10/27/2015 Gout and Pseudogout Treatment & Management: Approach Considerations, Treatment of Acute Attacks, Treatment of Chronic Gout

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Gout and Pseudogout Treatment & ManagementAuthor: Bruce M Rothschild, MD; Chief Editor: Herbert S Diamond, MD more...

Updated: Sep 21, 2015

Approach ConsiderationsGout is managed in the following 3 stages:

Treating the acute attackProviding prophylaxis to prevent acute flaresLowering excess stores of urate to prevent flares of gouty arthritis and toprevent tissue deposition of urate crystals

In 2012, the American College of Rheumatology (ACR) published guidelines on thetreatment and prophylaxis of acute gouty arthritis and the management ofhyperuricemia.[105, 106]

As a general rule, asymptomatic hyperuricemia should not be treated, thoughultrasonographic studies have demonstrated that urate crystal deposition into softtissues occurs in a minority of patients with asymptomatic hyperuricemia.[95, 97]Patients with levels higher than 11 mg/dL who overexcrete uric acid are at risk forrenal stones and renal impairment; therefore, renal function should be monitored inthese individuals.[31]

Uratelowering therapy appears to reduce the incidence of kidney damage in gout.[107] In a retrospective study of 16,186 patients with initial serum uric acid levelsabove 7 mg/dL, Levy and colleagues found that patients with gout who remained onuratelowering therapy were less likely to develop kidney damage leading to chronickidney disease than those who were untreated.[107] All patients were followed for 36months from their first documented high serum uric acid level.

Patients who achieved a serum uric acid level below 6 mg/dL had a 37%improvement in renal outcomes (P < .0001).[107] The hazard ratio for kidneydamage was 1.08 (95% confidence interval, 0.76–1.52) in patients who receiveduratelowering therapy more than 80% of the time and was 1.27 (95% confidenceinterval, 1.05–1.55) in those who received uratelowering therapy less than 80% ofthe time.

Tophi should not be surgically removed unless they are in a critical location or drainchronically. Surgery may be indicated for tophaceous complications, includinginfection, joint deformity, compression (eg, cauda equina or spinal cordimpingement), and intractable pain, as well as for ulcers related to tophaceouserosions. Delayed healing is noted in 50% of patients.

Treatment of the acute phase of pseudogout is identical to that of acute gout. Inpatients with idiopathic pseudogout, a deterrent regimen of colchicine may be used.If an underlying metabolic problem is responsible for pseudogout, the arthritis maybe cured when the underlying problem is addressed.

Treatment of Acute AttacksThe temptation to treat patients without a proven diagnosis must be resisted. Septicarthritis may clinically resemble gout or pseudogout, and unrecognized septicarthritis can lead to loss of life or limb. Distinguishing septic arthritis from crystalinduced arthritis is not possible without an examination of joint fluid.

Acute treatment of proven crystalinduced arthritis is directed at relief of the painand inflammation. Nonsteroidal antiinflammatory drugs (NSAIDs), corticosteroids,colchicine, and adrenocorticotropic hormone (ACTH) are treatment options. Thechoice is based primarily on whether the patient has any concomitant healthproblems (eg, renal insufficiency or peptic ulcer disease). Colchicine, a classictreatment, is now rarely indicated.

When comorbid conditions limit the use of NSAIDs or colchicine, a preferred optionmay be an intraarticular steroid injection, particularly when a large, easilyaccessible joint is involved. Septic arthritis must be reasonably excluded.

Therapy to control the underlying hyperuricemia generally is contraindicated until theacute attack is controlled (unless kidneys are at risk because of an unusually heavyuric acid load). Starting therapy to control hyperuricemia during an acute attack mayintensify and prolong the attack. If the patient has been on a consistent dosage ofprobenecid or allopurinol at the time of the acute attack, however, the drug shouldbe continued at that dosage during the attack.

