What is the recommended acute and chronic management for symptomatic hyperuricemia (gout)?

Management of Symptomatic Hyperuricemia (Gout)

For symptomatic hyperuricemia (gout), treatment requires both acute management of flares and chronic urate-lowering therapy, with the specific approach determined by disease severity, frequency of attacks, presence of tophi, and comorbidities. 1

Acute Gout Flare Management

First-line pharmacologic options for acute attacks are oral NSAIDs or colchicine, with NSAIDs being the most convenient and well-accepted choice when not contraindicated. 1

Colchicine Dosing

• Low-dose colchicine (0.5 mg three times daily) is sufficient and causes fewer side effects than traditional high-dose regimens. 1
• Dose reduction is mandatory in renal impairment and when combined with strong P-glycoprotein/CYP3A4 inhibitors. 2

Alternative Acute Treatments

• Intra-articular aspiration followed by long-acting corticosteroid injection is effective and safe for accessible joints. 1
• Systemic corticosteroids serve as alternatives when NSAIDs and colchicine are contraindicated. 2

Chronic Urate-Lowering Therapy (ULT)

Absolute Indications for ULT

Urate-lowering therapy is mandatory in patients with: 1, 2

• Any subcutaneous tophi (even after a single flare)
• Frequent gout attacks (≥2 per year)
• Radiographic joint damage from gout
• Chronic tophaceous gouty arthropathy

Conditional Indications After First Flare

Consider initiating ULT after the first gout flare if: 1

• Chronic kidney disease stage ≥3 (eGFR <60 mL/min)
• Serum urate >9 mg/dL
• History of urolithiasis

First-Line ULT: Allopurinol Protocol

Allopurinol is the strongly recommended first-line agent for all patients, including those with moderate-to-severe CKD. 1, 3

Starting Dose

• ≤100 mg/day for normal renal function 1, 3
• 50 mg/day for CKD stage 4 or worse 1, 3

Dose Titration

• Increase by 100 mg every 2-5 weeks based on serum urate monitoring 1, 3
• Maximum FDA-approved dose is 800 mg/day 1, 3
• Most patients require >300 mg/day to achieve target serum urate 1

Target Serum Urate Levels

The therapeutic goal is to maintain serum urate <6 mg/dL for all patients with gout. 1, 2

For severe gout with tophi, chronic arthropathy, or frequent attacks, target <5 mg/dL. 2, 4

This target promotes crystal dissolution and prevents new monosodium urate crystal formation. 1

Mandatory Flare Prophylaxis During ULT Initiation

Colchicine 0.5-1 mg/day must be given for at least 6 months when starting or escalating ULT. 1, 2

This prevents acute flares triggered by rapid uric acid reduction, which destabilizes existing crystals. 2, 4

If colchicine is contraindicated or not tolerated, use low-dose NSAIDs or low-dose glucocorticoids as alternatives. 1, 2

Monitoring Strategy

During dose titration: 1, 4

• Check serum urate every 2-5 weeks until target achieved

After achieving target: 1, 4

• Monitor serum urate every 6 months
• Continue ULT indefinitely to maintain serum urate <6 mg/dL

Alternative ULT Agents

If allopurinol fails to achieve target at 800 mg/day or causes intolerance: 1

• Switch to febuxostat (40 mg/day starting dose, titrate as needed)
• Consider adding probenecid if eGFR >50 mL/min (contraindicated when creatinine clearance <50 mL/min) 1

Pegloticase is reserved exclusively for severe refractory tophaceous gout that has failed appropriately dosed oral ULT. 1, 5

Non-Pharmacologic Management

Lifestyle modifications are core aspects of management: 1

• Weight reduction if obese
• Reduce alcohol consumption (especially beer)
• Avoid high-fructose corn syrup and sugar-sweetened beverages
• Limit purine-rich organ meats and shellfish
• Encourage low-fat dairy products and vegetables

Address associated comorbidities aggressively: 1

• Hyperlipidemia
• Hypertension
• Hyperglycemia
• Obesity
• Smoking cessation

Eliminate non-essential medications that elevate uric acid (e.g., thiazide and loop diuretics) when possible. 1

Critical Management Pitfalls

Never discontinue ULT during an acute flare—continue therapy and add anti-inflammatory treatment. 4

Starting ULT at high doses precipitates acute flares—always start low and titrate gradually. 1, 2

Stopping prophylaxis before 6 months significantly increases breakthrough flare risk. 2, 4

Monitor serum urate before each infusion if using pegloticase, and discontinue if levels rise above 6 mg/dL on two consecutive measurements. 5

When to Refer to Rheumatology

Consider specialist referral for: 1

• Unclear etiology of hyperuricemia
• Refractory gout symptoms despite appropriate therapy
• Difficulty achieving target serum urate, particularly with renal impairment after xanthine oxidase inhibitor trial
• Multiple or serious adverse events from ULT

Asymptomatic Hyperuricemia: Do Not Treat

Asymptomatic hyperuricemia (serum urate >6.8 mg/dL without prior gout flares or tophi) should NOT be treated with pharmacologic ULT. 1, 4, 6

The number needed to treat is 24 patients for 3 years to prevent a single gout flare, and potential harms (including severe allopurinol hypersensitivity reactions) outweigh benefits. 1, 6

For asymptomatic patients, focus on lifestyle modifications and addressing cardiovascular/metabolic comorbidities. 4, 6