Accumulations of uric acid crystals can intermittently cause severe joint or tissue pain and inflammation.
Doctors diagnose gout when uric acid crystals are seen in fluid removed from an inflamed joint.
Doctors treat acute gout flares with medication that decreases inflammation and relieves pain.
Most people with gout need to take medication, usually for life, that decreases blood levels of uric acid.
Over time, deposits of uric acid decrease, and flares stop 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 is caused by high blood levels of uric acid, a condition called hyperuricemia that often runs in families. High levels of uric acid in the blood result when too little is eliminated by the kidneys or the body produces too much. Although some foods contain high level of purines (chemical compounds that form uric acid when metabolized), most of the uric acid in the blood does not come from diet.
Blood levels of uric acid also 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.
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, to a lesser extent, through the gastrointestinal system.
Abnormally high uric acid levels in the blood occur because of the following:
Most commonly, from decreased elimination of uric acid by the kidneys or by the gastrointestinal system
Sometimes, from consumption of too much purine-rich food, such as shellfish or red meat and/or alcohol, particularly beer
Rarely, from 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, even if kidney function is otherwise normal. 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 shellfish, red meat, 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 and is rarely sufficient therapy for people with gout. In past times, when meat and fish were scarce, gout was considered a rich person’s disease.
Combining a high-purine diet with alcohol (particularly beer) 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 an abnormally high level of uric acid in their blood develop gout.
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, called 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 due to gout is called podagra. However, gout 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 flares of gout, called acute gouty arthritis, can occur without warning. They may be triggered by
Start of treatment with certain medications (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
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 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 sometimes include
A fast heart rate (tachycardia)
A general sick feeling
Chills (very rarely)
The first few flares 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. However, if gout progresses, untreated flares tend to last longer, occur more frequently, and affect several joints. If left untreated, later flares 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) 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 flares, gout can become severe and persistent and may lead to permanent 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 Achilles tendon in the back of the lower leg, 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.
Gout with joint damage increases the risk of developing 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 .
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 in people with gout.
Diagnosis of Gout
Microscopic examination of joint fluid to look for uric acid crystals
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 flares 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. Many people have high levels of uric acid in the blood but do not have symptoms 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 of one or more affected joints to check for uric acid deposits.
Gout may mimic other types of arthritis and is sometimes misdiagnosed.
Prognosis for Gout
With early diagnosis of gout, life-long 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 medications as prescribed, medications that are prescribed at too low a dosage, and having alcohol use disorder Alcohol Alcohol (ethanol) is a depressant. Consuming large amounts rapidly or regularly can cause health problems, including organ damage, coma, and death. Genetics and personal characteristics may... read more .
Treatment of Gout
Medications 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
Medications to prevent flares by preventing inflammation caused by crystals
Medications 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:
Relieve the pain of acute flares
Prevent further flares
Control gout long term to prevent deposits of uric acid in the tissues and eliminate the body's excess uric acid stores by lowering blood levels of uric acid
Relieving acute flares 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 during a gout flare. Sometimes additional pain relievers (called 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 medications 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 of a flare. In some people, 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 begin. A third pill is taken 1 hour later. This therapy is continued the next day by taking 1 pill once or twice a day for 7 to 10 days. Colchicine can cause diarrhea and rarely lower blood counts.
Corticosteroids, such as prednisone, are sometimes used to reduce joint inflammation (including the swelling) in people who cannot tolerate the other medications.
If only one or two joints are affected, a corticosteroid such as prednisolone tebutate along with an anesthetic can be injected into an inflamed joint.
As with NSAID and colchicine therapy, corticosteroids that are taken by mouth should be continued for a few days after the flare fully resolves to prevent relapse.
Sometimes combinations of these medications are given.
