Gout and Hyperuricemia
Chronic gout can lead to deposits of hard lumps of uric acid in and around the joints, decreased kidney function, and kidney stones.
Gout has the unique distinction of being one of the most frequently recorded medical illnesses throughout history. It is often related to an inherited abnormality in the body's ability to process uric acid. Uric acid is a breakdown product of purines, that are part of many foods we eat. An abnormality in handling uric acid can cause attacks of painful arthritis (gout attack), kidney stones, and blockage of the kidney filtering tubules with uric acid crystals, leading to kidney failure. On the other hand, some patients may only develop elevated blood uric acid levels (hyperuricemia) without having arthritis or kidney problems. The term "gout" commonly is used to refer to the painful arthritis attacks.
Gouty arthritis is usually an extremely painful attack with a rapid onset of joint inflammation. The joint inflammation is precipitated by deposits of uric acid crystals in the joint fluid (synovial fluid) and joint lining (synovial lining). Intense joint inflammation occurs as white blood cells engulf the uric acid crystals and release chemicals of inflammation, causing pain, heat, and redness of the joint tissues.
Approximately one million people in the United States suffer from attacks of gout. (Did you know that none other than Benjamin Franklin had terrible gouty arthritis!) Gout is nine times more common in men than in women. It predominantly attacks males after puberty, with a peak age of 75. In women, gout attacks usually occur after menopause.
While an elevated blood level of uric acid (hyperuricemia) may indicate an increased risk of gout, the relationship between hyperuricemia and gout is unclear. Many patients with hyperuricemia do not develop gout, while some patients with repeated gout attacks have normal or low blood uric acid levels. Among the male population in the United States, approximately ten percent have hyperuricemia. However, only a small portion of those with hyperuricemia will actually develop gout.
Who is affected by gout?
What are the risk factors for gouty arthritis?
In addition to an inherited abnormality in handling uric acid, other risk factors for developing gout include obesity, excessive weight gain, especially in youth, moderate to heavy alcohol intake, high blood pressure, and abnormal kidney function. Certain drugs, such as thiazide diuretics, low-dose aspirin, niacin, cyclosporine, tuberculosis medications (pyrazinamide and ethambutol), and others can also cause elevated uric acid levels in the blood and lead to gout. Furthermore, certain diseases lead to excessive production of uric acid in the body. Examples of these diseases include leukemias, lymphomas, and hemoglobin disorders.
Interestingly, a recent study demonstrated an increased prevalence of abnormally low thyroid hormone levels (hypothyroidism) in patients with gout.
In patients at risk of developing gout, certain conditions can precipitate acute attacks of gout. These conditions include dehydration, injury to the joint, fever, excessive dining, heavy alcohol intake, and recent surgery. Gout attacks triggered by recent surgery are probably related to changes in the body fluid balance as patients temporarily discontinue normal oral fluid intake in preparation for and after the surgery.
What are symptoms of gout?
The small joint at the base of the big toe is the most common site of an acute gout attack. Other joints that can be affected include the ankles, knees, wrists, fingers, and elbows. Acute gout attacks are characterized by a rapid onset of pain in the affected joint followed by warmth, swelling, reddish discoloration, and marked tenderness. Tenderness can be intense so that even a blanket touching the skin over the affected joint can be unbearable. Patients can develop fever with the acute gout attacks. These painful attacks usually subside in hours to days, with or without medication. In rare instances, an attack can last for weeks. Most patients with gout will experience repeated attacks of arthritis over the years.
Uric acid crystals can deposit in tiny fluid-filled sacs (bursae) around the joints. These urate crystals can incite inflammation in the bursae leading to pain and swelling around the joints, a condition called bursitis. In rare instances, gout leads to a more chronic type of joint inflammation which mimics rheumatoid arthritis.
In chronic (tophaceous) gout, nodular masses of uric acid crystals (tophi) deposit in different soft tissue areas of the body. Even though they are most commonly found as hard nodules around the fingers, at the tips of the elbows, and around the big toe, tophi nodules can appear anywhere in the body. They have been reported in unexpected areas such as in the ears, vocal cords, or (rarely) around the spinal cord!
How is gouty arthritis diagnosed?
