What Is Gout?
Gout is a painful condition that occurs when the bodily waste product uric acid is deposited as needle-like crystals in the joints and/or soft tissues. In the joints, these uric acid crystals cause inflammatory arthritis, which in turn leads to intermittent swelling, redness, heat, pain, and stiffness in the joints.
In many people, gout initially affects the joints of the big toe. But many other joints and areas around the joints can be affected in addition to or instead of the big toe. These include the insteps, ankles, heels, knees, wrists, fingers, and elbows. Chalky deposits of uric acid, also known as tophi, can appear as lumps under the skin that surrounds the joints and covers the rim of the ear. Uric acid crystals can also collect in the kidneys and cause kidney stones.
What Is Uric Acid?
Uric acid is a substance that results from the breakdown of purines. A normal part of all human tissue, purines are found in many foods. Normally, uric acid is dissolved in the blood and passed through the kidneys into the urine, where it is eliminated.
If there is an increase in the production of uric acid or if the kidneys do not eliminate enough uric acid from the body, levels of it build up in the blood (a condition called hyperuricemia). Hyperuricemia also may result when a person eats too many high-purine foods, such as liver, dried beans and peas, anchovies, and gravies. Hyperuricemia is not a disease, and by itself it is not dangerous. However, if excess uric acid crystals form as a result of hyperuricemia, gout can develop. The crystals form and accumulate in the joint, causing inflammation.
What Are the Four Stages of Gout?
Gout can progress through four stages:
- Asymptomatic (without symptoms) hyperuricemia.In this stage, a person has elevated levels of uric acid in the blood (hyperuricemia), but no other symptoms. Treatment is usually not required.
- Acute gout or acute gouty arthritis.In this stage, hyperuricemia has caused the deposit of uric acid crystals in joint spaces. This leads to a sudden onset of intense pain and swelling in the joints, which also may be warm and very tender. An acute attack commonly occurs at night and can be triggered by stressful events, alcohol or drugs, or the presence of another illness. Attacks usually subside within 3 to 10 days, even without treatment, and the next attack may not occur for months or even years. Over time, however, attacks can last longer and occur more frequently.
- Interval or intercritical gout.This is the period between acute attacks. In this stage, a person does not have any symptoms.
- Chronic tophaceous gout.This is the most disabling stage of gout. It usually develops over a long period, such as 10 years. In this stage, the disease may have caused permanent damage to the affected joints and sometimes to the kidneys. With proper treatment, most people with gout do not progress to this advanced stage.
When It’s Not Gout, It May Be Pseudogout
Gout is sometimes confused with other forms of arthritis because the symptoms—acute and episodic attacks of joint warmth, pain, swelling, and stiffness—can be similar. One form of arthritis often confused with gout is called pseudogout or calcium pyrophosphate deposition (CPPD). The pain, swelling, and redness of pseudogout can also come on suddenly and may be severe, closely resembling the symptoms of gout. However, the crystals that irritate the joint are calcium phosphate crystals, not uric acid. Therefore, pseudogout is treated somewhat differently and is not reviewed in this publication.
What Causes Gout?
A number of risk factors are associated with hyperuricemia and gout. They include:
- Many people with gout have a family history of the disease. Estimates range from 20 to 80 percent.
- Gender and age.It is more common in men than in women and more common in adults than in children.
- Being overweight increases the risk of developing hyperuricemia and gout because there is more tissue available for turnover or breakdown, which leads to excess uric acid production.
- Alcohol consumption.Drinking too much alcohol can lead to hyperuricemia, because alcohol interferes with the removal of uric acid from the body.
- Eating too many foods that are rich in purines can cause or aggravate gout in some people.
- Lead exposure.In some cases, exposure to lead in the environment can cause gout.
- Other health problems.Renal insufficiency, or the inability of the kidneys to eliminate waste products, is a common cause of gout in older people. Other medical problems that contribute to high blood levels of uric acid include:
- high blood pressure
- hypothyroidism (underactive thyroid gland)
- conditions that cause an excessively rapid turnover of cells, such as psoriasis, hemolytic anemia, or some cancers
- Kelley-Seegmiller syndrome or Lesch-Nyhan syndrome, two rare conditions in which the enzyme that helps control uric acid levels either is not present or is found in insufficient quantities.
