3/2/2014. Got Gout? Get a Plumber. Objectives. Disclosures

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1 Got Gout? Get a Plumber. Heidi Garcia, PA-C Department of Rheumatology Division of Internal Medicine Mayo Clinic Arizona 2013 MFMER slide-1 Objectives Recall some of the history of Gout. Describe the pathophysiology of Gout. Recognize how to diagnose Gout. Decide which medications are appropriate for the management of Gout. Decide when to implement treatment. Help patients better understand their disease and disease management MFMER slide-2 Disclosures None 2013 MFMER slide-3 1

2 History of Gout 2600 BC Egypt 400 BC Greece 400 AD Rome 1800 AD England The Latin gutta : a drop of fluid Humoural concept of physiology The disease of kings 2013 MFMER slide-4 Pacheco & Cavallasca N Engl J Med MFMER slide-5 70 Incidence New cases/100,000 people The most notable increase was noted in males > 60 years. An increase was also noted in upper extremity joints accounting for initial Gout attacks. Peak incidence: Males- 40 s & 50 s Females- post menopause Adapted from Arromdee, E. et al. J Rheumatol MFMER slide-6 2

3 Estimated U.S. Prevalence of Gout U.S. Population 3.9% of U.S. Population Men 6.1 million Women 2.2 million Adapted from Zhu, Y., et al. A & R MFMER slide-7 Gout Arthropathy: Acute and Chronic Acute Gout Attacks of joint inflammation 3-10 days 80% of initial Gout attacks are 1 LE joint Most commonly affects 1 st MTP - Podagra foot pain Can mimic/co-exist with infection Differential diagnosis: Infection Foreign body FX AVN Atypical RA Other arthritis Chronic Gout Rheumatoid-like Tophaceous Gout MSU in soft tissues & joints Increased risk: Early onset disease Untreated disease Higher serum uric acid 2013 MFMER slide MFMER slide-9 3

4 2013 MFMER slide MFMER slide MFMER slide-12 4

5 Mimics RA 2013 MFMER slide-13 Tophus Mayo Media Support Services 2013 MFMER slide-14 Tophi 2013 MFMER slide-15 5

6 Pathophysiology of Gout Hyperuricemia - Males - Serum uric acid levels above 8mg/dl Females - Serum uric acid levels above 6.1mg/dl The risk of Gout is 5X greater if the serum uric acid is > 9mg/dl compared to levels between 7-8.9mg/dl. Gout occurs when serum uric acid levels are greater than 6mg/dl. Result of the overproduction and/or under-excretion of uric acid Serum uric acid levels drop during acute attacks. For example, 66 y.o. male with acute onset great toe pain and swelling with an unremarkable xray has a serum uric acid level of 5.3mg/dL. Could he be experiencing Gout? 2013 MFMER slide-16 Uric acid 2013 MFMER slide Cell metabolism 2. Inherited enzyme defects G6PD deficiency 3. Clinical disorders: Obesity Polycythemia vera Malignancy Psoriasis Myelo/lymphoproliferative disorders 1. Drugs: Cytotoxic Warfarin 2. Diet: Ethanol Fructose Foods rich in purines Endogenous uric acid production Exogenous uric acid production 2013 MFMER slide-18 6

7 Purine rich foods The average daily diet for an adult in the U.S. contains approximately mg of purines. Very high levels of up to 1,000mg/3.5 oz serving Anchovies Brain Gravies Kidney Liver Sardines Sweetbreads 2013 MFMER slide-19 Purine rich foods High and moderately high levels of 5-100mg/3.5 oz serving Asparagus Bacon Beef Bouillon Calf tongue Cauliflower Chicken Duck Goose Ham Lamb Kidney beans, Lentils, Lima beans & Navy beans Mushrooms Oatmeal Pork Some fish: Cod, Crab, Halibut, Lobster, Oysters, Salmon, Shrimp, Snapper, Trout, & Tuna Spinach Turkey 2013 MFMER slide-20 Under-excretion of uric acid 1. Clinical disorders: Chronic renal failure Lead nephropathy Polycystic kidney disease Hypertension Dehydration Obesity Hyperparathyroidism Hypothyroidism drain pluggers 2. Drugs: Loop & Thiazide diuretics Salicylates (aspirin) Ethambutal Pyrazinamide Levodopa Cyclosporin kidney 2013 MFMER slide-21 7

8 Diagnosis Hyperuricemia and toe pain does not equal Gout. 1. Gold Standard = Get the crystals. 2. Dual-Energy Computed Tomography (DECT) 3. Ultrasound 2013 MFMER slide-22 Management of Gout 1. Mop the floor 2. Turn down the faucets. 3. Mop some more. 4. Unplug the drain MFMER slide-23 American College of Rheumatology (ACR) Arthritis Care Res Oct;64(10): American College of Rheumatology guidelines for management of gout. Part 1 and Part 2. Khanna D, et. al. 1. Mop the floor. Management of Acute Attack 2. Turn down the faucets. Urate Lowering Therapy 3. Continue to mop. Prophylaxis against Acute Attack 4. Unplug the drain. Lifestyle changes and dietary measures Optimum management of comorbidities 2013 MFMER slide-24 8

