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Treatment of acute gout
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Treatment of acute gout
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Literature review current through: Jul 2017. | This topic last updated: Jun 28, 2017.

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 systemic and intraarticular glucocorticoids, nonsteroidal antiinflammatory drugs (NSAIDs), colchicine, 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:

Early treatment – 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.

Duration of therapy – Complete cessation of treatment for the acute flare can usually be safely done within two to three days of complete resolution of the attack; however, in the case of oral glucocorticoids, we taper more slowly to lower the risk of a recurrent ("rebound") 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). Many patients require antiinflammatory treatment for an acute attack for no more than five to seven days if begun on therapy within 12 to 36 hours of symptom onset.

Gout flare prophylaxis – Low-dose antiinflammatory therapy should generally be continued during the early months of urate-lowering treatment [4-8]. The intent of this treatment, called antiinflammatory gout flare prophylaxis, is to reduce the risk of additional flares, which are common early in the course of antihyperuricemic treatment. (See "Prevention of recurrent gout: Pharmacologic urate-lowering therapy and treatment of tophi", section on 'Prophylaxis during initiation of antihyperuricemic therapy'.)

Continuing urate-lowering therapy during attacks – In patients already receiving urate-lowering pharmacotherapy at the time of an acute flare (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.

However, urate-lowering therapies are of no direct benefit in the treatment of an acute gout attack, and whether to initiate a urate-lowering agent along with antiinflammatory therapy during a flare is controversial, as discussed separately. (See "Prevention of recurrent gout: Pharmacologic urate-lowering therapy and treatment of tophi", section on 'Initiation and duration of urate-lowering pharmacotherapy'.)

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'.)

Tophaceous gout – 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 pharmacotherapy either during or following resolution of the acute attack 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".)

Comorbidities – Important comorbidities (and their ongoing therapies) that are frequent among gout patients may affect antiinflammatory 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:

Renal function

Cardiovascular disease, including heart failure or poorly controlled hypertension

Gastrointestinal disease, including peptic ulcer disease

Concurrent medication use

Diabetes mellitus, especially if poorly controlled

Drug allergy or intolerance

Adjunctive measures – Adjunctive measures, none of which are of proven efficacy, are often administered for symptom relief and include icing the affected joint [9], 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 — Several different therapies, including systemic and intraarticular glucocorticoids, nonsteroidal antiinflammatory drugs (NSAIDs), and colchicine, are each effective for the treatment of acute gout; there is no single best agent for all patients experiencing an acute flare of gout. The availability of multiple classes of agents and approaches likely to provide treatment benefit permits the opportunity to choose which therapy, based upon an assessment of specific features of the individual patient and the flare history, is most likely to achieve benefit and minimize the risk of adverse therapeutic consequences.

Factors affecting drug choice — Factors that may influence the choice of medication include:

Patient-related medical factors – These include patient comorbidities (nature, number, and current clinical status), past medical history, concomitant medication use, allergies, and childbearing status.

The patient's gout history – These include total flare number and recent rate of flare occurrence; and patient prior flare experience with specific therapies (antiinflammatory agent tolerability and effectiveness).

Characteristics of the acute flare – Variables that may influence the choice of agent and route of therapy with respect to the current flare include the duration of flare from symptom onset to therapeutic assessment, the number of affected joints and the injection accessibility of the inflamed joint(s), and the clinical setting in which the flare is occurring (eg, during initiation of urate-lowering, during a postoperative period, or when the patient is unable to take medications by mouth).

Logistic factors – These include issues such as drug availability and cost, the location of the patient (eg, home or clinic), and clinician expertise in arthrocentesis and joint injection.

Choice of agent — We take the following approach to patients with an acute gout flare, which depends upon knowledge of the contextual medical and other factors that influence the relative safety and efficacy of each agent in individual patients (see 'Factors affecting drug choice' above):

Can take oral medications – In most patients who can take oral medications, we suggest oral glucocorticoids or NSAIDs; colchicine is a safe and effective alternative for some patients:

Oral glucocorticoids – We use oral glucocorticoids in many patients, particularly those who are not candidates for intraarticular glucocorticoid injection and those who have contraindications to use of NSAIDs. The initial dose is 30 to 40 mg of prednisone or prednisolone given once daily or in a divided twice-daily dose; the duration of therapy depends upon several factors. (See 'Oral glucocorticoids' below.)

