What causes gout?

Causes of Gout

Gout is primarily caused by prolonged hyperuricemia which leads to the formation of monosodium urate (MSU) crystals that accumulate in joints and other tissues. 1 This fundamental pathophysiological process is the cornerstone of gout development and progression.

Major Risk Factors for Gout

Modifiable Risk Factors:

• Diuretic use: Particularly thiazide diuretics, which increase the risk of gout with an odds ratio of 1.72 (95% CI, 1.67 to 1.76) 1, 2
• Diet:
  • High purine foods (especially red meat and seafood)
  • Alcohol consumption (particularly beer)
  • Sugary beverages and fructose intake
  • Increased meat consumption (10g daily increase) with relative risk of 1.17 1

Medical Conditions Associated with Gout:

• Obesity: Associated with a 3.81-fold increased risk (95% CI, 1.22 to 11.84) 1
• Hypertension: Increases risk by 3.93 times (95% CI, 1.60 to 9.70) 1
• Chronic kidney disease: Significantly increases risk with odds ratio of 4.95 (95% CI, 4.28 to 5.72) 1
• Coronary heart disease: Associated with 1.75-fold increased risk (95% CI, 1.70 to 1.79) 1
• Diabetes mellitus: Modest increase in risk with odds ratio of 1.11 (95% CI, 1.06 to 1.16) 1

Metabolic Factors:

• Elevated triglycerides and apolipoprotein B: Significantly associated with gout development 1
• Metabolic syndrome components: Multiple components increase risk cumulatively

Pathophysiological Mechanism

Gout develops through several stages:

1. Asymptomatic hyperuricemia: Elevated serum uric acid above 6.8 mg/dL (saturation point) 3
2. MSU crystal formation: When uric acid levels exceed solubility threshold, crystals form and deposit in joints 1
3. Acute gout flare: Crystal-induced inflammatory response causing severe pain, swelling, and erythema
4. Intercritical gout: Asymptomatic periods between flares 1
5. Chronic tophaceous gout: Development of tophi (crystal deposits) and joint damage with inadequate treatment

Genetic Factors

Genetic predisposition plays a significant role in gout development, particularly affecting:

• Uric acid production
• Renal excretion of uric acid
• Inflammatory response to MSU crystals

Special Considerations

Medication-Induced Gout

Beyond diuretics, several medications can contribute to hyperuricemia:

• Low-dose aspirin
• Cyclosporine
• Tacrolimus
• Certain chemotherapeutic agents

Environmental Factors

• Lead exposure may affect serum uric acid levels, though evidence for direct causation of gout is limited 1

Clinical Implications

The identification of these risk factors is crucial for:

1. Early detection of high-risk individuals
2. Prevention strategies focusing on modifiable factors
3. Appropriate management targeting the underlying cause of hyperuricemia

Understanding that gout results from the complex interplay of these factors helps guide effective treatment approaches aimed at reducing serum uric acid levels below 6 mg/dL to prevent crystal formation and promote dissolution of existing crystals 3, 4.