Gout: Rapid Evidence Review

 

Am Fam Physician. 2020 Nov 1;102(9):533-538.

  Patient information: Handouts on this topic are available at https://familydoctor.org/condition/gout/ and https://familydoctor.org/low-purine-diet/.

Author disclosure: No relevant financial affiliations.

Gout is caused by monosodium urate crystal deposition in joints and tissues. Risk factors include male sex; obesity; hypertension; alcohol intake; diuretic use; a diet rich in meat and seafood; chronic kidney disease; a diet heavy in fructose-rich food and beverages; being a member of certain ethnic groups, including Taiwanese, Pacific Islander, and New Zealand Maori; and living in high-income countries. Gout is characterized by swelling, pain, or tenderness in a peripheral joint or bursa, including the development of a tophus. Diagnosis of gout can be made using several validated clinical prediction rules. Arthrocentesis should be performed when suspicion for an underlying septic joint is present; synovial fluid or tophus analysis should be performed if the diagnosis is uncertain. Colchicine, nonsteroidal anti-inflammatory drugs, and corticosteroids relieve pain in adults with acute gout episodes. Indications for long-term urate-lowering therapy include chronic kidney disease, two or more flare-ups per year, urolithiasis, the presence of tophus, chronic gouty arthritis, and joint damage. Allopurinol and febuxostat are used to prevent flare-ups, although febuxostat is associated with an increase in all-cause and cardiovascular mortality and is therefore not routinely recommended.

Gout, caused by monosodium urate crystal deposition in joints and tissues, is commonly encountered in primary care. This article provides a review of patient-oriented evidence to guide the diagnosis and management of gout.

 Enlarge     Print

SORT: TABLE OF KEY CLINICAL RECOMMENDATIONS

Clinical recommendationEvidence ratingComments

Lifestyle modifications to prevent recurrent gout include reducing the consumption of high-fructose soft drinks, fruit juices, fruits, and purine-rich foods (e.g., anchovies, sardines, scallops, mussels, bacon, beef, liver, turkey, veal, venison).14

C

Systematic review of mostly observational studies

A validated clinical prediction rule (Table 3) should be used to determine the likelihood of gout based on the presence of typical signs and symptoms and the uric acid level.17

C

Limited quality, patient-oriented evidence, individual validation trial

Nonsteroidal anti-inflammatory drugs and corticosteroids are equally effective for the treatment of acute gout, with no significant difference in pain relief or adverse effects.34

B

Limited quality, patient-oriented evidence, individual randomized controlled trial

In acute gout, low-dose colchicine (1.2 mg followed by 0.6 mg in 1 hour) is as effective as high-dose colchicine (1.2 mg followed by 0.6 mg every hour for 6 hours) with fewer adverse effects.35

B

Limited-quality, patient-oriented evidence, individual randomized controlled trial

Allopurinol is the preferred first-line urate-lowering therapy to prevent recurrent gout. It is as effective as febuxostat (Uloric) in preventing gout flare-ups; however, febuxostat increases all-cause and cardiovascular mortality.41,42

A

Good-quality, patient-oriented evidence, individual randomized controlled trial

The allopurinol hypersensitivity assay, or HLA-B*58:01 test, should be considered in select patients (Korean adults with stage 3 or higher chronic kidney disease and all adults of Han or Thai descent) before initiating allopurinol therapy.44

C

Expert opinion, consensus guideline


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.

The Authors

show all author info

KARL T. CLEBAK, MD, FAAFP, is the residency program director and an assistant professor in the Department of Family and Community Medicine at Penn State Health Milton S. Hershey (Pa.) Medical Center....

ASHLEY MORRISON, MD, is the director of geriatric medicine and an assistant professor in the Department of Family and Community Medicine at Penn State Health Milton S. Hershey Medical Center.

JASON R. CROAD, DO, is an assistant professor in the Department of Family and Community Medicine at Penn State Health Milton S. Hershey Medical Center.

Address correspondence to Karl T. Clebak, MD, FAAFP, Penn State College of Medicine, 121 Nyes Rd., Harrisburg, PA 17111 (email: kclebak@pennstatehealth.psu.edu). Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.

References

show all references

1. Dalbeth N, Merriman TR, Stamp LK. Gout. Lancet. 2016;388(10055):2039–2052....

2. Chen-Xu M, Yokose C, Rai SK, et al. Contemporary prevalence of gout and hyperuricemia in the United States and decadal trends: the National Health and Nutrition Examination Survey, 2007–2016. Arthritis Rheumatol. 2019;71(6):991–999.

3. Kuo CF, Grainge MJ, Mallen C, et al. Rising burden of gout in the UK but continuing suboptimal management: a nationwide population study. Ann Rheum Dis. 2015;74(4):661–667.

4. Choi HK, Atkinson K, Karlson EW, et al. Purine-rich foods, dairy and protein intake, and the risk of gout in men. N Engl J Med. 2004;350(11):1093–1103.

