gout

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Definition

Gout is a form of acute arthritis that causes severe pain and swelling in the joints. It most commonly affects the big toe, but may also affect the heel, ankle, hand, wrist, or elbow. Gout usually comes on suddenly, goes away after 5–10 days, and can keep recurring. Gout is different from other forms of arthritis because it occurs when there are high levels of uric acid circulating in the blood, which can cause urate crystals to settle in the tissues of the joints.

Description

Uric acid, which is found naturally in the blood stream, is formed as the body breaks down waste products, mainly those containing purine, a substance that is produced by the body and is also found in high concentrations in some foods, including brains, liver, sardines, anchovies, and dried peas and beans. Normally, the kidneys filter uric acid out of the blood and excrete it in the urine. Sometimes, however, the body produces too much uric acid or the kidneys aren't efficient enough at filtering it from the blood, and it builds up in the blood stream, a condition known as hyperuricemia. A person's susceptibility to gout may increase because of the inheritance of certain genes or from being overweight and eating a rich diet. In some cases, another disease (such as lymphoma, leukemia, or hemolytic anemia) may be the underlying cause of the uric acid buildup that results in gout.

Hyperuricemia doesn't always cause gout. However, over the course of years, sharp urate crystals build up in the synovial fluid of the joints. Often, some precipitating event, such as an infection, surgery, a stubbed toe, or even a heavy drinking binge can cause inflammation. White blood cells, mistaking the urate crystals for a foreign invader, flood into the joint and surround the crystals, causing inflammation—in other words, the redness, swelling, and pain that are the hallmarks of a gout attack.

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1. A disturbance of uric-acid metabolism occurring chiefly in males, characterized by painful inflammation of the joints, especially of the feet and hands, and arthritic attacks resulting from elevated levels of uric acid in the blood and the deposition of urate crystals around the joints. The condition can become chronic and result in deformity.
2. A large blob or clot: "and makes it bleed great gouts of blood" (Oscar Wilde).

[Middle English goute, from Old French, drop, gout, from Medieval Latin gutta, from Latin, drop (from the belief that gout was caused by drops of morbid humors).]

A hereditary disease due to abnormal purine metabolism. The disease is characterized by increased amounts of blood uric acid (hyperurilcemia), acute and chronic inflammatory arthritis, tophaceous deposits of uric acid crystals, and renal insufficiency. The increase of uric acid is thought to be caused by increased production or decreased excretion of uric acid from the kidney or both. See also Arthritis; Purine.

Primary gout occurs most frequently in middle-aged males and is passed as a familiar or hereditary trait which for some unknown reason does not appear as often in females. Secondary gout refers to the disease when associated with some underlying disorder causing an elevation in uric acid production (for example, myeloproliferative disorders).

The uric acid becomes deposited as urates in soft tissues, especially around the joints, in the cartilages of the ear, along the shafts of long bones, in the kidney, and occasionally on the heart valves. Such deposits, when superficial, can be seen grossly as reddish, inflamed masses called tophi. See also Protein metabolism; Uric acid.

Gout is a metabolic disorder characterized by excessive concentration of uric acid in the blood occasioning the deposition of sodium urate in the joints — particularly the extremities, and notoriously the great toe. Joints become swollen and very painful (‘like walking on my eyeballs’, remarked the Revd Sydney Smith, himself a sufferer). Chalky deposits called tophi (routinely likened to crab's eyes) often form around the joints and under the skin, especially of the ear. Thomas Sydenham, the illustrious clinician and another sufferer, gave the classical description of gout in the 1670s. The parts affected, according to Sydenham, became ‘so exquisitely painful as not to endure the weight of the clothes nor the shaking of the room from a person's walking briskly therein’. By the eighteenth century different kinds of gout were distinguished. The classic swelling of the toes, heels, ankles, and wrists was labelled ‘regular gout’. Then there was ‘irregular gout’ (also called ‘visceral’, ‘metastatic’, or ‘repelled gout’) — gout which, failing to be expelled in the standard way, allegedly rebounded from the extremities to the vital organs — head, brain, liver, heart — where it was judged more ominous. A third type was ‘flying gout’, where the pain flitted, apparently randomly, around the body.

Greek medicine had understood gout as a humoral disease, and the Hippocratic aphorisms inter alia noted that eunuchs do not get gout; nor women, unless their menses be stopped; nor even youths, till they indulged in coitus. Gout, in other words, was a disorder of mature, sexually-active males.

The sixteenth-century iconoclastic Swiss physician Paracelsus repudiated humoral thinking and sought a chemical explanation. Later developments supported Paracelsus' general outlook. In 1776, the Swedish chemist, Karl Scheele, isolated uric acid, and in A Treatise upon Gravel and Gout (1793), Murray Forbes speculated that gout was attended by an excess of uric acid. Four years later, William Hyde Wollaston obtained uric acid from a gouty tophus. And the victory of the theory was assured when, in 1859, Alfred Garrod tendered his classic analysis. In a normal healthy person, he argued, uric acid is excreted in the urine; if that process be interrupted, deposition of uric acid occurs in the form of urate of soda. Not least, Garrod devised an effective clinical test — the thread test — for uric acid. His The Nature and Treatment of Gout and Rheumatic Gout (1859) proved a milestone in the scientific understanding of the disorder.

Gout became one of those body-disfiguring diseases that acquired a distinctive personality, so much so that it could even be regarded as a desirable acquisition. It was widely viewed as exclusive to the upper classes, and therefore a mark of a good breeding, wealth, social status, and cultural superiority. ‘Gout is the distemper of a gentleman’, insisted Lord Chesterfield in the mid eighteenth century, ‘whereas the rheumatism is the distemper of a hackney coachman.’ ‘Gout loves ancestors and genealogy, ’ declared Sydney Smith, ‘it needs five or six generations of gentlemen or noblemen to give it its full vigour’. Hence, like melancholy in the Renaissance or tuberculosis in the Romantic era, gout achieved a social cachet.

More singularly, perhaps, gout assumed an identity, amongst doctors and sufferers alike, as a ‘healthy’ disease which protected sufferers against the depredations of worse diseases. ‘I have so good an opinion of the gout’, remarked the long-suffering Horace Walpole, ‘that when I am told of an infallible cure I laugh the proposal to scorn and declare that I do not desire to be cured … I am serious … I believe the gout a remedy and not a disease.’ For that reason, the apparent incurability of gout paradoxically caused no problems. If gout was indeed truly protective, then a cure might be worse than the disease.

