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'Podagra' redirects here. For the moth genus, see Podagra (moth).
Gout is usually characterized by recurrent attacks of inflammatory arthritis—a red, tender, hot, and swollen joint.[4] Pain typically comes on rapidly in less than twelve hours.[5] The joint at the base of the big toe is affected in about half of cases.[6] It may also result in tophi, kidney stones, or urate nephropathy.[5] The cause is a combination of diet and genetic factors. It occurs more commonly in those who eat a lot of meat, drink a lot of beer, or are overweight. The underlying mechanism involves elevated levels of uric acid in the blood. At high levels, the uric acid crystallizes and the crystals deposit in joints, tendons and surrounding tissues, an attack of gout occurs. Diagnosis may be confirmed by seeing the crystals in joint fluid or tophus. Blood uric acid levels may be normal during an attack.[5] Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, or colchicine improves symptoms. Once the acute attack subsides, levels of uric acid can be lowered via lifestyle changes and in those with frequent attacks, allopurinol or probenecid provides long-term prevention.[5] Taking vitamin C and eating a diet high in low fat dairy products may be preventive.[7] Gout affects about 1 to 2% of the Western population at some point in their lives. It has become more common in recent decades. This is believed to be due to increasing risk factors in the population, such as metabolic syndrome, longer life expectancy and changes in diet. Older males are most commonly affected.[5] Gout was historically known as 'the disease of kings' or 'rich man's disease'.[5][8] It has been recognized at least since the time of the ancient Egyptians.[5] ContentsSigns and symptomsGout can present in multiple ways, although the most usual is a recurrent attack of acute inflammatory arthritis (a red, tender, hot, swollen joint).[4] The metatarsal-phalangeal joint at the base of the big toe is affected most often, accounting for half of cases.[6] Other joints, such as the heels, knees, wrists and fingers, may also be affected.[6] Joint pain usually begins over 2–4 hours and during the night.[6] This is mainly due to lower body temperature.[9] Other symptoms may rarely occur along with the joint pain, including fatigue and a high fever.[9][6] Long-standing elevated uric acid levels (hyperuricemia) may result in other symptoms, including hard, painless deposits of uric acid crystals known as tophi. Extensive tophi may lead to chronic arthritis due to bone erosion.[10] Elevated levels of uric acid may also lead to crystals precipitating in the kidneys, resulting in stone formation and subsequent urate nephropathy.[11] CauseThe crystallization of uric acid, often related to relatively high levels in the blood, is the underlying cause of gout. This can occur because diet, genetic predisposition, or underexcretion of urate, the salts of uric acid.[4] Underexcretion of uric acid by the kidney is the primary cause of hyperuricemia in about 90% of cases, while overproduction is the cause in less than 10%.[5] About 10% of people with hyperuricemia develop gout at some point in their lifetimes.[12] 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.[9] LifestyleDietary causes account for about 12% of gout,[4] and include a strong association with the consumption of alcohol, fructose-sweetened drinks, meat and seafood.[10][13] Other triggers include physical trauma and surgery.[5] Studies in the early 2000s found that other dietary factors are not relevant.[14][15] Specifically, moderate consumption of purine-rich vegetables (e.g. beans, peas, lentils and spinach) are not associated with gout.[16] Neither is total consumption of protein.[14][16] Alcohol consumption is strongly associated with an increased risk, with wine presenting somewhat less of a risk than beer and spirits.[17][16] The consumption of coffee, vitamin C and dairy products, as well as physical fitness, appear to decrease the risk.[18][19][20] This is believed to be partly due to their effect in reducing insulin resistance.[20] GeneticsGout is partly genetic, contributing to about 60% of variability in uric acid level.[5] The SLC2A9, SLC22A12 and ABCG2 genes have been found to be commonly associated with gout and variations in them can approximately double the risk.[21][22] Loss-of-function mutations in SLC2A9 and SLC22A12 cause hereditary hypouricaemia by reducing urate absorption and unopposed urate secretion.[22] The rare genetic disorders familial juvenile hyperuricemic nephropathy, medullary cystic kidney disease, phosphoribosylpyrophosphate synthetase superactivity and hypoxanthine-guanine phosphoribosyltransferase deficiency as seen in Lesch-Nyhan syndrome, are complicated by gout.