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''[[Clinical treatment guidelines|'''Clinical treatment guidelines''']] for management of Gout are by American College of [[Rheumatology]].<ref name="pmid32390306">{{cite journal| author=FitzGerald JD, Dalbeth N, Mikuls T, Brignardello-Petersen R, Guyatt G, Abeles AM | display-authors=etal| title=2020 American College of Rheumatology Guideline for the Management of Gout. | journal=Arthritis Rheumatol | year= 2020 | volume= 72 | issue= 6 | pages= 879-895 | pmid=32390306 | doi=10.1002/art.41247 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32390306  }} </ref><ref name="pmid32391934">{{cite journal| author=FitzGerald JD, Dalbeth N, Mikuls T, Brignardello-Petersen R, Guyatt G, Abeles AM | display-authors=etal| title=2020 American College of Rheumatology Guideline for the Management of Gout. | journal=Arthritis Care Res (Hoboken) | year= 2020 | volume= 72 | issue= 6 | pages= 744-760 | pmid=32391934 | doi=10.1002/acr.24180 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32391934  }} </ref> Goal of Gout therapy is to''
*Treat Gout flares.
* Provide maintenance therapy to prevent flares and, dietary and life style modifications.
== Overview ==
== Overview ==
*The medical therapy of Gout differs for acute flares and maintenance therapy for prevention of acute flares.
*The main stay of therapy is pain managament, ideally achieved with [[NSAIDS]]<ref name="pmid25225849">{{cite journal| author=van Durme CM, Wechalekar MD, Buchbinder R, Schlesinger N, van der Heijde D, Landewé RB| title=Non-steroidal anti-inflammatory drugs for acute gout. | journal=Cochrane Database Syst Rev | year= 2014 | volume=  | issue= 9 | pages= CD010120 | pmid=25225849 | doi=10.1002/14651858.CD010120.pub2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25225849  }} </ref> and oral or intra articular [[Glucocorticoids]].<ref name="pmid23633379">{{cite journal| author=Wechalekar MD, Vinik O, Schlesinger N, Buchbinder R| title=Intra-articular glucocorticoids for acute gout. | journal=Cochrane Database Syst Rev | year= 2013 | volume=  | issue= 4 | pages= CD009920 | pmid=23633379 | doi=10.1002/14651858.CD009920.pub2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23633379  }} </ref>
*[[Colchicine]] is usually used for maintainance therapy, however; within 24 hours of symptom onset, low dose colchicine can be used.<ref name="pmid29272515">{{cite journal| author=Slobodnick A, Shah B, Krasnokutsky S, Pillinger MH| title=Update on colchicine, 2017. | journal=Rheumatology (Oxford) | year= 2018 | volume= 57 | issue= suppl_1 | pages= i4-i11 | pmid=29272515 | doi=10.1093/rheumatology/kex453 | pmc=5850858 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29272515  }} </ref>
*For treatment resistant Gout, [[lesinurad]] with [[Xanthine oxidase]] inhibitors as a combination is used. <ref name="pmidPMID: 28434436">{{cite journal| author=Engel B, Just J, Bleckwenn M, Weckbecker K| title=Treatment Options for Gout. | journal=Dtsch Arztebl Int | year= 2017 | volume= 114 | issue= 13 | pages= 215-222 | pmid=PMID: 28434436 | doi=10.3238/arztebl.2017.0215 | pmc=5624445 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28434436  }} </ref>
*Other, less standard methods of treatment include the use of topical creams, ice packing<ref name="pmid11838852">{{cite journal| author=Schlesinger N, Detry MA, Holland BK, Baker DG, Beutler AM, Rull M | display-authors=etal| title=Local ice therapy during bouts of acute gouty arthritis. | journal=J Rheumatol | year= 2002 | volume= 29 | issue= 2 | pages= 331-4 | pmid=11838852 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11838852  }} </ref> and increasing mobility for reducing pain.


== Medical Therapy ==
== Medical Therapy ==
Following medications are used in the management of gout.
===Treatment of acute flares===
Access the intensity of the attack based on severity of pain and the number of joints involved.
* For a mild/moderate gout severity (6 of 10 on a 0 –10 pain visual analog scale) involving 1 or a few small joints or 1 or 2 large joints, initiating monotherapy with options being oral nonsteroidal anti-inflammatory drugs (NSAIDs), systemic corticosteroids, or oral colchicine.
* [[NSAIDs]]: They should be initiated at their full dosing at [[Food and Drug Administration]] approved anti-inflammatory/ analgesic doses. It should not be tapered with symptomatic improvement; instead full dose should be administered till complete resolution.
* [[Colchicine]]: Acute gout can be treated with a loading dose of 1.2 mg, followed by 0.6 mg 1 hour later. This can then be followed by a gout attack prophylaxis dosing beginning 12 hours or later and continued till the attack resolves. If the patient was already on prophylactic colchicine and received acute gout regimen in the last 2 weeks, then consider other therapeutic options i.e. corticosteroid, NSAID.
* [[corticosteroids]]: Corticosteroids can be given as an initial monotherapy. [[Prednisolone]] or [[prednisone]] at a starting dosage of at least 0.5 mg/kg per day for 5–10 days and then discontinued (evidence A). Alternatively, a full dose for 2–5 days can be given, followed by tapering for 7–10 days, and then discontinued. While oral corticosteroid is the preferred route, intra-articular route can be considered for acute gout of 1 or 2 large joints.
* For a severe acute gout attack (7 of 10 on a 0 –10 pain visual analog scale) and in patients with an acute polyarthritis or involvement of more than 1 large joint, combination therapy should be considered. Recommendation is to initiate simultaneous use of full doses (or, where appropriate, a full dose of 1 agent and prophylaxis dosing of the other) of 2 of the pharmacologic modalities as recommended above.
* If the patient was previously on an established pharmacologic uric acid lowering therapy (ULT), it is recommended to be continued without interruption during an acute attack , i.e. do not stop ULT therapy during an acute flare.&nbsp;&nbsp;


=== Acute attacks ===
The first line of treatment should be pain relief. Once the diagnosis has been confirmed, the drugs of choice are [[indomethacin]], other [[Non-steroidal anti-inflammatory drug|nonsteroidal anti-inflammatory drugs]] ([[Non-steroidal anti-inflammatory drug|NSAIDs]]), oral [[glucocorticoids]], 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. [[Non-steroidal anti-inflammatory drug|NSAIDs]] are the preferred form of analgesia for patients with gout.
==== Local ice ====
Ice packs, applied for 30 minutes 4 times per day, can help when used as in conjunction with pharmacological treatment.<ref name="pmid11838852" /><ref name="pmid323903062">{{cite journal| author=FitzGerald JD, Dalbeth N, Mikuls T, Brignardello-Petersen R, Guyatt G, Abeles AM | display-authors=etal| title=2020 American College of Rheumatology Guideline for the Management of Gout. | journal=Arthritis Rheumatol | year= 2020 | volume= 72 | issue= 6 | pages= 879-895 | pmid=32390306 | doi=10.1002/art.41247 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32390306  }}</ref>


A [[randomized controlled trial]] found similar benefit from [[Non-steroidal anti-inflammatory drug|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 [[Non-steroidal anti-inflammatory drug|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.
====Medications====
{| class="wikitable" align="left"
|+Comparison of NSAID and steroids for acute gout
! rowspan="2" |&nbsp;!! rowspan="2" | Patients!! colspan="2" |Interventions !! rowspan="2" |Results
|-
![[Glucocorticoid|Steroid]]||[[Non-steroidal anti-inflammatory agent|NSAID]]
|-
| Janssens et al 2008<ref name="pmid18514729" />
||120 total patients with [[uric acid]] crystals on [[arthrocentesis]]
||[[Prednisolone]] 35 mg once daily for 5 days
||[[Naproxen]] 500 mg twice daily for 5 days
||NSAID trended better (88% versus 80% response; p=0.3)<br />No differences in rates of [[drug toxicity]].
|-
| Man et al 2007<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>
||90 total patients with clinical diagnosis of gout†
||Initially [[prednisolone]] 30 mg<br />Followed by prednisolone 30 mg daily for 5 days and as needed [[acetaminophen]]
||Initially [[diclofenac]] 75 mg with [[indomethacin]] 50 mg<br />Followed by indomethacin 50 mg every 8 hrs for 2 days then 25 mg every 8 hrs for 3 days and as needed [[acetaminophen]].
||Steroids faster reduction in pain.<br />Steroids used more [[acetaminophen]].<br />More adverse effects from [[indomethacin]].<br />
[[Indomethacin]] trended to more relapses at 2 weeks (11% vs 17%).
|-
| colspan="5" |Notes:<br />
† Clinical diagnosis of gout was "pain and warmth in a joint, and presented within 3 days of the onset of pain and also had 1 or more of the following: metatarsal-phalangeal joint involvement; knee or ankle joint involvement and aspirate containing crystals; or typical gouty arthritis, with either gouty tophi present or previous joint aspiration confirming the diagnosis of gout." Seven patients allowed arthrocentesis and all were positive for gout.
|}


