What is the recommended management plan for a typical adult with gout, including treatment of an acute flare and long‑term urate‑lowering therapy?

Management of Gout

For acute gout flares, initiate treatment within 24 hours using NSAIDs, low-dose colchicine (1.2 mg followed by 0.6 mg one hour later), or corticosteroids; for long-term management in patients with ≥2 attacks per year, start allopurinol 100 mg daily with mandatory colchicine prophylaxis 0.5–0.6 mg daily for at least 6 months, titrating allopurinol every 2–5 weeks to achieve serum urate <6 mg/dL. 1, 2

Acute Gout Flare Management

Timing and Drug Selection

• Start anti-inflammatory therapy within 24 hours of symptom onset—delaying beyond this window significantly reduces treatment effectiveness. 2, 3
• Choose among three equally effective first-line options based on contraindications and cost: NSAIDs, low-dose colchicine, or corticosteroids. 1
• NSAIDs should be dosed at full anti-inflammatory strength (e.g., naproxen 500 mg twice daily or indomethacin 50 mg three times daily) and continued until complete flare resolution. 2, 3

Low-Dose Colchicine Regimen

• Administer 1.2 mg orally immediately, followed by 0.6 mg one hour later (total 1.8 mg over one hour). 1, 2, 4
• This low-dose regimen provides pain relief equivalent to higher doses while causing markedly fewer gastrointestinal adverse effects. 1, 2
• Do not use high-dose colchicine (hourly dosing)—it offers no additional benefit and substantially increases toxicity. 2, 3

Corticosteroid Options

• Oral prednisone 30–40 mg daily for 5–10 days, or 2–5 days followed by a 7–10 day taper. 1, 2
• Intramuscular triamcinolone acetonide 60 mg as a single dose. 2, 3
• Intra-articular corticosteroid injection for monoarticular attacks, with dosing based on joint size. 1, 2

Management of Existing Urate-Lowering Therapy

• Never discontinue ongoing allopurinol or febuxostat during an acute flare—continuation prevents symptom prolongation and preserves long-term urate control. 2, 3
• Do not initiate urate-lowering therapy during a first gout attack or any acute flare; defer until after complete flare resolution. 1, 3

Severe Polyarticular Attacks

• For pain >6/10 involving multiple large joints, combine two anti-inflammatory agents from different classes (e.g., corticosteroid + colchicine or corticosteroid + NSAID). 3

Indications for Long-Term Urate-Lowering Therapy

Start ULT in Patients With Any of the Following:

• ≥2 gout attacks per year. 1, 2
• Presence of subcutaneous tophi (clinical or radiographic). 1, 2, 3
• Radiographic joint damage from gout. 2, 5
• Chronic kidney disease stage ≥3. 1, 2, 5
• Serum urate >9 mg/dL. 2, 5
• History of uric acid kidney stones. 1, 2, 5

Do Not Start ULT:

• After a single gout attack in the absence of high-risk features. 1, 2
• In patients with <2 attacks per year without tophi, CKD, or other high-risk features. 1, 2

Allopurinol: First-Line Urate-Lowering Agent

Starting Dose

• 100 mg daily for patients with normal renal function. 1, 2, 6
• 50 mg daily for chronic kidney disease stage ≥4 (creatinine clearance <30 mL/min). 3, 5, 6

Titration Protocol

• Increase by 100 mg every 2–5 weeks based on serum urate monitoring. 2, 5, 6
• Target serum urate <6 mg/dL (360 µmol/L) for all patients. 1, 2, 3
• Maximum dose 800 mg daily. 2, 5, 6
• For creatinine clearance 10–20 mL/min, maximum dose 200 mg daily; for creatinine clearance <10 mL/min, maximum dose 100 mg daily. 6

Treat-to-Target Strategy

• Titrate allopurinol based on serial serum urate measurements rather than using fixed doses—this approach is strongly superior for achieving and maintaining target urate levels. 2
• Check serum urate every 2–5 weeks during dose titration. 5
• Once stable at target, check serum urate every 6 months. 5

Mandatory Anti-Inflammatory Prophylaxis During ULT Initiation

Critical Principle

• All patients starting urate-lowering therapy must receive concomitant anti-inflammatory prophylaxis—failure to provide prophylaxis dramatically increases flare risk and leads to treatment abandonment. 1, 2, 3
• ULT does not reduce gout attacks during the first 6 months and may initially increase flare frequency due to mobilization of urate from tissue deposits. 2

First-Line Prophylaxis Options

• Colchicine 0.5–0.6 mg once or twice daily (preferred). 1, 2, 5, 4
• NSAID (e.g., naproxen 250 mg twice daily) if colchicine contraindicated. 1, 2
• Low-dose corticosteroid (e.g., prednisone 5–10 mg daily) if both colchicine and NSAIDs contraindicated. 1, 3