Glucocorticoids are similar in efficacy to other agents and have no greater risk of adverse effects in most patients, although other options may be preferred in patients with concomitant infection, prior glucocorticoid intolerance, brittle diabetes, and those who are in a postoperative period in whom glucocorticoids may increase risk of impaired wound healing. In addition, NSAIDs or low-dose colchicine may be preferred over glucocorticoids in patients with frequently recurrent attacks to avoid excessive total glucocorticoid dosing over time.

NSAIDs – A reasonable alternative to oral glucocorticoids is a potent oral NSAID, such as naproxen (500 mg twice daily) or indomethacin (50 mg three times daily). NSAIDs are a particularly appropriate alternative in younger patients (less than 60 years old) who lack renal, cardiovascular, or active gastrointestinal disease. Different NSAIDs appear comparably effective, and the ready availability of several NSAIDs without a prescription may favor their use in some patients. (See 'NSAID therapy' below.)

Colchicine – Another reasonable alternative to glucocorticoids or NSAIDs is colchicine, which is at least comparably effective to the other agents when taken within 24 hours of onset of an acute attack. Colchicine should be administered in a total dose on day 1 not to exceed 1.8 mg, either taken as 0.6 mg three times on the first day or by taking 1.2 mg for the first dose followed by 0.6 mg an hour later; on subsequent days colchicine is taken once or twice daily until flare resolution. In some countries, colchicine is available as a 0.5 mg rather than as a 0.6 mg pill. (See 'Colchicine therapy' below.)

Colchicine is a particularly convenient agent for patients already taking this medication for prophylaxis and for patients who have the drug available at home for use only at the onset of an acute flare. Colchicine should be avoided in patients with severe renal or hepatic impairment and in patients on certain medications that may adversely interact with it.

Unable to take oral medications – Patients unable to take oral medications can usually be treated with parenteral glucocorticoids:

Candidate for arthrocentesis and injection – In patients who are unable to take oral medications, have only one or two actively inflamed joints, and have ready access to a clinician with expertise in arthrocentesis and injection, we suggest arthrocentesis with joint fluid aspiration and analysis followed by intraarticular injection of glucocorticoids. Infection should be excluded before injecting glucocorticoids. This approach (arthrocentesis and glucocorticoid injection) is also an alternative to the use of orally administered NSAIDs or colchicine in patients with only one or two actively inflamed joints. (See 'Intraarticular glucocorticoids' below.)

Not a candidate for arthrocentesis and injection – In patients who are unable to take medications orally but are not candidates for intraarticular glucocorticoid injection, we suggest treatment with intravenous or intramuscular glucocorticoids. The choice of glucocorticoid and the route of administration depend upon the clinical context. (See 'Parenteral glucocorticoids' below.)

Concomitant anticoagulation therapy – In patients receiving anticoagulation, the treatment options include low-dose oral colchicine, which is most effective when taken within 24 hours of attack onset, and intraarticular or oral glucocorticoids. (See 'Patients on anticoagulation' below.)

Persistent symptoms – The management of patients with persistent symptoms due to a confirmed acute flare of gout depends upon the prior therapy and upon patient comorbidities. Useful interventions include more prolonged treatment courses than usual, switching or combining agents, and the use of interleukin (IL)-1 inhibitors. (See 'Resistant disease' below and 'Investigational therapy' below.)

Despite widespread use in the treatment of acute gout attacks, the various classes of antiinflammatory agents had, until about 2002 to 2005, only infrequently been compared with placebo [10,11] or with one another in randomized trials [4,7,12]. The results of efforts to obtain more evidence of the relative efficacy of these agents are reflected in the guidelines of the major professional groups [6-8], which state that treatment with a glucocorticoid (given orally, by intraarticular injection, or parenterally), or an oral NSAID, or oral colchicine in a low-dose regimen each has substantial efficacy in reducing or preventing full expression of the symptoms and signs of an acute gout flare [13-24].

Our approach to the patient with acute gout is based upon the available data and our clinical experience; this approach is generally consistent with that recommended by the European League Against Rheumatism (EULAR), the American College of Rheumatology (ACR), the American College of Physicians (ACP), and the British Society for Rheumatology (BSR) [4-8,25].

