Got Gout? Get a Plumber

3/2/2014

Got Gout? Get a Plumber.

Heidi Garcia, PA-C Department of Rheumatology Division of Internal Medicine Mayo Clinic Arizona

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.

Disclosures

• None

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History of Gout

400 AD Rome 2600 BC Egypt 400 BC Greece 1800 AD England

• The Latin “gutta”: a drop of fluid • Humoural concept of physiology • “The disease of kings”

Pacheco & Cavallasca N Engl J Med 2005

Incidence New cases/100,000 people 70

60 • The most notable increase 50 was noted in males > 60 years.

40 • An increase was also noted 30 in upper extremity joints accounting for initial Gout 20 attacks.

10 • Peak incidence: • Males- 40’s & 50’s 0 • Females- post menopause 1977-1978 1995-1996

Adapted from Arromdee, E. et al. J Rheumatol 2002

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Estimated U.S. Prevalence of Gout 2007-2008

U.S. Population

Men 6.1 million 3.9% of U.S. Population Women 2.2 million

Adapted from Zhu, Y., et al. A & R 2011

Gout Arthropathy: Acute and Chronic

Acute Gout Chronic Gout • Attacks of joint inflammation • Rheumatoid-like • 3-10 days • Tophaceous Gout • 80% of initial Gout attacks • MSU in soft tissues & are 1 LE joint joints • Most commonly affects 1 st • Increased risk: MTP - Podagra “foot pain” • Early onset disease • Can mimic/co-exist with • Untreated disease infection • Higher serum uric • Differential diagnosis: acid • Infection • Foreign body • FX • AVN • Atypical RA • Other arthritis

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Mimics RA

Tophus

Mayo Media Support Services

Tophi

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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?

Uric acid

1. Cell metabolism 1. Drugs: 2. Inherited enzyme defects • Cytotoxic • G6PD deficiency • Warfarin 3. Clinical disorders: 2. Diet: • Obesity • Ethanol • Polycythemia vera • Fructose • Malignancy • Foods rich in purines • Psoriasis • Myelo/lymphoproliferative disorders

Endogenous uric acid production Exogenous uric acid production

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The average daily diet for an adult in the U.S. contains approximately 600-1000mg of purines.

Purine rich foods

Very high levels of up to 1,000mg/3.5 oz serving • Anchovies • Brain • Gravies • Kidney • Liver • Sardines • Sweetbreads

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

drain pluggers 1. Clinical disorders: 2. Drugs: • Chronic renal failure • Loop & Thiazide diuretics • Lead nephropathy • Salicylates (aspirin) • Polycystic kidney disease • Ethambutal • Hypertension • Pyrazinamide • Dehydration • Levodopa • Obesity • Cyclosporin • Hyperparathyroidism • Hypothyroidism

kidney

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Diagnosis

• Hyperuricemia and toe pain does not equal Gout. • 1. Gold Standard = Get the crystals.

2. Dual-Energy Computed Tomography (DECT) 3. Ultrasound

Management of Gout

1. Mop the floor 2. Turn down the faucets. 3. Mop some more. 4. Unplug the drain.

American College of Rheumatology (ACR) Arthritis Care Res. 2012 Oct;64(10):1431-61. 2012 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

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Management of Acute Attack Anti-inflammatory medication Ideally, treat within 24 hours of onset step 1 Supplement Assess with topical ice Pain < 7/10 or severity as needed . Monotherapy 1-2 joints

Colchicine NSAID Corticosteroid ® (Colcrys ) Pain 7+ or polyarticular Full dose until the Prednisone 0.5mg/kg/day Only for attack when attack resolves – X 5-10 days Or, 2-5 days, onset was < 36 hrs with an option then taper 7-10 days Loading dose 1.2mg to taper IE- If 70kg, then followed by 35mg X 5-10 days 0.6mg 1 hr later Combination

Or, Medrol dose pack Then, 0.6mg 1-2X daily therapy until attack resolves. Optional – 1. NSAID + colchicine addition of an injection: 2. Corticosteroid + colchicine IM Kenalog OR IA cortisone Optional – addition of IA cortisone

American College of Rheumatology. Arthritis Care Res. 2012 Oct;64(10):1431-61. 2012 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

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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 2012

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 2012

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 2012

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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 2012

American College of Rheumatology. Arthritis Care Res. 2012 Oct;64(10):1431-61. 2012 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

Acute Gout Prophylaxis Anti-Inflammatory Regimens

• colchicine (Colcrys ®) 0.6mg 1-2X daily

• low dose NSAIDS w/PPI

• 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 2012

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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

• Comorbities associated with higher • Lifestyle changes and dietary risk of Gout recommendations • Obesity • Weight loss • DM/Metabolic syndrome • Healthy diet • HTN • Smoking cessation • Hyperlipidemia (as a • Exercise modifiable risk factor for CAD) • Staying well hydrated • CKD • 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 2012

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.

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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.

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

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.

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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.

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

Take Home Points

• Incidence of Gout is increasing. • Urate Lowering Therapy (ULT) ought to be initiated after anti-inflammatory • The differential diagnosis of Acute Gout therapy has been established and includes infection, fracture, atypical deemed effective. Rheumatoid Arthritis and other inflammatory arthritis. • ULT will increase the risk of Gout for several months. • Rheumatoid-like presentation is seen in post-menopausal women. • Do not stop ULT during acute Gout attacks. • Hyperuricemia with toe pain does not diagnose Gout. • The target serum uric acid level is < 6mg/dl. • Serum uric acid levels drop during acute Gout attacks. • Continue Gout anti-inflammatory medication for at least 6 months after • Tophi occur in soft tissues and in joints. starting ULT.

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Special thanks Dr. W. L. Griffing Kenna Atherton (copyright agent) Patrick Jochim (media support)

References

1. Arromdee E., Michet, C.J., Crowson, C.C., et al. Epidemiology of gout: is the incidence rising? Journal of Rheumatology 2002;29:2403-06.

2. Bhattacharjee, S. A Brief History of Gout. International Journal of Rheumatic Diseases 2009;12:61-63.

3. Dalbeth, N. & Choi, H.K. Dual-Energy Computed Tomography for gout diagnosis and management. Current Rheumatology Report 2013;15:301-7.

4. Hochberg, M.C., Silman, A.J., Smolen, J.S., et al. Third Edition Rheumatology. Volume Two. Elsevier Limited. 2003.

5. 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;64:1431-46.

6. 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;64:1447-61.

7. Koopman, W.J., Boulware, D.W., Heudebert, G., R., et al. Clinical Primer of Rheumatology. Lippincott Williams Wilkins. 2003.

8. Nuki, G. & Simkin, P.A. A Concise History of Gout and Hyperuricemia and Their Treatment. Arthritis Research and Therapy 2006;8(Suppl. 1): S1S5. .

9. Roddy, E. Revisiting the pathogenesis of podagra: Why does gout target the foot? Journal of Foot and Ankle Research 2011;4:13.

10. Roddy, E., Zhang, W., Doherty, M. The changing epidemiology of gout. Nature Clinical Practice Rheumatology 2007;3:443-9.

11. Uloric [package insert]. Deerfield (IL): Takeda pharmaceuticals America, Inc: Revised November 2012.

12. Zhu, Y., Pandya, B.J., Choi, H.K. Prevalence of gout and hyperuricemia in the US general population. Arthritis & Rheumatism 2011;63:3136-41.