Gout is a type of arthritis in which uric acid crystals deposit in joints, causing sudden pain and inflammation. The most commonly affected joint is at the base of the big toe. Gout is most common in middle-aged men. It often runs in families.
Gout can arise from metabolic deficits that cause uric acid overproduction or from renal underexcretion of urates, or it may be secondary to hyperuricemia induced by coexisting disease or medications. The most characteristic lesion of gout is the tophus, a deposit of crystals of monosodium urate that triggers a severe inflammatory reaction in the surrounding tissue. Although the first metatarsophalangeal joint (big toe) is the most common site of initial inflammatory disease (podagra), visible tophi can also develop on the helix of the ear, elbow, Achilles tendon, extensor surface of the forearm, knee, fingertips and toes.
Other factors that may contribute to the development of gout include alcohol use, hypertension, obesity, insulin resistance, high-purine diet or lead exposure. Secondary hyperuricemia may be due to myeloproliferative disease or renal insufficiency. Severe psoriasis and other diseases with high tissue nucleic acid turnover may also lead to hyperuricemia.
The writings of Hippocrates first described gout in the fifth century BC. Famous sufferers of gout include Alexander the Great, Kubla Khan, Isaac Newton, Henry VIII, Louis XIV, John Wesley, Martin Luther, Sir Francis Bacon, and Benjamin Franklin. It was called the "the disease of kings and the king of diseases" because it usually struck the affluent.
Uric acid is the terminal product of purine metabolism in humans; other mammals express uricase, which metabolizes uric acid to allantoin, a significantly more water-soluble product. The only other mammal prone to uric acid kidney stones is the Dalmatian dog, which suffers from these due to increased fractional excretion of uric acid.
Primary gout more commonly affects men, with the first attack occurring typically between the ages of 40 and 50 years. It is uncommon in premenopausal women and some speculate that oestrogen expedites renal excretion of uric acid. Family history of gout is reported by 10% to 20% of patients. The majority of patients with gout have tubular defects that reduce uric acid excretion. The metabolic disorders that predispose to gout are those that alter purine metabolism.