Source: American Family Physician, September 2007


Clinical recommendation

Evidence rating


Serum uric acid measurements are useful in the evaluation of gout; however, they should not be used alone to confirm or exclude the diagnosis.


12, 17, 19

Nonsteroidal anti-inflammatory drugs, corticosteroids, and colchicine are effective treatments for acute gout.


20, 22-25

In patients with gout, modifiable risk factors such as obesity, diuretic use, high-purine diet, and alcohol intake should be addressed.


13, 14, 17

Urate-lowering therapy is recommended for patients with recurrent gout attacks, tophi, or ongoing arthropathy with joint damage seen on a radiograph.



When initiating urate-lowering therapy, prophylaxis with low-dose colchicine for three to six months may reduce the risk of flare-ups.


20, 28

During urate-lowering therapy, the target serum uric acid level is less than 6 mg per dL (355 µmol per L).


20, 29

Allopurinol (Zyloprim) is the recommended first-line agent for urate-lowering therapy.



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, see page 749 or http://www.aafp.org/afpsort.xml.





Epidemiology and Pathophysiology


Risk Factors


Clinical Presentation

Acute Gout

Chronic Gout



Classification criteria to aid in the diagnosis of gout have been proposed by the American College of Rheumatology (Table 1),16 and a consensus panel of experts from the European League Against Rheumatism (EULAR) has reviewed the evidence and made recommendations for diagnosing gout.17 The main differential diagnosis (Table 2) of acute gout is pseudogout (calcium pyrophosphate deposition disease) and septic arthritis.

Table 1. American College of Rheumatology Preliminary Criteria for Gout

Gout may be diagnosed if one of the following criteria is present:

Monosodium urate crystals in synovial fluid

Tophi confirmed with crystal examination

At least six of the following findings:

Asymmetric swelling within a joint on a radiograph

First metatarsophalangeal joint is tender or swollen (i.e., podagra)


Maximal inflammation developed within one day

Monoarthritis attack

More than one acute arthritis attack

Redness observed over joints

Subcortical cysts without erosions on a radiograph

Suspected tophi

Synovial fluid culture negative for organisms during an acute attack

Unilateral first metatarsophalangeal joint attack

Unilateral tarsal joint attack

Adapted with permission from Wallace SL, Robinson H, Masi AT, Decker JL, McCarty DJ, Yu TF. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum 1977;20:896.

Table 2. Differential Diagnosis of Acute Gout

Synovial fluid findings


Joint distribution

WBC count*

Gram stain/culture

Synovial fluid crystals

Radiography findings


Lower extremities: metatarsophalangeal, midtarsal, or knee joints; initial attacks may be less common in upper extremities

2,000 to 50,000 per mm3 (2 × 109 to 50 × 109 per L)


Needle shaped, negative birefringence

Acute: asymmetric swelling

Chronic: periarticular erosions with overhanging edges

Pseudogout (calcium pyrophosphate deposition disease)

Knee, wrist, or first metatarsophalangeal

2,000 to 50,000 per mm3


Rhomboid shaped, weak positive birefringence

Soft tissue swelling, chondrocalcinosis (calcification of cartilage)

Septic arthritis

Knee is most commonly involved (may be any joint distribution)

> 50,000 per mm3


No crystals

Joint effusion; radiography results otherwise normal early in the disease

NOTE: This table applies to immunocompetent patients.

WBC = white blood cell.

*-The synovial fluid WBC count should not be used alone to exclude infection.

-Septic arthritis may coexist with crystalline arthritis.

Table 3 presents data for the accuracy of key elements in the diagnosis of gout.16-18 The presence of podagra or tophi strongly supports a gout diagnosis. The presence of monosodium urate crystals in synovial fluid is confirmatory, although a synovial fluid analysis is not always feasible. In the appropriate clinical scenario, a patient with hyperuricemia and classic podagra can be diagnosed and treated empirically. However, if a gout diagnosis is in question, synovial fluid analysis should be attempted. Serum uric acid measurements are not sufficient for confirming or ruling out gout because they may be normal during an acute attack.12,17,19

Table 3. Accuracy of Key Findings in the Diagnosis of Acute Gout


Sensitivity (%)

Specificity (%)



Asymmetric swelling shown on a radiograph16,17










Monosodium urate crystals in synovial fluid16,17





Podagra (first metatarsophalangeal joint involvement)16-18





Tophi confirmed16-18





LR+ = positive likelihood ratio; LR- = negative likelihood ratio.