Furthermore, control of hyperuricemia generally is not pursued for a single attack. Ifattacks are recurrent or evidence of tophaceous or renal disease is present, therapyfor control of hyperuricemia is indicated.[108, 109, 110]

Nonsteroidal antiinflammatory drugs

NSAIDs are the drugs of choice in most patients with acute gout who do not haveunderlying health problems. Although indomethacin is the NSAID traditionallychosen for acute gout, most of the other NSAIDs can be used as well. Select anagent with a quick onset of action. Do not use aspirin, because it can alter uric acidlevels and potentially prolong and intensify an acute attack. Lowdose aspirin altersuric acid levels, increasing the risk of gout attacks and requiring close uric acid

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monitoring when aspirin is added to a uric acid/gout treatment regimen.[111]

Cyclooxygenase2 (COX2) inhibitors have been used with success, but patientsmay require higher dosages than are typically used.[112]

Avoid NSAIDs in patients with a history of peptic ulcer disease or gastrointestinal(GI) bleeding, those with renal insufficiency or abnormal hepatic function, thosetaking warfarin (a selective COX2 inhibitor can be used), and those in the intensivecare unit (ICU) who are predisposed to gastritis. Limit NSAID use in elderlypatients, because of the potential for adverse central nervous system (CNS) effects.Use NSAIDs cautiously in patients with diabetes and those who are receivingconcomitant angiotensinconverting enzyme (ACE) inhibitors.

To control the acute attack, NSAIDs are prescribed at full dosage for 25 days.Once the acute attack is controlled. the dosage is reduced to approximately one halfto one fourth of that amount. Taper the dosage over approximately 2 weeks. Goutsymptoms should be absent for at least 2 days before the NSAID is discontinued.

Colchicine

Although colchicine was once the treatment of choice for acute gout, it is now lesscommonly used than NSAIDs because of its narrow therapeutic window and risk oftoxicity.[113, 114] To be effective, colchicine therapy is ideally initiated within 36hours of onset of the acute attack. When used for acute gout in classic hourlydosing regimens (no longer recommended), colchicine causes adverse GI effects,particularly diarrhea and vomiting, in 80% of patients.

Dosing recommendations for colchicine in the treatment of acute gout haveundergone modifications as awareness of its toxicities has increased. Newerrecommendations trend toward lowered daily and cumulative doses.[113, 115]

The regimen currently favored consists of 1.2 mg of colchicine, followed by 0.6 mg1 hour later to initiate treatment of the early gout flare. In a multicenter,randomized, doubleblind, placebocontrolled, parallelgroup study, Terkaltaub et alfound that this regimen yielded both maximum plasma concentration and early goutflare efficacy comparable with those of highdose colchicine (4.8 mg total over 6hours), with a safety profile indistinguishable from that of placebo.[116]

Data from 7 separate drugtodrug interaction (DDI) studies suggests colchicinedose reductions of 3366% for treatment of acute gout and 5075% for prophylaxiswhen colchicine is given in combination with the extendedrelease calcium channelblockers verapamil and diltiazem or with the numerous Pgp and/or CYP3A4inhibitors (eg, clarithromycin and cyclosporine); in addition, patients should avoidgrapefruit juice. Dosages of colchicine did not have to be adjusted when the drugwas used in combination with azithromycin.[117]

Colchicine should generally be avoided if the glomerular filtration rate (GFR) islower than 10 mL/min, and the dose should be decreased by at least half if theGFR is lower than 50 mL/min. Colchicine should also be avoided in patients withhepatic dysfunction, biliary obstruction, or an inability to tolerate diarrhea.

A clinical response to colchicine is not pathognomonic for gout. Responses mayalso occur in patients with pseudogout, sarcoid arthropathy, psoriatic arthritis, orcalcific tendonitis.

In February 2008, the US Food and Drug Administration (FDA) ruled thatintravenous (IV) colchicine can no longer be produced or shipped in the UnitedStates, because of its toxicities. Consequently, IV colchicine is no longer advocatedfor the treatment of acute gout in the United States.[118]

Corticosteroids

Corticosteroids can be given to patients with gout who cannot use NSAIDs orcolchicine. Steroids can be given orally, IV, intramuscularly (IM), or intraarticularly.Using parenteral corticosteroids confers no advantage unless the patient cannottake oral medications.

Prednisone can be given at a dose of approximately 40 mg for 13 days, which isthen tapered over approximately 2 weeks (tapering more rapidly can result in arebound flare). Monitor closely for corticosteroid effects. If treatment continues formore than 2 weeks, consider measures to prevent osteoporosis.