Glucocorticoid therapy

Administration and choice of glucocorticoid — Glucocorticoids are highly effective as rapidly acting antiinflammatory agents. The chosen route of administration depends upon several factors, including the number of involved joints, patient preference, the timely availability of the patient and the clinician, the experience of the clinician with joint injection techniques, and the need in some patients for parenteral rather than orally administered glucocorticoid therapy. 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 of the clinician and the need for direct patient-clinician interaction. For these reasons, as well as the generally favorable benefit/risk profile of oral glucocorticoid use [20-22,24], glucocorticoids are administered orally much more commonly in practice than by parenteral routes. (See 'Oral glucocorticoids' below and 'Intraarticular glucocorticoids' below and 'Parenteral glucocorticoids' below.)

Glucocorticoids should be used with caution and close monitoring in patients with heart failure, poorly controlled hypertension, or glucose intolerance, but they may be used in patients with moderate to severe renal insufficiency.

Several randomized trials comparing oral glucocorticoid (or, in one case, intramuscular glucocorticoid) with NSAID therapy for acute gout flare indicate that glucocorticoids are at least as efficacious as NSAID therapy and may have fewer serious adverse outcomes [20-22,24]. Glucocorticoid treatment also offers routes of administration appropriate for some patients who are either not candidates for oral antiinflammatory drug therapy or who might benefit from intraarticular glucocorticoid therapy. For these reasons, as well as the ready availability and modest cost, glucocorticoid therapy is increasingly favored by most [6-8], but not all [25], expert guideline panels for first-line gout flare treatment.

Oral glucocorticoids — We suggest oral glucocorticoids (eg, prednisone or prednisolone) for most patients with acute gout flare, particularly for those who are not candidates for intraarticular glucocorticoid injection because of polyarticular disease or who do not have ready access to a clinician with expertise in arthrocentesis and injection. We use prednisone (or an equivalent glucocorticoid) in doses of 30 to 40 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.

Rebound attacks are relatively common once glucocorticoids 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 antiinflammatory flare prophylaxis; in these groups of patients, slower tapering of the glucocorticoid dose with extension of the duration of the taper to 10 to 14 or even 21 days is advisable.

In the rare patient who keeps flaring during oral glucocorticoid tapering, and in whom urate-lowering therapy has never been initiated, urate-lowering therapy (eg, allopurinol) can often be successfully initiated with concomitant antiinflammatory treatment [26]. (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 (see "Major side effects of systemic glucocorticoids"), but most patients tolerate glucocorticoids well in the rapid tapering regimens used for acute gout. Frequent and repeated courses of glucocorticoids should be avoided to limit adverse effects. In the long term, such patients will benefit more from concomitant initiation of antiinflammatory gout flare prophylaxis and serum urate-monitored urate-lowering therapy. (See "Prevention of recurrent gout: Pharmacologic urate-lowering therapy and treatment of tophi", section on 'Prophylaxis during initiation of antihyperuricemic therapy'.)

Several randomized trials comparing oral glucocorticoids with NSAID therapy for acute gout flare indicate that glucocorticoids such as prednisone and prednisolone are at least as efficacious as NSAIDs and may have fewer serious adverse outcomes [20-22]. As an example, in one 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) [22]. 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 days 1 to 14. No serious adverse events were observed.

Intraarticular glucocorticoids — We suggest arthrocentesis with joint fluid aspiration and analysis followed by intraarticular injection of glucocorticoids for patients who are either unable to take oral medications or who have only one or two actively inflamed joints and in whom infection has been excluded. Use of this approach is contingent upon the ready availability of a clinician with expertise in such procedures and the accessibility of the joint.

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".)

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 acute calcium pyrophosphate crystal disease (pseudogout). (See "Clinical manifestations and diagnosis of calcium pyrophosphate crystal deposition (CPPD) disease".)

Importantly, septic arthritis and acute gout can coexist; therefore, 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.

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 [27]. A 2013 systematic review of the safety and efficacy of intraarticular glucocorticoid injection for acute gout could, however, 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 [28].

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 "Management of moderate to severe knee osteoarthritis", section on 'Intraarticular glucocorticoid injection'.)

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 reported to be effective [24,29] 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 randomized trials have adequately evaluated the benefit of systemic parenteral glucocorticoids [30]; the published 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 [1,12,31,32].

Corticotropin (adrenocorticotropic hormone [ACTH]) has also been reported to be efficacious for gout flare treatment, but cost and limited availability restrict the use of parenteral ACTH treatment.

