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 to confirm the diagnosis of gouty arthritis.
Drugs are given to relieve inflammation and pain resulting from flares, and different drugs (usually taken for life) are used to decrease blood levels of uric acid which, over time, decreases the deposits of uric acid and stops flares from recurring.
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 Metabolic Syndrome Metabolic syndrome is characterized by a large waist circumference (due to excess abdominal fat), high blood pressure, resistance to the effects of insulin (insulin resistance) or diabetes,... read more . 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 Overview of Coronary Artery Disease (CAD) Coronary artery disease is a condition in which the blood supply to the heart muscle is partially or completely blocked. The heart muscle needs a constant supply of oxygen-rich blood. The coronary... read more and metabolic syndrome Metabolic Syndrome Metabolic syndrome is characterized by a large waist circumference (due to excess abdominal fat), high blood pressure, resistance to the effects of insulin (insulin resistance) or diabetes,... read more are common among people with gout.
Causes of Gout
Uric acid is a by-product of the breakdown of the nucleic acids (ribonucleic acid [ RNA Transcription and translation Genes are segments of deoxyribonucleic acid (DNA) that contain the code for a specific protein that functions in one or more types of cells in the body. Chromosomes are structures within cells... read more ] and deoxyribonucleic acid [ DNA DNA Genes are segments of deoxyribonucleic acid (DNA) that contain the code for a specific protein that functions in one or more types of cells in the body. Chromosomes are structures within cells... read more ]) in cells. It 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. Uric acid is removed from the blood mainly through the kidneys and through the gastrointestinal system.
Abnormally high uric acid levels in the blood result from
Decreased elimination of uric acid by the kidneys (most common cause) or gastrointestinal system
Consumption of too much purine-rich food and/or alcohol (usually a smaller factor)
Production of too much uric acid (rarely)
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
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 especially 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 an abnormally high level of uric acid in the blood (hyperuricemia) develop gout. Thus, gout should not be diagnosed by blood test alone.
Did You Know...
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
Start of treatment with certain drugs (such as diuretics, allopurinol, febuxostat, probenecid, and nitroglycerin, particularly nitroglycerin given by vein, which contains alcohol) that may suddenly change the uric acid level in the blood (but often those drugs are medically necessary)
Consumption of large quantities of alcohol or purine-rich food
Symptoms of Gout
Typically during a flare, 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
A fast heart rate (tachycardia)
A general sick feeling
Chills (very rarely)
The first few flare-ups usually affect only one joint and last for a few days to a week.
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. A person with a flare who has fever higher than 101° F (38.3° C), shaking chills, or any other severe symptoms (for example, weakness, vomiting, a rash, or any shortness of breath), especially if not experienced with previous flares or if it is the first flare, should call the doctor or go to an emergency department, because these symptoms can also be from a joint infection or a different problem entirely.
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.
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 Osteoarthritis (OA) Osteoarthritis is a chronic disorder that causes damage to the cartilage and surrounding tissues and is characterized by pain, stiffness, and loss of function. Arthritis due to damage of joint... read more .
Complications of gout
People who have gout may develop kidney stones (urolithiasis Stones in the Urinary Tract Stones (calculi) are hard masses that form in the urinary tract and may cause pain, bleeding, or an infection or block of the flow of urine. Tiny stones may cause no symptoms, but larger stones... read more ) that are composed of calcium and sometimes 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 Diabetes Mellitus (DM) Diabetes mellitus is a disorder in which the body does not produce enough or respond normally to insulin, causing blood sugar (glucose) levels to be abnormally high. Urination and thirst are... read more or high blood pressure High Blood Pressure High blood pressure (hypertension) is persistently high pressure in the arteries. Often no cause for high blood pressure can be identified, but sometimes it occurs as a result of an underlying... read more ), increasingly poor kidney function reduces the excretion of uric acid and makes the gout and its joint damage progressively worse.
Diagnosis of Gout
Microscopic examination of joint fluid
Sometimes x-rays and/or ultrasonography or special CT scans
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 may be 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; therefore, a blood test alone is not sufficient for diagnosis.