Intraarticular longacting (depot) corticosteroids are particularly useful in patientswith a monoarticular flare to help reduce the systemic effects of oral steroids.Ensuring that the joint is not infected before injecting intraarticular corticosteroids isparticularly important.

An alternative to corticosteroid administration is to give ACTH (40 IUsubcutaneously, with repeat dosing as needed) to induce production ofcorticosteroid by the patient’s own adrenal glands. Such a regimen does not dependon the patient for proper tapering of prednisone.

Combination therapy

If the patient does not have an adequate response to initial therapy with a singledrug, ACR guidelines advises that adding a second appropriate agent is acceptable.Using combination therapy from the start is appropriate for an acute, severe goutattack, particularly if the attack involves multiple large joints or is polyarticular.Acceptable regimens include any of the following, in full or prophylactic doses asappropriate[106] :

Colchicine plus NSAIDsOral corticosteroids plus colchicineIntraarticular steroids plus colchicine or NSAIDs

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Treatment of Chronic GoutWhen a patient experiences a first attack of gout, any medication regimens thatmay have contributed to the gout attack must be altered, and any predisposingmedical conditions or habits must be addressed.[119] Patients should be instructedto go on a diet if obese, to stop drinking beer, and to avoid purinerich foods.

In many cases, patients who have a first attack of gout should undergo therapy withagents that lower uric acid, given the high risk for further inflammatory attacks andthe potential for destructive tophaceous deposition in the bone, synovium, andkidney, even without episodes of acute inflammation. If the first attack is notsevere, however, some rheumatologists advocate waiting for a second attack beforeinitiating such therapy; not all patients experience a second attack, and somepatients may require convincing that they need lifelong therapy.

The risk of a second attack of gout after the first attack is 62% after 1 year, 78%after 2 years, and 93% after 10 years. The decision to begin therapy depends partlyon the baseline serum uric acid levels (>9 mg/dL denotes a higher risk for recurrentgouty arthritis and tophi).

ACR guidelines recommend pharmacologic uratelowering therapy for patients withgout who have 1 or more tophi on clinical examination or imaging study or havefrequent attacks of acute gouty arthritis (≥2 attacks per year). Less robust evidencesupports pharmacologic therapy for patients with chronic kidney disease of stage 2or worse or a past history of urolithiasis.[105]

Longterm management of gout is focused on lowering uric acid levels. The goal oftherapy is to reduce serum uric acid levels to below 6 mg/dL, at minimum. In manycases, lowering uric acid levels to less than 5 mg/dL is necessary to improve thesigns and symptoms of gout. ACR guidelines recommend that once palpable tophiand all acute and chronic gout symptoms have resolved, serum uric acid levelsshould be maintained below 6 mg/dL indefinitely.[105]

In contrast, PerezRuiz et al have proposed that once dissolution of existing uratecrystals has been achieved, less stringent control may suffice to prevent formationof new crystals.[120] In their prospective cohort study of 211 patients from whomuratelowering therapy was withdrawn either after 5 years if no tophus was presentat baseline or 5 years after resolution of the last tophus, no patient who maintainedan average serum urate level lower than 7 mg/dL developed a crystalprovenrecurrence of gout.

Avoiding the use of medications that elevate uric acid in patients with gout isprudent. Thus, in patients with hypertension, other agents are preferable to athiazide diuretic, provided that blood pressure can be managed easily with a singledrug. Lowdose aspirin is also uricosuric. The angiotensinreceptor blocker (ARB)losartan should be considered, because it is uricosuric at 50 mg/day. However,medications that elevate uric acid can still be used, if required, by makingappropriate adjustments of allopurinol or probenecid doses.

Urinary excretion amounting to less than 800 mg per 24hour period on anunrestricted diet is considered underexcretion. Underexcreting patients arecandidates for uricosuric therapy with probenecid. The dosage is increased atmonthly intervals until the uric acid level is lowered to target. Urinary alkalization(eg, with potassium citrate) and ingestion of copious amounts of fluid are adjunctiverecommendations.

