Patient information: A handout on this topic is available at https://familydoctor.org/familydoctor/en/diseases-conditions/gout.html .

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, corticosteroids, 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 prevention 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 should be treated concurrently with nonsteroidal anti-inflammatory drugs, colchicine, or low-dose corticosteroids to prevent flares. Treatment 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.

Gout is the most common inflammatory arthropathy, affecting more than 8 million Americans.1 Gout accounts for approximately 7 million ambulatory visits in the United States annually at a cost of nearly $1 billion.2 Risk factors include genetics, age, sex, and diet.2,3 These factors may contribute to a high serum uric acid level, which is currently defined as a value of at least 6.8 mg per dL (405 μmol per L).4,5

Enlarge Print SORT: KEY RECOMMENDATIONS FOR PRACTICE Clinical recommendation Evidence rating References Oral corticosteroids and nonsteroidal anti-inflammatory drugs are equally effective in the treatment of acute gout. B 20 Febuxostat (Uloric) and allopurinol (Zyloprim) are equally effective in preventing recurrent gout. B 35, 36 To prevent recurrent gout, patients should reduce their consumption of high-fructose corn syrup–sweetened soft drinks, fruit juices, and fructose-rich vegetables and fruits (e.g., applesauce, agave). Reducing consumption of meat and seafood, and increasing consumption of dairy products help reduce the frequency of gouty symptoms. Consumption of low-fat or nonfat dairy products may help reduce the frequency of flares. C 8, 12, 26 SORT: KEY RECOMMENDATIONS FOR PRACTICE Clinical recommendation Evidence rating References Oral corticosteroids and nonsteroidal anti-inflammatory drugs are equally effective in the treatment of acute gout. B 20 Febuxostat (Uloric) and allopurinol (Zyloprim) are equally effective in preventing recurrent gout. B 35, 36 To prevent recurrent gout, patients should reduce their consumption of high-fructose corn syrup–sweetened soft drinks, fruit juices, and fructose-rich vegetables and fruits (e.g., applesauce, agave). Reducing consumption of meat and seafood, and increasing consumption of dairy products help reduce the frequency of gouty symptoms. Consumption of low-fat or nonfat dairy products may help reduce the frequency of flares. C 8, 12, 26

