Gout
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2008-07-16T02:45:41Z
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{{Infobox_Disease |
Name = Gout |
Image = Uric_acid.png |
Caption = [[Uric acid]] |
DiseasesDB = 29031 |
ICD10 = {{ICD10|M|10||m|05}} |
ICD9 = {{ICD9|274.0}} {{ICD9|274.1}} {{ICD9|274.8}} {{ICD9|274.9}} |
ICDO = |
OMIM = 138900 |
OMIM_mult = {{OMIM2|300323}} |
MedlinePlus = |
eMedicineSubj = med |
eMedicineTopic = 924 |
eMedicine_mult = {{eMedicine2|orthoped|124}} {{eMedicine2|emerg|221}} {{eMedicine2|med|1112}} {{eMedicine2|oph|506}} {{eMedicine2|radio|313}} |
MeshID = D006073 |
}}
'''Gout''' (also called ''metabolic arthritis'') is a disease created by a buildup of [[uric acid]]. In this condition, monosodium urate or uric acid [[crystal]]s are deposited on the articular [[cartilage]] of joints, tendons and surrounding tissues due to elevated concentrations of uric acid in the blood stream. This provokes an inflammatory reaction of these tissues.
==Signs and symptoms==
[[Image:The gout james gillray.jpg|right|thumb|150gpx|''The Gout'', Cartoon by [[James Gillray]] (1799). The artist memorably illustrates the excruciating pain and swelling that are symptoms of the disease.]]
Gout is characterized by excruciating, sudden, unexpected, burning pain, as well as swelling, redness, warmth, and stiffness in the affected joint. This occurs commonly in men in their toes but can appear in other parts of the body and affects women as well. Low-grade fever may also be present. The patient usually suffers from two sources of pain. The crystals inside the joint cause intense pain whenever the affected area is moved. The inflammation of the tissues around the joint also causes the skin to be swollen, tender and sore if it is even slightly touched. For example, a blanket or even the lightest sheet draping over the affected area could cause extreme pain.
Gout usually attacks the [[hallux|big toe]] (approximately 75 percent of first attacks); however, it also can affect other joints such as the ankle, heel, instep, knee, wrist, elbow, fingers, and spine. In some cases, the condition may appear in the joints of small toes that have become immobile due to impact injury earlier in life, causing poor blood circulation that leads to gout.
Patients with longstanding [[hyperuricemia]] (see below) can have uric acid crystal deposits called ''[[tophi]]'' (singular: [[tophus]]) in other tissues such as the [[Helix (ear)|helix of the ear]]. Elevated levels of uric acid in the urine can lead to uric acid crystals precipitating in the [[kidney]]s or [[bladder]], forming uric acid [[kidney stone]]s.
==Diagnosis==
A definitive [[diagnosis]] of gout is from [[light microscopy]] of fluid aspirated from the joints (this test may be difficult to perform) to demonstrate [[intracellular]] monosodium urate crystals in [[synovial fluid]] [[polymorphonuclear leukocytes]]. The [[urate]] crystal is identified by strong negative [[birefringence]] under polarised microscopy and its needle-like morphology. A trained observer does better in distinguishing them from other crystals.
[[Hyperuricemia]] is a common feature, although urate levels are not always raised.<!--
--><ref>{{cite journal | author = Sturrock R | title = Gout. Easy to misdiagnose | journal = [[British Medical Journal|BMJ]] | volume = 320 | issue = 7228 | pages = 132–3 | year = 2000 | pmid = 10634714 |url=http://bmj.bmjjournals.com/cgi/content/full/320/7228/132 | doi = 10.1136/bmj.320.7228.132}}</ref>
Hyperuricemia is defined as a [[blood plasma|plasma]] urate (uric acid) level greater than 420 ''μ''mol/L (7.0 mg/dL) in males, or 380 ''μ''mol/L in females. However, a high [[uric acid]] level does not necessarily mean a person will develop gout. [[Urate]] is within the normal range in up to two-thirds of cases.<!--Hypothyroidism as well
--><ref>{{cite journal | author = Siva C, Velazquez C, Mody A, Brasington R | title = Diagnosing acute monoarthritis in adults: a practical approach for the family physician | journal = Am Fam Pghysician | volume = 68 | issue = 1 | pages = 83–90 | year = 2003 | pmid = 12887114}}</ref>
If gout is suspected, the serum urate test should be repeated once the attack has subsided. Other blood tests commonly performed are [[full blood count]], [[electrolyte]]s, [[renal function]], [[thyroid function tests]] and [[erythrocyte sedimentation rate]] (ESR). This helps to exclude other causes of [[arthritis]], most notably [[septic arthritis]], and to investigate any underlying cause for the hyperuricaemia.
==Pathogenesis==
Gout occurs when mono-sodium urate crystals form on the articular cartilage of joints, on tendons, and in the surrounding tissues. [[Purine metabolism]] gives rise to uric acid, which is normally excreted in the urine. Uric acid is more likely to form into crystals when there is a [[hyperuricemia]], although it is 10 times more common without clinical gout than with it.<ref name="pmid17595458">{{cite journal |author=Virsaladze DK, Tetradze LO, Dzhavashvili LV, Esaliia NG, Tananashvili DE |title=[Levels of uric acid in serum in patients with metabolic syndrome] |language=Russian |journal=Georgian Med News |volume= |issue=146 |pages=35–7 |year=2007 |month=May |pmid=17595458 |doi= |url=}}</ref>
[[Purines]] can be generated by the body via breakdown of cells in normal cellular turnover, or can be ingested in purine-rich foods such as seafood. The kidneys are responsible for approximately two-third of uric acid excretion, with the gut responsible for the rest. It may be possible that defects in the kidney that may be genetically determined are responsible for the predisposition of individuals for developing gout.