[5] Medical conditionsGout frequently occurs in combination with other medical problems. Metabolic syndrome, a combination of abdominal obesity, hypertension, insulin resistance and abnormal lipid levels, occurs in nearly 75% of cases.[6] Other conditions commonly complicated by gout include: polycythemia, lead poisoning, kidney failure, hemolytic anemia, psoriasis and solid organ transplants.[5][23] A body mass index greater than or equal to 35 increases male risk of gout threefold.[15] Chronic lead exposure and lead-contaminated alcohol are risk factors for gout due to the harmful effect of lead on kidney function.[24] Lesch-Nyhan syndrome is often associated with gouty arthritis. MedicationDiuretics have been associated with attacks of gout. However, a low dose of hydrochlorothiazide does not seem to increase risk.[25] Other medicines that do increase the risk include niacin and aspirin (acetylsalicylic acid).[10] The immunosuppressive drugs ciclosporin and tacrolimus are associated with gout,[5] the former more so when used in combination with hydrochlorothiazide.[26] PathophysiologyGout is a disorder of purine metabolism,[5] and occurs when its final metabolite, uric acid, crystallizes in the form of monosodium urate, precipitating and forming deposits (tophi) in joints, on tendons and in the surrounding tissues.[10] Microscopic tophi may be walled off by a ring of proteins, which blocks interaction of the crystals with cells and therefore avoids inflammation.[27] Naked crystals may break out of walled-off tophi due to minor physical trauma to the joint, medical or surgical stress, or rapid changes in uric acid levels.[27] When they breach the tophi, they trigger a local immune-mediated inflammatory reaction,[10][27] with one of the key proteins in the inflammatory cascade being interleukin 1β.[5] An evolutionary loss of urate oxidase (uricase), which breaks down uric acid, in humans and higher primates has made this condition common.[5] The triggers for precipitation of uric acid are not well understood. While it may crystallize at normal levels, it is more likely to do so as levels increase.[10][28] Other triggers believed to be important in acute episodes of arthritis include cool temperatures, rapid changes in uric acid levels, acidosis,[29][30] articular hydration and extracellular matrix proteins, such as proteoglycans, collagens and chondroitin sulfate.[5] The increased precipitation at low temperatures partly explains why the joints in the feet are most commonly affected.[4] Rapid changes in uric acid may occur due to factors including trauma, surgery, chemotherapy, diuretics and stopping or starting allopurinol.[9] Calcium channel blockers and losartan are associated with a lower risk of gout compared to other medications for hypertension.[31] Diagnosis Gout on X-rays of a left foot. The typical location is the big toe joint. Note also the soft tissue swelling at the lateral border of the foot.  Spiked rods of uric acid crystals from a synovial fluid sample photographed under a microscope with polarized light. Formation of uric acid crystals in the joints is associated with gout. 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, however, if the diagnosis is in doubt.[9] X-rays, while useful for identifying chronic gout, have little utility in acute attacks.[5] Synovial fluidA definitive diagnosis of gout is based upon the identification of monosodium urate crystals in synovial fluid or a tophus.[6] All synovial fluid samples obtained from undiagnosed inflamed joints by arthrocentesis should be examined for these crystals.[5] Under polarized light microscopy, they have a needle-like morphology and strong negative birefringence. This test is difficult to perform and requires a trained observer.[32] The fluid must be examined relatively soon after aspiration, as temperature and pH affect solubility.[5] Blood testsHyperuricemia is a classic feature of gout, but it occurs nearly half of the time without hyperuricemia and most people with raised uric acid levels never develop gout.[6][33] Thus, the diagnostic utility of measuring uric acid level is limited.[6] Hyperuricemia is defined as a plasma urate level greater than 420 μmol/l (7.0 mg/dl) in males and 360 μmol/l (6.0 mg/dl) in females.[34] 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.[35][36] A white blood cell count as high as 40.0×109/l (40,000/mm3) has been documented.[9] Differential diagnosisThe most important differential diagnosis in gout is septic arthritis.[5][6] This should be considered in those with signs of infection or those who do not improve with treatment.[6] To help with diagnosis, a synovial fluid Gram stain and culture may be performed.