What is the recommended management of an acute gout flare and subsequent long‑term urate‑lowering therapy in an adult, including options if NSAIDs are contraindicated?

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

For an acute gout flare, initiate treatment within 24 hours using NSAIDs, colchicine, or oral corticosteroids as equally effective first-line options; when NSAIDs are contraindicated, use oral prednisone 30–35 mg daily for 5 days or intra-articular corticosteroid injection for monoarticular involvement. 1, 2, 3

Acute Gout Flare Management

First-Line Treatment Selection Algorithm

Step 1: Assess renal function and contraindications

• If eGFR < 30 mL/min (severe renal impairment): Use oral prednisone 30–35 mg daily for 5 days—colchicine and NSAIDs are both contraindicated due to fatal toxicity risk and acute kidney injury risk, respectively. 1, 2, 3
• If eGFR 30–59 mL/min (moderate renal impairment): Prefer corticosteroids; NSAIDs carry high risk of acute kidney injury, and colchicine requires dose reduction (0.6 mg once daily maximum). 2, 3
• If normal renal function: All three first-line options (NSAIDs, colchicine, corticosteroids) are appropriate. 1, 3

Step 2: Check for drug interactions

• If patient is taking strong CYP3A4 or P-glycoprotein inhibitors (clarithromycin, erythromycin, cyclosporine, ketoconazole, ritonavir, verapamil): Colchicine is absolutely contraindicated—use NSAIDs or corticosteroids instead. 1, 2, 3

Step 3: Evaluate cardiovascular and gastrointestinal risk

• If heart failure, established cardiovascular disease, active peptic ulcer disease, cirrhosis, or anticoagulation therapy: Avoid NSAIDs and use oral prednisone 30–35 mg daily for 5 days. 2, 3, 4
• If active systemic fungal infection: Corticosteroids are absolutely contraindicated—use NSAIDs or colchicine. 1, 2

Step 4: Consider timing and joint involvement

• If symptom onset ≤ 36 hours: Colchicine is most effective when started within 12 hours; give 1.2 mg orally followed 1 hour later by 0.6 mg (total 1.8 mg), then 0.6 mg once or twice daily after a 12-hour pause until attack resolves. 1, 2, 3
• If symptom onset > 36 hours: Do not use colchicine—efficacy drops sharply; choose NSAIDs or corticosteroids. 1, 3
• If 1–2 large, accessible joints involved: Intra-articular corticosteroid injection (triamcinolone 40 mg for knee, 20–30 mg for ankle) provides targeted therapy with minimal systemic effects. 1, 2, 3

Specific Dosing Regimens

NSAIDs (when not contraindicated):

• Use full FDA-approved anti-inflammatory doses throughout the entire attack without early tapering: naproxen 500 mg twice daily, indomethacin 50 mg three times daily, or sulindac 200 mg twice daily. 1, 3
• No single NSAID demonstrates superior efficacy; selection should be based on availability and individual tolerance. 1, 3

Colchicine (when appropriate):

• Acute loading: 1.2 mg orally at first sign of flare, followed 1 hour later by 0.6 mg (total 1.8 mg over one hour). 1, 2, 3
• Maintenance: After 12-hour pause, give 0.6 mg once or twice daily until attack resolves. 1, 3
• This low-dose regimen achieves ≥50% pain reduction with a number-needed-to-treat of 3–5 and causes diarrhea in only 23% of patients versus 77% with obsolete high-dose regimens. 2, 3

Oral Corticosteroids:

• Fixed-dose regimen (simplest): Prednisone 30–35 mg once daily for 5 days without taper. 1, 2, 4
• Weight-based regimen: Prednisone 0.5 mg/kg per day for 5–10 days at full dose then stop, or 2–5 days at full dose followed by 7–10 day taper for severe attacks. 1, 2
• Level A evidence demonstrates oral corticosteroids are equally effective as NSAIDs but cause fewer adverse events (27% vs 63%). 1, 2

Parenteral options (when oral route unavailable):

• Intramuscular triamcinolone acetonide 60 mg single injection is preferred over IL-1 inhibitors or ACTH for NPO patients. 1, 2
• Intravenous methylprednisolone 0.5–2.0 mg/kg can be repeated as clinically indicated. 2

Combination Therapy for Severe Attacks

Indications for combination therapy:

• Polyarticular gout (≥4 joints involved) or multiple large joints affected. 1, 3
• Inadequate response to monotherapy defined as <20% pain improvement within 24 hours or <50% improvement at ≥24 hours. 1, 2

Recommended combinations:

• Colchicine + NSAID (provides synergistic anti-inflammatory effects targeting different pathways). 1, 3
• Oral corticosteroid + colchicine. 1, 3
• Intra-articular steroid + any oral modality. 1, 3

Critical pitfall: Never combine systemic NSAIDs with systemic corticosteroids due to synergistic gastrointestinal toxicity. 1, 3

Management of Ongoing Urate-Lowering Therapy

• Do not discontinue allopurinol or febuxostat during an acute flare if the patient is already on urate-lowering therapy—continue the medication and treat the flare separately. 1, 3, 4
• Ongoing urate-lowering therapy does not prolong flare duration when appropriate anti-inflammatory coverage is provided. 3, 4

Long-Term Urate-Lowering Therapy

Indications to Initiate Urate-Lowering Therapy

Strong indications (initiate after first flare):

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

Conditional indications (consider after first flare):

• ≥2 gout attacks per year. 3
• Serum urate >9 mg/dL. 3
• Age <40 years at disease onset. 3
• Patient preference for early intervention. 3
• Urolithiasis. 3

Allopurinol Initiation and Titration Protocol

Critical principle: "Start low, go slow"

• Initial dose: 100 mg daily (or 50 mg daily if creatinine clearance 30–50 mL/min). 2, 3
• Titration: Increase by 100 mg every 2–4 weeks until serum urate <6 mg/dL is achieved. 2, 3
• Typical maintenance dose: 300–600 mg daily; maximum 800 mg daily may be needed in severe hyperuricemia. 2, 3
• Starting allopurinol at 300 mg daily significantly increases the risk of acute flares and allopurinol hypersensitivity syndrome—always start low. 2, 3

Timing: Do not initiate allopurinol during an acute flare; wait until the attack has completely resolved. 2, 3

Serum Urate Targets

• Standard target: <6 mg/dL (360 µmol/L) for all gout patients, maintained lifelong. 3
• Aggressive target: <5 mg/dL (300 µmol/L) for severe gout with tophi, chronic arthropathy, or frequent attacks until crystal dissolution occurs. 3
• Avoid maintaining serum urate <3 mg/dL long-term. 3

Mandatory Prophylaxis During Urate-Lowering Therapy Initiation

First-line prophylaxis:

• Colchicine 0.6 mg once or twice daily started concurrently with the first dose of allopurinol and continued for at least 6 months. 2, 3
• High-quality evidence shows colchicine prophylaxis reduces the proportion of patients experiencing flares from 77% to 33% during allopurinol initiation. 3
• Continue for 3 months after achieving target serum urate <6 mg/dL if no tophi present, or 6 months after reaching target if tophi are present. 3

Second-line prophylaxis (if colchicine contraindicated):

• Low-dose NSAID with proton-pump inhibitor (e.g., naproxen 250 mg twice daily with omeprazole 20 mg daily). 2, 3
• Low-dose prednisone <10 mg/day. 2, 3, 4
• Maintain second-line prophylaxis for ≥6 months during allopurinol initiation. 2, 3

Critical pitfall: Do not use high-dose prednisone (>10 mg/day) for prophylaxis—this increases adverse effects without additional benefit. 2, 3

Alternative Urate-Lowering Agents

• Febuxostat: Indicated when allopurinol at appropriate dose fails to achieve target urate or when allopurinol is intolerable; start 40 mg daily and titrate to 80 mg (or 120 mg if needed). 3
• Uricosuric agents (probenecid, benzbromarone): Appropriate for patients with normal renal function and no history of urolithiasis; relatively contraindicated in those with renal calculi. 3
• Pegloticase: Reserved for crystal-proven, severe, debilitating chronic tophaceous gout when all other therapies at maximal doses fail to reach serum urate target. 3, 5

Common Pitfalls to Avoid

• Do not delay acute treatment beyond 24 hours—effectiveness of all agents declines sharply after this window. 1, 2, 3
• Do not start colchicine after 36 hours from symptom onset—efficacy drops dramatically. 1, 3
• Do not taper NSAIDs early—maintain full dose throughout the attack until complete resolution. 1, 3
• Do not combine colchicine with strong CYP3A4/P-glycoprotein inhibitors in patients with any renal or hepatic impairment due to fatal toxicity risk. 1, 2, 3
• Do not use obsolete high-dose colchicine regimens (0.5 mg every 2 hours)—they cause severe diarrhea without added benefit. 2, 3
• Do not stop urate-lowering therapy during an acute flare if the patient is already on it. 1, 3
• Do not omit colchicine prophylaxis when starting urate-lowering therapy—flare rates roughly double without it. 3