In patients with gout who have renal disease, ACR guidelines recommend xanthineoxidase inhibitor therapy with either allopurinol or febuxostat as the firstlinepharmacologic approach. Probenecid can be used in patients who havecontraindications to or are intolerant of at least 1 of those firstline agents, or it maybe combined with a xanthine oxidase inhibitor if the inhibitor does not lower uricacid sufficiently.[105] Probenecid could also be used for those patients who considerthe risks of xanthine oxidase inhibitors to be too high.

The ACR advises, however, that monotherapy with probenecid is not a firstlinechoice in patients with a creatinine clearance of less than 50 mL/min.[105] Inaddition, drug interactions may occur with probenecid (see Medication).

Prophylaxis

Because allopurinol, febuxostat, and probenecid change serum and tissue uric acidlevels, they may precipitate acute attacks of gout. To reduce this undesired effect,colchicine or lowdose NSAID treatment is provided for at least 6 months. Inpatients who cannot take colchicine or NSAIDs, low doses of prednisone can beconsidered. When used prophylactically, colchicine can reduce such flares by 85%.[121] Patients with gout may be able to abort an attack by taking a single colchicinetablet at the first twinge of an attack.

The standard dosage of colchicine for prophylaxis is 0.6 mg twice daily, but lowerdosages have also been suggested. Significant dosage reduction is critical forpatients who are also taking calcium channel blockers (eg, verapamil or diltiazem)and any of the large number of Pgp or CYP3A4 inhibitors (eg, clarithromycin orcyclosporine). In patients with renal insufficiency, the dosing frequency may have tobe decreased to once daily or every other day.

Adverse GI effects are uncommon with this dosage, occurring in only 4% ofpatients. This stands in contrast to the 80% risk of adverse GI effects with theclassic hourly colchicine regimen for the treatment of acute gout.

Even in prophylactic doses, however, longterm use of colchicine can lead tomarrow toxicity and to neuromyopathy, with elevated levels of creatine kinase andresulting muscle weakness. Colchicineinduced neuromyopathy is a particular risk inpatients with renal insufficiency.[122]

If the patient develops a gout flare after beginning therapy with a uric acid–loweringagent, the agent should not be discontinued, because discontinuance will only

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cause another flux in the uric acid level, which may prolong and intensify the attack.

Allopurinol

Allopurinol blocks xanthine oxidase and thus reduces the generation of uric acid.Approximately 310% of patients taking allopurinol develop symptoms ofintolerance, such as dyspepsia, headache, diarrhea, or pruritic maculopapular rash.

Less frequently (1% of cases), patients taking allopurinol can develop severeallopurinol hypersensitivity syndrome, which carries a mortality of 2030%.[123]Features of this syndrome include fever, toxic epidermal necrolysis, bone marrowsuppression, eosinophilia, leukocytosis, renal failure, hepatic failure, and vasculitis.Corticosteroids are often used to treat severe allopurinol hypersensitivity syndrome.

Severe allopurinol hypersensitivity syndrome is more likely to occur in patients withrenal insufficiency, those who are taking a thiazide diuretic, and those started onallopurinol at a dosage of 300 mg/day.[124] In addition, strong associations havebeen found between severe allopurinol hypersensitivity reactions and carriage of theHLA–B*5801 allele.[125]

ACR guidelines recommend considering screening for HLA–B*5801 carriage, usinga polymerase chain reaction–based test, in selected highrisk patients beforestarting allopurinol. Patients at particularly high risk are known to include those ofHan Chinese or Thai descent; Koreans are also at risk, if they have stage 3 orworse chronic kidney disease.[105] It is unclear whether such precautions arenecessary with a 100mg starting dose of allopurinol. Additionally, availability of thistest may be an issue.

Severe allopurinol hypersensitivity syndrome may present as StevensJohnsonsyndrome or as drug rash with eosinophilia and systemic symptoms (DRESS)syndrome. DRESS syndrome affects the liver, kidney, and skin. It is a delayedhypersensitivity response occurring 68 weeks after initiation of allopurinol. Theunderlying mechanism is thought to be a cellmediated immune reaction toallopurinol and its metabolites. Although the frequency is only is 0.4%, the rate oforgan failure and death is high. Treatment is with IV N acetylcysteine and steroids.

Allopurinol should immediately be discontinued in patients who develop pruritus or arash consistent with allopurinol hypersensitivity.

