Gout is a disorder that results from deposits of sodium uric acid crystals, which accumulate in the joints because of high blood levels of uric acid (hyperuricemia), leading to attacks of painful joint inflammation.

• Accumulations of uric acid crystal can intermittently cause severe joint or tissue pain and inflammation.
• Doctors remove fluid from the joint and check it for uric acid crystals.
• Drugs are given to relieve inflammation and pain, prevent further attacks, and sometimes decrease blood levels of uric acid.

Urate Crystals

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.

Risk Factors for the Development of Gout
Beer and alcoholic beverages Low dairy intake Certain cancers and blood disorders Certain drugs (such as thiazide diuretics, cyclosporineSome Trade Names NEORAL SANDIMMUNE , pyrazinamideSome Trade Names RIFATER , ethambutolSome Trade Names MYAMBUTOL , nicotinic acidSome Trade Names See Niacin , and high doses of aspirinSome Trade Names BAYER ) Certain foods (such as anchovies, asparagus, consommé, herring, meat gravies and broths, mushrooms, mussels, all organ meats, sardines, and sweetbreads) Hypothyroidism Lead poisoning (from “moonshine” whiskey) Obesity Radiation therapy Chronic kidney disease Starvation

Did You Know... In past times, when protein was scarce, gout, which can be caused or worsened by eating too much protein, was considered a rich person's disease.

Causes

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 can result in uric acid crystals being formed and deposited in 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.

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. Some types of kidney disease and certain drugs (eg, thiazide diuretics) impair the kidneys' ability to eliminate uric acid, so levels of uric acid rise.

High levels of uric acid in the blood 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.

Symptoms

Attacks of gout (acute gouty arthritis) can occur without warning. They may be triggered by an injury, surgery, consumption of large quantities of alcohol or purine-rich food, or illness. 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 can include fever (which may reach 102° F [38.9° C]) 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.

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, under the skin on the ears, in the tough band extending from the calf muscles to the heel (Achilles tendon), or around the elbows. They commonly develop in the fingers, hands, and feet. If untreated, tophi can burst and discharge chalky masses of uric acid crystals through the skin.

About one fifth of people who have gout develop kidney stones (urolithiasis) that are composed of uric acid (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.

Diagnosis

Doctors often diagnose gout on the basis of its distinctive symptoms and an examination of the affected joints. A high level of uric acid in the blood supports the diagnosis; however, this level is often normal, especially during an acute (sudden severe) attack. The diagnosis is confirmed when needle-shaped uric acid crystals are identified in a sample of a tophus or in joint fluid removed (joint aspiration) with a needle 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.

Treatment

Treatment has three goals:

• Relieve the acute attack of inflammation
• Prevent further attacks
• Prevent further deposition of uric acid in the tissues by lowering blood levels of uric acid

Relieving the Acute Attack: Nonsteroidal anti-inflammatory drugs (NSAIDs) are often effective in relieving pain and swelling in the joint (see Pain: Nonsteroidal Anti-Inflammatory Drugs). Sometimes, additional analgesics such as oxycodoneSome Trade Names
OXYCONTIN
are needed to control pain. The inflamed joint may be immobilized with a splint, and ice can be applied to reduce pain.

Colchicine is the traditional, but no longer the most common, first-step treatment. Usually, joint pain begins to subside after 12 hours of treatment with colchicine and is gone within 36 to 48 hours. Colchicine is usually taken in tablet form each hour until symptoms are relieved. Colchicine can cause abdominal pain and diarrhea. It can occasionally cause more serious side effects, including damage to the bone marrow.

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.

Preventing Further Attacks: Avoiding alcoholic beverages, 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. 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. 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 most people. People who especially need their blood level of uric acid lowered include those who have the following:

• Frequent, severe attacks despite taking colchicine or NSAIDs
• Tophi
• Very high blood levels of uric acid
• Uric acid kidney stones
• Conditions that make NSAIDs or corticosteroids risky to take (such as peptic ulcer disease and chronic kidney disease)

People taking drugs to lower the blood level of uric acid should know their level, just as patients with hypertension should know their blood pressure. The goal of drug therapy is to decrease the level to 10 to 15% less than normal.