Before medical help is available, some over-the-counter medications can provide temporary relief from pain and swelling. [[Non-steroidal anti-inflammatory drug|NSAIDs]] such as [[ibuprofen]] can reduce the pain and inflammation slightly, although [[aspirin]] should not be used as it can worsen the condition. [[Preparation H]] [[hemorrhoid]]al [[ointment]] can be applied to the swollen skin to reduce the swelling temporarily. Professional medical care is needed for long-term management of gout.
=====Glucocorticoids=====
Oral glucocorticoids are always preferred over parental glucocorticoids due to benefit/risk profile. [[Glucocorticoids]] are proven to be equally effective as NSAIDs <ref name="pmid17276548" /> and associated with fewer adverse side effects<ref name="pmid172765482">{{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=Ann Emerg Med | year= 2007 | volume= 49 | issue= 5 | pages= 670-7 | pmid=17276548 | doi=10.1016/j.annemergmed.2006.11.014 | pmc=7115288 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17276548  }}  [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=18063735 Review in: Evid Based Med. 2007 Dec;12(6):175]</ref><ref name="pmid18425920">{{cite journal| author=Janssens HJ, Lucassen PL, Van de Laar FA, Janssen M, Van de Lisdonk EH| title=Systemic corticosteroids for acute gout. | journal=Cochrane Database Syst Rev | year= 2008 | volume=  | issue= 2 | pages= CD005521 | pmid=18425920 | doi=10.1002/14651858.CD005521.pub2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18425920  }}</ref> 


Ice may be applied for 20–30 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>  Keeping the affected area elevated above the level of the heart also may help.
Oral glucocorticoids include  


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]].
* Prednisone - 40mg for 4-5 days and then gradually tapered off over 7-10 days<ref name="pmid18842190">{{cite journal| author=Prasad S, Ewigman B| title=Acute gout: oral steroids work as well as NSAIDs. | journal=J Fam Pract | year= 2008 | volume= 57 | issue= 10 | pages= 655-7 | pmid=18842190 | doi= | pmc=3183840 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18842190  }}</ref><ref name="pmid2196674">{{cite journal| author=Groff GD, Franck WA, Raddatz DA| title=Systemic steroid therapy for acute gout: a clinical trial and review of the literature. | journal=Semin Arthritis Rheum | year= 1990 | volume= 19 | issue= 6 | pages= 329-36 | pmid=2196674 | doi=10.1016/0049-0172(90)90070-v | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2196674  }}</ref>


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. This can be particularly unfortunate if the sufferer is searching for work as the aggravation can interefere with mobility. 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 6-8 hours.  
Intra articular Glucocorticoids: [[Septic arthritis]] should be ruled out before initiating  intra articluar glucocorticoids.


Another possibility is use of [[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.<sup>35</sup>
* Triamcinolone acetate - dosage varies depending on the size of joint. Usually used in monoartiular or oligoarticular(1 or 2-3 joints) involvement.  
** 40 - 60 mg(large joints), 30 mg(medium joints), 10 mg(small joints) 


=== Chronic joint changes ===
Parental glucocorticoids include:
For ''extreme'' cases of gout, surgery may be necessary to remove large tophi and correct joint deformity.


== Preventive Medical Therapy ==
* [[Intramuscular]] - [[Triamcinolone]] acetate 40 - 60mg<ref name="pmid8441139">{{cite journal| author=Alloway JA, Moriarty MJ, Hoogland YT, Nashel DJ| title=Comparison of triamcinolone acetonide with indomethacin in the treatment of acute gouty arthritis. | journal=J Rheumatol | year= 1993 | volume= 20 | issue= 1 | pages= 111-3 | pmid=8441139 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8441139  }}</ref>, [[Betamethasone]] 7mg<ref name="pmid24472084">{{cite journal| author=Zhang YK, Yang H, Zhang JY, Song LJ, Fan YC| title=Comparison of intramuscular compound betamethasone and oral diclofenac sodium in the treatment of acute attacks of gout. | journal=Int J Clin Pract | year= 2014 | volume= 68 | issue= 5 | pages= 633-8 | pmid=24472084 | doi=10.1111/ijcp.12359 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24472084  }}</ref>
* [[Intravenous]] - [[Methylprednisolone]] 20mg for 4 - 5 days and then swirch to maintainance dose.


===Medications===
===== Non-steroidal anti-inflammatory agents =====
[[NSAIDs]] have proven efficacy than placebo according to [[Randomized controlled trial]]<ref>García de la Torre, Ignacio. (1987) Estudio doble-ciego paralelo, comparativo con tenoxicam vs placebo en artritis gotosa aguda (A comparative, double-blind, parallel study with tenoxicam vs placebo in acute gouty arthritis). ''Invet Med Int '14:'''92–7 [[http://bases.bireme.br/cgi-bin/wxislind.exe/iah/online/?IsisScript=iah/iah.xis&src=google&base=LILACS&lang=p&nextAction=lnk&exprSearch=62234&indexSearch=ID Abstract in Spanish]]</ref>  but proven to be equally efficacious( in particular, indomethacin<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 | year= 2008 | volume= 371 | issue= 9627 | pages= 1854-60 | pmid=18514729 | doi=10.1016/S0140-6736(08)60799-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18514729  }}  [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=18800446 Review in: J Fam Pract. 2008 Sep;57(9):576]  [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=18842190 Review in: J Fam Pract. 2008 Oct;57(10):655-7] </ref>,) compared to  [[Glucocorticoids]] <ref name="pmid17276548" /> . Can be given within 48hrs in patients age less than 60 with no [[Comorbidity]] and used as an alternative to [[glucocorticoids]]. Current FDA approved NSAIDS<ref name="pmidhttps://doi.org/10.1007/s40674-015-0013-8">{{cite journal| author=Schmoldt A, Benthe HF, Haberland G| title=Digitoxin metabolism by rat liver microsomes. | journal=Biochem Pharmacol | year= 1975 | volume= 24 | issue= 17 | pages= 1639-41 | pmid=https://doi.org/10.1007/s40674-015-0013-8 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10  }}</ref> include:


* [[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]
* [[Indomethacin]] - 50 mg PO q8h
* [[naproxen]] - 500 mg PO q12h
* [[Sulindac]] - 200 mg PO q12hr.  


* [[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; it is currently in [[Clinical trials#Phase III| Phase III trials]].<ref>{{cite journal | author = Becker M, Schumacher H, Wortmann R, MacDonald P, Eustace D, Palo W, Streit J, Joseph-Ridge N | title = Febuxostat compared with allopurinol in patients with hyperuricemia and gout | journal = N Engl J Med | volume = 353 | issue = 23 | pages = 2450&ndash;61 | year = 2005 | id = PMID 16339094}}</ref>
[[COX-2 selective inhibitor]]<nowiki/>s are proven to have similar benefits as [[NSAIDs]] with an added advantage of protection from [[NSAIDs]] induced [[Gastritis]]<ref name="pmid12077033">{{cite journal| author=Schumacher HR, Boice JA, Daikh DI, Mukhopadhyay S, Malmstrom K, Ng J | display-authors=etal| title=Randomised double blind trial of etoricoxib and indometacin in treatment of acute gouty arthritis. | journal=BMJ | year= 2002 | volume= 324 | issue= 7352 | pages= 1488-92 | pmid=12077033 | doi=10.1136/bmj.324.7352.1488 | pmc=116444 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12077033  }}</ref> <ref name="pmid12411331">{{cite journal| author=Fam AG| title=Treating acute gouty arthritis with selective COX 2 inhibitors. | journal=BMJ | year= 2002 | volume= 325 | issue= 7371 | pages= 980-1 | pmid=12411331 | doi=10.1136/bmj.325.7371.980 | pmc=1124536 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12411331  }}</ref> but yet to be approved by FDA.


* [[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>{{cite journal | author = Bardin T | title = Fenofibrate and losartan | journal = Ann Rheum Dis | volume = 62 | issue = 6 | pages = 497&ndash;8 | year = 2003 | id = PMID 12759281 | url=http://ard.bmjjournals.com/cgi/content/full/62/6/497}}</ref>
===== Colchicine =====


* 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.
[[Colchicine]] is usually used as maintainance theray to prevent flares; can be used as an alternate to [[NSAIDs]] and glucocorticoids in acute gout attack but effective when started within 24 hours<ref name="pmid17054279">{{cite journal |author=Schlesinger N, Schumacher R, Catton M, Maxwell L |title=Colchicine for acute gout |journal=Cochrane Database Syst Rev |volume= |issue=4 |pages=CD006190 |year=2006 |pmid=17054279 |doi=10.1002/14651858.CD006190 |url=http://dx.doi.org/10.1002/14651858.CD006190 |issn=}}</ref><ref name="pmid3314832">{{cite journal |author=Ahern MJ, Reid C, Gordon TP, McCredie M, Brooks PM, Jones M |title=Does colchicine work? The results of the first controlled study in acute gout |journal=Aust N Z J Med |volume=17 |issue=3 |pages=301–4 |year=1987 |month=June |pmid=3314832 |doi=10.1111/j.1445-5994.1987.tb01232.x |url= |issn=}} [http://www.medicine.ox.ac.uk/bandolier/booth/gout/colchrct.html Summary at Bandolier]</ref>.  