Pathophysiology and Risk Factors Jump to section + Abstract

Pathophysiology and Risk Factors

Clinical Presentation

Treatment

Prevention

References Genetic mutations may be associated with overproduction—or more often underexcretion—of uric acid because of defects in the renal urate transporter system.6 The prevalence of gout increases with age and peaks at more than 12% in persons older than 80 years.1 Because female sex hormones increase urinary excretion of uric acid, pre-menopausal women have a substantially lower prevalence of gout compared with men (2.0% vs. 5.9%).6 Black persons have a higher risk.7 Consuming alcoholic drinks (particularly beer), meat (especially red meat, wild game, and organ meat), some seafood (e.g., shellfish, some large saltwater fish), fruit juice, and beverages sweetened with high-fructose corn syrup increases the risk of gout.8,9 Purine-rich foods such as nuts, oatmeal, asparagus, legumes, and mushrooms do not seem to increase the risk.10 Consumption of dairy products appears to confer slight protection from gout10 (Table 111,12). Enlarge Print Table 1. Risk Factors for Gout Risk factor Notes Relative risk (95% confidence interval) Diuretic use* — 3.37 (2.75 to 4.12) Alcohol intake ≥ 50 g per day vs. none 2.53 (1.73 to 3.70) Beer ≥ 2 drinks per day vs. none 2.51 (1.77 to 3.55) Spirits ≥ 2 drinks per day vs. none 1.60 (1.19 to 2.16) Wine ≥ 2 drinks per day vs. none 1.05 (0.64 to 1.72) Hypertension — 2.31 (1.96 to 2.72) Body mass index ≥ 30 kg per m2 at 21 years of age 2.14 (1.37 to 3.32) Sweetened beverage consumption ≥ 2 drinks per day vs. none 1.85 (1.08 to 3.16) Fructose intake Highest vs. lowest quintile 1.81 (1.31, 2.50) Seafood consumption Highest vs. lowest quintile 1.51 (1.17, 1.95) Meat consumption Highest vs. lowest quintile 1.41 (1.07, 1.86) Dairy product consumption Highest vs. lowest quintile 0.56 (0.42, 0.74) Vitamin C intake ≥ 1,500 mg vs. < 250 mg per day 0.55 (0.38, 0.80) Coffee consumption ≥ 6 cups per day vs. none 0.41 (0.19, 0.88) Table 1. Risk Factors for Gout Risk factor Notes Relative risk (95% confidence interval) Diuretic use* — 3.37 (2.75 to 4.12) Alcohol intake ≥ 50 g per day vs. none 2.53 (1.73 to 3.70) Beer ≥ 2 drinks per day vs. none 2.51 (1.77 to 3.55) Spirits ≥ 2 drinks per day vs. none 1.60 (1.19 to 2.16) Wine ≥ 2 drinks per day vs. none 1.05 (0.64 to 1.72) Hypertension — 2.31 (1.96 to 2.72) Body mass index ≥ 30 kg per m2 at 21 years of age 2.14 (1.37 to 3.32) Sweetened beverage consumption ≥ 2 drinks per day vs. none 1.85 (1.08 to 3.16) Fructose intake Highest vs. lowest quintile 1.81 (1.31, 2.50) Seafood consumption Highest vs. lowest quintile 1.51 (1.17, 1.95) Meat consumption Highest vs. lowest quintile 1.41 (1.07, 1.86) Dairy product consumption Highest vs. lowest quintile 0.56 (0.42, 0.74) Vitamin C intake ≥ 1,500 mg vs. < 250 mg per day 0.55 (0.38, 0.80) Coffee consumption ≥ 6 cups per day vs. none 0.41 (0.19, 0.88) Gout results from the precipitation of monosodium urate crystals in a joint space. Crystal deposition then triggers immune activation with the release of several inflammatory cytokines and neutrophil recruitment.13 Over time, the joint space can be irreversibly damaged, leading to chronic pain and disability with grossly deformed joints. Tophi (i.e., subcutaneous nodules comprised of monosodium urate crystals in a matrix of lipids, protein, and mucopolysaccharides) may also form at the joint space14(Figure 1). The first metatarsophalangeal joint is most commonly affected. Other common sites include the midtarsal joints, ankles, knees, fingers (Figure 2), wrists, and elbows. Urate crystals may also be deposited throughout the body (e.g., vertebrae, skin, soft tissues), mimicking other disease states.15 Enlarge Print Figure 1. Hard nodules on distal digit. Copyright © Logical Images, Inc. Figure 1. Hard nodules on distal digit. Copyright © Logical Images, Inc. Enlarge Print Figure 2. Tender red papules on digit. Copyright © Logical Images, Inc. Figure 2. Tender red papules on digit. Copyright © Logical Images, Inc.

Clinical Presentation Jump to section + Abstract

Pathophysiology and Risk Factors

Clinical Presentation

Treatment

Prevention

References Gout is typically diagnosed clinically based on the rapid development of monoarticular arthritis marked by swelling and redness usually involving the first metatarsophalangeal joint. The American College of Rheumatology criteria are the most widely used for diagnosis of gout (Table 2).16 An online risk calculator is also available (http://www.gp-training.net/rheum/gout_calc.htm); it uses sex, uric acid level, and five findings from the history and physical examination to predict the likelihood of an acute gout flare.17 Enlarge Print Table 2. American College of Rheumatology Diagnostic Criteria for Gout Presence of characteristic urate crystals in the joint fluid or Presence of a tophus proven to contain urate crystals by chemical means or polarized light microscopy or Presence of six or more of the following clinical, laboratory, or radiologic findings: Asymmetric swelling within a joint on radiography Attack of monoarticular arthritis Culture of joint fluid negative for microorganisms during attack of joint inflammation Development of maximal inflammation within one day Hyperuricemia Joint redness More than one attack of acute arthritis Pain or redness in the first metatarsophalangeal joint Subcortical cyst without erosions on radiography Suspected tophus Unilateral attack involving first metatarsophalangeal joint Unilateral attack involving tarsal joint Table 2. American College of Rheumatology Diagnostic Criteria for Gout Presence of characteristic urate crystals in the joint fluid or Presence of a tophus proven to contain urate crystals by chemical means or polarized light microscopy or Presence of six or more of the following clinical, laboratory, or radiologic findings: Asymmetric swelling within a joint on radiography Attack of monoarticular arthritis Culture of joint fluid negative for microorganisms during attack of joint inflammation Development of maximal inflammation within one day Hyperuricemia Joint redness More than one attack of acute arthritis Pain or redness in the first metatarsophalangeal joint Subcortical cyst without erosions on radiography Suspected tophus Unilateral attack involving first metatarsophalangeal joint Unilateral attack involving tarsal joint Microscopy of joint fluid is used less often, primarily in equivocal cases. In these situations, the diagnosis is established by aspiration of a joint or tophus and identification of needle-shaped monosodium urate crystals, preferably intracellular, with bright, negative birefringence on compensated polarized light microscopy. Ultrasonography, magnetic resonance imaging, and computed tomography are typically not necessary for diagnosis. The differential diagnosis for acute monoarticular joint swelling includes pseudogout, infection, and trauma. Pseudogout, or calcium pyrophosphate deposition disease, can mimic gout in clinical appearance and may respond to nonsteroidal anti-inflammatory drugs (NSAIDs). Findings of calcium pyrophosphate crystals and normal serum uric acid levels on joint fluid analysis can differentiate pseudogout from gout. Septic arthritis may present without a fever or elevated white blood cell count; arthrocentesis is required to distinguish this condition from acute gout. Gout and septic arthritis can occur concomitantly, but this is rare.18 Trauma-associated joint swelling is typically identified by the history; however, trauma may result in an acute gout flare caused by increased concentrations of synovial urate.19 Imaging may be necessary to rule out fracture in a patient with gout-like symptoms after a joint injury.

