BETHESDA CLINIC

"Health is Wealth"

Gout

This patient information about gout from MD Consult, give some important details about a disease that affects many middle-aged men in Kenya.

What Is Gout?

Gout is a type of arthritis (inflammation of the joints) that mostly affects men age 40 and older. It is nearly always associated with chronic hyperuricemia, a long-lasting, abnormally high concentration of uric acid in the blood. The process leading to gout begins with the metabolism of purines, nitrogen-containing compounds, that are important for energy. Purines can be divided into two types, endogenous and exogenous. Endogenous purines are synthesized within the nuclei of cells in the human body itself, whereas the exogenous purines are obtained from foods. All mammals, except humans, possess an enzyme called uricase that breaks purines down into a very soluble product called allantoin. Humans, however, lack this enzyme, and the end point of their purine metabolism is uric acid, a useless substance that can build up in tissues in the body if it is not adequately eliminated in urine.

Uric acid is produced in the liver and enters the bloodstream. Most uric acid eventually passes through the kidneys and is excreted in the urine; the rest is disposed of in the intestines, where it is processed and oxidized by bacteria. Normally these processes keep the concentration of uric acid in the blood plasma (the liquid part of the blood) below 6.8 milligrams per deciliter (6.8 mg/dL). Under certain circumstances, however, the body produces too much uric acid or excretes too little. This results in higher levels and increased concentrations of uric acid in the blood, and hyperuricemia develops. At normal body temperature and below, uric acid concentrations increase; as they approach 7 mg/dL, the blood becomes supersaturated, and needlelike crystals of a salt called monosodium urate (MSU) form. In time, as MSU crystals accumulate, they cause inflammation and pain, symptoms typical of gout.

Effects of Hyperuricemia

High levels of uric acid are basically associated with four conditions, which can occur independently but may develop one after the other if gout is untreated: acute gouty arthritis, chronic tophaceous gout, uric acid nephrolithiasis (a form of kidney stone), and, possibly, uric acid nephropathy (kidney disease).

Acute Gouty Arthritis. Acute gouty arthritis is the stage at which the first symptoms of gout appear.

Chronic Tophaceous Gout. After several years, persistent gout can produce tophi, which are solid deposits of MSU crystals that form in the joints and elsewhere in the body (hence the term chronic tophaceous gout). Without anti-hyperuricemia treatment, tophi develop on average about 10 years after the onset of the disease although their first appearance can range from three to 42 years. Bones, cartilage, tendons, soft tissue, and membranes containing synovial fluid (the lubricating fluid surrounding joints) can all harbor tophi. Common locations include the helix of the outer ear (the curved ridge along the edge of the ear), the fingers, hands, forearms, knees, and feet, and the olecranon bursa (a sac at the elbow joint filled with synovial fluid). In some cases, tophi break through the skin and appear as white or yellowish-white, chalky nodules. (They have been described as looking like "crabs eyes.") In rare cases, they can settle in regions around the heart and spine. Today, drug therapy has reduced the prevalence of chronic tophaceous gout to as little as 3%, although certain groups, such as transplant patients receiving cyclosporine, still face a high risk of developing tophi.

Uric Acid Nephrolithiasis (Kidney Stones). Uric acid nephrolithiasis occurs when kidney stones form from uric acid. Uric acid and other kidney stones are present in 10% to 25% of patients with primary gout, a prevalence more than 1000 times that of the general population. In secondary gout, the reported incidence reaches 42%. Uric acid stones can also form in the absence of gout or hyperuricemia. Not all of the kidney stones in patients with gout are composed of uric acid; some are composed of calcium oxalate, calcium phosphate, or those substances combined with uric acid. Kidney stones can be extraordinarily painful and can cause infection and kidney failure if untreated.

Chronic Uric Acid Interstitial Nephropathy. Chronic uric acid interstitial nephropathy occurs when crystals slowly form in the structures and tubes that carry fluid from the kidney. It is reversible and not likely to injure the kidneys. (Sudden overproduction of uric acid, however, can occasionally block the kidneys and cause them to fail. This most often occurs in conjunction with chemotherapy for leukemia or lymphoma and can also occur after heat stress from vigorous exercise, following epileptic seizures, and after corticosteroid therapy for severe allergic reactions.)

What Causes Gout?

Gout is classified as either primary (the most common type) or secondary, depending on the cause of the associated hyperuricemia. In both types of gout, between 70% and 95% of hyperuricemia cases are the result of underexcretion of uric acid, rather than uric acid overproduction.

Primary Gout

More than 99% of primary gout cases are referred to as idiopathic, meaning that the cause of the hyperuricemia cannot be determined. They are most likely due to a combination of hormonal and genetic factors that cause metabolic abnormalities resulting in overproduction of uric acid or reduced excretion of uric acid. The remaining 1% of primary gout cases are traceable to either of two rare inherited enzyme defects that affect purine synthesis in the cells.