5. Krishnan E. Chronic kidney disease and the risk of incident gout among middle-aged men: a seven-year prospective observational study. Arthritis Rheum. 2013;65(12):3271–3278.

6. Choi HK, Atkinson K, Karlson EW, et al. Alcohol intake and risk of incident gout in men: a prospective study. Lancet. 2004;363(9417):1277–1281.

7. Choi HK, Atkinson K, Karlson EW, et al. Obesity, weight change, hypertension, diuretic use, and risk of gout in men: the health professionals follow-up study. Arch Intern Med. 2005;165(7):742–748.

8. Hainer BL, Matheson E, Wilkes RT. Diagnosis, treatment, and prevention of gout. Am Fam Physician. 2014;90(12):831–836. Accessed July 27, 2020. https://aafp.org/afp/2014/1215/p831.html

9. Eggebeen AT. Gout: an update. Am Fam Physician. 2007;76(6):801–808. Accessed July 27, 2020. https://aafp.org/afp/2007/0915/p801.html

10. Harris MD, Siegel LB, Alloway JA. Gout and hyperuricemia. Am Fam Physician. 1999;59(4):925–934. Accessed July 27, 2020. https://aafp.org/afp/1999/0215/p925.html

11. Kuo CF, Grainge MJ, Zhang W, et al. Global epidemiology of gout: prevalence, incidence and risk factors. Nat Rev Rheumatol. 2015;11(11):649–662.

12. Choi HK, Willett W, Curhan G. Fructose-rich beverages and risk of gout in women. JAMA. 2010;304(20):2270–2278.

13. Choi HK, Curhan G. Soft drinks, fructose consumption, and the risk of gout in men: prospective cohort study. BMJ. 2008;336(7639):309–312.

14. Singh JA, Reddy SG, Kundukulam J. Risk factors for gout and prevention: a systematic review of the literature. Curr Opin Rheumatol. 2011;23(2):192–202.

15. Neogi T. Gout. Ann Intern Med. 2016;165(1):ITC1–ITC16.

16. Roddy E. Revisiting the pathogenesis of podagra: why does gout target the foot? J Foot Ankle Res. 2011;4(1):13.

17. Kienhorst LBE, Janssens HJEM, Fransen J, et al. The validation of a diagnostic rule for gout without joint fluid analysis: a prospective study. Rheumatology (Oxford). 2015;54(4):609–614.

18. Janssens HJEM, Fransen J, van de Lisdonk EH, et al. A diagnostic rule for acute gouty arthritis in primary care without joint fluid analysis. Arch Intern Med. 2010;170(13):1120–1126.

19. Steinberg J. Clinical diagnosis of gout without joint aspirate. Am Fam Physician. 2016;94(6):505–506. Accessed July 27, 2020. https://aafp.org/afp/2016/0915/p505.html

20. Neogi T, Jansen TLTA, Dalbeth N, et al. 2015 gout classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative [published correction appears in Arthritis Rheumatol. 2016;68(2):515]. Arthritis Rheumatol. 2015;67(10):2557–2568.

21. Qaseem A, McLean RM, Starkey M, et al. Diagnosis of acute gout: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2017;166(1):52–57.

22. Horowitz DL, Katzap E, Horowitz S, et al. Approach to septic arthritis. Am Fam Physician. 2011;84(6):653–660. Accessed September 16, 2020. https://aafp.org/afp/2011/0915/p653.html

23. Becker JA, Daily JP, Pohlgeers KM. Acute monoarthritis: diagnosis in adults. Am Fam Physician. 2016;94(10):810–816. Accessed September 16, 2020. https://aafp.org/afp/2016/1115/p810.html

24. Urano W, Yamanaka H, Tsutani H, et al. The inflammatory process in the mechanism of decreased serum uric acid concentrations during acute gouty arthritis. J Rheumatol. 2002;29(9):1950–1953.

25. Schlesinger N, Norquist JM, Watson DJ. Serum urate during acute gout [published correction appears in J Rheumatol. 2009;36(8):1851]. J Rheumatol. 2009;36(6):1287–1289.

26. Pascart T, Lioté F. Gout: state of the art after a decade of developments. Rheumatology (Oxford). 2019;58(1):27–44.

27. Ogdie A, Taylor WJ, Neogi T, et al. Performance of ultrasound in the diagnosis of gout in a multicenter study: comparison with monosodium urate monohydrate crystal analysis as the gold standard. Arthritis Rheumatol. 2017;69(2):429–438.

28. Dalbeth N, McQueen FM. Use of imaging to evaluate gout and other crystal deposition disorders. Curr Opin Rheumatol. 2009;21(2):124–131.

29. Bongartz T, Glazebrook KN, Kavros SJ, et al. Dual-energy CT for the diagnosis of gout: an accuracy and diagnostic yield study. Ann Rheum Dis. 2015;74(6):1072–1077.