- A number of medications may put people at risk for developing hyperuricemia and gout. They include:
- Diuretics,which are taken to eliminate excess fluid from the body in conditions like hypertension, edema, and heart disease, and which decrease the amount of uric acid passed in the urine
- Salicylate-containing drugs,such as aspirin
- Niacin,a vitamin also known as nicotinic acid
- Cyclosporine,a medication that suppresses the body’s immune system (the system that protects the body from infection and disease). This medication is used in the treatment of some autoimmune diseases, and to prevent the body’s rejection of transplanted organs.
- Levodopa,a medicine used to support communication along nerve pathways in the treatment of Parkinson’s disease.
Who Is Likely to Develop Gout?
Scientists estimate that 6 million adults age 20 and older report having had gout at some time in their lives.1 It is rare in children and young adults. Men, particularly those between the ages of 40 and 50, are more likely to develop gout than women, who rarely develop the disorder before menopause. People who have had an organ transplant are more susceptible to gout.
1According to the National Arthritis Data Workgroup, this estimate is based on self-reports, which may produce an overestimation of prevalence, as cited in Helmick CG, Felson DT, Lawrence RC, Gabriel S, Hirsch R, Kwoh CK, et al.; National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part 1. Arthritis and Rheumatism 2008;1:15-25.
Gout is caused by a combination of genetic and environmental factors. Some of the factors that contribute to this condition have been confirmed by research, while others are unknown. The main risk factor for developing gout is hyperuricemia. About one-quarter of individuals with hyperuricemia go on to develop gout. It is unclear why others with hyperuricemia do not get gout.
Large studies have identified dozens of genes that play a role in the development of gout. Multiple genetic changes, each with a small effect, likely combine to increase the risk of developing this disorder. Most of the known genes play a role in transporting urate, which is a byproduct of normal biochemical processes. Many gout-associated genes play a role in releasing urate into the urine if levels are too high or reabsorbing it back into the bloodstream if more is needed in the body. Other associated genes are involved in transporting or breaking down sugars or transporting other small molecules. The roles of some associated genes are unclear. Of all the genes that have been studied, two genes, SLC2A9 and ABCG2, seem to have the greatest influence on urate levels.
The SLC2A9 gene provides instructions for making a protein that is found primarily in the kidneys where it plays a role in managing the body’s levels of urate. This protein helps reabsorb urate into the bloodstream or release it into the urine. Genetic changes in the SLC2A9 gene that can result in hyperuricemia increase the reabsorption of urate into the bloodstream and decrease its release into the urine.
The ABCG2 gene provides instructions for making a protein that helps release urate into the gut so that it can be removed from the body. Genetic changes in the ABCG2 gene that can result in hyperuricemia reduce the protein’s ability to release urate into the gut.
Nongenetic factors are also believed to play a role in gout, primarily by triggering flares. These factors also often increase urate levels in the body. Consuming foods and beverages that are high in molecules called purines, such as red meat, seafood, dried beans, alcohol, and sugar-sweetened beverages can lead to increased urate. When purines are broken down, urate is made, which can cause hyperuricemia and lead to gout in some individuals. The risk for gout also increases with age. In particular, women have an increased risk after menopause. Following menopause, production of the hormone estrogen, which plays a role in removing urate from the body, declines so older women have a rise in urate levels and an increased risk of developing gout.
How Is Gout Diagnosed?
Gout may be difficult for doctors to diagnose because the symptoms can be vague, and gout often mimics other conditions. Although most people with gout have hyperuricemia at some time during the course of their disease, it may not be present during an acute attack. In addition, having hyperuricemia alone does not mean that a person will get gout. In fact, most people with hyperuricemia do not develop the disease.
