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.
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.
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.
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, 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). Occurs in the setting of long-standing gout.
Extraarticular tophi: often occur in olecranon bursa, helix and anthelix of ears, ulnar surface of forearm, Achilles tendon.
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.