How should I manage an adult with an acute gout flare, including acute treatment and when to initiate urate‑lowering therapy?

Management of Acute Gout Flare and Urate-Lowering Therapy

For an acute gout flare, initiate treatment within 24 hours using NSAIDs, corticosteroids, or low-dose colchicine as first-line monotherapy, selecting based on patient comorbidities; do not initiate urate-lowering therapy after a first attack or infrequent attacks (<2 per year), but strongly consider it for recurrent gout (≥2 attacks/year) with mandatory prophylaxis during initiation. 1

Acute Gout Flare Treatment

Timing and General Approach

• Initiate pharmacologic therapy within 24 hours of symptom onset for optimal outcomes 1, 2
• Continue any established urate-lowering therapy without interruption during an acute attack 1, 2
• Treatment choice depends on number of joints involved, renal function, cardiovascular comorbidities, and gastrointestinal risk 1

First-Line Medication Options

NSAIDs:

• Use full anti-inflammatory doses when started promptly 3
• No evidence that indomethacin is superior to other NSAIDs like naproxen or ibuprofen 1
• Contraindicated in patients with renal disease, heart failure, cirrhosis, or peptic ulcer disease 1, 3
• Associated risks include dyspepsia and gastrointestinal bleeding 1

Corticosteroids:

• Oral prednisone 30-35 mg/day for 3-5 days or 0.5 mg/kg/day for 5-10 days 3
• Intra-articular injection is effective for monoarticular attacks in accessible joints 1
• Avoid in patients with diabetes, active infection, or high infection risk 3
• Particularly useful when NSAIDs and colchicine are contraindicated 1

Low-Dose Colchicine:

• Recommended dose: 1.2 mg (two tablets) at first sign of flare, followed by 0.6 mg one hour later 1, 4
• Maximum dose for acute treatment is 1.8 mg over one hour 4
• Most effective when started within 12 hours of symptom onset, but can be used up to 36 hours 1, 3
• Low-dose regimen (1.2 mg followed by 0.6 mg) is as effective as high-dose regimens with fewer gastrointestinal adverse effects 1, 2
• Contraindicated in patients with renal or hepatic impairment using potent CYP3A4 or P-glycoprotein inhibitors 1
• Dose adjustment required for renal impairment and drug interactions 3, 4

Severe or Polyarticular Attacks

• Consider combination therapy for severe attacks involving multiple joints 1, 3
• Intra-articular corticosteroid injection can be added for accessible joints 3

When to Initiate Urate-Lowering Therapy (ULT)

Do NOT Initiate ULT:

• After a first gout attack 1
• In patients with infrequent attacks (<2 per year) 1
• Some patients have no or few attacks over many years and do not require long-term therapy 1

DO Initiate ULT in:

• Recurrent gout attacks (≥2 episodes per year) 1
• Presence of tophi 1, 3
• Chronic gouty arthropathy or radiographic changes of gout 1
• Chronic kidney disease stage 2 or worse 1, 5
• History of urolithiasis 1

Shared Decision-Making

• Discuss benefits, harms, costs, and individual preferences before initiating ULT 1
• Patients with higher serum urate levels (>8 mg/dL or >476 µmol/L) are at greater risk for recurrent attacks 1
• Patients who initially decline ULT can revisit the decision if multiple recurrences occur 1

Urate-Lowering Therapy Initiation and Management

First-Line Agent: Allopurinol

• Start at 100 mg daily (50 mg daily in CKD stage 4 or worse) 2, 3, 6
• Increase by 100 mg every 2-5 weeks until target serum uric acid is achieved 2, 6
• Maximum recommended dose is 800 mg daily 6
• Target serum uric acid: <6 mg/dL (360 µmol/L or 6 mg/dL) 1, 3
• For patients with tophi, target <5 mg/dL for faster crystal dissolution 5
• Dose adjustment required in renal impairment: 200 mg/day with creatinine clearance 10-20 mL/min; ≤100 mg/day with creatinine clearance <10 mL/min 6

Alternative Agent: Febuxostat

• Febuxostat 40 mg/day and allopurinol 300 mg/day are equally effective at lowering serum urate 1
• Associated with abdominal pain, diarrhea, and musculoskeletal pain 1
• Not routinely recommended due to increased all-cause and cardiovascular mortality 7

Mandatory Prophylaxis During ULT Initiation

Why Prophylaxis is Essential

• ULT mobilizes urate from tissue deposits, increasing flare risk in the first 6 months 1
• Prophylaxis reduces acute gout attacks when initiating ULT 1

First-Line Prophylaxis Options

Low-Dose Colchicine:

• 0.6 mg once or twice daily 2, 3, 4
• Adjust dose for renal function and drug interactions 3, 4
• With CYP3A4 inhibitors, reduce to 0.3 mg once daily 4

Low-Dose NSAIDs:

• Naproxen 250 mg twice daily 8
• Add proton pump inhibitor if gastrointestinal risk factors present 3

Low-Dose Corticosteroids:

• Prednisone ≤10 mg/day for patients with contraindications to both colchicine and NSAIDs 3

Duration of Prophylaxis

• Continue for at least 6 months 1, 2, 4
• Continue for at least 3 months after achieving target serum urate in patients without tophi 3
• Continue for 6 months after achieving target serum urate AND resolution of tophi in patients with tophi 3
• Continuing prophylaxis >8 weeks is more effective than shorter durations 1

Lifestyle Modifications

• Limit purine-rich foods (organ meats, shellfish) 9, 7
• Avoid alcohol, especially beer and spirits 3, 9
• Avoid beverages sweetened with high-fructose corn syrup 9, 7
• Encourage weight loss in obese patients 2, 3, 5
• Encourage consumption of vegetables and low-fat/nonfat dairy products 9
• Maintain fluid intake sufficient for daily urinary output of at least 2 liters 6

Common Pitfalls to Avoid

• Never start or stop ULT during an acute flare—continue established therapy 1, 10
• Do not use colchicine doses higher than 1.8 mg for acute treatment—no additional benefit with increased toxicity 1, 4
• Do not initiate ULT without concurrent prophylaxis—this significantly increases flare risk 1, 2
• Do not use indomethacin preferentially—it offers no advantage over other NSAIDs 1
• Avoid NSAIDs in renal disease, heart failure, or cirrhosis 1, 3