There are also different racial propensities to develop gout. Gout is high among the peoples of the Pacific Islands, and the [[Māori]] of New Zealand, but rare in the Australian aborigine despite the latter's higher mean concentration of serum uric acid.<!--
--><ref name="pmid10225809">{{cite journal |author=Roberts-Thomson RA, Roberts-Thomson PJ |title=Rheumatic disease and the Australian aborigine |journal=Ann. Rheum. Dis. |volume=58 |issue=5 |pages=266–70 |year=1999 |month=May |pmid=10225809 |pmc=1752880 |doi= |url=http://ard.bmjjournals.com/cgi/content/full/58/5/266}}</ref> In the United States, gout is twice as prevalent in African American males as it is in European-Americans.<!--
--><ref>{{cite web | author = Rheumatology Therapeutics Medical Center | title = What Are the Risk Factors for Gout? | url=http://www.arthritisconsult.com/gout.html#risk | accessdate = 2007-01-26}}</ref>
A seasonal link also may exist, with significantly higher incidence of acute gout attacks occurring in the spring.<ref name="pmid9489831">{{cite journal |author=Schlesinger N, Gowin KM, Baker DG, Beutler AM, Hoffman BI, Schumacher HR |title=Acute gouty arthritis is seasonal |journal=J. Rheumatol. |volume=25 |issue=2 |pages=342–4 |year=1998 |month=February |pmid=9489831 |doi= |url=}}</ref><ref name="pmid10534553">{{cite journal |author=Gallerani M, Govoni M, Mucinelli M, Bigoni M, Trotta F, Manfredini R |title=Seasonal variation in the onset of acute microcrystalline arthritis |journal=Rheumatology (Oxford) |volume=38 |issue=10 |pages=1003–6 |year=1999 |month=October |pmid=10534553 |doi= |url=http://rheumatology.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=10534553}}</ref>
Hyperuricemia is considered an aspect of [[metabolic syndrome]], although its prominence has been reduced in recent classifications. This explains the increased prevalence of gout among [[obesity|obese]] individuals.
Gout is a form of arthritis that affects mostly men between the ages of 50 and 60. The high levels of uric acid in the blood are caused by protein rich foods. Alcohol intake often causes acute attacks of gout and hereditary factors may contribute to the elevation of uric acid. Typically, persons with gout are obese, predisposed to diabetes and hypertension, and at higher risk of heart disease. Gout is more common in affluent societies due to a diet rich in proteins, fat, and alcohol. When it follows as a consequence of other health conditions such as [[renal failure]], it is often regardless of the person's lifestyle.<ref name="isbn0-87477-986-3">{{cite book |author=Trivieri, Larry; Ivker, Robert S.; Anderson, Robert H. |title=The complete self-care guide to holistic medicine: treating our most common ailments |publisher=J.P. Tarcher/Putnam |location=New York, N.Y |year=1999 |pages= |isbn=0-87477-986-3 |oclc= |doi= |accessdate=}}</ref> Lin, et al have statistical evidence linking gout to lead poisoning,<ref name="pmid12459402">{{cite journal |author=Lin JL, Tan DT, Ho HH, Yu CC |title=Environmental lead exposure and urate excretion in the general population |journal=Am. J. Med. |volume=113 |issue=7 |pages=563–8 |year=2002 |month=November |pmid=12459402 |doi= |url=}}</ref> and lead level in the body is significantly correlated with urate excretion and gout.<ref name="pmid6434739">{{cite journal |author=Wright LF, Saylor RP, Cecere FA |title=Occult lead intoxication in patients with gout and kidney disease |journal=J. Rheumatol. |volume=11 |issue=4 |pages=517–20 |year=1984 |month=August |pmid=6434739 |doi= |url=}}</ref> It is known that [[Lead(II) acetate|lead sugar]] was used to sweeten wine, and that chronic [[lead poisoning]] is a cause of gout,<ref name="pmid8035397">{{cite journal |author=Lin JL, Huang PT |title=Body lead stores and urate excretion in men with chronic renal disease |journal=J. Rheumatol. |volume=21 |issue=4 |pages=705–9 |year=1994 |month=April |pmid=8035397 |doi= |url=}}</ref><ref name="pmid10914856">{{cite journal |author=Shadick NA, Kim R, Weiss S, Liang MH, Sparrow D, Hu H |title=Effect of low level lead exposure on hyperuricemia and gout among middle aged and elderly men: the normative aging study |journal=J. Rheumatol. |volume=27 |issue=7 |pages=1708–12 |year=2000 |month=July |pmid=10914856 |doi= |url=}}</ref> which condition is then known as '''saturnine gout,''' because of its association with alcohol and excess.<ref name="pmid4947583">{{cite journal |author=Ball GV |title=Two epidemics of gout |journal=Bull Hist Med |volume=45 |issue=5 |pages=401–8 |year=1971 |pmid=4947583 |doi= |url=}}</ref><!--poorly written statement-->
Gout also can develop as co-morbidity of other diseases, including [[polycythaemia]], [[leukaemia]], intake of [[cytotoxic]]s, [[obesity]], [[diabetes]], [[hypertension]], [[renal]] disorders, and [[hemolytic anemia]]. This form of gout is often called secondary gout. [[Diuretic]]s (particularly [[thiazide]] diuretics) have traditionally been blamed for precipitating attacks of gout because they compete at the same transporter, but a Dutch case-control study from 2006 appears to cast doubt on this conclusion.<!--
--><ref name="pmid16291814">{{cite journal |author=Janssens HJ, van de Lisdonk EH, Janssen M, van den Hoogen HJ, Verbeek AL |title=Gout, not induced by diuretics? A case-control study from primary care |journal=Ann. Rheum. Dis. |volume=65 |issue=8 |pages=1080–3 |year=2006 |month=August |pmid=16291814 |doi=10.1136/ard.2005.040360 |url=}}</ref>
[[Image:ChronicGout.jpg|right|thumb|220px|Gout with tophi on elbow and knee.]]
