garcia got gout - cdn.ymaws.com · 3/2/2014 6 ©2013 mfmer | slide-16 pathophysiology of gout...

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©2013 MFMER | slide-1

Got Gout? Get a Plumber.

Heidi Garcia, PA-CDepartment of RheumatologyDivision 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

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

2600 BC Egypt

400 BC Greece

400 AD Rome

1800 AD England


Pacheco & Cavallasca N Engl J Med 2005


Incidence

0

10

20

30

40

50

60

70

1977-1978 1995-1996

New cases/100,000 people

• The most notable increasewas noted in males > 60 years.

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

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

• Peak incidence: • Males- 40’s & 50’s• Females- post menopause

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Estimated U.S. Prevalence of Gout2007-2008

U.S. Population

Men 6.1 million

Women 2.2 million3.9% of U.S. Population

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


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 1st

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


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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


Endogenous uric acid production Exogenous uric acid production

1. Cell metabolism2. Inherited enzyme defects

• G6PD deficiency3. Clinical disorders:

• Obesity • Polycythemia vera• Malignancy• Psoriasis• Myelo/lymphoproliferativedisorders

1. Drugs:• Cytotoxic• Warfarin

2. Diet:• Ethanol• Fructose• Foods rich in purines

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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


Under-excretion of uric acid

1. Clinical disorders:• Chronic renal failure• Lead nephropathy• Polycystic kidney disease• Hypertension• Dehydration• Obesity• Hyperparathyroidism• Hypothyroidism

2. Drugs:• Loop & Thiazide diuretics• Salicylates (aspirin)• Ethambutal• Pyrazinamide• Levodopa• Cyclosporin

drain pluggers

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 floor2. 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.

2. Turn down the faucets.

3. Continue to mop.

4. Unplug the drain.

Management of Acute Attack

Urate Lowering Therapy

Prophylaxis against Acute Attack

Lifestyle changes and dietary measures

Optimum management of comorbidities

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Management of Acute AttackAnti-inflammatory medicationIdeally, treat within 24 hours of onset

Supplement with topical iceas needed.

Monotherapy

NSAID CorticosteroidColchicine(Colcrys ®)

Combination therapy

Assess severity

Full dose until theattack resolves –with an option to taper

Prednisone 0.5mg/kg/day X 5-10 days Or, 2-5 days, then taper 7-10 days

IE- If 70kg, then 35mg X 5-10 days

Or, Medrol dose pack

Optional –addition of an injection:IM Kenalog OR IA cortisone

Only for attack whenonset was < 36 hrs

Loading dose 1.2mg followed by0.6mg 1 hr later

Then, 0.6mg 1-2X dailyuntil attack resolves.

Pain < 7/10 or1-2 joints

Pain 7+ orpolyarticular

1. NSAID + colchicine2. Corticosteroid + colchicine

Optional – addition of IA cortisone

Adapted from Khanna, D. et al. Arth Care & Research 2012

step 1



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


1. Mop the floor.


3. Continue to mop.







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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



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.


1. Mop the floor.


3. Continue to mop.







ULT increases the risk of acute Gout attacks for several months.

Continue an anti-inflammatory regimen for at least 6 months.


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.


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1. Mop the floor.


3. Continue to mop.








• 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



Question #1

Mr. M. presents with acute onset pain, swelling, erythema, and warmth affecting his right 1st 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 #2Choose 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



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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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.



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.

• 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.

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Special thanksDr. W. L. GriffingKenna 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 Rheumatology2007;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.

garcia got gout - cdn.ymaws.com · 3/2/2014 6 ©2013 mfmer | slide-16 pathophysiology of gout...

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