* It is suspected that in many cases gout may be secondary to untreated [[sleep apnea]], when oxygen-starved cells break down and release purines as a by-product. Treatment for apnea can be effective in lessening incidence of acute gout attacks.<ref>{{cite journal | author = Abrams B | title = Gout is an indicator of sleep apnea | journal = Sleep | volume = 28 | issue = 2 | pages = 275 | year = 2005 | id = PMID 16171252}}</ref>
* Dosage - 1.2 mg followed by 0.6 mg in 1 hour followed by consequent dosages depending upon the response.<ref name="pmid20131255">{{cite journal| author=Terkeltaub RA, Furst DE, Bennett K, Kook KA, Crockett RS, Davis MW| title=High versus low dosing of oral colchicine for early acute gout flare: Twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study. | journal=Arthritis Rheum | year= 2010 | volume= 62 | issue= 4 | pages= 1060-8 | pmid=20131255
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=20131255 | doi=10.1002/art.27327 }} </ref>
**0.6 mg q8h followed by tapering doses
**0.5 mg q12h to q6h<ref>CKS (2007) Gout - Management (Topic Review). Clinical Knowledge Summaries. http://cks.library.nhs.uk/gout/management [Accessed: Date]</ref>


* A study in 2004 suggests that animal flesh sources of purine, such as beef and seafood, greatly increase the risk of developing gout. However, high-purine vegetable sources 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="Choi et al 2004">{{cite journal | author = Choi H, Atkinson K, Karlson E, 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&ndash;103 | year = 2004 | id = PMID 15014182 | url=http://www.nutritionaustralia.org/News_in_Nutrition/Journal_Articles/purine%20rich%20foods.pdf | format=PDF}}</ref>
To avoid [[drug toxicity]], lower doses of colchicine (0.6 per day) have been used in combination with [[glucocorticoid]]s.<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 |month=February |pmid=11838852 |doi= |url=http://www.jrheum.com/subscribers/02/02/331.html |issn=}}</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]
=== Gout prevention with Urate lowering therapy===


*[[Sodium bicarbonate]] (baking soda) is an old 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.
Can be further divided into ''non - pharmacological( dietary and life style modifications)'' and ''pharmacological([[xanthine oxidase]] inhibitors and [[Uricosuric]] drugs).''


*Research from the University of British Columbia suggests long-term coffee consumption is associated with a lower risk of gout.<ref>{{cite journal | author = Hyon K. Choi, Walter Willett, Gary Curhan | title =  
===== ''Non - Pharmacological urate lowering therapy'' =====
Coffee consumption and risk of incident gout in men: A prospective study | journal = Arthritis & Rheumatism | volume = 56 | issue = 6 | pages = 2049&ndash;2055 | year = 2007 | id = PMID 17530645}}</ref> <ref>{{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 & Rheumatism | volume = 57 | issue = 5 | pages = 816&ndash;821 | year = 2007 | id = PMID 17530681 }}</ref>


===Diet===
====== life style modifications<ref name="pmid16820041">{{cite journal| author=Saag KG, Choi H| title=Epidemiology, risk factors, and lifestyle modifications for gout. | journal=Arthritis Res Ther | year= 2006 | volume= 8 Suppl 1 | issue=  | pages= S2 | pmid=16820041 | doi=10.1186/ar1907 | pmc=3226107 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16820041  }}</ref> ======


''See Saag and Choi, 2006, an open-access review article, for detailed references and further information.''<ref>{{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=http://arthritis-research.com/content/8/S1/S2 }}</ref>
* weight reduction reduces serum uric acid levels<ref name="pmid10873964">{{cite journal| author=Dessein PH, Shipton EA, Stanwix AE, Joffe BI, Ramokgadi J| title=Beneficial effects of weight loss associated with moderate calorie/carbohydrate restriction, and increased proportional intake of protein and unsaturated fat on serum urate and lipoprotein levels in gout: a pilot study. | journal=Ann Rheum Dis | year= 2000 | volume= 59 | issue= 7 | pages= 539-43 | pmid=10873964 | doi=10.1136/ard.59.7.539 | pmc=1753185 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10873964  }}</ref>.
* Limiting alcohol intake and abstinence from alcohol in acute flares<ref name="pmid15641075">{{cite journal| author=Choi HK, Liu S, Curhan G| title=Intake of purine-rich foods, protein, and dairy products and relationship to serum levels of uric acid: the Third National Health and Nutrition Examination Survey. | journal=Arthritis Rheum | year= 2005 | volume= 52 | issue= 1 | pages= 283-9 | pmid=15641075 | doi=10.1002/art.20761 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15641075  }}</ref>.
*All general lifestyle changes( like smoking cessation, increased physical activity, limiting telivision watching, eating healthy, etc.) that play role in control of chronic diseases are found to be more beneficial in gout<ref name="pmid168200412">{{cite journal| author=Saag KG, Choi H| title=Epidemiology, risk factors, and lifestyle modifications for gout. | journal=Arthritis Res Ther | year= 2006 | volume= 8 Suppl 1 | issue= | pages= S2 | pmid=16820041 | doi=10.1186/ar1907 | pmc=3226107 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16820041  }}</ref>
*Prevention and optimal management of chronic diseases and metabolic syndromes, cardiovascular events<ref name="pmid16871533">{{cite journal| author=Krishnan E, Baker JF, Furst DE, Schumacher HR| title=Gout and the risk of acute myocardial infarction. | journal=Arthritis Rheum | year= 2006 | volume= 54 | issue= 8 | pages= 2688-96 | pmid=16871533 | doi=10.1002/art.22014 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16871533  }}</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).
====== Dietary changes ======


====Reduce intake of purines====
* Decreased levels of meat and sea food consumption<ref name="pmid150141822">{{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 | year= 2004 | volume= 350 | issue= 11 | pages= 1093-103 | pmid=15014182 | doi=10.1056/NEJMoa035700 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15014182  }}</ref> <ref name="pmid226489332">{{cite journal| author=Zhang Y, Chen C, Choi H, Chaisson C, Hunter D, Niu J | display-authors=etal| title=Purine-rich foods intake and recurrent gout attacks. | journal=Ann Rheum Dis | year= 2012 | volume= 71 | issue= 9 | pages= 1448-53 | pmid=22648933 | doi=10.1136/annrheumdis-2011-201215 | pmc=3889483 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22648933  }}</ref>and increased intake of low fat or non fat containing dairy products<ref name="pmid(21285714).">{{cite journal| author=Singh JA, Reddy SG, Kundukulam J| title=Risk factors for gout and prevention: a systematic review of the literature. | journal=Curr Opin Rheumatol | year= 2011 | volume= 23 | issue= 2 | pages= 192-202 | pmid=(21285714). | doi=10.1097/BOR.0b013e3283438e13 | pmc=4104583 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21285714  }}</ref> decreases gout attacks, where as foods rich in purine should be limited to moderate amounts.<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 | year= 2004 | volume= 350 | issue= 11 | pages= 1093-103 | pmid=15014182 | doi=10.1056/NEJMoa035700 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15014182  }}</ref>
*Increased dietary consumption of cherries decreases gout attacks.<ref name="pmid23023794">{{cite journal| author=Gelber AC, Solomon DH| title=If life serves up a bowl of cherries, and gout attacks are "the pits": implications for therapy. | journal=Arthritis Rheum | year= 2012 | volume= 64 | issue= 12 | pages= 3827-30 | pmid=23023794 | doi=10.1002/art.34676 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23023794  }}</ref>
*Limiting high [[Fructose]] corn syrup intake reduces attacks of gout.<ref name="pmid32390306">{{cite journal| author=FitzGerald JD, Dalbeth N, Mikuls T, Brignardello-Petersen R, Guyatt G, Abeles AM | display-authors=etal| title=2020 American College of Rheumatology Guideline for the Management of Gout. | journal=Arthritis Rheumatol | year= 2020 | volume= 72 | issue= 6 | pages= 879-895 | pmid=32390306 | doi=10.1002/art.41247 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32390306  }}</ref>
*


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).
====Pharmacological urate lowering therapy (ULT)====


A diet low in purines reduces the serum level of uric acid. Notable sources of dietary purines include:
Pharmacological therapy to lower serum uric acid levels is indicated in any patient with established diagnosis of gout with
*beer (high in [[guanosine]]


'''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.
* Prior gout attacks (2 or more per year) and current [[Hyperuricemia]].
* Tophus or tophi by clinical exam or imaging study.
* CKD stage 2–5 or end-stage renal disease, which by itself, is an appropriate indication for pharmacologic ULT.
* Past [[urolithiasis]].


