What is gout, its cause, and management?

Gout: Definition, Causes, and Management

Gout is a common inflammatory arthritis characterized by acute intermittent episodes of synovitis causing joint swelling and pain, resulting from the crystallization of excess urate in the body as monosodium urate crystals in joint fluid, cartilage, bones, tendons, and other tissues. 1, 2

Definition and Pathophysiology

Gout occurs when excess uric acid in the body crystallizes in joint fluid and other tissues, directly initiating an acute inflammatory attack. Key features include:

• Approximately 8 million people in the United States have gout 1
• Characterized by painful joint inflammation, most commonly in the first metatarsophalangeal joint 3
• Can progress from acute attacks to chronic inflammatory condition with tophi (deposits of urate crystals at the surface of joints, skin, or cartilage) 1, 2

Risk Factors

• Medications: Cyclosporine, tacrolimus, thiazide diuretics (odds ratio 1.72) 2
• Comorbidities: Chronic kidney disease, hypertension, heart failure, obesity 2
• Dietary factors: Alcohol (especially beer and spirits), purine-rich foods (organ meats, shellfish), beverages with high-fructose corn syrup 3
• Gender: More common in men than women prior to menopause 4

Diagnosis

• Gold standard: Synovial fluid analysis for monosodium urate crystal identification (100% specificity when properly performed) 2
• Clinical diagnosis based on:
  • Hyperuricemia
  • Rapid development of pain, tenderness, and swelling in a single joint
  • Family history
  • Imaging (particularly ultrasound) to search for MSU crystal deposition 2, 5

Management

1. Acute Gout Attack Management

• First-line treatments (high-strength evidence shows these reduce pain in acute gout) 1:

  • NSAIDs
  • Colchicine (low-dose is as effective as high-dose with fewer gastrointestinal adverse events)
  • Corticosteroids (oral, intravenous, or intra-articular)

• Non-pharmacological measures:

  • Topical ice
  • Rest of the inflamed joint 6

2. Long-term Management of Hyperuricemia

• Urate-lowering therapy (ULT) is indicated for:

  • Recurrent acute attacks
  • Tophi
  • Joint destruction
  • Uric acid lithiasis and/or nephropathy 7
  • NOT recommended for asymptomatic hyperuricemia 2, 7

• First-line ULT:

  • Allopurinol (preferred even in moderate-to-severe CKD) 2
  • Start with low dose (100 mg daily) and increase at weekly intervals by 100 mg until serum uric acid level of 6 mg/dL or less is attained (maximum 800 mg per day) 7

• Alternative ULT options:

  • Febuxostat (for patients who cannot tolerate allopurinol) 3
  • Probenecid (for allopurinol-allergic patients with normal renal function and no history of urolithiasis) 6

3. Prophylaxis to Prevent Acute Flares

• 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 be continued for:
  • At least 3 months after uric acid levels fall below target goal in those without tophi
  • At least 6 months in those with a history of tophi 3
  • Moderate-strength evidence indicates duration should be longer than 8 weeks 1

Lifestyle Modifications

• Limit consumption of purine-rich foods (organ meats, shellfish) 3
• Avoid alcoholic drinks (especially beer) and beverages sweetened with high-fructose corn syrup 3
• Encourage consumption of vegetables and low-fat or nonfat dairy products 3
• Maintain adequate fluid intake (at least 2 liters daily) and slightly alkaline urine 7

Special Considerations

• Renal impairment: Patients with decreased renal function require lower doses of allopurinol than those with normal renal function 7
• Medication interactions: Allopurinol inhibits the enzymatic oxidation of mercaptopurine, potentially requiring dose reduction of mercaptopurine by up to 75% when given together 7
• Monitoring: Regular monitoring of serum uric acid levels is essential to ensure target levels are achieved 2

Common Pitfalls and Caveats

1. Increased gout flares during ULT initiation: Acute attacks may increase during early stages of allopurinol administration, even with normal or subnormal serum uric acid levels 7

2. Renal function deterioration: Some patients with pre-existing renal disease have shown a rise in BUN during allopurinol administration; careful monitoring is required 7

3. Bone marrow depression: Reported in patients receiving allopurinol, particularly with concomitant drugs; can occur from 6 weeks to 6 years after initiation 7

4. Medication selection: Avoid NSAIDs in patients with renal, cardiovascular, and GI risks 2

5. Target serum urate level: Although lower urate levels reduce risk for recurrent acute attacks, treatment to a specific target level has not been tested in long-term studies 1