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Diagnosis, Treatment, and Prevention

of Gout
BARRY L. HAINER, MD; ERIC MATHESON, MD; and R. TRAVIS WILKES, MD, Medical University of South Carolina,
Charleston, South Carolina

Gout is characterized by painful joint inflammation, most commonly in the first metatarsophalangeal joint, resulting
from precipitation of monosodium urate crystals in a joint space. Gout is typically diagnosed using clinical criteria from
the American College of Rheumatology. Diagnosis may be confirmed by identification of monosodium urate crystals
in synovial fluid of the affected joint. Acute gout may be treated with nonsteroidal anti-inflammatory drugs, cortico-
steroids, or colchicine. To reduce the likelihood of recurrent flares, patients should limit their consumption of certain
purine-rich foods (e.g., organ meats, shellfish) and avoid alcoholic drinks (especially beer) and beverages sweetened
with high-fructose corn syrup. Consumption of vegetables and low-fat
or nonfat dairy products should be encouraged. The use of loop and
thiazide diuretics can increase uric acid levels, whereas the use of the
angiotensin receptor blocker losartan increases urinary excretion of
uric acid. Reduction of uric acid levels is key to avoiding gout flares.
Allopurinol and febuxostat are first-line medications for the preven-
tion of recurrent gout, and colchicine and/or probenecid are reserved
for patients who cannot tolerate first-line agents or in whom first-line
agents are ineffective. Patients receiving urate-lowering medications

ILLUSTRATION BY JONATHAN DIMES
should be treated concurrently with nonsteroidal anti-inflammatory
drugs, colchicine, or low-dose corticosteroids to prevent flares. Treat-
ment should continue for at least three months after uric acid levels
fall below the target goal in those without tophi, and for six months
in those with a history of tophi. (Am Fam Physician. 2014;90(12):831-
836. Copyright © 2014 American Academy of Family Physicians.)

G
CME This clinical content out is the most common inflam- increase urinary excretion of uric acid, pre-
conforms to AAFP criteria matory arthropathy, affecting menopausal women have a substantially
for continuing medical
education (CME). See more than 8 million Americans.1 lower prevalence of gout compared with men
CME Quiz Questions on Gout accounts for approximately (2.0% vs. 5.9%).6 Black persons have a higher
page 830. 7 million ambulatory visits in the United risk.7 Consuming alcoholic drinks (particu-
Author disclosure: No rel- States annually at a cost of nearly $1 bil- larly beer), meat (especially red meat, wild
evant financial affiliations. lion.2 Risk factors include genetics, age, sex, game, and organ meat), some seafood (e.g.,
Patient information: and diet.2,3 These factors may contribute to a shellfish, some large saltwater fish), fruit

A handout on this topic is high serum uric acid level, which is currently juice, and beverages sweetened with high-
available at http://family​ defined as a value of at least 6.8 mg per dL fructose corn syrup increases the risk of
doctor.org/family​doctor/
(405 µmol per L).4,5 gout.8,9 Purine-rich foods such as nuts, oat-
en/diseases-conditions/
gout.html. meal, asparagus, legumes, and mushrooms
Pathophysiology and Risk Factors do not seem to increase the risk.10 Consump-
Genetic mutations may be associated with tion of dairy products appears to confer
overproduction—or more often underex- slight protection from gout10 (Table 111,12).
cretion—of uric acid because of defects in Gout results from the precipitation
the renal urate transporter system.6 The of monosodium urate crystals in a joint
prevalence of gout increases with age and space. Crystal deposition then triggers
peaks at more than 12% in persons older immune activation with the release of sev-
than 80 years.1 Because female sex hormones eral inflammatory cytokines and neutrophil