The theory underlying such views was that gout was a healthy response through which a strongly constitutioned body attempted to divest itself of morbid matter by expelling it to the extremities, like the big toe, where it could do no harm. Hence, though a chronic disease, it was at bottom a symptom of basic good health. The poet William Cowper congratulated a friend on becoming gouty, ‘because it seems to promise us that we shall keep you long.’

Gout thus affords a good instance of what Susan Sontag has called ‘disease as metaphor’, one laden with meanings that transcend strict medico-scientific bounds.

Gout is still with us, but rarely in its florid form: an excess of uric acid in the blood can be recognized and controlled by drugs which diminish its excessive formation or enhance its deficient excretion — either of which may account for the excess. The link with affluence has some foundation, since a high protein diet can be a factor; uric acid is a breakdown product of purines, which are essential body constituents — for example of DNA. Purines are abundant in a protein-rich diet, and both ingested and internally synthesized purines contribute to the turnover which produces uric acid; so a high intake combined with subnormal ability of the kidneys to handle the load can cause excess in the blood.

— Roy Porter

Bibliography

• Copeman, W. S. (1964). A short history of the gout and the rheumatic diseases. University of California Press, Berkeley, CA.
• Sontag, S. (1978). Illness as metaphor. Farrar, Straus and Giroux, New York

Painful disease caused by accumulation of crystals of uric acid in the synovial fluid of joints; may be due to excessive synthesis and metabolism of purines, which are metabolized to uric acid, or to impaired excretion of uric acid. Traditionally associated with a rich diet, although there is little evidence for dietary factors in causing the condition. May be exacerbated by alcohol.

A defect in metabolism resulting in an excessive build up of uric acid crystals in the bloodstream and joints. Crystals may be deposited in the kidneys (where they may contribute to the formation of kidney stones), tendons, and joints. Usually, the first symptom of gout is an intense pain felt in the first joint of the big toe. There are a variety of causes, but the main one is poor excretion of uric acid. High intakes of alcohol or fructose can increase the risk of gout.

A disease associated with an inborn error of uric acid metabolism that increases production or interferes with the excretion of uric acid. Excess uric acid is converted to sodium urate crystals that precipitate from the blood and become deposited in joints and other tissues. The great toe is a common site for the accumulation of urate crystals. This condition can be exceedingly painful with swelling of a joint and may be accompanied by chills and fever.

Definition

Gout is a form of acute arthritis that causes severe pain and swelling in the joints. It most commonly affects the big toe, but may also affect the heel, ankle, hand, wrist, or elbow. It affects the spine often enough to be a factor in lower back pain. Gout is often a recurring condition. An attack usually comes on suddenly and goes away after 5–10 days. Gout occurs when there are high levels of uric acid circulating in the blood, and the acid crystallizes and settles in the body. According to the National Institutes of Health (NIH), gout accounts for about 5% of all cases of arthritis reported in the United States.

Gout appears to be on the increase in the American population. According to a study published in November 2002, there was a twofold increase in the incidence of gout over the 20 years between 1977 and 1997. It is not yet known whether this increase is the result of improved diagnosis or whether it is associated with risk factors that have not yet been identified.

Description

Uric acid is formed in the bloodstream when the body breaks down waste products, mainly those containing purines. Purines can be produced naturally by the body, and they can be ingested from such high-purine foods as meat. Normally, the kidneys filter uric acid particles out of the blood and excrete it into the urine. If the body produces too much uric acid or the kidneys aren't able to filter enough of it out, there is a buildup of uric acid in the bloodstream. This condition is known as hyperuricemia.

Uric acid does not tend to remain dissolved in the bloodstream. Over the course of years, or even decades, hyperuricemia may cause deposits of crystallized uric acid throughout the body. Joints, tendons, ear tips, and kidneys are favored sites. When the immune system becomes alerted to the urate crystals, it mounts an inflammatory response that includes the pain, redness, swelling, and damage to joint tissue that are the hallmarks of an acute gout attack.

The body's uric acid production tends to increase in males during puberty. Therefore, it should come as no surprise that nine out of ten of those suffering from gout are men. Since it can take up to 20 years of hyperuricemia to have gout symptoms, men don't commonly develop gout until reaching their late 30s or early 40s. If a woman does develop gout, typically, it will be later in her life. According to some medical experts, this is because estrogen protects against hyperuricemia. It is not until estrogen levels begin to fall during menopause that urate crystals can begin to accumulate.

Hyperuricemia does not necessarily lead to gout. The tendency to accumulate urate crystals may be due to genetic factors, excess weight, or overindulgence in the wrong kinds of food. In addition, regular use of alcohol to excess, the use of diuretics, and the existence of high levels of cholesterol and triglycerides in the blood can increase the risk of developing the disease. In some cases, an underlying disease such as lymphoma, leukemia, or hemolytic anemia may also lead to gout.

Causes & Symptoms

An acute episode of gout often starts without warning. The needle-like urate crystals may be present in the joints for a long time without causing symptoms. Then, there may be a triggering event such as a stubbed toe, an infection, surgery, stress, fatigue, or even a heavy drinking binge. Patients in intensive care units (ICUs) may have an acute flare-up of gout. In addition, it is now known that chronic occupational exposure to lead leads to decreased excretion of urates and an increased risk of developing gout.

In many cases, the gout attack begins in the middle of the night. There is intense pain, which usually involves only one joint. Often it is the first joint of the big toe. The inflamed skin over the joint is warm, shiny, and red or purplish, and the pain is often so excruciating that the sufferer cannot tolerate the pressure of bedcovers. The inflammation may be accompanied by a fever.

Acute symptoms of gout usually resolve in about a week, and then disappear altogether for months or years at a time. Eventually, however, the attacks may occur more frequently, last longer, and do more damage. The urate crystals may eventually settle into hard lumps under the skin around the joints, leading to joint deformity and decreased range of motion. These hard lumps, called tophi, may also develop in the kidneys and other internal organs, under the skin of the ears, or at the elbow. People with gout also face a heightened risk of kidney disease, and almost 20% of people with gout develop kidney stones. As of 2002, however, the relationship between gout and kidney stone formation is still not completely understood.

Diagnosis

Doctors can diagnose gout based on a physical examination and the patient's description of symptoms. In order to detect hyperuricemia, doctors can administer a blood test to measure serum urate levels. However, high urate levels merely point to the possibility of gout. Many people with hyperuricemia don't have urate crystal deposits. Also, it has been shown that up to 30% of gout sufferers have normal serum urate levels, even at the time of an acute gout attack. The most definitive way to diagnose gout is to take a sample of fluid from an affected joint and test it for the presence of the urate crystals.