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.
These include:


Some '''medical drugs''' are purine-based.  Notable among these are the purine-analog [[antimetabolite]] drugs, sometimes used as [[chemotherapy]] agents.
[[Xanthine oxidase]] ''inhibitors:''


====Increase output of uric acid====
*[[Allopurinol]] -  start with dosage of 100 mg/day can be escalated at the rate of 100 mg/2 - 5 weeks, maximum recommended dosage is 800 mg and should be continued indefinitely, once the target serum uric acid levels are achieved.<ref name="pmid23024028">{{cite journal| author=Khanna D, Fitzgerald JD, Khanna PP, Bae S, Singh MK, Neogi T | display-authors=etal| title=2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. | journal=Arthritis Care Res (Hoboken) | year= 2012 | volume= 64 | issue= 10 | pages= 1431-46 | pmid=23024028 | doi=10.1002/acr.21772 | pmc=3683400 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23024028  }}</ref>
** A nurse-led protocol, "allopurinol, started at 100 mg once per day and titrated upwards in 100 mg increments every 3–4 weeks according to serum urate concentrations, to a maximum of 900 mg once per day" for a goal of uric acid level < 6 mg/dl is effective<ref name="pmid30343856">{{cite journal| author=Doherty M, Jenkins W, Richardson H, Sarmanova A, Abhishek A, Ashton D | display-authors=etal| title=Efficacy and cost-effectiveness of nurse-led care involving education and engagement of patients and a treat-to-target urate-lowering strategy versus usual care for gout: a randomised controlled trial. | journal=Lancet | year= 2018 | volume= 392 | issue= 10156 | pages= 1403-1412 | pmid=30343856 | doi=10.1016/S0140-6736(18)32158-5 | pmc=6196879 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30343856  }} </ref>
**In patients with  [[CKD]] (stage 4 and 5), dosage started with 50 mg/ day and can be increased at the rate of 50 mg/ 2- 5 weeks.<ref name="pmid21279998">{{cite journal| author=Stamp LK, O'Donnell JL, Zhang M, James J, Frampton C, Barclay ML | display-authors=etal| title=Using allopurinol above the dose based on creatinine clearance is effective and safe in patients with chronic gout, including those with renal impairment. | journal=Arthritis Rheum | year= 2011 | volume= 63 | issue= 2 | pages= 412-21 | pmid=21279998 | doi=10.1002/art.30119 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21279998  }}</ref>
*[[Febuxostat]] - Start with an oral dosage of 40 mg/day<ref name="pmid21330679">{{cite journal| author=Gray CL, Walters-Smith NE| title=Febuxostat for treatment of chronic gout. | journal=Am J Health Syst Pharm | year= 2011 | volume= 68 | issue= 5 | pages= 389-98 | pmid=21330679 | doi=10.2146/ajhp100394 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21330679  }}</ref> and can be increased to a maximum of 80 mg/day.<ref name="pmid16339094">{{cite journal| author=Becker MA, Schumacher HR, Wortmann RL, MacDonald PA, Eustace D, Palo WA | display-authors=etal| title=Febuxostat compared with allopurinol in patients with hyperuricemia and gout. | journal=N Engl J Med | year= 2005 | volume= 353 | issue= 23 | pages= 2450-61 | pmid=16339094 | doi=10.1056/NEJMoa050373 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16339094  }}</ref><ref name="pmid20370912">{{cite journal| author=Becker MA, Schumacher HR, Espinoza LR, Wells AF, MacDonald P, Lloyd E | display-authors=etal| title=The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial. | journal=Arthritis Res Ther | year= 2010 | volume= 12 | issue= 2 | pages= R63 | pmid=20370912 | doi=10.1186/ar2978 | pmc=2888216 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20370912  }}</ref>


Ingestion of 500 mg of [[Vitamin C]] per day has been shown to bring about a 0.5 mg/dl decrease in serum uric acid through increased excretion. Some Gout sufferers have recently found that taking up to 1,000 mg of Vitamin C, combined with a small dosage (approx. 10-15 mg./day) of [[Lithium]] have had very beneficial effects on their uric acid levels.
Allopurinol is superior to Febuxostat in that all cause mortality rate is higher with Febuxostat<ref name="pmid29527974">{{cite journal| author=White WB, Saag KG, Becker MA, Borer JS, Gorelick PB, Whelton A | display-authors=etal| title=Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout. | journal=N Engl J Med | year= 2018 | volume= 378 | issue= 13 | pages= 1200-1210 | pmid=29527974 | doi=10.1056/NEJMoa1710895 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29527974  }}</ref> and hence people who show little or no response and severe [[Adverse effect (medicine)]] to Allopurinol should not be prescribed Febuxostat.<ref name="pmid203709122">{{cite journal| author=Becker MA, Schumacher HR, Espinoza LR, Wells AF, MacDonald P, Lloyd E | display-authors=etal| title=The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial. | journal=Arthritis Res Ther | year= 2010 | volume= 12 | issue= 2 | pages= R63 | pmid=20370912 | doi=10.1186/ar2978 | pmc=2888216 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20370912  }}</ref>


Vitamin C, taken in high doses, can help decrease blood uric acid levels, but should not be taken without a doctor's supervision. Note that there is a small subset of people with gout who will actually get worse with high levels of vitamin C. Also, a single high dose can free up too much uric acid and cause kidney stones. (University of Maryland Medical Center for Integrative Medicine).
<ref name="pmid163390942">{{cite journal| author=Becker MA, Schumacher HR, Wortmann RL, MacDonald PA, Eustace D, Palo WA | display-authors=etal| title=Febuxostat compared with allopurinol in patients with hyperuricemia and gout. | journal=N Engl J Med | year= 2005 | volume= 353 | issue= 23 | pages= 2450-61 | pmid=16339094 | doi=10.1056/NEJMoa050373 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16339094  }}</ref> <ref name="pmid21846852,2">{{cite journal| author=Sundy JS, Baraf HS, Yood RA, Edwards NL, Gutierrez-Urena SR, Treadwell EL | display-authors=etal| title=Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials. | journal=JAMA | year= 2011 | volume= 306 | issue= 7 | pages= 711-20 | pmid=21846852, | doi=10.1001/jama.2011.1169 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21846852  }}</ref>


====Other approaches====
[[Uricosuric]] ''drugs:'' 


Additional dietary recommendations can be made which reduce gout indirectly, by reducing gout risk factors such as [[obesity]], [[hypertension]], [[cardiovascular disease]], [[diabetes]], and [[metabolic syndrome]].
* [[Probenecid]]
* [[Sulfinpyrazone (patient information)]]  
*[[benzbromarone]]
*[[Lesinurad]]


'''The following suggestions do not meet with universal approval among medical practitioners.'''
Probenecid is the drug of choice among uricosuric drugs. It is used as second line therapy because of [[Creatinine clearance]] of 50 ml/minute; which warrants monitoring [[serum]] [[Uric acid]] levels. Probenecid cannot be used as first line [[Monotherapy]] in case of [[Contraindication]] to at least one Xanthine oxidase inhibitor and when [[Creatinine clearance]] is below 50 ml/minute. 


Low [[purine]] diet:
mg/dL was beneficial.
* To lower uric acid:
** cherries were reported to reduce uric acid in a small study.<ref>{{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 |pmid=12771324 |doi=}}</ref><ref>{{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=}}</ref>
** [[celery]] extracts (celery or celery seed either in capsule form or as a tea) is believed by many to reduce uric acid levels (although these are also [[diuretic]]s). Celery extracts have been reported to act synergistically with anti-inflammatory drugs.<ref>{{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}}</ref>
** Cheese has been recommended as a low-purine food,<ref>{{cite journal |author=Harris MD, Siegel LB, Alloway JA |title=Gout and hyperuricemia |journal=American family physician |volume=59 |issue=4 |pages=925-34 |year=1999 |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.
*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 flare up. 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>{{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=}}</ref>
***sweetbreads, [[kidney]]s, [[liver]], [[brain]]s, or other offal meats.<ref>{{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>{{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 |pmid=7904493 |doi=}}</ref>
***sardines and anchovies <ref>{{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>{{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 |pmid=15014182 |doi=10.1056/NEJMoa035700}}</ref>
***[[alcohol]].<ref>{{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 |pmid=15094272 |doi=10.1016/S0140-6736(04)16000-5}}</ref> Some claim that this applies especially to beer, on the basis that brewer's yeasts are very rich in purine. Since most modern commercial beer contains only trace amounts of yeast, this claim requires further substantiation. 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>{{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 |pmid=17136085 |doi=10.1038/444566a}}</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>{{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 |pmid=15125693 |doi=10.1111/j.1742-7843.2004.pto940506.x}}</ref> However, withdrawal of urate-lowering therapy is associated with recurrence of acute gouty arthritis.<ref>{{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 |pmid=17013833 |doi=10.1002/art.22232}}</ref>
***meat extracts, consommés, and gravies<ref>{{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>