Duration of Prophylaxis

• Minimum 3 months after ULT initiation—stopping before 3 months markedly increases flare risk. 2
• Optimal duration 3–6 months or until serum urate target achieved and patient remains flare-free. 1, 2, 5
• Prophylaxis extending beyond 8 weeks is significantly more effective; flares approximately double when prophylaxis is stopped after only 8 weeks. 2, 7
• Extend prophylaxis beyond 6 months if flares persist or serum urate target not yet reached. 2

Dose Adjustment for Renal Impairment

• Reduce colchicine dose to 0.3 mg once daily for prophylaxis in patients with creatinine clearance <50 mL/min. 1
• Avoid NSAIDs in severe renal impairment (creatinine clearance <30 mL/min). 1

Alternative Urate-Lowering Agents

Febuxostat

• Febuxostat 40 mg daily lowers serum urate as effectively as allopurinol 300 mg daily. 1, 2
• Reserve for patients with allopurinol hypersensitivity or inadequate response to allopurinol 800 mg daily. 2, 5
• Common adverse effects include abdominal pain, diarrhea, and musculoskeletal pain. 1, 2
• Caution: Febuxostat carries an increased risk of cardiovascular death and heart failure hospitalization compared to allopurinol—avoid in patients with established cardiovascular disease or heart failure. 8

Probenecid

• Uricosuric agent appropriate for patients with eGFR >50 mL/min and no history of kidney stones. 5
• Alternative for allopurinol-intolerant patients with normal renal function. 5

Pegloticase

• Reserved for severe refractory tophaceous gout unresponsive to oral agents. 5
• Not appropriate for first-line or routine use. 2

Lifestyle Modifications

• Weight reduction if obese or overweight. 1, 5
• Limit alcohol consumption, especially beer and spirits. 1, 5
• Avoid sugar-sweetened beverages and high-fructose corn syrup. 1, 5
• Reduce intake of organ meats and shellfish. 1, 5
• Encourage low-fat dairy products and vegetables. 1, 5
• Regular exercise. 1

Special Populations

Chronic Kidney Disease

• Allopurinol can be safely dose-escalated in CKD patients with appropriate dose adjustments based on creatinine clearance. 2, 6
• Start at 50 mg daily for CKD stage 4–5, titrate cautiously. 3, 5, 6
• Worse renal function modestly reduces urate-lowering efficacy; larger body size and concomitant diuretic use may necessitate higher allopurinol doses. 2

Hepatic Impairment

• Corticosteroids (oral, intravenous, or intra-articular) are the preferred first-line agents for acute gout when hepatic impairment is present—they are not dependent on hepatic metabolism and have minimal hepatotoxicity risk. 3
• Avoid NSAIDs due to risk of hepatotoxicity and acute liver injury. 3
• Colchicine is metabolized by the liver and its toxicity is markedly increased in hepatic dysfunction—use with extreme caution or avoid. 3

Cardiovascular Disease and Heart Failure

• Colchicine is considered safe and potentially reduces the risk of myocardial infarction in patients with CVD. 8
• Short durations of low-dose glucocorticoids are efficacious and may be safe. 8
• Avoid NSAIDs in patients with CVD or heart failure—they increase cardiovascular risk. 8
• Allopurinol is first-line ULT given its safety and potential for reducing cardiovascular outcomes. 8
• Avoid febuxostat in patients with CVD or heart failure due to increased risk of cardiovascular death and heart failure hospitalization. 8

Common Pitfalls to Avoid

• Never initiate ULT without concurrent anti-inflammatory prophylaxis—this virtually guarantees flares and treatment abandonment. 2, 3
• Never discontinue prophylaxis before 3 months—premature cessation leads to preventable flares. 2
• Never use a fixed-dose ULT regimen without monitoring and titration—a treat-to-target approach is superior. 2
• Never delay acute flare treatment beyond 24 hours—this significantly compromises effectiveness. 2
• Never stop allopurinol during an acute flare—continuation prevents prolongation of symptoms. 2, 3
• Never use high-dose colchicine for acute attacks—low-dose is equally effective with fewer adverse events. 2, 3
• Never discontinue ULT after symptoms resolve—lifelong therapy is required to prevent recurrence. 3, 5

Monitoring Strategy

• Check serum urate every 2–5 weeks while adjusting allopurinol dose. 5
• Once stable at target <6 mg/dL, check serum urate every 6 months. 5
• Continue urate-lowering therapy during acute flares. 5
• Consider switching agents if two consecutive serum urate levels remain >6 mg/dL despite maximum-dose allopurinol. 5

Comorbidity Screening

• Screen and manage hypertension, obesity, type 2 diabetes, chronic kidney disease, hyperlipidemia, and cardiovascular disease—these conditions both contribute to hyperuricemia and are worsened by it. 5