Treatment

The symptoms of gout will stop completely a week or so after an acute attack without any intervention. It is important, however, to be diagnosed and treated by a health care practitioner in order to avoid attacks of increasing severity in the future and to prevent permanent damage to the joints, kidneys, and other organs. During an acute attack, treatment should focus on relieving pain and inflammation. On an ongoing basis, the focus is on maintaining normal uric acid levels, repairing tissue damage, and promoting tissue healing.

Diet

Generally, gout is unheard of in vegetarians. It is a condition that responds favorably to improvements in diet and nutrition. Recurrent attacks can be avoided by maintaining a healthy weight and limiting the intake of purinerich foods. A diet high in fiber and low in fat is also recommended. Processed foods should be replaced by complex carbohydrates, such as whole grains. Protein intake should be limited to under 0.8g/kg of body weight per day.

Nutritional Supplements

Vitamin E and selenium are recommended to decrease the inflammation and tissue damage caused by the accumulation of urates.

Folic acid has been shown to inhibit xanthine oxidase, the main enzyme in uric acid production. The drug allopurinol (see below) is used for this same purpose in the treatment of gout. The therapeutic use of folic acid for this condition should be prescribed and monitored under the supervision of a heath care practitioner. The recommended dosage range is 400–800 micrograms per day.

The amino acids alanine, aspartic acid, glutamic acid, and glycine taken daily improve the kidneys' ability to excrete uric acid. Bromelain, an enzyme found in pineapples, is an effective anti-inflammatory. It can be used as an alternative to NSAIDs and other prescription anti-inflammatory drugs. It should be taken between meals at a dosage of 200–300 mg, three times per day.

The bioflavonoid quercetin helps the body absorb bromelain. It also helps decrease uric acid production and prevents the inflammation that leads to the acute symptoms of gout and the resulting tissue destruction. Quercetin should be taken at the same time and dosage as bromelain: 200–400 mg, between meals at a three times per day.

Herbs

Dark reddish-blue berries such as cherries, blackberries, hawthorn berries, and elderberries are very good sources of flavonoid compounds that have been found to help lower uric acid levels in the body. Flavonoids are effective in decreasing inflammation and preventing and repairing the destruction of joint tissue. An amount of the fresh, frozen, dried, juiced, or otherwise extracted berries equal to half a pound (about 1 cup) fresh should be consumed daily.

Devil's claw, Harpagophytum procumbens, has been shown to be of benefit. It can be used to reduce uric acid levels and to relieve joint pain.

Gout represents a serious strain on the kidneys. The dried leaves of nettles, Urtica dioica, can be made into a pleasant tea and consumed throughout the day to increase fluid intake and to support kidney functions. However, some people are allergic to nettles.

Therapy

Colchicum is a general homeopathic remedy that can be used for pain relief during a gout attack. It is formulated from the same plant, Autumn crocus, as the drug colchicine, used in the conventional treatment of gout. Gout may be improved by having a constitutional remedy prescribed that is based on the tendency to develop the disease and its symptoms.

During the acute phase of gout, acupuncture can be helpful with pain relief.

Applications of ice or cold water can reduce pain and inflammation during acute attacks.

Allopathic Treatment

Standard medical treatment of acute attacks of gout includes nonsteroidal anti-inflammatory drugs (NSAIDs) such as naproxen sodium (Aleve), ibuprofen (Advil), or indomethacin (Indocin). Daily doses until the symptoms have subsided are recommended. Colchicine (Colbenemid), is also used. Corticosteroids such as prednisone (Deltasone, prednisolone, and corticotropin [ACTH]) may be given orally or may be injected directly into the joint for a more concentrated effect. Because these drugs can cause undesirable side effects, they are used for only about 48 hours so as not to cause major problems. Aspirin and other salicylates should be avoided, because they can impair uric acid excretion and may interfere with the actions of other gout medications.

Once an acute attack has been successfully treated, doctors try to prevent future attacks of gout and long-term joint damage by lowering uric acid levels in the blood. Colchicine is the drug of choice to deter recurrence. This medication can be very hard on the vascular system and the kidneys, however, and it is incompatible with a number of antidepressants, tranquilizers, and antihistamines. It should be avoided by pregnant women and the elderly.

There are two types of drugs used for lowering uric acid levels. Sometimes these drugs resolve the problem completely. However, the use of low-level amounts may be required for a lifetime. Uricosuric drugs, such as probenecid (Benemid) and sulfinpyrazone (Anturane), decrease urates in the blood by increasing their excretion. These drugs may also promote the formation of kidney stones, and they are contraindicated for patients with kidney disease. Xanthine oxidase inhibitors block the production of urates in the body. They can dissolve kidney stones as well as treat gout. Allopurinol is the drug most used in this respect. Its adverse effects include reactions with other medications, and the aggravation of existing skin, vascular, kidney, and liver dysfunction.

Expected Results

Gout cannot be cured, but it can be managed successfully. Prompt attention to diet and reducing uric acid levels will rectify many of the problems associated with gout. Kidney problems can also be reversed or improved. Tophi can be dissolved or surgically removed, and with the tophi gone, joint mobility generally improves. Gout is generally more severe in those whose initial symptoms appear before age 30. The coexistence of hypertension, diabetes, or kidney disease can make for a much more serious condition.

Prevention

For centuries, gout has been known as the "rich man's disease," a disease of overindulgence in food and drink. While this view is perhaps oversimplified, lifestyle factors clearly influence a person's risk of developing gout. For example, losing weight and limiting alcohol intake can help ward off gout. Since purines are broken down into urates by the body, consumption of foods high in purine should be limited. Foods that are especially high in purines are red meat, organ meats, meat gravies, shellfish, sardines, anchovies, mushrooms, cooked spinach, rhubarb, yeast, asparagus, beer, and wine.

Dehydration promotes the formation of urate crystals, so people taking diuretics, or "water pills," may be better off switching to another type of blood pressure medication. Increased intake of fluids will dilute the urine and encourage excretion of uric acid. Therefore, six to eight glasses of water should be consumed daily, along with plenty of herbal teas and diluted fruit juices.

Consumption of saturated fats impedes uric acid excretion, and consumption of refined carbohydrates, such as sugar and white bread and pasta, increases uric acid production. Both should be seriously limited.

The use of vitamin C should be avoided by people with gout, due to the high levels of acidity.

Resources

Books

Parker, James N., M.D., and Philip M. Parker, Ph. D. The 2002 Official Patient's Sourcebook on Gout. San Diego, CA: ICON Health Publications, 2002.

Periodicals

Arromdee, E., C. J. Michet, C. S. Crowson, et al. "Epidemiology of Gout: Is the Incidence Rising?" Journal of Rheumatology 29 (November 2002): 2403–2406.

