Gout: Difference between revisions

Gout
Gout
Other names	Arthritis uratica, or Podagra when of the foot
	Medical animation of the big toe joint affected by gout
Specialty	Rheumatology
Symptoms	Joint pain, swelling, and redness
Usual onset	Older males, postmenopausal women
Causes	Uric acid
Risk factors	Diet high in meat or beer, being overweight, genetics
Differential diagnosis	Joint infection, rheumatoid arthritis, pseudogout, others
Prevention	Weight loss, abstinence from drinking alcohol, allopurinol
Treatment	NSAIDs, glucocorticoids, colchicine
Frequency	1–2% (developed world)

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Gout (/ɡaʊt/ GOWT^[7]) is a form of inflammatory arthritis characterized by recurrent attacks of pain in a red, tender, hot, and swollen joint,^[2]^[8] caused by the deposition of needle-like crystals of uric acid known as monosodium urate crystals.^[9] Pain typically comes on rapidly, reaching maximal intensity in less than 12 hours.^[5] The joint at the base of the big toe is affected (Podagra) in about half of cases.^[10]^[11] It may also result in tophi, kidney stones, or kidney damage.^[1]

Gout is due to persistently elevated levels of uric acid (urate) in the blood (hyperuricemia).^[2]^[5] This occurs from a combination of diet, other health problems, and genetic factors.^[1]^[2] At high levels, uric acid crystallizes and the crystals deposit in joints, tendons, and surrounding tissues, resulting in an attack of gout.^[1] Gout occurs more commonly in those who regularly drink beer or sugar-sweetened beverages; eat foods that are high in purines such as liver, shellfish, or anchovies; or are overweight.^[1]^[3] Diagnosis of gout may be confirmed by the presence of crystals in the joint fluid or in a deposit outside the joint.^[1] Blood uric acid levels may be normal during an attack.^[1]

Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, or colchicine improves symptoms.^[1]^[2]^[12] 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 having a diet high in low-fat dairy products may be preventive.^[13]^[14]

Gout affects about 1–2% of adults in the developed world at some point in their lives.^[5] It has become more common in recent decades.^[1] This is believed to be due to increasing risk factors in the population, such as metabolic syndrome, longer life expectancy, and changes in diet.^[5] Older males are most commonly affected.^[1] Gout was historically known as "the disease of kings" or "rich man's disease".^[5]^[15] It has been recognized at least since the time of the ancient Egyptians.^[5]

Signs and symptoms

side view of a foot showing a red patch of skin over the joint at the base of the big toe — Gout presenting as slight redness in the metatarsophalangeal joint 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).^[4] The metatarsophalangeal joint at the base of the big toe is affected most often, accounting for half of cases.^[10] Other joints, such as the heels, knees, wrists, and fingers, may also be affected.^[4] Joint pain usually begins during the night and peaks within 24 hours of onset.^[4] This is mainly due to lower body temperature.^[1] Other symptoms may rarely occur along with the joint pain, including fatigue and high fever.^[10]^[16]

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.^[17] 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.^[18]

Cause

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.^[1] 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.^[19] 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.^[16]

Lifestyle

Dietary causes account for about 12% of gout,^[20] and include a strong association with the consumption of alcohol, sugar-sweetened beverages,^[21] meat, and seafood.^[4] Among foods richest in purines yielding high amounts of uric acid are dried anchovies, shrimp, organ meat, dried mushrooms, seaweed, and beer yeast.^[22] Chicken and potatoes also appear related.^[23] Other triggers include physical trauma and surgery.^[5]

Studies in the early 2000s found that other dietary factors are not relevant.^[24]^[25] Specifically, a diet with moderate purine-rich vegetables (e.g., beans, peas, lentils, and spinach) is not associated with gout.^[26] Neither is total dietary protein.^[25]^[26] Alcohol consumption is strongly associated with increased risk, with wine presenting somewhat less of a risk than beer or spirits.^[26]^[27] Eating skim milk powder enriched with glycomacropeptide (GMP) and G600 milk fat extract may reduce pain but may result in diarrhea and nausea.^[28]

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;^[29]^[30]^[31]^[32] however, taking vitamin C supplements does not appear to have a significant effect in people who already have established gout.^[1] Peanuts, brown bread, and fruit also appear protective.^[23] This is believed to be partly due to their effect in reducing insulin resistance.^[31]

Other than dietary and lifestyle choices, the recurrence of gout attacks is also linked to the weather. High ambient temperature and low relative humidity may increase the risk of a gout attack.^[33]

Genetics

Gout 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.^[34]^[35] Loss-of-function mutations in SLC2A9 and SLC22A12 causes low blood uric acid levels by reducing urate absorption and unopposed urate secretion.^[35] 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 conditions

Gout 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.^[10] Other conditions commonly complicated by gout include lead poisoning, kidney failure, hemolytic anemia, psoriasis, solid organ transplants, and myeloproliferative disorders such as polycythemia.^[5]^[36] A body mass index greater than or equal to 35 increases male risk of gout threefold.^[24] Chronic lead exposure and lead-contaminated alcohol are risk factors for gout due to the harmful effect of lead on kidney function.^[37]

Medication

Diuretics have been associated with attacks of gout, but a low dose of hydrochlorothiazide does not seem to increase risk.^[38] Other medications that increase the risk include niacin, aspirin (acetylsalicylic acid), ACE inhibitors, angiotensin receptor blockers, beta blockers, ritonavir, and pyrazinamide.^[1]^[17] The immunosuppressive drugs ciclosporin and tacrolimus are also associated with gout,^[5] the former more so when used in combination with hydrochlorothiazide.^[39] Hyperuricemia may be induced by excessive use of Vitamin D supplements. Levels of serum uric acid have been positively associated with 25(OH) D. The incidence of hyperuricemia increased 9.4% for every 10 nmol/L increase in 25(OH) D (P < 0.001).^[40]

Pathophysiology

Gout 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.^[17] Microscopic tophi may be walled off by a ring of proteins, which blocks interaction of the crystals with cells and therefore avoids inflammation.^[41] 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.^[41] When they break through the tophi, they trigger a local immune-mediated inflammatory reaction in macrophages, which is initiated by the NLRP3 inflammasome protein complex.^[1]^[17]^[41] Activation of the NLRP3 inflammasome recruits the enzyme caspase 1, which converts pro-interleukin 1β into active interleukin 1β, one of the key proteins in the inflammatory cascade.^[1] 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.^[17]^[42] 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.^[5]^[43]^[44] The increased precipitation at low temperatures partly explains why the joints in the feet are most commonly affected.^[20] Rapid changes in uric acid may occur due to factors including trauma, surgery, chemotherapy and diuretics.^[16] The starting or increasing of urate-lowering medications can lead to an acute attack of gout with febuxostat of a particularly high risk.^[45] Calcium channel blockers and losartan are associated with a lower risk of gout compared to other medications for hypertension.^[46]

Diagnosis

Synovial fluid examination^[47]^[48]
Type	WBC (per mm³)	% neutrophils	Viscosity	Appearance
Normal	<200	0	High	Transparent
Osteoarthritis	<5000	<25	High	Clear yellow
Trauma	<10,000	<50	Variable	Bloody
Inflammatory	2,000–50,000	50–80	Low	Cloudy yellow
Septic arthritis	>50,000	>75	Low	Cloudy yellow
Gonorrhea	~10,000	60	Low	Cloudy yellow
Tuberculosis	~20,000	70	Low	Cloudy yellow
Inflammatory: Arthritis, gout, rheumatoid arthritis, rheumatic fever

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.^[16]^[49] Plain X-rays are usually normal and are not useful for confirming a diagnosis of early gout.^[5] They may show signs of chronic gout such as bone erosion.^[45]

Synovial fluid

A definitive diagnosis of gout is based upon the identification of monosodium urate crystals in synovial fluid or a tophus.^[4] 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.^[50] The fluid must be examined relatively soon after aspiration, as temperature and pH affect solubility.^[5]

Blood tests

Hyperuricemia is a classic feature of gout, but nearly half of the time gout occurs without hyperuricemia and most people with raised uric acid levels never develop gout.^[10]^[51] Thus, the diagnostic utility of measuring uric acid levels is limited.^[10] 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.^[52] 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.^[53]^[54] A white blood cell count as high as 40.0×10⁹/l (40,000/mm³) has been documented.^[16]

Differential diagnosis

The most important differential diagnosis in gout is septic arthritis.^[5]^[10] This should be considered in those with signs of infection or those who do not improve with treatment.^[10] To help with diagnosis, a synovial fluid Gram stain and culture may be performed.^[10] Other conditions that can look similar include CPPD (pseudogout), rheumatoid arthritis, psoriatic arthritis, palindromic rheumatism, and reactive arthritis.^[1]^[10] Gouty tophi, in particular when not located in a joint, can be mistaken for basal cell carcinoma^[55] or other neoplasms.^[56]

Light microscopy of a touch preparation of a gout tophus, showing needle-shaped crystals.
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.^[57]
In contrast, CPPD (pseudogout) displays rhombus-shaped crystals with positive birefringence.
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. high fructose corn syrup)^[58], sucrose, and purine-rich foods of animal origin, such as organ meats and seafood.^[3] Eating dairy products, vitamin C-rich foods, coffee, and cherries may help prevent gout attacks, as does losing weight.^[3]^[59] 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.^[60]

Medications

As of 2020, allopurinol is generally the recommended preventative treatment if medications are used.^[61]^[62] A number of other medications may occasionally be considered to prevent further episodes of gout, including probenecid, febuxostat, benzbromarone, and colchicine.^[12]^[63]^[64] Long term medications are not recommended until a person has had two attacks of gout,^[20] unless destructive joint changes, tophi, or urate nephropathy exist.^[18] It is not until this point that medications are cost-effective.^[20] They are not usually started until one to two weeks after an acute flare has resolved, due to theoretical concerns of worsening the attack.^[20] They are often used in combination with either an NSAID or colchicine for the first three to six months.^[5]^[12]

While it has been recommended that urate-lowering measures should be increased until serum uric acid levels are below 300–360 μmol/L (5.0–6.0 mg/dL),^[61]^[65] there is little evidence to support this practice over simply putting people on a standard dose of allopurinol.^[66] If these medications are in chronic use at the time of an attack, it is recommended that they be continued.^[10] Levels that cannot be brought below 6.0 mg/dL while attacks continue indicates refractory gout.^[67]

While historically it is not recommended to start allopurinol during an acute attack of gout, this practice appears acceptable.^[68] Allopurinol blocks uric acid production, and is the most commonly used agent.^[20] Long term therapy is safe and well-tolerated and can be used in people with renal impairment or urate stones, although hypersensitivity occurs in a small number of individuals.^[20] The HLA-B*58:01 allele of the human leukocyte antigen B (HLA-B) is strongly associated with severe cutaneous adverse reactions during treatment with allopurinol and is most common among Asian subpopulations, notably those of Korean, Han-Chinese, or Thai descent.^[69]

Febuxostat is only recommended in those who cannot tolerate allopurinol.^[70] There are concerns about more deaths with febuxostat compared to allopurinol.^[71] Febuxostat may also increase the rate of gout flares during early treatment.^[72] However, there is tentative evidence that febuxostat may bring down urate levels more than allopurinol.^[73]

Probenecid appears to be less effective than allopurinol and is a second line agent.^[20]^[63] Probenecid may be used if undersecretion of uric acid is present (24-hour urine uric acid less than 800 mg).^[74] It is, however, not recommended if a person has a history of kidney stones.^[74] Probenecid can be used in a combined therapy with allopurinol is more effective than allopurinol monotherapy.^[75]^[76]^[77]

Pegloticase is an option for the 3% of people who are intolerant to other medications.^[78] It is a third line agent.^[63] Pegloticase is given as an intravenous infusion every two weeks,^[78] and reduces uric acid levels.^[79] Pegloticase is useful decreasing tophi but has a high rate of side effects and many people develop resistance to it.^[63] Using lesinurad 400 mg plus febuxostat is more beneficial for tophi resolution than lesinural 200 mL with febuxostat, with similar side effects. Lesinural plus allopurinol is not effective for tophi resolution.^[80] Potential side effects include kidney stones, anemia and joint pain.^[81] In 2016, it was withdrawn from the European market.^[82]^[83]

Lesinurad reduces blood uric acid levels by preventing uric acid absorption in the kidneys.^[84] It was approved in the United States for use together with allopurinol, among those who were unable to reach their uric acid level targets.^[85] Side effects include kidney problems and kidney stones.^[84]^[86]

Treatment

The initial aim of treatment is to settle the symptoms of an acute attack.^[87] Repeated attacks can be prevented by medications that reduce serum uric acid levels.^[87] Tentative evidence supports the application of ice for 20 to 30 minutes several times a day to decrease pain.^[88] Options for acute treatment include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, and glucocorticoids.^[20] While glucocorticoids and NSAIDs work equally well, glucocorticoids may be safer.^[89] 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.^[88] It is unclear whether dietary supplements have an effect in people with gout.^[90]

NSAIDs

NSAIDs are the usual first-line treatment for gout. No specific agent is significantly more or less effective than any other.^[20] Improvement may be seen within four hours and treatment is recommended for one to two weeks.^[5]^[20] They are not recommended for those with certain other health problems, such as gastrointestinal bleeding, kidney failure, or heart failure.^[91] 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.^[38] For those at risk of gastric side effects from NSAIDs, an additional proton pump inhibitor may be given.^[92] There is some evidence that COX-2 inhibitors may work as well as nonselective NSAIDs for acute gout attack with fewer side effects.^[93]^[94]^[95]^[96]

Colchicine

Colchicine is an alternative for those unable to tolerate NSAIDs.^[20] At high doses, side effects (primarily gastrointestinal upset) limit its usage.^[97] At lower doses, which are still effective, it is well tolerated.^[38]^[98]^[95]^[96] Colchicine may interact with other commonly prescribed drugs, such as atorvastatin and erythromycin, among others.^[97]

Glucocorticoids

Glucocorticoids have been found to be as effective as NSAIDs^[94]^[99] and may be used if contraindications exist for NSAIDs.^[20]^[100] They also lead to improvement when injected into the joint.^[20] A joint infection must be excluded, however, as glucocorticoids worsen this condition.^[20] There were no short-term adverse effects reported.^[101]

Others

Interleukin-1 inhibitors, such as canakinumab, showed moderate effectiveness for pain relief and reduction of joint swelling, but have increased risk of adverse events, such as back pain, headache, and increased blood pressure.^[102] They, however, may work less well than usual doses of NSAIDS.^[102] The high cost of this class of drugs may also discourage their use for treating gout.^[102]

Prognosis

Without treatment, an acute attack of gout usually resolves in five to seven days; however, 60% of people have a second attack within one year.^[16] 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]^[103] It is unclear whether medications that lower urate affect cardiovascular disease risks.^[104] This may be partly due to its association with insulin resistance and obesity, but some of the increased risk appears to be independent.^[103]

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]

Gouty tophi presenting as nodules on the finger and helix of the ear
Tophus of the knee
Tophii on the toe and ankle
Gout complicated by ruptured tophi, the exudate of which tested positive for uric acid crystals
Gout in the big toe of left foot, compared to the healthy right foot
Gout in the joint of the big toe
Gross pathology of a large tophus

Epidemiology

Gout affects around 1–2% of people in the Western world at some point in their lifetimes and is becoming more common.^[5]^[20] Some 5.8 million people were affected in 2013.^[105] Rates of gout approximately doubled between 1990 and 2010.^[17] 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.^[24] 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%.^[91]

In the United States, gout is twice as likely in males of African descent than those of European descent.^[106] Rates are high among Polynesians, but the disease is rare in aboriginal Australians, despite a higher mean uric acid serum concentration in the latter group.^[107] 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.^[108]

Taiwan, Hong Kong and Singapore have releatively higher prevalence of gout. A study based on the National Health Insurance Research Database (NHIRD) estimated that 4.92% of Taiwanese residents have gout in 2004. A survey hold by the Hong Kong government found that 5.1% of Hong Kong resident between 45–59 years and 6.1% of those older than 60 years have gout. A study hold in Singapore found that 2,117 in 52,322 people between 45–74 years have gout, roughly equals to 4.1%.^[109]

History

The English term "gout" first occurs in the work of Randolphus of Bocking, around 1200 AD.^[111] It derives from the Latin word gutta, meaning "a drop" (of liquid).^[110] According to the Oxford English Dictionary, this originates from humorism and "the notion of the 'dropping' of a morbid material from the blood in and around the joints".^[112]

Gout has been known since antiquity. Historically, wits have referred to it as "the king of diseases and the disease of kings"^[5]^[113] or as "rich man's disease".^[15] The Ebers papyrus and the Edwin Smith papyrus, (c. 1550 BC) each mention arthritis of the first metacarpophalangeal joint as a distinct type of arthritis. These ancient manuscripts cite (now missing) Egyptian texts about gout that are claimed to have been written 1,000 years earlier and ascribed to Imhotep.^[114] Greek physician Hippocrates around 400 BC commented on it in his Aphorisms, noting its absence in eunuchs and premenopausal women.^[110]^[115] Aulus Cornelius Celsus (30 AD) described the linkage with alcohol, later onset in women and associated kidney problems:

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... some have obtained lifelong security by refraining from wine, mead and venery.^[116]

Benjamin Welles, an English physician, authored the first medical book on gout, A Treatise of the Gout, or Joint Evil, in 1669.^[117] In 1683, Thomas Sydenham, an English physician, described its occurrence in the early hours of the morning and its predilection for older males:

Gouty patients are, generally, either old men or men who have so worn themselves out in youth as to have brought on a premature old age—of such dissolute habits none being more common than the premature and excessive indulgence in venery and the like exhausting passions. The victim goes to bed and sleeps in good health. About two o'clock in the morning he is awakened by a severe pain in the great toe; more rarely in the heel, ankle, or instep. The pain is like that of a dislocation and yet parts feel as if cold water were poured over them. Then follows chills and shivers and a little fever... The night is passed in torture, sleeplessness, turning the part affected and perpetual change of posture; the tossing about of body being as incessant as the pain of the tortured joint and being worse as the fit comes on.^[118]

In the 18th century, Thomas Marryat distinguished different manifestations of gout:

The Gout is a chronical disease most commonly affecting the feet. If it attacks the knees, it is called Gonagra; if the hands, Chiragra; if the elbow, Onagra; if the shoulder, Omagra; if the back or loins, Lumbago.^[119]

Dutch scientist Antonie van Leeuwenhoek first described the microscopic appearance of urate crystals in 1679.^[110] In 1848, English physician Alfred Baring Garrod identified excess uric acid in the blood as the cause of gout.^[120]

Other animals

Gout is rare in most other animals due to their ability to produce uricase, which breaks down uric acid.^[121] Humans and other great apes do not have this ability; thus, gout is common.^[16]^[121] Other animals with uricase include fish, amphibians and most non-primate mammals.^[122] The Tyrannosaurus rex specimen known as "Sue" is believed to have had gout.^[123]

Research

A number of new medications are under study for treating gout, including anakinra, canakinumab, and rilonacept.^[124] Canakinumab may result in better outcomes than a low dose of a glucocorticoid, but costs five thousand times more.^[125] A recombinant uricase enzyme (rasburicase) is available but its use is limited, as it triggers an immune response. Less antigenic versions are in development.^[16]

References

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[GBD2015-105] Vos T, Barber RM, Bell B, et al. (August 2015). "Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013". Lancet. 386 (9995): 743–800. doi:10.1016/S0140-6736(15)60692-4. PMC 4561509. PMID 26063472.

