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

2. Diagnosis & Treatment of Gout
Gill
Diagnosis & Treatment of Gout
This image (or other media file) is in the public domain because its copyright has expired
Gillray James Punch Cures the Gout, the Colic and the Tisick. 2

3. Diagnosis & Treatment of Gout
Goals
Understand the patient script gout
Physical examination
Pathogenesis
Diagnostic studies
Treatment and prevention
Counsel to patients 3

4. Diagnosis & Treatment of GoutDe
Diagnosis & Treatment of Gout
Gout abnormal purine metabolism
Impaired urinary excretion
Renal impairment, diuretics
Endogenous synthesis purine
Fructose
Urate Pool
Increased tubular reabsorption
Dietary intake
Alcohol
Seafood, meat and beer 4
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5. Diagnosis & Treatment of Gout
Purine Metabolism
Purines
Hypoxanthine
Xanthine
Uric acid
Xanthine Oxidase
Xanthine Oxidase
90% reabsorbed
Urinary excretion 5

6. Diagnosis & Treatment of Goutl
Diagnosis & Treatment of Gout
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): 6

7. Diagnosis & Treatment of Gout
Urate Decreasing Agents
Probenecid
Losartan
High dose salicylate
Fenofibrate
Amlodipine
Xanthine Oxidase Inhibitors
Allopurinol
Febuxostat
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): 7

8. Diagnosis & Treatment of Gout
Pictures of Gout
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Source
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9. Diagnosis & Treatment of Gout
Pictures of Gout
Thomas Jefferson University
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10. Diagnosis & Treatment of Gout
Pictures of Gout
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Thomas Jefferson University
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11. Negatively Birefringent Crystal
Diagnosis & Treatment of Gout
Negatively Birefringent Crystal
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Sources 11

12. Diagnosis & Treatment of Gout
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
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 doi: /annrheumdis Accessed 9 September 2013 12

13. Diagnosis & Treatment of Gout
2. Important Co-morbidities
Check renal function !!!!
Evaluate cardiovascular risk factors
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 doi: /annrheumdis Accessed 9 September 2013 13

14. Diagnosis & Treatment of Gout
3. Acute Attack Treatment
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
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 doi: /annrheumdis Accessed 9 September 2013 14

15. Diagnosis & Treatment of Gout
4. Life-style changes
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)
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 doi: /annrheumdis Accessed 9 September 2013 15

16. Diagnosis & Treatment of Gout
5. Urate lowering therapy
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
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 doi: /annrheumdis Accessed 9 September 2013 16

17. Diagnosis & Treatment of Goutb
Diagnosis & Treatment of Gout
Allopurinol Hypersensitivity Syndrome
Major criteria : Worsening renal impairment, acute hepatocellular injury, rash
Minor criteria : Fever, Eosinophilia, Leukocytosis
Stamp K.L, Taylor W.J, Jones P.B et. al. 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 pp 17

18. Diagnosis & Treatment of Gout
Starting dose is a risk factor for allopurinol
hypersensitivity syndrome
Median time from starting allopurinol to the occurrence of AHS was 30 days (range 1-1,080 days)
Stamp K.L, Taylor W.J, Jones P.B et. al. 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 pp 18

19. Diagnosis & Treatment of Gout
6. Intercritical period: Initiating urate lowering therapy
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
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 doi: /annrheumdis Accessed 9 September 2013 19

20. Diagnosis & Treatment of Gout
7. Renal Impairment
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
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 doi: /annrheumdis Accessed 9 September 2013 20

21. Diagnosis & Treatment of Gout
8. Treat to target
Target 0.36 mmol/L (6 mg/dL) and the eventual absence of gout attacks
Resolution of tophi
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 doi: /annrheumdis Accessed 9 September 2013 21

22. Diagnosis & Treatment of Gout
9. Tophi
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)
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 doi: /annrheumdis Accessed 9 September 2013 22

23. Diagnosis & Treatment of Gout
10. Asymptomatic Hyperuricemia
Pharmacologic treatment is NOT recommended today to prevent gouty arthritis, renal disease or CV event
But…..
Would encourage lifestyle changes
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 doi: /annrheumdis Accessed 9 September 2013 23

24. Diagnosis & Treatment of Gout
Chronic Gout
We should NEVER see these changes with the availability of current therapies
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25. Diagnosis & Treatment of Gout
More images 1.
2. Search for “Gout” on Google images. 25

26. Diagnosis & Treatment of Gout
Goals
Understand the patient script gout
Physical examination
Pathogenesis
Diagnostic studies
Treatment and prevention
Counsel to patients 26

27. Diagnosis & Treatment of Gout
References
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):
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:
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):
Schumacher H.R, Taylor W, Edwards L, et al. Outcome domains for studies of acute and chronic gout.
J Rheumatol 2009;36:2342–5.
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 doi: /annrheumdis Accessed 9 September 2013 27

28. Diagnosis & Treatment of Gout
References
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 pp
Watanabe S, Kang D.H, Feng L, et al. Uric acid, hominoid evaluation and the pathogenesis of salt-sensitivity. Hypertension 2002;40:355-60
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:
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: 28