What is gout and how is it managed?

Gout: Understanding and Management

Gout is a common inflammatory arthritis caused by monosodium urate crystal deposition in joints that requires prompt treatment of acute flares with colchicine, NSAIDs, or corticosteroids, and long-term urate-lowering therapy to prevent recurrent attacks and complications. 1

Pathophysiology and Epidemiology

Gout affects approximately 8 million people in the United States, making it the most common form of inflammatory arthritis with a prevalence of 5.1% among US adults. 1, 2

The disease occurs when excess uric acid in the body crystallizes as monosodium urate (MSU) in:

• Joint fluid
• Cartilage
• Bones
• Tendons
• Bursas
• Other tissues

These crystals trigger acute inflammatory attacks that manifest as painful joint swelling. When serum urate levels exceed 6.8 mg/dL (400 μmol/L), which is the saturation threshold, MSU crystals may form or grow. 1, 2

Clinical Presentation and Diagnosis

Clinical Features

• Acute intermittent episodes of synovitis causing joint swelling and pain
• First metatarsophalangeal joint is most commonly affected
• Attacks may become more frequent, protracted, and severe over time
• May progress to chronic inflammatory arthritis
• Tophi (deposits of urate crystals) may develop at joint surfaces, skin, or cartilage 1, 3

Diagnosis

• Gold standard: Synovial fluid analysis for MSU crystal identification (100% specificity when properly performed) 4
• Clinical diagnosis based on suggestive features and hyperuricemia when synovial fluid analysis isn't feasible
• Imaging techniques (particularly ultrasound) can help identify MSU crystal deposition 4, 5

Management of Acute Gout Flares

Three primary medication options have high-strength evidence for reducing pain in acute gout: 1

1. NSAIDs:

   • First-line option for many patients
   • Caution in patients with renal, cardiovascular, or GI risks 4

2. Colchicine:

   • Moderate-strength evidence shows low-dose colchicine is as effective as high-dose with fewer gastrointestinal side effects
   • For patients with renal impairment:
     • No dose adjustment needed for mild to moderate impairment
     • For severe impairment: treatment course should not be repeated more than once every two weeks 1, 6

3. Corticosteroids:

   • Oral, intra-articular, or systemic options
   • Particularly useful when NSAIDs or colchicine are contraindicated 1, 4

Non-pharmacological measures:

• Topical ice application
• Rest of the inflamed joint 7

Long-Term Management

Urate-Lowering Therapy (ULT)

Moderate-strength evidence suggests that ULT reduces long-term risk for acute gout attacks after 1 year or more. 1

First-line agents:

• Allopurinol: Preferred first-line agent, even in moderate-to-severe CKD

  • Inhibits xanthine oxidase to reduce uric acid formation
  • Dosage is dependent on renal function
  • Generally results in fall in serum and urinary uric acid within 2-3 days 4, 8

• Febuxostat: Alternative xanthine oxidase inhibitor 3

Second-line agents:

• Probenecid: Uricosuric agent for patients who cannot tolerate first-line agents
• Reserved for patients with normal renal function and no history of urolithiasis 3, 7

Prophylaxis During ULT Initiation

High-strength evidence shows that prophylaxis with daily colchicine or NSAIDs reduces the risk for acute gout attacks by at least half in patients starting urate-lowering therapy. 1

• Prophylaxis should continue for at least 3-6 months
• Moderate-strength evidence indicates that duration should be longer than 8 weeks
• Continue for at least 3 months after uric acid levels fall below target in those without tophi
• Continue for 6 months in those with a history of tophi 1, 3

Target Uric Acid Levels

Although lower urate levels reduce risk for recurrent attacks, treatment to a specific target level has not been thoroughly tested in clinical trials. 1

However, the G-CAN expert panel and other rheumatology guidelines support a treat-to-target approach aimed at lowering serum urate levels below the saturation threshold at which MSU crystals form (approximately 6.8 mg/dL). 1

Lifestyle Modifications

• Limit consumption of:

  • Purine-rich foods (organ meats, shellfish)
  • Alcoholic drinks (especially beer)
  • Beverages sweetened with high-fructose corn syrup 3

• Encourage consumption of:

  • Vegetables
  • Low-fat or nonfat dairy products 3

Special Considerations

Medication Interactions

• Loop and thiazide diuretics can increase uric acid levels
• Losartan (angiotensin receptor blocker) increases urinary excretion of uric acid 3
• Thiazide diuretics have an odds ratio of 1.72 (95% CI: 1.67-1.76) for gout development 4

Comorbidity Management

• CKD, hypertension, heart failure, and obesity are common comorbidities in gout patients
• Consider alternative antihypertensives (ACE inhibitors, ARBs, calcium channel blockers) for patients at risk of gout
• Loop diuretics are preferred over thiazides in patients with eGFR <30 mL/min/m² 4

Common Pitfalls to Avoid

1. Failing to diagnose accurately: Rely on synovial fluid analysis whenever possible rather than just clinical presentation

2. Inadequate duration of prophylaxis: Ensure prophylaxis continues for at least 3-6 months when starting ULT

3. Poor medication adherence: Emphasize the chronic nature of gout and importance of continuous ULT to prevent flares and complications 5

4. Treating asymptomatic hyperuricemia: Asymptomatic hyperuricemia alone is not an indication for ULT 4

5. Discontinuing ULT during acute flares: Continue ULT during flares while treating the acute inflammation