Treatment Jump to section + Abstract

Pathophysiology and Risk Factors

Clinical Presentation

Treatment

Prevention

References To achieve rapid and complete resolution of symptoms, treatment of acute gout should commence within 24 hours of symptom onset20 (Table 321). Oral corticosteroids, intravenous corticosteroids, NSAIDs, and colchicine are equally effective in treating acute flares of gout.20 NSAIDs are the first-line treatment. Indomethacin (Indocin) has historically been the preferred choice; however, there is no evidence it is more effective than any other NSAID. Intramuscular ketorolac appears to have similar effectiveness.21 Any oral NSAID may be given at the maximal dosage and continued for one to two days after relief of symptoms. Enlarge Print Table 3. Medications for Treatment of Acute Gout Medication Example regimen Notes NSAIDs Indomethacin (Indocin), 50 mg three times per day First-line therapy; all NSAIDs are equally effective; adverse effects include gastric bleeding and kidney injury Colchicine (Colcrys) 1.2 mg initially, then 0.6 mg one hour later, then 0.6 to 1.2 mg per day No analgesic properties; gastrointestinal adverse effects are common; avoid use in patients with renal and hepatic insufficiency; contraindicated in patients receiving clarithromycin (Biaxin) Corticosteroids Oral, intramuscular, or intra-articular routes, variable dosing (e.g., prednisone, 40 mg for four days, then 20 mg for four days, then 10 mg for four days) Preferred therapy for patients in whom NSAIDs and colchicine are contraindicated; when discontinuing oral corticosteroids, taper to avoid rebound flares Table 3. Medications for Treatment of Acute Gout Medication Example regimen Notes NSAIDs Indomethacin (Indocin), 50 mg three times per day First-line therapy; all NSAIDs are equally effective; adverse effects include gastric bleeding and kidney injury Colchicine (Colcrys) 1.2 mg initially, then 0.6 mg one hour later, then 0.6 to 1.2 mg per day No analgesic properties; gastrointestinal adverse effects are common; avoid use in patients with renal and hepatic insufficiency; contraindicated in patients receiving clarithromycin (Biaxin) Corticosteroids Oral, intramuscular, or intra-articular routes, variable dosing (e.g., prednisone, 40 mg for four days, then 20 mg for four days, then 10 mg for four days) Preferred therapy for patients in whom NSAIDs and colchicine are contraindicated; when discontinuing oral corticosteroids, taper to avoid rebound flares Corticosteroids are an appropriate alternative for patients who cannot tolerate NSAIDs or colchicine.22 Patients with diabetes mellitus can be given corticosteroids for short-term use with appropriate monitoring for hyperglycemia. When gout is limited to a single joint, intra-articular corticosteroid injections may be preferable to systemic corticosteroids because of their lower adverse effect profile.23 Rebound flares are common after discontinuation of corticosteroid therapy for acute gout. To reduce the risk of a rebound flare, preventive treatment and initiation of a tapered course of corticosteroids over 10 to 14 days is recommended after resolution of symptoms. Colchicine is another treatment option for acute gout. Generic colchicine, which has been used for decades, did not undergo formal review by the U.S. Food and Drug Administration (FDA) for this indication until 2009, when branded colchicine (Colcrys) was approved. However, Colcrys is expensive, and generic colchicine is no longer available. In addition, colchicine does not have analgesic properties and may be less effective in treating acute flares when given beyond 72 to 96 hours after symptom onset. Common adverse effects include nausea, vomiting, and diarrhea.21,23 Colchicine should be used with caution in patients with hepatic or renal impairment.22