[6] Other conditions that look similar include pseudogout and rheumatoid arthritis.[6] Gouty tophi, in particular when not located in a joint, can be mistaken for basal cell carcinoma[37] or other neoplasms.[38] PreventionBoth lifestyle changes and medications can decrease uric acid levels. Dietary and lifestyle choices that are effective include reducing intake of food such as meat and seafood, consuming adequate vitamin C, limiting alcohol and fructose consumption and avoiding obesity.[4] A low-calorie diet in obese men decreased uric acid levels by 100 μmol/l (1.7 mg/dl).[25] Vitamin C intake of 1,500 mg per day decreases the risk of gout by 45%.[39] Coffee, but not tea, consumption is associated with a lower risk of gout.[40] 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.[41] TreatmentThe initial aim of treatment is to settle the symptoms of an acute attack.[42] Repeated attacks can be prevented by medications that reduce serum uric acid levels.[42] Tentative evidence supports the application of ice for 20 to 30 minutes several times a day to decrease pain.[43] Options for acute treatment include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine and steroids,[4] while options for prevention include allopurinol, febuxostat and probenecid. Lowering uric acid levels can cure the disease.[5] Treatment of associated health problems is also important.[5] Lifestyle interventions have been poorly studied.[43] It is unclear whether dietary supplements have an effect in people with gout.[44] NSAIDsNSAIDs are the usual first-line treatment for gout. No specific agent is significantly more or less effective than any other.[4] Improvement may be seen within four hours and treatment is recommended for one to two weeks.[4][5] They are not recommended, however, in those with certain other health problems, such as gastrointestinal bleeding, kidney failure, or heart failure.[45] While indometacin has historically been the most commonly used NSAID, an alternative, such as ibuprofen, may be preferred due to its better side effect profile in the absence of superior effectiveness.[25] For those at risk of gastric side effects from NSAIDs, an additional proton pump inhibitor may be given.[46] There is some evidence that COX-2 inhibitors may work as well as nonselective NSAIDs for acute gout attack with fewer side effects.[47][48] ColchicineColchicine is an alternative for those unable to tolerate NSAIDs.[4] At high doses, side effects (primarily gastrointestinal upset) limit its usage.[49] At lower doses, which are still effective, it is well tolerated.[25][50] Colchicine may interact with other commonly prescribed drugs, such as atorvastatin and erythromycin, among others.[49] SteroidsGlucocorticoids have been found to be as effective as NSAIDs[51][52] and may be used if contraindications exist for NSAIDs. They also lead to improvement when injected into the joint. A joint infection must be excluded, however, as steroids worsen this condition.[4] PegloticasePegloticase was approved in the USA to treat gout in 2010.[53] It is an option for the 3% of people who are intolerant to other medications.[53] Pegloticase is administered as an intravenous infusion every two weeks,[53] and reduces uric acid levels.[54] It is likely useful for tophi but has a high rate of side effects.[55] ProphylaxisA number of medications are useful for preventing further episodes of gout, including xanthine oxidase inhibitors (including allopurinol and febuxostat) and uricosurics (including probenecid and sulfinpyrazone). They are not usually started until one to two weeks after an acute flare has resolved, due to theoretical concerns of worsening the attack.[4] They are often used in combination with either an NSAID or colchicine for the first three to six months.[5] They are not recommended until a person has had two attacks of gout,[4] unless destructive joint changes, tophi, or urate nephropathy exist,[11] because the medications have not been found to be cost-effective.[4] Urate-lowering measures should be increased until serum uric acid levels are below 300–360 μmol/l (5.0–6.0 mg/dl) and continue indefinitely.[4][5] If these medications are in chronic use at the time of an attack, discontinuation is recommended.[6] Levels that cannot be brought below 6.0 mg/dl while attacks continue indicates treatment failure or refractory gout.[56] Overall, probenecid appears to be less effective than allopurinol.[4] Uricosuric medications are typically preferred if undersecretion of uric acid, as indicated by a 24-hour collection of urine results in a uric acid amount of less than 800 mg, is found.[57] They are, however, not recommended if a person has a history of kidney stones.