Gout is a disorder that results from deposits of uric acid crystals, which accumulate in the joints because of high blood levels of uric acid (hyperuricemia). The accumulations of crystals cause attacks of painful inflammation in and around joints.
Gout is more common among men than women. Usually, gout develops during middle age in men and after menopause in women. Gout is rare in younger people but is often more severe in people who develop the disorder before age 30. Gout often runs in families.
Normally, uric acid, a by-product of cell nucleic acid breakdown, is present in small amounts in the blood because the body continually breaks down cells and forms new cells. Also, the body readily transforms substances in foods called purines into uric acid. Purines are part of proteins. Foods high in purines include anchovies, asparagus, consommé, herring, meat gravies and broths, mushrooms, mussels, all organ meats, sardines, and sweetbreads.
Most often, the uric acid level in the blood becomes abnormally high when the kidneys cannot eliminate enough uric acid in the urine. Too much uric acid in the blood (hyperuricemia) can result in uric acid crystals being formed and deposited in and around joints. Additionally, combining a high-purine diet with alcohol can worsen matters because alcohol both increases the production of uric acid and interferes with its elimination by the kidneys. However, for unknown reasons, not all people who have hyperuricemia develop gout.
Less commonly, gout may be caused by an identifiable underlying disorder and is then called secondary gout. For instance, large amounts of uric acid may be produced because of an inherited enzyme abnormality or a disease such as leukemia, in which cells multiply and are rapidly destroyed. Lead poisoning, some types of kidney disease, and certain drugs that help the kidneys eliminate urine (such as thiazide diuretics) impair the kidneys' ability to eliminate uric acid, so levels of uric acid rise.
High levels of uric acid in the blood often lead to high levels of uric acid in the joints. This process may then result in the formation of uric acid crystals in the joint tissue and the fluid within the joints (synovial fluid). Gout most often affects the joints in the feet, particularly at the base of the big toe (podagra). However, it also commonly affects other areas: the ankle, instep, knee, wrist, and elbow. Gout tends to affect these cooler areas because uric acid crystals form more readily in cool than in warm areas. Rarely, gout affects the joints of the warmer, central part of the body, such as the spine, hips, or shoulders.
Sudden severe attacks of gout (called acute gouty arthritis) can occur without warning. They may be triggered by an injury, illness (such as pneumonia or another infection), surgery, use of thiazide diuretics or start of treatment with certain drugs (such as allopurinol and nitroglycerin), or consumption of large quantities of alcohol or purine-rich food.
Typically, severe pain occurs suddenly in one or more joints, often at night (probably because of the metabolic changes that occur when a person lies down). The pain becomes progressively worse and is often excruciating, particularly when the joint is moved or touched. The joint becomes inflamed—it swells and feels warm, and the skin over the joint may appear red or purplish, tight, and shiny.
Other symptoms of an attack sometimes include fever (which may reach 102° F [38.9° C]), a fast heart rate (tachycardia), chills, and a general sick feeling. The first few attacks usually affect only one joint and last for a few days. The symptoms gradually disappear, joint function returns, and no symptoms appear until the next attack. However, if the disorder progresses, untreated attacks last longer, occur more frequently, and affect several joints. If left untreated, later attacks can last up to 3 weeks.
After repeated attacks, gout can become severe and chronic and may lead to joint deformity.
Over time, joint motion becomes progressively restricted by damage caused by deposits of uric acid crystals in the joints and tendons. Hard lumps of uric acid crystals (tophi) are first deposited in the joint (synovial) lining or cartilage or in bone near the joints and then under the skin around joints. Tophi can also develop in the kidney and other organs and under the skin on the ears. They commonly develop in the fingers, hands, feet, the tough band extending from the calf muscles to the heel (Achilles tendon), or around the elbows. Tophi are normally painless but can become inflamed and painful. If untreated, tophi can burst and discharge chalky masses of uric acid crystals through the skin and may eventually cause deformities.
About 20% of people who have gout develop kidney stones (urolithiasis) that are composed of uric acid (see see Stones in the Urinary Tract). The stones may block the urinary tract, resulting in excruciating pain and, if untreated, infection and kidney damage. In people with gout who also have another disorder that damages the kidneys (such as diabetes or high blood pressure), increasingly poor kidney function reduces the excretion of uric acid and makes the gout and its joint damage progressively worse.
Doctors suspect gout on the basis of its distinctive symptoms and an examination of the affected joints. Podagra, recurrent instep inflammation, and a history of previous attacks that began suddenly and resolved spontaneously also suggest the diagnosis. A high level of uric acid in the blood supports the diagnosis. However, this level is often normal, especially during an acute attack. The diagnosis is usually confirmed when needle-shaped uric acid crystals are identified in a sample of a tophus or in joint fluid removed with a needle (joint aspiration) and viewed under a microscope with polarized light. X-rays may show joint damage and the presence of tophi (uric acid crystal tophi that displace bone and produce cysts). Gout is often similar to and sometimes misdiagnosed as another type of arthritis. Doctors may also do ultrasonography to detect uric acid crystals.
With early diagnosis, therapy enables most people to live a normal life. For many people with advanced disease, significant lowering of the serum urate level can resolve tophi and improve joint function. Gout is generally more severe in people whose initial symptoms appear before age 30. The metabolic syndrome and cardiovascular disease probably contribute to premature death in people with gout.
Some people do not improve sufficiently with treatment. The reasons can include nonadherence and alcoholism.
