Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
INTRODUCTION — Acute gout (or a gout flare) is an intensely painful and disabling inflammatory arthritis, usually involving a single joint but occasionally involving two or more joints. The goal of therapy in an acute gout attack is prompt and safe termination of pain and disability. Without therapy, acute gouty arthritis usually resolves completely within a few days to several weeks, particularly in early disease. However, symptoms improve more quickly with administration of any of a broad array of antiinflammatory drugs. (See "Clinical manifestations and diagnosis of gout", section on 'Acute gouty arthritis'.)
Upon resolution of an acute attack, the patient is said to have entered a symptom-free (interval, intercritical, or between attacks) period. However, flares of acute gout recur in the great majority of patients; with more frequent episodes, attacks may be more severe and prolonged, with consequent shortening of asymptomatic periods. Patients with recurrent flares and those who develop chronic arthritis can benefit from long-term prophylactic therapy with a urate-lowering agent to prevent further recurrences of acute gout and chronic tophaceous disease. (See "Prevention of recurrent gout: Pharmacologic urate-lowering therapy and treatment of tophi" and "Clinical manifestations and diagnosis of gout", section on 'Intercritical gout and recurrent gouty arthritis'.)
The management of acute gouty arthritis will be reviewed here. The approach to asymptomatic hyperuricemia; the pathophysiology, clinical manifestations and diagnosis of gout; and the prevention of recurrent gout after resolution of the acute attack are discussed separately. (See "Asymptomatic hyperuricemia" and "Pathophysiology of gouty arthritis" and "Clinical manifestations and diagnosis of gout" and "Prevention of recurrent gout: Pharmacologic urate-lowering therapy and treatment of tophi".)
GENERAL THERAPEUTIC PRINCIPLES — Several classes of antiinflammatory agents are effective for the treatment of acute gout, including nonsteroidal antiinflammatory drugs (NSAIDs), colchicine, systemic and intraarticular glucocorticoids, and biologic agents that inhibit the action of interleukin (IL)-1 beta [1-3]; a set of general principles is important in the effective management of acute gout, regardless of the specific antiinflammatory agent used. These include the following:
●Treatment should start as soon as possible after the patient perceives the beginning of an attack, preferably within several hours of symptom onset. More rapid and complete resolution of symptoms occurs the earlier that treatment is introduced, especially if treatment is initiated at the full recommended dose of the chosen antiinflammatory agent. Patients should be continued on treatment for the duration of the attack, usually at reduced doses once a significant reduction in symptoms is achieved.
Complete cessation of treatment can usually be safely done within two to three days of complete resolution of the attack, except in the case of oral glucocorticoids, for which slower dose tapering may be needed to avoid a recurrent attack. The duration of therapy for the acute attack may range from only a few days (eg, in a patient treated within hours of symptom onset) to several weeks (eg, in a patient begun on treatment after four or five days of symptoms). Most patients require treatment for no more than five to seven days if begun on therapy within 12 to 36 hours of symptom onset.
●Urate-lowering therapies are of no benefit for acute gout and should generally not be initiated during an acute attack. However, in patients already receiving these agents (eg, allopurinol, febuxostat, probenecid, benzbromarone, or pegloticase), the urate-lowering medication should be continued without interruption. There is no benefit to temporary discontinuation, and subsequent reintroduction after a period off the agent may predispose to another attack. Therapeutic recommendations for acute gout attacks in patients receiving urate-lowering agents are the same as those for patients not taking antihyperuricemic therapy. (See "Prevention of recurrent gout: Pharmacologic urate-lowering therapy and treatment of tophi", section on 'Initiation and duration of urate-lowering pharmacotherapy'.)
●Treatment of acute gout attacks does not differ substantially in patients with or without clinically apparent tophi, although the presence of tophi is an indication for the initiation of long-term urate-lowering therapy after attack resolution to prevent or reverse chronic gouty arthropathy. Urate-lowering therapy is discussed separately. (See "Prevention of recurrent gout: Pharmacologic urate-lowering therapy and treatment of tophi".)
●Important comorbidities (and their ongoing therapies) that are frequent among gout patients may affect drug safety or effectiveness, especially in older patients (see 'Older adults' below); consideration of these disorders is critical in the choice of antiinflammatory treatment for acute gout. The following factors are of particular importance in selecting an agent:
•Cardiovascular disease, including heart failure or poorly controlled hypertension
•Gastrointestinal disease, including peptic ulcer disease
•Concurrent medication use
•Diabetes mellitus, especially if poorly controlled
●Adjunctive measures, none of which are of proven efficacy, are often administered for symptom relief and include icing the affected joint , resting the joint that is involved, and administering analgesic medications (eg, acetaminophen or opioids). These measures do not substitute for effective antiinflammatory treatment of the acute gout attack.
INITIAL TREATMENT CHOICES — The choice of medications depends upon the comorbidities that are present, the effectiveness of past treatments, patient preferences for use, and the experience of the clinician with joint injection. Despite wide use in the treatment of acute gout attacks, the various antiinflammatory agents have only infrequently been compared with placebo or with each other in randomized trials. We take the following approach to the initial treatment of acute attacks of gout (algorithm 1):
●We treat most patients able to take an oral medication with a nonsteroidal antiinflammatory drug (NSAID). (See 'NSAID therapy' below.)
●An oral low-dose colchicine regimen may be used in patients who are able to take an oral medication but who have contraindications to NSAIDs (eg, moderate or more severe chronic kidney disease [CKD], active peptic ulcer disease, or a history of NSAID-intolerance). (See 'Colchicine therapy' below.)
●In patients with contraindications to the use of both NSAIDs and colchicine, we prefer intraarticular, oral, or parenteral glucocorticoids, depending upon the number of involved joints, the experience of the clinician with joint injection techniques, and the need, if present, for parenteral rather than orally administered therapy. (See 'Glucocorticoids' below.)
