Patient education: Gout (Beyond the Basics)

GOUT OVERVIEW — Gout is a form of arthritis. Like other types of arthritis, it causes pain and swelling in the joints. Gout develops in some people who chronically have a condition called "hyperuricemia," meaning high levels of urate (also known as uric acid) in the blood. In gout, urate forms crystals that build up in different parts of the body and cause symptoms such as joint swelling and pain. Not everyone with hyperuricemia develops gout; up to two-thirds of people with hyperuricemia never have any symptoms, although it is unclear why this is. In some people, uric acid crystals may form that can lead to kidney stones and other problems with kidney function.

Gout is different from another disease called calcium pyrophosphate crystal deposition (CPPD) disease (formerly called "pseudogout"), which is discussed separately. CPPD disease is caused by a different type of crystal known as calcium pyrophosphate (CPP). Nevertheless, symptoms of gout and CPPD disease may be quite similar for the joints that are involved in both diseases (such as the knee or the ankle). (See "Patient education: Calcium pyrophosphate crystal deposition (CPPD) disease (Beyond the Basics)".)

GOUT RISK FACTORS — Gout usually develops in adulthood and is rare in children. It commonly develops earlier in adult men (often between the ages of 30 and 45) than in women (usually after age 55); it is particularly common in people older than 65 regardless of gender. It is estimated that gout affects nearly 4 percent of adults in the United States.

There are several medical conditions and lifestyle factors that increase a person's risk of developing hyperuricemia and therefore gout, including:

●Obesity

●High blood pressure

●Chronic kidney disease

●Consuming excessive amounts of alcohol (particularly beer and spirits) on a regular basis

●Consuming large amounts of meat or seafood

●Consuming beverages containing high fructose corn syrup (such as non-diet sodas)

●Taking medications that affect blood levels of urate (especially diuretics)

In people already diagnosed with gout (referred to as "established gout"), there are also certain characteristics that increase the risk of repeated gout flares. These include:

●Overeating or prolonged fasting, including severe diets

●Consuming excessive amounts of alcohol

●Taking medications that cause sudden changes in blood urate levels

●Dehydration

GOUT SYMPTOMS — Gout flares (also called gout attacks) are sudden episodes of severe joint pain, usually involving redness, swelling, and tenderness of the joint. Although a gout flare typically affects a single joint, some people develop several inflamed joints at the same time. Gout flares can occur at any time of day but more often occur at night and in the early morning hours. The pain and inflammation usually peak in intensity within 12 to 24 hours and improve completely within a few days to several weeks, even if untreated. It is not clear how the body "turns off" a gout flare.

The characteristic pain and inflammation of gout develop when urate deposits shed crystals into the fluid inside of a joint (called synovial fluid). White blood cells and cells in the joint lining recognize the crystals as foreign material and attempt to surround and digest them. These cells release chemical signals that contribute to the pain, swelling, and redness associated with a gout flare.

PHASES OF GOUT — There are three main phases of gout: gout flare, intercritical gout, and tophaceous gout.

Gout flare — Initial gout flares usually involve a single joint, most often the big toe or knee. Over time, flares can begin to involve multiple joints at once and may be accompanied by fever. People with osteoarthritis in their fingers may experience their first gout flares in the fingers rather than the toes or knees.

Intercritical gout — The time between gout flares is known as an "intercritical" period. A second gout flare typically occurs within two years, and additional gout flares may occur thereafter. If your gout is untreated for several years, the time between gout flares may shorten, and your gout flares may involve more joints and become increasingly severe and prolonged.

Tophaceous gout — People who have repeated gout flares or persistent hyperuricemia for many years can develop tophaceous gout. This term describes the accumulation of large numbers of urate crystals in masses called "tophi." People with this form of gout can develop tophi in joints, bursae (the fluid-filled sacs that cushion and protect tissues), bones and cartilage, and under the skin. Tophi may cause erosion of the bone and eventually joint damage and deformity (called erosive gout or gouty arthropathy).

Developing tophi near the small joints of the feet or fingers can cause physical changes that can be distressing due to the cosmetic appearance. They can act as a "chalk splint" that restricts joint movement and causes disability. Over time, they can also cause bone and joint lesions (also known as erosive gout). Tophi are usually not painful or tender. However, they can become inflamed (picture 1) and can cause symptoms like those of a gout flare.