Information from references 16 through 18.

A 24-hour urine collection to detect uric acid excretion is not routinely performed. Collection and dietary restrictions are difficult, and most patients receive allopurinol for chronic urate-lowering therapy regardless of the cause of hyperuricemia.


The goals of gout treatment are symptom control for acute attacks, risk factor modification, and pharmacotherapy to prevent recurrence and chronic sequelae. Recommendations from the EULAR guideline for the treatment of gout are summarized below.20

Therapy for acute attacks

The most important symptoms of gout are pain and swelling, which may be accompanied by systemic symptoms such as fever and malaise. Table 4 summarizes pharmacotherapy for acute gout.21

Table 4. Pharmacotherapy for Acute Gout





Indomethacin (Indocin), 50 mg three times daily for four to 10 days

Naproxen (Naprosyn), 500 mg twice daily for four to 10 days

Sulindac (Clinoril), 200 mg twice daily for four to 10 days

Use with caution in older patients and in patients with renal insufficiency, heart failure, peptic ulcer disease, or liver disease and in those receiving anticoagulation therapy

Any NSAID is effective


Prednisone, 20 to 40 mg daily for two or three days, then taper over 10 to 14 days

Intra-articular methylprednisolone (Depo-Medrol), one 20- to 40-mg dose

Intramuscular methylprednisolone, one 80- to 120-mg dose

Avoid in patients with joint sepsis and use cautiously in patients with diabetes

Intra-articular therapy may be the treatment of choice if only one or two accessible joints are involved

Colchicine, 0.6 mg orally two or three times daily

Suggested renal dosing (based on creatinine clearance):

> 50 mL per minute (0.83 mL per second): 0.6 mg twice daily

35 to 50 mL per minute (0.58 to 0.83 mL per second): 0.6 mg daily

10 to 34 mL per minute (0.17 to 0.57 mL per second): 0.6 mg every two or three days

< 10 mL per minute (0.17 mL per second): avoid

Avoid in patients with severe renal or hepatic impairment because it can lead to bone marrow suppression and neuromyopathy

Avoid intravenous use; best if used within the first 24 hours of the attack; the most common adverse effects are nausea, vomiting, and diarrhea; reduce the dosage in older patients

NOTE: NSAIDs or corticosteroids are first-line therapies, depending on comorbidities; colchicine is an effective second-line therapy.

NSAID = nonsteroidal anti-inflammatory drug.

Information from reference 21.

Nonsteroidal anti-inflammatory drugs22,23 or corticosteroids24 are first-line therapies for acute gout, depending on patient comorbidities. Although colchicine is an effective second-line therapy, in higher doses the risks of adverse effects outweigh the benefits.25 Occasionally, these therapies may need to be supplemented by short-acting opioids such as hydrocodone (Hycodan) and oxycodone (Roxicodone). All medications should be used cautiously in older persons, in whom the threshold of toxicity is lower.

Urate-lowering therapy for chronic gout

About 60 percent of persons who experience a gout attack will have another attack within 12 months.26 Therefore, nonpharmacologic treatment of hyperuricemia should begin with the first gout attack and should initially focus on modifiable risk factors such as diet (i.e., less red meat and seafood, more dairy) and alcohol intake. Substitution of diuretic therapy with other antihypertensives reduces hyperuricemia in many patients.13,14,17

Urate-lowering pharmacotherapy (Table 521,27) using a xanthine oxidase inhibitor or uricosuric agent is recommended for patients with more than two gouty attacks per year, in patients with tophi, and in patients with joint damage seen on a radiograph.20 However, this therapy should not commence until the acute phase of gout has completely resolved because fluctuations in serum uric acid levels will exacerbate the inflammatory process. When initiating urate-lowering therapy, concurrent prophylaxis with low-dose colchicine (0.6 to 1.2 mg daily) for three to six months has been shown to reduce the risk of flare-ups.28 The target serum uric acid level is less than 6 mg per dL (355 µmol per L),29 and doses of the urate-lowering therapy should be titrated upward until this target is reached.