Our approach to the patient with acute gout is based upon the available data and our clinical experience. Our recommendations are generally consistent with the approaches recommended by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) [5-7].
Administration of NSAIDs — We suggest the administration of a potent oral NSAID, such as naproxen (500 mg twice daily) or indomethacin (50 mg three times daily), for reduction of acute gouty inflammation in most patients with acute gout.
We generally prefer nonselective NSAIDs over other agents because they are inexpensive, readily available to patients at the onset of an attack (some without a prescription), and, in our experience and in available studies, as effective and at least as safe as other agents [8-13]. NSAIDs are most effective if treatment is initiated within 48 hours of the onset of symptoms. The dose may be reduced after a significant reduction in symptoms has occurred, but the frequency of dosing should be maintained for several more days for optimal antiinflammatory effect. High-dose celecoxib (a single dose of 800 mg followed by 400 mg twice daily), a cyclooxygenase (COX)-2 selective inhibitor, is an alternative to nonselective NSAIDs . (See 'Efficacy and safety of NSAIDs' below.)
The NSAID can be discontinued one or two days after clinical signs have completely resolved. Typically, the total duration of NSAID therapy for an acute attack is five to seven days. It is likely to be shorter in patients treated within the first 24 hours of symptom onset and may be longer in patients in whom treatment is not begun until several days later.
There are important contraindications to NSAIDs, including:
●CKD with creatinine clearance (CrCl) of less than 60 mL/min per 1.73 m2 (see "Nonselective NSAIDs: Overview of adverse effects", section on 'Renal effects' and "Overview of the management of chronic kidney disease in adults", section on 'Definition and classification' and "Assessment of kidney function")
●Active duodenal or gastric ulcer (see "NSAIDs (including aspirin): Primary prevention of gastroduodenal toxicity" and "NSAIDs (including aspirin): Secondary prevention of gastroduodenal toxicity")
●Cardiovascular disease, particularly heart failure or hypertension that is difficult to control (see "Nonselective NSAIDs: Adverse cardiovascular effects" and "COX-2 selective inhibitors: Adverse cardiovascular effects")
●Ongoing treatment with anticoagulants
Adverse effects are uncommon with brief courses of therapy but may include gastrointestinal intolerance and worsening of renal function.
In an attack of several days’ duration prior to starting therapy, a longer course of treatment may be necessary. In such patients, added interventions to prevent NSAID gastropathy (eg, use of a proton pump inhibitor) may be of benefit, particularly in patients at increased risk due to advanced age or to a prior history of ulcer disease or of gastrointestinal bleeding. (See "NSAIDs (including aspirin): Primary prevention of gastroduodenal toxicity" and "NSAIDs (including aspirin): Secondary prevention of gastroduodenal toxicity".)
Aspirin is not used to treat acute gout because of the paradoxical effects of salicylates on serum urate, resulting from renal uric acid retention at low doses (<2 to 3 g/day) and from uricosuria at higher doses [15-18]. However, low-dose aspirin that is being used for cardiovascular prophylaxis generally does not need to be discontinued during the treatment of acute gout, although these very low doses can increase serum uric acid levels modestly in some patients [17,18]. There is one report that low-dose aspirin can increase the risk of acute gout attacks in patients with established gout who were not being treated with allopurinol [17-19].
Efficacy and safety of NSAIDs — Complete or nearly complete resolution of the pain and disability of an acute flare typically occurs within several days to one week. There are few high-quality randomized trials of NSAIDs for acute gouty arthritis [5,8,14,20], and there are no randomized trials that compare NSAIDs with colchicine. A number of trials have compared different NSAIDs with each other, without any apparent differences in efficacy [8-14]. One additional study showed superiority of an NSAID (tenoxicam) over placebo . In one randomized trial, treatment with high doses of celecoxib (a single dose of 800 mg followed by 400 mg twice daily) was of comparable efficacy to indomethacin (50 mg three times daily) .
Caution is necessary in patients with known cardiovascular disease or with multiple risk factors for atherosclerotic coronary disease, since an increased risk of myocardial infarction, stroke, and heart failure has been associated with use both of selective COX-2 inhibitors (coxibs) and some nonselective NSAIDs. Whether such risk is increased in patients receiving short courses of NSAIDs for acute gout is unknown. (See "COX-2 selective inhibitors: Adverse cardiovascular effects" and "Nonselective NSAIDs: Adverse cardiovascular effects".)
Administration of colchicine — In patients with NSAID intolerance or with an absolute (or often relative) contraindication to NSAIDs (see 'NSAID therapy' above), we suggest the use of oral colchicine. In our experience, oral colchicine is most likely to be effective if treatment is started within 12 to 24 hours of symptom onset, and incipient attacks may frequently be aborted by using low-dose oral colchicine as soon as the patient perceives the first sign of an attack. We generally do not use colchicine for acute attacks that have been ongoing for more than 72 to 96 hours because of the diminished likelihood of benefit. (See 'Efficacy of oral colchicine' below.)
There are several low-dose regimens that may be effective. As an example, the US Food and Drug Administration (FDA) has approved a schedule for the first 24 hours of colchicine treatment for acute gout flare, recommending an initial dose of 1.2 mg of oral colchicine, followed one hour later by another 0.6 mg, for a total dose on the first day of therapy of 1.8 mg . In our experience, an alternative low-dose colchicine regimen that has been equally effective calls for 0.6 mg (or 0.5 mg, available in countries other than the US) three times on the first day of flare treatment . Approximately 60 percent of patients will not achieve a 50 percent reduction in pain within 24 hours with either first day approach alone, but most patients will respond further over several days with these doses. Patients should be continued on treatment for the duration of the attack, usually at reduced doses (eg, 0.6 mg once or twice daily as tolerated) once a significant response is achieved. Complete cessation of treatment can be safely done within two to three days of complete resolution of the attack. In patients already receiving colchicine prophylaxis, the dose used for prevention of attacks during symptom-free intervals should be resumed after the higher dose is taken in place of the usual prophylactic dose on the first day of therapy for the acute attack. A colchicine dose reduction is required for patients with a CrCl of <45 mL/minute. (See 'General therapeutic principles' above.)
