Definition

Gout is a metabolic disease most often affecting middle-aged to elderly men and postmenopausal women. Hyperuricemia is the biologic hallmark of gout. When present, plasma and extracellular fluids become supersaturated with uric acid, which, under the right conditions, may crystallize and result in a spectrum of clinical manifestations that may occur singly or in combination.

Pathogenesis

Uric acid is the end product of purine nucleotide degradation; its production is closely linked to pathways of purine metabolism, with the intracellular concentration of 5-phosphoribosyl-1-pyrophosphate (PRPP) being the major determinant of the rate of uric acid biosynthesis. Uric acid is excreted primarily by the kidney through mechanisms of glomerular filtration, tubular secretion, and reabsorption. Hyperuricemia may thus arise in a wide range of settings that cause overproduction or reduced excretion of uric acid or a combination of the two.

Acute Gouty Arthritis

Monosodium urate (MSU) crystals present in the joint are phagocytosed by leukocytes; release of inflammatory mediators and lysosomal enzymes leads to recruitment of additional phagocytes into the joint and to synovial inflammation.

Clinical Manifestations

• Acute arthritis: most frequent early clinical manifestation of gout. Usually initially affects one joint, but may be polyarticular in later episodes. The first metatarsophalangeal joint (podagra) is often involved. Acute gout frequently begins at night with dramatic pain, swelling, warmth, and tenderness. Attack will generally subside spontaneously after 3-10 days. Although some pts may have a single attack, most pts have recurrent episodes with intervals of varying length with no symptoms between attacks. Acute gout may be precipitated by dietary excess, trauma, surgery, excessive ethanol ingestion, diuretic medications, hypouricemic therapy, and serious medical illnesses such as myocardial infarction and stroke.
• Chronic arthritis: a proportion of gout pts may have a chronic nonsymmetric synovitis; may rarely be the only manifestation. Can also present with periarticular tophi (aggregates of MSU crystals surrounded by a giant cell inflammatory reaction).
• Extraarticular tophi: often occur in olecranon bursa, helix and anthelix of ears, ulnar surface of forearm, Achilles tendon.
• Tenosynovitis
• Urate nephropathy: deposition of MSU crystals in renal interstitium and pyramids. Can cause chronic renal insufficiency.
• Acute uric acid nephropathy: reversible cause of acute renal failure due to precipitation of urate in the tubules; pts receiving cytotoxic treatment for neoplastic disease are at risk.
• Uric acid nephrolithiasis: responsible for 10% of renal stones in the United States.

Diagnosis

• Synovial fluid analysis: should be performed to confirm gout even when clinical appearance is strongly suggestive; joint aspiration and demonstration of both intracellular and extracellular needle-shaped negatively birefringent MSU crystals by polarizing microscopy. Gram stain and culture should be performed on all fluid to rule out infection. MSU crystals can also be demonstrated in chronically involved joints or tophaceous deposits.
• Serum uric acid: normal levels do not rule out gout.
• Urine uric acid: excretion of >800 mg/d on regular diet in the absence of drugs suggests overproduction.
• Screening for risk factors or sequelae: urinalysis; serum creatinine, liver function tests, glucose and lipids; complete blood counts.
• If overproduction is suspected, measurement of erythrocyte hypoxanthine guanine phosphoribosyl transferase (HGPRT) and PRPP levels may be indicated.
• Joint x-rays: may demonstrate cystic changes, erosions with sclerotic margins in advanced chronic arthritis.
• If renal stones suspected, consider abdominal flat plate (stones often radiolucent), ultrasound, IVP, or CT.
• Chemical analysis of renal stones.