[57] A 24-hour urine excretion of more than 800 mg, which indicates overproduction, is an indication for a xanthine oxidase inhibitor.[57] Xanthine oxidase inhibitors block uric acid production. Long-term therapy is safe and well tolerated and can be used in people with decreased kidney function or urate stones, although allopurinol has caused hypersensitivity in a small number of individuals.[4] In such cases febuxostat is recommended.[58] PrognosisWithout treatment, an acute attack of gout usually resolves in five to seven days; however, 60% of people have a second attack within one year.[9] Those with gout are at increased risk of hypertension, diabetes mellitus, metabolic syndrome and kidney and cardiovascular disease and thus are at increased risk of death.[5][59] This may be partly due to its association with insulin resistance and obesity, but some of the increased risk appears to be independent.[59] Without treatment, episodes of acute gout may develop into chronic gout with destruction of joint surfaces, joint deformity and painless tophi.[5] These tophi occur in 30% of those who are untreated for five years, often in the helix of the ear, over the olecranon processes, or on the Achilles tendons.[5] With aggressive treatment, they may dissolve. Kidney stones also frequently complicate gout, affecting between 10 and 40% of people and occur due to low urine pH promoting the precipitation of uric acid.[5] Other forms of chronic kidney dysfunction may occur.[5]
EpidemiologyGout affects around 1–2% of the Western population at some point in their lifetimes and is becoming more common.[4][5] Some 5.8 million people were affected in 2013.[60] Rates of gout approximately doubled between 1990 and 2010.[10] This rise is believed to be due to increasing life expectancy, changes in diet and an increase in diseases associated with gout, such as metabolic syndrome and high blood pressure.[15] Factors that influence rates of gout, include age, race and the season of the year. In men over 30 and women over 50, rates are 2%.[45] In the United States, gout is twice as likely in males of African descent than those of European descent.[61] Rates are high among Pacific Islanders and the Māori, but rare in aboriginal Australians, despite a higher mean uric acid serum concentration in the latter group.[62] It has become common in China, Polynesia and urban sub-Saharan Africa.[5] Some studies found that attacks of gout occur more frequently in the spring. This has been attributed to seasonal changes in diet, alcohol consumption, physical activity and temperature.[63] History._Natuurkundige_te_Delft_Rijksmuseum_SK-A-957.jpeg) The term 'gout' was initially used by Randolphus of Bocking, around 1200 AD. It is derived from the Latin word gutta, meaning 'a drop' (of liquid).[64] According to the Oxford English Dictionary, this is derived from humorism and 'the notion of the 'dropping' of a morbid material from the blood in and around the joints'.[65] Gout has been known since antiquity. Historically, it was referred to as 'the king of diseases and the disease of kings'[5][66] or 'rich man's disease'.[8] The first documentation of the disease is from Egypt in 2,600 BC in a description of arthritis of the big toe. Greek physician Hippocrates around 400 BC commented on it in his Aphorisms, noting its absence in eunuchs and premenopausal women.[64][67] Aulus Cornelius Celsus (30 AD) described the linkage with alcohol, later onset in women and associated kidney problems:
In 1683, Thomas Sydenham, an English physician, described its occurrence in the early hours of the morning and its predilection for older males:
The Dutch scientist Antonie van Leeuwenhoek first described the microscopic appearance of urate crystals in 1679.[64] In 1848, English physician Alfred Baring Garrod identified excess uric acid in the blood as the cause of gout.[70] Other animalsGout is rare in most other animals due to their ability to produce uricase, which breaks down uric acid.[71] Humans and other great apes do not have this ability, thus gout is common.[9][71] Other animals with uricase include fish, amphibians and most non primate mammals.[72] The Tyrannosaurus rex specimen known as 'Sue', however, is believed to have suffered from gout.[73] ResearchA number of new medications are under study for treating gout, including anakinra, canakinumab and rilonacept.[74] Canakinumab may result in better outcomes than a low dose of a steroid but costs five thousand times more.[75] A recombinant uricase enzyme (rasburicase) is available; its use, however, is limited, as it triggers an autoimmune response. Less antigenic versions are in development.[9] References
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来自： Cunfeng_Wang > 《待分类》
Chisholm, Hugh, ed. (1911). '
