Gout

Gout is a disease characterized by an abnormal metabolism of uric acid, resulting in an excess of uric acid in the tissues and blood. People with gout either produce too much uric acid, or more commonly, their kidneys are inadequate in removing it. There are a number of possible consequences of this buildup of uric acid in the body, including acute and chronic gouty arthritis, kidney stones, and local deposits of uric acid (tophi) in the skin and other tissues. Gout may occur alone (primary gout) or may be associated with other medical conditions or medications (secondary gout).

The prevalence of gout appears to be increasing. It is currently estimated to affect over 6 million Americans.

Gouty arthritis is a common cause of a sudden onset of a painful, hot, red, swollen joint, particularly in the foot at the big toe. Gouty arthritis is reportedly the most common cause of inflammatory arthritis in men over the age of 40. It is definitively diagnosed by detecting uric acid (monosodium urate) crystals in an aspirated sample of the joint fluid. These uric acid crystals can accumulate in the joint and tissues around the joint over years, intermittently triggering repeated bouts of acute inflammation. Repeated attacks of gouty arthritis, or "flares," can damage the joint and lead to chronic arthritis. Fortunately, while gout is a progressive disease, there are effective medications to treat gout.

Uric acid is generated as we metabolize the food we eat and as the body's tissues are broken down during normal cell turnover. Some people with gout generate too much uric acid (10% of those affected) and are medically referred to as "over-producers." Other people with gout do not effectively eliminate their uric acid into the urine (90%) and are medically referred to as "under-excreters."

The genes that we inherit, male gender, kidney function, and nutrition (alcoholism, obesity) play key roles in the development of gout. Gout is not contagious.

• If your parents have gout, then you have a 20% chance of developing it.
• British people are five times more likely to develop gout than others.
• American blacks, but not African blacks, are more likely to have gout than other populations.
• Post-pubertal males are at increased risk for gout compared with women.
• People with insufficient kidney function are at increased risk for gout.
• Intake of alcoholic beverages, especially beer, increases the risk for gout.
• Diets rich in red meats, internal organs, yeast, shellfish, and oily fish increase the risk for gout.
• Uric acid levels increase at puberty in men and at menopause in women, so men first develop gout at an earlier age (after puberty) than do women (after menopause). Gout in premenopausal women is distinctly unusual.

Attacks of gouty arthritis can be precipitated when there is a sudden change in uric acid levels, which may be caused by

• overindulgence in alcohol and red meats,
• trauma,
• starvation and dehydration,
• chemotherapy,
• medications,
  • diuretics and some other anti-hypertensive medications,
  • aspirin (Bayer, Ecotrin),
  • nicotinic acid (B-3-50, B3-500-Gr, Niacin SR, Niacor, Niaspan ER, Slo-Niacin),
  • cyclosporin A,
  • allopurinol (Zyloprim)
  • probenecid (Benemid), and
  • others,
• IV contrast dyes.

The first symptom of gouty arthritis is typically the sudden onset of a hot, red, swollen, stiff, painful joint. The most common joint involved is in the foot at the base of the big toe where swelling can be associated with severe tenderness, but almost any joint can be involved (for example, knee, ankle, and small joints of the hands). In some people, the acute pain is so intense that even a bed sheet on the toe causes severe pain. Acute gouty arthritis at the base of the big toe is referred to as podagra.

Even without treatment, the first attacks stop spontaneously, typically within one to two weeks. While the pain and swelling completely go away, gouty arthritis commonly returns in the same joint or in another joint.

With time, attacks of gouty arthritis can occur more frequently and may last longer. While the first attacks usually involve only one or two joints, multiple joints can be involved simultaneously over time. It is important to note that unrecognizable (subclinical), potentially damaging inflammation in joints can occur between attacks of obvious flares of gouty arthritis.

Kidney stones are more frequent in people with gout.

Uric acid crystals can form outside joints. Collections of these crystals, complications known as tophi, can occur in the earlobe, elbow, and Achilles tendon (back of the ankle), or in other tissues. Typically, these tophi are not painful. However, tophi can be a valuable clue for the diagnosis as the crystals that form them can be removed with a small needle for diagnosis by microscopic examination. Microscopic evaluation of a tophus reveals uric acid crystals.

Anyone who has a sudden onset of a hot, red, swollen joint should seek medical care, either with a primary-care physician, at an emergency department, or with a rheumatologist (arthritis and gout specialist). These symptoms can also be due to an infection, loss of cartilage in the joint, or other reasons. It is important to make an accurate diagnosis of gouty arthritis for optimal treatment.

