GOUTGOUTDisease caused by tissue deposition of Monosodium urate crystals as a result of supersatuaration of extra cellular fluid with MSU.

HyperuricemiaHyperuricemia

Serum uric acid above normal level for age and sex.

>7mg for adult men and > 6mg for adult women. Only 15-20% of all patient with hyperuricemia

develop gout.Why we produce uric acid :End product of purine

metabolism but human do not have enzyme uricase to convert it to allantoin (highly soluble)

Mechanism of HyperuricemiaMechanism of Hyperuricemia

PURINES DEGREDATION PRODUCT

OVERPRODUCTION OF URATEENDOGENOUS OR EXOGENOUS

UNDEREXCRETION OF URATE (RENAL) 90% OF GOUT PATIENT

COMBINATION OF THE ABOVE TWO

EPIDEMIOLOGYEPIDEMIOLOGY

Disease of adult men with peak in 5th decade.Very rare before puberty and in premenopausal

women.Less than 25% of hyperuricemic develop GOUTDuration and serum uric acid directly correlate

with Gout development20% family history

PrimaryPrimary

Under excretion:Idiopathic 90% of patients

with hyperuricemia.Normal excretion of uric

acid only when serum uric acid high

Over production :rareIdiopathicHypoxanthine-guanine

phosphoribosyltransferase deficiency

Phosphoribosyl-1-pyrophosphate synthetase super activity.

ACQUIRED CAUSES OF HYEPERURICEMIA

ACQUIRED CAUSES OF HYEPERURICEMIA

URATE OVERPRODUCTIONExcess dietary purine consumptionAccelerated ATP degradation : alcohol

abuse,glycogen storage disease,Myeloproliferative and Lymphoproliferative

disorders both causing increased nucleotide turnover.

ACQUIRED CAUSES OF HYEPERURICEMIA

ACQUIRED CAUSES OF HYEPERURICEMIA

Urate under excretionRenal diseasePoly cystic kidney diseaseHyperparathyroidismHypothyroidismHypertension

DRUGS CAUSE HYPERURICEMIA

DERCREASED RENAL EXCRETION

DRUGS CAUSE HYPERURICEMIA

DERCREASED RENAL EXCRETION

Decreased renal excretionCyclosporineAlcoholNicotinic acidThiazideLasix(furosemide)EthambutolAspirin (low dose)Pyrazinamdie

Unknown mechanismLevodopaTheophyllineDidanosine

ALCOHOL MECHANISM OF HYPERURICEMIA

ALCOHOL MECHANISM OF HYPERURICEMIA

Increases lactic acid production which reduces renal excretion of urate.

Increases Urate synthesis because of increased ATP degradation.

Beer also contain purine guanosine.

Stages of GoutStages of GoutProlonged a symptomatic hyperuricemia(years)Acute intermittent GoutChronic tophaceous Gout

GOUT: CLINICAL MANIFESATATIONGOUT: CLINICAL

MANIFESATATIONRecurrent Gouty Arthritis( articular and

periarticular.TophiUric acid urinary calculiInterstitial nephropathy with renal function

impairment

Gout involving DIPsGout involving DIPs

Podegra (gout of 1st MTP)Gout of ankle joint

Podegra (gout of 1st MTP)Gout of ankle joint

Acute onsetGout affect 1st MTP 75% Severe painErythemaVery tenderMay be febrileResolve 3-10 days

Tophacous GoutTophacous Gout

Tophi hands and olecranon bursaTophi hands and olecranon bursa

Olecranon bursitisOlecranon bursitis

Gout crystalsGout crystals

Needle likeCan be Intra or extra cellularNegatively birefringent

Gout Gout

Soft tissue swelling because of TophiLarge erosions involving DIPs,with hanging edges

GoutGout

Soft tissue swelling around 1st MTPErosion around 1st MTPThis takes time to develop(YEARS)

Deferential DiagnosisDeferential Diagnosis

Pseudo Gout (CPPD)Septic arthritisReactive arthritisOther inflammatory arthritis

MANAGEMENT OF ACUTE GOUT

MANAGEMENT OF ACUTE GOUT

NSAID:indomethacin used more than other NSAIDs my use any other NSAIDs at full dose like ibuprofen 800mg TID or Naprosyn 500mg bid expect to as effective as indomethacin and my be less toxic

Know NSAID toxicitiesKnow NSAIDs contraindications,

CONTINUE ACUTE GOUT MANAGMENT

CONTINUE ACUTE GOUT MANAGMENT

Colchicine: 0.6-1mg bid oralLimited because of toxicityMain side effects GI :abdominal pain/diarrhea/nauseaNeed adjustment in renal impairmentMay cause myelosuppressionMay be linked to azospermia and infertilityIV Colchicine very toxic to bone marrow

CONTINUE ACUTE GOUT MANAGEMENT

CONTINUE ACUTE GOUT MANAGEMENT

Steroids safe for acute management with fast results,and when NSAID and Colchicine use not warranted

Intra-articular injection of triamcinolone is fastest way to get relief ,at the same time can get synovial fluid for analysis

Oral or parentral steroids e.g.:prednisolone oral 20-40 mg daily for 5-7 days ,equivalent doses of IV steroids may be used if unable to take oral

Always make sure no infection coexist.

ProphylaxisTill hyperuricemia

controlled

ProphylaxisTill hyperuricemia

controlledMay use ColchicineNSAID

Prevention and control of hyperuricemia indicationsPrevention and control of hyperuricemia indications

1-recurrent attacks of Gout 2-renal stones3-tophaceous Gout4-chronic gout with joint damage and erosions5-hyperuricemia uric acid > 12mg/dl6-24 hr urine excretion of >1100 mg uric acid

Uricosuric agentsProbencid,sulfinprazone

Uricosuric agentsProbencid,sulfinprazone

Who is good candidate1-age <602-Creatinine clearance >50ml/min3-24 hr urine of uric acid < 700mg(under

excretion)4-No history of renal stone

Xanthine oxidase inhibitorAllopurinol

Xanthine oxidase inhibitorAllopurinol

Hyperuricemia with :Urinary uric acid >1000mgUric acid nephropathy NephrolithiasisBefore chemotherapyRenal insufficiency GFR<50Allergy to Uricosuric agents

AllopurinolAllopurinol

Average dose 300mgRenal impairment use lower doseMay precipitate acute gout when first used Side effects can be very serious range from

dyspepsia,headache,diarrhea,rash,to more severe including fever,esosinophilia,interstitial nephritis,hepatitis,vasculitis,acute renal failure,toxic epidermal necrolysis,and hypersensitivity syndrome.

Gout in transplnatGout in transplnat

Patient usually on Steroids,azathioprine,cyclosporineColchicine and NSAID use potentially toxicAllopurinol increase level of azathioprine and toxicity Steroids intra-articular ,oral or parentral can be used May need adjust or change transplant medications

ChondrocalcinosisChondrocalcinosis