Treatment of Uric Acid in Joints (Gout)

What Happens in the Joint

PART 1 - Treatment of an Acute Gout Attack

1. NSAIDs (First-Line)

• Indomethacin is the classic NSAID of choice for gout.
• Avoid in CKD, peptic ulcer disease, or patients on anticoagulation.

2. Colchicine

• A plant alkaloid; it works by binding to tubulin (a microtubular protein), causing depolymerization. This disrupts neutrophil migration into the inflamed joint.
• Most effective when started within 24-36 hours of attack onset; usually alleviates pain within 12 hours.
• Also used as prophylaxis when starting urate-lowering therapy.
• Adverse effects: Nausea, vomiting, diarrhea, abdominal pain. Chronic use can cause myopathy, neutropenia, aplastic anemia.
• Avoid in CKD; avoid concomitant use with carvedilol or grapefruit juice (both raise colchicine blood levels). Dose-adjust with CYP3A4 inhibitors (e.g., clarithromycin) or P-gp inhibitors (e.g., amiodarone, verapamil).

3. Corticosteroids

• Intra-articular: Triamcinolone or methylprednisolone - 40 mg for large joints, 10-20 mg for small joints. Best for monoarticular attacks; effective in ~90% of patients within 24 hours. Rule out septic arthritis first.
• Oral: Prednisone 40-60 mg once daily until flare begins to resolve, then taper over 7-10 days. Use when NSAIDs and colchicine are contraindicated. Use with caution in poorly controlled diabetes.

4. IL-1 Inhibitor (Anakinra) - for refractory cases

PART 2 - Urate-Lowering Therapy (ULT) for Long-Term Management

When to Start ULT

• Two or more acute flares per year
• Presence of tophi (urate crystal deposits in joints, bones, cartilage)
• Urate nephropathy or kidney stones
• Radiographic joint damage
• First gout attack with uric acid >9 mg/dL, or CKD stage ≥3

Uric Acid Targets (Treat-to-Target)

• No tophi: target uric acid <6 mg/dL
• With tophi: target <5 mg/dL

Drug Options

Xanthine Oxidase Inhibitors (First-Line)

• Starting dose: 100 mg/day (50 mg/day in CKD stage 4+). Titrate by 100 mg increments every 2-5 weeks up to 800 mg/day if needed.
• Mechanism: competitively inhibits xanthine oxidase, blocking the last two steps in uric acid biosynthesis (hypoxanthine → xanthine → uric acid).
• Preferred over febuxostat and probenecid as first-line agent.
• Screen for HLA-B*5801 in African Americans and Southeast Asians before starting - positive carriers have a high risk of severe cutaneous reactions (allopurinol hypersensitivity syndrome, ~25% mortality).
• Important interaction: Blocks metabolism of azathioprine and 6-mercaptopurine - reduce those doses by 60-75%.
• Side effects: diarrhea, nausea, transaminitis, rash.

• Dose: 40-80 mg/day. 40 mg is roughly equivalent to 300 mg allopurinol.
• Second-line; more expensive than allopurinol.
• Associated with higher rate of cardiovascular events.
• Side effects: transaminitis.

Uricosuric Agents (Second-Line)

• Increases uric acid excretion via renal tubule. For patients intolerant of or with inadequate response to xanthine oxidase inhibitors.
• Dose: 500 mg/day initially, titrate up weekly; usual dose 1-1.5 g/day in divided doses; max 3 g/day.
• Requires normal renal function - not suitable in CKD.

Uricase (Last Resort)

• 8 mg IV every 2 weeks.
• Reserved for uncontrolled gout when all other agents fail and patient continues to have 2+ flares/year or persistent tophi.
• ACR guidelines strongly recommend against using as first-line therapy.

PART 3 - Prophylaxis During ULT Initiation

• Low-dose colchicine
• Low-dose NSAIDs
• Low-dose corticosteroids

PART 4 - Lifestyle Modifications

• Avoid high-purine foods: organ meats, shellfish, red meat
• Limit alcohol (especially beer)
• Stay well hydrated (promotes uric acid excretion)
• Avoid fructose-rich drinks
• Manage contributing medications (e.g., diuretics raise uric acid)
• Weight loss if overweight

Summary Table