In most patients, start allopurinol at 100 mg/day (50 mg/day in patients with renalinsufficiency). Stamp et al have proposed that the risk of allopurinol hypersensitivitymay be reduced by starting allopurinol at a dose of 1.5 mg per unit of estimatedGFR.[126]

Adjust the dosage upward every 25 weeks according to the uric acid level until thegoal of a uric acid level of 6 mg/dL or less is achieved. Once the target uric acidlevel has been achieved and maintained for 6 months, discontinue colchicineprophylaxis, unless the patient has 1 or more tophi on clinical exam.

Previously, adjusting the allopurinol maintenance dosage to the creatinine clearancerate was recommended for patients with renal insufficiency. However, VázquezMellado et al found no increase in the prevalence of adverse reactions to allopurinolin patients who were started at an adjusted dosage but subsequently had theirdosage raised to meet therapeutic targets.[127]

ACR guidelines advise that the dosage of allopurinol can be raised above 300mg/day, even in patients with renal impairment, provided that the patient receivesadequate education and monitoring for drug toxicity (including measurement oftransaminase levels). The maximum dosage of allopurinol approved by the US Foodand Drug Administration (FDA) is 800 mg/day,[105] but the maximum dosage shouldbe lower in patients with chronic kidney disease.

Beware of drug interactions. For example, allopurinol prolongs the halflife ofazathioprine and 6mercaptopurine. It enhances the bone marrow toxicity ofcyclophosphamide. Patients taking concomitant ampicillin are at an increased risk ofrash.

Allopurinol can be used in combination with probenecid. However, note thatprobenecid increases the excretion of allopurinol.

In a retrospective 24month study of gout patients who had been prescribedallopurinol, Riedel et al found that only 18% of them filled all their prescriptionsthroughout the entire followup period and thus were presumably compliant; 10.4%filled only a single prescription.[128] In contrast, Rees et al reported that whenpatients receiving uratelowering therapy were given a predominantly nursedelivered intervention that included education and individualized lifestyle advice,92% achieved target serum uric acid levels at 1 year.[129]

Febuxostat

Febuxostat, a nonpurine selective inhibitor of xanthine oxidase, is a potentialalternative to allopurinol in patients with gout.[130, 131] Febuxostat is administeredorally and is metabolized mainly in the liver. In contrast, allopurinol and itsmetabolites are excreted primarily by the kidney. Therefore, febuxostat can be usedin patients with renal impairment with no dosage adjustment.[132] It is moreexpensive than allopurinol.

The CONFIRMS trial demonstrated the efficacy and safety of febuxostat in loweringhyperuricemia. By 6 months, the primary endpoint—a serum uric acid level of lessthan 6.0 mg/dL—was achieved in 45% of subjects on febuxostat 40 mg/day, 67%on febuxostat 80 mg/day, and 42% on allopurinol. In subjects with renalimpairment, the primary endpoint was achieved in 50% of subjects on febuxostat 40mg/day, 72% on febuxostat 80 mg/day, and 42% on allopurinol. Adverse eventrates were low and similar in all groups.[133]

In patients aged 65 years or older, the primary endpoint was achieved in 62% on

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febuxostat 40 mg/day, 82% on febuxostat 80 mg/day, and 47% on allopurinol.These figures remained essentially unchanged in subjects with mildtomoderaterenal impairment.[134]

In AfricanAmerican subjects, the primary endpoint was reached in 47% onfebuxostat 40 mg/day, 68% on febuxostat 80 mg/day, and 43% on allopurinol.Similar rates were seen in subjects with renal impairment.[135] Adverse event ratesin both subgroups were comparable with those in the overall trial.

The efficacy and safety of febuxostat in women was demonstrated in theCONFIRMS trial and in 2 other trials comparing febuxostat and allopurinol: FACT(Febuxostat Versus Allopurinol Controlled Trial) and APEX (Allopurinol andPlaceboControlled, Efficacy Study of Febuxostat). Achievement of a uric acid levelbelow 6.0 mg/dL rose with increasing daily doses of febuxostat doses, from 54.3%in patients receiving 40 mg to 100% in those receiving 240 mg, compared with45.9% with allopurinol. Results were similar in subjects with renal impairment.[136]

Uricase

Nonrecombinant urateoxidase (uricase) is used in Europe to prevent severehyperuricemia induced by chemotherapy in patients with malignancies, as well as inselected patients with treatmentrefractory gout. Shortterm use of such agents inpatients with severe tophaceous gout could debulk the totalbody urate load,allowing maintenance with probenecid or allopurinol.