Gout is suspected when a patient reports a history of repeated attacks of painful arthritis at the base of the toes. Ankles and knees are the next most commonly involved joints in gout. Gout usually attacks one joint at a time, while other arthritis conditions, such as systemic lupus and rheumatoid arthritis, usually attack multiple joints simultaneously.
The most reliable test for gout is finding uric acid crystals in the joint fluid obtained by joint aspiration (arthrocentesis). Arthrocentesis is a common office procedure performed under local anesthesia. Using sterile technique, fluid is withdrawn (aspirated) from the inflamed joint, using a syringe and needle. The joint fluid is then analyzed for uric acid crystals and for infection. Shiny, needle-like uric acid crystals are best viewed with a polarizing microscope. The diagnosis of gout can also be made by finding these urate crystals from material aspirated from tophi nodules and bursitis fluid.
Some patients with a classic history and symptoms of gout can be successfully treated and presumed to have gout without undergoing arthrocentesis. However, establishing a firm diagnosis is still preferable since other conditions can mimic gout. These include another crystal-induced arthritis called pseudogout, psoriatic arthritis, rheumatoid arthritis and even infection.
X-rays can sometimes be helpful, and may show tophi crystal deposits and bone damage as a result of repeated inflammations. X-rays can also be helpful for monitoring the effects of chronic gout on the joints.
How is gout treated?
Preventing acute gout attacks is equally as important as treating the acute arthritis. Prevention of acute gout involves maintaining adequate fluid intake, weight reduction, dietary changes, reduction in alcohol consumption, and medications to reduce hyperuricemia.
Maintaining adequate fluid intake helps prevent acute gout attacks. Adequate fluid intake also decreases the risk of kidney stone formation in patients with gout. Alcohol is known to have diuretic effects which can contribute to dehydration and precipitate acute gout attacks. Alcohol can also affect uric acid metabolism and cause hyperuricemia. It causes gout by impeding (slowing down) the excretion of uric acid from the kidneys as well as by causing dehydration, which precipitates the crystals in the joints.
Dietary changes can help reduce uric acid levels in the blood. Since purine chemicals are converted by the body into uric acid, purine rich foods are avoided. Examples of foods rich in purine include shellfish and organ meats, such as liver, brains, kidneys, and sweetbreads. Researchers have reported, in general, that meat or seafood consumption increases the risk of gout attacks, while dairy consumption seemed to reduce the risk! Protein intake or purine-rich vegetable consumption was not associated with an increased risk of gout. Total alcohol intake was strongly associated with an increased risk of gout (beer and liquor were particularly strong factors).
Weight reduction can be helpful in lowering the risk of recurrent attacks of gout. This is best accomplished by reducing dietary fat and calorie intake, combined with a regular aerobic exercise program.
There are three aspects to the medication treatment of gout. First, pain relievers such as acetaminophen/Tylenol or other more potent analgesics are used to manage pain. Secondly, anti-inflammatory agents such as nonsteroidal anti-inflammatory drugs (NSAIDS), colchicine, and corticosteroids are used to decrease joint inflammation. Finally, medications are considered for managing the underlying metabolic derangement that causes hyperuricemia and gout. This means treating the elevated levels of uric acid in the blood with medications that reduce these levels. NSAIDS such as indomethacin (Indocin) and naproxen (Naprosyn) are effective anti-inflammatory medications for acute gout. These medications are tapered after the arthritis resolves. Common side effects of NSAIDS include irritation of the gastrointestinal system, ulceration of the stomach and intestines, and even intestinal bleeding. Patients who have a history of allergy to aspirin or nasal polyps should avoid NSAIDS because of the risk of an intense allergic (anaphylactic) reaction.
Colchicine for acute gout is most commonly administered by mouth, but can also be given intravenously. Orally, it is given hourly or every two hours until there is significant improvement in pain or the patient develops gastrointestinal side effects such as severe diarrhea. Other common side effects of colchicine include nausea and vomiting.
Corticosteroids, such as prednisone, given in short courses, are powerful anti-inflammatory agents for treating acute gout. They can be administered orally or injected directly into the inflamed joint. Corticosteroids can be prescribed to patients who have accompanying kidney, liver, or gastrointestinal problems. Long-term chronic use of corticosteroids is discouraged because of serious long-term side effects.
