The Gout, Cartoon by James Gillray (1799). The artist memorably illustrates the excruciating pain and swelling that are symptoms of the diseaseThe classic picture is of excruciating, sudden, unexpected, burning pain, swelling, redness, warmness and stiffness in the joint. Low-grade fever may also be present. 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 draping over the affected area could cause extreme pain.

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

Patients with longstanding hyperuricemia (see below) can have uric acid crystal deposits called tophi (singular: tophus) in other tissues e.g. the helix of the ear. Uric acid stones can form as one kind of kidney stone in some common occasions.

The diagnosis is generally made on a clinical basis, although tests are required to confirm the disease.

Hyperuricemia is a common feature; however, urate levels are not always raised.[1] 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, high uric acid level does not necessarily mean a person will develop gout. Additionally, urate is within the normal range in up to two-thirds of cases.[2] 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 and erythrocyte sedimentation rate (ESR). This serves mainly to exclude other causes of arthritis, most notably septic arthritis.

A definitive diagnosis of gout is from light microscopy of joint fluid aspirated from the joint (this test may be difficult to perform) to demonstrate intracellular monosodium urate crystals in synovial fluid polymorphonuclear leukocytes. The urate crystal is identified by strong negative bi-refringence under polarised microscopy, and their needle-like morphology. A trained observer does better in distinguishing them from other crystals.

Gout occurs when mono-sodium urate crystals form on the articular cartilage of joints, on tendons, and in the surrounding tissues. Purine metabolism gives rise to uric acid. This is normally excreted in the urine. Uric acid is more likely to form into crystals when there is a hyperuricaemia. Hyperuricaemia is 10 times more common without clinical gout than with it[3]

Purines can be generated by the body itself (via the breakdown of cells in normal cellular turnover) or can be ingested in purine-rich foods (e.g. seafood, beer). Most people with gout, however, do not produce more than the normal amount of uric acid, but instead tend to be under-excretors. The kidney is responsible for approximately one third of uric acid excretion, with the gut responsible for the rest. It may be possible that defects in the kidney that may be genetically determined are responsible for the predisposition of individuals for developing gout.

There are also different racial propensities to develop gout. Gout is high among the peoples of the Pacific Islands, and the Maori of New Zealand, but rare in the Australian aborigine despite the latter's higher mean concentration of serum uric acid.[4] In the United States, gout is twice as prevalent in African American males as it is in Caucasians.[5]

Hyperuricemia is considered an aspect of metabolic syndrome, although its prominence has been reduced in recent classifications. This explains the increased prevalence of gout among obese individuals.

Gout is a form of arthritis which affects mostly men between the ages of 40 and 50. The high levels of uric acid in the blood are caused by protein rich foods. Alcohol intake often causes acute attacks of gout. There is correlation that there are hereditary factors that contribute to the elevation of uric acid. Typically persons with gout are: obese, predisposed to diabetes and hypertension, and at higher risk of heart disease. Gout is more common in affluent societies due to a diet rich in proteins, fat, and alcohol.[6] It is known that lead sugar was used to sweeten wine, and that chronic lead poisoning is a cause of gout,[7][8] which condition is then known as saturnine gout, because of its association with alcohol and excess.[9]

Gout can also develop as co-morbidity of other diseases, including polycythaemia, leukaemia, intake of cytotoxics, obesity, diabetes, hypertension, renal disorders, and hemolytic anemia. This form of gout is often called secondary gout. Diuretics (particularly thiazide diuretics) have traditionally been blamed for precipitating attacks of gout, but a Dutch case-control study from 2006 appears to cast doubt on this.[10]

Gout with tophi on elbow and knee.

The first line of treatment should be pain relief. Once the diagnosis has been confirmed, the drugs of choice are indomethacin, other nonsteroidal anti-inflammatory drugs (NSAIDs), or intra-articular glucocorticoids, administered via a joint injection.

Colchicine was previously the drug of choice in acute attacks of gout. It impairs the motility of granulocytes and can prevent the inflammatory phenomena that initiate an attack of gout. Colchicine should be taken within the first 12 hours of the attack and usually relieves the pain within 48 hours. Its main side-effects (gastrointestinal upset such as diarrhea and nausea) can complicate its use. NSAIDs are the preferred form of analgesia for patients with gout.

Before medical help is available, some over the counter medication can provide temporary relief to the 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. Preparation H hemorrhoidal ointment can be applied to the swollen skin to reduce the swelling temporarily. Professional medical care is needed for long term management of gout. Ice may be applied for 20–30 minutes several times a day. There are concerns that uric acid crystallization is accelerated by low temperature, but in a 2002 study in the Journal of Rheumatology[11] patients who used ice packs had better relief of pain with no negative side effects. Keeping the affected area elevated above the level of the heart may help as well.

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; it is usually treated in a similar fashion to athlete's foot.

Another treatment possibility is use of acetazolamide, one of the first diuretics discovered. This drug inhibits the action of carbonic anhydrase on the proximal convoluted tubules within kidneys, which effectively inhibits reabsorption of bicarbonate, thus alkalinizing the urine. After 2-3 days of usage, the diuretic effects of this drug no longer persist (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 like uric acid and cystine into the urine, thus increasing their urinary excretion.35

See Saag and Choi, 2006, an open-access review article, for detailed references and further information.[19]

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).

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. Notable sources of dietary purines include:

beer (high in guanosine[citation needed])
coffee, tea, and other caffeineated beverages
chocolate (theobromine)
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. Meat (particularly dark meat) and seafood are high in purine because muscle cells are packed with mitochondria, which have 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. Consumption of the more purine-rich vegetables or a high protein diet per se had no significant correlation.

Consumption of beer is associated with a 49% increase in relative risk per daily 12-oz 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.[citation needed]

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

Ingestion of 500 mg of Vitamin C per day has been shown[citation needed] to bring about a 0.5 mg/dl decrease in serum uric acid through increased excretion.

Vitamin C, taken in high doses, can help decrease blood uric acid levels, but should not be taken without a doctor's supervision. Note that there is a small subset of people with gout who will actually get worse with high levels of vitamin C. Also, a single high dose can free up too much uric acid and cause kidney stones. (University of Maryland Medical Center for Integrative Medicine).

Additional dietary recommendations can be made which reduce gout indirectly, by reducing gout risk factors such as obesity, 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:
cherries were reported to reduce uric acid in a small study.[20][21]
celery extracts (celery or celery seed either in capsule form or as a tea) 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.[22]
any kinds of cheese[citation needed]. Cheese has been recommended as a low-purine food,[23] and dairy products have been found to reduce the risk of gout.
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.[24]
sweetbreads, kidneys, liver, brains, or other offal meats.[25][26]
sardines and anchovies [27]
seafood [28]
alcohol.[29] Some claim that this applies especially to beer, 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,[30] contain procyanidins released from grape seeds during wine making, which have been reported to lower serum uric acid levels by an indirect mechanism.[31] However, withdrawal of urate-lowering therapy is associated with recurrence of acute gouty arthritis.[32]
meat extracts, consommés, and gravies[33]
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 from those suffering from gout, unless specified by a trained physician), vitamin C, tea and alcohol. The role of diuretics in triggering gout has been disputed.[34]
Moderate intake of purine-rich vegetables is not associated with increased gout.[15]

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. [2] "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." and "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."

The Roman gladiatorial surgeon Galen described gout as a discharge of the four humors of the body in unbalanced amounts into the joints. The Latin term for a drop, as a drop of discharge, is gutta -- the term gout descends from this word.