Secondary Gout

In secondary gout, hyperuricemia is caused by drug therapy or by medical conditions other than an inborn metabolic disorder that increase uric acid concentration.

Medications. The list of drugs that cause hyperuricemia is long. They include thiazide diuretics (the "water pills" used to control hypertension), pyrazinamide (used to treat tuberculosis), and the immunosuppressive drug cyclosporine (given to transplant recipients to prevent organ rejection). Low doses of aspirin decrease uric acid excretion and increase the chance for hyperuricemia; this is a particular problem for older people with heart disease who would benefit from baby aspirin. High doses have the opposite effect, however.

Kidney Problems. Renal (meaning kidney) insufficiency is the impaired ability of the kidneys to eliminate waste products, including uric acid, which then build up in the blood. It is one of the major risk factors for gout in older people. Hyperuricemia occurs in between 30% and 85% of people who have kidney transplants and who receive immunosuppressive and diuretic drugs.

Other Medical Conditions. A number of diseases, including leukemia, lymphoma, and psoriasis, can cause gout. Over exposure to lead can cause gout.

Alcohol Use. Alcohol use increases uric acid levels in three ways: by providing an additional dietary source of purines (the compounds from which uric acid is formed), by intensifying the body's production of uric acid, and by interfering with the kidneys' ability to excrete uric acid.

Purine-Rich Diet. A purine-rich diet rarely causes hyperuricemia, although it may precipitate an attack in some people with existing gout. [For a list of purine-rich foods, see What Lifestyle Measures Can Help Prevent Gout? below.]

What Are The Symptoms Of Gout?

Gout is often divided into four symptomatic stages: asymptomatic hyperuricemia, acute gouty arthritis, intercritical gout, and chronic tophaceous gout. Gout symptoms can be precipitated by stress, infection, joint injury, weight loss, surgery, certain kinds of drug treatment, overindulgence in alcohol or purine-rich foods, or even something as seemingly inconsequential as a long walk that one was not sufficiently physically fit to undertake. They tend to occur more in the spring, with the peak in April. Severe illnesses and drug treatments are probably the most significant triggers; in fact, 20% to 86% of patients with gout experienced a recurrence when they are hospitalized.

Asymptomatic Hyperuricemia

Asymptomatic hyperuricemia, in which MSU slowly builds up, always precedes gout and is considered the first stage of the disorder. It can last, however, for an average of 30 years. Hyperuricemia also does not inevitably lead to gout. In fact, less than 20% of the hyperuricemic population develops the full-blown arthritic disease.

Acute Gouty Arthritis

Acute gouty arthritis is the stage at which the first symptoms of gout appear. Sometimes gout is heralded by brief twinges of pain (petit attacks) in an affected joint, which can precede the actual full-blown condition by several years.

MSU crystals begin to form at normal body temperature when concentrations reach 7 mg/dL. They can form at lower concentrations, however, at lower body temperatures, which occur in areas farther from the heart; this explains why gout tends to favor joints in fingers and toes first. Symptoms usually begin as a sudden, severe, and unexpected arthritic attack affecting a single joint in one of the lower limbs, a condition known as monoarticular gout. The joint of the big toe is the site of about half of all first gout attacks, a specific condition called podagra. The site is often medically referred to as the big toe's metatarsophalangeal (MTP) joint, the point where one of the long five bones of the foot meets the first digit of a toe.

The joints of the foot, ankle, knee, wrist, elbow, and hand are other frequently affected sites. In such cases the condition is known as polyarticular gout. More than one joint is affected in 10% to 20% of first attacks. The pain usually occurs in joints on one side of the body and it is usually, although not always, in the lower extremities. People with polyarticular gout are more likely to have a more gradual onset of pain and a longer delay between attacks. They are also more likely to experience a low-grade fever, loss of appetite, and a general feeling of poor health.

The primary symptom, which usually takes eight to 12 hours to develop, is severe, sometimes crushing pain at and around the joint. In many cases the attack occurs late at night or early in the morning and announces itself by waking the sufferer. Some patients describe it as resembling a dislocated bone and one writer described it as "like walking on my eyeballs." Chills and mild fever may follow. The area can be so tender that walking and even the weight of bed sheets can be unbearable. Swelling may extend beyond the joint, indicating fluid build-up within. The skin over the affected area is often red, shiny, and tense. After a few days it may start to peel. An untreated attack will typically peak 24 to 48 hours after the initial appearance of symptoms, and subside after five to seven days, although it can last only hours to several weeks.

Intercritical Gout

Intercritical gout is the term used to describe the periods between attacks. The first attack is usually followed by a complete remission of symptoms, but in untreated cases most people can expect a recurrence. One study found that 62% of subjects experienced at least one further attack within a year. At the end of two years 78% and after 10 years 93% of patients experienced a recurrence of gout.

