Causes and Treatment of Gout
Causes of Gout
Gout results from monosodium urate crystal deposition in joints and tissues due to sustained hyperuricemia. 1
Primary Risk Factors
- Male sex, obesity, and hypertension are major predisposing factors 1
- Dietary factors including high intake of meat, seafood, alcohol (especially beer), and beverages sweetened with high-fructose corn syrup 2, 1
- Medications, particularly loop and thiazide diuretics, which increase uric acid levels 2
- Chronic kidney disease impairs uric acid excretion 1
- Genetic and ethnic predisposition, with higher rates in Taiwanese, Pacific Islander, and New Zealand Maori populations 1
Treatment of Acute Gout Attacks
For acute gout, initiate pharmacologic therapy within 24 hours of symptom onset with NSAIDs, corticosteroids, or low-dose colchicine as first-line options. 3, 4
First-Line Monotherapy Options (for mild-moderate pain involving 1-3 joints)
NSAIDs:
- Use full FDA-approved anti-inflammatory doses immediately 3
- Naproxen, indomethacin, and sulindac are FDA-approved for acute gout 3
- Continue at full dose until complete resolution 3
- Avoid in patients with heart failure, peptic ulcer disease, or significant renal disease 4
Low-Dose Colchicine:
- 1.2 mg followed by 0.6 mg one hour later (maximum 1.8 mg in first 12 hours) 3, 4, 5
- Most effective when started within 12-36 hours of symptom onset 3, 4
- This low-dose regimen is equally effective as high-dose with significantly fewer gastrointestinal side effects 3, 4
- Do not use if patient is already on prophylactic colchicine 5
Corticosteroids:
- Oral prednisone 30-35 mg daily (or 0.5 mg/kg/day) for 3-5 days, then stop or taper over 7-10 days 3, 4
- Particularly useful for patients with contraindications to NSAIDs or colchicine 3, 4
- Intra-articular corticosteroid injection is highly effective for single joint involvement 3, 4
Combination Therapy (for severe pain ≥7/10 or polyarticular involvement)
Recommended combinations include: 3, 4
- Colchicine plus NSAIDs
- Oral corticosteroids plus colchicine
- Intra-articular steroids with any other modality
Critical Management Principles
- Continue established urate-lowering therapy without interruption during acute attacks 3, 4
- Delaying treatment beyond 24 hours significantly reduces effectiveness 3, 4
- Consider inadequate response if <20% pain improvement within 24 hours or <50% improvement after 24 hours 3
Long-Term Management: Urate-Lowering Therapy
Urate-lowering therapy is indicated for patients with recurrent acute attacks (≥2 per year), tophi, radiographic changes of gout, chronic gouty arthritis, urolithiasis, or chronic kidney disease. 3, 4, 1
When NOT to Start Urate-Lowering Therapy
- Do not initiate after a first gout attack or in patients with infrequent attacks 4
Target Serum Urate Level
- Maintain serum uric acid below 6 mg/dL (360 μmol/L) to promote crystal dissolution and prevent crystal formation 3, 4
First-Line Urate-Lowering Agents
Allopurinol (Xanthine Oxidase Inhibitor):
- Start at 100 mg daily and increase by 100 mg every 2-4 weeks as needed 3
- Adjust dose in renal impairment 3
- First-line choice for patients with renal calculi, renal insufficiency, concomitant diuretic therapy, or urate overproduction 6
Febuxostat (Xanthine Oxidase Inhibitor):
- Alternative to allopurinol 4
- Note: Associated with increased all-cause and cardiovascular mortality; not routinely recommended as first choice 1
Alternative Agents
Uricosuric Drugs:
- Probenecid or benzbromarone can be used in patients with normal renal function 3, 4
- Contraindicated in patients with urolithiasis 3
- Preferred in allopurinol-allergic patients with normal renal function and no history of kidney stones 6
Anti-Inflammatory Prophylaxis During Urate-Lowering Therapy
Prophylaxis against acute flares is strongly recommended when initiating urate-lowering therapy. 3, 4
Prophylaxis Options
- Low-dose colchicine (0.5-1 mg daily) 3, 4
- Low-dose NSAIDs with gastroprotection if indicated 3, 4
- Low-dose prednisone 4
Duration of Prophylaxis
Continue prophylaxis for the greater of: 3, 4
- 6 months minimum duration, OR
- 3 months after achieving target serum urate in patients without tophi, OR
- 6 months after achieving target serum urate in patients with resolved tophi
Non-Pharmacologic Management
Lifestyle modifications are core aspects of gout management: 3
- Weight loss if obese 3, 4
- Avoid alcoholic drinks, especially beer 3, 4, 2
- Avoid beverages sweetened with high-fructose corn syrup 2
- Limit consumption of purine-rich foods (organ meats, shellfish) 2
- Encourage consumption of vegetables and low-fat or nonfat dairy products 2
- Topical ice application and rest of inflamed joint during acute attacks 6
Medication Adjustments
- Stop diuretic therapy if possible when gout is present 3
- Consider losartan for hypertension (modest uricosuric effect) 3
- Consider fenofibrate for hyperlipidemia (modest uricosuric effect) 3
Common Pitfalls and Caveats
Acute Attack Management
- High-dose colchicine regimens (>1.8 mg in 12 hours) cause significant gastrointestinal toxicity with no additional benefit 3, 4
- Colchicine has critical drug interactions with P-glycoprotein and CYP3A4 inhibitors (cyclosporine, clarithromycin, protease inhibitors) requiring dose adjustments 5
- Do not treat acute gout with colchicine in patients already on prophylactic colchicine 5
Renal Impairment Considerations
- For severe renal impairment (CrCl <30 mL/min), colchicine dose for acute gout should not be repeated more than once every 2 weeks 5
- For dialysis patients, use single 0.6 mg dose for acute gout, not repeated more than once every 2 weeks 5
Long-Term Management
- Never discontinue urate-lowering therapy during acute flares 3, 4
- Inadequate duration of prophylaxis (<6 months) leads to breakthrough flares and poor medication adherence 3, 4
- Starting urate-lowering therapy without prophylaxis commonly triggers acute attacks 3
Comorbidity Management
- Address associated cardiovascular risk factors (hyperlipidemia, hypertension, hyperglycemia, obesity, smoking) as integral part of gout management 3