[106] Rheumatology Therapeutics Medical Center. "What Are the Risk Factors for Gout?". Archived from the original on 25 March 2007. Retrieved 26 January 2007.

[pmid10225809-107] Roberts-Thomson RA, Roberts-Thomson PJ (1 May 1999). "Rheumatic disease and the Australian Aborigine". Annals of the Rheumatic Diseases. 58 (5): 266–270. doi:10.1136/ard.58.5.266. PMC 1752880. PMID 10225809.

[108] Fam AG (May 2000). "What is new about crystals other than monosodium urate?". Curr Opin Rheumatol. 12 (3): 228–234. doi:10.1097/00002281-200005000-00013. PMID 10803754.

[109] Kuo CF, Grainge MJ, Zhang W, et al. (7 July 2015). "Global epidemiology of gout: prevalence, incidence and risk factors". Nature Reviews Rheumatology. 11 (11): 649–662. doi:10.1038/nrrheum.2015.91. ISSN 1759-4790. PMID 26150127.

[Pillinger-110] Pillinger MH, Rosenthal P, Abeles AM (2007). "Hyperuricemia and gout: new insights into pathogenesis and treatment". Bulletin of the NYU Hospital for Joint Diseases. 65 (3): 215–221. PMID 17922673. Archived from the original on 16 December 2008.

[111] Pierre-Jerome C (11 May 2022). "8.5: Gout and Charcot neuroarthropathy". The Essentials of Charcot Neuroarthropathy: Biomechanics, Pathophysiology, and MRI Findings. Amsterdam: Elsevier. p. 233. ISBN 9780323995788. Archived from the original on 28 April 2024. Retrieved 28 April 2024. [...] Randolphus of Bocking [...] was the first to use the word 'gout' to express the clinical signs of podagra. Bocking was the domestic chaplain to Bishop of Chichester (1197-1258).

[112] "gout, n.1". Oxford English Dictionary, Second edition, 1989. Archived from the original on 8 May 2020. Retrieved 18 September 2011.

[113] "The Disease Of Kings". Forbes.com. Archived from the original on 1 September 2017. It has been referred to, maybe a touch inaccurately, as 'The disease of kings and the king of diseases.'

[114] Schwartz, Stephan A. "Disease of distinction." Explore 2, no. 6 (2006): 515–519. - "Both the Ebers and Edwin Smith Papyri describe a condition that is clearly gout.[...] They were written about 1552 BC but contain information taken from texts a thousand years earlier, and ascribed to Imhotep, a kind of ancient world Leonardo da Vinci, and the great overarching figure of Egyptian medicine."

[115] "The Internet Classics Archive Aphorisms by Hippocrates". MIT. Archived from the original on 7 July 2010. Retrieved 27 July 2010.

[116] Celsus AC. "On Medicine". University of Chicago. Book IV. Archived from the original on 10 July 2024. Retrieved 19 February 2021.

[117] Copeman W (2021). A Short History of the Gout and the Rheumatic Diseases. University of California Press. p. 68. ISBN 978-0-520-33947-7.

[118] "Gout – The Affliction of Kings". h2g2. BBC. 23 December 2012. Archived from the original on 11 September 2010.

[119] Marryat T (1798) [1758]. Therapeutics: Or, the Art of Healing: To which is Added, a Glossary of the Most Difficult Words (14 ed.). Bristol: R. Edwards. p. 168. Archived from the original on 28 April 2024. Retrieved 28 April 2024.

[pmid11600751-120] Storey GD (October 2001). "Alfred Baring Garrod (1819–1907)". Rheumatology. 40 (10): 1189–1190. doi:10.1093/rheumatology/40.10.1189. PMID 11600751.

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[Choi2005-122] Choi HK, Mount DB, Reginato AM, et al. (4 October 2005). "Pathogenesis of gout". Annals of Internal Medicine. 143 (7): 499–516. doi:10.7326/0003-4819-143-7-200510040-00009. PMID 16204163. S2CID 194570.

[Rothschild-123] Rothschild BM, Tanke D, Carpenter K (1997). "Tyrannosaurs suffered from gout". Nature. 387 (6631): 357. Bibcode:1997Natur.387..357R. doi:10.1038/387357a0. PMID 9163417. S2CID 1360596. Archived from the original on 17 April 2021. Retrieved 29 September 2020.