In 2009, the FDA approved recombinant uricase (rasburicase) for the prevention oftumor lysis syndrome. However, it is highly immunogenic and may causeanaphylaxis.[137]

In 2010, a polyethyleneglycol–conjugated uricase (pegloticase) was approved bythe FDA for gout. Pegloticase, which enzymatically catalyzes the oxidation of uricacid to allantoin, is an IV biologic agent to be considered when adjustment ofcontributing medications (eg, diuretics) and treatment with allopurinol, febuxostat,and uricosuric agents are insufficient to achieve appropriate reduction of serum uricacid levels.[105]

The European Medicines Agency (EMA) is now weighing approval of pegloticase inEurope. Approval was recommended by an expert advisory committee.[138]

Adverse effects of pegloticase include anaphylaxis, infusion reactions, gout flares,and exacerbation of congestive heart failure. At present, substantial expensecompromises its costeffectiveness as an initial approach.[139] The ACR guidelinesdo not recommend pegloticase as a firstline approach.

Other therapeutic options

Benzbromarone is an effective uricosuric agent available on a restricted basis onlyoutside the United States. However, it has been withdrawn because it causesfulminant hepatotoxicity.

Vitamin C, with its uricosuric effect, may reduce the serum concentration of uricacid. In one study, 500 mg/day for 2 months reduced uric acid by a mean of 0.5mg/dL in patients without gout.[140] However, gout patients appear to be lessresponsive to such a low dose of ascorbate. Vitamin C treatment should be avoidedin patients with nephrolithiasis, urate nephropathy, or cystinuria.

In an openlabel pilot study of 10 patients with refractory acute gout treated with theinterleukin (IL)1 antagonist anakinra, pain was substantially reduced in all patientswithin 2 days, without side effects. Clinical signs of inflammation had disappearedin 9 of 10 patients by day 3 of treatment.[141]

The lipidlowering drug fenofibrate, a fibric acid derivative, lowers serum uric acidlevels while reducing verylowdensity lipoprotein (VLDL), total cholesterol, andtriglyceride levels.[142] However, the creatinine level increases, and all effects arenegated once the drug has been discontinued.[137]

Canakinumab

In 2010, an 8week, singleblind, doubledummy, doseranging study showed thatthe selective IL1β antibody canakinumab yielded fast and lasting relief of pain inpatients with acute gouty arthritis flares refractory to treatment with NSAIDs orcolchicine.[143] However, in June 2011, canakinumab was denied approval by theFDA.[144] (See FDA Panel Says No to Canakinumab for Gout Attacks.)

Diet and ActivityBecause uric acid is a breakdown product of purine, highpurine foods should beeither avoided or consumed only in moderation. Foods very high in purines includeorgan meats such as sweetbreads (eg, pancreas and thymus), smelt, sardines, andmussels. Foods moderately high in purines include anchovies, trout, haddock,scallops, mutton, veal, liver, bacon, salmon, kidneys, and turkey.

Purines are found in all protein foods. All sources of purines cannot and should notbe eliminated.

Overall, purine restriction generally reduces serum uric acid levels by no more than1 mg/mL, with modest impact, and diets with very low purine content are notpalatable. Diet modifications alone are rarely able to lower uric acid levelssufficiently to prevent accumulation of urate, but they may help lessen the triggersof acute gout attacks.

Patients with gout should avoid excess ingestion of alcoholic drinks, particularlybeer, because alcohol use elevates uric acid levels and thus can precipitate attacksof gout. Indeed, heavy drinkers are much more likely to have recurrent gout attacks,

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even with allopurinol therapy. Moderate wine intake is not associated with increaseddevelopment of incident gout,[1] but excesses of any form of alcohol in gout patientsare associated with acute gout flares.