In addition to medications for acute gout attacks, other drugs can be taken over prolonged periods to lower blood uric acid levels. Lowering blood uric acid levels reduces the risk of recurrent attacks of arthritis, kidney stones, and kidney disease, and also dissolves hard tophi deposits. Medicines used to lower blood uric acid level work either by increasing the kidney excretion of uric acid, or by decreasing the body's production of uric acid from the purine in foods. These medicines are generally not started until after the inflammation from acute gouty arthritis has subsided because they can worsen the attack. If they are already being taken prior to the attack, they are continued and only adjusted after the attack has resolved. Since many patients with elevated blood uric acid levels may not develop gouty attacks or kidney stones, the decision for prolonged treatment with uric acid-lowering drugs should be individualized.
Probenecid (Benemid) and sulfinpyrazone (Anturane) are medications that are commonly used to decrease uric acid blood levels by increasing the excretion of uric acid into the urine. Since these drugs can, in rare instances cause kidney stones, they should be avoided by those patients with a history of kidney stones. These medications should be taken with plenty of fluid so as to promote the rapid passage of uric acid out of the urinary system in order to prevent stone formation.
Allopurinol (Zyloprim) lowers the blood uric acid level by preventing uric acid production. It actually blocks the metabolic conversion from purine in foods to uric acid. This medication should be used with caution in patients with poor kidney function, as they are at a particular risk of developing side effects, including rash and liver damage.
Again, uric acid-lowering medications, such as allopurinol (Zyloprim), are generally avoided in patients who are having acute attacks of gout (unless they are already taking them). For unknown reasons, these medications, when started during an acute attack, actually can worsen the acute inflammation. Therefore, uric acid-lowering drugs are usually instituted only after complete resolution of the acute arthritis attacks. If patients are already taking these medications, they are maintained at the same doses during the acute attacks. In some patients, increasing the dose of uric acid-lowering medications can precipitate gout attacks. In these patients, low doses of colchicine can be given to prevent the precipitation of acute gout. Home remedies which can alleviate the symptoms of acute gout include resting and elevating the inflamed joint. Ice pack applications can be helpful to reduce pain and decrease inflammation. Patients should avoid aspirin containing medications because aspirin prevents kidney excretion of uric acid.
What does the future hold for patients with gout and hyperuricemia?
Active research is ongoing in a variety of fields related to gout and hyperuricemia. Scientists recently reported that high animal protein slightly increased the risk for gout. Others found that dietary calcium intake may protect patients from getting gout attacks. For acute attacks of gouty arthritis, a new drug called etoricoxib that is taken once a day and has a favorable safety tolerability, is being used successfully in studies.
New medications to increase the elimination of uric acid in the urine (such as benzbromarone) are being evaluated in clinical trials with patients. Researchers are also reporting on an experimental drug called Y700 that can be used even in patients with kidney disease (where often other drugs cannot) because the drug is metabolized by the liver and not the kidneys like the traditional gout drug allopurinol.
A new medication, febuxostat, lowers the uric acid level in the blood as effectively as allopurinol in preliminary studies. If this drug is approved for use by the FDA, it will provide a reasonable alternative treatment for persons who have had adverse reactions to allopurinol.
The optimal regimens for the treatment of acute gout attacks and chronic gout conditions still require further long-term studies. Research scientists will continue to develop less toxic and more effective medications to battle this "scourge of the ages."
Gout And Hyperuricemia At A Glance
1. Painful gouty arthritis is caused by uric acid crystal deposits in joint tissue.
2. The tendency to develop gout and elevated blood uric acid level (hyperuricemia) is often inherited.
3. Gout and hyperuricemia can be promoted by obesity, weight gain, alcohol intake, high blood pressure, abnormal kidney function, and drugs.
4. Gouty arthritis attacks can be precipitated by dehydration, injury, fever, heavy eating, heavy drinking of alcohol, and recent surgery.
5. The most reliable diagnostic test for gout is the identification of crystals in joints, body fluids and tissues.
6. The treatment of an attack of gouty arthritis is different than the treatment of hyperuricemia.