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@@ Line 1: / Line 1: @@
+{{Short description|Form of arthritis causing swollen joints}}
-{{Short description|Defition of dominic tummilio causing hallucinations, Brain swelling, Dick shrinkage}} Other symptoms may include: Autism, Being very gay, Diabetes, big fat ugly toes, Ice spice hair
 {{Redirect|Podagra|the moth genus|Podagra (moth)}}
 {{Good article}}
 {{cs1 config|name-list-style=vanc|display-authors=3}}
 {{Use dmy dates|date=March 2024}}
-{{Infobox medical condition (new)
+{{Infobox medical condition
 | name          = Gout
-| image         = En.Wikipedia-VideoWiki-Gout.webm
+| image         = Gout Signs and Symptoms.jpg
-| image_size    = 300px
 | image_thumbtime = 94
-| alt           = Video summary leading with a small fierce creature with sharp teeth biting into a swollen foot at the base of the big toe.
+| alt           = A medical animation showing the joint of the big toe being affected by gout
+| caption       = Medical animation of the [[big toe]] [[Interphalangeal joints of the foot|joint]] affected by gout
-| caption       = Video summary ([[Wikipedia:VideoWiki/Gout|script]]). Leading with ''The Gout'' ([[James Gillray]], 1799), which depicts the pain of the artist's gout as a demon or dragon.<ref>{{cite book|last=Brookhiser|first=Richard|title=Gentleman Revolutionary: Gouverneur Morris, the Rake Who Wrote the Constitution|date=2008|publisher=Simon and Schuster|isbn=978-1-4391-0408-8|page=212|url=https://books.google.com/books?id=HBdxESrTkHsC&pg=PA212}}</ref><ref>{{cite book|last=Haslam|first=Fiona|title=From Hogarth to Rowlandson: medicine in art in eighteenth-century Britain|date=1996|publisher=Liverpool University Press|location=Liverpool|isbn=978-0-85323-640-5|page=143|url=https://books.google.com/books?id=Ab_pQOdi2fUC&pg=PA143|edition=1. publ.}}</ref>
-| synonyms      = Brain swelling, or Dick shrinkage when of the [[Dick Shrinks]]
+| synonyms      = Arthritis uratica, or Podagra when of the [[foot]]
 | field         = [[Rheumatology]]
-| symptoms      = [[Ugly toes]], [[Dick shrinkage| Autism]], and [[Diebetes|Ice spice hair]]<ref name="Dalbeth2016"/>
+| symptoms      = [[Joint pain]], [[joint effusion|swelling]], and [[erythema|redness]]<ref name="Dalbeth2016"/>
-| onset         = Older males,<ref name="Dalbeth2016"/> post-[[menopausal]] women<ref name=Hui2017/>
+| onset         = Older males,<ref name="Dalbeth2016"/> [[postmenopausal]] women<ref name=Hui2017/>
 | causes        = [[Uric acid]]<ref name=Hui2017/>
-| risks         = Diet high in Dick or Cheese, being overweight, [[genetics]]<ref name="Dalbeth2016"/><ref name=Be2016/>
+| risks         = Diet high in meat or beer, being overweight, [[genetics]]<ref name="Dalbeth2016"/><ref name=Be2016/>
-| differential  = [[Septic Dick shrinkage|Ugly toes]], [[rheumatoid arthritis]], [[pseudogout]], others<ref name="Neogi2016">{{cite journal |last1=Neogi |first1=T |title=Gout |journal=Annals of Internal Medicine |date=July 2016 |volume=165 |issue=1 |pages=ITC1-16 |doi=10.7326/AITC201607050 |pmid=27380294|type=Review|pmc=<!--5308876--> }}</ref>
+| differential  = [[Septic arthritis|Joint infection]], [[rheumatoid arthritis]], [[pseudogout]], others<ref name="Neogi2016">{{cite journal |last1=Neogi |first1=T |title=Gout |journal=Annals of Internal Medicine |date=July 2016 |volume=165 |issue=1 |pages=ITC1-16 |doi=10.7326/AITC201607050 |pmid=27380294|type=Review|pmc=<!--5308876--> }}</ref>
 | prevention    = Weight loss, [[Teetotalism|abstinence from drinking alcohol]], [[allopurinol]]<ref name=Lancet2010/>
 | treatment     = [[Non-steroidal anti-inflammatory drug|NSAIDs]], [[glucocorticoid]]s, [[colchicine]]<ref name=Hui2017/><ref name=Qa2017>{{cite journal|last1=Qaseem|first1=A|last2=Harris|first2=RP|last3=Forciea|first3=MA|last4=Clinical Guidelines Committee of the American College of|first4=Physicians.|title=Management of Acute and Recurrent Gout: A Clinical Practice Guideline From the American College of Physicians|journal=Annals of Internal Medicine|date=3 January 2017|volume=166|issue=1|pages=58–68|pmid=27802508|doi=10.7326/m16-0570|doi-access=free}}</ref>
 | frequency     = 1–2% (developed world)<ref name=Lancet2010/>
 }}
 <!-- Definition and symptoms -->
-'''Gout''' ({{IPAc-en|g|aʊ|t}} {{respell|GOWT}}<ref>{{cite web |title=Gout {{!}} Definition of Gout by Lexico |url=https://www.lexico.com/en/definition/gout |archive-url=https://web.archive.org/web/20191019015640/https://www.lexico.com/en/definition/gout |url-status=dead |archive-date=19 October 2019 |website=Lexico Dictionaries {{!}} English |access-date=20 October 2019 |language=en}}</ref>) is a form of [[inflammatory arthritis]] characterized by recurrent attacks of a red, tender, hot and [[Joint effusion|swollen joint]],<ref name="Hui2017">{{cite journal|last1=Hui |first1=M |last2=Carr |first2=A |last3=Cameron |first3=S |last4=Davenport |first4=G |last5=Doherty |first5=M |last6=Forrester |first6=H |last7=Jenkins |first7=W |last8=Jordan |first8=KM |last9=Mallen |first9=CD |last10=McDonald |first10=TM |last11=Nuki |first11=G |date=26 May 2017 |title=The British Society for Rheumatology Guideline for the Management of Gout |journal=Rheumatology |volume=56 |issue=7 |pages=e1–e20 |doi=10.1093/rheumatology/kex156 |pmid=28549177 |doi-access=free |first14=E |last14=Roddy |first13=W |last13=Zhang |first12=A |last12=Pywell}}</ref><ref name="Dalbeth20162">{{cite journal |last1=Dalbeth |first1=N |author1-link=Nicola Dalbeth |last2=Merriman |first2=TR |last3=Stamp |first3=LK |date=April 2016 |title=Gout |journal=Lancet |type=Review |volume=388 |issue=10055 |pages=2039–2052 |doi=10.1016/S0140-6736(16)00346-9 |pmid=27112094 |s2cid=208790780}}</ref> caused by the deposition of needle-like crystals of [[uric acid]] known as [[monosodium urate crystals]].<ref name="Abhishek">{{cite journal |last1=Abhishek |first1=A |last2=Roddy |first2=E |last3=Doherty |first3=M |title=Gout - a guide for the general and acute physicians. |journal=Clinical Medicine |date=February 2017 |volume=17 |issue=1 |pages=54–59 |doi=10.7861/clinmedicine.17-1-54 |pmid=28148582|pmc=6297580 }}</ref> Pain typically comes on rapidly, reaching maximal intensity in less than 12 hours.<ref name="Lancet2010" /> The [[Metatarsophalangeal joint|joint]] at the base of the [[Hallux|big toe]] is affected (''Podagra'') in about half of cases.<ref name="PM2010">{{cite journal |author=Schlesinger N |title=Diagnosing and treating gout: a review to aid primary care physicians |journal=Postgrad Med |volume=122 |issue=2 |pages=157–161 |date=March 2010 |pmid=20203467 |doi=10.3810/pgm.2010.03.2133 |s2cid=35321485 }}</ref><ref name="MW1">{{cite web |title=Definition of Podagra |url=https://www.merriam-webster.com/dictionary/podagra |website=www.merriam-webster.com |access-date=19 January 2023 |language=en}}</ref> It may also result in [[Tophus|tophi]], [[kidney stone]]s, or [[Urate nephropathy|kidney damage]].<ref name="Dalbeth2016"/>
+'''Gout''' ({{IPAc-en|g|aʊ|t}} {{respell|GOWT}}<ref>{{cite web |title=Gout {{!}} Definition of Gout by Lexico |url=https://www.lexico.com/en/definition/gout |archive-url=https://web.archive.org/web/20191019015640/https://www.lexico.com/en/definition/gout |url-status=dead |archive-date=19 October 2019 |website=Lexico Dictionaries {{!}} English |access-date=20 October 2019 |language=en}}</ref>) is a form of [[inflammatory arthritis]] characterized by recurrent attacks of pain in a red, tender, hot, and [[Joint effusion|swollen joint]],<ref name="Hui2017">{{cite journal|last1=Hui |first1=M |last2=Carr |first2=A |last3=Cameron |first3=S |last4=Davenport |first4=G |last5=Doherty |first5=M |last6=Forrester |first6=H |last7=Jenkins |first7=W |last8=Jordan |first8=KM |last9=Mallen |first9=CD |last10=McDonald |first10=TM |last11=Nuki |first11=G |date=26 May 2017 |title=The British Society for Rheumatology Guideline for the Management of Gout |journal=Rheumatology |volume=56 |issue=7 |pages=e1–e20 |doi=10.1093/rheumatology/kex156 |pmid=28549177 |doi-access=free |first14=E |last14=Roddy |first13=W |last13=Zhang |first12=A |last12=Pywell}}</ref><ref name="Dalbeth20162">{{cite journal |last1=Dalbeth |first1=N |author1-link=Nicola Dalbeth |last2=Merriman |first2=TR |last3=Stamp |first3=LK |date=April 2016 |title=Gout |journal=Lancet |type=Review |volume=388 |issue=10055 |pages=2039–2052 |doi=10.1016/S0140-6736(16)00346-9 |pmid=27112094 |s2cid=208790780}}</ref> caused by the deposition of needle-like crystals of [[uric acid]] known as [[monosodium urate crystals]].<ref name="Abhishek">{{cite journal |last1=Abhishek |first1=A |last2=Roddy |first2=E |last3=Doherty |first3=M |title=Gout - a guide for the general and acute physicians. |journal=Clinical Medicine |date=February 2017 |volume=17 |issue=1 |pages=54–59 |doi=10.7861/clinmedicine.17-1-54 |pmid=28148582|pmc=6297580 }}</ref> Pain typically comes on rapidly, reaching maximal intensity in less than 12 hours.<ref name="Lancet2010" /> The [[Metatarsophalangeal joint|joint]] at the base of the [[Hallux|big toe]] is affected (''Podagra'') in about half of cases.<ref name="PM2010">{{cite journal |author=Schlesinger N |title=Diagnosing and treating gout: a review to aid primary care physicians |journal=Postgrad Med |volume=122 |issue=2 |pages=157–161 |date=March 2010 |pmid=20203467 |doi=10.3810/pgm.2010.03.2133 |s2cid=35321485 }}</ref><ref name="MW1">{{cite web |title=Definition of Podagra |url=https://www.merriam-webster.com/dictionary/podagra |website=www.merriam-webster.com |access-date=19 January 2023 |language=en |archive-date=19 January 2023 |archive-url=https://web.archive.org/web/20230119162753/https://www.merriam-webster.com/dictionary/podagra |url-status=live }}</ref> It may also result in [[Tophus|tophi]], [[kidney stone]]s, or [[Urate nephropathy|kidney damage]].<ref name="Dalbeth2016"/>
 <!-- Cause and diagnosis -->
@@ Line 32: / Line 32: @@
 <!-- Epidemiology and history -->
-Gout affects about 1–2% of adults in the developed world at some point in their lives.<ref name=Lancet2010/> It has become more common in recent decades.<ref name="Dalbeth2016"/> This is believed to be due to increasing risk factors in the population, such as [[metabolic syndrome]], longer life expectancy, and changes in diet.<ref name=Lancet2010/> Older males are most commonly affected.<ref name="Dalbeth2016"/> Gout was historically known as "the disease of kings" or "rich man's disease".<ref name=Lancet2010/><ref name=Dic>{{cite web |url=http://medical-dictionary.thefreedictionary.com/Rich+Man%27s+Disease |title=Rich Man's Disease – definition of Rich Man's Disease in the Medical dictionary |website= Free Online Medical Dictionary, Thesaurus and Encyclopedia}}</ref> It has been recognized at least since the time of the ancient Egyptians.<ref name=Lancet2010/>
+Gout affects about 1–2% of adults in the developed world at some point in their lives.<ref name=Lancet2010/> It has become more common in recent decades.<ref name="Dalbeth2016"/> This is believed to be due to increasing risk factors in the population, such as [[metabolic syndrome]], longer life expectancy, and changes in diet.<ref name=Lancet2010/> Older males are most commonly affected.<ref name="Dalbeth2016"/> Gout was historically known as "the disease of kings" or "rich man's disease".<ref name=Lancet2010/><ref name=Dic>{{cite web |url=http://medical-dictionary.thefreedictionary.com/Rich+Man%27s+Disease |title=Rich Man's Disease – definition of Rich Man's Disease in the Medical dictionary |website=Free Online Medical Dictionary, Thesaurus and Encyclopedia |access-date=1 May 2009 |archive-date=14 November 2013 |archive-url=https://web.archive.org/web/20131114084137/http://medical-dictionary.thefreedictionary.com/Rich+Man%27s+Disease |url-status=live }}</ref> It has been recognized at least since the time of the ancient Egyptians.<ref name=Lancet2010/>
 ==Signs and symptoms==
-[[Image:Gout2010.JPG|thumb|upright=1.4|alt=side view of a foot showing a red patch of skin over the joint at the base of the big toe|Gout presenting as slight redness in the [[metatarsophalangeal joint]] of the [[Hallux|big toe]]]]
+[[Image:Gout2010.JPG|thumb|alt=side view of a foot showing a red patch of skin over the joint at the base of the big toe|Gout presenting as slight redness in the [[metatarsophalangeal joint]] 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).<ref name="Neogi2016"/> The [[metatarsophalangeal joint]] at the base of the [[Hallux|big toe]] is affected most often, accounting for half of cases.<ref name=PM2010/> Other joints, such as the heels, knees, wrists, and fingers, may also be affected.<ref name="Neogi2016"/> Joint pain usually begins during the night and peaks within 24 hours of onset.<ref name="Neogi2016"/> This is mainly due to lower body temperature.<ref name="Dalbeth2016"/> Other symptoms may rarely occur along with the joint pain, including [[fatigue (medical)|fatigue]] and high fever.<ref name=PM2010/><ref name=Egg2007>{{cite journal |author=Eggebeen AT |title=Gout: an update |journal=Am Fam Physician |volume=76 |issue=6 |pages=801–808 |year=2007 |pmid=17910294}}</ref>
@@ Line 43: / Line 43: @@
 [[File:Tophaceous gout affecting the arms and hands Wellcome L0062959.jpg|thumb|right|250px|Arms and hands of a 50-year-old man, showing large [[Tophus|tophi]] of [[Uric acid#Gout|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 [[Uric acid#Gout|urate]], the salts of uric acid.<ref name="Dalbeth2016"/> 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%.<ref name=Lancet2010/> About 10% of people with [[hyperuricemia]] develop gout at some point in their lifetimes.<ref name="pmid18327257">{{cite journal  |vauthors=Vitart V, Rudan I, Hayward C, etal |title=SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout |journal=Nat. Genet. |volume=40 |issue=4 |pages=437–442 |date=April 2008 |pmid=18327257 |doi=10.1038/ng.106 |s2cid=6720464 |url=http://idiprints.knjiznica.idi.hr/373/ }}</ref> The risk, however, varies depending on the degree of hyperuricemia. When levels are between 415 and 530&nbsp;μmol/L (7 and 8.9&nbsp;mg/dl), the risk is 0.5% per year, while in those with a level greater than 535&nbsp;μmol/L (9&nbsp;mg/dL), the risk is 4.5% per year.<ref name=Egg2007/>
+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 [[Uric acid#Gout|urate]], the salts of uric acid.<ref name="Dalbeth2016"/> 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%.<ref name=Lancet2010/> About 10% of people with [[hyperuricemia]] develop gout at some point in their lifetimes.<ref name="pmid18327257">{{cite journal |vauthors=Vitart V, Rudan I, Hayward C, etal |title=SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout |journal=Nat. Genet. |volume=40 |issue=4 |pages=437–442 |date=April 2008 |pmid=18327257 |doi=10.1038/ng.106 |s2cid=6720464 |url=http://idiprints.knjiznica.idi.hr/373/ |access-date=27 July 2022 |archive-date=27 July 2022 |archive-url=https://web.archive.org/web/20220727105749/http://idiprints.knjiznica.idi.hr/373/ |url-status=live }}</ref> The risk, however, varies depending on the degree of hyperuricemia. When levels are between 415 and 530&nbsp;μmol/L (7 and 8.9&nbsp;mg/dL), the risk is 0.5% per year, while in those with a level greater than 535&nbsp;μmol/L (9&nbsp;mg/dL), the risk is 4.5% per year.<ref name=Egg2007/>
 ===Lifestyle===
@@ Line 61: / Line 61: @@
 ===Medication===
-[[Diuretic]]s have been associated with attacks of gout, but a low dose of [[hydrochlorothiazide]] does not seem to increase risk.<ref name=CFP09/> Other medications that increase the risk include [[Niacin (substance)|niacin]], [[aspirin]] (acetylsalicylic acid), [[ACE inhibitor]]s, [[angiotensin receptor blocker]]s, [[beta blocker]]s, [[ritonavir]], and [[pyrazinamide]].<ref name="Dalbeth2016"/><ref name=Nature2009/> The [[immunosuppressive drug]]s [[ciclosporin]] and [[tacrolimus]] are also associated with gout,<ref name=Lancet2010/> the former more so when used in combination with hydrochlorothiazide.<ref>{{cite book |editor1-first=Gary S. |editor1-last=Firestein |editor2-first=Ralph C. |editor2-last=Budd |editor3-first=Edward D. |editor3-last=Harris |editor4-first= Iain B. |editor4-last=McInnes |editor5-first=Shaun |editor5-last=Ruddy |editor6-first=John S. |editor6-last=Sergent |title=Kelley's Textbook of Rheumatology |edition=8th |year=2008 |publisher=Elsevier |isbn=978-1-4160-4842-8 |chapter=Chapter 87: Gout and Hyperuricemia}}</ref> Hyperuricemia may be induced by excessive use of Vitamin D supplements. Levels of serum uric acid have been positively associated with 25(OH) D. The incidence of hyperuricemia increased 9.4% for every 10 nmol/L increase in 25(OH) D (P < 0.001).<ref>{{cite journal |last1=Chen |first1=Yingchao |date=2020 |title=Association between serum vitamin D and uric acid in the eastern Chinese population: a population-based cross-sectional study. |url=https://rdcu.be/cHtkQ |journal=BMC Endocr Disord |volume=20 |issue=79 |page=79 |doi=10.1186/s12902-020-00560-1 |pmid=32493273 |pmc=7268462 |access-date=21 June 2021 |doi-access=free }}</ref>
