GOUT OVERVIEW

Gout is a painful and debilitating condition that develops in some people who have chronically high blood levels of urate (commonly referred to as uric acid). Not everyone with high blood urate levels (called hyperuricemia) develops gout; up to two-thirds of individuals with hyperuricemia never develop symptoms. It is unclear why some people with hyperuricemia develop gout while others do not.

Although the joints are the most commonly affected part of the body, uric acid or urate crystals can be deposited in the kidney or urinary tract, causing kidney stones and occasionally impairing kidney function. Kidney stones caused by uric acid crystals occur in approximately 15 percent of people with gout. This compares with an 8 percent risk of kidney stones in people without gout.

Gout is different than pseudogout, which is discussed in a separate topic review. Pseudogout is a form of arthritis that develops in some people in response to the presence of calcium pyrophosphate dihydrate (CPPD) crystals. (See "Patient information: Pseudogout (Beyond the Basics)".)

GOUT RISK FACTORS

Gout most commonly first develops in men between ages of 30 and 45 and in women between 55 and 70. In both men and women, gout is particularly common in individuals over 65 years of age. It is estimated that gout affects approximately 2 percent of people in the United States.

The following characteristics increase the risk of developing gout and/or precipitating flares in established gout.

Increase the risk of developing gout:

• Obesity
• High blood pressure
• Injury or recent surgery
• Fasting
• Consuming excessive amounts of alcohol (particularly beer, whiskey, gin, vodka, and rum) on a regular basis
• Overeating
• Ingesting diets containing large amounts of meat, seafood, and high fructose corn syrup-containing beverages, such as non-diet sodas
• Taking medications that affect blood levels of urate (especially diuretics)

Precipitate gout flares in established gout:

• Injury or recent surgery
• Fasting
• Consuming excessive amounts of alcohol
• Overeating
• Taking medications that affect blood levels of urate

GOUT SYMPTOMS

Gout attacks cause sudden severe joint pain, often with redness, swelling, and tenderness of the joint. Although an attack typically affects a single joint, some people develop a few inflamed joints at the same time. The pain and inflammation are worst within several hours and generally improve completely over a few days to several weeks, even if untreated. It is not clear how the body “turns off” a gout attack.

The characteristic pain and inflammation of gout develop when white blood cells and cells in the joint linings attempt to surround and digest urate crystal deposits. These cells recognize the crystal deposits as foreign material and release chemical signals that contribute to the pain, swelling, and redness associated with a gout attack.

PHASES OF GOUT

There are three main phases of gout: acute gouty arthritis, intercritical gout, and chronic tophaceous gout.

Acute gouty arthritis — Attacks of gout usually involve a single joint, most often the big toe or knee. This attack is known as acute gouty arthritis. People with osteoarthritis in the fingers may experience their first gout attacks in the fingers rather than the toes or knees.

Intercritical period — The time between gout attacks is known as the intercritical period. A second attack typically occurs within two years, and additional attacks may occur thereafter. If gout is untreated over a period of several years, the time between attacks may shorten, and attacks may become increasingly severe and prolonged. Over time, the attacks can begin to involve multiple joints at once and may be accompanied by fever.

Chronic tophaceous gout — People who have repeated attacks of gout over many years can develop tophaceous gout. This designation describes the accumulation of large numbers of urate crystals in masses called tophi that appear over time in joints, bursae, bones, and cartilage or under the skin. Tophi may cause erosion of the bone and eventually joint damage and deformity.

The presence of tophi near the knuckles or small joints of the fingers can be a distressing cosmetic problem. Tophi are usually not painful or tender. However, they can become inflamed and can cause symptoms like those of an acute gouty attack (picture 1).

Tophaceous gout was more common in the past, when treatment for hyperuricemia was unavailable. Certain groups are still at risk for tophaceous gout, including:

• People who are treated with cyclosporine after organ transplantation
• Those who cannot tolerate or do not receive adequate doses of medications to treat hyperuricemia (for example, due to kidney failure or drug allergy)
• Women who are postmenopausal, especially those taking a diuretic

The risk factors listed previously for gout can also contribute to the development of tophaceous gout. (See 'Gout risk factors' above.)

GOUT COMPLICATIONS

People with gout are at increased risk of developing kidney stones. Uric acid crystals can collect in the urinary tract and form a stone. If a stone is large enough, it can block one of the tubes (ureters) that carry urine from the kidney to the bladder and out of the body.

Rarely, urate crystals collect in the kidney tissue itself, where they can cause inflammation and scar tissue, which reduce kidney function. Medications that increase the amount of uric acid excreted by the kidneys may increase the risk of developing kidney stones.