Tophaceous gout was more common in the past, before effective treatment for hyperuricemia became available. Certain groups are still at risk for tophaceous gout, including:

●People who have very high levels of urate in the blood (as may happen with chronic kidney disease, high-dose diuretics, and some transplant medications)

●Those who cannot tolerate or do not receive adequate doses of medications to properly control hyperuricemia (for example, due to kidney failure or drug allergy)

●Women who have already been through menopause, especially if they are taking a diuretic medication or develop chronic kidney disease, as well as those with osteoarthritis

The known risk factors for gout can also increase a person's risk of developing tophaceous gout. (See 'Gout risk factors' above.)

KIDNEY-RELATED COMPLICATIONS — Normally, the kidneys filter urate in the blood and excrete it from the body through urine. In people with gout, urate crystals can build up in the kidney or other parts of the urinary tract, leading to kidney stones. If a stone gets large enough, it can block one of the ureters (the tubes that carry urine from the kidney to the bladder and out of the body) (figure 1). Medications that increase the amount of urate excreted by the kidneys, which are commonly used in people with frequent or severe gout flares, may increase the risk of developing kidney stones. The most common symptom of kidney stones is pain in the side of the back ("flank pain").

GOUT DIAGNOSIS — There are many illnesses that can cause joint pain and inflammation. Gout is strongly suspected if a person has one or more acute attacks of intermittent and sudden joint pain, followed by a period in which there are no symptoms but the blood level of urate is still elevated. It is important to confirm the diagnosis of gout to help providers know if long-term medications might be needed.

The best way to diagnose gout is for a medical provider to take a sample of the fluid inside the affected joint (synovial fluid) and examine it under a microscope for urate crystals. To do this, the provider uses a needle and syringe to withdraw a small amount of fluid from inside the joint. Tophi located just beneath the skin can also be sampled with a needle to diagnose tophaceous gout.

If it is not possible to do a synovial fluid analysis, your provider will consider your symptoms, physical examination, and blood test results. Also, some imaging procedures may be useful to confirm a diagnosis of gout. Among the criteria for suspecting gout are:

●Rapidly developing pain and inflammation initially involving one joint at a time, especially the joint at the base of the large toe

●Complete resolution of symptoms between flares

●High levels of urate in the blood (this is most accurate for diagnosis after a gout flare resolves because urate levels may be within normal limits during the flare)

TREATMENT OF GOUT FLARES — The goal of treatment of gout flares is to quickly and safely reduce inflammation and therefore pain and disability. This treatment is usually short-term and limited to the duration of the flare. Deciding which medication to use is based upon several factors, including your risk of bleeding, kidney health, and whether you have a history of ulcers in the stomach or small intestines.

The best treatment for gout flares is an antiinflammatory medication, such as nonsteroidal antiinflammatory drugs (NSAIDs), colchicine, or glucocorticoids. Medications are most effective when started early in the course of a flare.

If you have a history of gout, your clinician can give you medication to keep on hand in the event of a flare. This is important because early treatment is key in minimizing the amount of time it takes to decrease the pain, severity, and duration of a flare.

Nonsteroidal antiinflammatory drugs — NSAIDs work to reduce swelling in a joint. They include ibuprofen, naproxen, indomethacin, and celecoxib. NSAIDs are generally recommended for people under age 65 who do not have a history of kidney or liver disease, bleeding problems, stomach or duodenal ulcers, difficult-to-control high blood pressure, significant heart failure, or previous cardiovascular events (such as a heart attack). They should also not be used for patients taking anticoagulant medications such as warfarin. Some NSAIDs are available over the counter, while others require a prescription. (See "Patient education: Nonsteroidal antiinflammatory drugs (NSAIDs) (Beyond the Basics)".)

NSAIDs are most effective in the treatment of a gout flare when they are started as early as possible in the flare. People who have had previous flares may start taking an NSAID at the first signs of a recurrence. The dose of NSAIDs to treat gout is often higher than the dose used to relieve minor pain, since these medications can reduce inflammation at higher doses. Your provider will work with you to figure out the most appropriate NSAID dose. NSAID treatment is stopped within a day or two after the gout flare resolves.

Although aspirin is an NSAID, it is not usually recommended for the treatment of gout because it can raise or lower urate levels in the blood, depending upon the dose.