Symptoms of Chronic Tophaceous Gout

When gout remains untreated, the intercritical periods typically become shorter and shorter, and the attacks, although sometimes less intense, can last longer. Gout may eventually affect several joints, including those that may have been free of symptoms at the first appearance of the disorder. In rare cases, the shoulders, hips, or spine are affected. Over the long term, about 10 to 20 years, in untreated gout the intercritical periods dwindle until gout becomes a chronic disorder characterized by constant low-grade pain and mild or acute inflammation in several joints. Persistent gout, moreover, can destroy cartilage and bone, causing irreversible joint deformities and loss of motion.

Symptoms of Tophi. Tophi, the solid, knobby MSU crystal deposits that form during this process are generally painless themselves, but they often cause pain and stiffness in an affected joint and can erode cartilage and bone, ultimately destroying the joint. Large tophi under the skin of the hands and feet can give rise to extreme deformities.

How Serious Is Gout?

Left untreated, gout can develop into a painful and disabling chronic disorder. Tophi are capable of growing to the size of handballs and can destroy bone and cartilage in the joints, similar to the process in rheumatoid arthritis. If they lodge in the spine, they can cause serious damage including compression, although this is a very rare event. In extreme cases, joint destruction results in complete disability. But now, after several decades of research into the causes of gout and the development of drugs for controlling hyperuricemia, gout rarely poses a long-term threat to health if properly treated. Still, it remains a source of short-term pain and incapacity for thousands of Americans. Kidney stones occur in between 10% and 40% of gout patients, and can occur at any time after the development of hyperuricemia. Although the stones are usually composed of uric acid, they may also be mixed with other materials. About 25% of patients with chronic hyperuricemia develop progressive kidney disease, which, in some cases, ends in kidney failure. Many experts believe, however, that chronic hyperuricemia is unlikely to be a common cause of kidney disease, and that, in most cases, the kidney abnormalities come first and cause high concentrations of uric acid. Gout also accompanies and can be exacerbated by other serious conditions that are associated with kidney and heart disease including diabetes, obesity, unhealthy cholesterol levels, insulin resistance, and high blood pressure. Hyperuricemia has also been associated with a higher risk of death from heart and circulatory diseases, although it is unknown whether hyperuricemia is a risk factor independent of the high-risk conditions it often accompanies.

What Are The Risk Factors For Gout?

Risk factors are attributes or activities associated with a greater-than-normal likelihood of developing a particular disorder. Sometimes a causal connection between the attribute or activity and the disorder can be established, but at other times there is simply a statistical correlation. The risk factors for gout, of which there are several, are identical to those for hyperuricemia.

Prevalence

Gout is one of the most common types of arthritis. In the United States there were an estimated 2.2 million cases of self-reported gout in 1986, and a 1991 publication noted that Americans lost an estimated 37 million working days a year to gout. It is estimated that approximately 15 of every 1,000 American males between 35 and 45 years of age have gout and some experts believe that one in 100 men may be at risk for it. It is very uncommon in less developed countries and in 1952 it was said to be unknown in China, Japan, the tropics, and rare among African Americans. The prevalence of gout not only in America but in other developed countries has, however, been rising in recent decades, possibly because of dietary and lifestyle changes, greater use of medications that cause hyperuricemia, and aging populations.

Gender and Age Differences

Among children, the levels of uric acid in both girls and boys are low, (on average 3 to 4 mg/dL). Except for rare inherited genetic disorders that cause hyperuricemia, gout in children is almost unheard of. In males, levels rise substantially at puberty, with the result that the level exceeds 7 mg/dL (considered to indicate hyperuricemia) in about 5% to 8% of American men. Gout typically strikes only after 20 to 40 years of persistent hyperuricemia, so men usually experience their first attack between the ages of 30 and 50 years old. Men over 40 years old account for about 90% of the population affected by gout. Less than 5% of patients with gout are female. The female hormone estrogen appears to facilitate uric acid excretion by the kidneys, so levels in women remain essentially stable until menopause, after which they approach male levels. Premenopausal women are thus much less likely than men of the same age to be hyperuricemic. Women are more likely to experience gout between the ages of 50 and 70.

Family History

A fairly substantial proportion of patients with gout (10% to 20%) has a family history of the arthritic condition.

Other Risk Factors

Obesity. Researchers report a clear link between body weight and uric acid levels; obesity may be an especially important risk factor for gout in men. In one Japanese study, overweight people had between 2 and 3.4 times the incidence of hyperuricemia as those of normal or low weights.

Hypertension. Hypertension (high blood pressure) is found in 25% to 50% of patients with gout, but whether it causes hyperuricemia is uncertain.

Alcohol Use. Alcohol use is associated with gout and in one study, it was the only notable risk factor for women with gout.

How Is Gout Diagnosed?

Standard diagnostic tools for gout may include a medical history and physical examination, a blood test for hyperuricemia, and urine sample. For a definitive diagnosis of gout, a sample of synovial fluid from the affected joint is required, which is examined for signs of the characteristic crystals. X-rays can provide helpful information in some cases.

