Gout and Pseudogout Guidelines

Updated: Jun 30, 2020
  • 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 gout [125]
  • ACR – Treatment and prophylaxis of acute gouty arthritis [124]
  • American College of Physicians (ACP) – Diagnosis of acute gout [187]
  • ACP – Management of acute and recurrent gout [125]
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American College of Rheumatology Guidelines

The 2012 ACR guidelines recommended the following general health, diet, and lifestyle measures for gout patients [123] :

  • 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

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 [123] :

  • 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

The ACR updated its guideline on management of gout in 2020. Recommendations are summarized below. [125]

Indications for pharmacologic urate-lowering therapy:

  • Initiating ULT is strongly recommended for gout patients with ≥1 subcutaneous tophi, evidence of radiographic damage (any modality) attributable to gout, or frequent gout flares (≥2 annually).
  • Initiating ULT is conditionally recommended for patients who have previously experienced >1 flare but have infrequent flares.
  • Initiating ULT is conditionally recommended against in patients with gout experiencing their first gout flare; however, initiating ULT is conditionally recommended for patients with comorbid moderate-to-severe (stage ≥3) chronic kidney disease (CKD), serum urate concentration >9 mg/dL, or urolithiasis.
  • Initiating ULT is conditionally recommended against in patients with asymptomatic hyperuricemia.

Choice of initial ULT for patients with gout

  • Treatment with allopurinol as the preferred first-line agent, over all other ULTs, is strongly recommended for all patients, including those with moderate-to-severe CKD (stage ≥3).
  • The choice of either allopurinol or febuxostat over probenecid is strongly recommended for patients with moderate-to-severe CKD (stage ≥3).
  • The choice of pegloticase as a first-line therapy is strongly recommended against.
  • Starting treatment with low-dose allopurinol (≤100 mg/day—lower in patients with CKD [stage ≥3]) and febuxostat (≤40 mg/day)—with subsequent dose titration is strongly recommended over starting at a higher dose.
  • Starting treatment with low-dose probenecid (500 mg once to twice daily) with subsequent dose titration over starting at a higher dose is conditionally recommended.
  • Administering concomitant anti-inflammatory prophylaxis therapy (eg, colchicine, nonsteroidal anti-inflammatory drugs [NSAIDs], prednisone/ prednisolone) over no anti-inflammatory prophylaxis therapy is strongly recommended.
  • Continuing concomitant anti-inflammatory prophylaxis therapy for 3–6 months over < 3 months, with ongoing evaluation and continued prophylaxis as needed if the patient continues to experience gout flares, is strongly recommended.

Timing of ULT initiation:

  • Starting ULT while the patient is experiencing a gout flare is conditionally recommended over starting ULT after the gout flare has resolved.
  • A treat-to-target management strategy that includes ULT dose titration and subsequent dosing guided by serial serum urate measurements to achieve a target serum urate level is strongly recommended over a fixed-dose ULT strategy for all patients receiving ULT.
  • For all patients receiving ULT, achieving and maintaining a serum uric acid target of < 6 mg/dL over the use of no target is strongly recommended for all patients receiving ULT.
  • Delivery of an augmented protocol of ULT dose management by nonphysician providers to optimize the treat-to-target strategy that includes patient education, shared decision-making, and treat-to-target protocol is conditionally recommended for all patients receiving ULT.

Duration of ULT:

  • Continuing ULT indefinitely over stopping ULT is conditionally recommended.

Allopurinol:

  • Testing for the HLA–B*5801 allele prior to starting allopurinol is conditionally recommended for patients of Southeast Asian descent (eg, Han Chinese, Korean, Thai) and for African-American patients, over not testing for the HLA–B*5801 allele. Universal testing for the HLA–B*5801 allele prior to starting allopurinol is conditionally recommended against in patients of other ethnic or racial background over testing for the HLA–B*5801 allele.
  • Starting allopurinol in daily doses of ≤100 mg (and lower doses in patients with CKD) is strongly recommended over starting at a higher dose.
  • Allopurinol desensitization is conditionally recommended for patients with a prior allergic response to allopurinol who cannot be treated with other oral ULT agents.

Febuxostat:

  • Switching to an alternative oral ULT agent, if available and consistent with other recommendations in this guideline, is conditionally recommended for patients taking febuxostat with a history of cardiovascular disease (CVD) or a new CVD-related event.

Uricosurics:

  • Checking urinary uric acid is conditionally recommended against for patients considered for or receiving uricosuric treatment.
  • Alkalinizing the urine is conditionally recommended against for patients receiving uricosuric treatment.

When to consider changing ULT strategy:

  • Switching to a second xanthine oxidase inhibitor (XOI) over adding a uricosuric agent is conditionally recommended for patients taking their first XOI, who have persistently high serum urate concentrations (>6 mg/dL) despite maximum tolerated or FDA-indicated XOI dose, and who have continued frequent gout flares (>2 flares/year) or who have nonresolving subcutaneous tophi.
  • Switching to pegloticase over continuing current ULT is strongly recommended for patients with gout for whom XOI treatment, uricosurics, and other interventions have failed to achieve the serum urate target, and who continue to have frequent gout flares (≥2 flares/year) or who have nonresolving subcutaneous tophi.
  • Switching to pegloticase over continuing current ULT is strongly recommended against for patients with gout for whom XOI treatment, uricosurics, and other interventions have failed to achieve the SU target, but who have infrequent gout flares (< 2 flares/year) AND no tophi>< 2 flares/year) and no tophi.

Management of gout flares 

  • For treatment of a gout flare, first-line therapy with colchicine, NSAIDs, or glucocorticoids (oral, intra-articular, or intramuscular) is strongly recommended over interleukin-1 (IL-1) inhibitors or adrenocorticotropic hormone (ACTH). Given similar efficacy and a lower risk of adverse effects, low-dose colchicine over high-dose colchicine is strongly recommended when colchicine is the chosen agent.
  • Using topical ice as an adjuvant treatment over no adjuvant treatment is conditionally recommended for patients experiencing a gout flare.
  • Using an IL-1 inhibitor over no therapy (beyond supportive/analgesic treatment) is conditionally recommended for patients experiencing a gout flare for whom the above anti-inflammatory therapies are ineffective, poorly tolerated, or contraindicated.
  • For patients who are unable to take oral medications, treatment with glucocorticoids (intramuscular, intravenous, or intra-articular) is strongly recommended over IL-1 inhibitors or ACTH.

Management of lifestyle factors

The ACR conditionally recommends the following for patients with gout, regardless of disease activity:

  • Limiting alcohol intake 
  • Limiting purine intake 
  • Limiting high-fructose corn syrup intake
  • Using a weight loss program (no specific program endorsed) for patients who are overweight or obese

Adding vitamin C supplementation is conditionally recommended against for patients with gout, regardless of disease activity.

Management of concurrent medications

The following conditional recommendations apply to patients with gout, regardless of disease activity:

  • Switch from hydrochlorothiazide to an alternate antihypertensive when feasible
  • Choose losartan preferentially as an antihypertensive agent when feasible
  • Do not stop low-dose aspirin (for patients taking this medication for appropriate indications)
  • Do not add or switch cholesterol-lowering agents to fenofibrate 
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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 [187]

  • 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. [187]

Management of acute and recurrent gout

ACP recommendations for the treatment of acute and recurrent gout attacks are as follows [151] :

  • 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. [151]

 

 

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