* To avoid [[dehydration]]:
==== Anti cytokines ====
** Drink plenty of liquids, especially [[water]], to dilute and assist excretion of urates;
The [[monoclonal antibody]] against [[interleukin]]-1 beta, [[canakinumab]]<ref name="pmid20533546">{{cite journal| author=So A, De Meulemeester M, Pikhlak A, Yücel AE, Richard D, Murphy V et al.| title=Canakinumab for the treatment of acute flares in difficult-to-treat gouty arthritis: Results of a multicenter, phase II, dose-ranging study. | journal=Arthritis Rheum | year= 2010 | volume= 62 | issue= 10 | pages= 3064-76 | pmid=20533546 | doi=10.1002/art.27600 | pmc= | url= }} </ref> and [[Anakinra]]<ref name="pmid24432362">{{cite journal| author=Ottaviani S, Moltó A, Ea HK, Neveu S, Gill G, Brunier L | display-authors=etal| title=Efficacy of anakinra in gouty arthritis: a retrospective study of 40 cases. | journal=Arthritis Res Ther | year= 2013 | volume= 15 | issue= 5 | pages= R123 | pmid=24432362 | doi=10.1186/ar4303 | pmc=3978950 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24432362  }}</ref> can be used in treatment resistant cases.
** Avoid [[diuretic]] foods or medicines like [[aspirin]](aspirin should be avoided from those suffering from gout, unless specified by a trained physician), [[vitamin C]], [[tea]] and alcohol.  The role of diuretics in triggering gout has been disputed.<ref>{{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 |pmid=16291814 |doi=10.1136/ard.2005.040360}}</ref>


* Moderate intake of purine-rich vegetables is not associated with increased gout.<!--
====Prophylaxis to prevent acute gout flares during initiation of uric acid lowering therapy====
  --><ref name="Choi et al 2004"/>
 
A new trial suggests benefit from colchicine over placebo during the first 6 months of allopurinol therapy<ref name="pmid37652661">{{cite journal| author=Stamp L, Horne A, Mihov B, Drake J, Haslett J, Chapman PT | display-authors=etal| title=Is colchicine prophylaxis required with start-low go-slow allopurinol dose escalation in gout? A non-inferiority randomised double-blind placebo-controlled trial. | journal=Ann Rheum Dis | year= 2023 | volume=  | issue=  | pages=  | pmid=37652661 | doi=10.1136/ard-2023-224731 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=37652661  }} </ref>.
 
* It is recommended that for all cases of gout, where urate lowering therapy is started, a prophylaxis for acute flares should be started as well, given that gout attacks are common in early ULT.<ref name="pmid163390943">{{cite journal| author=Becker MA, Schumacher HR, Wortmann RL, MacDonald PA, Eustace D, Palo WA | display-authors=etal| title=Febuxostat compared with allopurinol in patients with hyperuricemia and gout. | journal=N Engl J Med | year= 2005 | volume= 353 | issue= 23 | pages= 2450-61 | pmid=16339094 | doi=10.1056/NEJMoa050373 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16339094  }}</ref>
* The first-line for this purpose is oral [[Colchicine]] <ref name="pmid213531073">{{cite journal| author=Wortmann RL, Macdonald PA, Hunt B, Jackson RL| title=Effect of prophylaxis on gout flares after the initiation of urate-lowering therapy: analysis of data from three phase III trials. | journal=Clin Ther | year= 2010 | volume= 32 | issue= 14 | pages= 2386-97 | pmid=21353107 | doi=10.1016/j.clinthera.2011.01.008 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21353107  }}</ref>, or low-dose [[NSAIDs]]. A [[randomized controlled trial]] found that colchicine was more effective than steroids for this purpose<ref name="pmid28485997">{{cite journal| author=Yu J, Qiu Q, Liang L, Yang X, Xu H| title=Prophylaxis of acute flares when initiating febuxostat for chronic gouty arthritis in a real-world clinical setting. | journal=Mod Rheumatol | year= 2018 | volume= 28 | issue= 2 | pages= 339-344 | pmid=28485997 | doi=10.1080/14397595.2017.1318467 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28485997  }} </ref>.
* A low-dose of [[Colchicine]] as 0.5 mg or 0.6 mg taken orally once or twice a day is the recommendation, with dosing further adjusted downward for moderate to severe renal function impairment and potential drug–drug interactions.&nbsp;<ref name="pmid21480191">{{cite journal| author=Terkeltaub RA, Furst DE, Digiacinto JL, Kook KA, Davis MW| title=Novel evidence-based colchicine dose-reduction algorithm to predict and prevent colchicine toxicity in the presence of cytochrome P450 3A4/P-glycoprotein inhibitors. | journal=Arthritis Rheum | year= 2011 | volume= 63 | issue= 8 | pages= 2226-37 | pmid=21480191 | doi=10.1002/art.30389 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21480191  }}</ref>
* The duration of treatment should be greater of at least 6 months<ref name="pmid163390944">{{cite journal| author=Becker MA, Schumacher HR, Wortmann RL, MacDonald PA, Eustace D, Palo WA | display-authors=etal| title=Febuxostat compared with allopurinol in patients with hyperuricemia and gout. | journal=N Engl J Med | year= 2005 | volume= 353 | issue= 23 | pages= 2450-61 | pmid=16339094 | doi=10.1056/NEJMoa050373 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16339094  }}</ref>, 3 months after achieving target serum urate levels in patient with no tophi on physical exam, or 6 months after achieving desired urate levels appropriate for the patient with one of more tophi.&nbsp;
 
==== '''Management of chronic gout/chronic tophaceous gouty arthropathy:''' ====
Chronic gout can be managed by a combined approach of pharmacological and non pharmacological therapy.The goal is to attain a serum urate level less than 6 mg/dl. Maintaining serum urate levels as low as 5 mg/dl will improve the signs and symptoms of disease including palpable and visible tophi.&nbsp;This includes treatment options of [[Urate]] lowering therapy. Doses should be titrated by monitoring serum uric acid levels constantly until the target uric acid levels are achieved. Continued measurements for every 6 months should be obtained once the desired level is achieved. All of the following play a key role in maintaining desired serum uric acid levels.
 
* Patient education on the disease, its treatment options and their objectives, including the particular role of uric acid excess in gout and as the key long-term treatment target<ref name="pmid22679303.">{{cite journal| author=Rees F, Jenkins W, Doherty M| title=Patients with gout adhere to curative treatment if informed appropriately: proof-of-concept observational study. | journal=Ann Rheum Dis | year= 2013 | volume= 72 | issue= 6 | pages= 826-30 | pmid=22679303. | doi=10.1136/annrheumdis-2012-201676 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22679303  }}</ref>
 
* Dietary and lifestyle modification
* Careful review of patients medications and stopping those that elevate serum uric acid levels; for example, [[Thiazide diuretics]], [[Loop diuretic]], [[Niacin]], and [[Calcineurin inhibitor]].
* Evaluating secondary causes of [[Hyperuricemia]] for all gout patients
* A clinical evaluation of gout disease activity and its burden should be done for each patient by history and a thorough physical examination for symptoms of arthritis and signs such as tophi and acute and chronic synovitis.&nbsp;&nbsp;  <br />
 
<br />


== References ==
== References ==
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{{Reflist|2}}
 
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[[Category:Needs content]]
[[Category:Arthritis]]
[[Category:Rheumatology]]
[[Category:Disease]]

Latest revision as of 07:57, 10 September 2023

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Clinical treatment guidelines for management of Gout are by American College of Rheumatology.[1][2] Goal of Gout therapy is to

  • Treat Gout flares.
  • Provide maintenance therapy to prevent flares and, dietary and life style modifications.

Overview

  • The medical therapy of Gout differs for acute flares and maintenance therapy for prevention of acute flares.
  • Colchicine is usually used for maintainance therapy, however; within 24 hours of symptom onset, low dose colchicine can be used.[5]
  • Other, less standard methods of treatment include the use of topical creams, ice packing[7] and increasing mobility for reducing pain.

Medical Therapy

Following medications are used in the management of gout.

Treatment of acute flares

Access the intensity of the attack based on severity of pain and the number of joints involved.

