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Gout

By

N. Lawrence Edwards

, MD, Department of Medicine, University of Florida College of Medicine

Last full review/revision May 2018| Content last modified May 2018
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Gout is a disorder in which deposits of uric acid crystals accumulate in the joints because of high blood levels of uric acid (hyperuricemia). The accumulations of crystals cause flare-ups (attacks) of painful inflammation in and around joints.

  • Accumulations of uric acid crystals 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 flare-ups, and sometimes decrease blood levels of uric acid to decrease deposits of urate crystals in the 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, caused by high blood levels of uric acid (hyperuricemia), often runs in families.

Blood levels of uric acid tend to be high in people with metabolic syndrome. This syndrome is characterized by a large waist (due to excess abdominal fat), high blood pressure, resistance to the effects of insulin (called insulin resistance) or high blood sugar levels, and abnormal levels of cholesterol and other fats in the blood.

Coronary artery disease and metabolic syndrome are common among people with gout.

Causes

Normally, uric acid, which is a by-product of the breakdown of the nucleic acids (ribonucleic acid [RNA] and deoxyribonucleic acid [DNA]) in the cells, 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 building blocks of RNA and DNA.

Abnormally high uric acid levels in the blood result from

  • Decreased elimination of uric acid by the kidneys (most common cause)

  • Consumption of too much purine-rich food and/or alcohol

  • Production of too much uric acid

Most often, the uric acid level in the blood becomes abnormally high when the kidneys cannot eliminate enough uric acid in the urine. This cause is usually determined by the person's genes. Too much uric acid in the blood can result in uric acid crystals being formed and deposited in and around joints. Conditions that can impair the kidneys’ ability to eliminate uric acid also include

  • Some types of kidney disease

  • Certain drugs

  • Lead poisoning

Consuming too much purine-rich food (such as liver, kidney, anchovies, asparagus, consommé, herring, meat gravies and broths, mushrooms, mussels, sardines, and sweetbreads) can increase the uric acid level in blood. However, a strict low-purine diet lowers the uric acid level by only a small amount. In past times, when meat and fish were scarce, gout was considered a rich person’s disease.

Combining a high-purine diet with alcohol or beverages containing high-fructose corn syrup can worsen matters because all of these beverages can increase the production of uric acid and interfere with its elimination by the kidneys.

For unknown reasons, not all people who have hyperuricemia develop gout.

Risk Factors for the Development of Gout

Did You Know...

  • In past times, when meat and fish (purine-rich foods) were scarce, gout was considered a rich person’s disease.

Less commonly, another disorder causes the body to produce too much uric acid. (Gout caused by another disorder is called secondary gout.) These disorders include

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 (swelling, pain, and redness of the big toe is called 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 flare-ups (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

  • Start of treatment with certain drugs (such as allopurinol, febuxostat, probenecid, and nitroglycerin, particularly nitroglycerin given by vein, which contains alcohol) that may suddenly change the uric acid level in the blood

  • Consumption of large quantities of alcohol or purine-rich food

Symptoms

Typically, severe pain occurs suddenly in one or more joints, often at night. The nighttime pain occurs probably because fluid that has built up in the joint during the daytime leaves the joint faster than uric acid does when a person lies down, making the uric acid more concentrated and thus more ready to form crystals. 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 a flare-up sometimes include

  • Fever (which may reach 102° F [38.9° C])

  • A fast heart rate (tachycardia)

  • A general sick feeling

  • Chills (rarely)

The first few flare-ups 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 flare-up. However, if the disorder progresses, untreated flare-ups last longer, occur more frequently, and affect several joints. If left untreated, later flare-ups can last up to 3 weeks.

After repeated flare-ups, gout can become severe and persistent 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.

Tophi

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 in and around the joints can burst and discharge chalky masses of uric acid crystals through the skin and may eventually cause deformities and osteoarthritis.

Complications of gout

About 20% of people who have gout develop kidney stones (urolithiasis) that are composed of uric acid. 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.

Chronic gout increases the risk of developing osteoarthritis.