==Treatment==
===Acute attacks===
The first line of treatment should be pain relief. Once the diagnosis has been confirmed, the drugs of choice are [[indomethacin]], other [[nonsteroidal anti-inflammatory drugs]] (NSAIDs), oral [[glucocorticoids]],<ref name="pmid18514729">{{cite journal |author=Janssens HJ, Janssen M, van de Lisdonk EH, van Riel PL, van Weel C |title=Use of oral prednisolone or naproxen for the treatment of gout arthritis: a double-blind, randomised equivalence trial |journal=Lancet |volume=371 |issue=9627 |pages=1854–60 |year=2008 |month=May |pmid=18514729 |doi=10.1016/S0140-6736(08)60799-0 |url=}}</ref> or intra-articular [[glucocorticoids]] administered via a [[joint injection]].
[[Colchicine]] was previously the drug of choice in acute attacks of gout, as it impairs the motility of [[granulocyte]]s and can prevent the inflammatory phenomena that initiate an attack. Colchicine should be taken within the first 12 hours of the attack and usually relieves the pain within 48 hours, although side effects (gastrointestinal upset such as [[diarrhea]] and [[nausea]]) can complicate its use. NSAIDs are the preferred form of analgesia for patients with gout.
A [[randomized controlled trial]] found similar benefit from [[nonsteroidal anti-inflammatory drugs]] and oral [[glucocorticoids]]; however, less [[adverse drug reaction]]s occurred in the [[glucocorticoids]] group.<ref name="pmid17276548">{{cite journal |author=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=670–7 |year=2007 |pmid=17276548 |doi=10.1016/j.annemergmed.2006.11.014}}</ref> In the [[nonsteroidal anti-inflammatory drugs]] group, each patient initially received [[diclofenac]] (75 mg) intramuscularly, [[indomethacin]] 50 mg orally, and [[acetaminophen]] 1 g orally. The patient was received a 5-days of indomethacin (50 mg orally every 8 hours for 2 days, followed by indomethacin 25 mg every 8 hours for 3 days), and acetaminophen 1 g every 6 hours as needed. The [[glucocorticoids]] patients received [[prednisolone]] 30 mg orally, and acetaminophen 1 g orally. The patient was then given prednisolone 30 mg orally once per day for five days.
Before medical help is available, some over-the-counter medications can provide temporary relief from pain and swelling. NSAIDs such as [[ibuprofen]] can reduce the pain and inflammation slightly, although [[aspirin]] should not be used as it can worsen the condition. This is because aspirin raises plasma uric acid levels even at low doses by inhibiting uric acid secretion in the renal tubules{{Fact|date=May 2008}}. Aspirin also reduces vasodilatation due to inhibition of [[prostaglandin]] PGE2 and PGI2 synthesis in the [[renal medulla]] and [[glomeruli]] respectively (see [[mechanism of action of aspirin]]). This may be a contra-indication for the use of aspirin for gout pain as well.
The anti-[[hemorrhoid]]al [[ointment]] [[Preparation H]] can reduce gout-induced skin swelling temporarily. Ice may be applied for 20 to 30 minutes several times a day, and a [[randomized controlled trial]] found that patients who used ice packs had better relief of pain without side effects.<ref name="pmid11838852">{{cite journal |author=Schlesinger N, Detry MA, Holland BK, ''et al'' |title=Local ice therapy during bouts of acute gouty arthritis |journal=J. Rheumatol. |volume=29 |issue=2 |pages=331–4 |year=2002 |pmid=11838852 |doi=}}</ref> Since [[gout]] is caused by [[crystals]], it has been suggested that keeping very well hydrated and heating the affected joint in hot water (rather than cooling with ice) will promote the dissolution and clearance of the [[urate]] crytals.<ref>[http://www.bmj.com/cgi/eletters/332/7553/1315#135610 rapid response] from a GP to BMJ.com.</ref> Keeping the affected area elevated above the level of the heart also may help. Professional medical care is needed for long-term management of gout.
Due to swelling around affected joints for prolonged periods, shedding of skin may occur. This is particularly evident when small toes are affected and may promote fungal infection in the web region if dampness occurs, and treatment is similar to that for common [[athlete's foot]].
