Description

• Gout is an inflammatory arthritis related to a hyperuricemia (serum uric acid [SUA] level >6.8 mg/dL) (1)[C].
• Acute gouty arthritis can affect ≥1 joint; the 1st metatarsophalangeal joint is most commonly involved at presentation (podagra).
• Although hyperuricemia is necessary for the development of gout, it is not the only determining factor.
• Characterized by deposition of monosodium urate (MSU) crystals that accumulate in joints and soft tissues, resulting in acute and chronic arthritis, soft-tissue masses called tophi, urate nephropathy, and uric acid nephrolithiasis
• After an initial flare, a second flare occurs in ~60% of patients within 1 year and 78% within 2 years of the initial attack (2)[C].
• Management involves treating acute attacks and preventing recurrent disease by long-term reduction of SUA levels through pharmacology and lifestyle adjustments.

Epidemiology

Annual incidence of gout (3):

• Uric acid 7.0 to 8.9 mg/dL is 0.5%.
• Uric acid >9 mg/dL is 4.5%.

• Increasing prevalence over the past decades (3)
• Overall prevalence of 3.9% (8.3 million) in the United States in 2008 (3):
  • Men 5.8% (6.1 million)
  • Women 2.0% (2.2 million)

Etiology and Pathophysiology

• Hyperuricemia results from urate overproduction, underexcretion, or often a combination of the two.
• Gout occurs when MSU, a product of purine metabolism, precipitates out of solution and accumulates in joints and soft tissues.
• Transient changes in urate solubility caused by local temperature decrease, trauma, or acidosis may lead to an acute gouty attack.
• Urate crystals that precipitate trigger an immune response.
• Left untreated, this crystal deposition leads to permanent joint damage and tophus formation.
• Obesity predisposes to gout by promoting insulin resistance, which in turn reduces renal urate excretion resulting in hyperuricemia (4)[A].
• Hypertension and renal disease reduce renal urate excretion due to glomerular arteriolar damage (4)[A].

• Phosphoribosyl pyrophosphate (PRPP) deficiency and hypoxanthine guanine phosphoribosyltransferase (HGPRT) deficiency (Lesch-Nyhan syndrome) are inherited enzyme defects associated with overproduction of uric acid.
• Polymorphisms in the URAT1 and SLC2A9 (GLUT9) renal transporters are hereditary enzyme defects resulting in primary underexcretion of uric acid.

Risk Factors

• Age >40 years
• Male gender
• Increased purine uptake (meats and seafood)
• Alcohol intake (especially beer)
• Obesity (BMI >30)
• Heart disease and congestive heart failure
• Dyslipidemia
• Hypertension and renal disease
• Smoking
• Diabetes mellitus
• Diuretics raise SUA levels by increasing uric acid reabsorption and decreasing uric acid secretion in the kidneys (4)[A].
• Urate-elevating medications:
  • Thiazide diuretics: ethambutol
  • Loop diuretics (less of a risk vs. thiazides)
  • Niacin
  • Calcineurin inhibitors (cyclosporine and tacrolimus)

General Prevention

• Maintain optimal weight.
• Regular exercise
• Diet modification (purine-rich foods)
• Reduce alcohol consumption (beer and liquor).
• Smoking cessation
• Maintain fluid intake and avoid dehydration.

Commonly Associated Conditions

• Hypertension
• Dyslipidemia
• Nontraumatic joint disorders
• Heart disease
• Diabetes mellitus
• Metabolic syndrome
• Obesity (BMI >30)
• Renal disease