Conos, Juan J., and Robert Kalish. "Gout: Effective Drug Therapy for Acute Attacks and for the Long Term." Consultant (August 1996): 1752–55.

Emmerson, Bryan T. "The Management of Gout." New England Journal of Medicine (February 15, 1996): 445–451.

Hsu, C. Y., T. T. Shih, K. M. Huang, et al. "Tophaceous Gout of the Spine: MR Imaging Features." Clinical Radiology 57 (October 2002): 919–925.

Lin, J. L., D. T. Tan, H. H. Ho, and C. C. Yu. "Environmental Lead Exposure and Urate Excretion in the General Population." American Journal of Medicine 113 (November 2002): 563–568.

Perez-Ruiz, F., M. Calabozo, G. G. Erauskin, et al. "Renal Underexcretion of Uric Acid is Present in Patients with Apparent High Urinary Uric Acid Output." Arthritis and Rheumatism 47 (December 15, 2002): 610–613.

Raj, J. M., S. Sudhakar, K. Sems, and R. W. Carlson. "Arthritis in the Intensive Care Unit." Critical Care Clinics 18 (October 2002): 767–780.

Shekarriz, B., and M. L. Stoller. "Uric Acid Nephrolithiasis: Current Concepts and Controversies." Journal of Urology 168 (October 2002) (4 Pt 1): 1307–1314.

Organizations

Arthritis Foundation. 1330 W. Peachtree Street, P.O. Box 7669, Atlanta, GA 30357-0669. (800) 283-7800. http://www.arthritis.org.

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). National Institutes of Health (NIH), 1 AMS Circle, Bethesda, MD 20892-3675. .

Other

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Questions and Answers About Gout. Bethesda, MD: NIAMS, 2002. NIH Publication No. 02-5027. .

[Article by: Patience Paradox; Rebecca J. Frey, PhD]

For more information on gout, visit Britannica.com.

A disorder of metabolism characterized by attacks of painful inflammation in the joints, particularly those of the feet and hands. The inflammation is caused by the deposition of crystals of uric acid in the joints. Gout occurs most often in middle-aged men. The tendency toward developing gout is inherited. Stress, fatigue, or excessive exercise are among the factors that can bring on an attack.

A disorder of uric acid metabolism in which there is hyperuricemia and deposition of urates in and around the joints. Occurs in humans and anthropoid apes. Most animals possess the enzyme uricase that converts uric acid to allantoin. Dalmatian dogs excrete large amounts of uric acid in their urine, but the breed is not affected by gout. A disease called gout occurs in commercial chickens due to feeding of excessive amounts of protein.

• articular g. — caused by gross excesses of protein in the diet. A chronic disease manifested by swelling of the joints which contain a thick white fluid consisting largely of uric acid crystals.
• visceral g. — birds become weak and listless and die. The viscera are covered with a frosting of urea crystals. There is a primary renal disease and a fatal uremia. The high-protein diet exacerbates that original disease.

n.

A physician's name for the rheumatism of a rich patient.

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Gout
Classification and external resources
Uric acid
ICD-10	M10.
ICD-9	274.00 274.1 274.8 274.9
OMIM	138900 300323
DiseasesDB	29031
eMedicine	emerg/221 med/924 med/1112 oph/506 orthoped/124 radio/313
MeSH	D006073

Gout is a disease hallmarked by elevated levels of uric acid in the bloodstream. In this condition, crystals of monosodium urate (MSU) or uric acid are deposited on the articular cartilage of joints, tendons, and surrounding tissues.^[1]:546 It is marked by transient painful attacks of acute arthritis initiated by crystallization of urates within and about the joints and can eventually lead to chronic gouty arthritis and the deposition of masses of urates in joints and other sites, sometimes creating tophi.

Historically, it was known as "The Disease of Kings"^[2] or "Rich man's disease".^[3]

Contents 1 Signs and symptoms 2 Pathophysiology 3 Causes 3.1 Primary gout 3.2 Secondary gout 4 Diagnosis 5 Treatment 5.1 Acute attacks 5.2 Chronic joint changes 6 Prevention 6.1 Medication 6.2 Diet 6.2.1 Reduce intake of purines 6.2.2 Other approaches 6.3 Over the counter remedies 6.4 Heat therapy 7 Epidemiology 8 History 9 See also 10 References 11 External Links

Signs and symptoms

The Gout, cartoon by James Gillray (1799).

Gout is characterized by excruciating, sudden, unexpected, burning pain, as well as swelling, redness, warmth, and stiffness in the affected foot. This occurs most commonly in the toes of men but can appear in other parts of the body and affect women as well. Low-grade fever may also occur. The patient usually suffers from two sources of pain: The crystals inside the joint cause intense pain whenever the affected area is moved. The inflammation of the tissues around the joint also causes the skin to be swollen, tender and sore if it is even slightly touched. For example, a blanket or even the lightest sheet draped over the affected area can cause extreme pain.

Gout usually attacks the big toe (approximately 75 percent of first attacks); however, it also can affect other joints, such as the ankle, heel, instep, knee, wrist, elbow, fingers, or spine. In some cases, the condition may appear in the joints of small toes that have become immobile due to impact injury earlier in life; the resulting poor blood circulation can lead to gout.

Patients with long-standing hyperuricemia (see below) can have uric acid crystal deposits called tophi (singular: tophus) in other tissues such as the helix of the ear. Elevated levels of uric acid in the urine can lead to uric-acid crystals precipitating in the kidneys or bladder, forming uric-acid kidney stones.

Pathophysiology

Gout with tophi on elbow and knee.

Gout occurs when crystals of uric acid, in the form of monosodium urate, precipitate on the articular cartilage of joints, on tendons, and in the surrounding tissues. Uric acid is a normal component of blood serum. Uric acid is more likely to form into crystals when there is hyperuricemia, although hyperuricemia is 10 times more common without clinical gout than with it.^[4] Gout can also occur when serum uric acid is normal, and when it is abnormally low (hypouricemia). Paradoxically, acute attacks of gout can occur together with a sudden decrease in serum uric acid, such as due to use of drugs (uricosurics, xanthine oxidase inhibitors), or total parenteral nutrition.^[5] However, the sudden decrease may be a consequence of abrupt formation of crystals (removing uric acid from the serum), rather than a cause.

Regardless of the serum concentration of uric acid, precipitation of uric acid is markedly enhanced when the blood pH is low (acidosis). A similar pH-sensitive effect occurs in urine,^[6] contributing to uric acid nephrolithiasis.