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. AllopurinolSome Trade Names
LOPURIN ZYLOPRIM
is most often used to lower the blood level of uric acid. This drug blocks the production of uric acid in the body and is especially helpful for people who have a high blood level of uric acid and uric acid stones or kidney damage. However, allopurinolSome Trade Names
LOPURIN ZYLOPRIM
can upset the stomach, cause a skin rash, decrease the number of white blood cells, or cause liver damage or inflammation of vessels (vasculitis). AllopurinolSome Trade Names
LOPURIN ZYLOPRIM
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 for a few months as well.

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. AspirinSome Trade Names
BAYER
can block the effects of probenecid and sulfinpyrazone, and high doses of aspirinSome Trade Names
BAYER
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.

Although drugs that increase the excretion of uric acid in the urine (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 quarts a day—may help reduce the risk of uric acid stones developing in the urinary tract. Making the urine alkaline by taking acetazolamideSome Trade Names
DIAMOX
or potassium citrateSome Trade Names
UROCIT-K
(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. When starting a uricosuric drug, there is a risk of causing a gout attack. Low-dose colchicine or an NSAID is given at the same time for a few months to decrease this risk.

Other Treatments: Most tophi on the ears, hands, or feet shrink slowly when the uric acid level becomes sufficiently low. However, extremely 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 Stones in the Urinary Tract:Stones in the Urinary Tract).

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Drugs Used to Treat Gout Drug Some Side Effects Comments Nonsteroidal anti-inflammatory drugs (NSAIDs) All NSAIDs (see Pain: Nonsteroidal Anti-Inflammatory Drugs) Upset stomach Bleeding Kidney damage High potassium levels Retention of sodium and potassium Sometimes cause swelling or high blood pressure Used to treat an acute (sudden) attack or to prevent an attack Antigout drug Colchicine Diarrhea (occurs often) Suppression of blood cell production in the bone marrow (occurs very rarely if the drug is used properly) Muscle pain and weakness (uncommon) Used to prevent and treat attacks Corticosteroids Prednisone (taken by mouth) Retention of sodium, with swelling or high blood pressure Multiple side effects if used long term Used only if other treatments cannot be used, but the benefit is rapid Prednisolone tebutate or triamcinolone hexacetonideSome Trade Names ARISTOSPAN (taken by injection) Pain Discomfort Joint damage with overuse Inflammation (occasionally) Infection (rarely) Injected into the joint if only one or two joints are affected Uricosuric drugs (drugs that increase uric acid secretion in the urine) Probenecid Sulfinpyrazone Headache Nausea Vomiting Kidney stones Can be used long-term to lower blood levels of uric acid to prevent attack Drugs that block uric acid production AllopurinolSome Trade Names LOPURIN ZYLOPRIM Upset stomach Skin rash Decrease in the number of white blood cells Liver damage (rare) Can be used long-term to lower blood levels of uric acid to prevent attacks and to remove crystals in the body or stones in the kidneys Drugs Used to Treat Gout Drug Some Side Effects Comments Nonsteroidal anti-inflammatory drugs (NSAIDs) All NSAIDs (see Pain: Nonsteroidal Anti-Inflammatory Drugs) Upset stomach Bleeding Kidney damage High potassium levels Retention of sodium and potassium Sometimes cause swelling or high blood pressure Used to treat an acute (sudden) attack or to prevent an attack Antigout drug Colchicine Diarrhea (occurs often) Suppression of blood cell production in the bone marrow (occurs very rarely if the drug is used properly) Muscle pain and weakness (uncommon) Used to prevent and treat attacks Corticosteroids Prednisone (taken by mouth) Retention of sodium, with swelling or high blood pressure Multiple side effects if used long term Used only if other treatments cannot be used, but the benefit is rapid Prednisolone tebutate or triamcinolone hexacetonideSome Trade Names ARISTOSPAN (taken by injection) Pain Discomfort Joint damage with overuse Inflammation (occasionally) Infection (rarely) Injected into the joint if only one or two joints are affected Uricosuric drugs (drugs that increase uric acid secretion in the urine) Probenecid Sulfinpyrazone Headache Nausea Vomiting Kidney stones Can be used long-term to lower blood levels of uric acid to prevent attack Drugs that block uric acid production AllopurinolSome Trade Names LOPURIN ZYLOPRIM Upset stomach Skin rash Decrease in the number of white blood cells Liver damage (rare) Can be used long-term to lower blood levels of uric acid to prevent attacks and to remove crystals in the body or stones in the kidneys

Last full review/revision February 2008 by Daniel J. McCarty, MD