1 Diagnosis & Treatment of Gout Michele Meltzer MD MBE Associate Clinical Professor Medicine Department of Medicine, Rheumatology Thomas Jefferson University.

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Diagnosis & Treatment of Gout

Michele Meltzer MD MBEAssociate Clinical Professor Medicine

Department of Medicine, Rheumatology

Thomas Jefferson University

Gill Diagnosis & Treatment of Gout

Gillray James. 1757-1815. Punch Cures the Gout, the Colic and the Tisick.

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• Understand the patient script gout• Physical examination• Pathogenesis• Diagnostic studies• Treatment and prevention• Counsel to patients


Goals

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De Diagnosis & Treatment of Gout

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Gout abnormal purine metabolism

Increased tubular reabsorptionAlcohol

Endogenous synthesis purine

Fructose

Dietary intake Seafood, meat and beer

Urate Pool

Renal impairment, diuretics

Impaired urinary excretion

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Purine Metabolism

Purines Hypoxanthine

Xanthine Oxidase

Xanthine Uric acid

Urinary excretion

90% reabsorbed

Xanthine Oxidase

l Diagnosis & Treatment of Gout

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Urate Increasing Agents

• Pyrazinamide

• Low dose salicylate

• Diuretics

• Cyclosporine

• Tacrolimus

• Ethambutol

Choi H.K; D.B. Mount M.D; Reginato A.M. Pathogenesis of Gout, the Annals of Internal Med. American College of Physicians 2005; 143(7):499-519


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Urate Decreasing Agents

• Probenecid• Losartan• High dose salicylate• Fenofibrate• Amlodipine

Xanthine Oxidase Inhibitors• Allopurinol• Febuxostat



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Source http://www.health-pictures.com/gout-picture.htmlicensed under the Creative Commons Attribute-Share Alike 3.0 Unported license

Pictures of Gout

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Pictures of Gout

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Copyrights @ 2013 Thomas Jefferson University

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Pictures of Gout

This work is licensed under a Creative Commons Attribution 2,0 Generic Licensehttp://www.flickr.com/photos/handarmdoc/9209624939/

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Copyrights @ 2013 Thomas Jefferson University

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Negatively Birefringent Crystal


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Sivera F, Andrés M, Carmona L, et al. Multinational evidence-based recommendations for the diagnosis and management of gout:

Integrating systematic literature review and expert opinion of a broad panel of rheumatologists in the 3e initiative. Ann Rheum Dis.

Published Online First: 18 July 2013. doi:10.1136/annrheumdis-2013-203325. Accessed 9 September 2013

1. Diagnosis

Ideally, identify MSU crystals, otherwise, diagnose gout supported by classical history such as podagra, tophi and rapid response to colchicine, do not forget that r/o infection can occur with gout

X-Ray changes take years to develop

• Check renal function !!!!• Evaluate cardiovascular risk factors


2. Important Co-morbidities

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• If attack occurs less than 24 hours use Colchicine 1.2 mg followed one hour later by 0.6 mg

• NSAIDs and/or glucocorticoids can also be used (intra-articular, oral or intramuscular) but be aware of co-morbidities


3. Acute Attack Treatment

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• Lose weight

• Increase exercise

• Stop smoking

• Avoid excess alcohol, especially beer and high fructose drinks

• Ask about possible risks for lead exposure (this is not standard recommendation but may be a concern in some countries)

4. Life-style changes


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• Allopurinol should be the first line

• Alternatives are probenecid or febuxostat (very expensive and has been associated with allergic hypersensitivity)

• Use Uricase only in patients with severe gout and when other therapies failed

• In urate lowering therapy (except uricase), start with low dosage and then titrate to target

5. Urate lowering therapy


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b

• Major criteria : Worsening renal impairment, acute hepatocellular injury, rash

• Minor criteria : Fever, Eosinophilia, Leukocytosis


Allopurinol Hypersensitivity Syndrome

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Stamp K.L, Taylor W.J, Jones P.B et. al. Starting dose is a risk factor for allopurinol hypersensitivity syndrome: A proposedSafe starting dose of allopurinol. Arthritis & Rheumatism Vol 64 No 8 Aug 2012 pp2529-2538

• Median time from starting allopurinol to the occurrence of AHS was 30 days (range 1-1,080 days)


Starting dose is a risk factor for allopurinolhypersensitivity syndrome

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Stamp K.L, Taylor W.J, Jones P.B et. al. Starting dose is a risk factor for allopurinol hypersensitivity syndrome: A proposedSafe starting dose of allopurinol. Arthritis & Rheumatism Vol 64 No 8 Aug 2012 pp2529-2538

• Patient education on risk flares and management flares DO NOT STOP urate lowering therapy flare

• Colchicine can be used up to 0.6 mg. BID or NSAID or low dose glucocorticoids can also be used but duration of prophylaxis depends on individual patient

