What is gout? |

Causes and Symptoms

Gout, once called the "affliction of kings," is a hereditary disease that causes inflammation of the peripheral joints. It is also called gouty arthritis because
arthritis means joint inflammation and describes a number of related diseases. Gout has afflicted humans since antiquity, and it was first described by Hippocrates in the fifth century BCE. It usually first presents itself as an extremely painful swelling of the big toe of the left foot in men over the age of forty. Gout attacks, termed acute gout, are quite rare in premenopausal women. In fact, more than 90 percent of all gout sufferers are men. The prevalence of gout is extremely high in Pacific Islanders, with nearly 7 percent of adult males afflicted. One characteristic portrayal of gout sufferers, which may come from the “affliction of kings” concept, is of obese and obviously affluent individuals. This is partly a misconception because gout can affect anyone. Nevertheless, acute gout attacks are often brought on by very rich meals or by drinking sprees, so
obesity is accurately portrayed as a contributing factor. Gout is caused by high levels of uric acid in the body, which builds up during the metabolism of substances called purines. If a person eats a too many purine-rich foods or if the kidneys do not remove uric acid quickly enough, gout can occur.

An acute gout attack may occur in almost any joint, with the most common sites after the big toe being the ankles, fingers, feet, wrists, elbows, and knees. Such attacks are not often seen in the shoulders, hips, or spine and, if they do occur, appear only after a gout sufferer has had many previous attacks in other joints. Acute gout of the big toe occurs so often that it has been given its own name, podagra. Common explanations for the frequent occurrence of podagra are that considerable pressure is placed on the big toe in the process of walking and that most people are right-handed and are therefore “left-footed,” putting more pressure on the left foot than on the right one in walking or in sports.

An acute gout attack is preceded by feelings of weakness, nausea, chills, and excessive urination. Then, the area that is affected becomes red to purple, swollen, and so tender that the slightest touch is very painful. This pain is so severe that many sufferers describe it as being crushing, burning, or even excruciating. Acute gout attacks come on suddenly, and many victims report suddenly being jolted awake by pain in the night. Fortunately, such attacks are few and far between and usually last only from a few days to a week. In addition, many patients who have one attack of podagra will never have another gout attack.

The problems associated with acute gout are attributable to a chemical called uric acid. Uric acid does not dissolve well in the blood and other biological fluids, such as the synovial
fluid in joints. When overproduced by the body or excreted too slowly in urine, undissolved uric acid forms sharp crystals. These crystals and their interactions with other joint components cause the pain felt by gout sufferers. It is interesting to note that gout is caused by the overproduction of uric acid in some individuals and by uric acid underexcretion in others. Many of the foods that seem to cause gout are rich in chemicals called purines, which are converted to uric acid in the course of preparation for excretion by the kidneys.

Much more dangerous to gout victims than the acute attacks is leaving the disease untreated. When this happens, crystals of uric acid produce lumps or masses in the joints throughout the body and in the kidneys. In the joints, the masses, called tophi, lead to inflammation, scarring, and deformity that can produce an irreversible degenerative process. Tophi are most common in the fingers and the cartilage of various parts of the body, and external tophi are found in the cartilage of the ears of gout sufferers. The visible tophi, however, are only representative, and undetected uric acid masses may be widely spread throughout the body. Such untreated gout is called chronic or tophaceous gout.

Tophaceous gout is another disease with a long history. It was first described by the Greek physician Galen in the second century CE. Another extremely dangerous aspect of tophaceous gout is unseen kidney stones, which will cause great pain on urination, produce high blood pressure, and even cause fatal liver failure if left untreated.

The prime indicator of gout is high blood levels of uric acid, called hyperuricemia; however, this condition, without other symptoms, does not always signal existent, symptomatic gout. Therefore, the best indicator of the presence of the disease is a combination of hyperuricemia, acute attacks, and observed uric acid in the synovial fluid of all troublesome, gouty joints.

Some investigators propose that gout sufferers are highly intelligent because such famous individuals as Michelangelo, Leonardo da Vinci, Martin Luther, Charles Darwin, and Benjamin Franklin were afflicted with the disease. This trend, however, may indicate that famous people are usually able to afford a lifestyle that causes the predilection to high uric acid levels (for example, the eating of purine-rich foods and high alcohol consumption). Rheumatologists who have studied gout would argue that
alcoholism is a better predictor for the disease because gout is common in heavy drinkers. In fact, studies in which gout patients were given purine-rich diets or purine-rich diets plus alcoholic beverages showed that alcohol increased the number and severity of gout attacks.