Patients should avoid sodas and other beverages or foods sweetened with highfructose corn syrup. They should also limit their use of naturally sweet fruit juices,table sugar, and sweetened beverages and desserts, as well as table salt.[105]Patients taking colchicine should avoid grapefruit and grapefruit juice.

Maintaining a high level of hydration with water (at least 8 glasses of liquids perday) may be helpful in avoiding attacks of gout. In view of the association of goutwith atherosclerosis, the diagnosis of gout may afford a particularly good opportunityfor the clinician to advise a lowcholesterol, lowfat diet if such a diet is otherwiseappropriate for the patient. Although a diet of this type may help uric acid levels,such advice should be given primarily to help prevent atherosclerosis.

Weight reduction in patients who are obese can improve hyperuricemia. Ketosisinducing diets (eg, fasting) should be avoided, however.

Because acute attacks are already sufficiently limiting of activity, additionallimitations of activity are not necessary. The patient should avoid trauma to theaffected joint; otherwise, they should be active.

ConsultationsRheumatologists should be involved in the care of patients with difficult gout, asadvised in the ACR guidelines. They can establish the diagnosis with arthrocentesisand synovial fluid analysis for crystals. They also are skilled in the management ofthis disorder, and consultation may be helpful for patients with an acute gout attackthat does not respond to NSAIDs within 2 days or to colchicine within 1 day, as wellas for patients with refractory hyperuricemia.

Rheumatology or orthopedic consultation is indicated for any patient with septicarthritis or for any patient in whom a septic arthritis cannot be ruled out.

LongTerm MonitoringAfter diagnosis and treatment of an acute gouty arthritis episode, the patient shouldreturn for a followup visit in approximately 1 month to be evaluated for therapy tolower serum uric acid levels.

If uric acid–lowering therapy is begun, patients should be seen within 2 weeks toensure that no untoward toxicity has developed and then every 12 months whilemedication dosages are adjusted to achieve the target uric acid level of 56 mg/dL.Once this level is achieved and maintained, patients can be seen every 612 monthsand their serum uric acid monitored to help assess efficacy and adherence.

Medication

Contributor Information and DisclosuresAuthorBruce M Rothschild, MD Professor of Medicine, Northeast Ohio Medical University; Adjunct Professor,Department of Biomedical Engineering, University of Akron; Research Associate, University of Kansas Museumof Natural History; Research Associate, Carnegie Museum

Bruce M Rothschild, MD is a member of the following medical societies: American Association for theAdvancement of Science, American College of Rheumatology, International Skeletal Society, New YorkAcademy of Sciences, Sigma Xi, Society of Skeletal Radiology

Disclosure: Nothing to disclose.

Coauthor(s)Mark L Francis, MD Professor of Medical Education, Department of Medical Education, Paul L Foster School ofMedicine, Texas Tech University Health Sciences Center

Mark L Francis, MD is a member of the following medical societies: American College of Physicians, Phi BetaKappa

Disclosure: Nothing to disclose.

Anne V Miller, MD Chief, Rheumatology Division; Assistant Professor of Internal Medicine, Department ofMedicine, Division of Rheumatology, Southern Illinois University School of Medicine

Anne V Miller, MD is a member of the following medical societies: Alpha Omega Alpha, American College ofPhysicians, American College of Rheumatology, International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

Chief EditorHerbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New YorkDownstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American Collegeof Physicians, American College of Rheumatology, American Medical Association, Phi Beta Kappa

Disclosure: Nothing to disclose.

AcknowledgementsRichard W Allinson, MD Associate Professor, Department of Ophthalmology, Texas A&M University HealthScience Center; Senior Staff Ophthalmologist, Scott and White Clinic

Richard W Allinson, MD, is a member of the following medical societies: American Academy of Ophthalmology,American Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

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Lawrence H Brent, MD Associate Professor of Medicine, Jefferson Medical College of Thomas JeffersonUniversity; Chair, Program Director, Department of Medicine, Division of Rheumatology, Albert Einstein MedicalCenter

Lawrence H Brent, MD is a member of the following medical societies: American Association for theAdvancement of Science, American Association of Immunologists, American College of Physicians, andAmerican College of Rheumatology