Ruling Out Other Disorders

As part of the diagnostic process other disorders that resemble gout symptoms or cause hyperuricemia should be ruled out. In general, it is easy to distinguish acute gout that occurs in one joint from other arthritic conditions; the two disorders that may confuse this diagnosis are pseudogout and septic arthritis, a potentially life-threatening condition. Chronic gout can often resemble rheumatoid arthritis.

Pseudogout. Pseudogout is a condition most likely to be confused with gout. It is caused by deposits of calcium pyrophosphate dihydrate crystals in and around the joints. Though pseudogout resembles gout in some ways, the first attack typically strikes the knee rather than the joint of the big toe, and at least two-thirds of cases affects more than one joint. The symptoms of pseudogout also appear more slowly than those of gout, taking days rather than hours to develop. In addition pseudogout is more likely to occur in the autumn while gout attacks are most common in the spring.

Septic Arthritis. Septic arthritis is a bacterial infection that can cause inflamed joints, chills, and spiking fever. The severity of the fever and a high white-blood cell count in the joint fluid helps differentiate septic arthritis from gout, but at times it is difficult to tell the conditions apart. A correct diagnosis is critical. It is essential to administer potent antibiotics to treat septic arthritis.

Rheumatoid Arthritis. Rheumatoid arthritis can cause distortion in the joints of the fingers, inflammation, and pain that may mimic gout. A proper diagnosis can be made with a detailed medical history, laboratory tests, and identification of MSU crystals.

Other Causes of Arthritic Pain. The symptoms of gout can resemble those of many other disorders, including acute rheumatic fever, traumatic arthritis, osteoarthritis, serious skin infections, hallux rigidus (painful stiffness in the first joint of the big toe), and Reiter's syndrome (a disorder characterized by arthritis, urethritis, and conjunctivitis). Many of these disorders can be present at the same time as gout. [ See Box ]

Other Causes of Hyperuricemia. Binge drinking, fasting, lead toxicity, leukemia, certain uncommon anemias, multiple myeloma, and lymphomas are also uncommon causes of high uric acid concentrations.

Medical History and Physical Examination

Determining which joints are affected in a patient suspected of having gout is an obvious first step in any diagnosis. A physician is more likely to suspect gout as the cause of an acute attack of arthritis if it first appears in the first joint of the big toe than if arthritis attacked, for example, a shoulder or hip. The examiner also needs to determine whether the onset of pain and swelling was rapid, as symptoms that take days or weeks rather than hours to develop probably indicate a disorder other than gout. Another possible indicator of gout is previous damage to an affected joint, because gout often arises in injured joints.

Blood Test

A blood test is usually given, although some experts argue that it isn't necessary, given what is now known about the variability of uric acid levels in people with gout. Uric acid levels in the blood during an attack of gout do not necessarily mirror levels before the attack, and in fact can lie within or below the normal range. Even if hyperuricemia is present, it is very common in the population and does not necessarily indicate the presence of gout. A low level of uric acid in the blood however, makes a diagnosis of gout much less probable, and a very high level increases the likelihood of gout.

24-Hour Urine Sample

It is sometimes helpful to gauge the amount of uric acid excreted by the patient over the course of 24 hours, particularly if the patient is young and has pronounced hyperuricemia that might be related to a metabolic disorder. If the amount exceeds a particular value, further tests for an enzyme defect or other identifiable cause of gout arising from uric acid overproduction are justified. Greater-than-normal amounts of uric acid in the urine also indicate that the patient faces a greater risk of developing uric acid kidney stones, and can guide the physician in his or her choice of drug therapy for chronic gout. The urine is collected during an intercritical period, after the patient has been placed on a purine-reduced diet. The patient is also asked to temporarily stop using alcohol and any medications that can interfere with the test. On the first day of the test, the urine passed by the patient on waking up in the morning is discarded, but for the next 24 hours the patient collects all of his or her urine in a special container. The test concludes the next morning with the patient urinating into the container right after waking up. The container is then delivered to the patient's physician or sent directly to the laboratory.

Examination of Synovial Fluid

Examination of synovial fluid is the most accurate method for diagnosing gout; it may even be helpful in detecting gout during intercritical periods. The synovial fluid is the lubricating liquid that fills the synovium, the membrane that surrounds a joint and creates a protective sac. In addition to cushioning joints, this fluid supplies nutrients and oxygen to cartilage, the slippery tissue that coats the ends of bones. The procedure for taking a sample of synovial fluid from an affected joint is called aspiration. A needle attached to a syringe is inserted into the joint and suction is used to draw the fluid into the syringe. Local anesthesia is avoided because it can reduce the effectiveness of aspiration, but normally the procedure is only mildly uncomfortable. Following the procedure there can be some minor discomfort in the area where the needle was inserted, but it usually dissipates quickly. Aspiration can cause infection, though this occurs in less than 0.1% of patients. After the sample is taken, it is sent to a laboratory, where a microscope is used to look for monosodium urate (MSU) crystals, which can be detected with polarized light. The laboratory can also test the sample for infection (always a possibility in cases of gout). Another benefit of aspiration is that it sometimes eases a patient's symptoms by reducing swelling and pressure on the tissue surrounding the joint.