GOUT DIAGNOSIS

There are many illnesses that can cause joint pain and inflammation. Gout is strongly suspected if a person has an acute attack of joint pain, followed by a period in which there are no symptoms. It is important to confirm the diagnosis of gout to ensure that potentially harmful medications are not taken unnecessarily over a prolonged period of time.

The best way to diagnose gout is to examine synovial fluid from an affected joint to look for urate crystals in the sample. To obtain the fluid, 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.

However, some clinicians do not have the facilities to check for urate crystals in the synovial fluid when symptoms are present. In this case, the tentative diagnosis is based upon a person's symptoms and a physical examination. Criteria for suspecting gout include:

• Pain and inflammation involving one joint at a time, especially the joint at the base of the large toe
• Complete resolution of symptoms between attacks
• Blood testing showing high levels of urate

TREATMENT OF GOUT ATTACKS

The goal of treatment of flares of gouty arthritis is to reduce pain and inflammation quickly and safely. It may be necessary to use more than one drug to achieve this goal. Deciding which medication to use is based upon several factors, including a person's risk of bleeding, his kidney health, and whether there is a past history of an ulcer in the stomach or small intestine. Antiinflammatory medications are the best treatment for acute gout attacks and are best started early in the course of an attack.

People with a history of gout should keep medication on hand to treat an attack because early treatment is an important factor in determining how long it takes to decrease the pain and severity of an attack.

Nonsteroidal antiinflammatory drugs — Nonsteroidal antiinflammatory drugs (NSAIDs) work to reduce swelling in a joint and include ibuprofen (Advil®, Motrin®), naproxen (Aleve®, Anaprox®), and indomethacin (Indocin®). Among the NSAIDs, naproxen is considered one of the safer medications with regard to cardiovascular side effects and has documented efficacy in acute gout. NSAIDs are generally recommended for people who have no history of kidney or liver disease, who have no bleeding problems, who do not use anticoagulant medications (blood thinners such as warfarin (Coumadin®)), and who have no history of a stomach or duodenal ulcer. (See "Patient information: Nonsteroidal antiinflammatory drugs (NSAIDs) (Beyond the Basics)".)

NSAIDs are most effective in the treatment of a gout attack when they are started as soon as possible, before the attack is full blown. People who have had previous attacks may start taking an NSAID at the first signs of a recurrence.

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

Colchicine — Colchicine may be prescribed instead of an NSAID. Colchicine does not increase the risk of ulcers, has no known interaction with anticoagulants, and, in proper doses, does not affect kidney function. However, colchicine can have bothersome side effects, including diarrhea, nausea, vomiting, and crampy abdominal pain. For this reason, colchicine is generally reserved for patients who cannot tolerate NSAIDs. Lower doses of colchicine than formerly used have been shown to be as effective for acute gout as the higher doses recommended in the past, and the gastrointestinal side effects have been much less of a problem. Some people have a great deal of success with colchicine and do not have side effects; colchicine might be used first for this group. Colchicine is generally taken as a pill, and the intravenous preparation is avoided, even if available.

Steroids — Steroids, also known more properly as glucocorticoids or corticosteroids, are effective antiinflammatory agents. Commonly used oral steroids include prednisone, prednisolone, and methylprednisolone.

Steroids may be used if NSAIDs and colchicine cannot be used. They may be injected directly into the affected joint (called an intraarticular injection) or they can be given as pills or by intramuscular injection. People who have multiple affected joints or who cannot take NSAIDs or colchicine may be given oral steroids. However, there is an increased risk of recurrent gout attack (called a rebound attack) in people who take oral steroids. For this reason, steroids should be tapered slowly over a period of at least 7 to 14 days.

PROPHYLACTIC GOUT THERAPY

Prophylactic therapy aims to prevent or reduce the occurrence of acute flares of gouty arthritis. Colchicine is usually recommended as prophylactic therapy; it is taken daily at low doses to avoid gastrointestinal side effects. Colchicine reduces the frequency of acute gout attacks, particularly while starting drugs that lower urate levels.

Prophylactic colchicine is not usually used as a long-term (years) treatment but is a helpful bridge as a person progresses from an acute flare to preventive therapy. Although not nearly as well-documented as colchicine, daily NSAIDs are sometimes used for prophylactic therapy and may have an advantage (because of pain relieving properties) for people who also have osteoarthritis.

PREVENTIVE GOUT THERAPY

Therapy to prevent gout may include medications and dietary changes that can be used long-term to lower urate levels and to prevent the progression of gout. Progressive gout can cause bone destruction and deformity (gouty arthropathy), disability, kidney stone formation, and, possibly, kidney damage. People who have one or more of these complications are strongly encouraged to take a urate-lowering treatment.

Not everyone with gout will require preventive therapy; those fortunate few who have rare or mild attacks are often able to manage their gout by treating the acute attacks alone. On the other hand, people with increasingly frequent gout flares, with flares that are unusually prolonged, painful, and/or disabling, or with unusually high blood urate levels are generally encouraged to take preventive therapy.

