What is the recommended management for an adult with gout, including treatment of an acute flare, initiation and titration of urate‑lowering therapy, prophylaxis against flares, lifestyle modifications, monitoring, and options for refractory disease?

Comprehensive Gout Management

Acute Gout Flare Treatment

Initiate anti-inflammatory therapy within 12–24 hours of symptom onset; this timing is more critical to treatment success than which specific agent you choose. 1, 2

First-Line Agent Selection Algorithm

Choose based on patient contraindications:

• Oral corticosteroids (prednisone 30–35 mg daily for 5 days) when the patient has:

  • Severe renal impairment (eGFR < 30 mL/min) 1, 2
  • Heart failure or uncontrolled hypertension 1, 2
  • Active peptic ulcer disease or recent GI bleeding 1
  • Cirrhosis or hepatic impairment 1
  • Concurrent anticoagulation therapy 1

• Colchicine (1.2 mg immediately, then 0.6 mg one hour later) when:

  • Treatment can start within 12 hours of symptom onset 1, 2
  • Patient has NO severe renal impairment 1
  • Patient is NOT taking strong CYP3A4 or P-glycoprotein inhibitors (clarithromycin, erythromycin, cyclosporine, ketoconazole, ritonavir, verapamil) 1, 2
  • Do not start colchicine after 36 hours from symptom onset—efficacy drops dramatically 1, 2

• Full-dose NSAIDs (naproxen 500 mg BID or indomethacin 50 mg TID) when:

  • Patient has normal renal function 1
  • No cardiovascular disease or heart failure 1
  • No GI contraindications 1
  • Add a proton-pump inhibitor if any GI risk factors exist 1

Combination Therapy for Severe Attacks

For polyarticular gout (≥4 joints) or multiple large joints, initiate combination therapy: 1, 2

• Colchicine + NSAID 1
• Oral corticosteroid + colchicine 1
• Intra-articular steroid + any oral agent 1
• Never combine systemic NSAID with systemic corticosteroid—synergistic GI toxicity 1

Intra-Articular Injection

For monoarticular or oligoarticular gout involving 1–2 large, accessible joints, intra-articular corticosteroid injection is highly effective: 1, 2

• Triamcinolone acetonide 40 mg for the knee 1
• Triamcinolone acetonide 20–30 mg for the ankle 1

Critical Dosing Details

• Colchicine maintenance: After the initial 1.8 mg loading dose, wait 12 hours, then give 0.6 mg once or twice daily until the attack resolves 1
• NSAIDs: Continue full FDA-approved dose throughout the entire attack—do not taper early 3, 1
• Prednisone alternatives: 0.5 mg/kg/day for 5–10 days, or 2–5 days at full dose followed by 7–10 day taper 1

Absolute Contraindications

• Colchicine is absolutely contraindicated when:

  • CrCl < 30 mL/min (risk of fatal toxicity) 1
  • Concurrent strong CYP3A4/P-gp inhibitors in patients with ANY renal or hepatic impairment (risk of fatal toxicity) 1, 2

• NSAIDs are contraindicated when:

  • eGFR < 30 mL/min 1
  • Heart failure or significant cardiovascular disease 1
  • Active peptic ulcer disease or cirrhosis 1

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Urate-Lowering Therapy (ULT) Initiation

When to Start ULT

Strong indications (initiate after first flare): 1

• Subcutaneous tophi 1
• Radiographic joint damage from gout 1
• Chronic kidney disease stage ≥3 1

Conditional indications (consider after first flare): 3, 1

• ≥2 gout attacks per year 3
• Serum urate > 9 mg/dL 3, 1
• Age < 40 years at disease onset 1
• Urolithiasis 1
• Patient preference for early intervention 3, 1

Do NOT initiate ULT after a single or infrequent gout attack (< 2 per year) without high-risk features. 3

Timing of ULT Initiation

• Wait until the acute flare has completely resolved before starting ULT 1
• If the patient is already on ULT, continue it without interruption during an acute flare—stopping worsens the attack 1, 2