To confirm a diagnosis of gout, a doctor may insert a needle into an inflamed joint and draw a sample of synovial fluid, the substance that lubricates a joint. The joint fluid is placed on a slide and examined under a microscope for uric acid crystals. Their absence, however, does not completely rule out the diagnosis.
The doctor also may find it helpful to look for uric acid crystals around joints to diagnose gout. Gout attacks may mimic joint infections, and a doctor who suspects a joint infection (rather than gout) may also culture the joint fluid to see whether bacteria are present.
Signs and Symptoms of Gout
- presence of uric acid crystals in joint fluid
- more than one attack of acute arthritis
- arthritis that develops in a day, producing a swollen, red, and warm joint
- attack of arthritis in only one joint, often the toe, ankle, or knee.
How Is Gout Treated?
With proper treatment, most people who have gout are able to control their symptoms and live productive lives. Gout can be treated with one or a combination of therapies. The goals of treatment are to ease the pain associated with acute attacks, to prevent future attacks, and to avoid the formation of tophi and kidney stones. Successful treatment can reduce discomfort caused by the symptoms of gout, as well as long-term damage to the affected joints. Treatment will help to prevent disability due to gout.
The most common treatments for an acute attack of gout are nonsteroidal anti-inflammatory drugs (NSAIDs)2, 3taken orally (by mouth), or corticosteroids, which are taken orally or injected into the affected joint. NSAIDs reduce the inflammation caused by deposits of uric acid crystals, but have no effect on the amount of uric acid in the body.
2All medicines can have side effects. Some side effects may be more severe than others. You should review the package insert that comes with your medicine and ask your health care provider or pharmacist if you have any questions about the possible side effects.
3 Warning: Side effects of NSAIDs include stomach problems; skin rashes; high blood pressure; fluid retention; and liver, kidney, and heart problems. The longer a person uses NSAIDs, the more likely he or she is to have side effects, ranging from mild to serious. Many other drugs cannot be taken when a patient is being treated with NSAIDs, because NSAIDs alter the way the body uses or eliminates these other drugs. Check with your health care provider or pharmacist before you take NSAIDs. NSAIDs should only be used at the lowest dose possible for the shortest time needed.
Corticosteroids are strong anti-inflammatory hormones. The most commonly prescribed corticosteroid is prednisone. Patients often begin to improve within a few hours of treatment with a corticosteroid, and the attack usually goes away completely within a week or so.
When NSAIDs or corticosteroids do not control symptoms, the doctor may consider using colchicine. The doctor also may consider prescribing other medicines to treat hyperuricemia and reduce the frequency of sudden attacks and the development of tophi.
People who have other medical problems, such as high blood pressure or high blood triglycerides (fats), may find that the drugs they take for those conditions can also be useful for gout.
The doctor may also recommend losing weight, for those who are overweight; limiting alcohol consumption; and avoiding or limiting high-purine foods, which can increase uric acid levels.
What Can People With Gout Do to Stay Healthy?
Fortunately, gout can be controlled. People with gout can decrease the severity of attacks and reduce their risk of future attacks by taking their medications as prescribed. Acute gout is best controlled if medications are taken at the first sign of pain or inflammation. Other steps you can take to stay healthy and minimize gout’s effect on your life include the following:
- Tell your doctor about all the medicines and vitamins you take. He or she can tell you if any of them increase your risk of hyperuricemia.
- Plan follow-up visits with your doctor to evaluate your progress.
- Drink plenty of nonalcoholic fluids, especially water. Nonalcoholic fluids help remove uric acid from the body. Alcohol, on the other hand, can raise the levels of uric acid in your blood.
- Exercise regularly and maintain a healthy body weight. Lose weight if you are overweight, but avoid low-carbohydrate diets that are designed for quick weight loss. When carbohydrate intake is insufficient, your body can’t completely burn its own fat. As a consequence, substances called ketones form and are released into the bloodstream, resulting in a condition called ketosis. After a short time, ketosis can increase the level of uric acid in your blood.
- Avoid foods that are high in purines, such as:
- beef kidneys
- dried beans and peas
- game meats
What Research Is Being Conducted on Gout?