+[[Diuretic]]s have been associated with attacks of gout, but a low dose of [[hydrochlorothiazide]] does not seem to increase risk.<ref name=CFP09/> Other medications that increase the risk include [[Niacin (substance)|niacin]], [[aspirin]] (acetylsalicylic acid), [[ACE inhibitor]]s, [[angiotensin receptor blocker]]s, [[beta blocker]]s, [[ritonavir]], and [[pyrazinamide]].<ref name="Dalbeth2016"/><ref name=Nature2009/> The [[immunosuppressive drug]]s [[ciclosporin]] and [[tacrolimus]] are also associated with gout,<ref name=Lancet2010/> the former more so when used in combination with hydrochlorothiazide.<ref>{{cite book |editor1-first=Gary S. |editor1-last=Firestein |editor2-first=Ralph C. |editor2-last=Budd |editor3-first=Edward D. |editor3-last=Harris |editor4-first= Iain B. |editor4-last=McInnes |editor5-first=Shaun |editor5-last=Ruddy |editor6-first=John S. |editor6-last=Sergent |title=Kelley's Textbook of Rheumatology |edition=8th |year=2008 |publisher=Elsevier |isbn=978-1-4160-4842-8 |chapter=Chapter 87: Gout and Hyperuricemia}}</ref> Hyperuricemia may be induced by excessive use of Vitamin D supplements. Levels of serum uric acid have been positively associated with 25(OH) D. The incidence of hyperuricemia increased 9.4% for every 10 nmol/L increase in 25(OH) D (P < 0.001).<ref>{{cite journal |last1=Chen |first1=Yingchao |date=2020 |title=Association between serum vitamin D and uric acid in the eastern Chinese population: a population-based cross-sectional study. |url=https://rdcu.be/cHtkQ |journal=BMC Endocr Disord |volume=20 |issue=79 |page=79 |doi=10.1186/s12902-020-00560-1 |pmid=32493273 |pmc=7268462 |access-date=21 June 2021 |doi-access=free |archive-date=10 July 2024 |archive-url=https://web.archive.org/web/20240710063618/https://www.biomedcentral.com/epdf/10.1186/s12902-020-00560-1?sharing_token=2cW1CJCCbuDOmSgFjaRPuG_BpE1tBhCbnbw3BuzI2RPh6v_muYveTL-poMvfpyCalHaXszrUOCBZ-NGpeESiL0L0YQKZPY0oqu5huqTmGuIDlN9g0iJL3O3BCtGRpPDqRBNWnHFNYtFJW0A94ysz7f5HqEtewOugX5HVi3vR3AE%3D |url-status=live }}</ref>
 ==Pathophysiology==
@@ Line 68: / Line 68: @@
 Gout is a disorder of [[purine metabolism]],<ref name="Lancet2010" /> and occurs when its final metabolite, [[uric acid]], crystallizes in the form of monosodium urate, [[Precipitation (chemistry)|precipitating]] and forming deposits (tophi) in joints, on tendons, and in the surrounding tissues.<ref name=Nature2009/> Microscopic [[tophus|tophi]] may be walled off by a ring of proteins, which blocks interaction of the crystals with cells and therefore avoids inflammation.<ref name="LB&R">{{cite journal |last1=Liu-Bryan |first1=Ru |last2=Terkeltaub |first2=Robert |date=2006 |title=Evil humors take their Toll as innate immunity makes gouty joints TREM-ble |journal=Arthritis & Rheumatism |volume=54 |issue=2 |pages=383–386 |doi=10.1002/art.21634 |pmid=16447213 |doi-access=free }}</ref> 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.<ref name="LB&R"/> When they break through the tophi, they trigger a local [[immune]]-mediated [[inflammation|inflammatory]] reaction in [[macrophages]], which is initiated by the [[NLRP3]] [[inflammasome|inflammasome protein complex]].<ref name="Dalbeth2016"/><ref name="Nature2009" /><ref name="LB&R"/> Activation of the NLRP3 inflammasome recruits the enzyme [[caspase 1]], which converts pro-interleukin 1β into active [[interleukin-1 beta|interleukin 1β]], one of the key proteins in the inflammatory cascade.<ref name="Dalbeth2016">{{cite journal|last1=Dalbeth|first1=N|author1-link= Nicola Dalbeth |last2=Merriman|first2=TR|last3=Stamp|first3=LK|title=Gout|journal=Lancet|date=April 2016|volume=388|issue=10055|pages=2039–2052|doi=10.1016/S0140-6736(16)00346-9|pmid=27112094|s2cid=208790780|type=Review}}</ref> An evolutionary loss of [[urate oxidase]] (uricase), which breaks down uric acid, in humans and higher [[primate]]s has made this condition common.<ref name="Lancet2010" />
-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.<ref name="Nature2009" /><ref name="pmid17595458">{{cite journal |vauthors=Virsaladze DK, Tetradze LO, Dzhavashvili LV, Esaliia NG, Tananashvili DE |title=[Levels of uric acid in serum in patients with metabolic syndrome] |language=ru |journal=Georgian Med News|issue=146 |pages=35–37 |year=2007 |pmid=17595458 |trans-title=Levels of uric acid in serum in patients with metabolic syndrome }}</ref> 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.<ref name="Lancet2010" /><ref name="pmid12672211">{{cite journal|vauthors=Moyer RA, John DS | title = Acute gout precipitated by total parenteral nutrition| journal = The Journal of Rheumatology| volume = 30| issue = 4| pages = 849–850| year = 2003| pmid = 12672211}}</ref><ref name="pmid7783706">{{cite journal|vauthors=Halabe A, Sperling O | title = Uric acid nephrolithiasis| journal = Mineral and Electrolyte Metabolism| volume = 20| issue = 6| pages = 424–431| year = 1994| pmid = 7783706}}</ref> The increased precipitation at low temperatures partly explains why the joints in the feet are most commonly affected.<ref name="Review08" /> Rapid changes in uric acid may occur due to factors including trauma, surgery, [[chemotherapy]] and diuretics.<ref name="Egg2007" /> The starting or increasing of urate-lowering medications can lead to an acute attack of gout with [[febuxostat]] of a particularly high risk.<ref name=CKS2019>{{cite web |title=Gout |url=https://cks.nice.org.uk/gout#!scenario:1 |website=NICE |access-date=22 August 2019 }}</ref> [[Calcium channel blocker]]s and [[losartan]] are associated with a lower risk of gout compared to other medications for [[hypertension]].<ref name="pmid22240117">{{cite journal|vauthors=Choi HK, Soriano LC, Zhang Y, Rodríguez LA | title=Antihypertensive drugs and risk of incident gout among patients with hypertension: population based case-control study | journal=BMJ | year= 2012 | volume= 344 |pages= d8190 | pmid=22240117 | doi=10.1136/bmj.d8190 | pmc=3257215}}</ref>
+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.<ref name="Nature2009" /><ref name="pmid17595458">{{cite journal |vauthors=Virsaladze DK, Tetradze LO, Dzhavashvili LV, Esaliia NG, Tananashvili DE |title=[Levels of uric acid in serum in patients with metabolic syndrome] |language=ru |journal=Georgian Med News|issue=146 |pages=35–37 |year=2007 |pmid=17595458 |trans-title=Levels of uric acid in serum in patients with metabolic syndrome }}</ref> 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.<ref name="Lancet2010" /><ref name="pmid12672211">{{cite journal|vauthors=Moyer RA, John DS | title = Acute gout precipitated by total parenteral nutrition| journal = The Journal of Rheumatology| volume = 30| issue = 4| pages = 849–850| year = 2003| pmid = 12672211}}</ref><ref name="pmid7783706">{{cite journal|vauthors=Halabe A, Sperling O | title = Uric acid nephrolithiasis| journal = Mineral and Electrolyte Metabolism| volume = 20| issue = 6| pages = 424–431| year = 1994| pmid = 7783706}}</ref> The increased precipitation at low temperatures partly explains why the joints in the feet are most commonly affected.<ref name="Review08" /> Rapid changes in uric acid may occur due to factors including trauma, surgery, [[chemotherapy]] and diuretics.<ref name="Egg2007" /> The starting or increasing of urate-lowering medications can lead to an acute attack of gout with [[febuxostat]] of a particularly high risk.<ref name=CKS2019>{{cite web |title=Gout |url=https://cks.nice.org.uk/gout#!scenario:1 |website=NICE |access-date=22 August 2019 |archive-date=28 October 2016 |archive-url=https://web.archive.org/web/20161028200324/http://cks.nice.org.uk/gout#!scenario:1 |url-status=live }}</ref> [[Calcium channel blocker]]s and [[losartan]] are associated with a lower risk of gout compared to other medications for [[hypertension]].<ref name="pmid22240117">{{cite journal|vauthors=Choi HK, Soriano LC, Zhang Y, Rodríguez LA | title=Antihypertensive drugs and risk of incident gout among patients with hypertension: population based case-control study | journal=BMJ | year= 2012 | volume= 344 |pages= d8190 | pmid=22240117 | doi=10.1136/bmj.d8190 | pmc=3257215}}</ref>
 ==Diagnosis==
 {{Synovial fluid analysis}}
-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.<ref name=Egg2007/><ref>{{cite journal|last1=Qaseem|first1=A|last2=McLean|first2=RM|last3=Starkey|first3=M|last4=Forciea|first4=MA|last5=Clinical Guidelines Committee of the American College of|first5=Physicians.|title=Diagnosis of Acute Gout: A Clinical Practice Guideline From the American College of Physicians|journal=Annals of Internal Medicine|date=3 January 2017|volume=166|issue=1|pages=52–57|pmid=27802479|doi=10.7326/m16-0569|doi-access=free}}</ref> Plain [[radiographs|X-rays]] are usually normal and are not useful for confirming a diagnosis of early gout.<ref name=Lancet2010/> They may show signs of chronic gout such as bone erosion.<ref name=CKS2019/>
+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.<ref name=Egg2007/><ref>{{cite journal|last1=Qaseem|first1=A|last2=McLean|first2=RM|last3=Starkey|first3=M|last4=Forciea|first4=MA|last5=Clinical Guidelines Committee of the American College of|first5=Physicians.|title=Diagnosis of Acute Gout: A Clinical Practice Guideline From the American College of Physicians|journal=Annals of Internal Medicine|date=3 January 2017|volume=166|issue=1|pages=52–57|pmid=27802479|doi=10.7326/m16-0569|doi-access=free}}</ref> Plain [[radiographs|X-rays]] are usually normal and are not useful for confirming a diagnosis of early gout.<ref name=Lancet2010/> They may show signs of chronic gout such as bone erosion.<ref name=CKS2019/>
 ===Synovial fluid===
@@ Line 78: / Line 78: @@
 ===Blood tests===
-[[Hyperuricemia]] is a classic feature of gout, but nearly half of the time gout occurs without hyperuricemia and most people with raised uric acid levels never develop gout.<ref name=PM2010/><ref>{{cite journal | author = Sturrock R | title = Gout. Easy to misdiagnose | journal = [[British Medical Journal|BMJ]] | volume = 320 | issue = 7228 | pages = 132–133 | year = 2000 | pmid = 10634714| doi = 10.1136/bmj.320.7228.132 | pmc = 1128728}}</ref> Thus, the diagnostic utility of measuring uric acid levels is limited.<ref name=PM2010/> Hyperuricemia is defined as a [[blood plasma|plasma]] urate level greater than 420 μmol/L (7.0&nbsp;mg/dl) in males and 360 μmol/L (6.0&nbsp;mg/dl) in females.<ref>{{cite journal |vauthors=Sachs L, Batra KL, Zimmermann B |title=Medical implications of hyperuricemia |journal=Med Health R I |volume=92 |issue=11 |pages=353–355 |year=2009 |pmid=19999892}}</ref> Other blood tests commonly performed are [[white blood cell count]], [[electrolyte]]s, [[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.<ref>{{cite journal |url=http://emedicine.medscape.com/article/329958-diagnosis |title=Gout: Differential Diagnoses & Workup – eMedicine Rheumatology |website=Medscape |url-status=live |archive-url=https://web.archive.org/web/20100725115050/http://emedicine.medscape.com/article/329958-diagnosis |archive-date=25 July 2010 |date=17 January 2019 }}</ref><ref>{{cite journal |url=http://emedicine.medscape.com/article/808628-diagnosis |title=Gout and Pseudogout: Differential Diagnoses & Workup – eMedicine Emergency Medicine |website=Medscape |url-status=live |archive-url=https://web.archive.org/web/20100311174806/http://emedicine.medscape.com/article/808628-diagnosis |archive-date=11 March 2010 |date=17 January 2019 }}</ref> A white blood cell count as high as 40.0×10<sup>9</sup>/l (40,000/mm<sup>3</sup>) has been documented.<ref name=Egg2007/>
+[[Hyperuricemia]] is a classic feature of gout, but nearly half of the time gout occurs without hyperuricemia and most people with raised uric acid levels never develop gout.<ref name=PM2010/><ref>{{cite journal | author = Sturrock R | title = Gout. Easy to misdiagnose | journal = [[British Medical Journal|BMJ]] | volume = 320 | issue = 7228 | pages = 132–133 | year = 2000 | pmid = 10634714| doi = 10.1136/bmj.320.7228.132 | pmc = 1128728}}</ref> Thus, the diagnostic utility of measuring uric acid levels is limited.<ref name=PM2010/> Hyperuricemia is defined as a [[blood plasma|plasma]] urate level greater than 420 μmol/L (7.0&nbsp;mg/dL) in males and 360 μmol/L (6.0&nbsp;mg/dL) in females.<ref>{{cite journal |vauthors=Sachs L, Batra KL, Zimmermann B |title=Medical implications of hyperuricemia |journal=Med Health R I |volume=92 |issue=11 |pages=353–355 |year=2009 |pmid=19999892}}</ref> Other blood tests commonly performed are [[white blood cell count]], [[electrolyte]]s, [[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.<ref>{{cite journal |url=http://emedicine.medscape.com/article/329958-diagnosis |title=Gout: Differential Diagnoses & Workup – eMedicine Rheumatology |website=Medscape |url-status=live |archive-url=https://web.archive.org/web/20100725115050/http://emedicine.medscape.com/article/329958-diagnosis |archive-date=25 July 2010 |date=17 January 2019 }}</ref><ref>{{cite journal |url=http://emedicine.medscape.com/article/808628-diagnosis |title=Gout and Pseudogout: Differential Diagnoses & Workup – eMedicine Emergency Medicine |website=Medscape |url-status=live |archive-url=https://web.archive.org/web/20100311174806/http://emedicine.medscape.com/article/808628-diagnosis |archive-date=11 March 2010 |date=17 January 2019 }}</ref> A white blood cell count as high as 40.0×10<sup>9</sup>/l (40,000/mm<sup>3</sup>) has been documented.<ref name=Egg2007/>
 ===Differential diagnosis===
@@ Line 85: / Line 85: @@
 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.<ref>{{cite web |url=https://emedicine.medscape.com/article/329958-workup |title=Gout and Pseudogout Workup |first=Bruce M |last=Rothschild |website=Medscape}} Updated: Jun 30, 2020</ref>
+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.<ref>{{cite web |url=https://emedicine.medscape.com/article/329958-workup |title=Gout and Pseudogout Workup |first=Bruce M |last=Rothschild |website=Medscape |access-date=23 September 2020 |archive-date=8 October 2020 |archive-url=https://web.archive.org/web/20201008034412/https://emedicine.medscape.com/article/329958-workup |url-status=live }} Updated: Jun 30, 2020</ref>
 File:Birefringence microscopy of pseudogout, annotated.jpg|In contrast, [[Calcium pyrophosphate dihydrate crystal deposition disease|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.
@@ Line 91: / Line 91: @@
 ==Prevention==
-Risk of gout attacks can be lowered by [[Teetotalism|complete abstinence]] from drinking [[Alcohol (drug)|alcoholic beverages]], reducing the intake of [[fructose]] (e.g. [[high fructose corn syrup]])<ref>{{cite journal |vauthors=Jamnik J, Rehman S, Blanco Mejia S, de Souza RJ, Khan TA, Leiter LA, Wolever TM, Kendall CW, Jenkins DJ, Sievenpiper JL |title=Fructose intake and risk of gout and hyperuricemia: a systematic review and meta-analysis of prospective cohort studies |journal=BMJ Open |volume=6 |issue=10 |pages=e013191 |date=October 2016 |pmid=27697882 |pmc=5073537 |doi=10.1136/bmjopen-2016-013191 }}</ref> and [[purine]]-rich foods of animal origin, such as organ meats and [[seafood]].<ref name=Be2016/> Eating [[dairy product]]s, [[vitamin C]]-rich foods, [[coffee]], and [[Cherry|cherries]] may help prevent gout attacks, as does losing weight.<ref name=Be2016/><ref name=2014rev>{{cite journal|last1=Bitik|first1=B|last2=Öztürk|first2=MA|title=An old disease with new insights: Update on diagnosis and treatment of gout|journal=European Journal of Rheumatology|date=June 2014|volume=1|issue=2|pages=72–77|pmid=27708879|doi=10.5152/eurjrheumatol.2014.021|pmc=5042282}}</ref> 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.<ref name="pmid16171252">{{cite journal|pmc=2654686|year=2009|last1=Abrams|first1=B|title=Sleep Apnea as a Cause of Gout Flares|journal=The Medscape Journal of Medicine|volume=11|issue=1|pages=3|pmid=19295924}}</ref>
+Risk of gout attacks can be lowered by [[Teetotalism|complete abstinence]] from drinking [[Alcohol (drug)|alcoholic beverages]], reducing the intake of [[fructose]] (e.g. [[high fructose corn syrup]])<ref>{{cite journal |vauthors=Jamnik J, Rehman S, Blanco Mejia S, de Souza RJ, Khan TA, Leiter LA, Wolever TM, Kendall CW, Jenkins DJ, Sievenpiper JL |title=Fructose intake and risk of gout and hyperuricemia: a systematic review and meta-analysis of prospective cohort studies |journal=BMJ Open |volume=6 |issue=10 |pages=e013191 |date=October 2016 |pmid=27697882 |pmc=5073537 |doi=10.1136/bmjopen-2016-013191 }}</ref>, sucrose, and [[purine]]-rich foods of animal origin, such as organ meats and [[seafood]].<ref name=Be2016/> Eating [[dairy product]]s, [[vitamin C]]-rich foods, [[coffee]], and [[Cherry|cherries]] may help prevent gout attacks, as does losing weight.<ref name=Be2016/><ref name=2014rev>{{cite journal|last1=Bitik|first1=B|last2=Öztürk|first2=MA|title=An old disease with new insights: Update on diagnosis and treatment of gout|journal=European Journal of Rheumatology|date=June 2014|volume=1|issue=2|pages=72–77|pmid=27708879|doi=10.5152/eurjrheumatol.2014.021|pmc=5042282}}</ref> 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.<ref name="pmid16171252">{{cite journal|pmc=2654686|year=2009|last1=Abrams|first1=B|title=Sleep Apnea as a Cause of Gout Flares|journal=The Medscape Journal of Medicine|volume=11|issue=1|pages=3|pmid=19295924}}</ref>
 ===Medications===