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2. or calcium pyrophosphate deposition Figure 1. 832  American Family Physician www.37 to 3. with additional information from reference 12.38. Epidemiology of gout. Alcohol intake ≥ 50 g per day vs. and trauma.70) wrists.net/rheum/gout_calc. 1. leading to chronic pain and disability microscopy.51 (1.g. none 2.41 (1.negative birefringence on compensated polarized light versibly damaged. fingers (Figure 2). 2014 .37 (2. none 1. none 1. and elbows. with bright. none 2. protein. Arthritis tions.42. the joint space can be irre. Doherty M. Inc.95) geal joint.96 to 2. Ultrasonography.31. infection. Figure 2.85 (1. 0. Pseudogout.41 (0.14 (1.72) Body mass index ≥ 30 kg per m2 at 21 years 2. the diagnosis is established by aspira- Res Ther. Risk Factors for Gout Relative risk (95% Risk factor Notes confidence interval) Other common sites include the midtar- Diuretic use* — 3.55 (0. primarily in equivocal cases. and five findings per day from the history and physical examination to Coffee ≥ 6 cups per day vs.60 (1.. magnetic resonance with grossly deformed joints.16) Gout is typically diagnosed clinically based beverage on the rapid development of monoarticular consumption arthritis marked by swelling and redness Fructose intake Highest vs. uric acid level. consumption gp-training.aafp.31 (1. matrix of lipids. preferably intracellular. Inc.17 Microscopy of joint fluid is used less often. Number 12 ◆ December 15. Copyright © Logical Images.77 to 3. none 1.53 (1. Vitamin C intake ≥ 1.72) disease states.05 (0.55) be deposited throughout the body (e.500 mg vs. none 0. metatarsophalangeal joint is most commonly affected.e. lowest quintile 1. subcutaneous imaging.19. knees. and computed tomography are typically not nodules comprised of monosodium urate crystals in a necessary for diagnosis.16 An online Dairy product Highest vs. mimicking other Wine ≥ 2 drinks per day vs. The American College of Rheu- consumption matology criteria are the most widely used Meat consumption Highest vs.86) for diagnosis of gout (Table 2).50) usually involving the first metatarsophalan- Seafood Highest vs.88) consumption predict the likelihood of an acute gout flare. recruitment. lowest quintile 0. Tender red papules on digit..81 (1.12) sal joints. 2010. soft tissues). 1. lowest quintile 1.73 to 3.51 (1.80) it uses sex.16) tebrae.13 Over time. lowest quintile 1. ver- Spirits ≥ 2 drinks per day vs. Urate crystals may also Beer ≥ 2 drinks per day vs. < 250 mg 0.07.org/afp Volume 90. and mucopolysaccharides) The differential diagnosis for acute monoarticular joint may also form at the joint space14 (Figure 1).17.19 to 2.08 to 3.12(6):223. *—Adjusted for age. Tophi (i. 0.64 to 1.75 to 4. tion of a joint or tophus and identification of needle-shaped monosodium urate crys- tals. In these situa- Adapted with permission from Roddy E.htm).Gout Table 1. ankles.56 (0.15 Hypertension — 2. Copyright © Logical Images. 0.74) risk calculator is also available (http://www. skin.32) Clinical Presentation of age Sweetened ≥ 2 drinks per day vs. Hard nodules on distal digit. The first swelling includes pseudogout.