9 Management of Acute Attack Anti-inflammatory medication Ideally, treat within 24 hours of onset Supplement with topical ice as needed. Monotherapy Pain < 7/10 or 1-2 joints step 1 Assess severity NSAID Full dose until the attack resolves with an option to taper Corticosteroid Colchicine (Colcrys ) Prednisone 0.5mg/kg/day Only for attack when X 5-10 days Or, 2-5 days, onset was < 36 hrs then taper 7-10 days Loading dose 1.2mg IE- If 70kg, then followed by 35mg X 5-10 days 0.6mg 1 hr later Or, Medrol dose pack Then, 0.6mg 1-2X daily until attack resolves. Optional addition of an injection: IM Kenalog OR IA cortisone Combination therapy Pain 7+ or polyarticular 1. NSAID + colchicine 2. Corticosteroid + colchicine Optional addition of IA cortisone Adapted from Khanna, D. et al. Arth Care & Research MFMER slide MFMER slide-26 American College of Rheumatology. Arthritis Care Res Oct;64(10): American College of Rheumatology guidelines for management of gout. Part 1 and Part 2. Khanna D, et. al. 1. Mop the floor. Management of Acute Attack 2. Turn down the faucets. Urate Lowering Therapy 3. Continue to mop. Prophylaxis against Acute Attack 4. Unplug the drain. Lifestyle changes and dietary measures Optimum management of comorbidities 2013 MFMER slide-27 9

10 Urate Lowering Therapy (ULT) for patients diagnosed with Gout Indications: Frequent attacks (> 2/yr) CKD stage 2+ Past urolithiasis Tophi Patient preference Treat to target Serum uric acid < 6mg/dl Some may need serum uric acid < 5mg/dl ULT initially increases the risk of Gout Do not stop ULT even if an acute Gout attack occurs. Khanna, D. et al. Arth Care & Research MFMER slide-28 1st Line Urate Lowering Therapy (ULT) Xanthine Oxidase Inhibitor allopurinol allopurinol Starting dose 100mg/day CKD - 50mg/day Titrate every 2-5 weeks. Dose can exceed 300mg daily even in renal impairment. Monitor for AE: pruritis, rash, elevated LFTs Maximum dose 800mg/day Educate regarding acute hypersensitivity syndrome (AHS) Highest risk in first few months of therapy & RI Consider genetic testing in high risk populations Koreans with CKD Han Chinese and Thai irrespective of renal function Khanna, D. et al. Arth Care & Research MFMER slide-29 1st Line Urate Lowering Therapy (ULT) Xanthine Oxidase Inhibitor febuxostat febuxostat (Uloric ) Starting dose 40mg daily Monitor after 2 weeks. If serum uric acid is not yet < 6mg/dL, increase dose to 80mg daily. Khanna, D. et al. Arth Care & Research 2012 No dose adjustments in patients with mild to moderate renal or hepatic impairment. Contraindicated with azathioprine. Uloric [package insert]. Revised: November MFMER slide-30 10

11 Other ULT considerations Uricosouric Therapy (increase uric acid excretion) probenecid Copious water consumption needed Not to be used if CC < 50ml/min or h/o urolithiasis XOI + fenofibrate or losartan Biologic pegloticase (Krystexxa ) - Heavy disease burden with chronic tophaceous disease Khanna, D. et al. Arth Care & Research MFMER slide-31 American College of Rheumatology. Arthritis Care Res Oct;64(10): American College of Rheumatology guidelines for management of gout. Part 1 and Part 2. Khanna D, et. al. 1. Mop the floor. Management of Acute Attack 2. Turn down the faucets. Urate Lowering Therapy ULT increases the risk of acute Gout attacks for several months. 3. Continue to mop. Prophylaxis against Acute Attack Continue an anti-inflammatory regimen for at least 6 months. 4. Unplug the drain. Lifestyle changes and dietary measures Optimum management of comorbidities 2013 MFMER slide-32 Acute Gout Prophylaxis Anti-Inflammatory Regimens colchicine (Colcrys ) 0.6mg 1-2X daily or low dose NSAIDS w/ppi or prednisone < 10mg/day Continue at least 6 months or 3-6 months after achieving target serum uric acid. Khanna, D. et al. Arth Care & Research MFMER slide-33 11

12 1. Mop the floor. Management of Acute Attack 2. Turn down the faucets. Urate Lowering Therapy 3. Continue to mop. Prophylaxis against Acute Attack 4. Unplug the drain. Lifestyle changes and dietary measures Optimum management of comorbidities 2013 MFMER slide-34 Comorbities associated with higher risk of Gout Obesity DM/Metabolic syndrome HTN Hyperlipidemia (as a modifiable risk factor for CAD) CKD Lifestyle changes and dietary recommendations Weight loss Healthy diet Smoking cessation Exercise Staying well hydrated Avoiding organ meats, high fructose corn syrup, alcohol overuse Limiting serving sizes of beef, lamb, pork, and some seafood Limiting table sugar and salt Encouraging low/non-fat dairy Encouraging vegetables Khanna, D. et al. Arth Care & Research MFMER slide-35 Question #1 Mr. M. presents with acute onset pain, swelling, erythema, and warmth affecting his right 1 st MTP joint. His serum uric acid level is 10.2mg/dL. He has never had a joint aspirated. Is this enough information to conclude the patient has Gout? A. Yes. If it looks like a duck, quacks like a duck, and waddles like a duck, then it is a duck. B. No. Hyperuricemia and a painful swollen joint is not synonymous with a diagnosis of Gout MFMER slide-36 12

