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GOUT Disease caused by tissue deposition of Monosodium urate crystals as a result of supersatuaration of extra cellular fluid with MSU. Hyperuricemia 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 Hyperuricemia PURINES DEGREDATION PRODUCT OVERPRODUCTION OF URATE ENDOGENOUS OR EXOGENOUS UNDEREXCRETION OF URATE (RENAL) 90% OF GOUT PATIENT COMBINATION OF THE ABOVE TWO EPIDEMIOLOGY Disease of adult men with peak in 5th decade. Very rare before puberty and in premenopausal women. Less than 25% of hyperuricemic develop GOUT Duration and serum uric acid directly correlate with Gout development 20% family history Primary Under excretion: Idiopathic 90% of patients with hyperuricemia. Normal excretion of uric acid only when serum uric acid high Over production :rare Idiopathic Hypoxanthine-guanine phosphoribosyltransferase deficiency Phosphoribosyl-1-pyrophosphate synthetase super activity. ACQUIRED CAUSES OF HYEPERURICEMIA URATE OVERPRODUCTION Excess dietary purine consumption Accelerated ATP degradation : alcohol abuse,glycogen storage disease, Myeloproliferative and Lymphoproliferative disorders both causing increased nucleotide turnover. ACQUIRED CAUSES OF HYEPERURICEMIA Urate under excretion Renal disease Poly cystic kidney disease Hyperparathyroidism Hypothyroidism Hypertension DRUGS CAUSE HYPERURICEMIA DERCREASED RENAL EXCRETION Decreased renal excretion Cyclosporine Alcohol Nicotinic acid Thiazide Lasix(furosemide) Ethambutol Aspirin (low dose) Pyrazinamdie 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 Gout Prolonged a symptomatic hyperuricemia(years) Acute intermittent Gout Chronic tophaceous Gout GOUT: CLINICAL MANIFESATATION Recurrent Gouty Arthritis( articular and periarticular. Tophi Uric acid urinary calculi Interstitial nephropathy with renal function impairment Gout involving DIPs Podegra (gout of 1st MTP) Gout of ankle joint Acute onset Gout affect 1st MTP 75% Severe pain Erythema Very tender May be febrile Resolve 3-10 days Tophacous Gout Tophi hands and olecranon bursa Olecranon bursitis Gout crystals Needle like Can be Intra or extra cellular Negatively birefringent Gout Soft tissue swelling because of Tophi Large erosions involving DIPs,with hanging edges Gout Soft tissue swelling around 1st MTP Erosion around 1st MTP This takes time to develop (YEARS) Deferential Diagnosis Pseudo Gout (CPPD) Septic arthritis Reactive arthritis Other inflammatory arthritis 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 toxicities Know NSAIDs contraindications, CONTINUE ACUTE GOUT MANAGMENT Colchicine: 0.6-1mg bid oral Limited because of toxicity Main side effects GI :abdominal pain/diarrhea/nausea Need adjustment in renal impairment May cause myelosuppression May be linked to azospermia and infertility IV Colchicine very toxic to bone marrow 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. Prophylaxis Till Acute episode controlled May use Colchicine NSAID Prevention and control of hyperuricemia indications 1-recurrent attacks of Gout 2-renal stones 3-tophaceous Gout 4-chronic gout with joint damage and erosions 5-hyperuricemia uric acid > 12mg/dl 6-24 hr urine excretion of >1100 mg uric acid Uricosuric agents Probencid,sulfinprazone Who is good candidate 1-age <60 2-Creatinine clearance >50ml/min 3-24 hr urine of uric acid < 700mg(under excretion) 4-No history of renal stone Xanthine oxidase inhibitor Allopurinol Hyperuricemia with : Urinary uric acid >1000mg Uric acid nephropathy Nephrolithiasis Before chemotherapy Renal insufficiency GFR<50 Allergy to Uricosuric agents Allopurinol Average dose 300mg Renal impairment use lower dose May 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.
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"Stages of Gout Prolonged a symptomatic hyperuricemia years Acute intermittent Gout Chronic tophaceous Gout GOUT"Please download to view full document