NSAID therapy

Administration of NSAIDs — We use a potent oral NSAID, such as naproxen (500 mg twice daily) or indomethacin (50 mg three times daily), as an alternative to glucocorticoids for reduction of acute gouty inflammation, particularly in younger patients (less than 60 years old) with neither renal or cardiovascular comorbidities or active gastrointestinal disease. Nonselective NSAIDs are inexpensive, readily available to patients at the onset of an attack (some without a prescription), and, in our experience, probably as effective and safe as other agents [12-17] for this indication and with treatment for a limited duration [12,15-18].

NSAIDs are most effective when treatment is initiated within 48 hours of the onset of symptoms. The dose may be reduced after a significant decrease in symptoms has occurred, but the frequency of dosing should be maintained for several more days for optimal antiinflammatory effect. High-dose celecoxib, a cyclooxygenase (COX)-2 selective inhibitor, is an alternative to nonselective NSAIDs; in a randomized trial in acute gout, a single 800 mg dose of celecoxib followed by 400 mg twice daily was comparable in efficacy to indomethacin 50 mg three times daily [18]. (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:

Chronic kidney disease (CKD) with creatinine clearance (CrCl) of less than 60 mL/minute 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")

NSAID allergy

Ongoing treatment with anticoagulants (see 'Patients on anticoagulation' below)

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 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 [33-36]. 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 [35,36]. 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 [37].

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 relatively few high-quality randomized trials of NSAIDs for acute gouty arthritis [4,12,18,38], and there are no randomized trials that compare NSAIDs with colchicine. Several randomized trials comparing oral glucocorticoid (or in one case, intramuscular glucocorticoid) with NSAID therapy for acute gout flare indicate similar benefit, although glucocorticoids may have fewer adverse effects, particularly in comparison with indomethacin [20-22,24]. A number of trials have compared different NSAIDs with each other, without any apparent differences in efficacy [12-18]. One additional study showed superiority of an NSAID (tenoxicam) over placebo [11]. 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) [18].

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 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".)

Colchicine therapy — We preferentially use low-dose oral colchicine therapy for acute gout flare in two circumstances:

In patients with glucocorticoid and NSAID intolerance or with absolute (or often relative) contraindication to glucocorticoid and NSAID use. (See 'Glucocorticoid therapy' above and 'NSAID therapy' above.)

In patients initiating antiinflammatory gout flare therapy within 24 hours of symptom onset.

In our experience, incipient attacks may frequently be aborted by use of low-dose oral colchicine as soon as the patient perceives the first sign of an attack. For this reason, we use colchicine as an alternative to glucocorticoids or NSAIDs for flare treatment in patients with prior flares successfully treated with colchicine. We prescribe such patients a supply of this agent for home use to allow early initiation of low-dose treatment (see 'Administration of colchicine' below) at the first symptom of flare recurrence.

Patients receiving ongoing colchicine antiinflammatory gout flare prophylaxis should also be instructed in the low-dose colchicine acute flare regimen in the event that a gout flare develops during prophylaxis. (See "Prevention of recurrent gout: Pharmacologic urate-lowering therapy and treatment of tophi", section on 'Prophylaxis during initiation of antihyperuricemic therapy'.)

In patients who have initiated acute gout flare therapy with an NSAID and have either experienced an adverse event warranting an alternative antiinflammatory agent or have had no pain reduction, we would consider use of colchicine rather than an oral glucocorticoid as the second-line agent only if time since flare onset is within 36 hours. We generally do not initiate colchicine as first-line therapy for acute attacks that have been ongoing for more than 36 hours because of the diminished likelihood of benefit. (See 'Efficacy of oral colchicine' below.)

Administration of colchicine — There are several low-dose colchicine regimens that may be effective for management of acute flare. 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 [19,32,39]. 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 United States) three times on the first day of flare treatment [4].

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 [32]. (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/minute).

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 [32,39,40]. (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 [32,39,40]. (See 'Safety of colchicine' below.)

Colchicine dose reduction is required for patients with a CrCl of <45 mL/minute and with active hepatic disease.

Common adverse effects of colchicine include diarrhea and abdominal cramping [19,40], but these are less likely in patients who receive no more than 1.8 mg in total on the first day [19] 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) [10,19].

When low-dose colchicine therapy is ineffective or is minimally effective in suppressing acute gout in a timely fashion, alternative antiinflammatory agents, including glucocorticoids or NSAIDs, may be required. In patients without contraindications to NSAID or glucocorticoid use, supplemental oral therapy with an NSAID or with a glucocorticoid given orally, by intraarticular injection, or parenterally may also be used. (See 'Glucocorticoid therapy' above and 'NSAID therapy' above.)

