What is the recommended acute and long‑term management for an adult presenting with an acute gout flare?

Management of Acute Gout Flare

For an acute gout flare, initiate treatment within 24 hours using NSAIDs, colchicine, or corticosteroids as first-line monotherapy, selecting the agent based on renal function, cardiovascular risk, and gastrointestinal comorbidities; for long-term management after recurrent flares, start urate-lowering therapy with allopurinol (beginning at ≤100 mg daily and titrating to achieve serum urate <6 mg/dL) while providing colchicine prophylaxis for at least 6 months. 1, 2, 3

Acute Flare Management

First-Line Treatment Selection Algorithm

Step 1: Assess timing and contraindications

• Treatment must be started within 24 hours of symptom onset for optimal efficacy; delays beyond this window markedly reduce effectiveness of all agents. 2, 3
• For colchicine specifically, do not initiate after 36 hours from symptom onset—efficacy drops sharply beyond this timeframe. 2, 3

Step 2: Select agent based on patient factors

Choose NSAIDs when:

• Patient has normal renal function (eGFR ≥60 mL/min), no cardiovascular disease, no heart failure, no cirrhosis, no active peptic ulcer disease, and not on anticoagulation. 1, 2
• Use full FDA-approved doses: naproxen 500 mg twice daily, indomethacin 50 mg three times daily, or sulindac 200 mg twice daily. 1, 3
• Continue at full dose throughout the entire attack until complete resolution—do not taper early. 1, 3

Choose corticosteroids when:

• Patient has severe renal impairment (eGFR <30 mL/min), cardiovascular disease, heart failure, cirrhosis, peptic ulcer disease, or is on anticoagulation. 1, 2
• Prednisone 0.5 mg/kg per day (approximately 30–35 mg daily) for 5–10 days at full dose then stop abruptly, OR give 2–5 days at full dose followed by 7–10 day taper. 1, 2
• For monoarticular or oligoarticular involvement of large accessible joints, intra-articular corticosteroid injection (triamcinolone acetonide 40 mg for knee, 20–30 mg for ankle) is highly effective. 2, 3
• Intramuscular triamcinolone acetonide 60 mg is appropriate when oral access is not feasible (NPO status, surgical conditions). 2

Choose colchicine when:

• Symptom onset is ≤36 hours, patient has normal-to-moderate renal function (CrCl ≥30 mL/min), and is NOT taking strong CYP3A4 or P-glycoprotein inhibitors (clarithromycin, cyclosporine, ketoconazole, ritonavir, verapamil). 2, 3
• Loading dose: 1.2 mg at first sign of flare, followed 1 hour later by 0.6 mg (total 1.8 mg). 2, 3
• After 12-hour pause, resume 0.6 mg once or twice daily until attack resolves. 2, 3
• This low-dose regimen achieves ≥50% pain reduction with number needed to treat of 3–5, equivalent efficacy to obsolete high-dose protocols but with significantly fewer gastrointestinal adverse effects (23% vs 77% diarrhea). 3

Combination Therapy for Severe Attacks

Initiate combination therapy when:

• Polyarticular involvement (≥4 joints) or multiple large joints are affected. 3
• Severe pain requiring rapid control with sustained anti-inflammatory coverage. 2

Acceptable combinations:

• Colchicine + NSAID 3
• Oral corticosteroid + colchicine 3
• Intra-articular steroid + any oral agent 2, 3

Avoid:

• NSAIDs + systemic corticosteroids due to synergistic gastrointestinal toxicity. 3

Critical Contraindications

Colchicine absolute contraindications:

• Severe renal impairment (CrCl <30 mL/min). 2, 3
• Concurrent use of strong CYP3A4 or P-glycoprotein inhibitors (clarithromycin, cyclosporine, ketoconazole, ritonavir, verapamil), especially with any degree of renal or hepatic impairment—this combination can cause fatal multiorgan toxicity. 2, 3

NSAID absolute contraindications:

• Severe renal impairment (eGFR <30 mL/min)—NSAIDs can precipitate or worsen acute kidney injury. 2
• Active or recent gastrointestinal bleeding. 3

Corticosteroid absolute contraindications:

• Systemic fungal infections. 1, 2

Long-Term Management After Recurrent Flares

Indications to Initiate Urate-Lowering Therapy

Strongly recommended after first flare when:

• Subcutaneous tophi are present. 3
• Radiographic joint damage attributable to gout. 3
• Chronic kidney disease stage ≥3. 3

Conditionally recommended after first flare when:

• Recurrent flares (≥2 per year). 1, 4, 5
• Urolithiasis. 4
• Patient preference for early intervention. 3
• Young age at disease onset. 3
• Serum urate >9 mg/dL. 3

Do NOT initiate urate-lowering therapy:

• During an acute gout flare if patient is not already on therapy—wait until flare completely resolves. 3
• If patient is already on urate-lowering therapy when flare occurs, continue it without interruption. 2, 3

Urate-Lowering Therapy Protocol

Allopurinol initiation and titration:

• Start at low dose: ≤100 mg daily (lower in CKD—consider 50 mg daily in severe renal impairment). 3, 5
• Titrate upward by 100 mg every 2–4 weeks until serum urate target <6 mg/dL is achieved. 3, 5
• In patients with CKD stage 3 or worse, consider HLA-B*58:01 screening before starting allopurinol due to markedly increased risk of fatal hypersensitivity reactions. 3

Mandatory prophylaxis during urate-lowering therapy initiation:

• Provide colchicine prophylaxis 0.6 mg once or twice daily for at least 6 months when starting or adjusting urate-lowering therapy. 1, 3, 6
• Continue prophylaxis for 3 months after achieving target serum urate if no tophi present, or 6 months after achieving target if tophi present. 3
• If colchicine contraindicated or not tolerated, use low-dose NSAID with proton pump inhibitor, or low-dose prednisone (<10 mg/day) as second-line prophylaxis. 1, 2, 6

Febuxostat alternative:

• Start at ≤40 mg daily and titrate to achieve serum urate <6 mg/dL. 3
• Febuxostat is associated with increased all-cause and cardiovascular mortality compared to allopurinol and is not routinely recommended as first-line therapy. 4
• Same colchicine prophylaxis protocol applies when initiating febuxostat. 3

Common Pitfalls to Avoid

• Do not delay acute treatment beyond 24 hours—efficacy of all agents decreases significantly. 2, 3
• Do not use colchicine after 36 hours from symptom onset—it becomes ineffective. 2, 3
• Do not reduce NSAID dose early during acute attack—maintain full dose until complete resolution. 1, 3
• Do not use high-dose prednisone (>10 mg/day) for prophylaxis—increases adverse effects without proportional benefit. 2, 3
• Do not start allopurinol at 300 mg daily—"go low, go slow" approach (starting at 100 mg and titrating) reduces flares and toxicity risk. 3
• Do not stop urate-lowering therapy during an acute flare if patient is already on it—continuation maintains serum urate control and does not worsen the attack. 2, 3
• Do not omit colchicine prophylaxis when starting urate-lowering therapy—omission markedly raises the risk of acute flares during the first 6 months. 3, 6