org/afp American Family Physician 833 . No analgesic properties. Robinson H. Information from reference 21. arthrocentesis is required to distinguish this con- (NSAIDs). December 15. then 20 mg for four days. prednisone.20(3):896. gastrointestinal adverse effects (Colcrys) then 0.23 Rebound flares are common of the acute arthritis of primary gout. When gout is limited to a single joint. Yü TF. Indometha- Attack of monoarticular arthritis cin (Indocin) has historically been the preferred choice. treatment of acute gout should commence within chemical means or polarized light microscopy 24 hours of symptom onset20 (Table 321). Arthritis Rheum. or radiologic findings: chicine are equally effective in treating acute flares of Asymmetric swelling within a joint on radiography gout.18 Trauma-associated can differentiate pseudogout from gout. then 0. 1977.22 Subcortical cyst without erosions on radiography Patients with diabetes mellitus can be given corticoste- Suspected tophus roids for short-term use with appropriate monitoring for Unilateral attack involving first metatarsophalangeal joint hyperglycemia. how- ever. intramuscular. taper to avoid rebound flares 10 mg for four days) NSAIDs = nonsteroidal anti-inflammatory drugs.19 Imaging may Table 2. after discontinuation of corticosteroid therapy for acute gout. preventive Table 3.21 Any oral NSAID may be given at Hyperuricemia the maximal dosage and continued for one to two days Joint redness after relief of symptoms. then corticosteroids. Septic arthritis joint swelling is typically identified by the history.6 mg one hour later. American College of Rheumatology be necessary to rule out fracture in a patient with gout-like Diagnostic Criteria for Gout symptoms after a joint injury. Intramuscular ketorolac appears to have Development of maximal inflammation within one day similar effectiveness. and col- Presence of six or more of the following clinical. 50 mg three times First-line therapy. Number 12 www. adverse per day effects include gastric bleeding and kidney injury Colchicine 1. McCarty DJ. Findings of calcium pyrophosphate crystals dition from acute gout. Preferred therapy for patients in whom NSAIDs and variable dosing (e. Medications for Treatment of Acute Gout Medication Example regimen Notes NSAIDs Indomethacin (Indocin). can mimic gout in clinical appearance and may present without a fever or elevated white blood cell may respond to nonsteroidal anti-inflammatory drugs count.2 mg per day are common. Oral cortico- or steroids. NSAIDs. Unilateral attack involving tarsal joint intra-articular corticosteroid injections may be prefer- able to systemic corticosteroids because of their lower Adapted with permission from Wallace SL. Gout disease. or intra-articular routes. Masi AT.. Culture of joint fluid negative for microorganisms during however. contraindicated in patients receiving clarithromycin (Biaxin) Corticosteroids Oral. trauma may result in an acute gout flare caused by increased concentrations of synovial urate. More than one attack of acute arthritis Corticosteroids are an appropriate alternative for Pain or redness in the first metatarsophalangeal joint patients who cannot tolerate NSAIDs or colchicine. Gout and septic arthritis can and normal serum uric acid levels on joint fluid analysis occur concomitantly. To reduce the risk of a rebound flare. all NSAIDs are equally effective. when discontinuing oral four days.2 mg initially. there is no evidence it is more effective than any attack of joint inflammation other NSAID. Preliminary criteria for the classification adverse effect profile. intravenous corticosteroids. but this is rare.20 NSAIDs are the first-line treatment.g. Presence of characteristic urate crystals in the joint fluid Treatment or To achieve rapid and complete resolution of symp- Presence of a tophus proven to contain urate crystals by toms. 2014 ◆ Volume 90. avoid use in patients with renal and hepatic insufficiency.aafp. Decker JL. 40 mg for colchicine are contraindicated. laboratory.6 to 1.

