Harvard Men's Health Watch

Gout: Joint pain and more

It starts with a bang, often in the dead of night. The pain is severe, almost unbearable, and fever may make you feel even worse. Lying still helps a bit, but even the touch of a sheet can be excruciating. And, worst of all, your distress may be greeted with a sly smile instead of supportive sympathy. You are suffering from gout, a common disease that's often misunderstood.

Myths and realities

Gout is an old disease, and erroneous beliefs about it are almost just as old. The name, in fact, is based on a misconception It's derived from a Latin word that means "a drop"; ancient physicians chose the name because they believed the pain resulted from a drop of "a bad humor." Over the centuries, gout was considered a rich man's disease, a product of overeating, excessive drinking, and corpulence. Modern research, however, shows that gout has no relationship to wealth or social status and little to diet and drink. But one traditional view has proved correct: Gout is a man's disease, occurring seven to nine times more often in men than women. It's also a common disease, striking an estimated 3.4 million American men annually. That makes gout the most prevalent form of inflammatory arthritis in men older than 40.

The chemical culprit

Gout is caused by an accumulation of uric acid. Uric acid has no useful function in the human body; it is simply a breakdown product of purines, a group of chemicals present in all body tissues and many foods. In normal circumstances, the body rids itself of uric acid by excreting it in the urine, keeping blood levels low. But some men have inherited a metabolic glitch that allows blood uric acids to rise; 90% of the time it's because the kidneys don't excrete enough uric acid, but sometimes the body just produces too much of the pesky chemical. Certain medications, such as low-dose aspirin, thiazide diuretics, and niacin, can also increase uric acid levels. Binge drinking, prolonged fasting, kidney disease, lead toxicity, extreme muscular exertion, and leukemia and lymphomas are much less frequent causes of high uric acid levels.

These high levels lead to gout — but not right away. In fact, uric acid levels are typically elevated for 20 to 30 years before they cause any trouble, which is why gout usually occurs in middle-aged and older men. Uric acid levels are normally below 7 milligrams per deciliter (mg/dL). The higher the level, the more likely an attack of gout; men with levels above 10 mg/dL have a 90% chance of developing gout. But gout can also be triggered by a rapid drop in uric acid levels, which is why up to 30% of men with gout have normal uric acid levels at the time of an attack.

An attack of gout occurs when excess uric acid is deposited in a joint and forms urate crystals that irritate the joint lining. White blood cells try to help; they gobble up the crystals, but they are not equal to the task. The white blood cells are themselves damaged, releasing chemicals that cause inflammation, swelling, and pain.

Ouch

Gout is painful, very painful.

The most common manifestation of gout is acute arthritis, severe pain in a joint. In most cases, it strikes one joint at a time; in half, it's the first joint in the large toe. Other frequent sites include the forefoot, instep, heel, ankle, and knee. Gout is uncommon in the upper body, but it can strike fingers, wrists, and elbows. At any site, the attack usually begins abruptly, often at night. Within hours, the joint becomes red, swollen, hot, and painful. The pain and tenderness can be so severe that even gentle pressure from bedding is a problem. And even though only one small joint is affected, the inflammation can be intense enough to cause fever, muscle aches, and other flu-like symptoms.

Without treatment, gout can also cause long-term arthritis, with chronic swelling and permanent joint damage. Urate crystals can build up to a remarkable degree, producing large, even grotesque, deposits called tophi in joints and other tissues. Crystals may also be deposited in the kidneys, and they may precipitate in the urine, forming kidney stones.

Diagnosis

Gout is easy to recognize in the big toe, where it causes the characteristic inflammation called podagra. Doctors can often make the diagnosis over the phone, and most men with gout can diagnose themselves — particularly in their second or third attack of this recurring disease. But in other joints the diagnosis can be tricky. It's simple to measure the level of uric acid in the blood; a high level supports a diagnosis of gout, but it's not definitive, since many healthy men have high levels and some men with gout have normal levels. Other diseases can mimic gout, including rheumatoid arthritis, infections, and pseudogout, which is caused by crystals of another chemical (calcium pyrophosphate). If the diagnosis is in doubt, doctors can remove a small amount of fluid from the inflamed joint; in cases of gout, the fluid contains white blood cells and uric acid crystals, which can be seen through a special polarizing microscope.

