What is the recommended treatment for an adult patient with a history of chronic gout and tophi?

Management of Chronic Gout with Tophi

For adult patients with chronic gout and tophi, you must initiate urate-lowering therapy (ULT) immediately—this is a strong recommendation that is non-negotiable. 1

Mandatory Initiation of ULT

• Presence of tophi is an absolute indication for ULT, regardless of flare frequency or other factors 1
• The American College of Rheumatology provides a strong recommendation (not conditional) for initiating ULT in any patient with one or more subcutaneous tophi 1
• This strong recommendation reflects the evidence that tophi indicate advanced disease with significant urate crystal burden requiring aggressive treatment to prevent joint destruction and improve quality of life 1

Target Serum Uric Acid Levels

• Target serum uric acid <6 mg/dL for all patients on ULT to promote crystal dissolution and prevent new crystal formation 1, 2
• For patients with tophi specifically, target <5 mg/dL until complete resolution of tophi is achieved 2, 3
• The lower target of <5 mg/dL accelerates tophus resolution based on physicochemical principles—the rate of crystal dissolution increases substantially as serum urate drops further below the saturation point of 6.8 mg/dL 4, 5
• Once tophi resolve completely, you can liberalize the target back to <6 mg/dL for maintenance 2

First-Line ULT Selection

Start with allopurinol as first-line therapy unless contraindicated 1, 6

Allopurinol Dosing Strategy

• Start at ≤100 mg daily (or 50 mg daily if CKD stage ≥3) 1, 2
• Titrate upward by 100 mg every 2-5 weeks based on serial serum uric acid measurements 1, 2
• Continue dose escalation until target serum uric acid is achieved, even if this requires doses >300 mg daily 1
• Check serum uric acid every 2-5 weeks during titration phase 2

HLA-B*5801 Testing Considerations

• Test for HLA-B*5801 before starting allopurinol if the patient is of Southeast Asian descent (Han Chinese, Korean, Thai) or African American 1
• Do not routinely test patients of other ethnic backgrounds—this is a conditional recommendation against universal testing 1
• If HLA-B*5801 positive, choose febuxostat or probenecid instead 1

Mandatory Flare Prophylaxis

You must prescribe anti-inflammatory prophylaxis when initiating ULT—this is strongly recommended to prevent mobilization flares that occur as urate crystals dissolve 1, 2, 7

Prophylaxis Options (in order of preference)

1. Colchicine 0.5-1 mg daily for minimum 6 months 1, 2, 7

   • Reduce to 0.5 mg daily or every other day if creatinine clearance 30-50 mL/min 7
   • This is first-line prophylaxis 7

2. Low-dose NSAIDs if colchicine contraindicated 7

3. Low-dose corticosteroids (e.g., prednisone 5-10 mg daily) if both colchicine and NSAIDs contraindicated 7

Duration of Prophylaxis

• Continue for at least 6 months minimum 1, 2, 7
• Extend beyond 6 months if flares continue 2, 7
• Do not stop prophylaxis prematurely—this is a common pitfall that leads to treatment failure 7

Critical Management Principles

Continue ULT During Acute Flares

• Never stop ULT during an acute gout attack—this perpetuates the cycle of recurrent flares 7
• Treat the acute flare with anti-inflammatory therapy while maintaining ULT 7

Indefinite Treatment Duration

• Continue ULT indefinitely once started—this is a conditional recommendation, but stopping therapy leads to flare recurrence in 87% of patients within 5 years 1
• Even patients in clinical remission (no flares for ≥1 year, no tophi) who stop ULT experience high rates of disease recurrence 1

Monitoring Protocol

• Assess renal function before starting ULT 2
• Check serum uric acid every 2-5 weeks during dose titration 2
• Monitor for allopurinol hypersensitivity (rash, pruritus, elevated liver enzymes), especially during dose escalation 2
• Track tophus size at baseline and follow-up visits to assess treatment response 2

Second-Line Options

If allopurinol fails to achieve target despite dose optimization or causes adverse effects:

• Febuxostat is an alternative xanthine oxidase inhibitor 1

  • More potent than allopurinol but has cardiovascular safety concerns in patients with established CVD 1, 6
  • If patient develops new cardiovascular event while on febuxostat, switch to alternative ULT 1

• Probenecid (uricosuric) can be used if xanthine oxidase inhibitors are contraindicated 1

  • Less effective in patients with CKD stage ≥3 6

• Pegloticase is reserved for severe refractory tophaceous gout unresponsive to oral ULT 1, 8

  • Requires specialized administration in healthcare settings with anaphylaxis preparedness 8
  • Monitor serum uric acid before each infusion; consider discontinuing if levels rise above 6 mg/dL on two consecutive measurements 8

Common Pitfalls to Avoid

• Do not use fixed-dose allopurinol without titration—most patients require >300 mg daily to achieve target 1
• Do not start ULT without prophylaxis—this guarantees mobilization flares and treatment abandonment 1, 7
• Do not stop checking serum uric acid once target is reached—continue periodic monitoring to ensure sustained control 2
• Do not discontinue medications that raise uric acid (like low-dose aspirin for cardiovascular protection)—the cardiovascular benefit outweighs the modest uric acid elevation 7

Adjunctive Lifestyle Modifications

While ULT is mandatory, also counsel patients on 7:

• Weight loss if obese 7
• Avoid alcohol, especially beer and spirits 7
• Eliminate sugar-sweetened beverages and high-fructose foods 7
• Reduce red meat and seafood intake 7
• Encourage low-fat dairy products 7