Contraindications to the use of colchicine with these doses and schedules of administration include:
●Use of colchicine (eg, for prophylaxis) within the prior 14 days in patients with severe hepatic impairment or severe renal impairment (CrCl of <30 mL/min)
●Concomitant use of a medication that strongly inhibits the cytochrome P450 system component CYP3A4 (table 1) or that inhibits the membrane P-glycoprotein multidrug resistance transporter (P-gp) in the presence of renal or hepatic impairment  (see 'Safety of colchicine' below)
Concomitant use of a medication that moderately to strongly inhibits P-gp and/or CYP3A4 may be permitted in patients with normal renal and hepatic function if there is no other reasonable alternative to colchicine, but this generally requires significant dose reduction and limits on the frequency of colchicine administration . (See 'Safety of colchicine' below.)
Common adverse effects of colchicine may include diarrhea and abdominal cramping, but these are less likely in patients who receive no more than 1.8 mg in total on the first day compared with patients receiving higher doses, such as 0.6 mg every one to two hours until symptom relief or intolerance (as was historically employed) .
When low-dose colchicine therapy is ineffective or is minimally effective in suppressing acute gout in a timely fashion, alternative antiinflammatory agents, including oral and intraarticular glucocorticoids, may be required. In patients without contraindications to NSAID use, supplemental therapy with a NSAID in an antiinflammatory regimen may also be cautiously employed. (See 'Initial treatment choices' above and 'Glucocorticoids' below.)
Efficacy of oral colchicine — Colchicine for the treatment of acute gouty arthritis has not been extensively studied in randomized trials [24,25], even though it was used for centuries for the treatment of acute gout. Oral colchicine (uncombined with another active ingredient, such as probenecid) was first formally approved by the FDA for use in the US for the treatment of acute gout in 2009 [21,22].
In our experience, incipient gout attacks may be aborted with oral colchicine taken at the onset of the first symptom. Whether colchicine therapy offers more rapid or complete relief of gout flares than alternative antiinflammatory agents is not established and awaits adequate head-to-head comparisons. Side effects are less likely when a low-dose regimen is used at the onset of flare symptoms, and such regimens appear to achieve a degree of benefit comparable to that achieved with higher colchicine doses. These points were illustrated by the results of the Acute Gout Flare Receiving Colchicine Evaluation (AGREE) trial, a randomized trial that compared treatment administered within 12 hours of flare onset using low-dose colchicine (1.8 mg total over one hour), very high-dose colchicine (4.8 mg total over six hours), and placebo . A significantly greater proportion of patients in the low-dose and high-dose colchicine treatment groups (38 and 33 percent), compared with those receiving placebo (16 percent), achieved a 50 percent reduction in pain by 24 hours from treatment initiation without the use of rescue medication. This trial was limited by the short duration of treatment.
Safety of colchicine — Colchicine is contraindicated in patients with advanced renal or hepatic impairment (in both acute gout flare treatment and in long-term flare prophylaxis) because both the kidneys and liver participate in colchicine metabolism, in large part through the action of the cell membrane P-gp and through the availability of the cytochrome P450 system component CYP3A4. Similarly, long-term colchicine treatment in patients with milder renal or hepatic impairment in combination with agents strongly inhibiting P-gp or utilizing CYP3A4 (table 1) has been associated with a greater risk for colchicine toxicity due to the resulting increased serum concentration of colchicine .
Gastrointestinal symptoms (diarrhea, abdominal pain, nausea and vomiting) and readily reversible peripheral neuropathy are the most common adverse reactions to colchicine administration. More severe colchicine toxicity, which may include combinations of serious, life-threatening, or fatal adverse events such as blood cytopenias, rhabdomyolysis or myopathy, peripheral neuropathy, liver failure, or severe cutaneous eruption, has only rarely been reported in patients receiving brief administration of this agent for acute gout flare, as in a patient treated with very high-dose colchicine together with multiple drugs affecting colchicine levels over an eight-day period . We are cautious and do not use colchicine to treat acute gout in patients with mild renal or hepatic impairment if they are receiving strong P-gp inhibitors or agents strongly reducing CYP3A4 availability. In addition, we use colchicine for acute gout flare in patients with normal renal or hepatic function receiving concomitant agents of this type only if no alternative is available. Such patients require reduction of the colchicine dose, depending upon the affected pathways. Care should also be taken in combining use of colchicine with the wider array of less strong CYP3A4 inhibitors, including statins, other lipid-lowering drugs, erythromycin, and grapefruit juice (table 1). Dosing guidelines for colchicine have been proposed for those patients with normal renal and hepatic function who are receiving interacting agents or who have received them within 14 days . These guidelines limit the size of the initial dose and the frequency at which dosing may be repeated.
More commonly used inhibitors of P-gp include cyclosporine, tacrolimus, amiodarone, quinidine, azole antifungals, verapamil (and some other calcium channel blockers), vinca alkaloids, erythromycin, clarithromycin, and others . Commonly used strong CYP3A4 inhibitors include human immunodeficiency virus (HIV) protease inhibitors, clarithromycin (and other macrolide antibiotics), azole antifungals, and others (table 1) . A number of drugs inhibit both P-gp and CYP3A4, including cyclosporine, verapamil, diltiazem, erythromycin, clarithromycin, and others.
More detailed information on dosing requirements for colchicine and other specific drugs and on drug interactions, as well as a more detailed list of medications in each group, is available using Lexi-Interact, the drug interaction program, which can be accessed through a link in the drug information topic.
We do not administer colchicine intravenously, and we strongly advise against such use because of the risk of serious adverse effects, including death, which are associated with the intravenous administration of this drug.