Disclosure: Abbott Honoraria Speaking and teaching; Centocor Consulting fee Consulting; GenentechGrant/research funds Other; HGS/GSK Honoraria Speaking and teaching; Omnicare Consulting fee Consulting;Pfizer Honoraria Speaking and teaching; Roche Speaking and teaching; Savient Honoraria Speaking andteaching; UCB Honoraria Speaking and teaching

Andrew A Dahl, MD Director of Ophthalmology Teaching, MidHudson Family Practice Institute, The Institutefor Family Health; Assistant Professor of Surgery (Ophthalmology), New York College of Medicine

Andrew A Dahl, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy ofOphthalmology, American College of Surgeons, American Medical Association, American Society of Cataractand Refractive Surgery, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Paul E Di Cesare, MD, FACS Professor and Chair, Department of Orthopedic Sugery, University of California,Davis, School of Medicine

Paul E Di Cesare, MD, FACS is a member of the following medical societies: American Academy of OrthopaedicSurgeons, American College of Surgeons, and Sigma Xi

Disclosure: Stryker Consulting fee Consulting

Steven C Dronen, MD, FAAEM Chair, Department of Emergency Medicine, LeConte Medical Center

Steven C Dronen, MD, FAAEM is a member of the following medical societies: American Academy ofEmergency Medicine and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Gino A Farina, MD, FACEP, FAAEM Associate Professor of Clinical Emergency Medicine, Albert EinsteinCollege of Medicine; Program Director, Department of Emergency Medicine, Long Island Jewish Medical Center

Gino A Farina, MD, FACEP, FAAEM is a member of the following medical societies: American Academy ofEmergency Medicine, American College of Emergency Physicians, and Society for Academic EmergencyMedicine

Disclosure: Nothing to disclose.

Harris Gellman, MD Consulting Surgeon, Broward Hand Center; Voluntary Clinical Professor of OrthopedicSurgery and Plastic Surgery, Departments of Orthopedic Surgery and Surgery, University of Miami, Leonard MMiller School of Medicine

Harris Gellman, MD is a member of the following medical societies: American Academy of Medical Acupuncture,American Academy of Orthopaedic Surgeons, American Orthopaedic Association, American Society for Surgeryof the Hand, and Arkansas Medical Society

Disclosure: Nothing to disclose.

Joseph Kaplan, MD, MS, FACEP Attending Physician, Department of Emergency Medicine, Martin ArmyCommunity Hospital, Fort Benning

Joseph Kaplan, MD, MS, FACEP is a member of the following medical societies: American College ofEmergency Physicians

Disclosure: Nothing to disclose.

Jegan Krishnan, MBBS, FRACS, PhD Professor, Chair, Department of Orthopedic Surgery, Flinders Universityof South Australia; Senior Clinical Director of Orthopedic Surgery, Repatriation General Hospital; PrivatePractice, Orthopaedics SA, Flinders Private Hospital

Jegan Krishnan, MBBS, FRACS, PhD, is a member of the following medical societies: Australian MedicalAssociation, Australian Orthopaedic Association, and Royal Australasian College of Surgeons

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Edward A Michelson, MD Associate Professor, Program Director, Department of Emergency Medicine,University Hospital Health Systems of Cleveland

Edward A Michelson, MD is a member of the following medical societies: American College of EmergencyPhysicians, National Association of EMS Physicians, and Society for Academic Emergency Medicine

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Sriya K M Ranatunga, MD, MPH Associate Professor, Department of Clinical Medicine, Southern IllinoisUniversity School of Medicine

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Hampton Roy Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas forMedical Sciences

Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology,American College of Surgeons, and PanAmerican Association of Ophthalmology

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Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center Collegeof Pharmacy; EditorinChief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

R Christopher Walton, MD Professor, Director of Uveitis and Ocular Inflammatory Disease Service, Departmentof Ophthalmology, Assistant Dean for Graduate Medical Education, University of Tennessee College of

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Medicine; Consulting Staff, Regional Medical Center, Memphis Veterans Affairs Medical Center, St JudeChildren's Research Hospital

R Christopher Walton, MD is a member of the following medical societies: American Academy ofOphthalmology, American College of Healthcare Executives, American Uveitis Society, Association for Researchin Vision and Ophthalmology, and Retina Society

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