6. Intercritical period: Initiating urate lowering therapy


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• For mild to moderate renal impairment, allopurinol may be used with close monitoring, start low daily dose up titrated to achieve usual target of serum uric acid

• Febuxostat can be used but there is no data for severe renal impairment

• Do NOT use probenecid


7. Renal Impairment

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• Target 0.36 mmol/L (6 mg/dL) and the eventual absence of gout attacks

• Resolution of tophi

8. Treat to target


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• Should be treated medically

• If tophi is severe, target below 0.30 mmol/L (5mg/dL)

• Surgery indicated in selected cases (nerve compression, mechanical impingement or infection)


9. Tophi

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• Pharmacologic treatment is NOT recommended today to prevent gouty arthritis, renal disease or CV event

But…..• Would encourage lifestyle changes

10. Asymptomatic Hyperuricemia


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We should NEVER see these changes with the

availability of current therapies


Chronic Gout

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More images

1. http://images.rheumatology.org/

2. Search for “Gout” on Google images.

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http://images.rheumatology.org/

• Understand the patient script gout• Physical examination• Pathogenesis• Diagnostic studies• Treatment and prevention• Counsel to patients


Goals

26

Diagnosis & Treatment of GoutReferences


Johnson R.J, Kang D.H, Feig D, et al. Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? Hypertension 2003;41:1183-90. http://hyper.ahajournals.org/content/41/6/1183.abstract?ijkey=04cc5ea8e8a1c7bd48d927474864f25fc800b2c0&keytype2=tf_ipsecsha

Rees S, Jenkins W, Doherty M. Patients with gout adhere to curative treatment if informed appropriately: proof-of-concept observational study. Ann Rheum Dis (2013) 72 (6): 826-830

Schumacher H.R, Taylor W, Edwards L, et al. Outcome domains for studies of acute and chronic gout. J Rheumatol 2009;36:2342–5. http://www.jrheum.org/content/36/10/2342.abstract?ijkey=e101d6f0c28d93b1418afc1e78811b0145d0a922&keytype2=tf_ipsecsha

Sivera F, Andrés M, Carmona L, et al. Multinational evidence-based recommendations for the diagnosis and management of gout: Integrating systematic literature review and expert opinion of a broad panel of rheumatologists in the 3e initiative. Ann Rheum Dis. Published Online First: 18 July 2013. doi:10.1136/annrheumdis-2013-203325. Accessed 9 September 2013http://ard.bmj.com/content/early/2013/07/17/annrheumdis-2013-203325.full

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http://hyper.ahajournals.org/content/41/6/1183.abstract?ijkey=04cc5ea8e8a1c7bd48d927474864f25fc800b2c0&keytype2=tf_ipsecsha

http://hyper.ahajournals.org/content/41/6/1183.abstract?ijkey=04cc5ea8e8a1c7bd48d927474864f25fc800b2c0&keytype2=tf_ipsecsha

http://www.jrheum.org/content/36/10/2342.abstract?ijkey=e101d6f0c28d93b1418afc1e78811b0145d0a922&keytype2=tf_ipsecsha

http://www.jrheum.org/content/36/10/2342.abstract?ijkey=e101d6f0c28d93b1418afc1e78811b0145d0a922&keytype2=tf_ipsecsha

Stamp L.K, Taylor W.J, Jones P.B, Dockerty J. L, Drake J, Frampton C, Delbeth, N. Starting dose is a risk factor for allopurinol hypersensitivity syndrome: A proposed safe starting dose of allopurinol. Arthritis & Rheumatism Vol 64 No 8 Aug 2012 pp2529-2538

Watanabe S, Kang D.H, Feng L, et al. Uric acid, hominoid evaluation and the pathogenesis of salt-sensitivity. Hypertension 2002;40:355-60http://hyper.ahajournals.org/content/40/3/355.abstract?ijkey=4e54ce38f17f6266416fb9eb9c6ee0c68db72e13&keytype2=tf_ipsecsha

Zhang W, et. Al. EULAR evidence based recommendations for gout. Part I: Diagnosis. Report of a task force of the Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis. 2006;65:1301-11. http://www.ncbi.nlm.nih.gov/pubmed/16707533

Zhang W, et.al. EULAR evidence based recommendations for gout. Part II: Management. Report of a task force of the EULAR Standing Committee International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis. 2006; 65: 1312-24. http://www.ncbi.nlm.nih.gov/pubmed/16707532


References

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http://hyper.ahajournals.org/content/40/3/355.abstract?ijkey=4e54ce38f17f6266416fb9eb9c6ee0c68db72e13&keytype2=tf_ipsecsha

http://hyper.ahajournals.org/content/40/3/355.abstract?ijkey=4e54ce38f17f6266416fb9eb9c6ee0c68db72e13&keytype2=tf_ipsecsha

http://www.ncbi.nlm.nih.gov/pubmed/16707533

1 Diagnosis & Treatment of Gout Michele Meltzer MD MBE Associate Clinical Professor Medicine Department of Medicine, Rheumatology Thomas Jefferson University.

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