Allopurinol Initiation and Titration Protocol

Start low, go slow: 1

• Initial dose: 100 mg daily (or 50 mg daily if CrCl 30–50 mL/min) 1
• Titration: Increase by 100 mg every 2–4 weeks until serum urate < 6 mg/dL 1
• Typical maintenance dose: 300–600 mg daily; maximum 800 mg daily 1
• Do NOT start allopurinol at 300 mg daily—this increases risk of flares and hypersensitivity syndrome 1

Serum Urate Targets

• Standard target: < 6 mg/dL (360 µmol/L) for all gout patients, maintained lifelong 1
• Aggressive target: < 5 mg/dL (300 µmol/L) for severe gout with tophi, chronic arthropathy, or frequent attacks—until crystal dissolution 1
• Avoid maintaining serum urate < 3 mg/dL long-term 1

Alternative ULT Agents

• Febuxostat: Use when allopurinol at appropriate dose fails to achieve target or is intolerable 3, 1

  • Febuxostat 40 mg/day and allopurinol 300 mg/day are equally effective 3
  • Febuxostat is associated with increased cardiovascular and all-cause mortality—not routinely recommended 4

• Uricosuric agents (probenecid): For patients with normal renal function and no history of urolithiasis 1

• Pegloticase: Reserved for severe, debilitating chronic tophaceous gout when all other therapies at maximal doses fail 1

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Prophylaxis Against Flares During ULT Initiation

Mandatory prophylaxis when starting or adjusting ULT: 3, 1

First-Line Prophylaxis

• Colchicine 0.6 mg once or twice daily 3, 1
• Duration: At least 6 months 3, 1
  • Continue for 3 months after achieving target serum urate < 6 mg/dL if no tophi present 1
  • Continue for 6 months after achieving target if tophi are present 1
• Efficacy: Reduces flare incidence from 77% to 33% during allopurinol initiation 1

Second-Line Prophylaxis (if colchicine contraindicated)

• Low-dose NSAID with proton-pump inhibitor (e.g., naproxen 250 mg BID with omeprazole 20 mg daily) 1
• Low-dose prednisone < 10 mg/day 1, 2
• Never use prednisone > 10 mg/day for prophylaxis—increases adverse effects without benefit 1

Renal Dose Adjustments for Prophylactic Colchicine

• Mild-to-moderate renal impairment (CrCl 30–80 mL/min): 0.6 mg once daily 1
• Severe renal impairment (CrCl < 30 mL/min): 0.3 mg once daily with close monitoring, or avoid entirely 1

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Lifestyle Modifications

Dietary recommendations: 1, 5, 6

• Limit: Alcohol (especially beer and spirits), sugar-sweetened beverages, high-fructose corn syrup, organ meats, shellfish, and excessive red meat 1, 5
• Encourage: Low-fat or nonfat dairy products, coffee, cherries, vegetables 1, 5
• Weight loss program for overweight or obese patients 1, 2

Medication review: 1

• Replace loop or thiazide diuretics when possible 1
• Consider losartan for hypertension (increases urinary uric acid excretion) 5
• Use statins or fenofibrate for hyperlipidemia 1

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Monitoring

• Serum urate levels: Check every 2–4 weeks while titrating allopurinol to guide dose adjustments 1
• Continue monitoring until target < 6 mg/dL is achieved and maintained 1

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Refractory Disease Options

For patients with frequent flares despite optimal management and contraindications to all first-line agents: 1, 2

• Canakinumab 150 mg subcutaneously (IL-1 inhibitor) 1, 2
• Absolute contraindication: Active infection 1, 2
• Pegloticase for severe, debilitating chronic tophaceous gout when all other therapies fail 1

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Critical Pitfalls to Avoid

• Do not delay acute treatment beyond 12–24 hours—effectiveness declines sharply 1, 2
• Do not start colchicine after 36 hours from symptom onset 1, 2
• Do not taper NSAIDs early—maintain full dose throughout the attack 3, 1
• Do not initiate allopurinol at 300 mg daily—start at ≤100 mg 1
• Do not stop ULT during an acute flare if the patient is already on it 1, 2
• Do not omit colchicine prophylaxis when starting ULT—flare rates double without it 1
• Do not combine colchicine with strong CYP3A4/P-gp inhibitors in patients with any renal or hepatic impairment—risk of fatal toxicity 1, 2
• Do not use obsolete high-dose colchicine regimens (0.5 mg every 2 hours)—severe diarrhea without added benefit 1