Gout is also associated with a number of other diseases, including Down syndrome, lead poisoning, some types of diabetes, psoriasis, and kidney disease. Furthermore, a number of therapeutic drugs used in chemotherapy for cancer, diuretics, and some antibiotics can cause acute gout symptoms. These types of gout are differentiated from the hereditary disease already described—so-called primary gout—by the term “secondary gout.” Drug-induced secondary gout goes away quickly when the administration of the offending drug is stopped.

Another group of diseases that have symptoms somewhat similar to gout are called pseudogout. They have an entirely different cause (mineral crystals in the joints), occur in men and women with equal frequency, usually begin in extreme old age, and are treated quite differently.

It is also interesting that while premenopausal women are nearly gout-free, the disease becomes increasingly common after menopause. This fact supports a role for female hormones in preventing the disease. Primary gout in women is usually much more severe and destructive than gout in men. In those families in which maternal gout is observed, it is likely that occurrence of the disease in male offspring will occur earlier than is usual, such as near the age of thirty.

Treatment and Therapy

Once primary gout has been diagnosed, three methods are available for treating it: therapeutic drugs, surgery, and special diets. Most often, gout treatment uses therapeutic drugs, with the drug of choice being colchicine. Colchicine treatment can be traced back for thousands of years, to Egypt in 1500 BCE. Originally, it was given as an extract of the meadow saffron plant, Colchicum autumnale. In modern times, the pure chemical has been isolated for medicinal use.

Colchicine is reportedly a specific remedy for gout and has no effect on any other type of arthritis. In fact, the reversal of severe joint pain with colchicine is often used as a diagnostic tool that tells physicians that the joint disease being treated is indeed gout. Colchicine can be utilized to treat acute gout attacks or can be taken routinely for long periods of time. Its actions in the handling of acute attacks are quick and profound. In some cases, however, colchicine will have side effects, including severe stomach cramps, nausea, and diarrhea. When these effects occur, colchicine use is discontinued until they disappear, and then its use is reinstituted.

Most of the basis for colchicine action is its decrease of the inflammation that causes the pain of gout attacks. This action is believed to be attributable to colchicine’s interaction with white blood cells that destroy uric acid crystals and subsequent prevention of the cells from releasing inflammatory factors. Other drugs that work in this way are nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, indomethacin, naproxen, and phenylbutazone. Colchicine and NSAIDs are usually given by mouth. In some cases, anti-inflammatory steroid hormones called corticosteroids, such as prednisone and prednisolone, are used to treat acute gout. The corticosteroids are given by injection into the gouty joint. Despite the rapid, almost miraculous effects of these steroids, they are best avoided unless absolutely necessary because they can lead to serious medical problems.

Another group of antigout medications consists of the uricosuric drugs. Two favored examples of such drugs are probenecid (Benemid) and sulfinpyrazone (Anturane). These medications are given to patients whose kidneys underexcrete uric acid. The uricosuric drugs prevent the occurrence of hyperuricemia and eventual tophaceous gout by increasing uric acid excretion in the urine, therefore lowering the uric acid levels in the blood. This lowering has two effects: the prevention of the attainment of uric acid levels in the blood and joints that lead to crystal or tophus formation and the eventual dissolution of crystals and tophi as blood levels of uric acid drop.

Uricosuric drugs have no effect, however, on an acute gout attack and can sometimes make such attacks even more painful. For this reason, uricosuric drug therapy is always started after all acute gout attack symptoms have subsided. Aspirin blocks the effects of the uricosuric drugs and should be replaced with acetaminophen (for example, Tylenol). Side effects of excessive doses of uricosuric drugs can include headache, nausea and vomiting, itching, and dizziness. Their use should be discontinued immediately when such symptoms occur. Later reuse of the uricosuric drugs is usually possible.

The third category of antigout drugs is a single chemical, allopurinol (usually, Lopurin or Zyloprim). This drug lowers the body’s ability to produce uric acid. It is highly recommended for all gout-afflicted people who have kidney disease that is severe enough for kidney stones to form. It has undesired side effects, however, that include skin rashes, drowsiness, a diminished blood count, and severe allergic reactions. As a result, the use of allopurinol is disqualified for many patients. One advantage of allopurinol chemotherapy over the use of uricosuric agents is the fact that it can be taken along with aspirin.

The end result of a chemotherapeutic regimen with uricosuric drugs and/or allopurinol is the lowering of the blood and urinary uric acid levels so that crystals and tophi do not form or, where formed, redissolve. Often, their combination with colchicine is useful for preventing the occurrence of gout attacks during the initial chemotherapy period.