Efficacy of oral colchicine — Colchicine for the treatment of acute gouty arthritis has not been extensively studied in randomized trials [10,19] 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 United States for the treatment of acute gout in 2009 [41].

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 [19]. A significantly greater proportion of patients in the low- 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 [42,43]. 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 [42,43].

Gastrointestinal symptoms (diarrhea, abdominal pain, nausea, and vomiting) are the most common adverse reactions to colchicine administration [39]. A readily reversible peripheral neuropathy or more severe organ failure may occur in instances of acute or persistent colchicine overdosing but are rare during limited duration treatment of an acute flare. 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 [44].

We 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 potent 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 [39]. 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 [43]. Commonly used strong CYP3A4 inhibitors include human immunodeficiency virus (HIV) protease inhibitors, clarithromycin (and other macrolide antibiotics), azole antifungals, and others (table 1) [42]. 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.

SPECIAL CIRCUMSTANCES

Patients on anticoagulation — In patients on anticoagulants, we use one of the following approaches:

In patients initiating treatment promptly after flare onset, in the absence of contraindications, we use low-dose colchicine because of its efficacy, convenience, lack of effect on blood clotting, and lack of need for arthrocentesis and joint injection with a glucocorticoid preparation. (See 'Colchicine therapy' above.)

In patients with polyarticular involvement or if arthrocentesis cannot be performed for other reasons, oral glucocorticoids can be used. (See 'Oral glucocorticoids' above and 'Intraarticular glucocorticoids' above and "Joint aspiration or injection in adults: Technique and indications", section on 'Approach to the patient on anticoagulants'.)

Joint aspiration and injection with a glucocorticoid provide another option if only one or two joints are involved; this 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'.)

Selected patients on anticoagulation who are unable to be treated with either glucocorticoids or colchicine may be managed, if necessary, with celecoxib, which lacks the antiplatelet effect of the nonselective nonsteroidal antiinflammatory drugs (NSAIDs), but retains some potential for gastrointestinal toxicity. (See 'Efficacy and safety of NSAIDs' above and "Overview of selective COX-2 inhibitors", section on 'Reduction in gastroduodenal toxicity' and "Overview of selective COX-2 inhibitors", section on 'Lack of effect upon platelets' and "Overview of selective COX-2 inhibitors", section on 'Reduced risk of bleeding in anticoagulated patients'.)

Older adults — 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 [45,46], although a systematic review of clinical trials for treatment of gout suggested that all of the antiinflammatory agents discussed here were likely to be efficacious in older patients [47].

These safety concerns reduce the proportion of patients for whom NSAIDs or colchicine may be preferred agents, although 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 [48]. (See 'General therapeutic principles' above and "Drug prescribing for 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 'Administration and choice of glucocorticoid' above and 'Efficacy and safety of NSAIDs' above and 'Safety of colchicine' above.)

Contraindications to the use of NSAIDs that 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. (See 'Glucocorticoid therapy' above.)

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 (see 'NSAID therapy' above). Other concerns in patients on hemodialysis include concomitant use of anticoagulation and risk of gastrointestinal toxicity.

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. (See "NSAIDs: Acute kidney injury (acute renal failure)".)

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 'Safety of colchicine' 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'.)

Pregnancy and lactation

In pregnant women with an acute gout flare, we generally use oral glucocorticoid therapy (see 'Glucocorticoid therapy' above). The use of NSAIDs is limited to the first 20 to 30 weeks of gestation, and we avoid use of colchicine in pregnant women. (See 'NSAID therapy' above.)

Potential contraindications to glucocorticoids in such patients include poorly controlled hypertension or diabetes, in addition to other usual concerns. We also employ symptomatic treatment measures, such as icing and protection of the affected site of inflammation.

In breastfeeding women, we use either glucocorticoids or NSAID therapy (see 'Glucocorticoid therapy' above and 'NSAID therapy' above) while continuing to avoid the use of colchicine.

Acute gout is exceedingly uncommon during pregnancy and lactation, paralleling the low prevalence of hyperuricemia in women of childbearing age in most populations (see "Asymptomatic hyperuricemia", section on 'Epidemiology'). Thus, the occurrence of an acute inflammatory arthritis resembling gout during pregnancy or breastfeeding should direct attention to the exclusion of alternative diagnoses, such as septic arthritis. (See "Clinical manifestations and diagnosis of gout", section on 'Differential diagnosis'.)