Colchicine — A prescription oral medication called colchicine may be prescribed for a gout flare instead of an NSAID. Colchicine does not increase the risk of ulcers, has no known interaction with anticoagulants ("blood thinners"), and does not affect kidney function when dosed appropriately. However, colchicine can have bothersome side effects when given in excess, including diarrhea, nausea, vomiting, and crampy abdominal pain. Providers now use lower doses of colchicine than what was used in the past, and the gastrointestinal side effects are less problematic.

Colchicine therapy seems to be most effective when started within 24 hours of the first symptoms of a gout flare. Your provider will tell you what dose you should take if you have a flare; people with kidney or liver problems may need a lower dose.

Glucocorticoids — Steroid medications, also known as glucocorticoids, are effective and frequently used for treating gout flares. They may be given orally (as pills), by direct injection into an involved joint (called an intraarticular injection), or by intravenous (IV) or intramuscular injection in some circumstances. Commonly used oral glucocorticoids include prednisone, prednisolone, and methylprednisolone.

Oral glucocorticoids can be given to people with impaired kidney function or with an increased risk for bleeding, as well as those with multiple affected joints or who cannot take NSAIDs or colchicine. Glucocorticoids are avoided when patients have poorly controlled diabetes, a concern for infection, or other contraindications.

If you have increasingly frequent gout flares, reducing the dose of glucocorticoids too quickly can increase your risk of a recurrent (or "rebound") flare. In these cases, your dose of glucocorticoid should be reduced slowly over a period of at least 14 to 21 days. Your provider will work with you to figure out how to reduce (taper) your dose.

PREVENTIVE TREATMENT — Preventive (also called prophylactic) antiinflammatory therapy aims to prevent or reduce the occurrence of gout flares. Colchicine is usually recommended as preventive therapy; it is taken daily at low doses to avoid gastrointestinal side effects. Colchicine reduces the frequency of gout flares, particularly while starting drugs that lower urate levels.

Preventive colchicine is not usually used alone as a long-term treatment (ie, for years), but it can serve as a helpful "bridge" if you are transitioning from treating a gout flare to longer-term urate-lowering therapy. Daily nonsteroidal antiinflammatory drugs (NSAIDs) are less commonly used for preventive therapy.

LONG-TERM URATE-LOWERING THERAPY — Over time, medications and lifestyle changes can lower urate levels and prevent or reverse urate crystal deposits that can cause complications in gout such as joint damage, disability, kidney stone formation, and kidney damage. People who have one or more of these complications are especially encouraged to take a urate-lowering treatment.

The goal of urate-lowering therapy is to achieve and maintain blood urate levels below a specific level. In practice, the recommended goal for most people with gout is less than 6 mg/100 mL (360 micromol/L). The goal is lower for people with tophaceous or severe gout (less than 5 mg/dL [300 micromol/L]). Your clinician can talk to you about what your goal level should be.

Not everyone with gout will require urate-lowering therapy. If you only have rare or mild flares, you may be able to manage your gout by treating the flares as they happen. However, if you have frequent, prolonged, painful, or disabling gout flares, joint damage, or tophi, your health care provider will likely suggest urate-lowering therapy.

Medications — Medications lower urate levels in one of three ways: they increase urate excretion by the kidneys, they decrease the body's production of urate, or they break down urate. Urate-lowering therapy is usually started after a gout flare has resolved. People who take their medication regularly and maintain urate levels below the target range over months to years eventually experience fewer flares; sometimes, flares stop altogether. Patients often need to continue preventive therapy indefinitely; stopping treatment is commonly associated with a return to hyperuricemia and recurrence of gout.

Medications that lower urate levels include the following:

●Allopurinol and febuxostat work by preventing the formation of urate. Allopurinol is the most common urate-lowering therapy. Rarely, it can cause side effects, including skin reactions (rash), lowered white blood cell and platelet counts, diarrhea, and fever. The starting dose of allopurinol is lower for in people with impaired kidney function, but doses can usually be gradually increased to achieve the target urate level. The dose of febuxostat does not need to be changed for patients with impaired kidney function. Regular blood tests to check liver function are recommended during treatment with allopurinol or febuxostat. Febuxostat should be used with caution in people at high risk of cardiovascular disease or who have had a heart attack or stroke.