Diagnosis

  • Microscopic examination of joint fluid

  • Sometimes x-rays and/or ultrasonography or magnetic resonance imaging (MRI)

Doctors suspect gout on the basis of its distinctive symptoms and an examination of the affected joints. The following suggest the diagnosis of gout:

  • Podagra (sudden swelling, pain, and redness of the big toe)

  • Recurring instep inflammation

  • A history of previous flare-ups that began suddenly and resolved spontaneously

Many people with gout have a high level of uric acid in the blood. However, the uric acid level is often normal, especially during an acute flare-up. Many people have high levels of uric acid in the blood but do not have flare-ups of gout.

The diagnosis of gout 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 special microscope with polarized light.

X-rays may show joint damage and the presence of tophi. Doctors may also do ultrasonography or MRI to check for uric acid deposits.

Gout is often similar to and sometimes misdiagnosed as another type of arthritis.

Prognosis

With early diagnosis, treatment enables most people to live a normal life. For many people with advanced disease, significant lowering of the levels of uric acid in the blood can resolve tophi and improve joint function.

Gout is generally more severe in people whose initial symptoms appear before age 30. Metabolic syndrome and coronary artery disease probably contribute to premature death in people with gout.

Some people do not improve sufficiently with treatment. The reasons can include failure to take drugs as prescribed, drugs are prescribed at too low a dosage, and alcoholism.

Treatment

  • Drugs to relieve pain and swelling resulting from inflammation

  • Rest, immobilization of a painful joint with a splint, and ice

  • Dietary changes and weight loss to lower the uric acid levels and help prevent further flare-ups

  • Drugs to prevent flare-ups by preventing inflammation caused by crystals

  • Drugs to lower uric acid levels and dissolve the crystals

Gout treatment has three goals:

  • Relieving the acute flare-up of inflammation

  • Preventing further flare-ups

  • Preventing further deposition of uric acid in the tissues by lowering blood levels of uric acid

Relieving acute flare-ups of gout

Nonsteroidal anti-inflammatory drugs (NSAIDs) are often effective in relieving pain and swelling in the joint. Sometimes additional pain relievers (analgesics) are needed to control pain.

Treatment with NSAIDs should be continued for several days after the pain and inflammation have resolved to prevent them from appearing again (a condition called 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 usually as 2 pills as soon as possible after symptoms of a flare-up begin. A third pill is taken 1 hour later. This therapy is continued the next day by taking 1 pill daily or twice daily for 7 to 10 days.

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 and colchicine therapy, corticosteroids that are taken by mouth should be continued until after the flare-up fully resolves to prevent relapse.

Sometimes combinations of these drugs are given.

In addition to NSAIDs, colchicine, 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 and inflammatory system (such as anakinra) can be used. If there are underlying problems, such as chronic kidney disease or peptic ulcer disease, or if the person is taking certain drugs (such as anticoagulant drugs), the usual treatments for gout may not be used or may need to be modified.

Preventing further flare-ups of gout

The following can help:

  • Avoiding alcoholic beverages (such as beer and liquor) and nonalcoholic beer

  • Losing weight

  • Changing drugs that cause elevated blood levels of uric acid

  • Eating smaller amounts of purine-rich foods

  • Substituting low-fat dairy products for other foods

But these measures are rarely 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 flare-ups subsequently cease.

Preventive daily drug treatment may be needed for people who experience repeated, severe flare-ups. Colchicine may be taken daily to prevent flare-ups or to greatly reduce their frequency. NSAIDs taken daily can also prevent flare-ups. These drugs help prevent crystals from causing the inflammation that results in flare-ups. However, colchicine and NSAIDs may cause some side effects.

People with gout who take a diuretic (such as hydrochlorothiazide) to treat high blood pressure may have fewer flare-ups if they take losartan or a similar drug rather than a diuretic to control their blood pressure. However, preventing flare-ups by switching from a diuretic to losartan or another drug to treat high blood pressure does not prevent or heal existing joint damage caused by uric acid crystals because the crystals are still in the joints between flare-ups of gout. Also, these alternative drugs may have side effects.

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. Lowering the level of uric acid in the blood helps dissolve deposits of uric acid in the tissues and prevents future flare-ups as well as chronic damage to the kidneys and joints.