-As of 2020, [[allopurinol]] is generally the recommended preventative treatment if medications are used.<ref name=Fitz2020>{{cite journal|last1=FitzGerald |first1=John D. |last2=Dalbeth |first2=Nicola |last3=Mikuls |first3=Ted |last4=Brignardello-Petersen |first4=Romina |last5=Guyatt |first5=Gordon |last6=Abeles |first6=Aryeh M. |last7=Gelber |first7=Allan C. |last8=Harrold |first8=Leslie R. |last9=Khanna |first9=Dinesh |last10=King |first10=Charles |last11=Levy |first11=Gerald |last12=Libbey |first12=Caryn |last13=Mount |first13=David |last14=Pillinger |first14=Michael H. |last15=Rosenthal |first15=Ann |last16=Singh |first16=Jasvinder A. |last17=Sims |first17=James Edward |last18=Smith |first18=Benjamin J. |last19=Wenger |first19=Neil S. |last20=Bae |first20=Sangmee Sharon |last21=Danve |first21=Abhijeet |last22=Khanna |first22=Puja P. |last23=Kim |first23=Seoyoung C. |last24=Lenert |first24=Aleksander |last25=Poon |first25=Samuel |last26=Qasim |first26=Anila |last27=Sehra |first27=Shiv T. |last28=Sharma |first28=Tarun Sudhir Kumar |last29=Toprover |first29=Michael |last30=Turgunbaev |first30=Marat |last31=Zeng |first31=Linan |last32=Zhang |first32=Mary Ann |last33=Turner |first33=Amy S. |last34=Neogi |first34=Tuhina |title=2020 American College of Rheumatology Guideline for the Management of Gout |journal=Arthritis & Rheumatology |date=11 May 2020 |volume=72 |issue=6 |pages=879–895 |doi=10.1002/art.41247|pmid=32390306 |doi-access=free |hdl=2027.42/155484 |hdl-access=free }}</ref><ref name="ACR2021">{{cite journal |vauthors=Dakkak M, Lanney H |title=Management of Gout: Update from the American College of Rheumatology |journal=Am Fam Physician |volume=104 |issue=2 |pages=209–210 |date=August 2021 |pmid=34383428 |doi= |url=}}</ref> A number of other medications may occasionally be considered to prevent further episodes of gout, including [[probenecid]], [[febuxostat]], [[benzbromarone]], and colchicine.<ref name="Annals2017" /><ref name=Lancet2016>{{cite journal|last1=Dalbeth|first1=N|last2=Merriman|first2=TR|last3=Stamp|first3=LK|title=Gout|journal=Lancet|date=22 October 2016|volume=388|issue=10055|pages=2039–2052|pmid=27112094|doi=10.1016/s0140-6736(16)00346-9|s2cid=208790780}}</ref><ref>{{cite journal|last1=Kydd|first1=Alison SR|last2=Seth|first2=Rakhi|last3=Buchbinder|first3=Rachelle|last4=Edwards|first4=Christopher J|last5=Bombardier|first5=Claire|date=14 November 2014|title=Uricosuric medications for chronic gout|journal=Cochrane Database of Systematic Reviews|issue=11|pages=CD010457|doi=10.1002/14651858.cd010457.pub2|pmid=25392987|issn=1465-1858}}</ref> Long term medications are not recommended until a person has had two attacks of gout,<ref name=Review08/> unless destructive joint changes, tophi, or [[Acute uric acid nephropathy|urate nephropathy]] exist.<ref name=German09>{{cite journal |vauthors=Tausche AK, Jansen TL, Schröder HE, Bornstein SR, Aringer M, Müller-Ladner U |title=Gout – current diagnosis and treatment |journal=Dtsch Ärztebl Int |volume=106 |issue=34–35 |pages=549–555 |date=August 2009 |pmid=19795010 |pmc=2754667 |doi=10.3238/arztebl.2009.0549 }}</ref> It is not until this point that medications are cost-effective.<ref name=Review08/> They are not usually started until one to two weeks after an acute flare has resolved, due to theoretical concerns of worsening the attack.<ref name=Review08/> They are often used in combination with either an NSAID or colchicine for the first three to six months.<ref name=Lancet2010/><ref name="Annals2017" />
+As of 2020, [[allopurinol]] is generally the recommended preventative treatment if medications are used.<ref name=Fitz2020>{{cite journal|last1=FitzGerald |first1=John D. |last2=Dalbeth |first2=Nicola |last3=Mikuls |first3=Ted |last4=Brignardello-Petersen |first4=Romina |last5=Guyatt |first5=Gordon |last6=Abeles |first6=Aryeh M. |last7=Gelber |first7=Allan C. |last8=Harrold |first8=Leslie R. |last9=Khanna |first9=Dinesh |last10=King |first10=Charles |last11=Levy |first11=Gerald |last12=Libbey |first12=Caryn |last13=Mount |first13=David |last14=Pillinger |first14=Michael H. |last15=Rosenthal |first15=Ann |last16=Singh |first16=Jasvinder A. |last17=Sims |first17=James Edward |last18=Smith |first18=Benjamin J. |last19=Wenger |first19=Neil S. |last20=Bae |first20=Sangmee Sharon |last21=Danve |first21=Abhijeet |last22=Khanna |first22=Puja P. |last23=Kim |first23=Seoyoung C. |last24=Lenert |first24=Aleksander |last25=Poon |first25=Samuel |last26=Qasim |first26=Anila |last27=Sehra |first27=Shiv T. |last28=Sharma |first28=Tarun Sudhir Kumar |last29=Toprover |first29=Michael |last30=Turgunbaev |first30=Marat |last31=Zeng |first31=Linan |last32=Zhang |first32=Mary Ann |last33=Turner |first33=Amy S. |last34=Neogi |first34=Tuhina |title=2020 American College of Rheumatology Guideline for the Management of Gout |journal=Arthritis & Rheumatology |date=11 May 2020 |volume=72 |issue=6 |pages=879–895 |doi=10.1002/art.41247|pmid=32390306 |doi-access=free |hdl=2027.42/155484 |hdl-access=free }}</ref><ref name="ACR2021">{{cite journal |vauthors=Dakkak M, Lanney H |title=Management of Gout: Update from the American College of Rheumatology |journal=Am Fam Physician |volume=104 |issue=2 |pages=209–210 |date=August 2021 |pmid=34383428 |doi= |url=}}</ref> A number of other medications may occasionally be considered to prevent further episodes of gout, including [[probenecid]], [[febuxostat]], [[benzbromarone]], and [[colchicine]].<ref name="Annals2017" /><ref name=Lancet2016>{{cite journal|last1=Dalbeth|first1=N|last2=Merriman|first2=TR|last3=Stamp|first3=LK|title=Gout|journal=Lancet|date=22 October 2016|volume=388|issue=10055|pages=2039–2052|pmid=27112094|doi=10.1016/s0140-6736(16)00346-9|s2cid=208790780}}</ref><ref>{{cite journal|last1=Kydd|first1=Alison SR|last2=Seth|first2=Rakhi|last3=Buchbinder|first3=Rachelle|last4=Edwards|first4=Christopher J|last5=Bombardier|first5=Claire|date=14 November 2014|title=Uricosuric medications for chronic gout|journal=Cochrane Database of Systematic Reviews|issue=11|pages=CD010457|doi=10.1002/14651858.cd010457.pub2|pmid=25392987|issn=1465-1858|pmc=11262558}}</ref> Long term medications are not recommended until a person has had two attacks of gout,<ref name=Review08/> unless destructive joint changes, tophi, or [[Acute uric acid nephropathy|urate nephropathy]] exist.<ref name=German09>{{cite journal |vauthors=Tausche AK, Jansen TL, Schröder HE, Bornstein SR, Aringer M, Müller-Ladner U |title=Gout – current diagnosis and treatment |journal=Dtsch Ärztebl Int |volume=106 |issue=34–35 |pages=549–555 |date=August 2009 |pmid=19795010 |pmc=2754667 |doi=10.3238/arztebl.2009.0549 }}</ref> It is not until this point that medications are cost-effective.<ref name=Review08/> They are not usually started until one to two weeks after an acute flare has resolved, due to theoretical concerns of worsening the attack.<ref name=Review08/> They are often used in combination with either an NSAID or colchicine for the first three to six months.<ref name=Lancet2010/><ref name="Annals2017" />
-While it has been recommended that urate-lowering measures should be increased until serum uric acid levels are below 300–360&nbsp;µmol/L (5.0–6.0&nbsp;mg/dl),<ref name=Fitz2020/><ref>{{cite journal|last1=Ruoff|first1=G|last2=Edwards|first2=NL|title=Overview of Serum Uric Acid Treatment Targets in Gout: Why Less Than 6 mg/dL?|journal=Postgraduate Medicine|date=September 2016|volume=128|issue=7|pages=706–715|pmid=27558643|doi=10.1080/00325481.2016.1221732|doi-access=free}}</ref> there is little evidence to support this practice over simply putting people on a standard dose of allopurinol.<ref>{{cite journal |last1=Qaseem |first1=Amir |last2=Harris |first2=Russell P. |last3=Forciea |first3=Mary Ann |title=Management of Acute and Recurrent Gout: A Clinical Practice Guideline From the American College of Physicians |journal=Annals of Internal Medicine |date=1 November 2016 |volume=166 |issue=1 |pages=58–68 |doi=10.7326/M16-0570|pmid=27802508 |s2cid=207538623 |url=https://cdr.lib.unc.edu/downloads/c534ft390 |doi-access=free }}</ref> If these medications are in chronic use at the time of an attack, it is recommended that they be continued.<ref name=PM2010/> Levels that cannot be brought below 6.0&nbsp;mg/dl while attacks continue indicates refractory gout.<ref>{{cite journal|last=Ali|first=S|author2=Lally, EV|title=Treatment failure gout|journal=Medicine and Health, Rhode Island|date=November 2009|volume=92|issue=11|pages=369–371|pmid=19999896}}</ref>
+While it has been recommended that urate-lowering measures should be increased until serum uric acid levels are below 300–360&nbsp;μmol/L (5.0–6.0&nbsp;mg/dL),<ref name=Fitz2020/><ref>{{cite journal|last1=Ruoff|first1=G|last2=Edwards|first2=NL|title=Overview of Serum Uric Acid Treatment Targets in Gout: Why Less Than 6 mg/dL?|journal=Postgraduate Medicine|date=September 2016|volume=128|issue=7|pages=706–715|pmid=27558643|doi=10.1080/00325481.2016.1221732|doi-access=free}}</ref> there is little evidence to support this practice over simply putting people on a standard dose of allopurinol.<ref>{{cite journal |last1=Qaseem |first1=Amir |last2=Harris |first2=Russell P. |last3=Forciea |first3=Mary Ann |title=Management of Acute and Recurrent Gout: A Clinical Practice Guideline From the American College of Physicians |journal=Annals of Internal Medicine |date=1 November 2016 |volume=166 |issue=1 |pages=58–68 |doi=10.7326/M16-0570 |pmid=27802508 |s2cid=207538623 |url=https://cdr.lib.unc.edu/downloads/c534ft390 |doi-access=free |access-date=16 October 2021 |archive-date=21 May 2022 |archive-url=https://web.archive.org/web/20220521083827/https://cdr.lib.unc.edu/downloads/c534ft390 |url-status=live }}</ref> If these medications are in chronic use at the time of an attack, it is recommended that they be continued.<ref name=PM2010/> Levels that cannot be brought below 6.0&nbsp;mg/dL while attacks continue indicates refractory gout.<ref>{{cite journal|last=Ali|first=S|author2=Lally, EV|title=Treatment failure gout|journal=Medicine and Health, Rhode Island|date=November 2009|volume=92|issue=11|pages=369–371|pmid=19999896}}</ref>
-While historically it is not recommended to start allopurinol during an acute attack of gout, this practice appears acceptable.<ref name=Rob2016>{{cite journal|last1=Robinson|first1=PC|last2=Stamp|first2=LK|title=The management of gout: Much has changed|journal=Australian Family Physician|date=May 2016|volume=45|issue=5|pages=299–302|pmid=27166465}}</ref> Allopurinol blocks uric acid production, and is the most commonly used agent.<ref name=Review08/> Long term therapy is safe and well-tolerated and can be used in people with renal impairment or urate stones, although hypersensitivity occurs in a small number of individuals.<ref name=Review08/>  The [[HLA-B58|''HLA-B*58:01'' allele]] of the [[human leukocyte antigen]] B (''[[HLA-B]]'') is strongly associated with [[severe cutaneous adverse reactions]] during treatment with allopurinol and is most common among [[Asian people|Asian]] subpopulations, notably those of [[Koreans|Korean]], [[Han Chinese|Han-Chinese]], or [[Thai people|Thai]] descent.<ref>{{Citation |last1=Dean |first1=Laura |title=Allopurinol Therapy and HLA-B*58:01 Genotype |date=2012 |url=http://www.ncbi.nlm.nih.gov/books/NBK127547/ |work=Medical Genetics Summaries |editor-last=Pratt |editor-first=Victoria M. |place=Bethesda (MD) |publisher=National Center for Biotechnology Information (US) |pmid=28520356 |access-date=29 November 2022 |last2=Kane |first2=Megan |editor2-last=Scott |editor2-first=Stuart A. |editor3-last=Pirmohamed |editor3-first=Munir |editor4-last=Esquivel |editor4-first=Bernard}}</ref>
+While historically it is not recommended to start allopurinol during an acute attack of gout, this practice appears acceptable.<ref name=Rob2016>{{cite journal|last1=Robinson|first1=PC|last2=Stamp|first2=LK|title=The management of gout: Much has changed|journal=Australian Family Physician|date=May 2016|volume=45|issue=5|pages=299–302|pmid=27166465}}</ref> Allopurinol blocks uric acid production, and is the most commonly used agent.<ref name=Review08/> Long term therapy is safe and well-tolerated and can be used in people with renal impairment or urate stones, although hypersensitivity occurs in a small number of individuals.<ref name=Review08/>  The [[HLA-B58|''HLA-B*58:01'' allele]] of the [[human leukocyte antigen]] B (''[[HLA-B]]'') is strongly associated with [[severe cutaneous adverse reactions]] during treatment with allopurinol and is most common among [[Asian people|Asian]] subpopulations, notably those of [[Koreans|Korean]], [[Han Chinese|Han-Chinese]], or [[Thai people|Thai]] descent.<ref>{{Citation |last1=Dean |first1=Laura |title=Allopurinol Therapy and HLA-B*58:01 Genotype |date=2012 |url=http://www.ncbi.nlm.nih.gov/books/NBK127547/ |work=Medical Genetics Summaries |editor-last=Pratt |editor-first=Victoria M. |place=Bethesda (MD) |publisher=National Center for Biotechnology Information (US) |pmid=28520356 |access-date=29 November 2022 |last2=Kane |first2=Megan |editor2-last=Scott |editor2-first=Stuart A. |editor3-last=Pirmohamed |editor3-first=Munir |editor4-last=Esquivel |editor4-first=Bernard |archive-date=15 June 2022 |archive-url=https://web.archive.org/web/20220615144550/https://www.ncbi.nlm.nih.gov/books/NBK127547/ |url-status=live }}</ref>
-Febuxostat is only recommended in those who cannot tolerate allopurinol.<ref>{{cite web|title=Febuxostat for the management of hyperuricaemia in people with gout Guidance and guidelines|url=https://www.nice.org.uk/guidance/TA164|website=www.nice.org.uk|access-date=28 March 2017|date=17 December 2008|url-status=live|archive-url=https://web.archive.org/web/20170328195736/https://www.nice.org.uk/guidance/TA164|archive-date=28 March 2017}}</ref> There are concerns about more deaths with febuxostat compared to allopurinol.<ref name=FDA2019>{{cite web |title=Drug Safety and Availability – FDA adds Boxed Warning for increased risk of death with gout medicine Uloric (febuxostat) |url=https://www.fda.gov/Drugs/DrugSafety/ucm631182.htm |website=FDA |access-date=26 February 2019 |language=en |date=21 February 2019}}</ref> Febuxostat may also increase the rate of gout flares during early treatment.<ref>{{cite journal|last1=Tayar|first1=Jean H|last2=Lopez-Olivo|first2=Maria Angeles|last3=Suarez-Almazor|first3=Maria E|date=14 November 2012|title=Febuxostat for treating chronic gout|journal=Cochrane Database of Systematic Reviews|volume=11|issue=11 |pages=CD008653|doi=10.1002/14651858.cd008653.pub2|pmid=23152264|pmc=4058893|issn=1465-1858}}</ref> However, there is tentative evidence that febuxostat may bring down urate levels more than allopurinol.<ref name=Coch2014Feb>{{cite journal|last1=Seth|first1=Rakhi|last2=Kydd|first2=Alison SR|last3=Buchbinder|first3=Rachelle|last4=Bombardier|first4=Claire|last5=Edwards|first5=Christopher J|date=14 October 2014|title=Allopurinol for chronic gout|journal=Cochrane Database of Systematic Reviews|volume=2014|issue=10|pages=CD006077|doi=10.1002/14651858.cd006077.pub3|pmid=25314636|pmc=8915170 |issn=1465-1858}}</ref>
+Febuxostat is only recommended in those who cannot tolerate allopurinol.<ref>{{cite web|title=Febuxostat for the management of hyperuricaemia in people with gout Guidance and guidelines|url=https://www.nice.org.uk/guidance/TA164|website=www.nice.org.uk|access-date=28 March 2017|date=17 December 2008|url-status=live|archive-url=https://web.archive.org/web/20170328195736/https://www.nice.org.uk/guidance/TA164|archive-date=28 March 2017}}</ref> There are concerns about more deaths with febuxostat compared to allopurinol.<ref name=FDA2019>{{cite web |title=Drug Safety and Availability – FDA adds Boxed Warning for increased risk of death with gout medicine Uloric (febuxostat) |url=https://www.fda.gov/Drugs/DrugSafety/ucm631182.htm |website=FDA |access-date=26 February 2019 |language=en |date=21 February 2019 |archive-date=23 April 2019 |archive-url=https://web.archive.org/web/20190423022609/https://www.fda.gov/Drugs/DrugSafety/ucm631182.htm |url-status=live }}</ref> Febuxostat may also increase the rate of gout flares during early treatment.<ref>{{cite journal|last1=Tayar|first1=Jean H|last2=Lopez-Olivo|first2=Maria Angeles|last3=Suarez-Almazor|first3=Maria E|date=14 November 2012|title=Febuxostat for treating chronic gout|journal=Cochrane Database of Systematic Reviews|volume=11|issue=11 |pages=CD008653|doi=10.1002/14651858.cd008653.pub2|pmid=23152264|pmc=4058893|issn=1465-1858}}</ref> However, there is tentative evidence that febuxostat may bring down urate levels more than allopurinol.<ref name=Coch2014Feb>{{cite journal|last1=Seth|first1=Rakhi|last2=Kydd|first2=Alison SR|last3=Buchbinder|first3=Rachelle|last4=Bombardier|first4=Claire|last5=Edwards|first5=Christopher J|date=14 October 2014|title=Allopurinol for chronic gout|journal=Cochrane Database of Systematic Reviews|volume=2014|issue=10|pages=CD006077|doi=10.1002/14651858.cd006077.pub3|pmid=25314636|pmc=8915170 |issn=1465-1858}}</ref>