Some sufferers of gout report an aggravation of the condition in the knees and toes associated with long periods of immobility, such as when sitting at a computer desk for long hours. Sufferers who notice early swelling or early pain may appear to be able to arrest the aggravation when medical treatment is applied before the condition gets worse. Where this is the case, a medically prescribed anti-inflammatory oral treatment taken with food and [[bed rest]] may provide relief within 6 to 8 hours.
Another possibility is [[acetazolamide]], one of the first diuretics discovered. This drug inhibits the action of carbonic anhydrase on the proximal convoluted tubules within the kidneys, which effectively inhibits reabsorption of [[bicarbonate]], thus alkalinizing the urine. After two to three days of usage, the diuretic effects of this drug decline because of increased downstream reabsorption of ions and water by the renal tubules; however, the alkalinization of urine persists, and this basic urine attracts weak acids such as '''uric acid''' and cystine into the urine, thus increasing their urinary excretion.
===Chronic joint changes===
For ''extreme'' cases of gout, surgery may be necessary to remove large [[tophus|tophi]] and correct joint deformity.
==Prevention==
===Medications===
* [[Allopurinol]] is a xanthine-oxidase inhibitor, widely used in the prevention of attacks of gout, and well tolerated. It is safe to use in patients with renal impairment and urate stones.<ref>The British National Formulary website, www.bnf.org</ref>
*[[Sulfinpyrazone]] is an uricosuric. It is less widely used than allupurinol, and must not be used in patients with renal impairment, or a high urate excretion rate.<ref name="pmid16740561">{{cite journal |author=Underwood M |title=Diagnosis and management of gout |journal=BMJ |volume=332 |issue=7553 |pages=1315–9 |year=2006 |month=June |pmid=16740561 |pmc=1473078 |doi=10.1136/bmj.332.7553.1315 |url=}}</ref>
* [[Allopurinol]] and [[azathioprine]] ([[Imuran]]) used together present a risk of a potentially fatal [[drug interaction]], a severe risk of allopurinol use which is of importance to transplant patients being treated with azathioprine for [[immunosuppression]].[http://www.medsafe.govt.nz/Profs/PUarticles/azathioprine.htm]
* [[Febuxostat]] ((2-[3-cyano-4-isobutoxyphenyl]-4-methylthiazole-5-carboxylic acid) - a non-purine inhibitor of xanthine oxidase seems to be an alternative that is superior to allopurinol at reducing serum urate levels, but not at reducing attacks of gout; it is currently in [[Clinical trials#Phase III| Phase III trials]].<!--
--><ref name="pmid16339094">{{cite journal |author=Becker MA, Schumacher HR, Wortmann RL, ''et al'' |title=Febuxostat compared with allopurinol in patients with hyperuricemia and gout |journal=N. Engl. J. Med. |volume=353 |issue=23 |pages=2450–61 |year=2005 |month=December |pmid=16339094 |doi=10.1056/NEJMoa050373 |url=}}</ref>
* [[Probenecid]], a uricosuric drug that promotes the excretion of uric acid in urine, is also commonly prescribed - often in conjunction with [[colchicine]]. The drug [[fenofibrate]] (which is used in treating [[hyperlipidemia]]) also exerts a beneficial uricosuric effect.<!--
--><ref name="pmid12759281">{{cite journal |author=Bardin T |title=Fenofibrate and losartan |journal=Ann. Rheum. Dis. |volume=62 |issue=6 |pages=497–8 |year=2003 |month=June |pmid=12759281 |pmc=1754575 |doi= |url=http://ard.bmjjournals.com/cgi/content/full/62/6/497}}</ref>
* As arterial hypertension quite often coexists with gout, treating it with [[losartan]], an [[angiotensin II receptor antagonist]], might have an additional beneficial effect on uric acid plasma levels. This way losartan can offset the negative side-effect of [[thiazide]]s (a group of [[diuretic]]s used for [[arterial hypertension|high blood pressure]]) on uric acid metabolism in patients with gout.
* Gout is suspected to be secondary to untreated [[sleep apnea]] in some cases, caused by the release of purines as a by-product of the breakdown of oxygen-starved cells. Treatment for apnea can therefore be effective in lessening incidence of acute gout attacks.<!--
--><ref name="pmid16171252">{{cite journal |author=Abrams B |title=Gout is an indicator of sleep apnea |journal=Sleep |volume=28 |issue=2 |pages=275 |year=2005 |month=February |pmid=16171252 |doi= |url=}}</ref>
* A 2004 study suggests that animal flesh sources of purine (such as beef and seafood) greatly increase the risk of developing gout. However, high-purine vegetable sources (such as asparagus, cauliflower, spinach, and green peas) did not. Dairy products such as milk and cheese significantly reduced the chances of gout. The study followed over 40000 men over a period of 12 years, in which 1300 cases of gout were reported.<!--
--><ref name="pmid15014182">{{cite journal |author=Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G |title=Purine-rich foods, dairy and protein intake, and the risk of gout in men |journal=N. Engl. J. Med. |volume=350 |issue=11 |pages=1093–103 |year=2004 |month=March |pmid=15014182 |doi=10.1056/NEJMoa035700 |url=http://www.nutritionaustralia.org/News_in_Nutrition/Journal_Articles/purine%20rich%20foods.pdf |format=PDF}}</ref>
*[[PEG-uricase]], a polyethylene glycol ("PEG") conjugate of recombinant porcine uricase (urate oxidase), which breaks down the uric acid deposits is being studied in [[clinical trial#Phase III|Phase III clinical trials]] for the treatment of severe, treatment-refractory gout in the United States in [[2006]].[http://www.savientpharma.com/pipeline/puricase.asp Pipeline]
*[[Sodium bicarbonate]] (baking soda) is a traditional remedy,<ref>The British Pharmaceutical Codex. Published by direction of the Council of the Pharmaceutical Society of Great Britain, 1911. [http://www.henriettesherbal.com/eclectic/bpc1911/sodium.html Sodium]</ref> thought to work by raising blood [[pH]] (lowering blood acidity). However, the added sodium may be inappropriate for some people.