X-Rays

For the most part, x-rays do not reveal any abnormalities during the early stages of gout, and their usefulness where gout is concerned lies in assessing the progress of the disorder in its chronic phase and in identifying other health problems whose symptoms may resemble those of gout. Tophi can be seen on x-rays before they become apparent on physical examination.

Trial of Colchicine

Until recently a standard diagnostic test was administering a trial of the traditional antigout drug colchicine. Improvement in the patient's condition after taking the drug is an indication of gout. There are limitations, however, to this approach. Colchicine often has distressing side effects including nausea, vomiting, diarrhea, and abdominal cramps when taken orally. In any event, its attractiveness as a diagnostic tool is limited because it can also relieve symptoms in other arthritic conditions, including pseudogout.

How Is Gout Treated?

General Guidelines

Acute attacks of gout and long-term treatment of gout and its associated hyperuricemia require different approaches. All phases are treated mainly with drugs. There are also specific treatment regimes for conditions associated with gout, including uric acid nephropathy and uric acid nephrolithiasis.

Treatments for Asymptomatic Hyperuricemia. Because asymptomatic hyperuricemia usually does not lead to gout or other health problems, and would have to be treated with drugs that present certain risks and can be expensive, treatment to prevent a first attack of gout in hyperuricemic patients is considered inadvisable. In unusual circumstances, for example when very high uric acid levels threaten the kidney, treatment may be justified.

Treatment of Acute Gouty Arthritis. Drug treatments for acute attacks of gout are aimed at relieving pain and reducing inflammation. Powerful forms of nonsteroidal anti-inflammatory drugs (NSAIDs) are the drugs of choice for an acute attack. Colchicine or corticosteroids may also be used. Rest, applying cold, and protecting the affected joint with a splint can also promote recovery. Acute attacks respond best to immediate treatment. After the first attack, some physicians advise their patients to keep a supply of medications on hand so that self-medication can begin at the first sign of symptoms of a second acute attack.

Treatment for Intercritical Period and Tophaceous Gout. During the period between gout attacks, patients are advised to avoid foods high in purines and to maintain a healthy weight. Patients should also avoid alcohol and reduce any stress. Many patients do not require medications. Usually preventive drug therapy is used only if there are two or three attacks that occur within a year. Some physicians prescribe low-dose NSAIDs or colchicine to prevent recurrent attacks. Increasing the dose when a patient believes an attack is pending can often abort it. These are simply anti-inflammatory drugs, however, and have no effect on hyperuricemia.

The goals of antihyperuricemic therapy are to reduce uric acid levels to normal, decrease the frequency of attacks, and to dissolve monosodium urate (MSU) crystals and tophi. Allopurinol and drugs known as uricosurics, which include probenecid and sulfinpyrazone, are available for these purposes and are all very effective. Which drug to prescribe depends on individual conditions. [ See Specific Drugs for Long-Term Treatment, below.] When and if to prescribe them at all, however, is not entirely clear. Some physicians do not prescribe them if hyperuricemia is mild or until a patient has had two attacks. Others prescribe them immediately after a single attack. It should be noted that any of these drugs can actually precipitate acute gout symptoms and so should not be used until symptoms have subsided, and then the patient should start with small doses that gradually increase. Colchicine or an immediate-acting NSAID, such as naprosyn, should be given during the initial months of therapy to prevent symptom attacks. Most of the time, antihyperuricemic therapy means taking a drug routinely throughout life, which many people find difficult to adhere to. In rare cases, surgery is used to treat the effects of chronic gout.

Specific Drugs Used for Acute Attacks

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs ). Nonsteroidal anti-inflammatory drugs (NSAIDs) block prostaglandins, the substances that dilate blood vessels and cause inflammation and pain. They are taken orally at their highest safe dosage as long as symptoms persist and for three or four days after. There are dozens of NSAIDs. Indomethacin (Indocin) in doses up to 200 mg a day is the usual choice for gout. The first dose of indomethacin usually begins to act against the pain and inflammation of gout within 24 hours, and often much sooner. Ibuprofen, naproxen, sulindac, or others are good alternatives particularly for elderly patients who might experience confusion or bizarre sensations with indomethacin [ see below ]. (Aspirin is also an NSAID, but in low doses is associated with a higher risk for gout and should be avoided.)