Uric acid is a product of purine metabolism, and in humans is normally excreted in the urine. Purines are generated by the body via breakdown of cells in normal cellular turnover, and also are ingested as part of a normal diet. The kidneys are responsible for approximately two-thirds of uric acid excretion, with the liver responsible for the rest.

Causes

Gout may be primary --(including idiopathic), or secondary to (a complication of) another condition.

Primary gout

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High levels of uric acid in the blood can be caused by foods with high purine content, the body creating too much uric acid itself, or the body's inability to excrete the uric acid fast enough. Grain alcohol intake often causes acute attacks of gout in those already afflicted. A family history of gout can pre-dispose individuals to high uric acid levels (see: inborn errors of purine-pyrimidine metabolism).

Gout is traditionally considered more common among affluent individuals, who may regularly drink and eat rich food and wines such as champagne, port, lobster, crab and other foods that contain the highest levels of purines, such as Foie gras. It is not rare, however, to find gout among all levels of society. Regular consumption of grain alcohol may also result in developing the disease. This is known as "poor man's gout." A sedentary lifestyle also increases the risk of developing the disease.^[7] When gout follows as a consequence of other health conditions such as renal failure, it is often regardless of the person's lifestyle.^[8]

Some studies have established a statistical connection between gout and lead poisoning,^[9] and a significant correlation between levels of lead in the body, urate excretion and gout.^[10] It is known that lead sugar was formerly used to sweeten wine.^[11][12] This condition is then known as saturnine gout (Saturnus being the alchemical term for metallic lead).^[13]

Diuretics (particularly thiazide diuretics) have often been blamed for precipitating attacks of gout because they compete at the same transporter, but a Dutch case-control study from 2006 appears to cast doubt on this conclusion.^[14]

About 10% of people with hyperuricemia develop gout.^[15]

Secondary gout

Secondary gout is a complication of other medical conditions. Medical conditions that commonly result in gout include:

• Metabolic syndrome (the combination of hypertension, diabetes, dyslipidemia, truncal obesity, increased cardiovascular disease risk)^[16]
• Leukemia

Gout also can develop as a co-morbidity of other diseases, including polycythaemia, intake of cytotoxics, obesity, diabetes, hypertension, renal disorders, and hemolytic anemia. Gout is an important complication in a minority of solid organ transplant.^[17]

Because some approved treatments for these other conditions also reduce serum uric acid, individualized treatment of gout has the potential to improve outcome.^[18]

Diagnosis

Spiked rods of uric acid (MSU) crystals photographed under a microscope with polarized light from a synovial fluid sample. Formation of uric acid crystals in the joints are associated with gout.

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Clinically, gout can be hard to distinguish from several other conditions, including chondrocalcinosis. Chondrocalcinosis is a very similar disease, caused by deposition of calcium pyrophosphate rather than uric acid.

The urate crystal has a needle-like morphology and strong negative birefringence under polarised light. This test may be difficult to perform, and a trained observer does better in distinguishing this crystal from others. Many physicians do not perform this test, relying instead on a variety of less specific clinical signs and laboratory tests.^[19]

The most informative clinical signs are the presence of classic podagra (sudden, unexplained swelling and pain of the big toe joint on just one foot) and the presence of tophi.^[20] Gouty tophi, particularly when not located in a joint, can be mistaken for basal cell carcinoma^[21] or other neoplasm.^[22]

Hyperuricemia is a common feature of gout, so its presence supports a diagnosis of gout. However, gout can occur without hyperuricemia.^[23] Hyperuricemia is defined as a plasma urate (uric acid) level greater than 420 μmol/L (7.0 mg/dL) in males, or 380 μmol/L in females. However, a high uric acid level does not necessarily mean a person will develop gout. Urate is within the normal range in up to two-thirds of cases.^[24] If gout is suspected, the serum urate test should be repeated once the attack has subsided. Other blood tests commonly performed are full blood count, electrolytes, renal function, thyroid function tests and erythrocyte sedimentation rate (ESR). This helps to exclude other causes of arthritis, most notably septic arthritis, and to investigate any underlying cause for the hyperuricaemia.

Ultrasound imaging (US) can be helpful. US signs of gouty joints include a double-contour appearance of the cartilage and a snowstorm appearance of the synovial membrane.^[25] US can also be used to guide aspiration.^[25]

Treatment

Treatment has three objectives: manage symptoms of acute attacks, prevent acute attacks, and reduce serum uric acid.^[26]

Patients are often started on a drug such as allopurinol, which inhibits the conversion of purine into uric acid. In this case, the purines are voided harmlessly in urine and feces.

A number of sufferers do not get relief from this class of drug, so the next class of drugs recommended are the uricosurics, which increase the excretion of uric acid from the body. This excretion is controlled by kidney hormones, which also control the reuptake of other chemicals. For this reason probenecid may cause other drugs to be retained in the body for longer periods of time.

Because of these side effects probenecid is often reserved as the second line of defense against gout. If the patient does not obtain relief from allopurinol, though, the patient should be switched to probenecid promptly.

Acute attacks

The first line of treatment should be pain relief. Once the diagnosis has been confirmed, the drug options are nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine and oral glucocorticoids,^[27] or intra-articular glucocorticoids administered via a joint injection.

NSAIDs such as diclofenac, etoricoxib, indomethacin, ketoprofen, naproxen or sulindac may be prescribed.^[28] For those at risk of gastric irritation from NSAIDs, an additional proton pump inhibitor may be given.^[29]

Colchicine remains a second line drug in the UK for those unable to tolerate NSAIDs,^[29][30] but its side effect profile has resulted in its role being relegated, at least in the US, to after that of oral glucocorticoids.^[31] It impairs the motility of granulocytes and can prevent the inflammatory phenomena that initiate an attack. Colchicine should be taken within the first 12 hours of the attack and usually relieves the pain within 48 hours, although side effects (gastrointestinal upset such as diarrhea, nausea and death^[32]) can greatly complicate its use. Colchicine can be become very toxic if taken with other common prescription drugs such as Lipitor, Prilosec, erythromycin, Prozac, and Imodium ^[32]). NSAIDs are the preferred form of analgesia for patients with gout.

A randomized controlled trial found similar benefit from nonsteroidal anti-inflammatory drugs (single injection of diclofenac and then oral indomethacin) as from the oral glucocorticoid prednisolone; however, less adverse drug reactions occurred in the glucocorticoid group.^[33]

Another possibility is acetazolamide, one of the first diuretics discovered. This drug inhibits the action of carbonic anhydrase on the proximal convoluted tubules within the kidneys, which effectively inhibits reabsorption of bicarbonate, thus alkalinizing the urine. After two to three days of usage, the diuretic effects of this drug decline because of increased downstream reabsorption of ions and water by the renal tubules; however, the alkalinization of urine persists, and this basic urine attracts weak acids such as uric acid and cystine into the urine, thus increasing their urinary excretion.