Table 5. Pharmacologic Options for Urate-Lowering Therapy in Patients with Chronic Gout




Monthly cost (generic)*

Allopurinol (Zyloprim), 50 to 300 mg daily (maximal daily dosage: 800 mg)

Suggested initial daily renal dosing (based on creatinine clearance):

>= 90 mL per minute (1.50 mL per second): 300 mg

60 to 89 mL per minute (1.00 to 1.49 mL per second): 200 mg

30 to 59 mL per minute (0.50 to 0.98 mL per second): 100 mg

10 to 29 mL per minute (0.16 to
0.48 mL per second): 50 to 100 mg

< 10 mL per minute (0.16 mL per second): use very cautiously

May precipitate acute gout, hypersensitivity syndrome, or mild rash; avoid using with azathioprine (Imuran); interacts with warfarin (Coumadin)

Do not initiate until four to six weeks after an acute attack; concurrent prophylaxis with colchicine (0.6 mg once or twice daily for six months) may prevent flare-ups; titrate dose until the uric acid level is less than 6 mg per dL (355 µmol per L); continue therapy during acute flare-ups

Thirty 300-mg tablets: $34 (6 to 18)

Probenecid, initially 250 mg twice daily, gradually titrated to 500 mg to 2 g per day

May precipitate acute gout, nephrolithiasis, gastrointestinal upset, or rash; modifies renal handling of other drugs; use cautiously with heparin

Maintain hydration (about 2 L per day); avoid using with low-dose aspirin; ineffective if creatinine clearance is less than 50 mL per minute

Sixty 500-mg tablets: (59 to 131)

Febuxostat, 80 mg daily

Avoid in patients with hepatic impairment

Investigational medication not yet approved by the U.S. Food and Drug Administration


note: Urate-lowering therapy should not commence until the acute phase of gout has completely resolved because fluctuations in serum uric acid will exacerbate the inflammatory process.

*-Estimated cost to the pharmacist based on average wholesale prices (rounded to the nearest dollar) in Red Book. Montvale, N.J.: Medical Economics Data, 2007. Cost to the patient will be higher, depending on prescription filling fee.

-No brand available for probenecid.

Information from references 21 and 27.

Allopurinol is the first-line urate-lowering therapy. In patients with normal renal function, the initial dosage may be 300 mg daily, although many physicians advocate starting with a lower dosage (e.g., 50 to 100 mg) and then titrating upward by 50 to 100 mg every two to four weeks (maximal daily dosage: 800 mg) until the target serum uric acid level is reached.

In patients with renal insufficiency, the allopurinol dosage should be adjusted based on the estimated creatinine clearance. Approximately 2 to 5 percent of patients taking allopurinol have minor rashes and other adverse effects. Rarely, a severe hypersensitivity syndrome occurs with fever, toxic epidermal necrolysis, hepatitis, and eosinophilia; this syndrome has been shown to have a 20 percent mortality rate.27 Those intolerant of allopurinol may undergo desensitization30 or may take oxypurinol (the active metabolite of allopurinol), if available.

Uricosuric agents are second-line therapy for patients who are intolerant of allopurinol, or they may be used in combination with allopurinol in patients with refractory hyperuricemia. Probenecid is the uricosuric agent most often used in the United States. Uricosuric therapy is contraindicated in patients with a history of nephrolithiasis and is ineffective in those with a creatinine clearance of less than 50 mL per minute (0.83 mL per second). Losartan (Cozaar) and fenofibrate (Tricor) have uricosuric properties and may be useful adjunctive therapies for patients with gout, hypertension, and hyperlipidemia.31

Newer therapeutic options

Febuxostat (investigational drug not yet approved by the U.S. Food and Drug Administration) is a novel nonpurine, xanthine oxidase antagonist that was recently shown to be comparable with allopurinol in lowering uric acid levels.32 Compared with patients taking 300 mg of allopurinol daily, more patients taking 80 mg of febuxostat reached target uric acid levels. However, the allopurinol dosage could not be titrated, and the febuxostat group had a high dropout rate because of adverse effects. At 52 weeks, the groups had similar rates of gout flare-ups. Febuxostat is cleared primarily through the liver and may be useful in those with chronic renal insufficiency who have elevated uric acid levels despite renal dosing of allopurinol.