  • For a mild/moderate gout severity (6 of 10 on a 0 –10 pain visual analog scale) involving 1 or a few small joints or 1 or 2 large joints, initiating monotherapy with options being oral nonsteroidal anti-inflammatory drugs (NSAIDs), systemic corticosteroids, or oral colchicine.
  • NSAIDs: They should be initiated at their full dosing at Food and Drug Administration approved anti-inflammatory/ analgesic doses. It should not be tapered with symptomatic improvement; instead full dose should be administered till complete resolution.
  • Colchicine: Acute gout can be treated with a loading dose of 1.2 mg, followed by 0.6 mg 1 hour later. This can then be followed by a gout attack prophylaxis dosing beginning 12 hours or later and continued till the attack resolves. If the patient was already on prophylactic colchicine and received acute gout regimen in the last 2 weeks, then consider other therapeutic options i.e. corticosteroid, NSAID.
  • corticosteroids: Corticosteroids can be given as an initial monotherapy. Prednisolone or prednisone at a starting dosage of at least 0.5 mg/kg per day for 5–10 days and then discontinued (evidence A). Alternatively, a full dose for 2–5 days can be given, followed by tapering for 7–10 days, and then discontinued. While oral corticosteroid is the preferred route, intra-articular route can be considered for acute gout of 1 or 2 large joints.
  • For a severe acute gout attack (7 of 10 on a 0 –10 pain visual analog scale) and in patients with an acute polyarthritis or involvement of more than 1 large joint, combination therapy should be considered. Recommendation is to initiate simultaneous use of full doses (or, where appropriate, a full dose of 1 agent and prophylaxis dosing of the other) of 2 of the pharmacologic modalities as recommended above.
  • If the patient was previously on an established pharmacologic uric acid lowering therapy (ULT), it is recommended to be continued without interruption during an acute attack , i.e. do not stop ULT therapy during an acute flare.  


Local ice

Ice packs, applied for 30 minutes 4 times per day, can help when used as in conjunction with pharmacological treatment.[7][8]

Medications

Comparison of NSAID and steroids for acute gout
  Patients Interventions Results
Steroid NSAID
Janssens et al 2008[9] 120 total patients with uric acid crystals on arthrocentesis Prednisolone 35 mg once daily for 5 days Naproxen 500 mg twice daily for 5 days NSAID trended better (88% versus 80% response; p=0.3)
No differences in rates of drug toxicity.
Man et al 2007[10] 90 total patients with clinical diagnosis of gout† Initially prednisolone 30 mg
Followed by prednisolone 30 mg daily for 5 days and as needed acetaminophen 		Initially diclofenac 75 mg with indomethacin 50 mg
Followed by indomethacin 50 mg every 8 hrs for 2 days then 25 mg every 8 hrs for 3 days and as needed acetaminophen. 		Steroids faster reduction in pain.
Steroids used more acetaminophen.
More adverse effects from indomethacin.

Indomethacin trended to more relapses at 2 weeks (11% vs 17%).

Notes:

† Clinical diagnosis of gout was "pain and warmth in a joint, and presented within 3 days of the onset of pain and also had 1 or more of the following: metatarsal-phalangeal joint involvement; knee or ankle joint involvement and aspirate containing crystals; or typical gouty arthritis, with either gouty tophi present or previous joint aspiration confirming the diagnosis of gout." Seven patients allowed arthrocentesis and all were positive for gout.

Glucocorticoids

Oral glucocorticoids are always preferred over parental glucocorticoids due to benefit/risk profile. Glucocorticoids are proven to be equally effective as NSAIDs [10] and associated with fewer adverse side effects[11][12]

Oral glucocorticoids include

  • Prednisone - 40mg for 4-5 days and then gradually tapered off over 7-10 days[13][14]

Intra articular Glucocorticoids: Septic arthritis should be ruled out before initiating intra articluar glucocorticoids.

  • Triamcinolone acetate - dosage varies depending on the size of joint. Usually used in monoartiular or oligoarticular(1 or 2-3 joints) involvement.
    • 40 - 60 mg(large joints), 30 mg(medium joints), 10 mg(small joints)

Parental glucocorticoids include:

Non-steroidal anti-inflammatory agents

NSAIDs have proven efficacy than placebo according to Randomized controlled trial[17] but proven to be equally efficacious( in particular, indomethacin[9],) compared to Glucocorticoids [10] . Can be given within 48hrs in patients age less than 60 with no Comorbidity and used as an alternative to glucocorticoids. Current FDA approved NSAIDS[18] include:

COX-2 selective inhibitors are proven to have similar benefits as NSAIDs with an added advantage of protection from NSAIDs induced Gastritis[19] [20] but yet to be approved by FDA.

Colchicine

Colchicine is usually used as maintainance theray to prevent flares; can be used as an alternate to NSAIDs and glucocorticoids in acute gout attack but effective when started within 24 hours[21][22].

  • Dosage - 1.2 mg followed by 0.6 mg in 1 hour followed by consequent dosages depending upon the response.[23]
    • 0.6 mg q8h followed by tapering doses
    • 0.5 mg q12h to q6h[24]

To avoid drug toxicity, lower doses of colchicine (0.6 per day) have been used in combination with glucocorticoids.[7]

Gout prevention with Urate lowering therapy

Can be further divided into non - pharmacological( dietary and life style modifications) and pharmacological(xanthine oxidase inhibitors and Uricosuric drugs).

Non - Pharmacological urate lowering therapy
life style modifications[25]
  • weight reduction reduces serum uric acid levels[26].
  • Limiting alcohol intake and abstinence from alcohol in acute flares[27].
  • All general lifestyle changes( like smoking cessation, increased physical activity, limiting telivision watching, eating healthy, etc.) that play role in control of chronic diseases are found to be more beneficial in gout[28]
  • Prevention and optimal management of chronic diseases and metabolic syndromes, cardiovascular events[29]
Dietary changes
  • Decreased levels of meat and sea food consumption[30] [31]and increased intake of low fat or non fat containing dairy products[32] decreases gout attacks, where as foods rich in purine should be limited to moderate amounts.[33]
  • Increased dietary consumption of cherries decreases gout attacks.[34]
  • Limiting high Fructose corn syrup intake reduces attacks of gout.[1]

Pharmacological urate lowering therapy (ULT)

Pharmacological therapy to lower serum uric acid levels is indicated in any patient with established diagnosis of gout with

  • Prior gout attacks (2 or more per year) and current Hyperuricemia.
  • Tophus or tophi by clinical exam or imaging study.
  • CKD stage 2–5 or end-stage renal disease, which by itself, is an appropriate indication for pharmacologic ULT.
  • Past urolithiasis.

These include:

Xanthine oxidase inhibitors:

  • Allopurinol - start with dosage of 100 mg/day can be escalated at the rate of 100 mg/2 - 5 weeks, maximum recommended dosage is 800 mg and should be continued indefinitely, once the target serum uric acid levels are achieved.[35]
    • A nurse-led protocol, "allopurinol, started at 100 mg once per day and titrated upwards in 100 mg increments every 3–4 weeks according to serum urate concentrations, to a maximum of 900 mg once per day" for a goal of uric acid level < 6 mg/dl is effective[36]
    • In patients with CKD (stage 4 and 5), dosage started with 50 mg/ day and can be increased at the rate of 50 mg/ 2- 5 weeks.[37]
  • Febuxostat - Start with an oral dosage of 40 mg/day[38] and can be increased to a maximum of 80 mg/day.[39][40]

Allopurinol is superior to Febuxostat in that all cause mortality rate is higher with Febuxostat[41] and hence people who show little or no response and severe Adverse effect (medicine) to Allopurinol should not be prescribed Febuxostat.[42]

[43] [44]

Uricosuric drugs:

Probenecid is the drug of choice among uricosuric drugs. It is used as second line therapy because of Creatinine clearance of 50 ml/minute; which warrants monitoring serum Uric acid levels. Probenecid cannot be used as first line Monotherapy in case of Contraindication to at least one Xanthine oxidase inhibitor and when Creatinine clearance is below 50 ml/minute.

mg/dL was beneficial.

Anti cytokines

The monoclonal antibody against interleukin-1 beta, canakinumab[45] and Anakinra[46] can be used in treatment resistant cases.

Prophylaxis to prevent acute gout flares during initiation of uric acid lowering therapy

A new trial suggests benefit from colchicine over placebo during the first 6 months of allopurinol therapy[47].

  • It is recommended that for all cases of gout, where urate lowering therapy is started, a prophylaxis for acute flares should be started as well, given that gout attacks are common in early ULT.[48]
  • The first-line for this purpose is oral Colchicine [49], or low-dose NSAIDs. A randomized controlled trial found that colchicine was more effective than steroids for this purpose[50].
  • A low-dose of Colchicine as 0.5 mg or 0.6 mg taken orally once or twice a day is the recommendation, with dosing further adjusted downward for moderate to severe renal function impairment and potential drug–drug interactions. [51]
  • The duration of treatment should be greater of at least 6 months[52], 3 months after achieving target serum urate levels in patient with no tophi on physical exam, or 6 months after achieving desired urate levels appropriate for the patient with one of more tophi. 

