Description

• Gout refers to a group of disorders related to hyperuricemia. Although hyperuricemia is necessary for the development of gout, it is not the only determining factor.
• Characterized by deposition of monosodium urate (MSU) crystals in tissue, resulting in acute and chronic arthritis, soft-tissue masses called tophi, urate nephropathy, and uric acid nephrolithiasis
• Natural history involves 4 stages:
  • Asymptomatic hyperuricemia
  • Acute arthritis
  • Intercritical gout
  • Chronic tophaceous gout
• Acute gouty arthritis can affect ≥1 joints. The 1st metatarsophalangeal joint is most commonly involved at presentation (podagra).
• Other common sites include midtarsal, ankle, and knee joints.
• After an initial attack, patients can be attack-free for months or even years. Some patients will develop more frequent attacks or go on to develop chronic tophaceous gout.
• Management involves treating acute attacks and preventing recurrent disease by long-term reduction of serum uric acid (SUA) levels through pharmacology and lifestyle adjustments.

• Presentation may lack acute pain, swelling, and inflammation
• More common in women >80
• Can present with tophi and finger joint pain
• Commonly triggered by diuretic use, especially in women

Pediatric Considerations
Often due to an inborn error of metabolism or other disease

Epidemiology

Incidence
Increases with age, especially in women

Prevalence
6:1,000 population for men; 1:1,000 population for women

Risk Factors

• Hyperuricemia
• Male gender (age <65)
• Increasing age
• Ethanol ingestion (beer and liquor > wine)
• Obesity (50%)
• Hypertension (HTN) (50%)
• Diabetes
• Metabolic syndrome
• Medications: Diuretics induce 20% of secondary gout
• Diet: High-purine animal-origin foods (e.g., meats and seafood)
• Family history
• Keto- and lactic acidosis
• Surgery or trauma
• Renal impairment
• Hypothyroidism
• Parathyroid disease
• Hyperlipidemia types II, IV, V
• Paget disease
• Hyperproliferative skin disorders (psoriasis)
• Lymphoproliferative disorders, hemolytic anemia, hemoglobinopathies, pernicious anemia
• Glycogen storage diseases

• Primary gout runs in families and follows multifactorial inheritance.
• Phosphoribosyl pyrophosphate (PRPP) deficiency and hypoxanthine-guanine-phosphoribosyltransferase (HGPRT) deficiency are inherited enzyme defects associated with a primary overproduction of uric acid.
• URAT1 (urate transporter) deficiency is also a hereditary enzyme defect resulting in primary underexcretion of uric acid.

General Prevention

• Treat underlying cardiovascular risk factors.
• Maintain weight at optimal BMI of <26.
• Regular exercise
• Diet modification
• Reduce alcohol consumption (beer and liquor).
• Maintain fluid intake and avoid dehydration.

Pathophysiology

• Humans have a narrow window for urate to remain soluble before crystal precipitation due to lack of uricase enzyme.
• Precipitation of MSU crystals can occur in the synovium, joint cartilage, kidneys, and soft tissue.
• MSU crystals can initiate and sustain an inflammatory response, leading to an acute gout attack.
• Chronic and untreated hyperuricemia lead to tophi formation in and around the joint space.
• Tophi contribute to chronic synovitis, often resulting in joint damage.

Etiology

• Increased uric acid production
• Renal underexcretion of uric acid
• Enzyme defects
• Increased purine turnover
• Dehydration or starvation
• Malignancy

Commonly Associated Conditions

• Metabolic syndrome (obesity, hyperglycemia, hyperlipidemia, HTN)
• Myeloproliferative disorders
• Lymphoproliferative disorders
• Alcoholism
• Endocrinopathies
• Lesch-Nyhan syndrome