Treatment has three goals:
Relieving acute attacks:
Nonsteroidal anti-inflammatory drugs (NSAIDs) are often effective in relieving pain and swelling in the joint (see see Nonsteroidal Anti-Inflammatory Drugs). Sometimes, additional analgesics such as oxycodone are needed to control pain. Treatment with NSAIDs should be continued for several days after the pain and inflammation have resolved to prevent relapse.
Colchicine is the traditional, but no longer the most common, first-step treatment. Usually, joint pain begins to subside after 12 to 24 hours of treatment with colchicine and is sometimes gone within 3 to 7 days. Colchicine is taken in tablet form, often as 2 pills given an hour apart.
Corticosteroids, such as prednisone, are sometimes useful to reduce joint inflammation (including the swelling) in people who cannot tolerate the other drugs. If only one or two joints are affected, a corticosteroid suspension, such as prednisolone tebutate, can be injected using the same needle that is used to remove fluid from the joint. As with NSAID therapy, corticosteroids that are taken by mouth should be continued until after the attack fully resolves to prevent relapse.
In addition to NSAIDs or corticosteroids, other pain relievers, rest, immobilization with a splint, and ice can be used to reduce pain. If people cannot tolerate corticosteroids, colchicine, or NSAIDs, drugs that suppress the immune system (such as anakinra) can be used but they are expensive.
Preventing further attacks:
Avoiding alcoholic beverages and nonalcoholic beer, losing weight, stopping drugs that cause elevated blood levels of uric acid, and eating smaller amounts of purine-rich foods will help and rarely be all that is needed. People should eat low-fat dairy products. Most people who have primary gout are overweight. As they gradually lose weight, their blood levels of uric acid often return to normal or near normal, and gout attacks subsequently cease.
Preventive daily drug treatment may be needed for people who experience repeated, severe attacks. Colchicine may be taken daily to prevent attacks or to greatly reduce their frequency. NSAIDs taken daily can also prevent attacks. People with gout who take a diuretic (such as hydrochlorothiazide) to treat high blood pressure may have fewer attacks if they take losartan or a similar drug rather than a diuretic to control their blood pressure. However, preventing attacks does not prevent or heal existing joint damage caused by uric acid crystals because the crystals still persist in the joints, and the drugs do pose some risks for people who have kidney or liver disease.
Lowering blood levels of uric acid:
A high level of uric acid in the blood causes problems for people with gout and may increase the risk of kidney disease in people without gout. People with gout who especially need their blood level of uric acid lowered include those who have the following:
People taking drugs to lower the blood level of uric acid should know their level, just as patients with high blood pressure should know their blood pressure. The goal of drug therapy is to decrease the level to less than 6 milligrams per deciliter. If the blood level is maintained below 6, uric acid will stop being deposited around the joints and in soft tissues and the existing deposits will eventually dissolve.
Drugs can lower blood levels of uric acid by decreasing the body's production of uric acid or increasing the excretion of uric acid in the urine. Allopurinol is most often used to lower the blood level of uric acid. This drug blocks the production of uric acid in the body. However, allopurinol can upset the stomach and can rarely cause a rash, decrease the number of white blood cells, or cause liver damage or inflammation of vessels (vasculitis). Allopurinol also can cause a gout attack when it is first taken. Because low-dose colchicine or an NSAID can decrease this risk, one of these drugs is usually given at the same time for a few months as well.
Febuxostat is another drug that lowers blood levels of uric acid. It is especially useful in patients who cannot take or have not been helped by allopurinol. As with allopurinol, attacks can occur as the uric acid level in the blood first decreases.
Uricase is used less often. It is given by vein (intravenously) and can decrease uric acid by a large amount but can often cause acute flare-ups of gouty arthritis or allergic reactions.
Drugs that cause excretion of uric acid in the urine (uricosuric drugs), such as probenecid or sulfinpyrazone also can be used to lower the levels of uric acid in the blood (in people who have normal kidney function) by increasing the kidney's excretion of uric acid. Aspirin can block the effects of probenecid and sulfinpyrazone, and high doses of aspirin should not be used at the same time as either of these drugs. Low doses that protect the heart (81 milligrams daily) should be continued, because heart disease is a considerable risk in people with gout.
Any treatment that decreases levels of uric acid in the blood can trigger an acute attack (sometimes called a mobilization attack). Mobilization attacks are particularly likely soon after a drug is started. A mobilization attack may be a sign that a drug is working well to decrease uric acid levels. During a mobilization attack, people should not stop taking the drugs that decrease the uric acid level. Low-dose colchicine or an NSAID can be given for a few months after treatment with such a drug begins to help prevent or treat mobilization attacks.
Although uricosuric drugs lower the concentration of uric acid in the blood, they can increase the concentration of uric acid in the urine. Drinking plenty of fluids—at least 3 liters a day—may help reduce the risk of uric acid stones developing in the urinary tract. Making the urine alkaline by taking acetazolamide or potassium citrate (which increases the solubility of uric acid in the urine) can further help reduce the risk of uric acid stones forming in the urinary tract. However, if the urine becomes too alkaline, crystals or stones of another and more dangerous kind—calcium oxalate—may form.
Most tophi on the ears, hands, or feet shrink slowly when the uric acid level becomes sufficiently low. However, large tophi may have to be removed surgically.
Uric acid stones in the urinary tract can be broken up, and thereby washed out in the urine, by using ultrasound directed at the stones from outside the body (extracorporeal shock wave lithotripsy—see Fig. 2: Removing a Stone With Sound Waves).
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Last full review/revision May 2013 by Lawrence M. Ryan, MD