When should hyperuricemia be treated?

When to Treat Hyperuricemia

Do not treat asymptomatic hyperuricemia—treatment is indicated only when patients develop gout symptoms (flares, tophi, radiographic damage) or meet specific high-risk criteria. 1, 2, 3

Asymptomatic Hyperuricemia: Do Not Treat

The American College of Rheumatology conditionally recommends against initiating urate-lowering therapy (ULT) for asymptomatic hyperuricemia, even at very high levels. 1, 2 The FDA drug label for allopurinol explicitly states: "THIS IS NOT AN INNOCUOUS DRUG. IT IS NOT RECOMMENDED FOR THE TREATMENT OF ASYMPTOMATIC HYPERURICEMIA." 3

Why Not Treat?

• The number needed to treat is prohibitively high: 24 patients require ULT for 3 years to prevent a single gout flare. 1, 2
• Among patients with serum urate >9 mg/dL, only 20% developed gout within 5 years. 1, 2
• Treatment risks (including severe hypersensitivity reactions, drug interactions, and medication burden) outweigh benefits for the vast majority of asymptomatic patients. 1, 2
• This recommendation applies even when crystal deposition is detected on imaging—the same risk-benefit analysis holds. 2

Management of Asymptomatic Hyperuricemia

Instead of pharmacologic treatment, focus on: 1

• Lifestyle modifications: Weight reduction, regular exercise, avoiding excess alcohol and sugar-sweetened beverages
• Medication review: Eliminate non-essential medications that induce hyperuricemia (especially diuretics when possible)
• Patient education: Teach recognition of gout symptoms and when to seek care
• Screen for secondary causes: Evaluate for chronic kidney disease, medication effects

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Symptomatic Hyperuricemia: Strong Indications for Treatment

Treat Immediately (Strong Recommendations)

Initiate ULT for patients with any of the following: 1, 4

• ≥2 gout flares per year (frequent flares)
• One or more subcutaneous tophi (regardless of flare frequency)
• Radiographic damage attributable to gout (any imaging modality showing urate arthropathy)
• Renal stones/urolithiasis related to uric acid

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Symptomatic Hyperuricemia: Conditional Indications for Treatment

Consider Treatment (Conditional Recommendations)

Initiate ULT for patients with >1 previous gout flare but infrequent attacks (<2/year) who have any of these features: 1, 4

• Chronic kidney disease stage ≥3
• Serum urate >9 mg/dL
• History of urolithiasis
• Young age (<40 years) at first flare
• Significant comorbidities: Hypertension, ischemic heart disease, heart failure

Even after a first gout flare, consider ULT if the patient has CKD stage ≥3, serum urate >9 mg/dL, or urolithiasis. 1, 4

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Treatment Approach When ULT Is Indicated

First-Line Agent: Allopurinol

Allopurinol is the preferred first-line agent for all patients, including those with moderate-to-severe CKD. 1, 4, 2

Dosing Strategy

• Start low: ≤100 mg/day in normal renal function; 50 mg/day in CKD stage ≥4 1, 4
• Titrate gradually: Increase by 100 mg every 2-5 weeks based on serum urate monitoring 1, 4
• Target serum urate: <6 mg/dL for all patients; <5 mg/dL for severe gout with tophi until resolution 1, 4
• Maximum dose: Can exceed 300 mg/day even in renal impairment with appropriate monitoring (FDA-approved up to 800 mg/day) 1, 2, 3

Flare Prophylaxis (Critical)

Always provide anti-inflammatory prophylaxis when initiating ULT to prevent flares: 1, 4

• Colchicine 0.5-1 mg/day for the first 3-6 months (reduce dose in renal impairment; avoid with strong P-glycoprotein/CYP3A4 inhibitors)
• Low-dose NSAIDs if colchicine contraindicated or not tolerated
• Low-dose glucocorticoids as alternative

Timing of Initiation

You can start allopurinol during an acute gout flare rather than waiting for resolution—this does not prolong flare duration or worsen severity. 4 Continue allopurinol without interruption if the patient is already taking it when a flare occurs. 4

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Monitoring and Long-Term Management

• Check serum urate every 2-5 weeks during dose titration, then every 6 months once target achieved 1, 4
• Maintain serum urate <6 mg/dL lifelong once ULT is initiated 1, 4
• Continue ULT indefinitely in patients with persistent tophi, radiographic damage, frequent flares, CKD stage ≥3, or urolithiasis history 1

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Common Pitfalls to Avoid

• Do not treat asymptomatic hyperuricemia even at levels >9 mg/dL without gout symptoms or high-risk features—the evidence does not support this despite associations with cardiovascular and renal disease. 1, 2, 3
• Do not start allopurinol at 300 mg daily without checking renal function first—always start low and titrate. 1, 4
• Do not stop allopurinol during an acute flare if the patient is already taking it—this causes urate fluctuations that may trigger additional flares. 4
• Do not initiate ULT without flare prophylaxis—this is a major cause of treatment failure and patient non-adherence. 1, 4
• Do not use probenecid or other uricosurics as first-line when creatinine clearance <50 mL/min. 1

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Special Considerations

HLA-B*5801 Testing

Consider testing before starting allopurinol in: 4

• Patients of Southeast Asian descent (Han Chinese, Korean, Thai)
• African American patients
• (Due to higher risk of severe allopurinol hypersensitivity syndrome)

Alternative Agents

If target serum urate cannot be reached with appropriate allopurinol dosing, consider switching to febuxostat or adding a uricosuric agent. 4