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Dr Bhupesh Dhananjayan MD MPH

which sometimes lead to deformity and crippling Renal disease involving glomerular.Definition Heterogeneous group of diseases involving : An elevated serum urate concentration (hyperuricemia) Recurrent attacks of acute arthritis in which monosodium urate monohydrate crystals are demonstrable in synovial fluid leukocytes Aggregates of sodium urate monohydrate crystals (tophi) deposited chiefly in and around joints. and interstitial tissues and blood vessels Uric acid nephrolithiasis Hyperuricemia : serum uric acid >7mg% (males) and >6mg% (females) . tubular.

or body mass index) has proved to be one of the most important predictors of hyperuricemia in people of widely differing races and cultures.2/1000 RR for blacks slightly higher (1.Epidemiology Prevalence of hyperuricemia 2. and alcohol intake. height. (Taiwan) Body bulk (as estimated by body weight. surface area. Corresponds with serum creatinine /BUN levels. blood pressure.3) . Incidence of Gout Varies depending on population studied – 1.3 – 41. age. body weight.4% in various populations.8 /1000 – 3.

Redness observed over joints 5. Subcortical cysts without erosions on x ray 12. laboratory. Unilateral tarsal joint attack 8. or the presence of 6 of the following 12 clinical. More than one attack of acute arthritis 2. Maximum inflammation developed within 1 day 3. Tophus (proven or suspected) 9. Monoarthritis attack 4.1977 ACR criteria for acute gout The presence of characteristic urate crystals in the joint fluid. Monosodium urate monohydrate microcrystals in joint fluid during attack 13. First metatarsophalangeal joint painful or swollen 6. Unilateral first metatarsophalangeal joint attack 7. Asymmetric swelling within a joint on x ray/exam 11. or a tophus proved to contain urate crystals by chemical means or polarized light microscopy. Hyperuricemia 10. and radiographic phenomena: 1. Joint fluid culture negative for organisms during attack .

Hypoxemia and hypoperfusion .Niaci n. Pyrazinamide. Cyclosporine.Salicylates (low dose). ETOH. Ethambutol. Didanosine ) Urate overproduction Myeloproliferative/ Lymphoproliferative diseases / Hemolytic anemias/ Polycythemia vera/Other malignancies Psoriasis/Glycogen storage disease Dual mechanism Obesity.Classification of Hyperuricemia and Gout Primary Hyperuricemia and Gout with No Associated Condition Uric acid undersecretion(80%–90%) Idiopathic Urate overproduction (10%–20%) Idiopathic HGPRT deficiency PRPP synthetase overactivity Secondary Hyperuricemia and Gout with Identifiable Associated Condition Uric acid undersecretion Renal insufficiency Polycystic kidney disease Lead nephropathy Drugs(Diuretics.

managed care study) Direct burden annually is 27. (men only) Patients with acute gout miss 3-5 days of work annually.Outcomes in Gout Clinical outcomes    60% of untreated gout have attacks within 1 yr .4 million USD. 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. Adherence to allopurinol only 56%.(Oduffy et al)------’colchicine’ effect’ Hyperuricemia control superior to self medication alone. Humanistic outcomes   Economic outcomes    . Treatment outcomes decrease QOL in pts with gout. Chronic tophaceous gout develops after 10 -20 yrs of untreated gout. Incidence decreased from 14% in 1949 –> 3% in 1972. (Riedel et al . only 7% have no attacks in 10 yrs. 78% have recurrence in 2 yrs.

GOLD STANDARD    SF Analysis – WBC ct – 2000-100 000/ml MSU crystals. Often begins at night. helix/ antihelix . (hands/tarsal jts/knees) Precipitants – Minor trauma . hands. hypouricemic Rx. Serum Uric acid level – important in monitoring treatment . severely painful. assoc with systemic signs. diuretic Rx. Laboratory:. Usually abrupt .needle shaped . negatively birefringent. severe medical illness. more common .but rare . Complications : ulceration/infection. feet.(42% normal levels) 24 hr uric acid collection –useful in young pts with gout/ + fam h/o .Diagnosis Clinical :     In men .. olecranon bursa. ETOH. Later attacks – polyarticular . most often initial presenting complaint in women. Tophi – Classically . Surgery. initial attack monoarticular – 1st MTP joint(50% of cases) Other jts involved – instep/knees/wrists/ olecranon bursa.

non specific . takes 6 yrs to develop Martel’s sign  CT/MRI/US/Bone scan Sensitive .Diagnosis Radiologic  X RAY : Punched out erosions – only 45% of pts have them.

Newer agents – Etoricoxcib 120 OD comparable to indomethacin 50 TID. Continue till serum urate levels stabilize and no attacks for 3 – 6 mths. Prophylaxis :      .Treatment Acute gouty arthritis:   Anti. Any NSAID can be used . If long term prophylactic colchicine given.creat < 2mg/dl. Does not alter crystal deposition and development of tophi.  NSAIDs if diagnosis confirmed. Endpoints – improvement in jt symptoms/ GI symptoms/ 10 doses taken. check CBC .IM ACTH .inflammatory drugs ( if s. Only indicated if patient is started on urate lowering Rx. Colchicine( 1-3 pills a day)/ NSAID( in colchicine intolerant). no PUD) Colchicine preferred in pts without confirmed diagnosis of gout. Avoid adjusting dosage of urate lowering agents. oral /iv prednisone.   In c/o renal failure /PUD .CK every 6 mths.

Choice of agents : Xanthine oxidase inhibitor Uricosuric agents. Equal efficacy in pts with normal renal function and who excrete < 800 mg/day of uric acid. Goal : s. around 1st attack. .Treatment (contd) Control of hyperuricemia      Differing opinions regarding initiation esp. uric acid at least once every 6 mths upon initiation. urate levels < 6 mg%. Serial s. Clear evidence if erosions + on X-ray / chronic tophaceous gout/ >2 gout attacks per year.

pts <60 yrs. renal insufficiency Limit ASA to 81 mg/day Probenecid/ Benzbromarone Uricosuric agents     .Treatment (contd) Xanthine oxidase inhibitors        Allopurinol.A excretion < 800 mg/d CI . U.+ nephrolithiasis. S/E – GI / rash / sarcoid like reaction/Allopurinol hypersensitivity syndrome Drug interaction – esp. Renally excreted. therefore adjust dose if s. Oxypurinol – possible option Indications – no h/o renal calculi . Desensitization protocols exist.only prescription drug available.creat > 2mg% or CrCl <50 Usually DOC in most patients. with 6 MP/azathioprine/ warfarin/theophylline.

uric acid. Yeast. kidneys. Mushrooms. other alcoholic beverages. sweetbreads) Legumes (dried beans. gravies. peas) Meat extracts. consommé. spinach. cauliflower        . Anchovies. Makes a difference of up to 1mg % in s. herring.HTN Losartan / fenofibrate – weakly uricosuric Diet – moderation in purine intake. asparagus. Organ meat (liver.Treatment (contd) Adjuvant Rx    Control obesity . sardines in oil.ETOH intake. Beer. hyperlipidemia . fish roes.

uricase  Febuxostat Asymptomatic hyperuricemia  Investigate cause  No recommendations for Rx.Treatment (contd) Newer agents  PEG. .