If one has been diagnosed with gout and has had more than one attack of arthritis, take the medication prescribed by a physician for these attacks. The individual should be seen by a physician, in the emergency department, or urgent-care center if the attack does not respond to this treatment. The individual may need regular medications to prevent further arthritis flares.

Attacks of abdominal pain due to kidney stones (renal colic) may be related to uric acid kidney stones from gout.

Gout is treated by primary-care doctors, including generalists, internists, and family medicine physicians. Rheumatologists have a special interest in diagnosing and managing gout.

Joint aspiration

• This is the most important diagnostic test. It is the ultimate method of being certain of a diagnosis of gouty arthritis, as opposed to other causes such as an infection in the joint.
• A needle is inserted into the joint to withdraw a sample of fluid for testing.
• The fluid is examined under a microscope to see if there are gout crystals or signs of a bacterial infection present. Sometimes other crystals can be found in the joint fluid, such as calcium pyrophosphate, which is caused by an entirely different condition called pseudogout ("like gout").
• Gouty arthritis is sometimes diagnosed based on the typical clinical presentation without a joint aspiration.

Blood tests

• A doctor may obtain a blood sample to look at cell counts, uric acid levels, kidney function, etc.
• Unfortunately, the level of uric acid in the blood cannot be reliably used to make a diagnosis of gout. It is normal in approximately 10% of people during an acute attack of gouty arthritis. Moreover, uric acid levels are elevated in 5%-8% of the general population, so the presence of an elevated level does not necessarily mean that gout is the cause of an inflamed joint. Interestingly, the uric acid is typically lowered during a flare of inflammatory gouty arthritis. Therefore, the optimal time to measure the uric acid is after a flare has resolved when acute inflammation is not present.

Radiographs

• X-rays are primarily used to assess underlying joint damage, especially in those who have had multiple episodes of gouty arthritis.

• Take medications as prescribed.
• While a joint is hot and swollen, one may want to use a cane or similar support to keep weight off that joint.
• It may be helpful to keep the swollen joint elevated above the chest as much as possible.
• Ice packs can be helpful in relieving pain and reducing inflammation.
• Maintaining adequate hydration is key for minimizing the frequency and intensity of attacks.
• Drinking cherry juice may decrease the intensity and severity of attacks.
• Avoiding eating red meats, internal organs, yeast, shellfish, and oily fish because these increase the risk for gout.

While some medications are used to treat the hot, swollen joint, other medications are used to prevent further attacks of gout. With any of these medications, an individual should call a doctor if he or she thinks they are not working or if he or she is having other problems with the medication.

Medicines used to treat acute gout and/or prevent further attacks are as follows:

• Nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Examples include indomethacin (Indocin), ibuprofen (Advil), and naproxen (Aleve). Newer drugs such as celecoxib (Celebrex) can also be used. Aspirin should not be used for this condition.
  • High doses of anti-inflammatory medications are used to control the inflammation and can be tapered off within a couple of weeks.
  • Tell a doctor about other health problems, particularly if one has a history of peptic ulcer disease or intestinal bleeding, if one is taking warfarin (Coumadin), or if one has problems with kidney function.
  • The primary complications of these medications include upset stomach, bleeding ulcers, and decreased kidney function.
• Colchicine (Colcrys)
  • This medication is given in two different ways, either to treat the acute attack of arthritis or to prevent recurring attacks.
  • To treat the hot, swollen joint, colchicine is given rapidly (generally, two tablets at once followed by another tablet an hour later).
  • To help prevent an attack from coming back, colchicine can be given once or twice a day. While the chronic use of colchicine can reduce the attacks of gout, it does not prevent the accumulation of uric acid that can lead to joint damage even without attacks of hot, swollen joints.
  • Tell a doctor if experiencing any problems with kidney or liver function.
• Corticosteroids
  • Corticosteroids such as prednisone (Meticorten, Sterapred, Sterapred DS) are generally given when a doctor feels this is a safer approach than using NSAIDs.
  • When given by mouth, high-dose corticosteroids are used initially and tapered off within a couple of weeks. It is important to take these medications as prescribed to avoid problems.
  • Some complications with the short-term use of corticosteroids include altered mood, elevated blood pressure, and problems with control of glucose in patients with diabetes.
  • Corticosteroids can also be injected into the swollen joint. Resting the joint temporarily, after it is injected with steroids, can be helpful.
  • Occasionally, corticosteroids or a related compound, corticotropin (ACTH), can also be injected into the muscle or given intravenously.

