Causes and Treatment of Gout
Causes of Gout
Gout results from sustained hyperuricemia leading to precipitation of monosodium urate crystals in joint spaces, most commonly affecting the first metatarsophalangeal joint. 1
Primary Risk Factors
- Elevated serum uric acid levels above the saturation point (approximately 6.8 mg/dL or 404 µmol/L), which triggers crystal formation and inflammatory responses 2
- Dietary factors including excessive consumption of purine-rich foods (organ meats, shellfish), alcoholic beverages (especially beer), and high-fructose corn syrup sweetened drinks 2, 1
- Obesity and metabolic syndrome contributing to increased uric acid production 2, 1
- Medication use, particularly loop and thiazide diuretics that increase uric acid levels 2, 1
- Renal insufficiency impairing uric acid excretion 3
- Occupational lead exposure 4
Treatment of Acute Gout Attacks
For acute gout, corticosteroids should be considered first-line therapy because they are generally safer, equally effective as NSAIDs, and low-cost, with treatment initiated within 24 hours of symptom onset for optimal outcomes. 2, 5
First-Line Monotherapy Options (for 1-3 small joints or 1-2 large joints)
Corticosteroids 2
- Oral prednisolone 30-35 mg daily for 5 days 2, 6
- Intra-articular injection for single joint involvement (dose based on joint size) 2
- Fewer adverse effects than NSAIDs, particularly safer in renal disease, heart failure, or cirrhosis 2
NSAIDs at full anti-inflammatory doses 2
- Naproxen, indomethacin, or sulindac are FDA-approved options 2
- No evidence that indomethacin is superior to other NSAIDs despite traditional preference 2
- Continue at full dose until attack completely resolves 2
- Contraindicated in renal disease, heart failure, cirrhosis, peptic ulcer disease, or patients on anticoagulation 2
Low-dose colchicine 2
- 1.2 mg followed by 0.6 mg one hour later (total 1.8 mg in first 12 hours) 2
- Only effective when started within 36 hours of symptom onset 2, 6
- After 12 hours, may continue 0.6 mg twice daily until attack resolves 2
- Avoid high-dose regimens - they cause significant gastrointestinal toxicity without additional benefit 2, 5
- Contraindicated in renal/hepatic impairment with concurrent use of potent CYP3A4 or P-glycoprotein inhibitors (clarithromycin, cyclosporine) 2, 7
Combination Therapy (for severe pain ≥7/10 or polyarticular involvement ≥4 joints)
- Colchicine plus NSAIDs 2
- Oral corticosteroids plus colchicine 2
- Intra-articular steroids with any other modality 2
Special Populations
NPO (nil per os) patients 2
- Intra-articular corticosteroid injection for 1-2 affected joints 2
- Intravenous/intramuscular methylprednisolone 0.5-2.0 mg/kg for multiple joint involvement 2
- Subcutaneous ACTH 25-40 IU as alternative 2
Renal impairment patients 5
- Corticosteroids are safest option 5
- Avoid NSAIDs 2
- Colchicine requires dose adjustment: for severe impairment (CrCl <30 mL/min), treatment course should not be repeated more than once every two weeks 7
Critical Management Principle
Continue established urate-lowering therapy without interruption during acute attacks - discontinuing worsens outcomes 5, 6, 8
Long-Term Management and Prevention
Indications for Urate-Lowering Therapy (ULT)
Urate-lowering therapy is indicated for patients with recurrent acute attacks, tophi, chronic gouty arthropathy, or radiographic changes of gout. 2, 5, 6
Do NOT initiate ULT after a first gout attack or in patients with infrequent attacks. 5
First-Line Urate-Lowering Agents
Xanthine oxidase inhibitors (allopurinol or febuxostat) 2, 6, 8
- Allopurinol: Start at 100 mg daily, increase by 100 mg every 2-4 weeks as needed 2
- Adjust dose in renal impairment 2
- High-quality evidence shows no difference between lower doses of febuxostat and allopurinol for preventing gout flares 2
- Febuxostat has higher costs than allopurinol 2
Alternative: Uricosuric agents 2, 8
- Probenecid or benzbromarone for patients with normal renal function 2
- Contraindicated in patients with urolithiasis 2
Target Serum Urate Level
Maintain serum uric acid below 6 mg/dL (360 µmol/L) to promote crystal dissolution and prevent crystal formation. 2, 6, 8
Mandatory Prophylaxis During ULT Initiation
Anti-inflammatory prophylaxis must be provided when starting urate-lowering therapy to prevent acute flares. 2, 6
First-line prophylactic options 2, 6
- Low-dose colchicine 0.5-0.6 mg once or twice daily 2
- Low-dose NSAIDs (e.g., naproxen 250 mg twice daily) with gastroprotection if indicated 2, 6
- Low-dose prednisone (<10 mg/day) if colchicine and NSAIDs contraindicated 6
- Minimum 6 months, OR 2
- 3 months after achieving target serum urate in patients without tophi, OR 2
- 6 months after achieving target serum urate where tophi have resolved 2
High-quality evidence shows prophylaxis reduces acute gout attacks by at least half, and moderate-quality evidence indicates duration should exceed 8 weeks 2
Non-Pharmacologic Measures
Essential lifestyle modifications 2, 6, 8
- Weight loss if obese 2, 6
- Limit purine-rich foods (organ meats, shellfish) 1
- Avoid alcoholic drinks, especially beer 2, 1
- Avoid beverages sweetened with high-fructose corn syrup 1
- Encourage consumption of vegetables and low-fat/nonfat dairy products 1
- Topical ice application as adjunctive measure during acute attacks 2, 6
Medication adjustments 2
- Discontinue diuretics if possible 2
- Consider losartan for hypertension (modest uricosuric effect) 2
- Consider fenofibrate for hyperlipidemia (modest uricosuric effect) 2
Common Pitfalls and How to Avoid Them
Delaying treatment beyond 24 hours significantly reduces effectiveness - educate patients for "pill in the pocket" self-initiation at first warning symptoms 5, 8
Using high-dose colchicine regimens causes severe gastrointestinal toxicity without additional benefit - always use low-dose regimen (1.2 mg + 0.6 mg) 2, 5, 8
Discontinuing ULT during acute attacks worsens outcomes - continue established therapy without interruption 5, 6, 8
Inadequate prophylaxis duration when initiating ULT leads to breakthrough flares and poor medication adherence - continue for at least 6 months 2, 6, 8
Ignoring drug interactions with colchicine can cause serious toxicity - avoid concurrent use with strong CYP3A4/P-glycoprotein inhibitors in patients with renal or hepatic impairment 2, 7
Prescribing NSAIDs without considering comorbidities - avoid in heart failure, peptic ulcer disease, significant renal disease, or patients on anticoagulation 2, 6, 8