Medications — Urate-lowering (antihyperuricemic) medications lower urate levels by helping to eliminate or by decreasing production of uric acid. Antihyperuricemic therapy is usually started after a gout attack has resolved. People who take their medication regularly and lower their urate levels eventually experience fewer attacks. At present, it is recommended that preventive therapy be continued indefinitely because there is no benefit to taking a break from medication.

• Probenecid increases the efficiency of uric acid excretion by the kidney and is called a uricosuric drug. Benzbromarone is a more potent uricosuric drug but is not available in the United States. Both drugs can cause side effects, including rash, upset stomach, and kidney stone formation.
• Losartan is used to treat high blood pressure but also has a useful, though weak, urate-lowering effect, as does the lipid-lowering drug fenofibrate.
• Allopurinol (Alloprim®, Zyloprim®) and febuxostat (Uloric®) work by preventing the formation of uric acid. Allopurinol is the most commonly used drug for lowering urate levels in gout. Allopurinol can cause side effects, including rash, lowered white cell and platelet counts, diarrhea, and fever, although these problems occur in a relatively small percentage of patients. There has been controversy as to whether the dose of allopurinol needs to be reduced in people with impaired kidney function, but no such dose-lowering concern is present with febuxostat when used at the approved doses. Periodic measurement of liver function is recommended during treatment with febuxostat and with allopurinol.
• Pegloticase (Krystexxa®) works by breaking down urate into allantoin, an end product that is more easily disposed. Pegloticase is given by repeated intravenous infusions and can lower urate levels rapidly and profoundly. This biological agent is expensive and may cause allergic-like infusion reactions, some of which can be severe. For these reasons, it is recommended that pegloticase use be limited to patients with advanced gout that cannot be controlled with oral urate-lowering therapies.

Lowering urate levels to a goal range is a process that should take a number weeks or months to achieve. During this period, doses of the uric acid-lowering medications should be gradually adjusted to meet the goal (usually a blood uric acid level <6 mg/dL). Very rapid urate lowering can cause more frequent acute flares of gout. Increased fluids are recommended during this time (at least two liters per day are recommended).

The prophylactic therapy (colchicine or NSAIDs) (see 'Prophylactic gout therapy' above) may be discontinued when blood levels of urate are normal and have been stable for about six months. Longer prophylactic therapy may be needed in some patients, especially those with tophi. Blood levels of urate are monitored periodically to ensure that the goal urate level is maintained.

Dietary changes — Changing your diet may reduce the frequency of gout attacks. Because obesity is a risk factor for gout, as well as for many other health conditions (heart disease, diabetes, high blood pressure), losing weight is an important goal. However, starvation or fad diets are not recommended [1]. (See "Patient information: Weight loss treatments (Beyond the Basics)".)

Diet guidelines for patients with gout have changed over time, and it is not completely clear which combination of foods is best. The current recommendations are shown in the table (table 1):

You are encouraged to eat and drink:

• Low-fat dairy products
• Foods made with complex carbohydrates (whole grains, brown rice, oats, beans)
• A moderate amount of wine (up to two 5 ounce servings per day [about 300 mL per day] is not likely to increase the risk of a gout attack)
• Coffee (may decrease serum uric acid levels)
• Vitamin C (500 mg per day has a mild urate-lowering effect)

Changes in diet are often recommended along with medications. Making changes in your diet, without taking a medicine, is not likely to make a big difference in your blood urate levels; following a very strict gout diet only lowers blood urate levels slightly (15 to 20 percent).

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 information: Gout (The Basics)
Patient information: Pseudogout (The Basics)
Patient information: 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 information: Pseudogout (Beyond the Basics)
Patient information: Kidney stones in adults (Beyond the Basics)
Patient information: Nonsteroidal antiinflammatory drugs (NSAIDs) (Beyond the Basics)
Patient information: Weight loss treatments (Beyond the Basics)

Professional level information — Professional level articles are designed to keep doctors and other 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 doctors are reading.

Asymptomatic hyperuricemia
Clinical manifestations and diagnosis of gout
Diuretic-induced hyperuricemia and gout
Hyperuricemia and gout in renal transplant recipients
Pathophysiology of gouty arthritis
Prevention of recurrent gout
Treatment of acute gout

The following organizations also provide reliable health information.

• National Library of Medicine
  (www.nlm.nih.gov/medlineplus/healthtopics.html)
• National Institute of Arthritis and Musculoskeletal and Skin Diseases
  (301) 496-8188
  (www.nih.gov/niams/)
• American College of Rheumatology
  (404) 633-3777
  (www.rheumatology.org)
• The Arthritis Foundation
  (800) 283-7800
  (www.arthritis.org)

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