Despite its rarity, gout flares during pregnancy and/or lactation have been reported among women with familial juvenile hyperuricemic nephropathy [49,50] (see "Autosomal dominant tubulointerstitial kidney disease (medullary cystic kidney disease)", section on 'Uromodulin kidney disease (UKD)'), unspecified "renal impairment," and gestational diabetes [51].

Although antiinflammatory doses of an NSAID (eg, naproxen, ibuprofen, or indomethacin) have been effective in some pregnant patients with acute gout, use of NSAIDs is limited to the first two trimesters of pregnancy because of concerns about NSAID-induced premature closure of the ductus arteriosus later in pregnancy. NSAID therapy should also be withheld during pregnancy in the presence of impaired renal function. The use of NSAIDs during pregnancy and lactation is described in detail separately. (See "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation", section on 'NSAIDs and moderate to high-dose aspirin'.)

Data directly derived from treatment of gout in pregnant and lactating women are fragmentary, although studies of colchicine in pregnant and breastfeeding patients with familial Mediterranean fever (FMF) and patients with pericardial diseases have not found increased adverse effects with its use [52,53]. However, reports of chromosomal damage associated with colchicine exposure and the detection of colchicine in breast milk [54] raise concerns regarding the safety of colchicine during pregnancy and lactation [25,53].

In the infrequent patient with recurrent flares during pregnancy or breastfeeding who require prophylaxis to prevent acute attacks, we use daily low-dose glucocorticoids, given the need to avoid both colchicine and NSAIDs.

RESISTANT DISEASE — In patients with symptoms that are not improving as expected, the patients' adherence to the treatment program should be assessed. Additionally, 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 joint aspiration was not already performed during the attack.

It is important not to 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 'Glucocorticoid therapy' above.)

In patients who are being treated with colchicine but who do not have contraindications to glucocorticoids or NSAIDs, it may be necessary to switch to one of these therapies if no improvement is seen within several days, especially if the attack was not treated early. (See 'Administration of colchicine' above and 'NSAID therapy' above and 'Glucocorticoid therapy' 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, although canakinumab has been approved in the European Union for use in patients with more than three attacks of acute gout annually that are refractory to treatment with alternative agents. (See 'Investigational therapy' below.)

INVESTIGATIONAL THERAPY — Interleukin (IL)-1 is an important mediator of gouty inflammation and a potential therapeutic target in acute gout [55]. Thus, agents inhibiting IL-1 action are under study for the treatment of acute gout (see "Pathophysiology of gouty arthritis"). These include:

Anakinra – 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. (See "Randomized clinical trials in rheumatoid arthritis of biologic agents that inhibit IL-1, IL-6, and RANKL", section on '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 [56-58]. However, some patients responded only partially to such treatment, and recurrent flares are common within one to six weeks after stopping therapy. The short biologic 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 has been evaluated [59] and approved in the European Union for treatment of refractory acute gout. It is indicated for use in the treatment of patients with at least three attacks of acute gouty arthritis annually, which cannot be effectively managed with other antiinflammatory treatment options. (See "Cryopyrin-associated periodic syndromes and related disorders", section on '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 [59,60].

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 United States and the other in Europe and other non-United States countries) involving a total of 456 patients [60]. Canakinumab administration resulted in a significantly greater reduction in 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 education: Gout (The Basics)")

Beyond the Basics topics (see "Patient education: Gout (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

The goal of therapy in an acute gout attack ("flare") is prompt and safe termination of pain and disability. Symptoms will usually resolve without therapy within a few days to several weeks but improve more quickly with administration of one of several classes of antiinflammatory drugs. More rapid and complete resolution of symptoms occurs the earlier that treatment is introduced. Initiation of treatment with urate-lowering pharmacotherapies is of no direct benefit in treating an acute gout flare, but ongoing urate-lowering therapy should not be 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".)

The choice of therapy for an acute gout flare depends upon an individual patient assessment of multiple factors, including patient age, comorbidities, and associated medical therapies; flare characteristics and past responses to therapy; the number of affected joints and their accessibility to arthrocentesis and injection; and patient and clinician preferences. (See 'Initial treatment' above.)

In most patients who can take oral medications, we suggest oral glucocorticoids or NSAIDs for the treatment of acute gout flares. Colchicine is a safe and effective alternative for some patients. (See 'Choice of agent' above.)