All NSAIDs are capable of damaging the mucous layer and causing ulcers and gastrointestinal (GI) bleeding. One study indicated that taking NSAIDs for only six months posed a risk for symptomatic ulcers that was greater than 1%. Regular use of even over-the-counter NSAIDs may be hazardous for anyone. They also appear to delay the emptying of the stomach, which may interfere with the actions of other RA drugs. The elderly, in any case, are at special risk. Younger nonsmoking adults adapt better to NSAIDs. Bleeding and ulcers can occur at any time, with or without symptoms. The risk for bleeding is continuous as long as a patient is on these drugs and may even persist as long as a year after the drug is discontinued. One study ranked the sixteen most commonly used NSAIDs according to risk for ulcers and bleeding. Those at lowest risk were nabumetone (Relafen), etodolac (Lodine), salsalate, and sulindac (Clinoril). At medium risk were diclofenac (Voltaren), ibuprofen (Motrin, Advil, Nuprin, Rufen), naproxen (Aleve, Naprosyn, Naprelan, Anaprox), and tolmetin (Tolectin). Drugs within this group, however, vary in risk. Studies show, for example, that short-term use of naproxen is twice as likely as ibuprofen to be associated with hospitalization from GI bleeding. Although ketoprofen (Actron, Orudis KT) was considered a medium-risk drug, another study reported that even one week of taking the drug at low doses causes significant GI injury. The highest risk for GI bleeding were flurbiprofen (Ansaid), piroxicam (Feldene), fenoprofen, indomethacin (Indocin), meclofenamate (Meclomen), and oxaprozin. Others not compared in this analysis were diflunisal (Dolobid) and ketorolac (Toradol).

A gel containing ibuprofen can be applied to sore joints and may pose less risk for gastrointestinal side effects. The drug omeprazole (Prilosec), known as a proton-pump inhibitor, may both heal and help prevent NSAID-related ulcers. Misoprostol (Cytotec) is also commonly used to prevent NSAID-induced ulcers; in one study, a combination of the NSAID diclofenac and misoprostol (Arthrotec) resulted in 65% to 80% fewer ulcers than in patients who took NSAIDs alone. Side effects of misoprostol include diarrhea, cramps, and gas. Common antacids, or H2 blockers, such as ranitidine (Zantac), cimetidine (Tagamet), famotidine (Pepcid), and nizatidine (Axid), reduce symptoms caused by gas but do not keep NSAIDs from causing ulcers. In fact, such drugs may pose a danger by masking symptoms of developing ulcers.

Other side effects of NSAIDs include dizziness, ringing in the ear, headache, and skin rash. Depression has also been noted. Kidney abnormalities have been reported in people taking NSAIDs, which resolves when the drugs are withdrawn. NSAIDs may also increase blood pressure, particularly in those on medications to reduce hypertension. Piroxicam (Feldene), naproxen (Aleve), and indomethacin (Indocin) appear to pose the greatest risks for high blood pressure. (Sulindac has the smallest effect.) People with hypertension, severe vascular disease, kidney, or liver problems, and those taking diuretics must be closely monitored if they need to take NSAIDs. Any sudden weight gain or swelling should be reported to a physician. Because NSAIDs reduce the clotting of the blood, anyone undergoing surgery should stop taking the medication a week before the operation. Diabetics taking oral hypoglycemics may need to adjust the dosage if they also need to take NSAIDs because of possible harmful interactions between the drugs. Alcohol abuse may increase the risks for bleeding.

Colchicine. Colchicine, a derivative of the autumn crocus (also called the meadow saffron), has been used against gout for centuries. It is highly effective though no longer the first drug of choice because of its frequent and unpleasant side effects. The oral regimen requires doses every hour until the patient either improves or side effects develop; improvement should be evident by the tenth dose. Although oral colchicine usually eliminates the pain of an acute attack within 48 hours, it is unsuitable for many patients because of nausea, vomiting, diarrhea, or abdominal cramps after taking the drug. Cimetidine (Tagamet) and the antibiotic erythromycin can intensify the gastrointestinal side effects of colchicine. Overdose can be fatal. Intravenous administration of colchicine relieves episodes of gout without gastrointestinal effects and for a time, physicians hoped it could be used routinely. The intravenous route has some serious side effects, however, and poses an increased risk for injury to the kidney, liver, central nervous system, and bone marrow. The drug, in general, is not appropriate for patients with kidney, liver, or bone marrow disorders. It can also effect fertility.

Corticosteroids. The corticosteroids, known commonly as steroids, are used only when patients cannot tolerate other anti-inflammatory drugs or they are ineffective. They include triamcinolone (administered by injection) and prednisone (taken orally). Corticotropin (ACTH), a drug that converts to a steroid, is another option. A single intravenous dose is usually sufficient, and some physicians believe it is the most rapid and reliable method for terminating an attack. If only one joint is affected, an injection may be administered directly to the site. Oral doses are usually given for seven to 10 days to prevent a rebound attack, which can occur after a corticosteroid injection. Colchicine is sometimes given two or three times daily along with the steroid and for several days after discontinuing it. These drugs should only be administered for short periods and not used for long-term treatment.