Because uric acid’s role in gout is well understood and medications to ease attacks and reduce the risk or severity of future attacks are widely available, gout is one of the most—if not the most—controllable forms of arthritis. But researchers continue to make advances that help people live with gout. Perhaps someday these advances will prevent this extremely painful disease.
Some current areas of gout research include the following:
- Refining current treatments.Although many medications are available to treat gout, doctors are trying to determine which of the treatments are most effective and at which dosages. Recent studies have compared the effectiveness of different pharmaceuticals in treating the pain and inflammation of gout and have looked at the optimal dosages of other treatments to control and/or prevent painful attacks.
- Evaluating new therapies.A number of new therapies have shown promise in recent studies including biologic agents.
- Discovering the role of foods.Gout is the one form of arthritis for which there is proof that specific foods worsen the symptoms. Research is suggesting that certain foods may also prevent gout. In one study scientists found that a high intake of low-fat dairy products reduces the risk of gout in men by half. The reason for this protective effect is not yet known. Another study examining the effects of vitamin C on uric acid suggests that it may be beneficial in the prevention and management of gout and other diseases that are associated with uric acid production.
- Searching for new treatment approaches.Scientists are also studying the contributions of different types of cells that participate in both the acute and chronic joint manifestations of gout. The specific goals of this research are to better understand how urate crystals activate white blood cells called neutrophils, leading to acute gout attacks; how urate crystals affect the immune system, leading to chronic gout; and how urate crystals interact with bone cells in a way that causes debilitating bone lesions among people with chronic gout. The hope is that a better understanding of the various inflammatory reactions that occur in gout will provide innovative clues for treatment.
- Examining how genetics and environmental factors can affect hyperuricemia.Researchers are studying different populations in which gout is prevalent to determine how certain genes and environmental factors may affect blood levels of uric acid, which can leak out and crystallize in the joint, leading to gout.
Corticosteroids. Powerful anti-inflammatory hormones made naturally in the body or man-made for use as medicine. Injections of corticosteroid drugs are sometimes used to treat inflammation in the shoulder, knee, and other joints.
Diuretics. A type of medication that promotes the formation and output of urine. Diuretics are prescribed to treat the accumulation of excess fluid in bodily tissues that can result from diseases of the kidneys, liver, lungs, or heart. They may also be used to treat high blood pressure or glaucoma, a condition in which pressure builds up inside the eye.
Hemolytic anemia. A form of anemia (deficiency of red blood cells) caused by the destruction of the cells rather than the body’s inability to produce them in adequate numbers.
Hyperuricemia. The presence of elevated levels of uric acid in the blood.
Hypothyroidism. A condition in which the thyroid gland (the gland that makes and stores hormones that regulate heart rate, blood pressure, body temperature, and the rate at which food is converted to energy) is underactive. Without treatment, this condition can result in fatigue, weight gain, other serious medical problems, and even death.
NSAIDs. A class of medications, available over the counter or with a prescription, that ease pain and inflammation.
Podagra. Gout in the big toe.
Pseudogout. A condition often mistaken for gout that results from the deposit of calcium phosphate crystals (not uric acid crystals as in gout) in the joints and other tissues. This condition is also called chondrocalcinosis.
Psoriasis. An autoimmune disease characterized by a red scaly rash that is often located over the surfaces of the elbows, knees, and scalp, and around or in the ears, navel, genitals, or buttocks. Approximately 10 to 15 percent of people with psoriasis develop an associated arthritis referred to as psoriatic arthritis.
Purines. Found in the DNA and RNA within the nuclei of cells, purines are part of all human tissue and are found in many foods, especially those high in protein.
Synovial fluid. The slippery fluid produced by the synovium (joint lining) to lubricate the joints.
Tophi. Nodular masses of uric acid crystals that sometimes form in the soft tissue of people with chronic gout. Although tophi are most common around the fingers, elbows, and big toe, they can occur in virtually any part of the body. (The singular is tophus.)
Uric acid. A substance that results from the breakdown of purines, which are part of all human tissue and are found in many foods.