Before medical help is available, some over-the-counter medications can provide temporary relief from pain and swelling. NSAIDs such as ibuprofen can reduce the pain and inflammation slightly, although aspirin should not be used as it can worsen the condition. This is because aspirin raises plasma uric acid levels even at low doses by inhibiting uric acid secretion in the renal tubules^{[citation needed]}. Aspirin also reduces vasodilatation due to inhibition of prostaglandin PGE2 and PGI2 synthesis in the renal medulla and glomeruli respectively (see mechanism of action of aspirin). This may be a contra-indication for the use of aspirin for gout pain as well.

The anti-hemorrhoidal ointment Preparation H can reduce gout-induced skin swelling temporarily. Ice may be applied for 20 to 30 minutes several times a day, and a randomized controlled trial found that patients who used ice packs had better relief of pain without side effects.^[34] Since gout is caused by crystals, it has been suggested^{[citation needed]} that keeping very well hydrated and heating the affected joint in hot water (rather than cooling with ice) will promote the dissolution and clearance of the urate crystals. Adequate hydration is a standard recommendation. However, a small study found that only icing, not heating, was beneficial.^[35] Keeping the affected area elevated above the level of the heart also may help.^{[citation needed]} Professional medical care is needed for long-term management of gout.

Due to swelling around affected joints for prolonged periods, shedding of skin may occur. This is particularly evident when small toes are affected and may promote fungal infection in the web region if dampness occurs, and treatment is similar to that for common athlete's foot.

Some people who have gout report an aggravation of the condition in the knees and toes associated with long periods of immobility, such as when sitting at a computer desk for long hours. Individuals who notice early swelling or early pain may appear to be able to arrest the aggravation when medical treatment is applied before the condition gets worse. Where this is the case, a medically prescribed anti-inflammatory oral treatment taken with food and bed rest may provide relief within 6 to 8 hours.

Chronic joint changes

In general, gout can be controlled as long as medication begins before the tophi can be felt or seen. For extreme cases of gout (known as chronic tophaceous gout), surgery may be necessary to remove the large tophi and correct joint deformity. People whose gout has reached this stage will require continuous medication as well as lifestyle changes.

Extensive tophi that invade bone are associated with arthritis due to bone erosion.^[36]

Prevention

Prevention of chronic gout has a different objective than management of acute episodes (flareups). In an acute attack, the objective is to reduce pain and inflammation. The objective of prevention is to stop any future attacks and associated cumulative tissue damage. Prevention strategies include reducing the supply of purine, dissolving crystals of uric acid so the uric acid can return to the blood, and increasing the excretion of uric acid from the blood into the urine, without causing lithiasis there. Prevention tactics involve careful diagnosis of the factors contributing to the gout, followed by appropriate use of medication, diet, and over the counter remedies.

Medication

This section may require cleanup to meet Wikipedia's quality standards. Please improve this section if you can. (February 2009)

Prescription drugs used to treat gout belong to several functional classes. These include xanthine oxidase inhibitors, uricosurics, and urate oxidases.

• Allopurinol is a xanthine-oxidase inhibitor, widely used in the prevention of attacks of gout, and well tolerated. It is safe to use in patients with renal impairment and urate stones.^[37] However, allopurinol and azathioprine (Imuran) used together present a risk of a potentially fatal drug interaction, a severe risk of allopurinol use which is of importance to transplant patients being treated with azathioprine for immunosuppression.^[38]
• Febuxostat (2-[3-cyano-4-isobutoxyphenyl]-4-methylthiazole-5-carboxylic acid) - a non-purine inhibitor of xanthine oxidase seems to be an alternative that is superior to allopurinol at reducing serum urate levels, but not at reducing attacks of gout. The drug was approved by European Medicines Agency on April 21, 2008^[39] and recommended for approval by the U.S. Food and Drug Administration on November 26, 2008.^[40] It was approved by the FDA in February 2009.^[41]
• Pegloticase, a polyethylene glycol (PEG) conjugate of recombinant porcine uricase (urate oxidase), which breaks down the uric acid deposits is being studied in Phase III clinical trials for the treatment of severe, treatment-refractory gout in the United States in 2006.
• Probenecid, a uricosuric drug, is often prescribed for gout in conjunction with colchicine: see probenecid and colchicine.
• Ethylenediaminetetraacetic acid (EDTA), a chelator of lead, has successfully increased uric acid excretion.^[42] This should be an advantageous treatment for those people whose gout was caused by lead poisoning. Care should be taken to increase intake of trace essential elements since chelation often removes these elements also.
• In some cases, gout may be secondary to untreated sleep apnea, via the release of purines as a by-product of the breakdown of oxygen-starved cells. Treatment for apnea can therefore be effective in lessening incidence of acute gout attacks.^[43]

Diet

See Saag and Choi, 2006, an open-access review article, for detailed references and further information.^[44]

The serum level of uric acid is the primary risk factor for gout. The serum level is the result of both intake (diet) and output (excretion). Diet should be low fat and low protein.

A 2009 study found that Vitamin C prevented outbreaks of gout. The study, published in the March 9, 2009, issue of Archives of Internal Medicine, showed that men who had the highest vitamin C intake—1,500 milligrams or higher per day—had a 45% lower risk of gout than those with the lowest daily intake—less than 250 milligrams per day.^[45]

A 2004 study suggests that animal flesh sources of purine (such as beef and seafood) greatly increase the risk of developing gout. However, high-purine vegetable sources (such as asparagus, cauliflower, spinach, and green peas) did not. Dairy products such as milk and cheese significantly reduced the chances of gout. The study followed over 40,000 men over a period of 12 years, in which 1,300 cases of gout were reported.^[46]

Reduce intake of purines

The solubility threshold for uric acid is approximately 6.7 mg/dl; above this threshold crystals may form. Healthy subjects in the Normative Aging Study who had serum levels of uric acid over 9.0 mg/dl suffered a 22% incidence of gout over six years, compared to less than one percent for those with 7.0–8.9 mg/dl. The average uric acid level in men is 5.0 mg/dl, and substitution of a purine-free formula diet reduces this to 3.0 mg/dl. A purine-restricted diet lowers the level nearly as much (1–2 mg/dl).

A diet low in purines reduces the serum level of uric acid, unless these levels are caused by other health conditions and not as responsive to dietary changes. For notable sources of dietary purines, see "Foods to avoid" section below.

