What is the evaluation and management of gout?

Evaluation and Management of Gout

The management of gout requires a two-pronged approach: treating acute flares with anti-inflammatory medications and implementing long-term urate-lowering therapy (ULT) to prevent recurrent attacks and complications by maintaining serum uric acid levels below 6 mg/dL.

Diagnosis and Evaluation

Clinical Presentation

• Acute monoarticular arthritis, most commonly affecting the first metatarsophalangeal joint
• Sudden onset of severe pain, erythema, swelling, and tenderness
• Attacks typically peak within 12-24 hours and resolve within 7-10 days without treatment

Diagnostic Workup

• Synovial fluid analysis: Identification of monosodium urate crystals (needle-shaped, negatively birefringent under polarized light)
• Serum uric acid measurement: Often elevated (>6.8 mg/dL), but may be normal during acute attacks
• Imaging: Not required for diagnosis but may show characteristic changes in chronic gout
• Assessment of comorbidities: Renal function, cardiovascular disease, hypertension, obesity

Management of Acute Gout Flares

First-Line Options 1

1. Colchicine:

   • Most effective when started within 12 hours of flare onset
   • Low-dose regimen: 1.2 mg initially, followed by 0.6 mg one hour later on day 1
   • Continue with 0.6 mg once or twice daily until flare resolves
   • Avoid in patients with severe renal impairment and those taking strong P-glycoprotein/CYP3A4 inhibitors

2. NSAIDs:

   • Use with proton pump inhibitor if appropriate
   • Avoid in patients with severe renal impairment, cardiovascular disease, or heart failure 2

3. Corticosteroids:

   • Oral: 30-35 mg/day of prednisolone equivalent for 3-5 days
   • Intra-articular injection: Particularly useful for monoarticular flares
   • Good alternative for patients with contraindications to colchicine or NSAIDs

Second-Line Options 1

• IL-1 blockers (anakinra, canakinumab): Consider for patients with frequent flares and contraindications to first-line treatments
• Contraindicated in patients with active infections

Long-Term Management and Prevention

Urate-Lowering Therapy (ULT)

Indications for ULT 1

• Recurrent acute attacks (≥2 per year)
• Tophaceous gout
• Radiographic damage due to gout
• Urolithiasis
• Chronic kidney disease

First-Line ULT 1, 3

• Allopurinol:
  • Starting dose: ≤100 mg/day (lower in CKD)
  • Titrate dose by 100 mg every 2-5 weeks
  • Target serum uric acid level: <6 mg/dL (<5 mg/dL in severe gout with tophi)
  • Typical maintenance dose: 200-300 mg/day for mild gout, 400-600 mg/day for moderate-severe tophaceous gout
  • Maximum dose: 800 mg/day
  • Adjust dose based on renal function:
    • CrCl 10-20 mL/min: 200 mg/day
    • CrCl <10 mL/min: ≤100 mg/day

Second-Line ULT 1, 4

• Febuxostat:

  • Starting dose: <40 mg/day
  • More effective than allopurinol in lowering serum urate levels
  • Can be used without dose adjustment in moderate-severe renal impairment
  • Caution in patients with cardiovascular disease

• Uricosuric agents (probenecid, benzbromarone):

  • Consider when allopurinol or febuxostat are ineffective or not tolerated
  • Probenecid is effective with normal renal function but contraindicated in urolithiasis
  • Benzbromarone can be used in mild-moderate renal impairment but may be hepatotoxic

Third-Line ULT 1, 4

• Combination therapy: Adding a uricosuric agent to a xanthine oxidase inhibitor
• Pegloticase: For severe, refractory cases with high disease burden who failed other ULTs

Prophylaxis During ULT Initiation 1, 4

• Essential to prevent flares during ULT initiation or dose adjustment
• Colchicine: 0.5-1 mg/day for 3-6 months
• Alternative: Low-dose NSAIDs if colchicine is not tolerated or contraindicated

Lifestyle and Dietary Modifications 1, 4

• Weight loss if overweight/obese
• Limit alcohol consumption, especially beer and spirits
• Avoid sugar-sweetened beverages and high-fructose corn syrup
• Reduce intake of purine-rich foods (organ meats, shellfish)
• Encourage low-fat dairy products
• Regular exercise
• Adequate hydration (2.5-3L fluid intake daily)

Monitoring and Follow-up

• Serum uric acid levels: Every 2-5 weeks during ULT dose titration, then every 6 months
• Renal function: Regular monitoring, especially with allopurinol
• Liver function: With febuxostat and benzbromarone
• Clinical assessment: Frequency of attacks, resolution of tophi

Special Considerations

Cardiovascular Disease 2

• Colchicine is preferred for acute flares (may reduce MI risk)
• Avoid NSAIDs
• Consider allopurinol as first-line ULT (potential cardiovascular benefits)
• Use caution with febuxostat due to potential increased cardiovascular risk

Chronic Kidney Disease

• Adjust allopurinol dose based on renal function
• Febuxostat can be used without dose adjustment
• Avoid probenecid if CrCl <50 mL/min

Common Pitfalls to Avoid

1. Failing to treat to target serum uric acid level (<6 mg/dL)
2. Inadequate dose titration of allopurinol
3. Discontinuing ULT during acute flares
4. Insufficient duration of prophylaxis when initiating ULT
5. Not addressing comorbidities and lifestyle factors
6. Starting with high-dose allopurinol in patients with renal impairment

By following these evidence-based recommendations, gout can be effectively managed to reduce pain, prevent joint damage, and improve quality of life.