In addition to low-dose colchicine, other medicines used to prevent further attacks of gout and lower the level of uric acid in the blood include the following:

• Probenecid (Benemid)
  • This medication helps the body eliminate excess uric acid through the kidneys and into the urine.
  • Individuals should drink at least 2 liters of fluid a day while taking this medication (to help prevent uric acid kidney stones from forming).
  • Advise a doctor if one has kidney problems or a history of kidney stones or if taking aspirin. One may need to take allopurinol (see below) instead.
  • There are a number of drug interactions with probenecid, so advise a doctor of other medications. If prescribed a new medication, let a doctor know that you are taking probenecid.
• Allopurinol
  • This medication decreases the formation of uric acid by the body and is a very reliable way to lower the blood uric acid level. Allopurinol is currently the gold standard of maintenance therapy.
  • Advise your doctor if you have kidney problems. Allopurinol can be still used, but the dose may need to be adjusted.
  • Common side effects include stomach pain, headache, diarrhea, and rash.
  • Discontinue allopurinol if you develop a rash or a fever, and call your doctor.
  • A very rare risk of allopurinol hypersensitivity exists. This problem can cause a severe skin rash, fever, kidney failure, liver failure, bone marrow failure, and can be fatal.
  • Advise your doctor if you are taking azathioprine (Azasan, Imuran), 6-mercaptopurine, or cyclophosphamide (Cytoxan, Cytoxan Lyophilized, Neosar); dose adjustments of allopurinol may be needed.
  • Ampicillin (Principen) is more likely to cause a rash if you are taking allopurinol.
• Febuxostat (Uloric)
  • Febuxostat is first new medication developed specifically for the control of gout in over 40 years.
  • Febuxostat decreases the formation of uric acid by the body and is a very reliable way to lower the blood uric acid level.
  • Febuxostat can be used in patients with mild to moderate kidney impairment.
  • Febuxostat should not be taken with 6-mercaptopurine (6-MP), or azathioprine.
• Pegloticase (Krystexxa)
  • Pegloticase is a PEGylated uric acid-specific enzyme given intravenously that is indicated for the treatment of chronic gout in adult patients refractory to conventional therapies described above.
  • Pegloticase should be avoided if you have G6PD enzyme deficiency.
  • Serious allergic reactions can occur with pegloticase, including life-threatening anaphylaxis.

It is important to understand that these maintenance medications are used to lower the uric acid well below normal to prevent recurrent gouty arthritis attacks. Generally, doctors want the blood uric acid level to be below 6.0 mg/dL. This level of uric acid is referred to as the "target level" or "goal" of therapy.

Surgery is rarely needed for gout unless significant joint damage has occurred from lack of effective treatment. Surgery can be used to remove tophi.

It is critically important to follow up with a doctor. Gouty arthritis is treated in two stages. The first stage is to treat the acute arthritis. The second stage is to prevent gouty arthritis attacks from happening again.

Low doses of colchicine or anti-inflammatory medications may be used for an acute attack. One will need to follow up with a doctor after the acute attack has resolved to determine if it is necessary to start medications to lower the blood uric acid level.

If you are at risk for gout, you should do the following:

• Eat a low-cholesterol, low-fat diet. People with gout have a higher risk for heart disease. This diet would not only lower your risk for gout but also your risk for heart disease. Control your cholesterol.
• Use a low-purine diet and avoid foods that are high in purines (the biochemical in foods that is metabolized into uric acid), including shellfish and red meats.
• Slowly lose weight. This can lower your uric acid levels. Losing weight too rapidly can occasionally precipitate gout attacks.
• Restrict your intake of alcohol, especially beer.
• Stay hydrated.
• Increase your intake of dairy products, such as nonfat milk and yogurt, because they can lower the frequency of gout attacks.
• Avoid fructose, such as in corn syrup.
• Talk to your doctor if you are taking thiazide diuretics (hydrochlorothiazide, HCTZ), low-dose aspirin, levodopa (Larodopa), cyclosporine (Gengraf, Neoral, Sandimmune), or nicotinic acid.

If you have had an attack of gouty arthritis, you should do all of the above and follow the regimen prescribed by your physician. Optimal prevention of gouty arthritis may involve lifelong medical therapy.

The prognosis for gout is excellent if you are properly diagnosed and treated.

American College of Rheumatology

Arthritis Foundation