Protein is a crude proxy for purines; a more precise proxy is muscle. Apart from the notable dietary purines above, the main source of dietary purines is DNA and RNA, via their bases adenine and guanine. All sources of dietary protein supply some purines, but some sources provide far more purines than others. This has to do with the number of mitochondria per cell. Meat (particularly dark meat) and seafood are high in purine because muscle cells are packed with thousands of mitochondria, each with their own DNA and RNA. In a large prospective study, high consumption of meat and seafood were found associated with an elevated risk of gout onset (41% and 50%, respectively). High consumption of dairy products, high in protein but very low in DNA and RNA, was associated with a 44% decrease in the incidence of gout. In plants, in addition to mitochondria (in very low numbers) some cells have chloroplasts, also with their own DNA and RNA. For this reason, both relatively high-protein vegetables and dark green leafy vegetables are expected to have more purines than other vegetables. However, the contribution of these to the total purine content of plant tissues is relatively low due to the relatively low copy number. Consumption of the more purine-rich vegetables or a high protein diet per se had no significant correlation.

A study on soft drinks and fructose consumption shows that men who consume two or more sugary soft drinks a day have an 85% higher risk of gout compared with those who drink less than one a month.^[47] This is because in countries like United States and Japan, processed foods and beverages may contain large quantities of high-fructose corn syrup (HFCS), a common sweetener and sugar substitute, which results in hyperuricemia in blood.^[48][49] Hyperuricemia, in turn predisposes the body for gout.^[50]

Consumption of beer is associated with a 49% increase in relative risk per daily 12 oz (354 ml) serving. By contrast, consumption of spirits was associated with only a 15% increase in relative risk, and no association at all was found with consumption of wine.

Some medical drugs are purine-based. Notable among these are the purine-analog antimetabolite drugs, sometimes used as chemotherapy agents.

Other approaches

Additional dietary recommendations can be made which reduce gout indirectly, hypertension, cardiovascular disease, diabetes, and metabolic syndrome.

The following suggestions do not meet with universal approval among medical practitioners.

Low purine diet:

• To lower uric acid:
  • Tart cherries were reported to reduce uric acid in a small study. Tart cherry juice or tart cherry capsules are believed to help dissolve the needle-like crystals that deposit themselves between the joints and connective tissue.^[51][52]
  • Celery extracts (celery or celery seed either in capsule form or as a tisane/infusion) is believed by many to reduce uric acid levels (although these are also diuretics).^{[citation needed]} Celery extracts have been reported to act synergistically with anti-inflammatory drugs.^[53]
  • Cheese has been recommended as a low-purine food,^[54] and dairy products have been found to reduce the risk of gout.
  • Carbonated beverages and sugar have also been recommended as a low-purine food,^[54] even though it was established that men who consume two or more fructose-rich soft drinks a day have an 85% higher risk of gout compared with those who drink less than one a month.^[47]
  • Dietary supplements Quercetin, a flavonoid, can decrease uric acid levels. Quercetin can be taken with bromelain to improve its absorption. In addition, Pantothenic acid (vitamin B5) is said to help with the excretion process of uric acid.^[55] Vitamin C has been demonstrated to increase excretion on uric acid and in turn lower serum urate levels.
• Food to avoid:
  • Foods high in purines
    • Limit food high in protein such as meat, fish, poultry, or tofu to 8 ounces (226 grams) a day. Avoid entirely during a flare-up.^{[citation needed]} Tofu has been proposed as a safe source of protein for gout patients due to its small and transient effect on plasma urate levels.^[56]
    • Sweetbreads, kidneys, liver, brains, or other offal meats.^[57][58]
    • Sardines and anchovies^[57]
    • Seafood^[46] particularly shellfish such as clam, oyster, scallop, shrimp, crab, lobster, and crayfish.
    • Asparagus. Cauliflower. Mushrooms. Spinach. (Even though above says "Consumption of the more purine-rich vegetables or a high protein diet per se had no significant correlation.")
    • Dry beans (lentils & peas).
    • Alcohol.^[59] Some claim that this applies especially to beer (high in guanosine), on the basis that brewer's yeasts are very rich in purine. Since most modern commercial beer contains only trace amounts of yeast, this claim requires further substantiation.^{[citation needed]} Formerly, port wine was sweetened with litharge, causing lead poisoning, of which gout is a complication. Ironically, red wines, particularly those produced by traditional methods,^[60] contain procyanidins released from grape seeds during wine making, which have been reported to lower serum uric acid levels by an indirect mechanism.^[61] However, withdrawal of urate-lowering therapy is associated with recurrence of acute gouty arthritis.^[62] Alcohol also increases dehydration, causing the proportion of the uric acid levels in the blood to increase.
    • Meat extracts, consommés, and gravies^[57]
  • Foods high in fructose, as discussed above, especially high-fructose corn syrup (HFCS) as main ingredient.^[50]
    • All soft drinks (non-diet), wherein HFCS is second ingredient next to water
    • Fruit preserves, jam, jelly
    • Syrup
    • Candy
    • To lesser extent, depending on fructose content, ice cream, cakes, and cookies
  • Foods high in sucrose

• To avoid dehydration:
  • Drink plenty of liquids, especially water, to dilute and assist excretion of urates;
  • Avoid diuretic foods or medicines like aspirin (aspirin should be avoided by those suffering from gout, unless specified by a qualified physician), rapid increases/decreases in vitamin C, tea and alcohol. This applies only to low-dose aspirin, commonly referred to as a baby aspirin (81 mg). High-dose aspirin (325 mg) increases uric acid excretion. The role of diuretics in triggering gout has been disputed.^[14]

• Moderate intake of purine-rich vegetables is not associated with increased gout.^[46]

Over the counter remedies

• Sodium bicarbonate (baking soda) is a traditional remedy,^[63] thought to work by raising blood pH (lowering blood acidity). However, the added sodium may be inappropriate for some people.

• Research from the University of British Columbia suggests long-term coffee consumption is associated with a lower risk of gout.^[64] Other studies extend this benefit to tea and other caffeinated foods and drinks.^[65]

• Potassium supplements should be advantageous to treat gout. Gout can be triggered by the same agents that cause potassium losses such as fasting, surgery, and potassium losing diuretics.^[66] A potassium deficiency can increase urate levels in the blood.^[67]

• Chondroitin sulfate reduces the rate of crystallization of uric acid in urine. This has been demonstrated in vitro,^[68][69] but has not been tested in clinical trial. One study^[70] shows an opposite effect.