Treatment

Gout responds very well to nonsteroidal anti-inflammatory drugs (NSAIDs) if two rules are observed. First, the NSAID should be started as promptly as possible, and second, it should be used at the maximum recommended dose. Many physicians prescribe indomethacin (Indocin) at a dose of 50 milligrams (mg) three or four times a day, but the other prescription and over-the-counter NSAIDs are also effective. One exception: Aspirin should not be used for gout because it can raise uric acid levels. After two to three days at full strength, the NSAID dose can be reduced by half, and in most cases, treatment can be stopped after just five to seven days.

Men who can't take NSAIDs because of gastritis, peptic ulcers, or bleeding can get relief from a closely related drug, the selective COX-2 inhibitor, celecoxib (Celebrex). And if this new drug can't be used, an old standby, colchicine, can help, though it's fallen out of favor because it often produces vomiting or diarrhea in the high doses needed. Fortunately, a brief course of prednisone or a similar steroid will usually do the job for men who can't take NSAIDs or celecoxib. Steroids can also be given intravenously to people who can't take oral medications, and they can be injected directly into the inflamed joint to provide rapid relief.

Joints that are inflamed should be rested, but men can resume their normal activities as soon as their gouty attacks settle down.

Prevention

For centuries, diet was the mainstay of prevention, but since only about 10% of the body's uric acid is derived from dietary sources, it didn't work very well. Still, every little bit helps. Four reports from Harvard's Health Professionals Follow-up Study show the best way to get that help. The first report implicates red meat and seafood as the villains and low-fat dairy products as the heroes. Although certain vegetables are also high in purines (see sidebar), the study did not confirm previous observations that linked veggies to gout.

High-purine foods that may increase the risk of gout

  • All meats, especially organ meats

  • Meat extracts and gravies

  • Seafood, especially sardines and anchovies

  • Yeast and yeast extracts

  • Beans, peas, and lentils

  • Spinach and asparagus

  • Cauliflower

  • Mushrooms

Modified from Emmerson BT, New England Journal of Medicine, Vol. 334, No. 7, pp. 445–51.

The second Harvard report identifies beer as a culprit but exonerates wine; spirits were associated with a slight increase in risk. The third study tells us that men who lose 10 pounds of excess weight and keep it off reduce their risk of gout by 39%. And the newest study tells us that long-term coffee consumption appears to reduce the risk of gout. Even if coffee is not your cup of tea, a high fluid intake is important to help prevent uric acid kidney stones. But a 2007 study cautioned against a high consumption of sugary drinks, which were linked to high uric acid levels in men.

Although months or years can elapse between attacks, more than 75% of patients with gout have several episodes. Men whose attacks are infrequent don't need any preventive medication, but they should have an NSAID on hand to use at the first sign of another attack. If episodes occur often, if they prove hard to treat, or if very high uric acid levels predict frequent attacks, medications can help.

There are three ways to prevent gout:

  • Anti-inflammatory medication. Taken daily, low doses of NSAIDs (indomethacin, 25 mg twice a day, for example) or colchicine (0.6 mg once or twice a day) can prevent acute attacks.

  • Medication to promote uric acid excretion. Probenecid (Benemid) is the traditional choice; the usual dose is 250 to 500 mg two or three times a day. A rash and intestinal upsets are the most common side effects. Since the drug increases uric acid in the urine, it can predispose a person to kidney stones, and it should be avoided in patients with kidney disease. Since it lowers blood uric acid levels, it can trigger gout early on, so men should always take an NSAID or colchicine during the first two to three months of probenecid therapy. Aspirin is a poor choice, however, because it blocks the activity of probenecid.

  • Medication to reduce uric acid production. Allopurinol (Zyloprim) is the only currently available drug in this category, and it is the treatment of choice for men with chronic gouty arthritis or uric acid kidney stones. The typical dose is 300 mg per day, but some men need more, others less. The most common side effects are rash and intestinal upset; severe allergic reactions can occur, but they are rare. Because allopurinol produces such a rapid decrease in uric acid that it can precipitate gout, men should always take colchicine or an NSAID for the first two to three months of therapy. Febuxostat, a new drug to lower uric acid production, may soon be available.

Gout is an old disease that has plagued men for centuries. Thomas Sydenham, a great 17th-century physician, wrote, "Gout, unlike any other disease, kills more rich men than poor, more wise men than simple." But the modern era has witnessed major changes in gout. It never kills, and it rarely results from errant behavior. Moreover, wise men need not fear the disease; instead, they can learn to treat and prevent attacks themselves with just a little help from a physician wise to the ways of gout.