There has been growing interest in reducing total body urate load using a recombinant uricase enzyme (rasburicase [Elitek]) in patients with advanced tophaceous gout. This therapy has been available for the treatment of tumor lysis syndrome and has been used for refractory tophaceous gout.33 Long-term use is limited because of induction of antigenic responses. A pegylated uricase enzyme has been developed and is currently undergoing trials.34

The author thanks Eswar Krishnan, MD, for his assistance in the preparation of the manuscript.

The Author

Aaron T. Eggebeen, MD, is a senior rheumatology fellow at the University of Pittsburgh (Pa.) Arthritis Institute. He received his medical degree from Michigan State University College of Human Medicine, East Lansing, where he also completed an internal medicine/pediatrics residency.

Address correspondence to Aaron T. Eggebeen, MD, University of Pittsburgh Arthritis Institute, S700 Biomedical Science Tower, 3500 Terrace St., Pittsburgh, PA 15261. Reprints are not available from the author.

Author disclosure: Nothing to disclose.


1. Krishnan E, Griffith C, Kwoh C. Burden of illness from gout in ambulatory care in the United States. Abstracts of the American College of Rheumatology 69th annual meeting and the Association of Rheumatology Health Professionals 40th annual meeting. November 12-17, 2005, San Diego, Calif. Arthritis Rheum 2005;52 (9 suppl):S656.

2. Mikuls TR, Farrar JT, Bilker WB, Fernandes S, Saag KG. Suboptimal physician adherence to quality indicators for the management of gout and asymptomatic hyperuricaemia: results from the UK General Practice Research Database (GPRD). Rheumatology (Oxford) 2005;44:1038-42.

3. Kramer HM, Curhan G. The association between gout and nephrolithiasis: the National Health and Nutrition Examination Survey III, 1988-1994. Am J Kidney Dis 2002;40:37-42.

4. Wallace KL, Riedel AA, Joseph-Ridge N, Wortmann R. Increasing prevalence of gout and hyperuricemia over 10 years among older adults in a managed care population. J Rheumatol 2004;31:1582-7.

5. Vasan RS, Pencina MJ, Cobain M, Freiberg MS, D'Agostino RB. Estimated risks for developing obesity in the Framingham Heart Study. Ann Intern Med 2005;143:473-80.

6. Wu XW, Lee CC, Muzny DM, Caskey CT. Urate oxidase: primary structure and evolutionary implications. Proc Natl Acad Sci USA 1989;86:9412-6.

7. Johnson WD, Kayser KL, Brenowitz JB, Saedi SF. A randomized controlled trial of allopurinol in coronary bypass surgery. Am Heart J 1991;121(1 pt 1):20-4.

8. Sundstrom J, Sullivan L, D'Agostino RB, Levy D, Kannel WB, Vasan RS. Relations of serum uric acid to longitudinal blood pressure tracking and hypertension incidence. Hypertension 2005;45:28-33.

9. Feig DI, Nakagawa T, Karumanchi SA, Oliver WJ, Kang DH, Finch J, et al. Hypothesis: uric acid, nephron number, and the pathogenesis of essential hypertension. Kidney Int 2004;66:281-7.

10. Wheeler JG, Juzwishin KD, Eiriksdottir G, Gudnason V, Danesh J. Serum uric acid and coronary heart disease in 9,458 incident cases and 155,084 controls: prospective study and meta-analysis. PLoS Med 2005;2:e76.

11. Krishnan E, Baker JF, Furst DE, Schumacher HR. Gout and the risk of acute myocardial infarction. Arthritis Rheum 2006;54:2688-96.