• Wu Jia Pi, the cortex of Siberian ginseng, can be used intermittently between outbreaks of gout in patients with a chronic condition to prevent future occurrences.^{[citation needed]}

Heat therapy

The normally lower temperature of extremities, compared to the body core, is believed to explain the characteristic prevalence of first gout attacks involving the big toe, later the knee, rarely more proximal joints (hip, shoulder, spine). This observation, and the fact that crystals in general dissolve more readily at higher temperatures, supports the idea that heat therapy may help to resolve both acute and chronic gout. Thus the use of hot pads and hot baths.

Epidemiology

Gout is a form of arthritis that affects mostly middle-aged men and postmenopausal women.

Different populations have different propensities to develop gout. Gout is high among the peoples of the Pacific Islands, and the Māori of New Zealand, but rare in Australian aborigines despite the latter's higher mean concentration of serum uric acid.^[71] In the United States, gout is twice as prevalent in African American males as it is in European-Americans.^[72]

A seasonal link may also exist, with significantly higher incidence of acute gout attacks occurring in the spring.^[73][74]

History

The first written description of gout dates from 2,600 BC, when Egyptians noted gouty arthritis of the big toe. Around 400 BC, the Greek physician Hippocrates also commented on gout.^[75] Writing ca. 30 AD, Aulus Cornelius Celsus appeared to recognize many of the features of gout, including its link with a urinary solute, late onset in women, linkage with alcohol, and perhaps even prevention by dairy products:

"Again thick urine, the sediment from which is white, indicates that pain and disease are to be apprehended in the region of joints or viscera. … Joint troubles in the hands and feet are very frequent and persistent, such as occur in cases of podagra and cheiragra. These seldom attack eunuchs or boys before coition with a woman, or women except those in whom the menses have become suppressed. Upon the commencement of pain blood should be let; for when this is carried out at once in the first stages it ensures health, often for a year, sometimes for always. Some also, when they have washed themselves out by drinking asses' milk, evade this disease in perpetuity; some have obtained lifelong security by refraining from wine, mead and venery for a whole year; indeed this course should be adopted especially after the primary attack, even although it has subsided."^[76]

Anton van Leeuwenhoek described the microscopic appearance of uric acid crystals.

Around 200 AD, the Roman gladiatorial surgeon Galen described gout as a discharge of the four humors of the body in unbalanced amounts into the joints. The word "gout" was initially used by Randolphus of Bocking, around 1200 AD. It is derived from the Latin word "gutta", meaning "a drop" (of liquid).^[75]

The Dutch scientist Antonie van Leeuwenhoek described the microscopic appearance of urate crystals in 1679.^[75] In 1848 English physician Alfred Baring Garrod realised that excess uric acid in the blood was the cause of gout.^[77]

Some animals, such as birds and alligators, may suffer from gout^{[citation needed]}. Even the Tyrannosaurus rex specimen known as "Sue" appears to have suffered from gout.^[78]

Historical treatments for gout include gin and numerous medications that have since been found to be not effective. These include medications that were effective in dissolving uric acid crystals during in vitro laboratory studies but not clinical trials: lycetol, lysidine, piperazine, and sidonal.^{[citation needed]}

See also

• List of cutaneous conditions
• Pseudogout, one of the names for calcium pyrophosphate deposition disease
• Uric acid nephrolithiasis
• Uricosuria

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External Links

• Gout: Medline Plus

v • d • e Antigout preparations (M04) Uricosurics primary: Probenecid · Sulfinpyrazone · Benzbromarone · Isobromindione secondary: Amlodipine · Atorvastatin · Fenofibrate · Guaifenesin · Losartan Xanthine oxidase inhibitors purine analogues: Allopurinol# · Oxypurinol · Tisopurine other: Febuxostat · Inositols (Phytic acid, Myo-inositol) Mitotic inhibitors Colchicine Other Cinchophen · NSAIDs except aspirin · Sevelamer · Urate oxidase (Rasburicase, Pegloticase†) #WHO-EM. ‡Withdrawn from market. CLINICAL TRIALS: †Phase III. §Never to phase III

v • d • e Musculoskeletal disorders: Arthropathies (M00-M19, 711-719) Arthritis (monoarthritis/ polyarthritis) Inflammation (Neutrophilia) Infectious Septic arthritis · Tuberculosis arthritis · Reactive arthritis (indirectly) Noninfectious Seronegative spondyloarthropathy: Reactive arthritis · Psoriatic arthritis · Ankylosing spondylitis Rheumatoid arthritis: Juvenile idiopathic arthritis · Adult-onset Still's disease · Felty's syndrome Crystal arthropathy: Gout · Chondrocalcinosis Noninflammatory Osteoarthritis: Heberden's node · Bouchard's nodes Other hemorrhage (Hemarthrosis) · pain (Arthralgia) · Osteophyte · Hypermobility · villonodular synovitis (Pigmented villonodular synovitis) · Joint stiffness joint navs: anat, non-congenital arthropathies/deformities/dorsopathies/soft tissue arthropathy/congenital, eponymous signs, proc

v • d • e Inborn error of purine-pyrimidine metabolism (E79, 277.2) Purine metabolism Anabolism Adenylosuccinate lyase deficiency - Myoadenylate deaminase deficiency Nucleotide salvage Lesch-Nyhan syndrome/Hyperuricemia - Adenine phosphoribosyltransferase deficiency Catabolism Adenosine deaminase deficiency - Purine nucleoside phosphorylase deficiency - Xanthinuria - Gout Pyrimidine metabolism Anabolism Orotic aciduria Catabolism Dihydropyrimidine dehydrogenase deficiency see also nucleotide metabolism, intermediates

This entry is from Wikipedia, the leading user-contributed encyclopedia. It may not have been reviewed by professional editors (see full disclaimer)

Dansk (Danish)
n. - gigt, podagra, stænk, klat, stråle, cigarsyge

Nederlands (Dutch)
jicht, (bloed)druppel, klonter, straal

Français (French)
n. - (Méd) goutte

Deutsch (German)
n. - Gicht

Ελληνική (Greek)
n. - (παθολ.) ουρική αρθρίτιδα, ποδάγρα

Italiano (Italian)
gotta

Português (Portuguese)
n. - gota (f) (Med.)

Русский (Russian)
подагра, капля, пятно, шлюз

Español (Spanish)
n. - gota

Svenska (Swedish)
n. - gikt, droppe

中文（简体）(Chinese (Simplified))
味, 嗜好, 趣味

中文（繁體）(Chinese (Traditional))
n. - 味, 嗜好, 趣味

한국어 (Korean)
n. - (병) 통풍, (피 등의) 응어리

日本語 (Japanese)
n. - したたり, 痛風

العربيه (Arabic)
‏(الاسم) النقرس, : داء المفاصل‏

עברית (Hebrew)
n. - ‮שיגדון, פודגרה, צינית‬

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