What is the management for tophus in gout?

Management of Tophus in Gout

Tophi should be treated medically by achieving sustained serum uric acid reduction, preferably below 5 mg/dL (0.30 mmol/L), using urate-lowering therapy with allopurinol as first-line treatment, titrated to target; surgery is reserved only for specific complications such as nerve compression, mechanical impingement, or infection. 1

Primary Medical Management Strategy

Urate-Lowering Therapy (ULT) Initiation

• Start allopurinol at 100 mg/day in patients with normal kidney function, escalating by 100 mg increments every 2-4 weeks until the serum uric acid target is achieved 1
• In patients with renal impairment, begin allopurinol at 50-100 mg/day with close monitoring, up-titrating to achieve the usual target 1
• If allopurinol fails to achieve target at maximum appropriate dose, switch to febuxostat or add/switch to a uricosuric agent (benzbromarone or probenecid) 1
• For severe debilitating chronic tophaceous gout where the serum uric acid target cannot be reached with any other available drug at maximal dosage (including combinations), pegloticase is indicated 1

Serum Uric Acid Targets

• For patients with tophi, target serum uric acid below 5 mg/dL (300 mmol/L) to facilitate faster crystal dissolution until complete tophus resolution 1
• The standard target of <6 mg/dL (360 mmol/L) applies to less severe gout, but tophi require the more aggressive lower target 1
• Maintain serum uric acid at target lifelong once achieved 1
• Avoid long-term serum uric acid levels <3 mg/dL 1

Anti-Inflammatory Prophylaxis During ULT

Mandatory Prophylaxis

• Provide prophylaxis for at least 6 months when initiating ULT, or continue for 6 months after achieving target serum uric acid in patients with tophi 1
• First-line prophylaxis is colchicine 0.5-1 mg/day (reduce dose in renal impairment) 1
• If colchicine is contraindicated or not tolerated, use low-dose NSAIDs with proton pump inhibitor if appropriate 1
• Low-dose corticosteroids (≤10 mg prednisone daily) are acceptable second-line prophylactic agents 1, 2

Critical Prophylaxis Considerations

• Avoid colchicine in patients receiving strong P-glycoprotein and/or CYP3A4 inhibitors (cyclosporin, clarithromycin) 1
• Monitor for neurotoxicity and muscular toxicity with prophylactic colchicine, especially in renal impairment or concurrent statin use 1
• Never stop ULT during acute flares—continue without interruption while treating the flare separately 3

Management of Acute Flares During Tophus Treatment

• Treat acute flares promptly with NSAIDs at full anti-inflammatory doses, low-dose colchicine (1 mg loading dose followed by 0.5 mg one hour later), or corticosteroids (oral 30-35 mg/day prednisolone equivalent for 3-5 days, intra-articular, or intramuscular) 1, 3
• Continue ULT without interruption during acute attacks—stopping worsens and prolongs the attack 3
• Colchicine should be given within 12 hours of flare onset for optimal efficacy 1

Surgical Intervention

Surgery is indicated only in selected cases and should not replace medical management: 1

• Nerve compression or entrapment neuropathy 1, 4
• Mechanical impingement causing severe functional limitation 1, 4
• Infection of tophus 1, 4
• Ulceration with risk of permanent joint destruction 4

Surgery should be considered only after medical therapy has been optimized or when urgent complications arise 4

Monitoring and Follow-Up

• Monitor serum uric acid levels regularly and adjust ULT dose to maintain target 1
• Track tophus size as a clinical endpoint alongside serum uric acid levels and gout attack frequency 1
• Calculate estimated glomerular filtration rate at diagnosis and monitor regularly, as chronic kidney disease is present in 53% of gout patients 1
• Screen for cardiovascular comorbidities (hypertension, ischemic heart disease, heart failure) as these are independent risk factors associated with gout 1

Common Pitfalls to Avoid

• Stopping ULT during acute attacks is the most common error—this worsens crystal mobilization and prolongs the attack 3
• Failing to provide anti-inflammatory prophylaxis when initiating ULT leads to increased flare frequency 3
• Using inadequate allopurinol doses without proper titration—many patients remain undertreated at fixed low doses 1
• Targeting serum uric acid to only <6 mg/dL in patients with tophi—these patients require the lower target of <5 mg/dL for faster crystal dissolution 1
• Considering surgery before optimizing medical therapy—tophi are preventable and treatable with appropriate ULT in the vast majority of cases 4

Special Populations

Renal Impairment

• Adjust allopurinol maximum dosage to creatinine clearance 1
• If target cannot be achieved at adjusted dose, switch to febuxostat or benzbromarone (except in eGFR <30 mL/min) 1
• Avoid colchicine and NSAIDs in severe renal impairment 1

Refractory Tophaceous Gout

• Pegloticase 8 mg biweekly infusion achieved complete tophus resolution in 40% of participants with severe disease versus 7% with placebo (NNTB 3) 5
• Pegloticase carries significant risk of infusion reactions (withdrawal rate 18% versus 2% with placebo, NNTH 7) 5
• Reserve pegloticase for crystal-proven severe debilitating chronic tophaceous gout with poor quality of life when all other therapies have failed 1, 6