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15 Pearls of Gout Management: how to be the best gout doctor ever!

15 Pearls of Gout Management: how to be the best gout doctor ever!. Obesity epidemic + High fructose corn syrup. Fructose. Fructose 1- phosphate. Inosine. Uric acid. Increasing prevalence of gout. Y-axis = prevalence per 1000 individuals. Prevalence of gout. 1990s :

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15 Pearls of Gout Management: how to be the best gout doctor ever!

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  1. 15 Pearls of Gout Management:how to be the best gout doctor ever!

  2. Obesity epidemic +High fructose corn syrup Stamp et al, Arth & Rheum, 63(2)

  3. Fructose Fructose 1- phosphate Inosine Uric acid

  4. Increasing prevalence of gout Y-axis = prevalence per 1000 individuals Wallace, et al, J Rheum, 31(8):1582

  5. Prevalence of gout • 1990s: • “Gout is the 2nd most common inflammatory arthritis” • Today: • Gout is THE MOST COMMON inflammatory arthritis • 2008 Prevalence: • 1 out 25 adults • 1 out of 16 men • 1 out of 8 elderly • Gout Epidemic! National Health and Nutrition Examination Survey (NHANES) data

  6. Obesity Obesity increases sUA -increases urate synthesis -decreased renal excretion BMI 30-34.9 = RR 2.33 for gout BMI ≥ 35 = RR 2.97 Marasini, J of Rheum, 36(4), 2009 Choi et al, Arch of Int Med, 165(7), 2005

  7. Obesity Hypertension -Harvard: 47,150 men over 12 years -HTN→ RR 2.31 new onset gout -diuretics→ RR 1.7 -another study: diuretics RR 2.36 losartan RR .71 -Baylor study: 30 adolescents: HTN + sUA ≥ 6 allopurinol 400 mg qd vs placebo 4 weeks 1/3 normal BP on allopurinol 1/30 normal BP on placebo Choi et al, Arch Int Med, 165, 2005 Choi et al, BMJ, 334, 2012 Feig et al, JAMA, 300 (8), 2008

  8. Obesity Hypertension Dyslipidemia -JHH: 1216 men, average age 22 yo -followed 45 years -those with top quintile cholesterol, average of 217 mg/dl -60% higher prevalence of gout over next 45 years adjusted for BMI and HTN Gelber A, Rheumatology News, January 2010

  9. Obesity Hypertension Chronic kidney disease Dyslipidemia -25-40% of gout pts have CKD -Gout tx allop→ improved GFR 267 pts, over 5 years 74 ml/min → 80 ml/min -Gout tx febuxostat→ 1 mg/dl improvement in sUA → 1 ml/min incr. in GFR Johnson RJ et al, Hypertension, vol 41, 2003 Jo et al., J of Rheum Dis, 18(1), 2011 Whelton et al, J of Clin Rheum, 17(1), 2011

  10. Obesity Hypertension Chronic kidney disease Dyslipidemia Insulin resistance/ DM type II -22% of men with DM II have gout -41% of men > 65yo have DM II -New onset DM II RR in pts with gout = 1.34 -Insulin resistance increases sUA hyperinsulinemia decreases renal clearance -Gout and DMII share genetic risk factors Suppiah et al, New Zealand Med Journal, 121(1283), 2008 Choi et al, Rheumatology, 47(10, 2008 Marasini, J of Rheum, 36(4), 2009 Lai et al, Rheumatology (Oxford), 2011

  11. Obesity Hypertension Chronic kidney disease Dyslipidemia Cardiovascular disease • ≥ 20% have a very high 5 year risk for CVD event • -additional 15% were at high risk • -Men with gout = 30% increase in CVD death in 6 yrs • -Another 6 yr study: RR for CV death = 1.97 • -Gout = independent risk factor for CVD Insulin resistance/DMII Colvine K. et al, New Zealand Med Journal, 121(1285), 2008 Krishnan et al, Archives Int Med, 10(26), 2008 Kuo et al, Rheumatology, 49(1), 2010

  12. Pearl 1: Every gout patient needs a good PCP Obesity Hypertension Chronic kidney disease Dyslipidemia Insulin resistance/DMII Cardiovascular disease