While surgery is not a common treatment for gout, people who have large tophi that have opened up, become infected, or interfere with joint mobility may elect to have them removed in this fashion. In some cases, severe disability or joint pain caused by the degenerative effects of long-term tophaceous gout is also corrected surgically. Care should be taken, however, to evaluate the consequences of such surgery carefully because the postoperative
healing process is often quite slow and many other problems can be encountered.

Media sources often praise special diets in treating gout, without firm proof of their effectiveness. The finding that gout is usually a hereditary disease resulting from metabolic defects that either prevent uric acid excretion or cause its accumulation has underscored that most dietary factors have a relatively small effect on the disease. Consequently, chemotherapy is much more effective than dietary intervention for diminishing gout symptoms. Nevertheless, there are several incontestable dietary aspects essential to the well-being of persons afflicted with gout.

First, dieting is quite useful, and overweight gout sufferers should lose weight. Such action is best taken slowly and under medical supervision. In fact, excessively fast weight loss can temporarily worsen gout symptoms by elevating blood uric acid levels. In addition, gout sufferers should limit their intake of a number of foods because they are overly rich in the purines that give rise to uric acid when the body processes them. Some examples are the organ meats (liver, kidneys, and sweetbreads), mushrooms, anchovies, sardines, caviar, gravy and meat extracts, shellfish, wine, and beer. Modest intake of these foods is allowable. For example, the daily intake of one can of beer, a glass of wine, or an ounce or two of hard liquor is permissible. The gout sufferer should remember that excessive alcohol intake often brings on acute gout attacks and, even worse, will contribute to worsening tophus and kidney stone formation.

Another adjunct to the prevention or diminution of gout symptoms is the daily intake of at least a half gallon of water or other nonalcoholic beverages. This will help to flush uric acid out of the body in the urine, and may help to dissipate both tophi and kidney stones. Plain water is best, as it contains no calories that will increase body weight, potentially aggravating gout and leading to other health problems.

Perspective and Prospects

Many sources agree that if primary gout is under the control of afflicted patients, they can look forward to a normal life without permanent adverse effects from the disease. Those individuals who seek medical treatment at the first appearance of gout symptoms may combine chemotherapy, an appropriate diet regimen, and alcohol avoidance to prevent all but a few acute attacks of the disease. In addition, they will not develop tophi or kidney problems.

Even those afflicted persons who put off treatment until kidney stones or tophi appear can be helped easily. Again, an appropriate diet and chemotherapy agents will make up the principal treatment. Only the patients who neglect all gout treatment until excessive joint damage and severe kidney disease occur are at serious risk, yet even with these individuals, remission of most severe symptoms is usually possible. The long-term neglect of gout symptoms is unwise, however, because severe tophaceous gout can be both deforming and fatal.

Currently, the eradication of most primary gout, not gout treatment, is seen as the desired goal of research. It is believed that a prime methodology for the eradication of gout will be the use of genetic engineering for gene replacement therapy. Primary gout sufferers are victims of gene lesion diseases: Their bodies lack the ability, because of defective genes, to control either the production or the excretion of uric acid. It is hoped that gene replacement technology will enable medical science to add the missing genes back into their bodies. Other research aspects viewed worthy of exploration in the attempts to vanquish primary gout are the understanding of how to cause white blood cells to destroy uric acid crystals in the joints more effectively and safely and to decode the basis for the gout-preventing effects of female hormones related to their presence in premenopausal women.

Bibliography:

Devlin, Thomas M., ed. Textbook of Biochemistry: With Clinical Correlations. 7th ed. Hoboken, N.J.: Wiley-Liss, 2010.

Fries, James F. Arthritis: A Take-Care-of-Yourself Health Guide for Understanding Your Arthritis. 5th ed. Reading, Mass.: Addison-Wesley, 1999.

Hollenstein, Jenna. "Gout." Health Library, September 1, 2011.

Parker, James N., and Philip M. Parker, eds. The Official Patient’s Sourcebook on Gout. Rev ed. San Diego, Calif.: Icon Health, 2005.

Porter, Robert S., and Justin L. Kaplan, eds. The Merck Manual of Diagnosis and Therapy. 19th ed. Whitehouse Station, N.J.: Merck, 2011.

Schumacher, H. Ralph. "Gout." American College of Rheumatology, September 2012.

Scriver, Charles R., et al., eds. The Metabolic and Molecular Basis of Inherited Disease. 8th ed. New York: McGraw-Hill, 2001.

"What Is Gout?" National Institute of Arthritis and Musculoskeletal and Skin Diseases, July 2010.