12. Campion EW, Glynn RJ, DeLabry LO. Asymptomatic hyperuricemia. Risks and consequences in the Normative Aging Study. Am J Med 1987;82:421-6.

13. Choi HK, Atkinson K, Karlson EW, Curhan G. Obesity, weight change, hypertension, diuretic use, and risk of gout in men: the health professionals follow-up study. Arch Intern Med 2005;165:742-8.

14. Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G. Purine-rich foods, dairy and protein intake, and the risk of gout in men. N Engl J Med 2004;350:1093-103.

15. De Souza AW, Fernandes V, Ferrari AJ. Female gout: clinical and laboratory features. J Rheumatol 2005;32:2186-8.

16. Wallace SL, Robinson H, Masi AT, Decker JL, McCarty DJ, Yu TF. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum 1977;20:895-900.

17. Zhang W, Doherty M, Pascual E, Bardin T, Barskova V, Conaghan P, 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.

18. Rigby AS, Wood PH. Serum uric acid levels and gout: what does this herald for the population? Clin Exp Rheumatol 1994;12:395-400.

19. McCarty DJ. Gout without hyperuricemia. JAMA 1994;271:302-3.

20. Zhang W, Doherty M, Bardin T, Pascual E, Barskova V, Conaghan P, et al. EULAR evidence based recommendations for gout. Part II: management. Report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2006;65:1312-24.

21. Terkeltaub RA. Clinical practice. Gout. N Engl J Med 2003;349:1647-55.

22. Altman RD, Honig S, Levin JM, Lightfoot RW. Ketoprofen versus indomethacin in patients with acute gouty arthritis: a multicenter, double blind comparative study. J Rheumatol 1988;15:1422-6.

23. Shrestha M, Morgan DL, Moreden JM, Singh R, Nelson M, Hayes JE. Randomized double-blind comparison of the analgesic efficacy of intramuscular ketorolac and oral indomethacin in the treatment of acute gouty arthritis. Ann Emerg Med 1995;26:682-6.

24. Groff GD, Franck WA, Raddatz DA. Systemic steroid therapy for acute gout: a clinical trial and review of the literature. Semin Arthritis Rheum 1990;19:329-36.

25. Schlesinger N, Schumacher R, Catton M, Maxwell L. Colchicine for acute gout. Cochrane Database Syst Rev 2006;(4):CD006190.

26. Gutman AB. The past four decades of progress in the knowledge of gout, with an assessment of the present status. Arthritis Rheum 1973;16:431-45.

27. Hande KR, Noone RM, Stone WJ. Severe allopurinol toxicity. Description and guidelines for prevention in patients with renal insufficiency. Am J Med 1984;76:47-56.

28. Borstad GC, Bryant LR, Abel MP, Scroggie DA, Harris MD, Alloway JA. Colchicine for prophylaxis of acute flares when initiating allopurinol for chronic gouty arthritis. J Rheumatol 2004;31:2429-32.

29. Li-Yu J, Clayburne G, Sieck M, Beutler A, Rull M, Eisner E, et al. Treatment of chronic gout. Can we determine when urate stores are depleted enough to prevent attacks of gout? J Rheumatol 2001;28:577-80.

30. Fam AG, Dunne SM, Iazzetta J, Paton TW. Efficacy and safety of desensitization to allopurinol following cutaneous reactions. Arthritis Rheum 2001;44:231-8.

31. Schumacher HR Jr, Chen LX. Newer therapeutic approaches: gout. Rheum Dis Clin North Am 2006;32:235-44.

32. Becker MA, Schumacher HR Jr, Wortmann RL, MacDonald PA, Eustace D, Palo WA, et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med 2005;353:2450-61.

33. Vogt B. Urate oxidase (rasburicase) for treatment of severe tophaceous gout. Nephrol Dial Transplant 2005;20:431-3.

34. Ganson NJ, Kelly SJ, Scarlett E, Sundy JS, Hershfield MS. Control of hyperuricemia in subjects with refractory gout, and induction of antibody against poly(ethylene glycol) (PEG), in a phase I trial of subcutaneous PEGylated urate oxidase. Arthritis Res Ther 2006;8:R12.