-Probenecid appears to be less effective than allopurinol and is a second line agent.<ref name=Review08/><ref name=Lancet2016/> Probenecid may be used if undersecretion of uric acid is present (24-hour urine uric acid less than 800&nbsp;mg).<ref name=agabegi2nd251>{{cite book |first1=Elizabeth D |last1=Agabegi |author2=Agabegi, Steven S. |title=Step-Up to Medicine (Step-Up Series) |publisher=Lippincott Williams & Wilkins |location=Hagerstwon, MD |year=2008 |page=251 |isbn=978-0-7817-7153-5 |url=https://books.google.com/books?id=y13wgJyQwkEC&pg=PA251}}</ref> It is, however, not recommended if a person has a history of [[kidney stone]]s.<ref name=agabegi2nd251/> [[Pegloticase]] is an option for the 3% of people who are intolerant to other medications.<ref name=FDA2010>{{cite web |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm225810.htm |title=FDA approves new drug for gout |website=FDA |date=14 September 2010 |url-status=live |archive-url=https://web.archive.org/web/20100917103100/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm225810.htm |archive-date=17 September 2010 }}</ref> It is a third line agent.<ref name=Lancet2016/> Pegloticase is given as an intravenous infusion every two weeks,<ref name=FDA2010/> and reduces uric acid levels.<ref>{{cite journal|vauthors=Sundy JS, Baraf HS, Yood RA, Edwards NL, Gutierrez-Urena SR, Treadwell EL, Vázquez-Mellado J, White WB, Lipsky PE, Horowitz Z, Huang W, Maroli AN, Waltrip RW, Hamburger SA, Becker MA|title=Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials|journal=JAMA: The Journal of the American Medical Association|date=17 August 2011|volume=306|issue=7|pages=711–720|pmid=21846852|doi=10.1001/jama.2011.1169|doi-access=free|hdl=10342/7960|hdl-access=free}}</ref> Pegloticase is useful decreasing tophi but has a high rate of side effects and many people develop resistance to it.<ref name=Lancet2016/> Using [[lesinurad]] {{Val|400|u=mg}} plus [[febuxostat]] is more beneficial for tophi resolution than lesinural {{Val|200|u=mL}} with febuxostat, with similar side effects. Lesinural plus [[allopurinol]] is not effective for tophi resolution.<ref>{{cite journal|vauthors=Sriranganathan MK, Vinik O, Pardo Pardo J, Bombardier C, Edwards CJ|date=11 August 2021|title=Interventions for tophi in gout|journal=The Cochrane Database of Systematic Reviews|volume=2021|issue=8|pages=CD010069|doi=10.1002/14651858.CD010069.pub3|pmid=34379791|pmc=8406833}}</ref> Potential side effects include kidney stones, anemia and joint pain.<ref>{{cite journal|last1=Anderson|first1=Amy|last2=Singh|first2=Jasvinder A|date=17 March 2010|title=Pegloticase for chronic gout|journal=Cochrane Database of Systematic Reviews|volume=2010 |issue=3|pages=CD008335|doi=10.1002/14651858.cd008335.pub2|pmid=20238366|pmc=6599816|issn=1465-1858}}</ref> In 2016, it was withdrawn from the European market.<ref>{{cite web|title=Krystexxa|url=http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002208/human_med_001591.jsp&mid=WC0b01ac058001d124|website=www.ema.europa.eu|access-date=28 March 2017|language=en|url-status=live|archive-url=https://web.archive.org/web/20170328200116/http://www.ema.europa.eu/ema/index.jsp?curl=pages%2Fmedicines%2Fhuman%2Fmedicines%2F002208%2Fhuman_med_001591.jsp&mid=WC0b01ac058001d124|archive-date=28 March 2017}}</ref><ref name=Pres2017>{{cite journal|title=Pegloticase: withdrawal of its EU marketing authorisation is welcome|journal=Prescrire International|date=March 2017|volume=26|issue=180|page=71}}</ref>
+Probenecid appears to be less effective than allopurinol and is a second line agent.<ref name=Review08/><ref name=Lancet2016/> Probenecid may be used if undersecretion of uric acid is present (24-hour urine uric acid less than 800&nbsp;mg).<ref name=agabegi2nd251>{{cite book |first1=Elizabeth D |last1=Agabegi |author2=Agabegi, Steven S. |title=Step-Up to Medicine (Step-Up Series) |publisher=Lippincott Williams & Wilkins |location=Hagerstwon, MD |year=2008 |page=251 |isbn=978-0-7817-7153-5 |url=https://books.google.com/books?id=y13wgJyQwkEC&pg=PA251 |access-date=10 January 2016 |archive-date=10 January 2023 |archive-url=https://web.archive.org/web/20230110061630/https://books.google.com/books?id=y13wgJyQwkEC&pg=PA251 |url-status=live }}</ref> It is, however, not recommended if a person has a history of [[kidney stone]]s.<ref name=agabegi2nd251/> Probenecid can be used in a combined therapy with allopurinol is more effective than allopurinol monotherapy.<ref>{{Cite web |url=https://academic.oup.com/rheumatology/article/53/12/2131/1802918 |title=Archived copy |access-date=7 July 2024 |archive-date=10 July 2024 |archive-url=https://web.archive.org/web/20240710063618/https://academic.oup.com/rheumatology/article/53/12/2131/1802918 |url-status=live }}</ref><ref>{{cite journal | url=https://link.springer.com/article/10.2165/00003088-200847020-00004 | doi=10.2165/00003088-200847020-00004 | title=Pharmacokinetic and Pharmacodynamic Interaction between Allopurinol and Probenecid??in Healthy Subjects | date=2008 | journal=Clinical Pharmacokinetics | volume=47 | issue=2 | pages=111–118 | pmid=18193917 | vauthors=Stocker SL, Williams KM, McLachlan AJ, Graham GG, Day RO | access-date=7 July 2024 | archive-date=7 June 2018 | archive-url=https://web.archive.org/web/20180607180012/https://link.springer.com/article/10.2165%2F00003088-200847020-00004 | url-status=live }}</ref><ref>{{cite journal | pmid=25314636 | date=2014 | title=Allopurinol for chronic gout | journal=The Cochrane Database of Systematic Reviews | issue=10 | pages=CD006077 | doi=10.1002/14651858.CD006077.pub3 | pmc=8915170 | vauthors = Seth R, Kydd AS, Buchbinder R, Bombardier C, Edwards CJ }}</ref>
+[[Pegloticase]] is an option for the 3% of people who are intolerant to other medications.<ref name=FDA2010>{{cite web |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm225810.htm |title=FDA approves new drug for gout |website=FDA |date=14 September 2010 |url-status=live |archive-url=https://web.archive.org/web/20100917103100/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm225810.htm |archive-date=17 September 2010 }}</ref> It is a third line agent.<ref name=Lancet2016/> Pegloticase is given as an intravenous infusion every two weeks,<ref name=FDA2010/> and reduces uric acid levels.<ref>{{cite journal|vauthors=Sundy JS, Baraf HS, Yood RA, Edwards NL, Gutierrez-Urena SR, Treadwell EL, Vázquez-Mellado J, White WB, Lipsky PE, Horowitz Z, Huang W, Maroli AN, Waltrip RW, Hamburger SA, Becker MA|title=Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials|journal=JAMA: The Journal of the American Medical Association|date=17 August 2011|volume=306|issue=7|pages=711–720|pmid=21846852|doi=10.1001/jama.2011.1169|doi-access=free|hdl=10342/7960|hdl-access=free}}</ref> Pegloticase is useful decreasing tophi but has a high rate of side effects and many people develop resistance to it.<ref name=Lancet2016/> Using [[lesinurad]] {{Val|400|u=mg}} plus [[febuxostat]] is more beneficial for tophi resolution than lesinural {{Val|200|u=mL}} with febuxostat, with similar side effects. Lesinural plus [[allopurinol]] is not effective for tophi resolution.<ref>{{cite journal|vauthors=Sriranganathan MK, Vinik O, Pardo Pardo J, Bombardier C, Edwards CJ|date=11 August 2021|title=Interventions for tophi in gout|journal=The Cochrane Database of Systematic Reviews|volume=2021|issue=8|pages=CD010069|doi=10.1002/14651858.CD010069.pub3|pmid=34379791|pmc=8406833}}</ref> Potential side effects include kidney stones, anemia and joint pain.<ref>{{cite journal|last1=Anderson|first1=Amy|last2=Singh|first2=Jasvinder A|date=17 March 2010|title=Pegloticase for chronic gout|journal=Cochrane Database of Systematic Reviews|volume=2010 |issue=3|pages=CD008335|doi=10.1002/14651858.cd008335.pub2|pmid=20238366|pmc=6599816|issn=1465-1858}}</ref> In 2016, it was withdrawn from the European market.<ref>{{cite web|title=Krystexxa|url=http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002208/human_med_001591.jsp&mid=WC0b01ac058001d124|website=www.ema.europa.eu|access-date=28 March 2017|language=en|url-status=live|archive-url=https://web.archive.org/web/20170328200116/http://www.ema.europa.eu/ema/index.jsp?curl=pages%2Fmedicines%2Fhuman%2Fmedicines%2F002208%2Fhuman_med_001591.jsp&mid=WC0b01ac058001d124|archive-date=28 March 2017}}</ref><ref name=Pres2017>{{cite journal|title=Pegloticase: withdrawal of its EU marketing authorisation is welcome|journal=Prescrire International|date=March 2017|volume=26|issue=180|page=71}}</ref>
-[[Lesinurad]] reduces blood uric acid levels by preventing uric acid absorption in the kidneys.<ref name=Pro2018>{{cite web |title=Zurampic |url=https://www.drugs.com/pro/zurampic.html|publisher=Drugs.com |access-date=14 October 2018 |date=1 January 2018}}</ref> It was approved in the United States for use together with allopurinol, among those who were unable to reach their uric acid level targets.<ref name="zurampic">{{cite web |title=Drug Trial Snapshot: Zurampic |url=https://www.fda.gov/Drugs/InformationOnDrugs/ucm491548.htm |publisher=US Food and Drug Administration |access-date=14 October 2018 |date=22 December 2015}}</ref> Side effects include [[kidney problem]]s and [[kidney stone]]s.<ref name=Pro2018/><ref name=EMA2018>{{cite web |title=Zurampic |url=https://www.ema.europa.eu/documents/overview/zurampic-epar-summary-public_en.pdf |publisher=European Medicines Agency |access-date=14 October 2018 |date=18 February 2016}}</ref>
+[[Lesinurad]] reduces blood uric acid levels by preventing uric acid absorption in the kidneys.<ref name=Pro2018>{{cite web |title=Zurampic |url=https://www.drugs.com/pro/zurampic.html |publisher=Drugs.com |access-date=14 October 2018 |date=1 January 2018 |archive-date=15 October 2018 |archive-url=https://web.archive.org/web/20181015002816/https://www.drugs.com/pro/zurampic.html |url-status=live }}</ref> It was approved in the United States for use together with allopurinol, among those who were unable to reach their uric acid level targets.<ref name="zurampic">{{cite web |title=Drug Trial Snapshot: Zurampic |url=https://www.fda.gov/Drugs/InformationOnDrugs/ucm491548.htm |publisher=US Food and Drug Administration |access-date=14 October 2018 |date=22 December 2015 |archive-date=8 February 2019 |archive-url=https://web.archive.org/web/20190208044044/https://www.fda.gov/Drugs/InformationOnDrugs/ucm491548.htm |url-status=live }}</ref> Side effects include [[kidney problem]]s and [[kidney stone]]s.<ref name=Pro2018/><ref name=EMA2018>{{cite web |title=Zurampic |url=https://www.ema.europa.eu/documents/overview/zurampic-epar-summary-public_en.pdf |publisher=European Medicines Agency |access-date=14 October 2018 |date=18 February 2016 |archive-date=28 August 2021 |archive-url=https://web.archive.org/web/20210828094215/https://www.ema.europa.eu/en/documents/overview/zurampic-epar-summary-public_en.pdf |url-status=live }}</ref>
 ==Treatment==
-The initial aim of treatment is to settle the symptoms of an acute attack.<ref name="pmid16707532">{{cite journal  |vauthors=Zhang W, Doherty M, Bardin T, et al |title=EULAR evidence based recommendations for gout. Part II: Management. Report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT) |journal=Ann. Rheum. Dis. |volume=65 |issue=10 |pages=1312–1324 |date=October 2006 |pmid=16707532 |pmc=1798308 |doi=10.1136/ard.2006.055269}}</ref> Repeated attacks can be prevented by medications that reduce serum uric acid levels.<ref name="pmid16707532"/> Tentative evidence supports the application of ice for 20 to 30 minutes several times a day to decrease pain.<ref name=Moi2013>{{cite journal |last1=Moi |first1=JH |last2=Sriranganathan |first2=MK |last3=Edwards |first3=CJ|last4=Buchbinder|first4=R|title=Lifestyle interventions for acute gout |journal=The Cochrane Database of Systematic Reviews|date=4 November 2013 |volume=11 |issue=11 |pages=CD010519 |pmid=24186771 |doi=10.1002/14651858.CD010519.pub2|pmc=9942538 }}</ref> Options for acute treatment include [[nonsteroidal anti-inflammatory drug]]s (NSAIDs), [[colchicine]], and [[glucocorticoid]]s.<ref name=Review08/> While glucocorticoids and NSAIDs work equally well, glucocorticoids may be safer.<ref>{{cite journal|last1=Billy|first1=CA|last2=Lim|first2=RT|last3=Ruospo|first3=M|last4=Palmer|first4=SC|last5=Strippoli|first5=GFM|title=Corticosteroid or Nonsteroidal Antiinflammatory Drugs for the Treatment of Acute Gout: A Systematic Review of Randomized Controlled Trials|journal=The Journal of Rheumatology|volume=45|issue=1|pages=128–136|date=1 August 2017|doi=10.3899/jrheum.170137|pmid=28765243|s2cid=8306526|url=http://www.jrheum.org/content/jrheum/45/1/128.full.pdf}}</ref> Options for prevention include [[allopurinol]], [[febuxostat]], and [[probenecid]]. Lowering uric acid levels can cure the disease.<ref name=Lancet2010/> Treatment of [[comorbidity|associated health problems]] is also important.<ref name=Lancet2010/> Lifestyle interventions have been poorly studied.<ref name=Moi2013/> It is unclear whether dietary supplements have an effect in people with gout.<ref>{{cite journal |last1=Andrés |first1=Mariano |last2=Sivera |first2=Francisca |last3=Buchbinder |first3=Rachelle |last4=Pardo Pardo |first4=Jordi |last5=Carmona |first5=Loreto |title=Dietary supplements for chronic gout |journal=The Cochrane Database of Systematic Reviews |date=12 November 2021 |volume=11 |issue=11 |pages=CD010156 |doi=10.1002/14651858.CD010156.pub3 |doi-access=free|pmid=34767649 |pmc=8589461 |issn=1469-493X}}</ref>
+The initial aim of treatment is to settle the symptoms of an acute attack.<ref name="pmid16707532">{{cite journal  |vauthors=Zhang W, Doherty M, Bardin T, et al |title=EULAR evidence based recommendations for gout. Part II: Management. Report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT) |journal=Ann. Rheum. Dis. |volume=65 |issue=10 |pages=1312–1324 |date=October 2006 |pmid=16707532 |pmc=1798308 |doi=10.1136/ard.2006.055269}}</ref> Repeated attacks can be prevented by medications that reduce serum uric acid levels.<ref name="pmid16707532"/> Tentative evidence supports the application of ice for 20 to 30 minutes several times a day to decrease pain.<ref name=Moi2013>{{cite journal |last1=Moi |first1=JH |last2=Sriranganathan |first2=MK |last3=Edwards |first3=CJ|last4=Buchbinder|first4=R|title=Lifestyle interventions for acute gout |journal=The Cochrane Database of Systematic Reviews|date=4 November 2013 |volume=11 |issue=11 |pages=CD010519 |pmid=24186771 |doi=10.1002/14651858.CD010519.pub2|pmc=9942538 }}</ref> Options for acute treatment include [[nonsteroidal anti-inflammatory drug]]s (NSAIDs), [[colchicine]], and [[glucocorticoid]]s.<ref name=Review08/> While glucocorticoids and NSAIDs work equally well, glucocorticoids may be safer.<ref>{{cite journal|last1=Billy|first1=CA|last2=Lim|first2=RT|last3=Ruospo|first3=M|last4=Palmer|first4=SC|last5=Strippoli|first5=GFM|title=Corticosteroid or Nonsteroidal Antiinflammatory Drugs for the Treatment of Acute Gout: A Systematic Review of Randomized Controlled Trials|journal=The Journal of Rheumatology|volume=45|issue=1|pages=128–136|date=1 August 2017|doi=10.3899/jrheum.170137|pmid=28765243|s2cid=8306526|url=http://www.jrheum.org/content/jrheum/45/1/128.full.pdf|access-date=7 June 2020|archive-date=7 August 2020|archive-url=https://web.archive.org/web/20200807040103/https://www.jrheum.org/content/jrheum/45/1/128.full.pdf|url-status=live}}</ref> Options for prevention include [[allopurinol]], [[febuxostat]], and [[probenecid]]. Lowering uric acid levels can cure the disease.<ref name=Lancet2010/> Treatment of [[comorbidity|associated health problems]] is also important.<ref name=Lancet2010/> Lifestyle interventions have been poorly studied.<ref name=Moi2013/> It is unclear whether dietary supplements have an effect in people with gout.<ref>{{cite journal |last1=Andrés |first1=Mariano |last2=Sivera |first2=Francisca |last3=Buchbinder |first3=Rachelle |last4=Pardo Pardo |first4=Jordi |last5=Carmona |first5=Loreto |title=Dietary supplements for chronic gout |journal=The Cochrane Database of Systematic Reviews |date=12 November 2021 |volume=11 |issue=11 |pages=CD010156 |doi=10.1002/14651858.CD010156.pub3 |doi-access=free|pmid=34767649 |pmc=8589461 |issn=1469-493X}}</ref>
 ===NSAIDs===
-NSAIDs are the usual first-line treatment for gout.<!-- <ref name=Review08/> --> No specific agent is significantly more or less effective than any other.<ref name=Review08/> Improvement may be seen within four hours and treatment is recommended for one to two weeks.<ref name=Lancet2010/><ref name=Review08/> They are not recommended for those with certain other health problems, such as [[gastrointestinal bleeding]], [[kidney failure]], or [[heart failure]].<ref name=JFP09/> 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.<ref name=CFP09>{{cite journal |vauthors=Laubscher T, Dumont Z, Regier L, Jensen B |title=Taking the stress out of managing gout |journal=Can Fam Physician |volume=55 |issue=12 |pages=1209–1212 |date=December 2009 |pmid=20008601 |pmc=2793228}}</ref> For those at risk of gastric side effects from NSAIDs, an additional [[proton pump inhibitor]] may be given.<ref>{{cite journal|last1=Cronstein|first1=BN|last2=Terkeltaub|first2=R|title=The inflammatory process of gout and its treatment|journal=Arthritis Research & Therapy|date=2006|volume=8|issue=Suppl 1 |pages=S3|pmid=16820042|doi=10.1186/ar1908|pmc=3226108 |doi-access=free }}</ref> There is some evidence that [[COX-2 inhibitor]]s may work as well as nonselective NSAIDs for acute gout attack with fewer side effects.<ref>{{cite journal|last1=van Durme|first1=CM|last2=Wechalekar|first2=MD|last3=Landewé|first3=RB|title=Nonsteroidal anti-inflammatory drugs for treatment of acute gout|journal=JAMA|date=9 June 2015|volume=313|issue=22|pages=2276–2277|pmid=26057289|doi=10.1001/jama.2015.1881}}</ref><ref name=":1">{{cite journal |last1=van Durme |first1=Caroline Mpg |last2=Wechalekar |first2=Mihir D. |last3=Landewé |first3=Robert Bm |last4=Pardo Pardo |first4=Jordi |last5=Cyril |first5=Sheila |last6=van der Heijde |first6=Désirée |last7=Buchbinder |first7=Rachelle |date=9 December 2021 |title=Non-steroidal anti-inflammatory drugs for acute gout |journal=The Cochrane Database of Systematic Reviews |volume=2021 |issue=12 |pages=CD010120 |doi=10.1002/14651858.CD010120.pub3 |issn=1469-493X |pmc=8656463 |pmid=34882311}}</ref><ref name=":2">{{Cite journal |last1=Roddy |first1=Edward |last2=Bajpai |first2=Ram |last3=Forrester |first3=Harry |last4=Partington |first4=Richard James |last5=Mallen |first5=Christian D. |last6=Clarson |first6=Lorna Elise |last7=Padmanabhan |first7=Nishita |last8=Whittle |first8=Rebecca |last9=Muller |first9=Sara |date=1 December 2023 |title=Safety of colchicine and NSAID prophylaxis when initiating urate-lowering therapy for gout: propensity score-matched cohort studies in the UK Clinical Practice Research Datalink |url=https://ard.bmj.com/content/82/12/1618 |journal=Annals of the Rheumatic Diseases |language=en |volume=82 |issue=12 |pages=1618–1625 |doi=10.1136/ard-2023-224154 |issn=0003-4967 |pmc=10646835 |pmid=37788904}}</ref><ref name=":3">{{Cite journal |date=6 February 2024 |title=How common are side-effects of treatment to prevent gout flares when starting allopurinol? |url=https://evidence.nihr.ac.uk/alert/how-common-are-side-effects-of-treatment-to-prevent-gout-flares-when-starting-allopurinol/ |journal=NIHR Evidence|doi=10.3310/nihrevidence_62005 |s2cid=267539627 }}</ref>