Administration and choice of glucocorticoid — In patients with contraindications to the use of both NSAIDs and colchicine, the choice of therapy depends upon several factors, including the number of involved joints, the experience of the clinician with joint injection techniques, and the need, if present, for parenteral rather than orally administered therapy:
●One or two actively inflamed joints – Arthrocentesis followed by intraarticular injection of glucocorticoids may be used in patients unable to take NSAIDs or colchicine who have only one or two actively inflamed joints. However infection should be excluded, and expertise with this technique is required. (See 'Intraarticular glucocorticoids' below.)
Glucocorticoid joint injection should be withheld in patients in whom a diagnosis of gout has not previously been established or in whom the clinical history and physical examination suggest the alternative or additional possibility of joint infection. To achieve this critical distinction, joint aspiration should be carried out with examination of the synovial fluid by Gram stain and culture, by cell count and differential white cell count, and by polarized light microscopy for urate or other crystals that are pathognomonic either for gout (urate crystals) or pseudogout (acute calcium pyrophosphate crystal arthritis). (See "Clinical manifestations and diagnosis of calcium pyrophosphate crystal deposition (CPPD) disease".)
It is important to note that septic arthritis and acute gout can coexist, so, even if gout has been diagnosed in the past, caution should be taken in the use of glucocorticoid joint injection if the current clinical picture is uncertain, even in a patient with well-established gout.
●Not candidates for joint injection – Oral glucocorticoids may be used for patients who cannot take NSAIDs or colchicine and who are not candidates for intraarticular glucocorticoid injection because of polyarticular disease. Glucocorticoids should be used with caution in patients with heart failure, poorly controlled hypertension, or glucose intolerance, but they may be used in patients with moderate to severe renal insufficiency. (See 'Oral glucocorticoids' below.)
●Need for parenteral (non-intraarticular) therapy – In patients who are unable to take oral agents and who are not appropriate candidates for intraarticular injection, we use parenteral glucocorticoids. Although reported to be efficacious for gout flare treatment, corticotropin (adrenocorticotropic hormone [ACTH]) cost and limited availability restrict the use of parenteral ACTH treatment. (See 'Parenteral glucocorticoids' below.)
Intraarticular glucocorticoids — We suggest arthrocentesis with joint fluid aspiration and analysis followed by intraarticular injection of glucocorticoids for patients who are unable to take oral medications, who have only one or two actively inflamed joints, and in whom infection has been excluded. We use triamcinolone acetonide (40 mg for a large joint [eg, knee], 30 mg for a medium joint [eg, wrist, ankle, elbow], and 10 mg for a small joint) or equivalent doses of methylprednisolone acetate. (See "Joint aspiration or injection in adults: Technique and indications" and "Joint aspiration or injection in adults: Complications".)
Joint aspiration and injection are commonly used in rheumatology and orthopedic practice but, except for knee injection, are much less frequently done in primary care practice because of the experience required.
Evidence of the benefit of intraarticular glucocorticoids has been limited to small, open-label trials, although, in our experience, such treatment is usually highly effective and works quickly, often within 24 hours . A 2013 systematic review of the safety and efficacy of intraarticular glucocorticoid injection for acute gout could not identify any randomized trials of intraarticular glucocorticoids that met the inclusion criteria, illustrating the very limited formal evidence available regarding the efficacy and safety of this approach . Indirect evidence supporting the use of intraarticular glucocorticoid injections in gout includes the significant benefit that may result from such injections for the treatment of rheumatoid arthritis and osteoarthritis. (See "Use of glucocorticoids in the treatment of rheumatoid arthritis", section on 'Intraarticular therapy' and "Initial pharmacologic therapy of osteoarthritis", section on 'Intraarticular glucocorticoids'.)
Oral glucocorticoids — We suggest primary use of oral glucocorticoids for patients who cannot take NSAIDs or colchicine and who are not candidates for intraarticular glucocorticoid injection because of polyarticular disease. We also suggest the use of oral glucocorticoids if a clinician with adequate expertise in these techniques is not readily available. We use prednisone (or other equivalent glucocorticoid) in doses of 30 to 50 mg once daily or in two divided doses until flare resolution begins, and we then taper the dose of glucocorticoids, usually over 7 to 10 days.
The data on efficacy of oral glucocorticoids are increasingly optimistic and support the view that prednisone and prednisolone are safe and effective when administered in this fashion and that these agents reduce symptoms to a similar extent as NSAIDs [32-35]. In a randomized trial, 416 patients with acute gout presenting to an emergency department within three days of symptom onset were treated with either prednisolone (30 mg administered orally once daily for five days) or indomethacin (50 mg administered orally three times daily for two days, then 25 mg three times daily for three days) . There was no significant difference between the groups in the degree to which pain was reduced either in the emergency department or during the subsequent two weeks. During the first two hours in the emergency department, adverse events (mostly dizziness, sleepiness, and nausea) were more frequent in the group receiving indomethacin (19 versus 6 percent), but the frequency of side effects did not differ between the groups from day 1 to 14. No serious adverse events were observed.
Despite the demonstrated antiinflammatory efficacy of oral glucocorticoids, which suggests a first-line role for oral glucocorticoids, rebound attacks are relatively common once they are withdrawn, especially in patients who have previously suffered a number of prior attacks, whose intercritical periods have progressively shortened, and who are not receiving prophylactic therapy. For this reason, slower tapering of the glucocorticoid dose with extension of the course to 10 to 14 or even 21 days is advisable in such patients. In the rare patient who keeps flaring during oral glucocorticoid tapering, such that urate-lowering therapy has never been initiated, allopurinol treatment can often be successfully initiated with concomitant antiinflammatory treatment . (See "Prevention of recurrent gout: Pharmacologic urate-lowering therapy and treatment of tophi".)