We use oral glucocorticoids in many patients, particularly for those who are not candidates for intraarticular glucocorticoid injection and those who have contraindications to use of NSAIDs: prednisone or prednisolone, at an initial dose of 30 to 40 mg once daily or in a divided twice-daily dose until flare resolution begins, then we taper the dose, usually over 7 to 10 days. Because rebound flares occur more frequently with glucocorticoids than with alternative agents, especially among patients with multiple recent flares, we extend the course of glucocorticoid tapering to 14 to 21 days in such individuals. (See 'Oral glucocorticoids' above.)

Other options (eg, NSAIDs, colchicine) may be preferred in patients with concomitant infection, prior glucocorticoid intolerance, brittle diabetes, and those who are in a postoperative period in whom glucocorticoids may increase risk of impaired wound healing. NSAIDs or low-dose colchicine may also be preferred over glucocorticoids in patients with frequently recurrent attacks to avoid excessive total glucocorticoid dosing over time.

A reasonable alternative to oral glucocorticoids for an acute gout flare is a potent oral NSAID, such as naproxen (500 mg twice daily) or indomethacin (50 mg three times daily). NSAIDs are particularly appropriate in younger patients (less than 60 years old) who lack renal, cardiovascular, or active gastrointestinal disease. (See 'NSAID therapy' above.)

NSAIDs are most effective when treatment is initiated within 48 hours of the onset of symptoms. 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 not used for the treatment of acute gout flares because of the paradoxical effects of salicylates on serum urate.

Another reasonable alternative to glucocorticoids or NSAIDs is colchicine, which is at least comparably effective to the other agents when taken within 24 hours of onset of an acute attack. Colchicine should be administered in a total dose on day 1 not to exceed 1.8 mg, either taken as 0.6 mg three times on the first day or by taking 1.2 mg for the first dose followed by 0.6 mg an hour later; most patients will not achieve complete resolution of pain within 24 hours but will respond further over several days of continued dosing at 0.6 mg once or twice daily, as tolerated, with reduction in the dose as the flare gradually resolves (at which time the acute flare treatment can be discontinued). In some countries, colchicine is available as a 0.5 mg rather than as a 0.6 mg pill. (See 'Colchicine therapy' above.)

Colchicine is a particularly convenient agent for patients already taking this medication for flare prophylaxis and for patients who have the drug available at home for use only at the onset of an acute flare. Patients already receiving colchicine gout flare prophylaxis should resume the prophylaxis dose after the first day of acute flare therapy. Particular attention should be given to avoidance of colchicine administration in patients with moderate to severe renal or hepatic disease receiving inhibitors of the cytochrome P450 system component CYP3A4 or inhibitors of the membrane P-glycoprotein multidrug resistance transporter (P-gp). (See 'Colchicine therapy' above and 'Safety of colchicine' above.)

In patients who are unable to take oral medications and/or who have only one or two actively inflamed joints (and in whom infection has been excluded), we suggest arthrocentesis and intraarticular injection of glucocorticoids. 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.)

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. The dose and frequency depend upon the agent chosen. A typical dose is 20 mg methylprednisolone twice daily, with stepwise reduction to 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.)

For patients who are unresponsive to any other available approach and who have frequent recurrent attacks, an additional option is an interleukin (IL)-1 inhibitor, such as anakinra or canakinumab. 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 colchicine or oral glucocorticoids. We use intraarticular glucocorticoids for the treatment of acute attacks if oral agents are 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.)