COX-2 Inhibitors. Celecoxib (Celebrex) and rofecoxib (Vioxx) are new drugs known as COX-2 (cyclooxygenase-2) inhibitors, the so-called super-aspirins. Standard NSAIDs block two prostaglandin-producing enzymes called cyclooxygenase 1 and 2 (COX-1 and 2). The new drugs block COX-2, which is responsible for most inflammatory effects, but not COX-1, which normally protects the stomach. Short-term studies comparing them to a number of NSAIDs, are indicating that they may be as effective and less harmful to the GI tract than NSAIDs. It is not yet known if they are safe and effective for gout or other chronic conditions.

Specific Drugs for Long-Term Treatment

Long-term treatment of hyperuricemia is recommended for tophi prevention and when the patient has suffered several acute attacks of gout over a number of years, when the attacks are unusually severe or affect more than one joint, or when hyperuricemia is caused by an identifiable inborn metabolic deficiency. A number of effective agents are available. Before starting one of these drugs, any acute attack should be completely controlled and the joints should not be inflamed; some physicians prefer to wait about a month after an attack before starting a prevention program. Urine tests should be performed to determine if the patient is an under- or over-excreter of uric acid. The uricosuric drugs probenecid or sulfinpyrazone enhance uric acid excretion and so are appropriate when gout is caused by under-excretion of uric acid, which occurs in about 80% of cases. Normal kidney function is essential for taking these drugs. Allopurinol inhibits uric acid production and is useful for those who overproduce uric acid, who have kidney disorders, or who have kidney stones.

Uricosuric Drugs. Probenecid (Benemid, Parbenem, Probalan) and sulfinpyrazone (Anturane) are uricosurics, which are drugs that prevent the kidney from reabsorbing uric acid and so increase the amount excreted in the urine. Uricosuric drugs are usually the choice for patients under 60 years old who have normal diets and kidney function and have no risk of kidney stones. Uricosuric drug candidates should also produce no more than 700 to 800 mg of uric acid in urine over a 24-hour period. These drugs may actually intensify gout symptoms if they are not started until acute attacks have stopped. The initial doses should be low and then gradually built up. Adding low-dose colchicine or an NSAID may help prevent gout attacks. Probenecid is taken twice to three times a day and sulfinpyrazone begins at twice a day and increases to three or four times daily. The possible side effects of these two drugs include skin rashes, gastrointestinal problems, anemia, and kidney stone formation. Sufficient fluid intake is important to help reduce acidity and so prevent uric acid kidney stones. To reduce the urine acidity as quickly as possible, patients may also be given sodium bicarbonate supplemented by acetazolamide. NSAIDs, particularly aspirin, as well as other salicylate drugs, interfere with these drugs and reduce effectiveness, so they should be avoided; patients who require minor pain relief should take acetaminophen (Tylenol and others). Uricosurics also interact with many other drugs, and a patient should be sure to inform the physician of any medications they are taking. A uricosuric combined with allopurinol is occasionally effective in cases where using just one drug is not. Probenecid combined with colchicine is more effective than probenecid alone, but patients respond differently to this regimen depending on the dosage balance, so it needs to be carefully individualized.

Allopurinol. Allopurinol (Lopurin, Zyloprim) blocks uric acid production and is the drug most often used in long-term treatment for older patients and those who are over-producers of uric acid (levels of excreted uric acid are over 800 mg during a 14-hour period). It is also considered the drug of choice for patients with impaired kidney function, a history of kidney stones, and for tophaceous gout. Allopurinol is taken orally only once a day in doses of 100 mg to 600 mg, depending on the patient's response to treatment. The drug's side effects, experienced by 3% to 5% of patients, include skin rashes, leukopenia (a reduction in the number of white blood cells), thrombocytopenia (a reduction in the number of platelets), diarrhea, headache, and fever. It may also increase the risk for cataracts. When it is first used, allopurinol can trigger further attacks of gout, and thus during the first months (or longer) of therapy the patient is also given a NSAID or colchicine to forestall that possibility. Some patients experience an allergic reaction to allopurinol, which can be fatal in rare cases. Such individuals may be able to build up their tolerance for the drug by undergoing a desensitization process. Even if a first attempt at desensitization fails, one case study suggested that subsequent attempts may still be successful.

Colchicine and NSAIDs. Low doses of NSAIDs or colchicine are used to prevent gout attacks in patients who are starting anti-hyperuricemic therapies. For patients who cannot take either allopurinol or a uricosuric, low daily doses of oral colchicine provide a possible alternative treatment for hyperuricemia, although not among patients with kidney or liver disease.

Surgery

Surgery is sometimes used to remove large tophi that are draining, infected, or interfering with the movement of joints. Several other surgical procedures are available for relieving pain in and improving the function of affected joints. It is sometimes necessary to replace joints.