Common adverse effects of short-term, moderate- to high-dose glucocorticoid use include mood changes, hyperglycemia, increased blood pressure, and fluid retention, but most patients tolerate glucocorticoids in the rapidly tapering regimens used for acute gout. Frequent and repeated courses of glucocorticoids should be avoided to limit adverse effects. This can usually be achieved by appropriate preventive therapy. (See "Major side effects of systemic glucocorticoids" and "Prevention of recurrent gout: Pharmacologic urate-lowering therapy and treatment of tophi".)
Parenteral glucocorticoids — In patients who are unable to take medications orally and who are not candidates for intraarticular glucocorticoid injection, we generally suggest treatment with intravenous or intramuscular glucocorticoids. The choice of glucocorticoid and the route of administration depend upon the clinical context:
●In hospitalized patients with polyarticular involvement, with existing or easily established intravenous access, and with no contraindications to glucocorticoids, we suggest intravenous administration of a parenteral glucocorticoid. The dose and frequency depend upon the agent chosen. A typical dose is 20 mg of methylprednisolone administered intravenously twice daily, with stepwise reduction by half of each dose when improvement begins and with maintenance of at least 4 mg twice daily (or oral equivalent) for five days.
●Intramuscular glucocorticoid injection has also been widely used for acute gout management, usually with an initial dose of triamcinolone acetate (40 to 60 mg) that may need to be repeated once or twice (at intervals of at least 48 hours) if benefit fades or if resolution of the flare is not achieved.
Few studies have adequately evaluated the benefit of systemic parenteral glucocorticoids ; these studies and the few randomized trials had significant limitations in quality and strength of evidence. Nonetheless, some experts report this approach to be effective and well-tolerated [1,5,8,38].
Patients on anticoagulation — In patients on anticoagulants, we use one of the following approaches:
●We use low-dose colchicine, in the absence of contraindications and in patients initiating treatment promptly after flare onset, because of its efficacy, convenience, lack of effect on blood clotting, and lack of need for a procedure. (See 'Colchicine therapy' above.)
●Joint aspiration and injection with glucocorticoids are another option, if only one or two joints are involved, and can be done safely even with anticoagulation. (See 'Intraarticular glucocorticoids' above and "Joint aspiration or injection in adults: Technique and indications", section on 'Approach to the patient on anticoagulants'.)
●Oral glucocorticoids can be used if there is polyarticular involvement or if arthrocentesis cannot be performed for other reasons. (See 'Oral glucocorticoids' above.)
Older adults — A systematic review of clinical trials for treatment of gout suggested that all of these agents were likely to be efficacious in older patients ; however, the management of acute gout in older patients is complicated by the greater prevalence of comorbidities, the use of multiple medications, and reductions in renal function associated with aging [40,41]. These safety concerns reduce the proportion of patients for whom nonsteroidal antiinflammatory drugs (NSAIDs) or colchicine may be preferred agents, but these drugs can be used in patients who lack such contraindications. However, we avoid the use of indomethacin in older adults because of the greater risk of adverse effects with this medication compared with other NSAIDs, consistent with the Beers Criteria for potentially inappropriate medication use in older adults . Glucocorticoids are generally tolerated in short-term use for acute attacks in patients in whom NSAIDs or colchicine may pose an increased risk. (See 'General therapeutic principles' above and "Drug prescribing for older adults".)
Contraindications to the use of NSAIDs which are of particular concern in older adults include the presence of heart failure, renal impairment, or gastrointestinal disease. Contraindications to colchicine include gastrointestinal intolerance, dosing restrictions in patients with renal and hepatic dysfunction, and potential drug interactions and also may include the high cost of therapy. General principles and special concerns in prescribing drugs in this population are discussed in more detail separately. (See "Drug prescribing for older adults".)
End-stage renal disease and transplantation — We generally treat patients with advanced chronic kidney disease (CKD) or end-stage renal disease requiring maintenance dialysis with intraarticular, oral, or parenteral glucocorticoids. In patients with residual kidney function, including patients on peritoneal dialysis, NSAIDs should be avoided because of the risk of worsening of renal function; any use of NSAIDs in this setting should only be done in consultation with the patient’s nephrologist. In patients on chronic hemodialysis, NSAIDs may be used as an alternative to glucocorticoids, particularly in patients with milder attacks in whom lower doses and shorter courses can be employed. Other concerns in patients on hemodialysis include concomitant use of anticoagulation and risk of gastrointestinal toxicity. Colchicine is generally avoided in hemodialysis patients with acute gout flares because it is not removed by dialysis, and therefore these patients have a heightened risk of colchicine toxicity. (See "NSAIDs: Acute kidney injury (acute renal failure)" and 'Intraarticular glucocorticoids' above and 'Oral glucocorticoids' above and 'Parenteral glucocorticoids' above.)
Acute gout in organ transplant recipients should only be managed by clinicians experienced with these clinical problems because of the complexities of management due to reduced uric acid excretion and because of the frequent accompanying use of cyclosporine. Colchicine, NSAIDs, and glucocorticoids can potentially be used, but limits on dosing, frequency, and duration of therapy usually apply. Treatment in this setting is discussed in more detail separately. (See "Hyperuricemia and gout in renal transplant recipients", section on 'Colchicine' and "Hyperuricemia and gout in renal transplant recipients", section on 'Nonsteroidal anti-inflammatory agents' and "Hyperuricemia and gout in renal transplant recipients", section on 'Increased glucocorticoid dose'.)