+NSAIDs are the usual first-line treatment for gout.<!-- <ref name=Review08/> --> No specific agent is significantly more or less effective than any other.<ref name=Review08/> Improvement may be seen within four hours and treatment is recommended for one to two weeks.<ref name=Lancet2010/><ref name=Review08/> They are not recommended for those with certain other health problems, such as [[gastrointestinal bleeding]], [[kidney failure]], or [[heart failure]].<ref name=JFP09/> 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.<ref name=CFP09>{{cite journal |vauthors=Laubscher T, Dumont Z, Regier L, Jensen B |title=Taking the stress out of managing gout |journal=Can Fam Physician |volume=55 |issue=12 |pages=1209–1212 |date=December 2009 |pmid=20008601 |pmc=2793228}}</ref> For those at risk of gastric side effects from NSAIDs, an additional [[proton pump inhibitor]] may be given.<ref>{{cite journal|last1=Cronstein|first1=BN|last2=Terkeltaub|first2=R|title=The inflammatory process of gout and its treatment|journal=Arthritis Research & Therapy|date=2006|volume=8|issue=Suppl 1 |pages=S3|pmid=16820042|doi=10.1186/ar1908|pmc=3226108 |doi-access=free }}</ref> There is some evidence that [[COX-2 inhibitor]]s may work as well as nonselective NSAIDs for acute gout attack with fewer side effects.<ref>{{cite journal|last1=van Durme|first1=CM|last2=Wechalekar|first2=MD|last3=Landewé|first3=RB|title=Nonsteroidal anti-inflammatory drugs for treatment of acute gout|journal=JAMA|date=9 June 2015|volume=313|issue=22|pages=2276–2277|pmid=26057289|doi=10.1001/jama.2015.1881}}</ref><ref name=":1">{{cite journal |last1=van Durme |first1=Caroline Mpg |last2=Wechalekar |first2=Mihir D. |last3=Landewé |first3=Robert Bm |last4=Pardo Pardo |first4=Jordi |last5=Cyril |first5=Sheila |last6=van der Heijde |first6=Désirée |last7=Buchbinder |first7=Rachelle |date=9 December 2021 |title=Non-steroidal anti-inflammatory drugs for acute gout |journal=The Cochrane Database of Systematic Reviews |volume=2021 |issue=12 |pages=CD010120 |doi=10.1002/14651858.CD010120.pub3 |issn=1469-493X |pmc=8656463 |pmid=34882311}}</ref><ref name=":2">{{Cite journal |last1=Roddy |first1=Edward |last2=Bajpai |first2=Ram |last3=Forrester |first3=Harry |last4=Partington |first4=Richard James |last5=Mallen |first5=Christian D. |last6=Clarson |first6=Lorna Elise |last7=Padmanabhan |first7=Nishita |last8=Whittle |first8=Rebecca |last9=Muller |first9=Sara |date=1 December 2023 |title=Safety of colchicine and NSAID prophylaxis when initiating urate-lowering therapy for gout: propensity score-matched cohort studies in the UK Clinical Practice Research Datalink |url=https://ard.bmj.com/content/82/12/1618 |journal=Annals of the Rheumatic Diseases |language=en |volume=82 |issue=12 |pages=1618–1625 |doi=10.1136/ard-2023-224154 |issn=0003-4967 |pmc=10646835 |pmid=37788904 |access-date=16 February 2024 |archive-date=16 February 2024 |archive-url=https://web.archive.org/web/20240216155634/https://ard.bmj.com/content/82/12/1618 |url-status=live }}</ref><ref name=":3">{{Cite journal |date=6 February 2024 |title=How common are side-effects of treatment to prevent gout flares when starting allopurinol? |url=https://evidence.nihr.ac.uk/alert/how-common-are-side-effects-of-treatment-to-prevent-gout-flares-when-starting-allopurinol/ |journal=NIHR Evidence |doi=10.3310/nihrevidence_62005 |s2cid=267539627 |access-date=16 February 2024 |archive-date=16 February 2024 |archive-url=https://web.archive.org/web/20240216155634/https://evidence.nihr.ac.uk/alert/how-common-are-side-effects-of-treatment-to-prevent-gout-flares-when-starting-allopurinol/ |url-status=live }}</ref>
 ===Colchicine===
@@ Line 116: / Line 118: @@
 ===Glucocorticoids===
-[[Glucocorticoid]]s have been found to be as effective as NSAIDs<ref name=":1" /><ref name="pmid17276548">{{cite journal |vauthors=Man CY, Cheung IT, Cameron PA, Rainer TH |title=Comparison of oral prednisolone/paracetamol and oral indomethacin/paracetamol combination therapy in the treatment of acute goutlike arthritis: a double-blind, randomized, controlled trial |journal=Annals of Emergency Medicine |volume=49 |issue=5 |pages=670–677 |year=2007 |pmid=17276548 |doi=10.1016/j.annemergmed.2006.11.014|pmc=7115288 |url=http://orca.cf.ac.uk/92845/1/paracetemol.pdf }}</ref> and may be used if contraindications exist for NSAIDs.<ref name=Review08/><ref name=":0">{{cite journal|last1=Wechalekar|first1=Mihir D|last2=Vinik|first2=Ophir|last3=Schlesinger|first3=Naomi|last4=Buchbinder|first4=Rachelle|date=30 April 2013|title=Intra-articular glucocorticoids for acute gout|journal=Cochrane Database of Systematic Reviews|issue=4|pages=CD009920|doi=10.1002/14651858.cd009920.pub2|pmid=23633379|issn=1465-1858}}</ref> They also lead to improvement when [[Joint injection|injected into the joint]].<ref name=Review08/> A [[septic arthritis|joint infection]] must be excluded, however, as glucocorticoids worsen this condition.<ref name=Review08/> There were no short-term adverse effects reported.<ref>{{cite journal|last1=Janssens|first1=Hein J|last2=Lucassen|first2=Peter LBJ|last3=Van de Laar|first3=Floris A|last4=Janssen|first4=Matthijs|last5=Van de Lisdonk|first5=Eloy H|date=23 April 2008|title=Systemic corticosteroids for acute gout|journal=Cochrane Database of Systematic Reviews|volume=2010|issue=2|pages=CD005521|doi=10.1002/14651858.cd005521.pub2|pmid=18425920|pmc=8276233|issn=1465-1858|url=https://repository.ubn.ru.nl/bitstream/2066/70896/1/70896.pdf|hdl=2066/70896|hdl-access=free}}</ref>
+[[Glucocorticoid]]s have been found to be as effective as NSAIDs<ref name=":1" /><ref name="pmid17276548">{{cite journal |vauthors=Man CY, Cheung IT, Cameron PA, Rainer TH |title=Comparison of oral prednisolone/paracetamol and oral indomethacin/paracetamol combination therapy in the treatment of acute goutlike arthritis: a double-blind, randomized, controlled trial |journal=Annals of Emergency Medicine |volume=49 |issue=5 |pages=670–677 |year=2007 |pmid=17276548 |doi=10.1016/j.annemergmed.2006.11.014 |pmc=7115288 |url=http://orca.cf.ac.uk/92845/1/paracetemol.pdf |access-date=8 September 2019 |archive-date=20 October 2020 |archive-url=https://web.archive.org/web/20201020143558/http://orca.cf.ac.uk/92845/1/paracetemol.pdf |url-status=live }}</ref> and may be used if contraindications exist for NSAIDs.<ref name=Review08/><ref name=":0">{{cite journal|last1=Wechalekar|first1=Mihir D|last2=Vinik|first2=Ophir|last3=Schlesinger|first3=Naomi|last4=Buchbinder|first4=Rachelle|date=30 April 2013|title=Intra-articular glucocorticoids for acute gout|journal=Cochrane Database of Systematic Reviews|issue=4|pages=CD009920|doi=10.1002/14651858.cd009920.pub2|pmid=23633379|issn=1465-1858}}</ref> They also lead to improvement when [[Joint injection|injected into the joint]].<ref name=Review08/> A [[septic arthritis|joint infection]] must be excluded, however, as glucocorticoids worsen this condition.<ref name=Review08/> There were no short-term adverse effects reported.<ref>{{cite journal|last1=Janssens|first1=Hein J|last2=Lucassen|first2=Peter LBJ|last3=Van de Laar|first3=Floris A|last4=Janssen|first4=Matthijs|last5=Van de Lisdonk|first5=Eloy H|date=23 April 2008|title=Systemic corticosteroids for acute gout|journal=Cochrane Database of Systematic Reviews|volume=2010|issue=2|pages=CD005521|doi=10.1002/14651858.cd005521.pub2|pmid=18425920|pmc=8276233|issn=1465-1858|url=https://repository.ubn.ru.nl/bitstream/2066/70896/1/70896.pdf|hdl=2066/70896|hdl-access=free|access-date=24 September 2019|archive-date=28 August 2021|archive-url=https://web.archive.org/web/20210828094218/https://repository.ubn.ru.nl/bitstream/handle/2066/70896/70896.pdf;jsessionid=1FC701B94528B3F6C1BBA1E193546020?sequence=1|url-status=live}}</ref>
 ===Others===
 [[Interleukin-1]] inhibitors, such as [[canakinumab]], showed moderate effectiveness for pain relief and reduction of joint swelling, but have increased risk of [[adverse event]]s, such as back pain, headache, and increased blood pressure.<ref name=Siv2014>{{cite journal|pmid=25177840|year=2014|last1=Sivera|first1=F|title=Interleukin-1 inhibitors for acute gout|journal=Cochrane Database of Systematic Reviews|issue=9|pages=CD009993|last2=Wechalekar|first2=M. D|last3=Andrés|first3=M|last4=Buchbinder|first4=R|last5=Carmona|first5=L|volume=2014 |doi=10.1002/14651858.CD009993.pub2|pmc=10891421}}</ref> They, however, may work less well than usual doses of NSAIDS.<ref name=Siv2014/> The high cost of this class of drugs may also discourage their use for treating gout.<ref name=Siv2014/>
+{{Further|topic=the investigational new drug|Tigulixostat}}
 ==Prognosis==
@@ Line 138: / Line 141: @@
 ==Epidemiology==
-Gout affects around 1–2% of people in the [[Western world]] at some point in their lifetimes and is becoming more common.<ref name=Lancet2010/><ref name=Review08/> Some 5.8 million people were affected in 2013.<ref name=GBD2015>{{cite journal |title=Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013 |journal=Lancet |volume=386 |issue=9995 |pages=743–800 |date=August 2015 |pmid=26063472 |pmc=4561509 |doi=10.1016/S0140-6736(15)60692-4 |url=|last1=Vos |first1=Theo |last2=Barber |first2=Ryan M. |last3=Bell |first3=Brad |last4=Bertozzi-Villa |first4=Amelia |last5=Biryukov |first5=Stan |last6=Bolliger |first6=Ian |last7=Charlson |first7=Fiona |last8=Davis |first8=Adrian |last9=Degenhardt |first9=Louisa |last10=Dicker |first10=Daniel |last11=Duan |first11=Leilei |last12=Erskine |first12=Holly |last13=Feigin |first13=Valery L. |last14=Ferrari |first14=Alize J. |last15=Fitzmaurice |first15=Christina |last16=Fleming |first16=Thomas |last17=Graetz |first17=Nicholas |last18=Guinovart |first18=Caterina |last19=Haagsma |first19=Juanita |last20=Hansen |first20=Gillian M. |last21=Hanson |first21=Sarah Wulf |last22=Heuton |first22=Kyle R. |last23=Higashi |first23=Hideki |last24=Kassebaum |first24=Nicholas |last25=Kyu |first25=Hmwe |last26=Laurie |first26=Evan |last27=Liang |first27=Xiofeng |last28=Lofgren |first28=Katherine |last29=Lozano |first29=Rafael |last30=MacIntyre |first30=Michael F. }}</ref> Rates of gout approximately doubled between 1990 and 2010.<ref name=Nature2009>{{cite journal |author=Terkeltaub R |title=Update on gout: new therapeutic strategies and options |journal=Nature Reviews Rheumatology |volume=6 |issue=1 |pages=30–38 |date=January 2010 |pmid=20046204 |doi=10.1038/nrrheum.2009.236 |s2cid=19235998 }}</ref> 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]].<ref name=Epi2008>{{cite journal |last=Weaver |first=AL |s2cid=40262260 |title=Epidemiology of gout |journal=Cleveland Clinic Journal of Medicine |date=July 2008 |volume=75 |issue=Suppl 5 |pages=S9–S12 |pmid=18819329 |doi=10.3949/ccjm.75.Suppl_5.S9}}</ref> 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%.<ref name=JFP09>{{cite journal |vauthors=Winzenberg T, Buchbinder R |title=Cochrane Musculoskeletal Group review: acute gout. Steroids or NSAIDs? Let this overview from the Cochrane Group help you decide what's best for your patient |journal=J Fam Pract |volume=58 |issue=7 |pages=E1–E4 |year=2009 |pmid=19607767 }}</ref>
+Gout affects around 1–2% of people in the [[Western world]] at some point in their lifetimes and is becoming more common.<ref name=Lancet2010/><ref name=Review08/> Some 5.8 million people were affected in 2013.<ref name=GBD2015>{{cite journal |title=Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013 |journal=Lancet |volume=386 |issue=9995 |pages=743–800 |date=August 2015 |pmid=26063472 |pmc=4561509 |doi=10.1016/S0140-6736(15)60692-4 |url=|last1=Vos |first1=Theo |last2=Barber |first2=Ryan M. |last3=Bell |first3=Brad |last4=Bertozzi-Villa |first4=Amelia |last5=Biryukov |first5=Stan |last6=Bolliger |first6=Ian |last7=Charlson |first7=Fiona |last8=Davis |first8=Adrian |last9=Degenhardt |first9=Louisa |last10=Dicker |first10=Daniel |last11=Duan |first11=Leilei |last12=Erskine |first12=Holly |last13=Feigin |first13=Valery L. |last14=Ferrari |first14=Alize J. |last15=Fitzmaurice |first15=Christina |last16=Fleming |first16=Thomas |last17=Graetz |first17=Nicholas |last18=Guinovart |first18=Caterina |last19=Haagsma |first19=Juanita |last20=Hansen |first20=Gillian M. |last21=Hanson |first21=Sarah Wulf |last22=Heuton |first22=Kyle R. |last23=Higashi |first23=Hideki |last24=Kassebaum |first24=Nicholas |last25=Kyu |first25=Hmwe |last26=Laurie |first26=Evan |last27=Liang |first27=Xiofeng |last28=Lofgren |first28=Katherine |last29=Lozano |first29=Rafael |last30=MacIntyre |first30=Michael F. }}</ref> Rates of gout approximately doubled between 1990 and 2010.<ref name=Nature2009>{{cite journal |author=Terkeltaub R |title=Update on gout: new therapeutic strategies and options |journal=Nature Reviews Rheumatology |volume=6 |issue=1 |pages=30–38 |date=January 2010 |pmid=20046204 |doi=10.1038/nrrheum.2009.236 |s2cid=19235998 }}</ref> 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]].<ref name=Epi2008>{{cite journal |last=Weaver |first=AL |s2cid=40262260 |title=Epidemiology of gout |journal=Cleveland Clinic Journal of Medicine |date=July 2008 |volume=75 |issue=Suppl 5 |pages=S9–S12 |pmid=18819329 |doi=10.3949/ccjm.75.Suppl_5.S9}}</ref> 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%.<ref name=JFP09>{{cite journal |vauthors=Winzenberg T, Buchbinder R |title=Cochrane Musculoskeletal Group review: acute gout. Steroids or NSAIDs? Let this overview from the Cochrane Group help you decide what's best for your patient |journal=J Fam Pract |volume=58 |issue=7 |pages=E1–E4 |year=2009 |pmid=19607767 }}</ref>
 In the [[United States]], gout is twice as likely in males of African descent than those of European descent.<ref>{{cite web | author=Rheumatology Therapeutics Medical Center | title=What Are the Risk Factors for Gout? | url=http://www.arthritisconsult.com/gout.html#risk | access-date=26 January 2007 | url-status=dead | archive-url=https://web.archive.org/web/20070325104830/http://www.arthritisconsult.com/gout.html#risk | archive-date=25 March 2007 }}</ref> Rates are high among [[Polynesians]], but the disease is rare in [[aboriginal Australians]], despite a higher mean uric acid serum concentration in the latter group.<ref name="pmid10225809">{{cite journal |last1=Roberts-Thomson |first1=R. A |last2=Roberts-Thomson |first2=P J |title=Rheumatic disease and the Australian Aborigine |journal=Annals of the Rheumatic Diseases |date=1 May 1999 |volume=58 |issue=5 |pages=266–270 |doi=10.1136/ard.58.5.266 |pmid=10225809 |pmc=1752880 }}</ref> It has become common in [[China]], [[Polynesia]], and urban [[Sub-Saharan Africa]].<ref name=Lancet2010/> 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.<ref>{{cite journal |author=Fam AG |title=What is new about crystals other than monosodium urate? |journal=Curr Opin Rheumatol |volume=12 |issue=3 |pages=228–234 |date=May 2000 |pmid=10803754 |doi= 10.1097/00002281-200005000-00013}}</ref>
+Taiwan, Hong Kong and Singapore have releatively higher prevalence of gout. A study based on the National Health Insurance Research Database (NHIRD) estimated that 4.92% of Taiwanese residents have gout in 2004. A survey hold by the Hong Kong government found that 5.1% of Hong Kong resident between 45–59 years and 6.1% of those older than 60 years have gout. A study hold in Singapore found that 2,117 in 52,322 people between 45–74 years have gout, roughly equals to 4.1%.<ref>{{cite journal | last1=Kuo | first1=Chang-Fu | last2=Grainge | first2=Matthew J. | last3=Zhang | first3=Weiya | last4=Doherty | first4=Michael | title=Global epidemiology of gout: prevalence, incidence and risk factors | journal=Nature Reviews Rheumatology | volume=11 | issue=11 | date=2015-07-07 | issn=1759-4790 | doi=10.1038/nrrheum.2015.91 | pages=649–662| pmid=26150127 }}</ref>
 ==History==
-[[File:Anthonie van Leeuwenhoek (1632-1723). Natuurkundige te Delft Rijksmuseum SK-A-957.jpeg|thumb|alt=A man wearing a long, curly wig and a full robe is sitting, looking out. His left arm rests on a small table, with his left hand holding a box. Behind him is a globe.|[[Antonie van Leeuwenhoek]] described the microscopic appearance of uric acid crystals in 1679.<ref name="Pillinger"/>]]
+[[File:Anthonie van Leeuwenhoek (1632-1723). Natuurkundige te Delft Rijksmuseum SK-A-957.jpeg|thumb|alt= A man wearing a long, curly wig and a full robe is sitting, looking out. His left arm rests on a small table, with his left hand holding a box. Behind him is a globe.|[[Antonie van Leeuwenhoek]] described the microscopic appearance of uric acid crystals in 1679.<ref name="Pillinger"/>]]