when branded colchicine (Colcrys) was approved.21. may increase risk of rhabdomyolysis when used with statins or clarithromycin (Biaxin) Pegloticase (Krystexxa) 8 mg intravenously every two weeks Indicated for refractory gout. colchicine does not Weight gain is a significant risk factor for gout in men.20 Normal serum with hypertension and gout because these agents can urate levels do not exclude the diagnosis of gout.28 Although avoidance of loop and 5 to 6 mg per dL (297 to 357 µmol per L). pork.. may increase up to 80 mg Contraindicated in patients receiving azathioprine per day if serum uric acid level > 6 mg per dL (Imuran) and mercaptopurine (357 µmol per L) after two weeks Information from references 21 and 28.21. Number 12 ◆ December 15.20 Purine- Prevention rich vegetables do not increase the risk of gout.6 to 1. continued for three to six months after a flare if there are Generic colchicine. but higher dosages may be hypersensitivity skin reaction (those of Han needed Chinese or Thai descent. multiple drug interactions Xanthine oxidase inhibitors: Allopurinol (Zyloprim) 100 mg per day initially.22 rich animal protein (e. a systematic review found only Table 4. common effective dosage treatment in patients at risk of severe is 300 mg per day.12 Intake of high- treating acute flares when given beyond 72 to 96 hours fructose corn syrup should be restricted25.20 Pharmacologic options for prevention of chronic gout are Serum urate should be lowered to a target of less than outlined in Table 4. Therapy should continue indefi- did not undergo formal review by the U. one or Drug Administration (FDA) for this indication until more tophi on examination). except in patients with Genetic testing recommended before initiating renal dysfunction.23 Colchicine should a byproduct of adenosine triphosphate catabolism.22 Urate-lowering therapy should be Colchicine is another treatment option for acute gout.20. 834  American Family Physician www. titrate up to High risk of nephrolithiasis. should be monitored periodically to assess preventive steroids over 10 to 14 days is recommended after resolu. lamb.000 per dose28 ) Probenecid 250 mg two times per day initially. Colcrys is expensive. expensive (more than $5. and diarrhea. or Koreans with chronic kidney disease stage 3 or greater) Febuxostat (Uloric) 40 mg once per day.org/afp Volume 90. regardless of kidney function. They increase uric acid levels.9 Con- Serum urate–lowering therapy should be initiated to sumption of vegetables9 and low-fat or nonfat dairy prevent recurrences in persons with a history of gout and products9 should be encouraged.g. encourage hydration 2 g per day and urine alkalization with potassium citrate. Medications for Prevention of Chronic Gout Medication Dosage Notes Colchicine (Colcrys) 0. Common adverse effects include fructose contributes to increased uric acid production as nausea.2 mg per day May cause reversible axonal neuromyopathy. 2014 .8. and generic colchicine is no longer available. therapy in patients with recurrent gout and a history of tion of symptoms.26 because the after symptom onset. shellfish) and avoid alcohol (especially beer).g. vomiting. beef.aafp.Gout treatment and initiation of a tapered course of cortico. organ meats. no ongoing symptoms. which has been used for decades. elevated urate levels. or a history of nephrolithiasis.27 be used with caution in patients with hepatic or renal Patients with gout should limit their intake of purine- impairment. any one of the following: at least two flares per year (one PHARMACOLOGIC OPTIONS per year in persons with chronic kidney disease stage 2 or greater). depending thiazide diuretics has been recommended for patients on the crystal and tophaceous burden.. DIETARY MODIFICATIONS However. In addition.20 2009. tophi.S. have analgesic properties and may be less effective in whereas weight loss reduces the risk. Food and nitely if there are ongoing signs or symptoms (e.