People with gout who especially need their blood level of uric acid lowered include those who have the following:

  • Frequent, severe flare-ups (more than 2 per year) despite taking colchicine, an NSAID, or both

  • Tophi

  • 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 people 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 in 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 sometimes cause a rash, decrease the number of white blood cells, or cause liver damage or inflammation of vessels (vasculitis). Allopurinol also can trigger an acute flare-up when it is first taken (mobilization flare-up). Because low-dose colchicine or an NSAID can decrease this risk, one of these drugs is usually given at the time allopurinol (or febuxostat) is started and continued for a few months.

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, flare-ups can occur as the uric acid level in the blood first decreases.

Pegloticase is another drug that is used to lower blood levels of uric acid. It is given by intravenous infusion every 2 weeks and is used primarily in people who have long-standing gout that has not been successfully treated with other therapies. Pegloticase is not used with other drugs that lower blood levels of uric acid.

Uricosuric drugs (drugs that increase excretion of uric acid in the urine) also can be used to lower the levels of uric acid in the blood in people who have normal kidney function. Probenecid and lesinurad are uricosuric drugs.

Probenecid is taken more than once a day and may be combined with either allopurinol or febuxostat.

Lesinurad is taken daily and needs to be taken with either allopurinol or febuxostat.

Aspirin can block the effects of probenecid, and high doses of aspirin should not be used at the same time. Low doses that protect the heart (81 milligrams daily) should be continued because coronary artery disease is a considerable risk in people with gout. Low doses of aspirin may further increase high blood levels of uric acid (hyperuricemia) but only a little bit.

The blood pressure–lowering drug losartan and the triglyceride–lowering drug fenofibrate both cause uric acid to be excreted in the urine. These drugs can decrease uric acid in people who are taking them for other reasons.

Mobilization flare-ups

Any treatment that decreases levels of uric acid in the blood can trigger an acute flare-up (sometimes called a mobilization flare-up). Mobilization flare-ups are particularly likely soon after a drug is started. A mobilization flare-up may be a sign that a drug is working well to decrease uric acid levels.

During a mobilization flare-up, 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 to help prevent or treat mobilization flare-ups.

Other treatments

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 basic (alkaline) or less acidic by taking acetazolamide or potassium citrate (which helps uric acid dissolve 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 and, less often, calcium phosphate—may form.

Most tophi on the ears, hands, or feet shrink slowly when the uric acid level becomes sufficiently low (less than 6 milligrams per deciliter).

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 Removing a Stone With Sound Waves).

Table
icon

Drugs Used to Treat Gout

Drug

Some Side Effects

Comments

Nonsteroidal anti-inflammatory drugs (NSAIDs)

All NSAIDs

Upset stomach

Bleeding

Kidney damage

High potassium levels

Retention of sodium and potassium

Swelling or high blood pressure (sometimes)

Used to treat an acute (sudden) flare-up (attack) or to prevent a flare-up

Antigout drugs

Colchicine

Upset stomach and diarrhea

Suppression of blood cell production in the bone marrow (occurs very rarely if the drug is used properly)

Muscle pain and weakness (uncommon)

Interaction with many other drugs, sometimes causing severe side effects

Used to prevent and treat flare-ups

Corticosteroids

Prednisone (taken by mouth)

Retention of sodium, with swelling or high blood pressure

Multiple side effects if used long-term

Used to treat acute flare-ups

Prednisolone tebutate or triamcinolone hexacetonide (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

Rash

Nausea

Vomiting

Kidney stones

Can be used long-term to lower blood levels of uric acid to prevent flare-ups

Lesinurad

Kidney problems

Must be used with allopurinol or febuxostat

Drugs that block uric acid production

Allopurinol

Upset stomach

Rash (which can be serious)

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 flare-ups and to remove crystals in the body or stones in the kidneys

Febuxostat

Nausea

Joint pains

Rash

Especially useful in patients who cannot take or have not been helped by high doses of allopurinol

Pegloticase

Bruising

Constipation

Nausea and vomiting

High risk of mobilization flare-up

Allergic reactions

Can be used long-term to treat long-standing gout

Drugs Mentioned In This Article

Generic Name Select Brand Names
MICROZIDE
KENALOG
DIAMOX
NITRO-DUR
NEORAL, SANDIMMUNE
No US brand name
ORAPRED, PRELONE
KRYSTEXXA
ZYLOPRIM
ULORIC
COLCRYS
RAYOS
MYAMBUTOL
KINERET
COZAAR
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