Management of chronic gout/chronic tophaceous gouty arthropathy:

Chronic gout can be managed by a combined approach of pharmacological and non pharmacological therapy.The goal is to attain a serum urate level less than 6 mg/dl. Maintaining serum urate levels as low as 5 mg/dl will improve the signs and symptoms of disease including palpable and visible tophi. This includes treatment options of Urate lowering therapy. Doses should be titrated by monitoring serum uric acid levels constantly until the target uric acid levels are achieved. Continued measurements for every 6 months should be obtained once the desired level is achieved. All of the following play a key role in maintaining desired serum uric acid levels.

  • Patient education on the disease, its treatment options and their objectives, including the particular role of uric acid excess in gout and as the key long-term treatment target[53]
  • Dietary and lifestyle modification
  • Careful review of patients medications and stopping those that elevate serum uric acid levels; for example, Thiazide diuretics, Loop diuretic, Niacin, and Calcineurin inhibitor.
  • Evaluating secondary causes of Hyperuricemia for all gout patients
  • A clinical evaluation of gout disease activity and its burden should be done for each patient by history and a thorough physical examination for symptoms of arthritis and signs such as tophi and acute and chronic synovitis.  


References

  1. ↑ 1.0 1.1 FitzGerald JD, Dalbeth N, Mikuls T, Brignardello-Petersen R, Guyatt G, Abeles AM; et al. (2020). "2020 American College of Rheumatology Guideline for the Management of Gout". Arthritis Rheumatol. 72 (6): 879–895. doi:10.1002/art.41247. PMID 32390306 Check |pmid= value (help).
  2. ↑ FitzGerald JD, Dalbeth N, Mikuls T, Brignardello-Petersen R, Guyatt G, Abeles AM; et al. (2020). "2020 American College of Rheumatology Guideline for the Management of Gout". Arthritis Care Res (Hoboken). 72 (6): 744–760. doi:10.1002/acr.24180. PMID 32391934 Check |pmid= value (help).
  3. ↑ van Durme CM, Wechalekar MD, Buchbinder R, Schlesinger N, van der Heijde D, Landewé RB (2014). "Non-steroidal anti-inflammatory drugs for acute gout". Cochrane Database Syst Rev (9): CD010120. doi:10.1002/14651858.CD010120.pub2. PMID 25225849.
  4. ↑ Wechalekar MD, Vinik O, Schlesinger N, Buchbinder R (2013). "Intra-articular glucocorticoids for acute gout". Cochrane Database Syst Rev (4): CD009920. doi:10.1002/14651858.CD009920.pub2. PMID 23633379.
  5. ↑ Slobodnick A, Shah B, Krasnokutsky S, Pillinger MH (2018). "Update on colchicine, 2017". Rheumatology (Oxford). 57 (suppl_1): i4–i11. doi:10.1093/rheumatology/kex453. PMC 5850858. PMID 29272515.
  6. ↑ Engel B, Just J, Bleckwenn M, Weckbecker K (2017). "Treatment Options for Gout". Dtsch Arztebl Int. 114 (13): 215–222. doi:10.3238/arztebl.2017.0215. PMC 5624445. PMID 28434436 PMID: 28434436 Check |pmid= value (help).
  7. ↑ 7.0 7.1 7.2 Schlesinger N, Detry MA, Holland BK, Baker DG, Beutler AM, Rull M; et al. (2002). "Local ice therapy during bouts of acute gouty arthritis". J Rheumatol. 29 (2): 331–4. PMID 11838852.
  8. ↑ FitzGerald JD, Dalbeth N, Mikuls T, Brignardello-Petersen R, Guyatt G, Abeles AM; et al. (2020). "2020 American College of Rheumatology Guideline for the Management of Gout". Arthritis Rheumatol. 72 (6): 879–895. doi:10.1002/art.41247. PMID 32390306 Check |pmid= value (help).
  9. ↑ 9.0 9.1 Janssens HJ, Janssen M, van de Lisdonk EH, van Riel PL, van Weel C (2008). "Use of oral prednisolone or naproxen for the treatment of gout arthritis: a double-blind, randomised equivalence trial". Lancet. 371 (9627): 1854–60. doi:10.1016/S0140-6736(08)60799-0. PMID 18514729. Review in: J Fam Pract. 2008 Sep;57(9):576 Review in: J Fam Pract. 2008 Oct;57(10):655-7
  10. ↑ 10.0 10.1 10.2 Man CY, Cheung IT, Cameron PA, Rainer TH (2007). "Comparison of oral prednisolone/paracetamol and oral indomethacin/paracetamol combination therapy in the treatment of acute goutlike arthritis: a double-blind, randomized, controlled trial". Annals of emergency medicine. 49 (5): 670–7. doi:10.1016/j.annemergmed.2006.11.014. PMID 17276548.
  11. ↑ Man CY, Cheung IT, Cameron PA, Rainer TH (2007). "Comparison of oral prednisolone/paracetamol and oral indomethacin/paracetamol combination therapy in the treatment of acute goutlike arthritis: a double-blind, randomized, controlled trial". Ann Emerg Med. 49 (5): 670–7. doi:10.1016/j.annemergmed.2006.11.014. PMC 7115288 Check |pmc= value (help). PMID 17276548. Review in: Evid Based Med. 2007 Dec;12(6):175
  12. ↑ Janssens HJ, Lucassen PL, Van de Laar FA, Janssen M, Van de Lisdonk EH (2008). "Systemic corticosteroids for acute gout". Cochrane Database Syst Rev (2): CD005521. doi:10.1002/14651858.CD005521.pub2. PMID 18425920.
  13. ↑ Prasad S, Ewigman B (2008). "Acute gout: oral steroids work as well as NSAIDs". J Fam Pract. 57 (10): 655–7. PMC 3183840. PMID 18842190.
  14. ↑ Groff GD, Franck WA, Raddatz DA (1990). "Systemic steroid therapy for acute gout: a clinical trial and review of the literature". Semin Arthritis Rheum. 19 (6): 329–36. doi:10.1016/0049-0172(90)90070-v. PMID 2196674.
  15. ↑ Alloway JA, Moriarty MJ, Hoogland YT, Nashel DJ (1993). "Comparison of triamcinolone acetonide with indomethacin in the treatment of acute gouty arthritis". J Rheumatol. 20 (1): 111–3. PMID 8441139.
  16. ↑ Zhang YK, Yang H, Zhang JY, Song LJ, Fan YC (2014). "Comparison of intramuscular compound betamethasone and oral diclofenac sodium in the treatment of acute attacks of gout". Int J Clin Pract. 68 (5): 633–8. doi:10.1111/ijcp.12359. PMID 24472084.
  17. ↑ García de la Torre, Ignacio. (1987) Estudio doble-ciego paralelo, comparativo con tenoxicam vs placebo en artritis gotosa aguda (A comparative, double-blind, parallel study with tenoxicam vs placebo in acute gouty arthritis). Invet Med Int '14:'92–7 [Abstract in Spanish]
  18. ↑ Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMID https://doi.org/10.1007/s40674-015-0013-8 Check |pmid= value (help).
  19. ↑ Schumacher HR, Boice JA, Daikh DI, Mukhopadhyay S, Malmstrom K, Ng J; et al. (2002). "Randomised double blind trial of etoricoxib and indometacin in treatment of acute gouty arthritis". BMJ. 324 (7352): 1488–92. doi:10.1136/bmj.324.7352.1488. PMC 116444. PMID 12077033.
  20. ↑ Fam AG (2002). "Treating acute gouty arthritis with selective COX 2 inhibitors". BMJ. 325 (7371): 980–1. doi:10.1136/bmj.325.7371.980. PMC 1124536. PMID 12411331.
  21. ↑ Schlesinger N, Schumacher R, Catton M, Maxwell L (2006). "Colchicine for acute gout". Cochrane Database Syst Rev (4): CD006190. doi:10.1002/14651858.CD006190. PMID 17054279.
  22. ↑ Ahern MJ, Reid C, Gordon TP, McCredie M, Brooks PM, Jones M (1987). "Does colchicine work? The results of the first controlled study in acute gout". Aust N Z J Med. 17 (3): 301–4. doi:10.1111/j.1445-5994.1987.tb01232.x. PMID 3314832. Unknown parameter |month= ignored (help) Summary at Bandolier
  23. ↑ Terkeltaub RA, Furst DE, Bennett K, Kook KA, Crockett RS, Davis MW (2010). "High versus low dosing of oral colchicine for early acute gout flare: Twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study". Arthritis Rheum. 62 (4): 1060–8. doi:10.1002/art.27327. PMID 20131255.
  24. ↑ CKS (2007) Gout - Management (Topic Review). Clinical Knowledge Summaries. http://cks.library.nhs.uk/gout/management [Accessed: Date]