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REFERENCES

  1. Neogi T. Clinical practice. Gout. N Engl J Med 2011; 364:443.
  2. Terkeltaub R. Update on gout: new therapeutic strategies and options. Nat Rev Rheumatol 2010; 6:30.
  3. Sundy JS. Progress in the pharmacotherapy of gout. Curr Opin Rheumatol 2010; 22:188.
  4. 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.
  5. 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.
  6. 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.
  7. Qaseem A, Harris RP, Forciea MA, Clinical Guidelines Committee of the American College of Physicians. Management of Acute and Recurrent Gout: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med 2017; 166:58.
  8. Richette P, Doherty M, Pascual E, et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis 2017; 76:29.
  9. Schlesinger N, Detry MA, Holland BK, et al. Local ice therapy during bouts of acute gouty arthritis. J Rheumatol 2002; 29:331.
  10. 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.
  11. Garcia de la Torre I. A comparative, double-blind, parallel study with tenoxicam vs placebo in acute gouty arthritis. Invest Med Int 1987; 14:92.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. 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.
  22. 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.
  23. Liu Y, Li ZC, Chen JB, et al. Therapeutic efficacy of small doses of colchicine combined with glucocorticoid for acute gouty arthritis. Med J Chin Peoples Liberation Army 2015; 40:652.
  24. Zhang YK, Yang H, Zhang JY, et al. Comparison of intramuscular compound betamethasone and oral diclofenac sodium in the treatment of acute attacks of gout. Int J Clin Pract 2014; 68:633.
  25. Hui M, Carr A, Cameron S, et al. The British Society for Rheumatology Guideline for the Management of Gout. Rheumatology (Oxford) 2017.
  26. 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.
  27. 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.
  28. Wechalekar MD, Vinik O, Schlesinger N, Buchbinder R. Intra-articular glucocorticoids for acute gout. Cochrane Database Syst Rev 2013; :CD009920.
  29. Alloway JA, Moriarty MJ, Hoogland YT, Nashel DJ. Comparison of triamcinolone acetonide with indomethacin in the treatment of acute gouty arthritis. J Rheumatol 1993; 20:111.
  30. Janssens HJ, Lucassen PL, Van de Laar FA, et al. Systemic corticosteroids for acute gout. Cochrane Database Syst Rev 2008; :CD005521.
  31. 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.
  32. Colchicine and other drugs for gout. Med Lett Drugs Ther 2009; 51:93.
  33. 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.
  34. Yu 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.
  35. 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.
  36. Segal R, Lubart E, Leibovitz A, et al. Renal effects of low dose aspirin in elderly patients. Isr Med Assoc J 2006; 8:679.
  37. Zhang Y, Neogi T, Chen C, et al. Low-dose aspirin use and recurrent gout attacks. Ann Rheum Dis 2014; 73:385.
  38. van Durme CM, Wechalekar MD, Buchbinder R, et al. Non-steroidal anti-inflammatory drugs for acute gout. Cochrane Database Syst Rev 2014; :CD010120.
  39. Colcrys (colchicine, USP) full prescribing information http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022351lbl.pdf (Accessed on April 25, 2011).
  40. Terkeltaub RA. Colchicine update: 2008. Semin Arthritis Rheum 2009; 38:411.
  41. Colcrys FDA Approval Letter. http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2009/022351s000ltr.pdf (Accessed on February 10, 2010).
  42. Yu DK. The contribution of P-glycoprotein to pharmacokinetic drug-drug interactions. J Clin Pharmacol 1999; 39:1203.
  43. P450 Drug interaction table. http://medicine.iupui.edu/clinpharm/ddis/ClinicalTable.asp (Accessed on June 07, 2010).
  44. 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.
  45. Stamp LK, Jordan S. The challenges of gout management in the elderly. Drugs Aging 2011; 28:591.
  46. Singh H, Torralba KD. Therapeutic challenges in the management of gout in the elderly. Geriatrics 2008; 63:13.
  47. Fravel MA, Ernst ME. Management of gout in the older adult. Am J Geriatr Pharmacother 2011; 9:271.
  48. 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.
  49. Simmonds HA, Cameron JS, Goldsmith DJ, et al. Familial juvenile hyperuricaemic nephropathy is not such a rare genetic metabolic purine disease in Britain. Nucleosides Nucleotides Nucleic Acids 2006; 25:1071.
  50. Lhotta K, Gehringer A, Jennings P, et al. Familial juvenile hyperuricemic nephropathy: report on a new mutation and a pregnancy. Clin Nephrol 2009; 71:80.
  51. van Veen TR, Haeri S. Gout in pregnancy: a case report and review of the literature. Gynecol Obstet Invest 2015; 79:217.
  52. Rabinovitch O, Zemer D, Kukia E, et al. Colchicine treatment in conception and pregnancy: two hundred thirty-one pregnancies in patients with familial Mediterranean fever. Am J Reprod Immunol 1992; 28:245.
  53. Adler Y, Charron P, Imazio M, et al. 2015 ESC Guidelines for the diagnosis and management of pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC)Endorsed by: The European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2015; 36:2921.
  54. Ben-Chetrit E, Scherrmann JM, Levy M. Colchicine in breast milk of patients with familial Mediterranean fever. Arthritis Rheum 1996; 39:1213.
  55. Martinon F, Pétrilli V, Mayor A, et al. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 2006; 440:237.
  56. 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.
  57. 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.
  58. Tran AP, Edelman J. Interleukin-1 inhibition by anakinra in refractory chronic tophaceous gout. Int J Rheum Dis 2011; 14:e33.
  59. 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.
  60. 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.
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