or for six months in those with a history should be advised to stop taking colchicine and tell their of tophi. Febuxostat (Uloric) is a xanthine oxi- losartan (Cozaar) are associated with a decreased risk dase inhibitor that was approved by the FDA in 2009.34 channel blockers and the angiotensin receptor blocker Febuxostat. probenecid increases blood lev- of preventing chronic disease progression. go to http://www. B 35.29 Calcium Koreans with chronic kidney disease stage 3 or greater. applesauce. 26 sweetened soft drinks. Probenecid. low initial doses are recommended with Nephrolithiasis is a common adverse effect that may be slow titration to achieve target uric acid levels. but recent evidence suggests considered a first-line agent to prevent recurrent gout. is a first-line agent to prevent recurrent gout. Probenecid increases urinary excre- tor.28 December 15. Febuxostat (Uloric) and allopurinol (Zyloprim) are equally effective in preventing recurrent gout.9. A = consistent.31 Patients receiving a urate-lowering medi.9 that allopurinol (Zyloprim) can be started during an but it is considerably more expensive than allopurinol.aafp. B = inconsistent or limited-quality patient-oriented evidence. therefore.aafp.33 Dosages avoided by high fluid intake and urine alkalization with higher than 300 mg may be used—even in those with potassium citrate.32 The start.20 disease.6 to 1. For information about the SORT evidence rating system..37 Allopurinol. of 0. or in than $5. the medication should especially in older adults or those with chronic kidney be continued while the flare is treated acutely. Colchicine prevents gout flares at a dosage colchicine. It is usually administered by a rheuma- before initiating treatment in patients of Han Chinese tologist and is given every two weeks at a cost of more or Thai descent. close monitoring is recommended. Gout SORT: KEY RECOMMENDATIONS FOR PRACTICE Evidence Clinical recommendation rating References Oral corticosteroids and nonsteroidal anti-inflammatory drugs are equally effective in the treatment B 20 of acute gout.30 Losartan is the only angiotensin Although febuxostat is superior to 300 mg allopurinol at receptor blocker with this property. despite a lack of pain or clinical of rhabdomyolysis is increased when colchicine is used signs of inflammation. which may result in ing dosage is 100 mg per day.20 NSAIDs and corticosteroids should not be physician if they experience leg weakness or pain.2 mg per day. 2014 ◆ Volume 90. C = consensus. and increasing consumption of dairy products help reduce the frequency of gouty symptoms. ment should be discontinued if any signs or symptoms tion because uric acid crystals continue to accumulate of nerve or muscle damage are present.24. patients with chronic kidney disease and when used with colchicine. Screening for human It is a third-line agent and is indicated for treatment of leukocyte antigen-B*5801 genotype is recommended refractory gout. or low-dose corticosteroid to prevent a flare. Treat- used for long periods without a urate-lowering medica. Probenecid may be used in combination common maintenance dosage. expert opinion. Dosing is guided by the with allopurinol or febuxostat when one drug does not target serum uric acid level.22 In patients with chronic independently lower serum uric acid to target levels. a xanthine oxidase inhibi. Pegloticase (Krystexxa) is an intravenous tored for adverse effects.35. The rare risk and damage the joint. receiving a urate-lowering agent. Pegloticase. disease-oriented evidence. allopurinol has the added benefit particular concern. 12. and 300 mg per day is a severe toxicity. Allopurinol. cytochrome P450 3A4 or P-glycoprotein inhibitors. Patients without tophi. and fructose-rich vegetables and fruits (e.g.36 Febuxostat is to worsen acute gout flares. lowering serum uric acid levels.9 In tion of uric acid and is typically used as a second-line patients with gout and chronic kidney disease or con. els of methotrexate and ketorolac. Consumption of low-fat or nonfat dairy products may help reduce the frequency of flares. acute flare if it is used in conjunction with an NSAID and Colchicine. usual practice. good-quality patient-oriented evidence. agave). Of gestive heart failure. treatment because of numerous drug interactions. The Treatment should continue for at least three months long-term adverse effects of colchicine include revers- after uric acid levels fall below the target goal in those ible axonal neuromyopathy (less than 1%).9 renal impairment—as long as patients are closely moni. The mechanism a higher risk of a severe hypersensitivity skin reaction of action involves metabolism of uric acid to allantoin. kidney disease. Number 12 www. The dose should be adjusted in cation should be treated concurrently with an NSAID.31. patients should reduce their consumption of high-fructose corn syrup– C 8. 36 To prevent recurrent gout. urate-lowering medication was thought at reducing the frequency of gout flares. it is not more effective Historically. Reducing consumption of meat and seafood. of incident gout. or case series.org/afp American Family Physician 835 .000 per dose.9 Certain ethnic groups have uricase approved by the FDA in 2010. small increases in the risk of gouty flares.org/afpsort. regardless of kidney function. fruit juices.22 If a patient has a gout flare while concomitantly with statins or clarithromycin (Biaxin). when starting allopurinol therapy.

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