13 Question #2 Choose one best answer. Which of the following statements is true? A. Gout is the result of the overproduction and/or underexcretion of urate. B. In the midst of an acute Gout attack, the serum uric acid level may drop below normal. C. Tests to diagnose Gout include arthrocentesis and/or DECT. D. All of the above MFMER slide-37 Question #3 Microscopic evaluation of synovial fluid aspirated from Mr. M s Great toe MTP joint confirms the diagnosis of Gout. The pain and swelling started 2 days ago. He has no contraindications for NSAIDs, colchicine, prednisone, or allopurinol. According to ACR guidelines, choose treatment options to be started immediately. A. Naproxen B. Colchicine C. Medrol dose pack D. Naproxen and allopurinol 2013 MFMER slide-38 Question #4 Choose one best answer. The majority of patients with confirmed Gout should: A. Start a daily aspirin B. Eat more shrimp and drink more beer. C. Stop allopurinol whenever they have an attack of acute Gout. D. Receive education on a healthy diet, lifestyle changes, and management of comorbidities to lessen the risk of Gout MFMER slide-39 13

14 Question #5 Choose one best answer. Mrs. G. has recently been diagnosed with Gout. Her PMHX includes diabetes mellitus, nephrolithiasis, and moderate chronic kidney disease. The starting dose of allopurinol for her should not exceed: A. 50mg daily B. 100mg daily C. 300mg daily D. None of the above. She should not start allopurinol MFMER slide-40 Question #6 Choose one best answer. The target serum uric acid level for Mrs. G. is: A. < 9mg/dL B. < 8mg/dL C. < 7mg/dL D. < 6mg/dL 2013 MFMER slide-41 Take Home Points Incidence of Gout is increasing. The differential diagnosis of Acute Gout includes infection, fracture, atypical Rheumatoid Arthritis and other inflammatory arthritis. Rheumatoid-like presentation is seen in post-menopausal women. Hyperuricemia with toe pain does not diagnose Gout. Serum uric acid levels drop during acute Gout attacks. Tophi occur in soft tissues and in joints. Urate Lowering Therapy (ULT) ought to be initiated after anti-inflammatory therapy has been established and deemed effective. ULT will increase the risk of Gout for several months. Do not stop ULT during acute Gout attacks. The target serum uric acid level is < 6mg/dl. Continue Gout anti-inflammatory medication for at least 6 months after starting ULT MFMER slide-42 14

15 Special thanks Dr. W. L. Griffing Kenna Atherton (copyright agent) Patrick Jochim (media support) 2013 MFMER slide-43 References 1. Arromdee E., Michet, C.J., Crowson, C.C., et al. Epidemiology of gout: is the incidence rising? Journal of Rheumatology 2002;29: Bhattacharjee, S. A Brief History of Gout. International Journal of Rheumatic Diseases 2009;12: Dalbeth, N. & Choi, H.K. Dual-Energy Computed Tomography for gout diagnosis and management. Current Rheumatology Report 2013;15: Hochberg, M.C., Silman, A.J., Smolen, J.S., et al. Third Edition Rheumatology. Volume Two. Elsevier Limited Khanna, D., Khanna, P.P., Fitzgerald, J.D., et al. American College of Rheumatology Guidelines for Management of Gout. Part 1: Systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care and Research 2012;64: Khanna, D., Fitzgerald, J.D., Khanna, P.P., et al. American College of Rheumatology Guidelines for Management of Gout. Part 2: Therapy and anti-inflammatory prophylaxis of acute gouty arthritis. Arthritis Care and Research 2012;64: Koopman, W.J., Boulware, D.W., Heudebert, G., R., et al. Clinical Primer of Rheumatology. Lippincott Williams Wilkins Nuki, G. & Simkin, P.A. A Concise History of Gout and Hyperuricemia and Their Treatment. Arthritis Research and Therapy 2006;8(Suppl. 1): S1S Roddy, E. Revisiting the pathogenesis of podagra: Why does gout target the foot? Journal of Foot and Ankle Research 2011;4: Roddy, E., Zhang, W., Doherty, M. The changing epidemiology of gout. Nature Clinical Practice Rheumatology 2007;3: Uloric [package insert]. Deerfield (IL): Takeda pharmaceuticals America, Inc: Revised November Zhu, Y., Pandya, B.J., Choi, H.K. Prevalence of gout and hyperuricemia in the US general population. Arthritis & Rheumatism 2011;63: MFMER slide-44 15