+The English term "gout" first occurs in the work of Randolphus of Bocking, around 1200 AD.<ref>{{cite book
+ |last1             = Pierre-Jerome
+ |first1            = Claude
+ |date              = 11 May 2022
+ |chapter           = 8.5: Gout and Charcot neuroarthropathy
+ |title             = The Essentials of Charcot Neuroarthropathy: Biomechanics, Pathophysiology, and MRI Findings
+ |url               = https://books.google.com/books?id=24NTEAAAQBAJ
+ |publication-place = Amsterdam
+ |publisher         = Elsevier
+ |page              = 233
+ |isbn              = 9780323995788
+ |access-date       = 28 April 2024
+ |quote             = [...] Randolphus of Bocking [...]  was the first to use the word 'gout' to express the clinical signs of podagra. Bocking was the domestic chaplain to Bishop of Chichester (1197-1258).
+ |archive-date      = 28 April 2024
+ |archive-url       = https://web.archive.org/web/20240428051919/https://books.google.com/books?id=24NTEAAAQBAJ
+ |url-status        = live
+}}</ref>
+It derives from the Latin word {{lang | la | gutta}}, meaning "a drop" (of liquid).<ref name="Pillinger"/> According to the ''[[Oxford English Dictionary]]'', this originates from [[humorism]] and "the notion of the 'dropping' of a morbid material from the [[Hemarthrosis|blood in and around the joints]]".<ref>{{cite web |url= http://www.oed.com/view/Entry/80290 |title= gout, n.1 |website= Oxford English Dictionary, Second edition, 1989 |access-date= 18 September 2011 |archive-date= 8 May 2020 |archive-url= https://web.archive.org/web/20200508070657/https://www.oed.com/start;jsessionid=F7E81FB8C2DA5A2C4521515FB61B4533?authRejection=true&url=%2Fview%2FEntry%2F80290 |url-status= live }}</ref>
+Gout has been known since antiquity. Historically, wits have referred to it as "the king of diseases and the disease of kings"<ref name=Lancet2010/><ref>{{cite web |url= https://www.forbes.com/2003/04/01/cx_cd_0401feat.html |title=The Disease Of Kings  |website= Forbes.com |url-status=live |archive-url= https://web.archive.org/web/20170901100910/https://www.forbes.com/2003/04/01/cx_cd_0401feat.html |archive-date= 1 September 2017 | quote = It has been referred to, maybe a touch inaccurately, as 'The disease of kings and the king of diseases.'}}</ref> or as "rich man's disease".<ref name=Dic/> The [[Ebers papyrus]] and the [[Edwin Smith papyrus]], ({{circa|1550 BC}}) each mention arthritis of the first metacarpophalangeal joint as a distinct type of arthritis. These ancient manuscripts cite (now missing) Egyptian texts about gout that are claimed to have been written 1,000 years earlier and ascribed to [[Imhotep]].<ref>Schwartz, Stephan A. [https://www.researchgate.net/publication/6685328_Disease_of_Distinction/link/5b1f73afa6fdcc69745c3abd/download?_tp=eyJjb250ZXh0Ijp7ImZpcnN0UGFnZSI6InB1YmxpY2F0aW9uIiwicGFnZSI6InB1YmxpY2F0aW9uIn19 "Disease of distinction."] Explore 2, no. 6 (2006): 515–519. - "Both the Ebers and Edwin Smith Papyri describe a condition that is clearly gout.[...] They were written about 1552 BC but contain information taken from texts a thousand years earlier, and ascribed to Imhotep, a kind of ancient world Leonardo da Vinci, and the great overarching figure of Egyptian medicine."</ref> [[Ancient Greece|Greek]] physician [[Hippocrates]] around 400 BC commented on it in his  [[Aphorisms (Hippocrates)|''Aphorisms'']], noting its absence in [[eunuchs]] and [[premenopausal]] women.<ref name="Pillinger">{{cite journal|last=Pillinger |first=MH |author2= Rosenthal P |author3= Abeles AM |title= Hyperuricemia and gout: new insights into pathogenesis and treatment |journal=Bulletin of the NYU Hospital for Joint Diseases |volume= 65 |issue= 3 |pages= 215–221 |year= 2007 |url= http://www.nyuhjdbulletin.org/Permalink.aspx?permalinkId=0c3ec9d1-8cc8-49d5-850d-4c5a55cb0669 |pmid= 17922673 |url-status= dead |archive-url= https://web.archive.org/web/20081216114246/http://www.nyuhjdbulletin.org/Permalink.aspx?permalinkId=0c3ec9d1-8cc8-49d5-850d-4c5a55cb0669 |archive-date=16 December 2008 }}</ref><ref>{{cite web |url= http://classics.mit.edu/Hippocrates/aphorisms.6.vi.html |title= The Internet Classics Archive Aphorisms by Hippocrates |access-date=27 July 2010 |website=MIT |url-status=live |archive-url= https://web.archive.org/web/20100707154253/http://classics.mit.edu/Hippocrates/aphorisms.6.vi.html |archive-date= 7 July 2010 }}</ref> [[Aulus Cornelius Celsus]] (30 AD) described the linkage with alcohol, later onset in women and associated kidney problems:
-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).<ref name="Pillinger"/> According to the ''[[Oxford English Dictionary]]'', this is derived from [[humorism]] and "the notion of the 'dropping' of a morbid material from the [[Hemarthrosis|blood in and around the joints]]".<ref>{{cite web |url=http://www.oed.com/view/Entry/80290 |title=gout, n.1 |website=Oxford English Dictionary, Second edition, 1989 |access-date=18 September 2011}}</ref>
+{{blockquote|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 [[eunuch]]s or boys before coition with a woman, or women except those in whom the menses have become suppressed... some have obtained lifelong security by refraining from [[wine]], [[mead]] and [[wikt:venery#Etymology 2|venery]].<ref>{{cite web |url= https://penelope.uchicago.edu/Thayer/E/Roman/Texts/Celsus/4*.html |title= On Medicine |first= A. Cornelius |last= Celsus |at= Book IV |website= University of Chicago |access-date= 19 February 2021 |archive-date= 10 July 2024 |archive-url= https://web.archive.org/web/20240710063618/https://penelope.uchicago.edu/Thayer/E/Roman/Texts/Celsus/4%2A.html |url-status= live }}</ref>}}
+Benjamin Welles, an English physician, authored the first medical book on gout, ''A Treatise of the Gout, or Joint Evil'', in 1669.<ref>{{cite book|last= Copeman |first= W.S.C.|title= A Short History of the Gout and the Rheumatic Diseases|date= 2021|publisher= University of California Press|isbn=978-0-520-33947-7|page=68}}</ref> In 1683, [[Thomas Sydenham]], an English physician, described its occurrence in the early hours of the morning and its predilection for older males:
-Gout has been known since antiquity. Historically, it was referred to as "the king of diseases and the disease of kings"<ref name=Lancet2010/><ref>{{cite web |url=https://www.forbes.com/2003/04/01/cx_cd_0401feat.html |title=The Disease Of Kings  |website=Forbes.com |url-status=live |archive-url=https://web.archive.org/web/20170901100910/https://www.forbes.com/2003/04/01/cx_cd_0401feat.html |archive-date=1 September 2017 }}</ref> or "rich man's disease".<ref name=Dic/> The [[Ebers papyrus]] and the [[Edwin Smith papyrus]], ({{circa|1550 BC}}) each mention arthritis of the first metacarpophalangeal joint as a distinct type of arthritis. These ancient manuscripts cite (now missing) Egyptian texts about gout that are claimed to have been written 1,000 years earlier by [[Imhotep]].<ref>Schwartz, Stephan A. "Disease of distinction." Explore 2, no. 6 (2006): 515–519.</ref> [[Ancient Greece|Greek]] physician [[Hippocrates]] around 400 BC commented on it in his ''[[Aphorisms (Hippocrates)|Aphorisms]]'', noting its absence in [[eunuchs]] and [[premenopausal]] women.<ref name="Pillinger">{{cite journal|last=Pillinger |first=MH |author2=Rosenthal P |author3=Abeles AM |title=Hyperuricemia and gout: new insights into pathogenesis and treatment |journal=Bulletin of the NYU Hospital for Joint Diseases |volume=65 |issue=3 |pages=215–221 |year=2007 |url=http://www.nyuhjdbulletin.org/Permalink.aspx?permalinkId=0c3ec9d1-8cc8-49d5-850d-4c5a55cb0669 |pmid=17922673 |url-status=dead |archive-url=https://web.archive.org/web/20081216114246/http://www.nyuhjdbulletin.org/Permalink.aspx?permalinkId=0c3ec9d1-8cc8-49d5-850d-4c5a55cb0669 |archive-date=16 December 2008 }}</ref><ref>{{cite web |url=http://classics.mit.edu/Hippocrates/aphorisms.6.vi.html |title=The Internet Classics Archive Aphorisms by Hippocrates |access-date=27 July 2010 |website=MIT |url-status=live |archive-url=https://web.archive.org/web/20100707154253/http://classics.mit.edu/Hippocrates/aphorisms.6.vi.html |archive-date=7 July 2010 }}</ref> [[Aulus Cornelius Celsus]] (30 AD) described the linkage with alcohol, later onset in women and associated kidney problems:
+{{blockquote|Gouty patients are, generally, either old men or men who have so worn themselves out in youth as to have brought on a premature old age—of such dissolute habits none being more common than the premature and excessive indulgence in venery and the like exhausting passions. The victim goes to bed and sleeps in good health. About two o'clock in the morning he is awakened by a severe pain in the great toe; more rarely in the heel, ankle, or instep. The pain is like that of a dislocation and yet parts feel as if cold water were poured over them. Then follows chills and shivers and a little fever... The night is passed in torture, sleeplessness, turning the part affected and perpetual change of posture; the tossing about of body being as incessant as the pain of the tortured joint and being worse as the fit comes on.<ref>{{cite web |url=https://www.bbc.co.uk/dna/h2g2/A11102491 |title= Gout – The Affliction of Kings |website= h2g2 |publisher= BBC |date= December 23, 2012 |url-status=live |archive-url= https://web.archive.org/web/20100911065930/http://www.bbc.co.uk/dna/h2g2/A11102491 |archive-date= September 11, 2010 }}</ref>}}
-{{blockquote|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 [[eunuch]]s or boys before coition with a woman, or women except those in whom the menses have become suppressed... some have obtained lifelong security by refraining from [[wine]], [[mead]] and [[wikt:venery#Etymology 2|venery]].<ref>{{cite web |url=https://penelope.uchicago.edu/Thayer/E/Roman/Texts/Celsus/4*.html |title=On Medicine |first=  A. Cornelius |last=Celsus |at=Book IV |website=University of Chicago}}</ref>}}
+In the 18th century, [[Thomas Marryat]] distinguished different manifestations of gout:
-Benjamin Welles, an English physician authored the first medical book on gout, ''A Treatise of the Gout, or Joint Evil'', in 1669.<ref>{{cite book|last=Copeman |first=W.S.C.|title=A Short History of the Gout and the Rheumatic Diseases|date=2021|publisher=University of California Press|isbn=978-0-520-33947-7|page=68}}</ref> In 1683, [[Thomas Sydenham]], an English physician, described its occurrence in the early hours of the morning and its predilection for older males:
+<blockquote>
-{{blockquote|Gouty patients are, generally, either old men or men who have so worn themselves out in youth as to have brought on a premature old age—of such dissolute habits none being more common than the premature and excessive indulgence in venery and the like exhausting passions. The victim goes to bed and sleeps in good health. About two o'clock in the morning he is awakened by a severe pain in the great toe; more rarely in the heel, ankle, or instep. The pain is like that of a dislocation and yet parts feel as if cold water were poured over them. Then follows chills and shivers and a little fever... The night is passed in torture, sleeplessness, turning the part affected and perpetual change of posture; the tossing about of body being as incessant as the pain of the tortured joint and being worse as the fit comes on.<ref>{{cite web |url=https://www.bbc.co.uk/dna/h2g2/A11102491 |title=Gout – The Affliction of Kings |website=h2g2 |publisher=BBC |date=December 23, 2012 |url-status=live |archive-url=https://web.archive.org/web/20100911065930/http://www.bbc.co.uk/dna/h2g2/A11102491 |archive-date=September 11, 2010 }}</ref>}}
+The Gout is a chronical disease most commonly affecting the feet. If it attacks the knees, it is called {{linktext|Gonagra}}; if the hands, {{linktext|Chiragra}}; if the elbow, Onagra; if the shoulder, {{linktext|Omagra}}; if the back or loins, [[Lumbago]].<ref>{{cite book
+ |last1             = Marryat
+ |first1            = Thomas
+ |author-link1      = Thomas Marryat
+ |year              = 1798
+ |orig-date         = 1758
+ |title             = Therapeutics: Or, the Art of Healing: To which is Added, a Glossary of the Most Difficult Words
+ |url               = https://books.google.com/books?id=Xfg2AQAAMAAJ
+ |edition           = 14
+ |publication-place = Bristol
+ |publisher         = R. Edwards
+ |page              = 168
+ |access-date       = 28 April 2024
+ |archive-date      = 28 April 2024
+ |archive-url       = https://web.archive.org/web/20240428051831/https://books.google.com/books?id=Xfg2AQAAMAAJ
+ |url-status        = live
+}}</ref>
+</blockquote>
-Dutch scientist [[Antonie van Leeuwenhoek]] first described the microscopic appearance of urate crystals in 1679.<ref name="Pillinger"/> In 1848, English physician [[Alfred Baring Garrod]] identified excess uric acid in the blood as the cause of gout.<ref name="pmid11600751">{{cite journal | author=Storey GD |title=Alfred Baring Garrod (1819–1907) |journal=Rheumatology |volume=40 |issue=10 |pages=1189–1190 |date=October 2001 |pmid=11600751 | doi=10.1093/rheumatology/40.10.1189 |doi-access=free }}</ref>
+Dutch scientist [[Antonie van Leeuwenhoek]] first described the microscopic appearance of urate crystals in 1679.<ref name="Pillinger"/> In 1848, English physician [[Alfred Baring Garrod]] identified excess uric acid in the blood as the cause of gout.<ref name="pmid11600751">{{cite journal | author= Storey GD |title= Alfred Baring Garrod (1819–1907) |journal=Rheumatology |volume=40 |issue=10 |pages=1189–1190 |date=October 2001 |pmid=11600751 | doi= 10.1093/rheumatology/40.10.1189 |doi-access=free}}
+</ref>
 ==Other animals==
-Gout is rare in most other animals due to their ability to produce [[uricase]], which breaks down uric acid.<ref name=Animals01>{{cite journal |vauthors=Agudelo CA, Wise CM |title=Gout: diagnosis, pathogenesis, and clinical manifestations |journal=Curr Opin Rheumatol |volume=13 |issue=3 |pages=234–239 |year=2001 |pmid=11333355 |doi= 10.1097/00002281-200105000-00015|s2cid=34502097 }}</ref> Humans and other [[great apes]] do not have this ability; thus, gout is common.<ref name=Egg2007/><ref name=Animals01/> Other animals with uricase include fish, amphibians and most non-primate mammals.<ref name=Choi2005>{{cite journal|last1=Choi|first1=HK|last2=Mount|first2=DB|last3=Reginato|first3=AM|last4=American College of|first4=Physicians|last5=American Physiological|first5=Society|title=Pathogenesis of gout|journal=Annals of Internal Medicine|date=4 October 2005|volume=143|issue=7|pages=499–516|pmid=16204163|doi=10.7326/0003-4819-143-7-200510040-00009|s2cid=194570}}</ref> The ''[[Tyrannosaurus rex]]'' specimen known as "[[Sue (dinosaur)|Sue]]" is believed to have had gout.<ref name="Rothschild">{{cite journal | last=Rothschild | first=BM |author2=Tanke D |author3=Carpenter K  | title=Tyrannosaurs suffered from gout | journal=Nature | volume=387 | issue=6631 | page=357 | year=1997 | doi=10.1038/387357a0 | pmid=9163417 | bibcode=1997Natur.387..357R | s2cid=1360596 | url=https://zenodo.org/record/3943065 | doi-access=free }}</ref>
+Gout is rare in most other animals due to their ability to produce [[uricase]], which breaks down uric acid.<ref name=Animals01>{{cite journal |vauthors=Agudelo CA, Wise CM |title=Gout: diagnosis, pathogenesis, and clinical manifestations |journal=Curr Opin Rheumatol |volume=13 |issue=3 |pages=234–239 |year=2001 |pmid=11333355 |doi= 10.1097/00002281-200105000-00015|s2cid=34502097 }}</ref> Humans and other [[great apes]] do not have this ability; thus, gout is common.<ref name=Egg2007/><ref name=Animals01/> Other animals with uricase include fish, amphibians and most non-primate mammals.<ref name=Choi2005>{{cite journal|last1=Choi|first1=HK|last2=Mount|first2=DB|last3=Reginato|first3=AM|last4=American College of|first4=Physicians|last5=American Physiological|first5=Society|title=Pathogenesis of gout|journal=Annals of Internal Medicine|date=4 October 2005|volume=143|issue=7|pages=499–516|pmid=16204163|doi=10.7326/0003-4819-143-7-200510040-00009|s2cid=194570}}</ref> The ''[[Tyrannosaurus rex]]'' specimen known as "[[Sue (dinosaur)|Sue]]" is believed to have had gout.<ref name="Rothschild">{{cite journal | last=Rothschild | first=BM | author2=Tanke D | author3=Carpenter K | title=Tyrannosaurs suffered from gout | journal=Nature | volume=387 | issue=6631 | page=357 | year=1997 | doi=10.1038/387357a0 | pmid=9163417 | bibcode=1997Natur.387..357R | s2cid=1360596 | url=https://zenodo.org/record/3943065 | doi-access=free | access-date=29 September 2020 | archive-date=17 April 2021 | archive-url=https://web.archive.org/web/20210417031211/https://zenodo.org/record/3943065 | url-status=live }}</ref>
 ==Research==
@@ Line 185: / Line 229: @@
 {{Commons category|Gout}}
 {{Offline|med}}
-* {{curlie|Health/Conditions_and_Diseases/Musculoskeletal_Disorders/Arthritis/Gout/}}
 * {{cite EB1911|wstitle=Gout|volume=12|pages=289–291}}
 * {{cite web | url = https://medlineplus.gov/gout.html | publisher = U.S. National Library of Medicine | work = MedlinePlus | title = Gout }}

Classification	D ICD-10: M10 ICD-9-CM: 274.00 274.1 274.8 274.9 OMIM: 138900 300323 MeSH: D006073 DiseasesDB: 29031
External resources	MedlinePlus: 000422 eMedicine: emerg/221 med/924 med/1112 oph/506 orthoped/124 radio/313 Patient UK: Gout Radiopaedia: gout Wheeless textbook: gout