RESISTANT DISEASE — In patients with symptoms that are not improving as expected, the patients’ adherence to the treatment program should be assessed. Also, alternative agents should be considered, depending upon what has already been tried, and the diagnosis should be reevaluated. Arthrocentesis may be required to exclude other causes of a flare of acute inflammatory arthritis, including infection, if it was not already performed during the attack. It is important to not become overly concerned if attacks do not resolve within one to three days of starting treatment. Most acute flares of gout resolve within 7 to 10 days, regardless of the type of therapy, and resolution is much more rapid if the patient is treated early in the attack. Thus, truly resistant disease is uncommon, although some attacks may resolve slowly, especially if treatment is not started early or if there is extensive polyarticular disease leading to chronic gouty arthritis, where near continuous joint inflammation is noted. (See "Clinical manifestations and diagnosis of gout", section on 'Acute gouty arthritis' and "Clinical manifestations and diagnosis of gout", section on 'Differential diagnosis of acute gouty arthritis'.)
The management of patients with persistent symptoms due to a confirmed acute flare of gout depends upon the prior therapy and upon the patients’ comorbidities:
●In patients being treated with nonsteroidal antiinflammatory drugs (NSAIDs), a more prolonged course of therapy than usual may be required in some patients with persistent symptoms, especially if treatment was not started until the flare was ongoing for several days. Patients with a flare that appears resistant to an adequate course of NSAID therapy may respond to treatment with glucocorticoids. (See 'Glucocorticoids' above.)
●In patients who are being treated with colchicine but who do not have contraindications to NSAIDs, it may be necessary to switch to NSAID therapy if no improvement is seen within several days, especially if the attack was not treated early. In patients in whom NSAIDs are contraindicated, glucocorticoids may be required. (See 'NSAID therapy' above and 'Administration of colchicine' above and 'Glucocorticoids' above.)
●The management of recurrent (or “rebound”) attacks following treatment with glucocorticoids is discussed above. (See 'Oral glucocorticoids' above.)
●Interleukin (IL)-1 inhibition may be of benefit in selected patients. We use anakinra, an IL-1 receptor antagonist protein, only in gout patients with frequent flares in whom all other available treatments have failed or in whom “rebound flares” occur even when glucocorticoid treatment is appropriately tapered. Although IL-1 antagonist agents are available in some countries for the treatment of conditions other than gout, such as anakinra for rheumatoid arthritis and canakinumab and rilonacept for cryopyrin-associated periodic syndromes, only the first two have shown clear efficacy in treatment of acute gout and their use for this indication remains investigational in the United States (see 'Investigational therapy' below).
INVESTIGATIONAL THERAPY — IL-1 is an important mediator of gouty inflammation and a potential therapeutic target in acute gout . Thus, agents inhibiting IL-1 action are under study for the treatment of acute gout. (See "Pathophysiology of gouty arthritis".)
Anakinra (100 mg daily, administered subcutaneously) is the preferred IL-1 antagonist for use in acute gout because of its short half-life of IL-1 blockade and its relatively modest cost compared with other alternative IL-1 inhibitors, such as canakinumab. Canakinumab has been evaluated and approved for acute gout in the European Union ; it is expected to become available in Europe for use in the treatment of patients with acute gouty arthritis who have frequent attacks and who cannot be effectively managed with other treatment options. (See "Randomized clinical trials in rheumatoid arthritis of biologic agents that inhibit IL-1, IL-6, and RANKL", section on 'Anakinra' and "Cryopyrin-associated periodic syndromes and related disorders", section on 'Canakinumab'.)
Evidence of benefit from the inhibition of IL-1 effects includes the following:
●Anakinra – Beneficial effects of IL-1 inhibition were seen in some patients in open-label pilot studies of the recombinant IL-1 receptor antagonist, anakinra, with 100 mg daily given subcutaneously until symptoms of acute gouty arthritis improved [45-47]. However, some patients respond only partially to such treatment, and recurrent flares are common within one to six weeks after stopping therapy. The short biological half-life of anakinra, which mandates daily subcutaneous administration, makes this agent an unlikely candidate for gout flare prophylaxis but may, in the case of acute gout flares, provide an advantage in safety, since blocking of IL-1 beta action is rapidly reversed when treatment of this agent is discontinued.
●Canakinumab – Canakinumab is a fully humanized, long-acting monoclonal antibody that blocks IL-1 beta signaling; it can be effective for the treatment of acute gout in patients who have a history of multiple flares and who have either refractoriness or contraindication to acute flare treatment with NSAIDs and/or colchicine [44,48].
The efficacy and safety of canakinumab (a single subcutaneous injection of 150 mg plus a placebo intramuscular injection) were evaluated in such patients in comparison with triamcinolone acetonide (a single intramuscular injection of 40 mg plus a placebo subcutaneous injection) in two identically designed randomized trials (one in the US and the other in Europe and other non-US countries) involving a total of 456 patients . Canakinumab resulted in a significantly greater reduction in a mean 72-hour pain score using a 100 mm visual analog scale (decrease of 35.7 versus 25 mm).
Four patients in the published trials, all receiving canakinumab, required hospitalization for treatment of infections (one abscess of the jaw, one abscess of the forearm, pneumonia, and gastroenteritis), but there were no opportunistic infections. Other adverse events that were most common with canakinumab included low neutrophil counts and low platelet counts.
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)
●Basics topics (see "Patient information: Gout (The Basics)")
●Beyond the Basics topics (see "Patient information: Gout (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●The goal of therapy in an acute gout attack is prompt and safe termination of pain and disability. While symptoms will usually resolve without therapy within a few days to several weeks, symptoms improve more quickly with administration of antiinflammatory drugs. More rapid and complete resolution of symptoms occurs the earlier that treatment is introduced. Treatment with urate-lowering therapies is ineffective for acute gout, but urate-lowering therapy should not be initiated during an acute attack nor interrupted in patients on such therapy at the time of an acute attack. (See 'General therapeutic principles' above and "Prevention of recurrent gout: Pharmacologic urate-lowering therapy and treatment of tophi".)
