyme that converts urate Uricase, an enzyme that converts urate to a more soluble molecule ( allantoin). to a more soluble molecule ( allantoin).

uricase can reduce the size of tophi in uricase can reduce the size of tophi in patients with tophaceous disease, patients with tophaceous disease,

Conversion of urate to allantoin by Conversion of urate to allantoin by uricase action thus has the potential to uricase action thus has the potential to be helpful in patients who are allergic or be helpful in patients who are allergic or refractory to treatment with allopurinol. refractory to treatment with allopurinol.

Other drugs that enhance Other drugs that enhance uric acid excretionuric acid excretion

LLosartan osartan FenofibrateFenofibrate

gout. case a 45y/o obese male with h/o painfull ankle associated with hottness and redness since 2...

underexcretion of uric

hemoglobinopathy hemolysis

pernicious anemia

muscle exertion

g6pd fruoctose intolerancef1p

urate greater

byproduct of purine

percent of primary

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