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 Chronic Kidney Disease Chronic kidney disease is a slowly progressive (months to years) decline in the kidneys’ ability to filter metabolic waste products from the blood. Major causes are diabetes and high blood pressure... read more or peptic ulcer disease Peptic Ulcer Disease A peptic ulcer is a round or oval sore where the lining of the stomach or duodenum has been eaten away by stomach acid and digestive juices. Peptic ulcers can result from Helicobacter pylori... read more , or if the person is taking certain medications (such as anticoagulant drugs Anticoagulation Pulmonary embolism is the blocking of an artery of the lung (pulmonary artery) by a collection of solid material brought through the bloodstream (embolus)—usually a blood clot (thrombus) or... read more ), some of the usual treatments for gout may not be used or may need to be modified.
In addition to medications, rest, immobilization with a splint, and ice can be used to reduce pain.
Preventing further flares of gout
Preventive daily drug treatment may be needed for people who experience repeated, severe flares. Colchicine may be taken daily to prevent flares or to greatly reduce their frequency. NSAIDs taken daily can also prevent flares. These medications help prevent crystals from causing the inflammation that results in flares. However, colchicine and NSAIDs may cause some side effects and do not prevent excess deposits of uric acid in and around joints.
Although medication is almost always required, the following can help prevent further gout flare-ups:
Avoiding alcoholic beverages (such as beer and liquor) and nonalcoholic beer
Eating smaller amounts of purine-rich foods
Substituting low-fat dairy products for other foods
Changing medications that cause elevated blood levels of uric acid
Most people who have primary gout have overweight. As they gradually lose weight, their blood levels of uric acid often decrease but usually not enough to dissolve the uric acid deposits.
People with gout who take a diuretic to treat high blood pressure Treatment 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 may have fewer flares if they take losartan or a similar medication rather than a diuretic to control their blood pressure. However, preventing flares 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 flares of gout. Also, these alternative medications 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 over time prevent flares.
People with gout who especially need their blood level of uric acid lowered include those who have the following:
Frequent or severe flares (more than 2 per year) or continuing need for colchicine, an NSAID, or both to prevent flares
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 Peptic Ulcer Disease A peptic ulcer is a round or oval sore where the lining of the stomach or duodenum has been eaten away by stomach acid and digestive juices. Peptic ulcers can result from Helicobacter pylori... read more , 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 , treatment with anticoagulants Anticoagulation Pulmonary embolism is the blocking of an artery of the lung (pulmonary artery) by a collection of solid material brought through the bloodstream (embolus)—usually a blood clot (thrombus) or... read more (blood thinners), and chronic kidney disease Chronic Kidney Disease Chronic kidney disease is a slowly progressive (months to years) decline in the kidneys’ ability to filter metabolic waste products from the blood. Major causes are diabetes and high blood pressure... read more )
People taking medications 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 is maintained at less than 6 milligrams per deciliter (0.4 millimoles per litre).
Medications 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 therefore 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 medication 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 Overview of Vasculitis Vasculitic disorders are caused by inflammation of the blood vessels (vasculitis). Vasculitis can be triggered by certain infections or drugs or can occur for unknown reasons. People may have... read more ). Allopurinol, like all uric acid lowering drugs, can trigger acute flares when it is first taken (mobilization flare Mobilization flares 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 flares (attacks)... 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 about 6 months or longer if flares continue or tophi are present.
Febuxostat is another medication 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, flares can occur as the uric acid level in the blood first decreases.
Pegloticase is a specialized medication 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 quickly and become less visible over months. However, many people develop antibodies that prevent this medication from continuing to work. Doctors may give immunosuppressive medications to prevent this from happening.
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 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 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 medications 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 medications can decrease uric acid slightly 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 (mobilization flare). Mobilization flares are particularly likely soon after a medication that lowers the blood level of uric acid is started. A mobilization flare may be a sign that a medication is working well to decrease uric acid levels.
During a mobilization flare, people should not stop taking the medications that decrease the uric acid level.
Low-dose colchicine or an NSAID can be given for a few months after starting the medication to lower the uric acid level to help prevent mobilization flares.