Gout: Difference between revisions

{{Use dmy dates|date=NovemberMarch 20202024}}

| 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=978-14391040881-4391-0408-8|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=978-08532364050-85323-640-5|page=143|url=https://books.google.com/books?id=Ab_pQOdi2fUC&pg=PA143|edition=1. publ.}}</ref>

'''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 |last15=British Society for Rheumatology Standards, Audit and Guidelines Working |first14=E |last14=Roddy |first13=W |last13=Zhang |first12=A |last12=Pywell |first15=Group.}}</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"/>

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/dldL), 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/>

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.<ref>{{cite journal |last1=Neogi |first1=Tuhina |last2=Chen |first2=Clara |last3=Niu |first3=Jingbo |last4=Chaisson |first4=Christine |last5=Hunter |first5=David J. |last6=Choi |first6=Hyon |last7=Zhang |first7=Yuqing |date=2014-08-15 August 2014 |title=Relation of Temperature and Humidity to the Risk of Recurrent Gout Attacks |journal=American Journal of Epidemiology |volume=180 |issue=4 |pages=372–377 |doi=10.1093/aje/kwu147 |issn=0002-9262 |pmc=4184385 |pmid=24993733}}</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, MD |editor2-first=Ralph C. |editor2-last=Budd, MD |editor3-first=Edward D. |editor3-last=Harris Jr., MD |editor4-first= Iain B. |editor4-last=McInnes PhD, FRCP |editor5-first=Shaun |editor5-last=Ruddy, MD |editor6-first=John S. |editor6-last=Sergent, MD |title=Kelley's Textbook of Rheumatology |edition=8th |year=2008 |publisher=Elsevier |isbn=978-14160484281-4160-4842-8 |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=June 21, June 2021 |doi-access=free }}</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-url=http://webcache.googleusercontent.com/search?q=cache:dWsae4b6adYJ:https://cks.nice.org.uk/gout&hl=en&gl=ca&strip=1&vwsrc=0 |archive-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>

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/>

[[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/dldL) in males and 360 μmol/L (6.0&nbsp;mg/dldL) 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 40.0×10⁹/l (40,000/mm³) has been documented.<ref name=Egg2007/>

While it has been recommended that urate-lowering measures should be increased until serum uric acid levels are below 300–360&nbsp;µmolμmol/L (5.0–6.0&nbsp;mg/dldL),<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 simplesimply 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/dldL 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=2022-11-29 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>

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=978-07817715350-7817-7153-5 |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 11, 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>

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 2021-12-09 |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>

[[Colchicine]] is an alternative for those unable to tolerate NSAIDs.<ref name=Review08/> At high doses, side effects (primarily gastrointestinal upset) limit its usage.<ref name="FDA Warning">{{cite web | title=Information for Healthcare Professionals: New Safety Information for Colchicine (marketed as Colcrys) | url=https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm174315.htm | publisher=[[U.S. Food and Drug Administration]] | url-status=live | archive-url=https://web.archive.org/web/20091018113639/https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm174315.htm | archive-date=18 October 2009 }}</ref> At lower doses, which are still effective, it is well tolerated.<ref name=CFP09/><ref>{{cite journal|vauthors=McKenzie BJ, Wechalekar MD, Johnston RV, Schlesinger N, Buchbinder R|date=August 26, August 2021|title=Colchicine for acute gout|journal=The Cochrane Database of Systematic Reviews|volume=2021|issue=8|pages=CD006190|doi=10.1002/14651858.CD006190.pub3|pmid=34438469|pmc=8407279}}</ref><ref name=":2" /><ref name=":3" /> Colchicine may interact with other commonly prescribed drugs, such as [[atorvastatin]] and [[erythromycin]], among others.<ref name="FDA Warning" />

[[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/>

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, 1990-20131990–2013: 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 Pacific Islanders and the [[Māori people|MāoriPolynesians]], 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>

[[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"/>]]

Gout has been known since antiquity. Historically, itwits washave 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 byand 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:

{{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_2Etymology 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>}}

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=978-05203394770-520-33947-7|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|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>}}

A number of new medications are under study for treating gout, including [[anakinra]], [[canakinumab]], and [[rilonacept]].<ref>{{cite journal |url=http://www.musculoskeletalnetwork.com/gout/content/article/1145622/1533314 |title=New therapeutic options for gout here and on the horizon |journal=Journal of Musculoskeletal Medicine |date=8 March 2010 |author1=Abeles, A. M. |author2=Pillinger, M. H. |url-status=dead |archive-url=https://web.archive.org/web/20100520024113/http://www.musculoskeletalnetwork.com/gout/content/article/1145622/1533314 |archive-date=20 May 2010 |access-date=23 April 2010 }}</ref> Canakinumab may result in better outcomes than a low dose of a glucocorticoid, but costs five thousand times more.<ref>{{cite journal|last1=Sivera|first1=F|last2=Wechalekar|first2=MD|last3=Andrés|first3=M|last4=Buchbinder|first4=R|last5=Carmona|first5=L|title=Interleukin-1 inhibitors for acute gout|journal=The Cochrane Database of Systematic Reviews|date=1 September 2014|volume=92014|issue=9|pages=CD009993|pmid=25177840|doi=10.1002/14651858.CD009993.pub2|pmc=10891421}}</ref> A [[Recombinant DNA|recombinant]] [[uricase]] enzyme ([[rasburicase]]) is available but its use is limited, as it triggers an [[immune]] response. Less [[antigenic]] versions are in development.<ref name=Egg2007/>