  13. Does hyperuricemia cause metabolic syndrome? Nakagawa et al, Am J of Phys - Renal Physiology, 290(3), 2006 • Rats fed high fructose diet • Normally develop metabolic syndrome • Prophylactic allopurinol or a uricosuric agent • No change in dietary intake • ↓ weight gain • ↓ HTN • ↓ triglyceride elevations • ↓ hyperinsulinemia • [sUA] proportional to amount of vasoconstriction

  14. Definition of hyperuricemia • Hyperuricemia is sUA > 6.8 mg/dL • At a pH of 7.4 • Urate limit of solubility = 6.8 mg/dL

  15. Pearl 2:Normal sUA ≤ 6.8mg/dL(ignore what the lab sheet says)

  16. Is it gout? • Try to make a crystal proven diagnosis • Most hyperuricemics don’t have gout • 1/3 of acute gout flares have normal sUA • 1/3 of polyarticular gout patients have +RF • When gout is “diagnosed” clinically • Sensitivity = 70% • Specificity = 79% Malik et al: J of Clinical Rheum, 15(1), 2009

  17. Pearl 3:Make a crystal-proven diagnosis whenever possible

  18. 1st:Stop Acute Gout Attacks ASAP • Anti-inflammatory Drugs • NSAIDS • Use around the clock, maximum doses • No NSAID better than another • Most gout patients can’t take NSAIDs • low eGFR • Elevated BP • GI issues • Colchicine • Corticosteroids

  19. Stop Acute Gout Attacks ASAP • Anti-inflammatory Drugs • NSAIDS • Colchicine (Colcrys) • .6 mg tablets • 2 tablets ASAP • Then 1 more tablet 1 hour later • Corticosteroids

  20. Stop Acute Gout Attacks ASAP • Anti-inflammatory Drugs • NSAIDS • Colchicine • Corticosteroids • Oral • Prednisone 40 mg qam for 7 days • Intramuscular • 1cc depoMEDROL + 1cc dexamethasone IM buttock • Intra-articular • Safest steroid approach

  21. Pearl 4:Some patients (severe gout) may need more than one type of therapy for acute gout attacks

  22. In all gout patients: • Rx weight loss • Educate patient about gout • Adjust cardiovascular meds • Stop non-critical diuretics • Rx losartan • Rx fenofibrate • Rx vitamin C • Rx gout diet

  23. Stop non-critical diuretics • Loop diuretics (furosemide) • Thiazide diuretics (HCTZ) • HCTZ • increases sUA .8 – 1.53 mg/dl

  24. Rx losartan Handler, Hypertension, 12(9), 2010 • Uricosuric • Works even if CKD • ↑s urine pH (prevents stones) • Not other ARBs • Decreases sUA .32 mg/dl – 1.33 • Probably dose related

  25. Rx fenofibrate Feher et al, Rheumatology (Oxford), 42(2), 2003 Lee, Korean J of Int Med, 2006 Li, J of Peking Univ, 41(5), 2009 Noguchi, J of Atherosclerosis and Thrombosis, 11(6), 2004 • An even stronger uricosuric! • English study: • Added to allopurinol → 19% addition reduction in sUA • Korean group = 23% decrease • Chinese study: • 200 mg/d→ sUA decreased 28% • Japanese study: • 300 mg/d: sUA 7.0 mg/dL→ 5.2 mg/dL (26%)

  26. Rx Vitamin C 1000 mg a day Huang et al, Arthritis & Rheum, 52(6), 2005 • Vit C is uricosuric • Vit C 500 mg qd • Normal subjects • Decreased sUA .5 mg/dL • Another 20 year study, men • Vit C 500 mg/d = RR for gout .83 • Vit C 1000 – 1499 mg/d = .66 • Vit C ≥ 1500 mg/d = .55

  27. Rx a gout diet Dussein, Ann of Rheum Disease, 59(7)2000 Choi et al, NEJM, 350(11), 2004 • Decreases sUA 1.0 – 1.7 mg/dL

  28. Rx a gout diet Choi, NEJM, 350(11), 2000 • Decrease intake of meat purines • Eat in moderation • Smaller quantities at a time

  29. Rx a gout diet Choi, NEJM, 350(11), 2000 • Decrease intake of meat purines • No restrictions in vegetables • High purine vegetables don’t cause gout when eaten in moderation

  30. Rx a gout diet Choi, NEJM, 350(11), 2000 • Decrease intake of meat purines • No restrictions in vegetables • Consume more dairy products • Increased dairy = Lower gout prevalence