*[[EDTA|Ethylenediaminetetraacetic acid (EDTA)]], a [[chelation|chelator]] of lead, has successfully increased uric acid excretion.<ref name="pmid11422760">{{cite journal |author=Lin JL, Yu CC, Lin-Tan DT, Ho HH |title=Lead chelation therapy and urate excretion in patients with chronic renal diseases and gout |journal=Kidney Int. |volume=60 |issue=1 |pages=266–71 |year=2001 |month=July |pmid=11422760 |doi=10.1046/j.1523-1755.2001.00795.x |url=}}</ref> This should be an advantageous treatment for those people whose gout was caused by lead poisoning. Care should be taken to increase intake of trace essential elements since chelation often remove these elements also.
*[[Potassium]] supplements should be advantageous to treat gout. Gout can be triggered by the same agents that cause potassium losses such as fasting, surgery, and potassium losing diuretics.<ref>Rodman JS 2002 Intermittent versus continuous alkaline therapy for uric acid stones and uretal stones of uncertain composition. Urology 60; 378-382.</ref> A potassium deficiency can increase urate levels in the blood.<ref> Davis WH 1970 Does potassium deficiency hold a clue to metabolic disorders associated with liability to heart disease?. South African Med. Journal 44; 1297.</ref>
*Research from the [[University of British Columbia]] suggests long-term coffee consumption is associated with a lower risk of gout.<!--
--><ref name="pmid17530645">{{cite journal |author=Choi HK, Willett W, Curhan G |title=Coffee consumption and risk of incident gout in men: a prospective study |journal=Arthritis Rheum. |volume=56 |issue=6 |pages=2049–55 |year=2007 |month=June |pmid=17530645 |doi=10.1002/art.22712 |url=}}</ref> Other studies extend this benefit to tea and other caffeinated foods and drinks.<!--
--><ref name="pmid17530681">{{cite journal |author=Choi HK, Curhan G |title=Coffee, tea, and caffeine consumption and serum uric acid level: the third national health and nutrition examination survey |journal=Arthritis Rheum. |volume=57 |issue=5 |pages=816–21 |year=2007 |month=June |pmid=17530681 |doi=10.1002/art.22762 |url=}}</ref>
Dr James Compton Burnett used to prescribe Urtica Urens mother tincture, 10 drops in water 3 times a day with great success for gout sufferers. Gout and its Cure was published in London and Philadelphia in 1895, ran to several editions and reprints are still available from India.
===Diet===
''See Saag and Choi, 2006, an open-access review article, for detailed references and further information.''<ref name="pmid16820041">{{cite journal |author=Saag KG, Choi H |title=Epidemiology, risk factors, and lifestyle modifications for gout |journal=Arthritis Res. Ther. |volume=8 Suppl 1 |issue= |pages=S2 |year=2006 |pmid=16820041 |doi=10.1186/ar1907 |url=}}</ref>
The serum level of uric acid is the primary risk factor for gout. The serum level is the result of both intake (diet) and output (excretion). Diet should be low fat and low protein.
====Reduce intake of purines====
The solubility threshold for uric acid is approximately 6.7 mg/dl; above this threshold crystals may form. Healthy subjects in the Normative Aging Study who had serum levels of uric acid over 9.0 mg/dl suffered a 22% incidence of gout over six years, compared to less than one percent for those with 7.0-8.9 mg/dl. The average uric acid level in men is 5.0 mg/dl, and substitution of a purine-free formula diet reduces this to 3.0 mg/dl. A purine-restricted diet lowers the level nearly as much (1-2 mg/dl).
A diet low in purines reduces the serum level of uric acid, unless these levels are caused by other health conditions and not as responsive to dietary changes. For notable sources of dietary purines, see "Foods to avoid" section below.
'''Protein''' is a crude proxy for purines; a more precise proxy is '''muscle'''. Apart from the notable dietary purines above, the main source of dietary purines is [[DNA]] and [[RNA]], via their bases [[adenine]] and [[guanine]]. All sources of dietary protein supply some purines, but some sources provide far more purines than others. Meat (particularly dark meat) and seafood are high in purine because [[muscle]] cells are packed with [[mitochondrion|mitochondria]], which have their own DNA and RNA. In a large prospective study, high consumption of meat and seafood were found associated with an elevated risk of gout onset (41% and 50%, respectively). High consumption of dairy products, high in protein but very low in DNA and RNA, was associated with a 44% ''decrease'' in the incidence of gout. Consumption of the more purine-rich vegetables or a high protein diet per se had no significant correlation.
