What are the guidelines for the treatment of gout?

Treatment of Gout

Acute Gout Attack Management

For acute gout attacks, initiate treatment within 24 hours with NSAIDs, low-dose colchicine, or corticosteroids as first-line monotherapy options, selecting based on comorbidities and contraindications. 1, 2, 3

First-Line Treatment Options for Mild-Moderate Attacks (1-2 joints):

• NSAIDs at full anti-inflammatory doses (e.g., naproxen, indomethacin) are appropriate first-line therapy when started promptly 1, 2, 3

  • Avoid in patients with chronic kidney disease (CKD), congestive heart failure, peptic ulcer disease, or cirrhosis 1, 2
  • Continue at full dose until complete resolution of the attack 1

• Low-dose oral colchicine: 1.2 mg followed by 0.6 mg one hour later (total 1.8 mg) 2, 3

  • Most effective when started within 12 hours of symptom onset, but can be used up to 36 hours 1, 2
  • Adjust dose for renal impairment: reduce by 50% when creatinine clearance <50 mL/min 1, 4
  • For severe renal impairment (CrCl <30 mL/min), use single 0.6 mg dose and do not repeat for 2 weeks 4
  • Low-dose regimen has equal efficacy to high-dose with significantly fewer gastrointestinal side effects 3, 5

• Oral corticosteroids: Prednisone 30-35 mg/day for 3-5 days or 0.5 mg/kg/day for 5-10 days 2, 3

  • Avoid in patients with diabetes, active infection, or high infection risk 1

• Intra-articular corticosteroid injection for 1-2 accessible affected joints (dose depends on joint size) 1, 2, 3

Treatment for Severe/Polyarticular Attacks:

• Combination therapy is appropriate for polyarticular involvement (≥4 joints or >1 anatomic region) 1, 2
• Consider intravenous or intramuscular methylprednisolone 0.5-2.0 mg/kg for severe attacks 1
• Subcutaneous ACTH 25-40 IU is an alternative for NPO patients 1

Critical Management Principles:

• Continue established urate-lowering therapy without interruption during acute attacks 2, 3, 5
• Topical ice application is recommended as adjunctive therapy 1, 5
• Do not use complementary oral agents (cherry juice, ginger, etc.) as they lack evidence 1

Long-Term Urate-Lowering Therapy (ULT)

Initiate ULT in patients with recurrent attacks (≥2 per year), tophi, chronic gouty arthropathy, radiographic changes of gout, or history of nephrolithiasis. 2, 3, 5

First-Line ULT:

• Allopurinol is the first-line xanthine oxidase inhibitor 2, 3, 5

  • Start at ≤100 mg/day (50 mg/day if CKD stage 4 or worse) 2
  • Titrate upward every 2-5 weeks to reach target serum urate 3
  • Consider HLA-B*5801 testing before initiation in high-risk populations (Korean with CKD, Han Chinese, Thai) 3

• Febuxostat is an alternative xanthine oxidase inhibitor 2, 5

• Target serum urate level: <6 mg/dL (357 μmol/L) for all patients 2, 3, 5

  • Target <5 mg/dL for patients with tophi 5

Alternative ULT:

• Uricosuric agents (probenecid) are appropriate when xanthine oxidase inhibitors cannot be used, particularly in underexcretors with normal renal function and no history of urolithiasis 3, 6

Anti-Inflammatory Prophylaxis During ULT Initiation

All patients starting ULT must receive anti-inflammatory prophylaxis to prevent acute flares, as ULT initiation significantly increases attack frequency. 1, 2

First-Line Prophylaxis Options:

• Low-dose colchicine: 0.5-0.6 mg once or twice daily 1, 2, 3

  • Adjust for renal impairment: 0.3 mg once daily for severe CKD, 0.3 mg twice weekly for dialysis patients 1, 4
  • Adjust for drug interactions with CYP3A4 inhibitors (reduce to 0.3 mg once daily or every other day) 4

• Low-dose NSAIDs (e.g., naproxen 250 mg twice daily) with proton pump inhibitor if indicated 1, 2

• Low-dose prednisone (≤10 mg/day) for patients with contraindications to both colchicine and NSAIDs 1

Duration of Prophylaxis:

• Continue for the greater of 6 months OR 3 months after achieving target serum urate in patients without tophi 2, 3, 5
• Continue for 6 months after achieving target serum urate AND resolution of tophi in patients with tophi 2, 3

Critical Prophylaxis Considerations:

• Do not treat acute gout flares with colchicine in patients already receiving prophylactic colchicine with CYP3A4 inhibitors 4
• Failure to provide prophylaxis leads to acute flares and poor medication adherence 3

Lifestyle Modifications

• Weight loss is recommended for obese patients 2, 5
• Avoid alcohol (especially beer and spirits) and sugar-sweetened beverages with high-fructose corn syrup 2, 5, 7
• Limit purine-rich foods (organ meats, shellfish) 5, 7
• Encourage consumption of vegetables and low-fat or nonfat dairy products 5, 7

Common Pitfalls to Avoid

• Delaying treatment beyond 24 hours significantly reduces effectiveness 3
• Discontinuing ULT during acute attacks worsens outcomes and should never be done 2, 3, 5
• Using high-dose colchicine regimens causes unnecessary gastrointestinal toxicity without added benefit 3, 5
• Failing to provide prophylaxis when starting ULT leads to preventable acute flares and treatment abandonment 3
• Starting allopurinol at high doses increases risk of severe cutaneous reactions; always start low and titrate slowly 2