  25. ↑ Saag KG, Choi H (2006). "Epidemiology, risk factors, and lifestyle modifications for gout". Arthritis Res Ther. 8 Suppl 1: S2. doi:10.1186/ar1907. PMC 3226107. PMID 16820041.
  26. ↑ Dessein PH, Shipton EA, Stanwix AE, Joffe BI, Ramokgadi J (2000). "Beneficial effects of weight loss associated with moderate calorie/carbohydrate restriction, and increased proportional intake of protein and unsaturated fat on serum urate and lipoprotein levels in gout: a pilot study". Ann Rheum Dis. 59 (7): 539–43. doi:10.1136/ard.59.7.539. PMC 1753185. PMID 10873964.
  27. ↑ Choi HK, Liu S, Curhan G (2005). "Intake of purine-rich foods, protein, and dairy products and relationship to serum levels of uric acid: the Third National Health and Nutrition Examination Survey". Arthritis Rheum. 52 (1): 283–9. doi:10.1002/art.20761. PMID 15641075.
  28. ↑ Saag KG, Choi H (2006). "Epidemiology, risk factors, and lifestyle modifications for gout". Arthritis Res Ther. 8 Suppl 1: S2. doi:10.1186/ar1907. PMC 3226107. PMID 16820041.
  29. ↑ Krishnan E, Baker JF, Furst DE, Schumacher HR (2006). "Gout and the risk of acute myocardial infarction". Arthritis Rheum. 54 (8): 2688–96. doi:10.1002/art.22014. PMID 16871533.
  30. ↑ Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G (2004). "Purine-rich foods, dairy and protein intake, and the risk of gout in men". N Engl J Med. 350 (11): 1093–103. doi:10.1056/NEJMoa035700. PMID 15014182.
  31. ↑ Zhang Y, Chen C, Choi H, Chaisson C, Hunter D, Niu J; et al. (2012). "Purine-rich foods intake and recurrent gout attacks". Ann Rheum Dis. 71 (9): 1448–53. doi:10.1136/annrheumdis-2011-201215. PMC 3889483. PMID 22648933.
  32. ↑ Singh JA, Reddy SG, Kundukulam J (2011). "Risk factors for gout and prevention: a systematic review of the literature". Curr Opin Rheumatol. 23 (2): 192–202. doi:10.1097/BOR.0b013e3283438e13. PMC 4104583. PMID (21285714). Check |pmid= value (help).
  33. ↑ Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G (2004). "Purine-rich foods, dairy and protein intake, and the risk of gout in men". N Engl J Med. 350 (11): 1093–103. doi:10.1056/NEJMoa035700. PMID 15014182.
  34. ↑ Gelber AC, Solomon DH (2012). "If life serves up a bowl of cherries, and gout attacks are "the pits": implications for therapy". Arthritis Rheum. 64 (12): 3827–30. doi:10.1002/art.34676. PMID 23023794.
  35. ↑ Khanna D, Fitzgerald JD, Khanna PP, Bae S, Singh MK, Neogi T; et al. (2012). "2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia". Arthritis Care Res (Hoboken). 64 (10): 1431–46. doi:10.1002/acr.21772. PMC 3683400. PMID 23024028.
  36. ↑ Doherty M, Jenkins W, Richardson H, Sarmanova A, Abhishek A, Ashton D; et al. (2018). "Efficacy and cost-effectiveness of nurse-led care involving education and engagement of patients and a treat-to-target urate-lowering strategy versus usual care for gout: a randomised controlled trial". Lancet. 392 (10156): 1403–1412. doi:10.1016/S0140-6736(18)32158-5. PMC 6196879. PMID 30343856.
  37. ↑ Stamp LK, O'Donnell JL, Zhang M, James J, Frampton C, Barclay ML; et al. (2011). "Using allopurinol above the dose based on creatinine clearance is effective and safe in patients with chronic gout, including those with renal impairment". Arthritis Rheum. 63 (2): 412–21. doi:10.1002/art.30119. PMID 21279998.
  38. ↑ Gray CL, Walters-Smith NE (2011). "Febuxostat for treatment of chronic gout". Am J Health Syst Pharm. 68 (5): 389–98. doi:10.2146/ajhp100394. PMID 21330679.
  39. ↑ Becker MA, Schumacher HR, Wortmann RL, MacDonald PA, Eustace D, Palo WA; et al. (2005). "Febuxostat compared with allopurinol in patients with hyperuricemia and gout". N Engl J Med. 353 (23): 2450–61. doi:10.1056/NEJMoa050373. PMID 16339094.
  40. ↑ Becker MA, Schumacher HR, Espinoza LR, Wells AF, MacDonald P, Lloyd E; et al. (2010). "The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial". Arthritis Res Ther. 12 (2): R63. doi:10.1186/ar2978. PMC 2888216. PMID 20370912.
  41. ↑ White WB, Saag KG, Becker MA, Borer JS, Gorelick PB, Whelton A; et al. (2018). "Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout". N Engl J Med. 378 (13): 1200–1210. doi:10.1056/NEJMoa1710895. PMID 29527974.
  42. ↑ Becker MA, Schumacher HR, Espinoza LR, Wells AF, MacDonald P, Lloyd E; et al. (2010). "The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial". Arthritis Res Ther. 12 (2): R63. doi:10.1186/ar2978. PMC 2888216. PMID 20370912.
  43. ↑ Becker MA, Schumacher HR, Wortmann RL, MacDonald PA, Eustace D, Palo WA; et al. (2005). "Febuxostat compared with allopurinol in patients with hyperuricemia and gout". N Engl J Med. 353 (23): 2450–61. doi:10.1056/NEJMoa050373. PMID 16339094.
  44. ↑ Sundy JS, Baraf HS, Yood RA, Edwards NL, Gutierrez-Urena SR, Treadwell EL; et al. (2011). "Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials". JAMA. 306 (7): 711–20. doi:10.1001/jama.2011.1169. PMID 21846852, Check |pmid= value (help).
  45. ↑ So A, De Meulemeester M, Pikhlak A, Yücel AE, Richard D, Murphy V; et al. (2010). "Canakinumab for the treatment of acute flares in difficult-to-treat gouty arthritis: Results of a multicenter, phase II, dose-ranging study". Arthritis Rheum. 62 (10): 3064–76. doi:10.1002/art.27600. PMID 20533546.
  46. ↑ Ottaviani S, Moltó A, Ea HK, Neveu S, Gill G, Brunier L; et al. (2013). "Efficacy of anakinra in gouty arthritis: a retrospective study of 40 cases". Arthritis Res Ther. 15 (5): R123. doi:10.1186/ar4303. PMC 3978950. PMID 24432362.
  47. ↑ Stamp L, Horne A, Mihov B, Drake J, Haslett J, Chapman PT; et al. (2023). "Is colchicine prophylaxis required with start-low go-slow allopurinol dose escalation in gout? A non-inferiority randomised double-blind placebo-controlled trial". Ann Rheum Dis. doi:10.1136/ard-2023-224731. PMID 37652661 Check |pmid= value (help).
  48. ↑ Becker MA, Schumacher HR, Wortmann RL, MacDonald PA, Eustace D, Palo WA; et al. (2005). "Febuxostat compared with allopurinol in patients with hyperuricemia and gout". N Engl J Med. 353 (23): 2450–61. doi:10.1056/NEJMoa050373. PMID 16339094.
  49. ↑ Wortmann RL, Macdonald PA, Hunt B, Jackson RL (2010). "Effect of prophylaxis on gout flares after the initiation of urate-lowering therapy: analysis of data from three phase III trials". Clin Ther. 32 (14): 2386–97. doi:10.1016/j.clinthera.2011.01.008. PMID 21353107.
  50. ↑ Yu J, Qiu Q, Liang L, Yang X, Xu H (2018). "Prophylaxis of acute flares when initiating febuxostat for chronic gouty arthritis in a real-world clinical setting". Mod Rheumatol. 28 (2): 339–344. doi:10.1080/14397595.2017.1318467. PMID 28485997.
  51. ↑ Terkeltaub RA, Furst DE, Digiacinto JL, Kook KA, Davis MW (2011). "Novel evidence-based colchicine dose-reduction algorithm to predict and prevent colchicine toxicity in the presence of cytochrome P450 3A4/P-glycoprotein inhibitors". Arthritis Rheum. 63 (8): 2226–37. doi:10.1002/art.30389. PMID 21480191.
  52. ↑ Becker MA, Schumacher HR, Wortmann RL, MacDonald PA, Eustace D, Palo WA; et al. (2005). "Febuxostat compared with allopurinol in patients with hyperuricemia and gout". N Engl J Med. 353 (23): 2450–61. doi:10.1056/NEJMoa050373. PMID 16339094.
  53. ↑ Rees F, Jenkins W, Doherty M (2013). "Patients with gout adhere to curative treatment if informed appropriately: proof-of-concept observational study". Ann Rheum Dis. 72 (6): 826–30. doi:10.1136/annrheumdis-2012-201676. PMID 22679303. Check |pmid= value (help).

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