Men who consume two or more sugary soft drinks a day have an 85% higher risk of gout compared with those who drink less than one a month.[http://news.bbc.co.uk/2/hi/health/7219473.stm] This is because soft drinks contain large quantities of [[high-fructose corn syrup]] (HFCS), a common sweetener in soft drinks, which results in [[Hyperuricemia]] in blood.<ref name="pmid16234313">{{cite journal |author=Nakagawa T, Hu H, Zharikov S, ''et al'' |title=A causal role for uric acid in fructose-induced metabolic syndrome |journal=Am. J. Physiol. Renal Physiol. |volume=290 |issue=3 |pages=F625–31 |year=2006 |month=March |pmid=16234313 |doi=10.1152/ajprenal.00140.2005 |url=}}</ref><ref name="pmid8213607">{{cite journal |author=Mayes PA |title=Intermediary metabolism of fructose |journal=Am. J. Clin. Nutr. |volume=58 |issue=5 Suppl |pages=754S–765S |year=1993 |month=November |pmid=8213607 |doi= |url=http://www.ajcn.org/cgi/pmidlookup?view=long&pmid=8213607}}</ref> Hyperuricemia, in turn predispose the body for gout.<ref name="isbn1-59486-665-1">{{cite book |author=Gower, Timothy; Johnson, Richard R. |title=The Sugar Fix: The High-Fructose Fallout That Is Making You Fat and Sick |publisher=Rodale Books |location=Emmaus, Pa |year=2008 |pages=304 |isbn=1-59486-665-1 |oclc= |doi= |accessdate=}}</ref>
Consumption of '''beer''' is associated with a 49% increase in relative risk per daily 12-oz serving. By contrast, consumption of [[spirits]] was associated with only a 15% increase in relative risk, and no association at all was found with consumption of wine.
Some '''medical drugs''' are purine-based. Notable among these are the purine-analog [[antimetabolite]] drugs, sometimes used as [[chemotherapy]] agents.
====Increase output of uric acid====
As mentioned above, medicines to induce uric acid output are called [[uricosuric]] drugs. Two such drugs are [[Probenecid]] and [[Sulfinpyrazone]].
====Other approaches====
Additional dietary recommendations can be made which reduce gout indirectly, [[hypertension]], [[cardiovascular disease]], [[diabetes]], and [[metabolic syndrome]].
The following suggestions do not meet with universal approval among medical practitioners.
Low [[purine]] diet:
* To lower uric acid:
** [[bing cherry| bing cherries]] were reported to reduce uric acid in a small study.<ref name="pmid12771324">{{cite journal |author=Jacob RA, Spinozzi GM, Simon VA, ''et al'' |title=Consumption of cherries lowers plasma urate in healthy women |journal=J. Nutr. |volume=133 |issue=6 |pages=1826–9 |year=2003 |month=June |pmid=12771324 |doi= |url=http://jn.nutrition.org/cgi/pmidlookup?view=long&pmid=12771324}}</ref><ref name="pmid14776685">{{cite journal |author=Blau LW |title=Cherry diet control for gout and arthritis |journal=Tex. Rep. Biol. Med. |volume=8 |issue=3 |pages=309–11 |year=1950 |pmid=14776685 |doi= |url=}}</ref>
** [[celery]] extracts (celery or celery seed either in capsule form or as a tisane/infusion) is believed by many to reduce uric acid levels (although these are also [[diuretic]]s).{{Fact|date=March 2007}} Celery extracts have been reported to act synergistically with anti-inflammatory drugs.<ref name="pmid15035799">{{cite journal |author=Whitehouse MW, Butters DE |title=Combination anti-inflammatory therapy: synergism in rats of NSAIDs/corticosteroids with some herbal/animal products |journal=Inflammopharmacology |volume=11 |issue=4 |pages=453–64 |year=2003 |pmid=15035799 |doi=10.1163/156856003322699636 |url=}}</ref>
** Cheese has been recommended as a low-purine food,<ref name="pmid10068714">{{cite journal |author=Harris MD, Siegel LB, Alloway JA |title=Gout and hyperuricemia |journal=Am Fam Physician |volume=59 |issue=4 |pages=925–34 |year=1999 |month=February |pmid=10068714 |doi= |url=http://newcms.aafp.org/afp/990215ap/925.html}}</ref> and dairy products have been found to reduce the risk of gout.