●Probenecid increases the efficiency of urate excretion by the kidney and is called a "uricosuric" drug. Benzbromarone is a more potent uricosuric drug, but it is not available in all countries (eg, it is not available in the United States). Probenecid must be taken twice a day and is not effective in people with advanced kidney disease. Probenecid can cause side effects, including rash, upset stomach, and kidney stone formation. Benzbromarone may infrequently cause liver problems. Both medications can increase the risk of kidney stones.

●Pegloticase works by breaking down urate. Pegloticase is a biologic compound that is given by repeated intravenous (IV) infusions and can lower urate levels rapidly and profoundly. However, pegloticase is usually reserved for patients with advanced gout that cannot be controlled with oral urate-lowering therapies due to its cost, need for careful monitoring, and potential to cause potentially severe allergic-like reactions. In the long term, it is effective in only about 50 percent of cases.

It takes weeks or months to lower urate levels to where they should be. During this period, your provider will gradually adjust your medication doses to meet the goal. Lowering the blood urate level rapidly can cause more frequent gout flares. People taking uricosuric medications should make sure they stay hydrated to reduce the risk of developing kidney stones.

If you also take antiinflammatory preventive therapy (with colchicine or nonsteroidal antiinflammatory drugs [NSAIDs]) (see 'Preventive treatment' above), this can usually be safely stopped when blood levels of urate have been at or below the goal level for about six months. Some people may need a longer period of preventive therapy, particularly if they have tophi. Blood levels of urate should be monitored periodically to ensure that the goal urate level is maintained.

Some other medications reduce blood urate levels. Losartan is used to treat high blood pressure but also has a useful, though weak, urate-lowering effect, as do the lipid-lowering drugs fenofibrate and atorvastatin. However, their effects on uric acid are relatively weak. Patients who have gout and a condition like high blood pressure or high lipids should talk with their provider to see if they should adjust their other medications.

Dietary changes — Improving your diet may reduce the frequency of gout flares. However, extreme or "fad" diets are not recommended. Reaching and maintaining a healthy weight is also important for patients with gout since obesity is a risk factor for developing gout and other related health conditions. (See "Patient education: Losing weight (Beyond the Basics)".)

Changes in diet are often recommended along with urate-lowering medications. Changing your diet alone is unlikely to lower blood urate levels by more than about 15 percent, even if you make major changes to your diet. Dietary guidelines for people with established gout have changed over time, and it is not completely clear which combination of foods is best. Until validated diet guidelines for gout are available, a reasonable approach is to try to establish and maintain a healthy body weight, eat a balanced diet, drink adequate water to avoid dehydration, and limit your intake of alcohol, sugar-sweetened drinks, and high-purine foods (eg, red meat, shellfish).

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.

Patient level information — UpToDate offers two types of patient education materials.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient education: Gout (The Basics)
Patient education: Calcium pyrophosphate deposition disease (The Basics)
Patient education: Ganglion cyst (The Basics)

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Patient education: Calcium pyrophosphate crystal deposition (CPPD) disease (Beyond the Basics)
Patient education: Kidney stones in adults (Beyond the Basics)
Patient education: Nonsteroidal antiinflammatory drugs (NSAIDs) (Beyond the Basics)
Patient education: Losing weight (Beyond the Basics)

Professional level information — Professional level articles are designed to keep health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their providers are reading.

Asymptomatic hyperuricemia
Clinical manifestations and diagnosis of gout
Diuretic-induced hyperuricemia and gout
Kidney transplantation in adults: Hyperuricemia and gout in kidney transplant recipients
Pathophysiology of gout
Pharmacologic urate-lowering therapy and treatment of tophi in patients with gout
Treatment of gout flares
Nonpharmacologic strategies for the prevention and treatment of gout

The following organizations also provide reliable health information.

●National Library of Medicine

(www.medlineplus.gov/healthtopics.html)

●National Institute of Arthritis and Musculoskeletal and Skin Diseases

(301) 496-8188

(www.niams.nih.gov/)

●American College of Rheumatology

(404) 633-3777

(www.rheumatology.org)

●The Arthritis Foundation

(800) 283-7800

(www.arthritis.org)

ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Michael A Becker, MD, who contributed to an earlier version of this topic review.