30. Rai SK, Fung TT, Lu N, et al. The Dietary Approaches to Stop Hypertension (DASH) diet, Western diet, and risk of gout in men: prospective cohort study. BMJ. 2017;357:j1794.

31. Hui M, Carr A, Cameron S, et al.; British Society for Rheumatology Standards, Audit and Guidelines Working Group.. The British Society for Rheumatology guideline for the management of gout [published correction appears in Rheumatology (Oxford). 2017;56(7):1246]. Rheumatology (Oxford). 2017;56(7):e1–e20.

32. Schlesinger N, Detry MA, Holland BK, et al. Local ice therapy during bouts of acute gouty arthritis. J Rheumatol. 2002;29(2):331–334.

33. Shekelle PG, Newberry SJ, FitzGerald JD, et al. Management of gout: a systematic review in support of an American College of Physicians clinical practice guideline. Ann Intern Med. 2017;166(1):37–51.

34. Janssens HJEM, Janssen M, van de Lisdonk EH, et al. Use of oral prednisolone or naproxen for the treatment of gout arthritis: a double-blind, randomised equivalence trial. Lancet. 2008;371(9627):1854–1860.

35. Terkeltaub RA, Furst DE, Bennett K, et al. High versus low dosing of oral colchicine for early acute gout flare: twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study. Arthritis Rheum. 2010;62(4):1060–1068.

36. Sivera F, Wechalekar MD, Andrés M, et al. Interleukin-1 inhibitors for acute gout. Cochrane Database Syst Rev. 2014;(9):CD009993.

37. American Academy of Family Physicians. Management of acute and recurrent gout; April 2017. Accessed January 29, 2020. https://www.aafp.org/patient-care/clinical-recommendations/all/gout-cpg.html

38. Khanna D, Fitzgerald JD, Khanna PP, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken). 2012;64(10):1431–1446.

39. FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology guideline for the management of gout [practice guideline]. Arthritis Rheumatol. 2020;72(6):879–895.

40. Allopurinol 300mg tablets [package insert]. Accord Healthcare Limited. Updated September 2, 2020. Accessed September 16, 2020. https://www.medicines.org.uk/emc/product/6006/smpc#gref

41. White WB, Saag KG, Becker MA, et al.; CARES Investigators. Cardiovascular safety of febuxostat or allopurinol in patients with gout. N Engl J Med. 2018;378(13):1200–1210.

42. Becker MA, Schumacher HR Jr, Wortmann RL, et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med. 2005;353(23):2450–2461.

43. Richette P, Doherty M, Pascual E, et al. 2018 updated European League Against Rheumatism evidence-based recommendations for the diagnosis of gout. Ann Rheum Dis. 2020;79(1):31–38.

44. Bryce C. Allopurinol hypersensitivity assay HLA-B*58:01 genotyping. Am Fam Physician. 2019;100(9):530–531. Accessed July 27, 2020. https://aafp.org/afp/2019/1101/p530.html

45. U.S. Food and Drug Administration. Drug approval package: Krystexxa (pegloticase) injection: Savient Pharmaceuticals, Inc. November 12, 2010. Accessed May 12, 2020. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/125293s0000TOC.cfm

46. Wechalekar MD, Vinik O, Schlesinger N, et al. Intra-articular glucocorticoids for acute gout. Cochrane Database Syst Rev. 2013;(4):CD009920.

47. Stamp LK, O'Donnell JL, Frampton C, et al. Clinically insignificant effect of supplemental vitamin C on serum urate in patients with gout: a pilot randomized controlled trial. Arthritis Rheum. 2013;65(6):1636–1642.

48. Lee WB, Woo SH, Min BI, et al. Acupuncture for gouty arthritis: a concise report of a systematic and meta-analysis approach. Rheumatology (Oxford). 2013;52(7):1225–1232.

49. Zhang T, Pope JE. Cardiovascular effects of urate-lowering therapies in patients with chronic gout: a systematic review and meta-analysis. Rheumatology (Oxford). 2017;56(7):1144–1153.

50. Pittman JR, Bross MH. Diagnosis and management of gout. Am Fam Physician. 1999;59(7):1799–1806. Accessed July 28, 2020. https://www.aafp.org/afp/1999/0401/p1799.html

 

 

Copyright © 2020 by the American Academy of Family Physicians.
This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact afpserv@aafp.org for copyright questions and/or permission requests.

Want to use this article elsewhere? Get Permissions

CME Quiz

More in AFP


Editor's Collections


Related Content


More in Pubmed

MOST RECENT ISSUE


Dec 1, 2020

Access the latest issue of American Family Physician

Read the Issue


Email Alerts

Don't miss a single issue. Sign up for the free AFP email table of contents.

Sign Up Now

Navigate this Article