  31. Rx a gout diet Choi, NEJM, 350(11), 2000 • Decrease intake of meat purines • No restrictions in vegetables • Consume more dairy products • Drink plenty of fluids • Avoid volume depletion

  32. Rx a gout diet Choi, NEJM, 350(11), 2000 • Decrease intake of meat purines • No restrictions in vegetables • Consume more dairy products • Drink plenty of fluids • Avoid beer and hard liquor • 1 beer a day RR for gout = 1.5 • Beer = high in guanosine • Beer → volume depletion and lactic acidosis

  33. Rx a gout diet Choi, NEJM, 350(11), 2000 • Decrease intake of meat purines • No restrictions in vegetables • Consume more dairy products • Drink plenty of fluids • Avoid beer and hard liquor • Liquor 2 shots a day or more RR = 1.6

  34. Rx a gout diet Choi, NEJM, 350(11), 2000 • Decrease intake of meat purines • No restrictions in vegetables • Consume more dairy products • Drink plenty of fluids • Avoid beer and hard liquor • Wine 8 oz a day = No increase in gout

  35. Rx a gout diet Choi, Lancet, 363(9417), 2004 • Decrease intake of meat purines • No restrictions in vegetables • Consume more dairy products • Drink plenty of fluids • Avoid beer and hard liquor • Avoid high fructose corn syrup foods • HFCS→ inosine → ↑ sUA levels • HFCS→ increases fat production

  36. Pearl 5: In all gout patients • Adjust cardiovascular meds • Stop non-critical loop and thiazide diuretics • Rx losartan in HTN regimen • Rx fenofibrate in dyslipidemia regimen • Rx vitamin C 1000 mg a day • Rx a gout diet • Rx weight loss • Educate patient about gout

  37. Next question to address : • Rx urate lowering therapy or not?

  38. Urate lowering meds:Review urate metabolism Purines from meats, beer, fructose, and body cell turnover Xanthine oxidase Overproduction 10% of gout patients Uric acid Renal excretion

  39. Urate lowering meds:Review urate metabolism Purines from meats, beer, fructose, and body cell turnover Xanthine oxidase Uric acid Underexcretion 90% of gout patients Renal excretion

  40. Urate lowering meds:Uricosurics Purines from meats, beer, fructose, and body cell turnover Xanthine oxidase Uric acid Excretion= Uricosurics Renal excretion

  41. Urate lowering meds:Uricosurics Purines from meats, beer, fructose, and body cell turnover Xanthine oxidase Uric acid Excretion= Uricosurics Vitamin C Losartan Fenofibrate Renal excretion

  42. Urate lowering meds:Uricosurics Purines from meats, beer, fructose, and body cell turnover Xanthine oxidase Uric acid Excretion= Uricosurics Losartan Fenofibrate Vitamin C Probenecid Renal excretion

  43. Urate lowering meds:Xanthine oxidase inhibitors Purines from meats, beer, fructose, and body cell turnover Allopurinol Febuxostat (Uloric) Xanthine oxidase Uric acid Renal excretion

  44. Urate lowering meds:Uricase Purines from meats, beer, fructose, and body cell turnover Xanthine oxidase Pegloticase (Krystexxa) Uricase Uric acid Allantoin Renal excretion

  45. Next question to address: • Rx urate lowering therapy or not? • End organ damage or large body stores of UA? • Joint damage • Renal insufficiency • Nephrolithiasis • Tophi on PE • The above require a xanthine oxidase inhibitor • Allopurinol • Febuxostat (Uloric)

  46. Pearl 6: Rx allopurinol or febuxostat to anyone with gout and: Joint damage Renal insufficiency Nephrolithiasis Tophi

  47. Pearl 7: Prophylactic anti-inflammatory before urate lowering medicine • Anti-inflammatory drugs • NSAIDs, daily full dose (eg , meloxicam 15 mg qd) • Colchicine (Colcrys) 0.6 mg bid • If CKD • ↓ to 0.6 mg qd after stable on urate lowering med • Prednisone, lowest dose needed • E.g. 2.5 – 7.5 mg a day • May need a combination in severe patients • Stop 6 – 12 months after sUA is at goal • Or after all tophi resolved

  48. Pearl 8:Don’t use prophylaxis without concomitant urate lowering tx

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