** Carbonated beverages and sugar have also been recommended as a low-purine food,<ref name="pmid10068714"/> even though it was established that men who consume two or more sugary soft drinks a day have an 85% higher risk of gout compared with those who drink less than one a month.[http://news.bbc.co.uk/2/hi/health/7219473.stm]
**Dietary supplements [[Quercetin]], a [[flavonoid]], can decrease uric acid levels. Quercetin can be taken with [[bromelain]] to improve its absorption. In addition, [[Pantothenic acid]] (vitamin B5) is said to help with the excretion process of uric acid. <ref name=Kroner> [http://www.drhoffman.com/page.cfm/547 "Gout" by Zina Kroner] ,</ref>
*Food to avoid:
**foods high in [[purine]]s
*** limit food high in protein such as [[meat]], [[fish]], [[poultry]], or [[tofu]] to 8 ounces (226 grams) a day. Avoid entirely during a flareup.{{Fact|date=March 2007}} Tofu has been proposed as a safe source of protein for gout patients due to its small and transient effect on plasma urate levels.<ref name="pmid9598181">{{cite journal |author=Yamakita J, Yamamoto T, Moriwaki Y, Takahashi S, Tsutsumi Z, Higashino K |title=Effect of Tofu (bean curd) ingestion and on uric acid metabolism in healthy and gouty subjects |journal=Adv. Exp. Med. Biol. |volume=431 |issue= |pages=839–42 |year=1998 |pmid=9598181 |doi= |url=}}</ref>
***[[sweetbread]]s, [[kidney]]s, [[liver]], [[brain]]s, or other [[offal]] meats.<ref name="pmid13188851">{{cite journal |author=ROBINSON CH |title=The low purine diet |journal=Am. J. Clin. Nutr. |volume=2 |issue=4 |pages=276–7 |year=1954 |pmid=13188851 |doi= |url=http://www.ajcn.org/cgi/reprint/2/4/276}}</ref><ref name="pmid7904493">{{cite journal |author=Chou P, Soong LN, Lin HY |title=Community-based epidemiological study on hyperuricemia in Pu-Li, Taiwan |journal=J. Formos. Med. Assoc. |volume=92 |issue=7 |pages=597–602 |year=1993 |month=July |pmid=7904493 |doi= |url=}}</ref>
***[[sardine]]s and [[anchovy|anchovies]]<ref name="pmid13188851">{{cite journal |author=Robinson CH |title=The low purine diet |journal=Am. J. Clin. Nutr. |volume=2 |issue=4 |pages=276–7 |year=1954 |pmid=13188851 |doi= |url=http://www.ajcn.org/cgi/reprint/2/4/276}}</ref>
***[[seafood]]<ref name="pmid15014182">{{cite journal |author=Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G |title=Purine-rich foods, dairy and protein intake, and the risk of gout in men |journal=N. Engl. J. Med. |volume=350 |issue=11 |pages=1093–103 |year=2004 |month=March |pmid=15014182 |doi=10.1056/NEJMoa035700 |url=}}</ref> particularly shellfish such as clam, oyster, scallop, shrimp, crab, lobster, and crayfish.
***Asparagus. Cauliflower. Mushrooms. Spinach. (Even though above says "Consumption of the more purine-rich vegetables or a high protein diet per se had no significant correlation.")
***Dry beans (lentils & peas).
***[[alcohol]].<ref name="pmid15094272">{{cite journal |author=Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G |title=Alcohol intake and risk of incident gout in men: a prospective study |journal=Lancet |volume=363 |issue=9417 |pages=1277–81 |year=2004 |month=April |pmid=15094272 |doi=10.1016/S0140-6736(04)16000-5 |url=}}</ref> Some claim that this applies especially to [[beer]] (high in [[guanosine]]), on the basis that [[brewer's yeast]]s are very rich in purine. Since most modern commercial beer contains only trace amounts of yeast, this claim requires further substantiation.{{Fact|date=September 2007}} Formerly, [[port wine]] was sweetened with [[litharge]], causing [[lead poisoning]], of which gout is a complication. Ironically, red wines, particularly those produced by traditional methods,<ref name="pmid17136085">{{cite journal |author=Corder R, Mullen W, Khan NQ, ''et al'' |title=Oenology: red wine procyanidins and vascular health |journal=Nature |volume=444 |issue=7119 |pages=566 |year=2006 |month=November |pmid=17136085 |doi=10.1038/444566a |url=}}</ref> contain [[procyanidins]] released from grape seeds during [[wine making]], which have been reported to lower serum uric acid levels by an indirect mechanism.<ref name="pmid15125693">{{cite journal |author=Wang Y, Zhu JX, Kong LD, Yang C, Cheng CH, Zhang X |title=Administration of procyanidins from grape seeds reduces serum uric acid levels and decreases hepatic xanthine dehydrogenase/oxidase activities in oxonate-treated mice |journal=Basic Clin. Pharmacol. Toxicol. |volume=94 |issue=5 |pages=232–7 |year=2004 |month=May |pmid=15125693 |doi=10.1111/j.1742-7843.2004.pto940506.x |url=}}</ref> However, withdrawal of urate-lowering therapy is associated with recurrence of acute gouty arthritis.<ref name="pmid17013833">{{cite journal |author=Perez-Ruiz F, Atxotegi J, Hernando I, Calabozo M, Nolla JM |title=Using serum urate levels to determine the period free of gouty symptoms after withdrawal of long-term urate-lowering therapy: a prospective study |journal=Arthritis Rheum. |volume=55 |issue=5 |pages=786–90 |year=2006 |month=October |pmid=17013833 |doi=10.1002/art.22232 |url=}}</ref>
***meat extracts, [[consommé]]s, and [[gravy|gravies]]<ref name="pmid13188851">{{cite journal |author=Robinson CH |title=The low purine diet |journal=Am. J. Clin. Nutr. |volume=2 |issue=4 |pages=276–7 |year=1954 |pmid=13188851 |doi= |url=http://www.ajcn.org/cgi/reprint/2/4/276}}</ref>
**Foods high in [[fructose]], as discussed above, especially [[high-fructose corn syrup]] (HFCS) as main ingredient (READ LABEL).<ref name="isbn1-59486-665-1"/>
*** All [[soft drink]]s (non-diet), wherein HFCS is second ingredient next to water
*** [[Fruit preserves]], [[jam]], [[jelly]]
*** [[Syrup]]
*** [[Candy]]
*** To lesser extent, depending on fructose content, [[ice cream]], [[cake]]s, and [[cookie]]s
* To avoid [[dehydration]]:
** Drink plenty of liquids, especially [[water]], to dilute and assist excretion of urates;
** Avoid [[diuretic]] foods or medicines like [[aspirin]](aspirin should be avoided by those suffering from gout, unless specified by a qualified physician), [[vitamin C]], [[tea]] and alcohol. The role of diuretics in triggering gout has been disputed.<ref name="pmid16291814">{{cite journal |author=Janssens HJ, van de Lisdonk EH, Janssen M, van den Hoogen HJ, Verbeek AL |title=Gout, not induced by diuretics? A case-control study from primary care |journal=Ann. Rheum. Dis. |volume=65 |issue=8 |pages=1080–3 |year=2006 |month=August |pmid=16291814 |doi=10.1136/ard.2005.040360 |url=}}</ref>
* Moderate intake of purine-rich vegetables is not associated with increased gout.<!--
--><ref name="pmid15014182"/>
==History==
Writing ca. 30 AD, [[Aulus Cornelius Celsus]] appeared to recognize many of the features of gout, including its link with a urinary solute, late onset in women, linkage with alcohol, and perhaps even prevention by dairy products. [http://penelope.uchicago.edu/Thayer/E/Roman/Texts/Celsus/5*.html] "Again thick urine, the sediment from which is white, indicates that pain and disease are to be apprehended in the region of joints or viscera." and "Joint troubles in the hands and feet are very frequent and persistent, such as occur in cases of podagra and cheiragra. These seldom attack eunuchs or boys before coition with a woman, or women except those in whom the menses have become suppressed. Upon the commencement of pain blood should be let; for when this is carried out at once in the first stages it ensures health, often for a year, sometimes for always. Some also, when they have washed themselves out by drinking asses' milk, evade this disease in perpetuity; some have obtained lifelong security by refraining from wine, mead and venery for a whole year; indeed this course should be adopted especially after the primary attack, even although it has subsided."
The [[Ancient Rome|Roman]] gladiatorial surgeon [[Galen]] described gout as a discharge of the four [[Four Temperaments|humors]] of the body in unbalanced amounts into the joints. The [[Latin]] term for a drop, as a drop of discharge, is gutta -- the term gout descends from this word.
==See also==
* [[Pseudogout]] is a very similar disease, but caused by deposition of [[calcium pyrophosphate]], not uric acid.
* [[Arthritis Care]]
==References==
{{reflist|2}}
==External links==
* {{cite web | title=American College of Rheumatology | url=http://www.rheumatology.org/public/factsheets/gout.asp?aud=pat| American College of Rheumatology |g publisher= |date=[[March 23]], [[2007]] | accessdate=2007-03-23}}- (ACR Fact Sheet on Gout)
* {{cite web | title=Questions and Answers on Gout from NIAMS| url=http://www.niams.nih.gov/Health_Info/Gout/default.asp | title = Answers and Questions on Gout | publisher= U.S. [[National Institutes of Health]]—[[National Institute of Arthritis and Musculoskeletal and Skin Diseases]] |date=[[September 28]], [[2007]] | accessdate=2007-08-28}}
* {{cite web | title=Diet and gout | url=http://my.webmd.com/hw/health_guide_atoz/ty2036.asp?navbar=hw69013 | work=A-Z Health Guide | publisher=webMD.com |date=[[July 1]], [[2004]] | accessdate=2006-09-18}}
* {{cite web | title=Coffee Consumption and Reduced Gout Risk | url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17530645 | work= Drinking coffee reduces risk of gout in middle age men | publisher= U.S. [[National Institutes of Health]] | accessdate=2007-05-25}}
* {{cite web | title=Purine content in food | url=http://www.britishdalmatianclub.org.uk/downloads/Purine%20Table%202003_files/sheet001.htm | publisher=British Dalmatian Club | accessdate=2006-09-18}}
* [http://health.howstuffworks.com/gout-in-depth.htm Gout in Depth - How Stuff Works]
* [http://www.thepatientconnections.com/blog.asp?uid=z0nsrl Online discussion of patients' experience of gout]
{{Diseases of the musculoskeletal system and connective tissue}}
{{Purine, pyrimidine, porphyrin, bilirubin metabolic pathology}}
[[Category:Arthritis]]
[[Category:Rheumatology]]
[[ar:نقرس]]
[[bg:Подагра]]
[[cs:Dna]]
[[da:Gigt]]
[[de:Gicht]]
[[el:Ουρική αρθρίτιδα]]
[[es:Gota (enfermedad)]]
[[eo:Podagro]]
[[fa:نقرس]]
[[fr:Arthrite goutteuse]]
[[io:Kiragro]]
[[id:Pirai]]
[[it:Gotta]]
[[he:שיגדון]]
[[lb:Giicht]]
[[ms:Gout]]
[[nl:Jicht]]
[[ja:痛風]]
[[no:Urinsyregikt]]
[[pl:Dna moczanowa]]
[[pt:Gota (doença)]]
[[ru:Подагра]]
[[simple:Gout]]
[[sk:Dna]]
[[sr:Гихт]]
[[fi:Kihti]]
[[sv:Gikt]]
[[te:గౌటు]]
[[th:โรคเกาต์]]
[[tr:Gut hastalığı]]
[[uk:Подагра]]
[[zh:痛风]]