Gout and Pseudogout Guidelines

Updated: Aug 27, 2017
  • Author: Bruce M Rothschild, MD; Chief Editor: Herbert S Diamond, MD  more...
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Guidelines

Guidelines Summary

Guidelines on hyperuricemia and gout have been developed by the following organizations:

  • American College of Rheumatology (ACR) – Management of hyperuricemia. [108]
  • ACR – Treatment and prophylaxis of acute gouty arthritis [109]
  • American College of Physicians (ACP) – Diagnosis of acute gout [157]
  • ACP – Management of acute and recurrent gout [128]
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American College of Rheumatology Guidelines

ACR guidelines on gout use the following evidence grades for recommendations:

  • Level A – Supported by more than one randomized clinical trial or meta-analysis
  • Level B – Derived from a single randomized trial or nonrandomized studies
  • Level C – Consensus opinion of experts, case studies, or standard of care

Baseline treatment recommendations

ACR baseline recommendations for treatment of patients with gout are as follows (all evidence level C) [108] :

  • Patient education, with diet and lifestyle recommendations
  • Consider secondary causes of hyperuricemia
  • Consider elimination of nonessential prescription drugs that induce hyperuricemia
  • Clinically evaluate gout disease burden (ie, palpable tophi, frequency and severity of acute and chronic symptoms and signs)

Patient education

The ACR guidelines recommend the following general health, diet, and lifestyle measures for gout patients [108] :

  • Weight loss for obese patients, to achieve a body mass index (BMI) that promotes general health
  • Healthy overall diet
  • Exercise (achieve physical fitness
  • Smoking cessation
  • Staying well hydrated

Specific dietary recommendations are listed in Table 1, below. [108]

Table 1. American College of Rheumatology Dietary Recommendations for Gout Patients (Open Table in a new window)

Avoid Limit Encourage
Organ meats high in purine content (eg, sweetbreads, liver, kidney) Serving sizes of beef, lamb, pork, and seafood with high purine content (eg, sardines, shellfish) Low-fat or non-fat dairy products
High-fructose corn syrup–sweetened sodas, other beverages, foods
  • Servings of naturally sweet fruit juices
  • Table sugar, sweetened beverages, desserts
  • Table salts, including in sauces and gravies
Vegetables
Alcohol overuse (ie, >2 servings/day for men, >1/d for women Alcohol—particularly beer, but also wine and spirits  

Secondary causes of hyperuricemia

The ACR recommends the following checklist of comorbidities as appropriate to consider in the clinical evaluation of patients with gout, and to evaluate if clinically indicated (all level C) [108] :

  • Obesity, dietary factors
  • Excessive alcohol intake
  • Metabolic syndrome, type 2 diabetes mellitus
  • Hypertension
  • Hyperlipidemia, modifiable risk factors for coronary artery disease or stroke
  • Serum urate–elevating medications
  • History of urolithiasis
  • Chronic kidney, glomerular, or interstitial renal disease (eg, analgesic nephropathy, polycystic kidney disease)
  • In selected cases, potential genetic or acquired causes of uric acid overproduction (eg, inborn error of purine metabolism or psoriasis, myeloproliferative or lymphoproliferative disease)
  • Lead intoxication

Pharmacologic therapy

ACR indications for pharmacologic therapy to lower serum uric acid levels in patients with an established diagnosis of gouty arthritis include the following:

  • Tophus or tophi identified on clinical examination or imaging study (evidence A)
  • Frequent (≥2/yr) of acute gouty arthritis (evidence A)
  • Chronic kidney disease (CKD) stage ≥2 (evidence C)
  • Previous urolithiasis (evidence C)

Treatment to target

The ACR recommends treatment to target serum uric acid level, as follows:

  • The minimum serum uric acid target is <6 mg/dL
  • A lower target (<5 mg/dL) may be needed to improve signs and symptoms
  • Allopurinol or febuxostat is a first-line xanthine oxidase inhibitor for urate-lowering therapy (ULT) (evidence A)
  • If at least one xanthine oxidase inhibitor is contraindicated or not tolerated, probenecid is an alternative first-line agent (evidence B)

Allopurinol

ACR recommendations for use of allopurinol ULT in gout include the following:

  • Starting dosage should be no greater than 100 mg/day for any patient (evidence level B)
  • Start at 50 mg/day in patients with stage 4 or worse CKD (evidence B)
  • Gradually titrate maintenance dose upward every 2–5 weeks to appropriate maximum dose in order to treat to chosen serum uric acid target (evidence C)
  • Dose can be raised above 300 mg daily, even in patients with renal impairment, if it is accompanied by adequate patient education and monitoring for drug toxicity (eg, pruritus, rash, elevated hepatic transaminases) (evidence B)
  • Before starting allopurinol, consider testing for HLA–B*5801 in selected patients, specifically in subpopulations at higher risk for severe allopurinol hypersensitivity reaction (eg, Koreans with stage 3 or worse CKD, Han Chinese and Thai irrespective of renal function (evidence A)

Uricosuric urate-lowering therapy

ACR recommendations for use of uricosuric ULT in gout include the following:

  • Probenecid is the first choice among uricosuric agents for ULT (evidence B)
  • In gout patients with a creatinine clearance <50 mL/min, probenecid is not recommended as first-line ULT monotherapy (evidence C)
  • Agents other than probenecid that have clinically significant uricosuric effects (eg, fenofibrate, losartan) can be useful as components of a comprehensive ULT strategy (evidence B)
  • A history of urolithiasis is a contraindication to first-line uricosuric urate-lowering monotherapy (evidence C)
  • Urinary uric acid should be measured before initiation of uricosuric ULT (evidence C)
  • Elevated urine uric acid indicative of uric acid overproduction is a contraindication to uricosuric ULT (evidence C)
  • Continue to monitor urinary uric acid during uricosuric ULT (evidence C)
  • Consider urine alkalinization (eg, with potassium citrate) with monitoring of urine pH, in addition to increased fluid intake, as a risk management strategy for urolithiasis (evidence C)

ACR recommendations for refractory disease in gout include the following:

  • Attempt upward titration of one xanthine oxidase inhibitor to its maximum appropriate dose (evidence A)
  • Febuxostat can be substituted for allopurinol or vice versa in the event of drug intolerance and adverse events, and such substitution should be considered after initial failure of upward dose titration of either drug (evidence C); however, febuxostat and allopurinol should not be used together
  • A uricosuric agent (eg, probenecid, fenofibrate, or losartan) may be added to a xanthine oxidase inhibitor (evidence B) or vice versa (evidence C)
  • Pegloticase is appropriate for patients with severe gout disease burden and refractoriness to, or intolerance of, conventional and appropriately dosed ULT (evidence A)
  • Pegloticase therapy is not recommended as first-line ULT agent

The ACR notes that the pegloticase package insert advises discontinuing other oral ULT agents during the course of pegloticase therapy. The ACR was unable to reach consensus on the appropriate duration of pegloticase therapy relative to intended and achieved decrease in symptoms and signs of gout.

Long-term management

ACR recommendations for long-term management of gout are as follows:

  • Continue gout attack prophylaxis in patients with ongoing gout manifestations (eg, ≥1 tophus on physical exam)
  • Continue regular monitoring of serum urate and monitoring for adverse effects
  • After resolution of palpable tophi and all acute and chronic symptoms of chronic gouty arthritis, continue all measures needed to maintain serum urate levels <6 mg/dL indefinitely

Referral

Consider specialist referral in situations such as the following:

  • Unclear etiology of hyperuricemia
  • Difficulty reaching target serum urate level, particularly in patients with renal impairment who have had a trial of xanthine oxidase inhibitor treatment
  • Multiple and/or serious adverse effects from pharmacologic ULT

Prophylaxis

ACR recommendations for prophylaxis of acute gouty arthritis are as follows [109] :

● Pharmacologic anti-inflammatory prophylaxis is recommended for all gout patients when pharmacologic urate lowering is initiated, and should be continued if the patient has any clinical evidence of continuing gout disease activity and/or the serum urate target has not yet been achieved

● Oral colchicine is an appropriate first-line drug for prevention of gout attacks; with appropriate dose adjustments, it may be used in patients with CKD and those with drug interactions, unless medically contraindicated or not tolerated

● Low-dose NSAID therapy in an appropriate first-line choice for prevention of gout attacks, unless medically contraindicated or not tolerated

Treatment of acute attacks

ACR recommendations for treatment of attacks of acute gouty arthritis are as follows [109] :

● An acute gouty arthritis attack should be treated with pharmacologic therapy, started within 24 hours of onset

● Established pharmacologic ULT should be continued, without interruption, during an acute attack of gout.

● Nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or oral colchicine are appropriate first-line options for treatment of acute gout, and certain combinations can be employed for severe or refractory attacks

The ACR recommends tailoring therapy according to the severity of the attack. For a mildly to moderately painful attack, particularly one affecting only one or a few small joints, or one to two large joints, monotherapy is recommended (evidence A). Choices for monotherapy include the following (all evidence A):

  • An NSAID
  • Systemic corticosteroids
  • Colchicine, if started within 36 hours after symptom onset
  • Supplemental topical ice, as needed

For patients with gastrointestinal contraindications or intolerance to other NSAIDs, use of selective COX-2 inhibitors available outside the United States (eg, etoricoxib) is an option (evidence A). However, these against share many adverse events with nonselective NSAIDs. Therapy with the agent available in the US, celecoxib, requires high doses and its risk-benefit ratio is currently unclear.

For severely painful attacks, particularly those that are polyarticular or affect multiple large joints, initial combination therapy is an option. Both agents are started at full—or, when appropriate, prophylactic—doses. Acceptable combinations include any of the following (evidence C):

  • Colchicine and NSAIDs
  • Oral corticosteroids and colchicine
  • Intra-articular steroids with all other modalities

In patients with an inadequate response to treatment (ie, <20% improvement in their pain score within 24 h, or <50% improvement at ≥24 h, the ACR recommends switching to an alternate monotherapy or considering add-on combination therapy (both evidence C). If the attack still fails to respond, off-label use of investigational agents may be considered (eg, interleukin-1 inhibitors such as anakinra, canakinumab, or rilonacept).

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American College of Physicians Guidelines

Diagnosis of acute gout

The ACP guideline recommends using synovial fluid analysis when clinical judgment indicates that diagnostic testing is necessary in patients with possible acute gout (weak recommendation, low-quality evidence). The guideline advises that synovial fluid analysis is considered the reference standard for gout diagnosis but may be difficult to perform in a primary care setting. Synovial fluid analysis is recommended if the following criteria can be met [157]

  • An experienced clinician can aspirate the joint without substantial patient discomfort and can minimize the risk of infection
  • A reliable and accurate source (including a trained operator with a polarizing microscope) is available to assess the fluid for the presence of urate crystals
  • The clinical situation is ambiguous and a probability of joint infection exists

If the criteria for synovial fluid analysis cannot be met, the ACP recommends that clinicians either refer the patient to a source that can meet the criteria or use their clinical judgment regarding the need for joint aspiration. Clinical judgment is especially appropriate in situations that are less clinically ambiguous and the probability of infection is not significant. For example, a patient with podagra, appropriate risk factors (eg, age), and no sign of an overlying skin wound) could be considered to have gout without undergoing joint aspiration.

The ACP notes that algorithms for clinical diagnosis of gout exist and have sensitivities and specificities >80%, but little evidence exists that they can be used to identify septic joints. Current evidence is insufficient to support the use of dual-energy computed tomography or ultrasonography to diagnose acute gout. [157]

Management of acute and recurrent gout

ACP recommendations for the treatment of acute and recurrent gout attacks are as follows [128] :

  • Use corticosteroids, NSAIDS, or colchicine to treat acute gout
  • Use low-dose colchicine (1.2 mg, then 0.6 mg 1 hr later) when using colchicine for acute gout
  • Recommend against initiating long-term urate-lowering therapy in most patients after a first gout attack or in patients with infrequent attacks
  • Discuss benefits, harms, costs, and individual preferences with patients before initiating urate-lowering therapy, including concomitant prophylaxis, in patients with recurrent gout attacks

In contrast to American College of Rheumatology recommendations, the ACP concluded that evidence was insufficient to determine whether the benefits of escalating urate-lowering therapy to reach a serum urate target outweigh the harms associated with repeated monitoring and medication escalation. [128]

 

 

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