The diagnosis of gout is usually confirmed when uric acid crystals are identified in a sample of a tophus or in joint fluid removed with a needle (joint aspiration Joint aspiration (arthrocentesis) A doctor can often diagnose a musculoskeletal disorder based on the history and the results of a physical examination. Laboratory tests, imaging tests, or other diagnostic procedures are sometimes... read more ) and viewed under a special microscope with polarized light.
X-rays X-rays A doctor can often diagnose a musculoskeletal disorder based on the history and the results of a physical examination. Laboratory tests, imaging tests, or other diagnostic procedures are sometimes... read more may show joint damage and the presence of tophi. Doctors may also do ultrasonography Ultrasonography A doctor can often diagnose a musculoskeletal disorder based on the history and the results of a physical examination. Laboratory tests, imaging tests, or other diagnostic procedures are sometimes... read more or a special CT scan to check for uric acid deposits.
Gout may mimic and is sometimes misdiagnosed as another type of arthritis.
Prognosis of Gout
With early diagnosis of gout, 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 Metabolic Syndrome Metabolic syndrome is characterized by a large waist circumference (due to excess abdominal fat), high blood pressure, resistance to the effects of insulin (insulin resistance) or diabetes,... read more and coronary artery disease Overview of Coronary Artery Disease (CAD) Coronary artery disease is a condition in which the blood supply to the heart muscle is partially or completely blocked. The heart muscle needs a constant supply of oxygen-rich blood. The coronary... read more 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 of Gout
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 (most effective way to cure gout and end flares, but it takes time to dissolve all of the deposits)
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 Nonsteroidal Anti-Inflammatory Drugs Pain relievers (analgesics) are the main drugs used to treat pain. Doctors choose a pain reliever based on the type and duration of pain and on the drug's likely benefits and risks. Most pain... read more (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). Concerns with these drugs relate to irritation of the stomach, interactions with blood thinners, and temporary decrease in kidney function.
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. Colchicine can cause diarrhea.
Corticosteroids, such as prednisone, are sometimes used 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 for a few days 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, particular drugs that suppress the immune system and inflammatory system (such as anakinra daily injections) 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 prevent further gout flare-ups:
Avoiding alcoholic beverages (such as beer and liquor) and nonalcoholic beer
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 decrease but usually not enough to dissolve the uric acid deposits.
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. Most importantly, diuretics may be necessary to control blood pressure and prevent strokes or heart attacks.
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 prevent flare-ups.
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 that are found on examination
Uric acid kidney stones
Conditions that make NSAIDs or corticosteroids more complicated to take (such as peptic ulcer disease, diabetes, treatment with blood thinners, 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 (0.4 millimoles per litre). If the blood level is maintained below 6 [0.4], uric acid will stop being deposited in the joints and in soft tissues, and the existing deposits will eventually dissolve, although this may take several years. Most tophi on the ears, hands, or feet shrink slowly when the uric acid level decreases to less than 6 milligrams per deciliter (0.4 millimoles per litre).
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. The lower the blood uric acid level, the faster the deposits will dissolve. As the deposits start to dissolve (mobilize), crystals can be released and cause mobilization flares. These flares are a sign that the drugs are working and should not be stopped. These drugs may be used long-term or for a person's lifetime.
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 can trigger an acute flare-up when it is first taken (mobilization flare-up Mobilization flare-ups 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 ... read more ). 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 a specialized drug that is used to lower blood levels of uric acid dramatically in people with severe gout. 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. If people respond to pegloticase, deposits, including tophi, may begin to dissolve and become less visible over months.
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 is a uricosuric drug, usually taken twice a day and may be combined with either allopurinol or febuxostat.
Aspirin can block the effects of probenecid, but 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 very slightly increase levels of uric acid (hyperuricemia), but this is generally not a problem. Similarly, hydrochlorothiazide can increase slightly the blood level of uric acid, but if it is effective in reducing blood pressure it should generally be continued while other drugs are used to lower the uric acid blood level.
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.
Any treatment that decreases levels of uric acid in the blood can trigger an acute flare-up (mobilization flare-up). Mobilization flare-ups are particularly likely soon after a drug that lowers the blood level of uric acid 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 starting the drug to lower the uric acid level to help prevent mobilization flare-ups.