Gout / Hyperuricemia

Known as "the disease of kings and the king of diseases", gout has been studied by physicians and has caused suffering in countless humans since at least the days of Hippocrates.  Formerly a leading cause of painful and disabling chronic arthritis, gout has been all but conquered by advances in research.  Unfortunately, many people with gout continue to suffer because knowledge of effective treatments has been slow to spread to patients and their physicians. The four phases of gout include elevated uric acid levels without symptoms, acute gouty arthritis, multiple attacks with intervals between attacks, and chronic tophaceous gout, in which nodular masses of uric acid crystals (tophi) are deposited in different soft tissue areas of the body.  Patients with asymptomatic hyperuricemia do not require treatment, but efforts should be made to lower their urate levels by encouraging them to make changes in diet or lifestyle.

Uric acid is a product of the chemical breakdown of the purine bases that compose the genetic material, DNA.  As cells die and release DNA from their chromosomes, purines are converted into uric acid which is excreted in the urine and, to a lesser extent, the intestinal tract.  The level of uric acid dissolved in the bloodstream is directly related to this delicate balance between uric acid production and excretion.  The normal level is approximately 2-7mg/dl.

Though an excess of uric acid is known to cause gout, recent studies show that, in proper concentrations in the blood, it has antioxidant properties and helps protect the cells and tissues from irritation and damage caused by singlet oxygens and hydroxyl free radicals.  This protection may prevent tissue wear and aging, in addition to other free-radical diseases.

Thus, uric acid has a new image as being an important part of balanced human function and not just a waste product.  With its different effects, uric acid is somewhat like cholesterol in its biochemistry: As with cholesterol, it is both made in the body and obtained through the diet; some people are genetically inclined to elevated levels; and, whereas the right amount is essential to important functions, excesses can lead to problems (cholesterol appears to be much more of a concern on this count than uric acid).

Incidence; Causes and Development

Gout in women occurs almost exclusively after menopause.  Women develop gout at an older age than men and have twice the prevalence of hypertension, renal insufficiency and exposure to diuretics.  The onset of gout before age 30 in men or before menopause in women is unusual and raises concern about an associated inherited enzyme defect or renal disease.

An attack of acute gouty arthritis is caused by the body's inflammatory reaction to intermittent deposition of needle-like uric acid crystals.  When these crystals are ingested by white blood cells, the cells release enzymes that evoke inflammation.

The inflammatory process in gout is unrelated to infection.  Rather, it is incited by the deposition in the joint of uric acid crystals usually due to an excess of uric acid in the bloodstream.  This can be caused by an increase in production by the body, by under-elimination of uric acid by the kidneys or by increased intake of foods containing purines which are metabolized to uric acid in the body.  Certain meats, seafood, dried peas and beans are particularly high in purines.  Alcoholic beverages may also significantly increase uric acid levels and precipitate gout attacks.  Gout is strongly associated with obesity, hypertension, hyperlipidemia, diabetes and dehydration.  A familial pattern is observed in 5-15% of cases.

In most cases, an under-excretion of uric acid by the kidneys is responsible.  Among the more common predisposing factors are kidney failure from any cause, diuretics, dehydration, hormonal diseases, alcohol consumption and using low doses of aspirin.  About 10% of people with hyperuricemia are overproducers of uric acid.  For some of these patients, diseases of the blood and bone marrow or inherited enzyme abnormalities can be implicated.  Some are associated with metabolic alterations due to obesity, but for most the exact cause is indeterminable.

Signs and Symptoms

Attacks are usually marked by intermittent joint pain, swelling, redness and warmth.  Other symptoms include:

• Rapid onset of severe joint pain, swelling and redness, often beginning at night after ingestion of alcoholic beverages, uric acid-elevating medications or high-purine foods.
• In 90% of initial episodes a single joint is involved - especially the joint at the base of the big toe.  Gouty arthritis of the big toe afflicts some 90% of patients some time during the course of their disease.  The foot, heel, ankle, knee, hands, wrists and elbows are some of the other joints that are frequently involved.
• Attacks tend to last a few days to a few weeks.
• Attacks respond well to medications.
• The frequency of subsequent attacks is variable.  5-10% of patients will never be bothered again, but most relapse within a year.

Diagnosis and Tests

Since several other kinds of arthritis can mimic a gout attack, and since treatment is specific to gout, proper diagnosis is essential.  The definitive diagnosis of gout is dependent on finding uric acid crystals in the joint fluid during an acute attack.  However, uric acid levels in the blood alone are often misleading and may be transiently normal or even low.  Additionally, uric acid levels are often elevated in individuals without gout.  While sudden swelling and pain in a joint, especially the big toe, suggests the diagnosis of gout, many other arthritic conditions and some infections present themselves in a similar manner.  Gout is the diagnosis if gout medications resolve the symptoms.  Uric acid levels are usually elevated around an attack, and reduced when treated successfully.

Treatment and Prevention

Serum uric acid can be elevated due to reduced excretion by the kidneys, and or high intake of dietary purine. 
In many instances, people have elevated uric acid levels for hereditary reasons.  Diet may also be a factor; eating large amounts of sea salt can cause increased levels of uric acid.

Moderate intake of purine-containing food is not associated with an increased risk of gout.  Sources of uric acid to be avoided as far as possible:

Purines are excreted as uric acid.  Purines are found in high amounts in animal food products, such as liver and sardines.  A moderate amount of purine is also contained in beef, pork, poultry, fish and seafood, asparagus, cauliflower, spinach, mushrooms, green peas, lentils, dried peas, beans, oatmeal, wheat bran and wheat germ.

Examples of high purine sources include: sweetbreads, anchovies, sardines, liver, beef kidneys, brains, meat extracts (e.g.  Oxo, Bovril), herring, mackerel, scallops, game meats, and gravy.

Prognosis

Untreated cases may develop chronic gouty arthritis in which multiple joints are involved by a long-term destructive process.  Tophi (small nodules consisting of uric acid and inflammatory tissues) may be seen on the ear cartilage and along tendons.