Gout

of the big toe Gout can present in several ways, although the most common is a recurrent attack of acute inflammatory arthritis (a red, tender, hot, swollen joint). Other joints, such as the heels, knees, wrists, and fingers, may also be affected. Long-standing elevated uric acid levels (hyperuricemia) may result in other symptoms, including hard, painless deposits of uric acid crystals called tophi. Extensive tophi may lead to chronic arthritis due to bone erosion. Elevated levels of uric acid may also lead to crystals precipitating in the kidneys, resulting in kidney stone formation and subsequent acute uric acid nephropathy. ==Cause==

of sodium urate affecting the elbow, knuckles, and finger joints. The crystallization of uric acid, often related to relatively high levels in the blood, is the underlying cause of gout. This can occur because of diet, genetic predisposition, or underexcretion of urate, the salts of uric acid. The risk, however, varies depending on the degree of hyperuricemia. When levels are between 415 and 530 μmol/L (7 and 8.9 mg/dL), the risk is 0.5% per year, while in those with a level greater than 535 μmol/L (9 mg/dL), the risk is 4.5% per year. and include a strong association with the consumption of alcohol, sugar-sweetened beverages, meat, and seafood. Among foods richest in purines yielding high amounts of uric acid are dried anchovies, shrimp, organ meat, dried mushrooms, seaweed, and beer yeast. Chicken and potatoes also appear related. Other triggers include physical trauma and surgery. Specifically, a diet with moderate purine-rich vegetables (e.g., beans, peas, lentils, and spinach) is not associated with gout. Neither is total dietary protein. Eating skim milk powder enriched with glycomacropeptide (GMP) and G600 milk fat extract may reduce pain but may result in diarrhea and nausea. Physical fitness, healthy weight, low-fat dairy products, and to a lesser extent, coffee and taking vitamin C, appear to decrease the risk of gout; however, taking vitamin C supplements does not appear to have a significant effect in people who already have established gout. Genetics Gout is partly genetic, contributing to about 60% of variability in uric acid level. Loss-of-function mutations in SLC2A9 and SLC22A12 causes low blood uric acid levels by reducing urate absorption and unopposed urate secretion. A body mass index greater than or equal to 35 increases male risk of gout threefold. Medication Diuretics have been associated with attacks of gout, but a low dose of hydrochlorothiazide does not seem to increase risk. ==Pathophysiology==

Gout is a disorder of purine metabolism, Naked crystals may break out of walled-off tophi due to minor physical damage to the joint, medical or surgical stress, or rapid changes in uric acid levels. An evolutionary loss of urate oxidase (uricase), which breaks down uric acid, in humans and higher primates has made this condition common. Other triggers believed to be important in acute episodes of arthritis include cool temperatures, rapid changes in uric acid levels, acidosis, articular hydration and extracellular matrix proteins. The increased precipitation at low temperatures partly explains why the joints in the feet are most commonly affected. Calcium channel blockers and losartan are associated with a lower risk of gout compared to other medications for hypertension. ==Diagnosis==

Gout may be diagnosed and treated without further investigations in someone with hyperuricemia and the classic acute arthritis of the base of the great toe (known as podagra). Synovial fluid analysis should be done if the diagnosis is in doubt. Plain X-rays are usually normal and are not useful for confirming a diagnosis of early gout. The fluid must be examined relatively soon after aspiration, as temperature and pH affect solubility. Thus, the diagnostic utility of measuring uric acid levels is limited. Other blood tests commonly performed are white blood cell count, electrolytes, kidney function and erythrocyte sedimentation rate (ESR). However, both the white blood cells and ESR may be elevated due to gout in the absence of infection. A white blood cell count as high as 40.0×109/l (40,000/mm3) has been documented. or other neoplasms. File:Light microscopy of a touch preparation of a gout tophus, showing urate crystals.jpg|Light microscopy of a touch preparation of a gout tophus, showing needle-shaped crystals. File:Birefringence microscopy of gout, annotated.jpg|Uric acid crystals in polarized light, showing negative birefringence, with yellow color when aligned parallel to the axis of the red compensator, and blue when aligned perpendicularly to it. File:Birefringence microscopy of pseudogout, annotated.jpg|In contrast, CPPD (pseudogout) displays rhombus-shaped crystals with positive birefringence. File:Gichtfuss im Roentgenbild 002.png|Gout on X-rays of a left foot in the metatarsal-phalangeal joint of the big toe. Note also the soft tissue swelling at the lateral border of the foot. ==Prevention==

Risk of gout attacks can be lowered by complete abstinence from drinking alcoholic beverages, reducing the intake of fructose (e.g., sucrose and high fructose corn syrup), and purine-rich foods of animal origin, such as organ meats and seafood. Gout may be secondary to sleep apnea via the release of purines from oxygen-starved cells. Treatment of apnea can lessen the occurrence of attacks. Medications As of 2020, allopurinol is generally the recommended preventative treatment if medications are used. A number of other medications may occasionally be considered to prevent further episodes of gout, including probenecid, febuxostat, benzbromarone, and colchicine. Long term medications are not recommended until a person has had two attacks of gout, It is not until this point that medications are cost-effective. there is little evidence to support this practice over simply putting people on a standard dose of allopurinol. If these medications are in chronic use at the time of an attack, it is recommended that they be continued. While historically it is not recommended to start allopurinol during an acute attack of gout, this practice appears acceptable. Allopurinol blocks uric acid production, and is the most commonly used agent. Febuxostat is only recommended in those who cannot tolerate allopurinol. There are concerns about more deaths with febuxostat compared to allopurinol. Febuxostat may also increase the rate of gout flares during early treatment. However, there is tentative evidence that febuxostat may bring down urate levels more than allopurinol. Probenecid appears to be less effective than allopurinol and is a second-line agent. It is, however, not recommended if a person has a history of kidney stones. Pegloticase is an option for the 3% of people who are intolerant to other medications. It is a third line agent. Pegloticase is useful decreasing tophi but has a high rate of side effects and many people develop resistance to it. Potential side effects include kidney stones, anemia and joint pain. In 2016, it was withdrawn from the European market. Lesinurad reduces blood uric acid levels by preventing uric acid absorption in the kidneys. It was approved in the United States for use together with allopurinol, among those who were unable to reach their uric acid level targets. Side effects include kidney problems and kidney stones. ==Treatment==

The initial aim of treatment is to settle the symptoms of an acute attack. Repeated attacks can be prevented by medications that reduce serum uric acid levels. Options for acute treatment include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, and glucocorticoids. Options for prevention include allopurinol, febuxostat, and probenecid. Lowering uric acid levels can cure the disease. NSAIDs NSAIDs are the usual first-line treatment for gout.