●We suggest nonsteroidal antiinflammatory drugs (NSAIDs), rather than colchicine or glucocorticoids, as first-line therapy for most patients with acute gout and with no contraindications to their use (Grade 2B). We typically administer a potent NSAID (such as naproxen 500 mg twice daily or indomethacin 50 mg three times daily) for reduction of acute gouty inflammation. The NSAID can be discontinued one or two days after clinical signs have completely resolved. Typically, the total duration of NSAID therapy for an acute attack is five to seven days. It is likely to be shorter in patients who are treated within the first 24 hours of symptom onset and may be longer in patients in whom treatment is not begun until several days later. Aspirin is usually avoided because of the paradoxical effects of salicylates on serum urate. (See 'Administration of NSAIDs' above and 'Efficacy and safety of NSAIDs' above.)
●In patients with NSAID intolerance or with an absolute or relative contraindication to NSAIDs, we suggest the use of low-dose oral colchicine (1.5 to 1.8 mg in two or three divided doses in the first 24 hours, followed by tapering of the dose until resolution of the attack), rather than glucocorticoids (Grade 2B). We limit colchicine therapy to patients seen during the first 48 hours of an acute flare. Particular attention should be given to dose adjustment in patients receiving inhibitors of the cytochrome P450 system component CYP3A4 or inhibitors of the membrane P-glycoprotein multidrug resistance transporter (P-gp). Patients should not be treated with intravenously administered colchicine. (See 'Administration of colchicine' above and 'Efficacy of oral colchicine' above and 'Safety of colchicine' above.)
●In patients who are unable to take oral medications, who have only one or two actively inflamed joints, and in whom infection has been excluded, we suggest intraarticular injection of glucocorticoids (Grade 2B). We prefer triamcinolone acetonide (40 mg for a large joint [eg, knee], 30 mg for a medium joint [eg, wrist, ankle, elbow], and 10 mg for a small joint) or equivalent doses of methylprednisolone acetate. (See 'Intraarticular glucocorticoids' above.)
●In patients who cannot take NSAIDs or colchicine and who are not candidates for intraarticular glucocorticoid injection, we suggest use of oral glucocorticoids (Grade 2B). We often use prednisone in doses of 30 to 50 mg per day (as a single dose or two divided doses) or another equivalent glucocorticoid until pain and disability begin to resolve, and we then taper over at least 7 to 10 days and over at least 10 to 14 days in patients with multiple prior flares. Rebound flares occur more frequently with glucocorticoids than with alternative agents unless doses are tapered over periods of one to three weeks, according to the patient’s gout history. (See 'Oral glucocorticoids' above.)
●For patients with polyarticular involvement who are unable to take oral medications, have existing or easily established intravenous access, and have no contraindications to glucocorticoids, we suggest systemic administration of an intravenous glucocorticoid (Grade 2B). The dose and frequency depend upon the agent chosen. A typical dose is 20 mg methylprednisolone twice daily, with stepwise reduction by half of each dose when improvement begins and with maintenance of at least 4 mg twice daily (or oral equivalent) for at least five days. For patients with no intravenous access, intramuscular glucocorticoids may be used. (See 'Parenteral glucocorticoids' above.)
●An additional alternative for patients who are unresponsive to any other available approach and who have frequent recurrent attacks is an interleukin (IL)-1 inhibitor, such as anakinra or canakinumab (where available). The benefits of these agents for symptomatic relief need to be balanced with the potential for increased risk for serious infections. (See 'Resistant disease' above.)
●In patients who are anticoagulated, we use low-dose oral colchicine. We use intraarticular or oral glucocorticoids for the treatment of acute attacks if colchicine is contraindicated. We generally treat acute gout in patients with advanced chronic kidney disease (CKD) or with end-stage renal disease requiring maintenance dialysis with intraarticular, oral, or systemic glucocorticoids. (See 'Patients on anticoagulation' above and 'End-stage renal disease and transplantation' above.)
- Neogi T. Clinical practice. Gout. N Engl J Med 2011; 364:443.
- Terkeltaub R. Update on gout: new therapeutic strategies and options. Nat Rev Rheumatol 2010; 6:30.
- Sundy JS. Progress in the pharmacotherapy of gout. Curr Opin Rheumatol 2010; 22:188.
- Schlesinger N, Detry MA, Holland BK, et al. Local ice therapy during bouts of acute gouty arthritis. J Rheumatol 2002; 29:331.
- Zhang W, Doherty M, Bardin T, et al. EULAR evidence based recommendations for gout. Part II: Management. Report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2006; 65:1312.
- Khanna D, Fitzgerald JD, Khanna PP, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken) 2012; 64:1431.
- Khanna D, Khanna PP, Fitzgerald JD, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 2: therapy and antiinflammatory prophylaxis of acute gouty arthritis. Arthritis Care Res (Hoboken) 2012; 64:1447.
- Sutaria S, Katbamna R, Underwood M. Effectiveness of interventions for the treatment of acute and prevention of recurrent gout--a systematic review. Rheumatology (Oxford) 2006; 45:1422.
- Schumacher HR Jr, Boice JA, Daikh DI, et al. Randomised double blind trial of etoricoxib and indometacin in treatment of acute gouty arthritis. BMJ 2002; 324:1488.
- Rubin BR, Burton R, Navarra S, et al. Efficacy and safety profile of treatment with etoricoxib 120 mg once daily compared with indomethacin 50 mg three times daily in acute gout: a randomized controlled trial. Arthritis Rheum 2004; 50:598.
- Maccagno A, Di Giorgio E, Romanowicz A. Effectiveness of etodolac ('Lodine') compared with naproxen in patients with acute gout. Curr Med Res Opin 1991; 12:423.
- Lomen PL, Turner LF, Lamborn KR, et al. Flurbiprofen in the treatment of acute gout. A comparison with indomethacin. Am J Med 1986; 80:134.
- Altman RD, Honig S, Levin JM, Lightfoot RW. Ketoprofen versus indomethacin in patients with acute gouty arthritis: a multicenter, double blind comparative study. J Rheumatol 1988; 15:1422.
