Description

• Gout is an inflammatory arthritis 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.
• Acute gouty arthritis can affect ≥1 joint; the 1st metatarsophalangeal joint is most commonly involved at presentation (podagra).
• Gout is related to a hyperuricemia (serum uric acid level >6.8 mg/dL) (1)[C] and although hyperuricemia is necessary for the development of gout, it is not the only determining factor.
• 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 serum uric acid levels through pharmacology and lifestyle adjustments.

Epidemiology

• The incidence and prevalence of gout has been increasing over the past several decades (3).
• Gout has a higher incidence in males than females.

• Overall prevalence of gout is 3.9% (8.3 million people) in the United States in 2008 (3):
  • Men 5.8% (6.1 million)
  • Women 2.0% (2.2 million)
• Prevalence increases with age and serum uric acid levels.

Etiology and Pathophysiology

• Hyperuricemia results from uric acid 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 uric acid solubility caused by local temperature decrease, trauma, or acidosis may lead to an acute gouty attack.
• Uric acid crystals that precipitate can trigger an immune response and inflammation in the affected joint.
• 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 uric acid excretion resulting in hyperuricemia (4)[A].
• Hypertension and renal disease reduce renal uric acid 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 serum uric acid 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