Treatment for Pseudogout

There is no cure for pseudogout, but there are treatments to relieve the pain and inflammation and reduce the frequency of attacks. NSAIDs are effective for treating inflammation and pain from pseudogout. For acute attacks in large joints, fluid aspiration alone or with steroids may help. Intravenous colchicine is also helpful but may be toxic. Pseudogout is a progressive disorder that can destroy joints, and joint replacement may be required.

Treatment of Kidney Disorders Related to Gout

Uric Acid Nephropathy. Uric acid nephropathy is common in chemotherapy patients. In such cases it is preventable if they are adequately hydrated and given allopurinol before chemotherapy begins. Treatment has reduced the death rate in cases of uric acid nephropathy from about 50% to close to zero.

Uric Acid Nephrolithiasis. Uric acid stones are dissolved by giving the patient allopurinol to reduce the concentration of uric acid in his or her urine. The patient also takes oral sodium bicarbonate or acetazolamide (Diamox) to alkalinize the urine. Drinking at least 10 to 12 eight-ounce glasses of water and other nonalcoholic beverages every day is important as well. [For more information see Kidney Stones. ]

What Lifestyle Measures Can Help Prevent Gout?

Avoiding Excessive Energy Demands

Any activities that increase energy demands also increase metabolism or purines that produce uric acid. Avoiding stress and staying healthy are important for preventing attacks.

Dietary Recomendations

Avoid Foods Containing Purines. Because uric acid levels are only minimally affected by diet, dietary therapy does not play a large role in the prevention of gout. Still, people who have suffered an attack of gout may benefit from reducing their intake of purine-rich foods if they habitually eat unusually large quantities of such foods. They include beer and other alcoholic beverages, anchovies, sardines (in oil), fish roes, herring, yeast, organ meats (eg, liver, kidneys, sweetbreads), legumes (eg, dried beans, peas, and soybeans), meat extracts, consommé, gravies, mushrooms, spinach, asparagus, and cauliflower. Any meat, fish, or poultry has moderate amounts of purines.

Protein Restriction. Diets high in protein, particularly animal protein, increase uric acid. Although few studies have been conducted and none have determined the value of reducing protein, one study of gout patients suggested that eating tofu, which is made from soy and is a source of complete protein, may be a better choice than meats.

Possibly Helpful Foods and Supplements. Dark berries and cherries may contain chemicals that lower uric acid and reduce inflammation. Vitamin C and folic acid supplements may also have some benefits. (Vitamin A may increase the risk for gout attacks.)

Maintain Healthy Weight

A supervised weight-loss program may be a very effective way to reduce uric acid levels if the patient is overweight. Crash dieting, on the other hand, is counterproductive because it can increase uric acid levels and can cause an acute attack.

Maintain Fluids

Drinking plenty of water and other nonalcoholic beverages helps remove MSU crystals from the body. Some researchers are studying the anti-inflammatory properties of green tea, which might have some benefit for gout. It should be noted, a Japanese study reported a higher association between gout and tea drinking (although the study did not describe the type of tea).

Avoid Alcohol

Alcohol should be avoided, since it promotes purine metabolism and uric acid production; it also may reduce excretion of uric acid. Heavy drinking, especially binge drinking of beer or distilled spirits, should especially be avoided.

Avoid Joint Injury

People with gout should also attempt to identify and avoid activities that cause repetitive joint trauma, such as wearing tight shoes.

Prevention during Travel

Travel is an example of an activity that increases the risk for gout; it not only places increased demands on the patient, but eating and drinking patterns may change. Before traveling, patients should discuss preventive measures with their physicians. The doctor may prescribe a prednisone tablet to be taken immediately at the first sign of a gout attack; in most cases this stops the episode.

Where Else Can Help Be Obtained For Gout?

The Arthritis Foundation, 1330 Peachtree St., Atlanta GA 30309. Call(800-283-7800) or on the Internet (http://www.arthritis.org/ )
This is an excellent source for many types of services. The foundation funds research and provide brochures, video tapes, exercise programs, physician referrals, and local chapters.


The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), One AMS Circle, Bethesda MD 20892-3675. Call (301-495-4484) or on the Internet (http://www.nih.gov/niams/ )


American Academy of Orthopedic Surgeons, PO Box 2058, Des Plaines, IL 60017.
This organization will send information on arthritis by sending a self-addressed stamped business envelope. Be sure to designate "Arthritis" on the outside envelope.


Aids for Arthritis, Inc., (Call 609-654-6918).
Enrichments. Call (800-323-5547) or on the Internet (www.sammonspreston.com )
Both companies offer supportive devices and products for people with arthritis. Call for catalogs.

The above information from MD Consult, with permission.

[ Home ] [ Up ]

Send mail to daktari@bethesdaclinic.com with questions or comments about this web site.
Copyright © 2001 Bethesda Clinic

                                        10/27/2001