- Schumacher HR, Berger MF, Li-Yu J, et al. Efficacy and tolerability of celecoxib in the treatment of acute gouty arthritis: a randomized controlled trial. J Rheumatol 2012; 39:1859.
- YU TF, GUTMAN AB. Study of the paradoxical effects of salicylate in low, intermediate and high dosage on the renal mechanisms for excretion of urate in man. J Clin Invest 1959; 38:1298.
- YUE TF, DAYTON PG, GUTMAN AB. MUTUAL SUPPRESSION OF THE URICOSURIC EFFECTS OF SULFINPYRAZONE AND SALICYLATE: A STUDY IN INTERACTIONS BETWEEN DRUGS. J Clin Invest 1963; 42:1330.
- Caspi D, Lubart E, Graff E, et al. The effect of mini-dose aspirin on renal function and uric acid handling in elderly patients. Arthritis Rheum 2000; 43:103.
- Segal R, Lubart E, Leibovitz A, et al. Renal effects of low dose aspirin in elderly patients. Isr Med Assoc J 2006; 8:679.
- Zhang Y, Neogi T, Chen C, et al. Low-dose aspirin use and recurrent gout attacks. Ann Rheum Dis 2014; 73:385.
- van Durme CM, Wechalekar MD, Buchbinder R, et al. Non-steroidal anti-inflammatory drugs for acute gout. Cochrane Database Syst Rev 2014; :CD010120.
- Colcrys FDA Approval Letter. http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2009/022351s000ltr.pdf (Accessed on February 10, 2010).
- Colcrys (colchicine USP) Medication Guide. Revision 02, September 2009. Mutual Pharmaceutical Company, Inc, Philadelphia, PA 19124 USA. (Approved by the US Food and Drug Administration).
- Colcrys (colchicine, USP) full prescribing information http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022351lbl.pdf (Accessed on April 25, 2011).
- Ahern MJ, Reid C, Gordon TP, et al. Does colchicine work? The results of the first controlled study in acute gout. Aust N Z J Med 1987; 17:301.
- Terkeltaub RA, Furst DE, Bennett K, et al. 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 2010; 62:1060.
- Terkeltaub RA. Colchicine update: 2008. Semin Arthritis Rheum 2009; 38:411.
- Bouquié R, Deslandes G, Renaud C, et al. Colchicine-induced rhabdomyolysis in a heart/lung transplant patient with concurrent use of cyclosporin, pravastatin, and azithromycin. J Clin Rheumatol 2011; 17:28.
- Yu DK. The contribution of P-glycoprotein to pharmacokinetic drug-drug interactions. J Clin Pharmacol 1999; 39:1203.
- P450 Drug interaction table. http://medicine.iupui.edu/clinpharm/ddis/ClinicalTable.asp (Accessed on June 07, 2010).
- Fernández C, Noguera R, González JA, Pascual E. Treatment of acute attacks of gout with a small dose of intraarticular triamcinolone acetonide. J Rheumatol 1999; 26:2285.
- Wechalekar MD, Vinik O, Schlesinger N, Buchbinder R. Intra-articular glucocorticoids for acute gout. Cochrane Database Syst Rev 2013; :CD009920.
- Janssens HJ, Janssen M, van de Lisdonk EH, et al. Use of oral prednisolone or naproxen for the treatment of gout arthritis: a double-blind, randomised equivalence trial. Lancet 2008; 371:1854.
- Groff GD, Franck WA, Raddatz DA. Systemic steroid therapy for acute gout: a clinical trial and review of the literature. Semin Arthritis Rheum 1990; 19:329.
- Man CY, Cheung IT, Cameron PA, Rainer TH. 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 2007; 49:670.
- Rainer TH, Cheng CH, Janssens HJ, et al. Oral Prednisolone in the Treatment of Acute Gout: A Pragmatic, Multicenter, Double-Blind, Randomized Trial. Ann Intern Med 2016; 164:464.
- Taylor TH, Mecchella JN, Larson RJ, et al. Initiation of allopurinol at first medical contact for acute attacks of gout: a randomized clinical trial. Am J Med 2012; 125:1126.
- Janssens HJ, Lucassen PL, Van de Laar FA, et al. Systemic corticosteroids for acute gout. Cochrane Database Syst Rev 2008; :CD005521.
- Colchicine and other drugs for gout. Med Lett Drugs Ther 2009; 51:93.
- Fravel MA, Ernst ME. Management of gout in the older adult. Am J Geriatr Pharmacother 2011; 9:271.
- Stamp LK, Jordan S. The challenges of gout management in the elderly. Drugs Aging 2011; 28:591.
- Singh H, Torralba KD. Therapeutic challenges in the management of gout in the elderly. Geriatrics 2008; 63:13.
- American Geriatrics Society 2012 Beers Criteria Update Expert Panel. American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2012; 60:616.
- Martinon F, Pétrilli V, Mayor A, et al. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 2006; 440:237.
- Schlesinger N, Alten RE, Bardin T, et al. Canakinumab for acute gouty arthritis in patients with limited treatment options: results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions. Ann Rheum Dis 2012; 71:1839.
- So A, De Smedt T, Revaz S, Tschopp J. A pilot study of IL-1 inhibition by anakinra in acute gout. Arthritis Res Ther 2007; 9:R28.
- Chen K, Fields T, Mancuso CA, et al. Anakinra's efficacy is variable in refractory gout: report of ten cases. Semin Arthritis Rheum 2010; 40:210.
- Tran AP, Edelman J. Interleukin-1 inhibition by anakinra in refractory chronic tophaceous gout. Int J Rheum Dis 2011; 14:e33.
- So A, De Meulemeester M, Pikhlak A, et al. Canakinumab for the treatment of acute flares in difficult-to-treat gouty arthritis: Results of a multicenter, phase II, dose-ranging study. Arthritis Rheum 2010; 62:3064.