What is the recommended management of an acute gout flare and the appropriate long‑term urate‑lowering therapy?

Management of Gout: Acute Flares and Long-Term Urate-Lowering Therapy

Acute Gout Flare Treatment

For an acute gout attack, initiate corticosteroids, NSAIDs, or low-dose colchicine within 24 hours of symptom onset, with corticosteroids preferred as first-line therapy when no contraindications exist due to superior safety profile and lower cost. 1, 2

First-Line Treatment Options

• Corticosteroids are the preferred initial choice: prednisolone 30-35 mg daily (approximately 0.5 mg/kg/day) for 5-10 days provides rapid symptom control with fewer adverse effects than NSAIDs 1, 2
• Oral prednisone can be given as a single 5-day course or followed by a 7-10 day taper 2
• Intramuscular triamcinolone acetonide 60 mg is effective for patients unable to take oral medications 2
• Intra-articular corticosteroid injection (knee 40 mg, ankle 20-30 mg) is highly effective for monoarticular or oligoarticular involvement of accessible large joints 2

Alternative Acute Treatments

• NSAIDs at full FDA-approved anti-inflammatory doses (e.g., naproxen, indomethacin) should be continued at that dose until complete resolution 2
• Indomethacin provides no superiority over other NSAIDs despite traditional preference 2
• Low-dose colchicine: 1.2 mg at first sign of flare followed by 0.6 mg one hour later (total 1.8 mg maximum) 2, 3
• This low-dose regimen is equally effective as higher doses with markedly fewer gastrointestinal adverse effects 2, 3

Critical Timing and Contraindications

• Treatment must be initiated within 24 hours of symptom onset; efficacy declines dramatically with delays 2
• Colchicine must be started within 36 hours; efficacy drops sharply beyond this window 2
• NSAID contraindications: severe renal impairment (eGFR <30 mL/min), heart failure, cirrhosis, active peptic ulcer disease, concurrent anticoagulation 2
• Colchicine contraindications: creatinine clearance <30 mL/min; concomitant strong CYP3A4 or P-glycoprotein inhibitors (clarithromycin, cyclosporine, ketoconazole, ritonavir, verapamil) due to risk of fatal toxicity 2, 3
• Corticosteroid contraindications: systemic fungal infections, uncontrolled diabetes mellitus 2

Severe or Polyarticular Attacks

• For polyarticular gout (≥4 joints) or severe attacks involving multiple large joints, combination therapy is recommended: colchicine + NSAID, oral corticosteroid + colchicine, or intra-articular steroid + any oral agent 2
• Never combine NSAIDs with systemic corticosteroids due to synergistic gastrointestinal toxicity 2
• Inadequate response (<20% pain improvement within 24 hours or <50% improvement at ≥24 hours) requires switching to alternative monotherapy or adding a second agent 2

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Long-Term Urate-Lowering Therapy (ULT)

Do not initiate ULT after a first gout attack or in patients with infrequent attacks (<2 per year); strongly recommend ULT for patients with recurrent gout (≥2 episodes per year), subcutaneous tophi, gouty arthropathy, radiographic changes, or history of urolithiasis. 1, 4, 2

Indications for ULT Initiation

• Recurrent acute attacks (≥2 episodes per year) 4, 2
• Presence of subcutaneous tophi 4, 2
• Chronic gouty arthropathy or radiographic changes of gout 4, 2
• History of uric acid nephrolithiasis 4, 2

Allopurinol Dosing Strategy

• Start allopurinol at 100 mg daily (50-100 mg in chronic kidney disease) 2, 5
• Titrate upward by 100 mg every 2-4 weeks to achieve target serum urate <6 mg/dL 2, 5
• Maximum recommended dose is 800 mg daily 5
• Never start at 300 mg daily—this increases risk of gout flares and hypersensitivity reactions 2

Renal Dosing Adjustments for Allopurinol

• Creatinine clearance 10-20 mL/min: maximum 200 mg daily 2, 5
• Creatinine clearance <10 mL/min: maximum 100 mg daily 2, 5
• Creatinine clearance <3 mL/min: extend dosing interval 2, 5

Alternative ULT Agent

• Febuxostat 40 mg daily is equally effective as allopurinol 300 mg daily for lowering serum urate 1, 2
• Use febuxostat in allopurinol-intolerant patients 2
• Febuxostat is associated with higher costs than allopurinol 1

Target Serum Urate Levels

• Target serum urate <6 mg/dL (360 μmol/L) for all patients 4, 2
• Consider stricter target <5 mg/dL in presence of tophi or severe disease 2
• Monitor serum urate every 2-4 weeks during titration, then every 6 months once at target 2

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Mandatory Flare Prophylaxis During ULT Initiation

All patients initiating or titrating ULT must receive prophylactic anti-inflammatory therapy for at least 6 months to prevent acute flares; this is non-negotiable. 4, 2, 6

Prophylaxis Regimens

• First-line: Low-dose colchicine 0.6 mg once or twice daily 4, 2, 3
• Alternative: Low-dose NSAID (naproxen 250 mg twice daily with proton-pump inhibitor if indicated) 2
• Second-line (if colchicine/NSAIDs contraindicated): Low-dose prednisone <10 mg/day 2

Duration of Prophylaxis

• Continue for at least 6 months when starting ULT 4, 2
• Extend to 3 months after target urate is reached without tophi, or 6 months if tophi are present 2
• High-quality evidence demonstrates prophylaxis extending beyond 8 weeks is more effective than shorter courses 1, 2

Colchicine Dose Adjustments with Drug Interactions

• With strong CYP3A4 inhibitors (atazanavir, clarithromycin, ketoconazole, ritonavir): reduce prophylaxis dose from 0.6 mg twice daily to 0.3 mg once daily 3
• Absolute contraindication to combine colchicine with strong CYP3A4/P-gp inhibitors in patients with renal or hepatic impairment 2, 3

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Management of ULT During Acute Gout Attack

Continue established ULT without interruption during an acute gout attack; stopping ULT causes serum urate fluctuations that may prolong or worsen the attack. 4, 6

• Patients already on allopurinol or febuxostat should continue the medication during acute flares 4, 2
• ULT can be started during an acute attack only if simultaneous anti-inflammatory treatment and prophylaxis are provided 6
• In practice, it is safer to wait until complete resolution of the acute attack before initiating ULT 4

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Critical Pitfalls to Avoid

• Delaying acute treatment beyond 24 hours markedly diminishes efficacy of all therapeutic options 2
• Initiating allopurinol at 300 mg daily increases risk of gout flares and hypersensitivity reactions 2
• Omitting prophylactic anti-inflammatory therapy when starting ULT dramatically raises risk of acute flares during first 6 months 2
• High-dose colchicine regimens (>1.8 mg within first hour) provide no additional benefit and substantially increase gastrointestinal toxicity 2
• Interrupting established ULT during acute attack worsens outcomes 4
• Fatal colchicine toxicity has been reported with concurrent strong CYP3A4/P-gp inhibitors (clarithromycin, verapamil, cyclosporine, ketoconazole, ritonavir)—this combination is absolutely contraindicated, especially in renal or hepatic impairment 2, 3