What is the management of acute gout?

Management of Acute Gout

Pathophysiology

Gout results from hyperuricemia leading to deposition of monosodium urate crystals in joints, triggering an intense inflammatory response that causes the characteristic acute gouty arthritis. 1

• Urate becomes insoluble above approximately 404 µmol/L (6.8 mg/dL), at which point crystal precipitation occurs in joint spaces, cartilage, bones, tendons, and bursas 1
• The inflammatory cascade triggered by these crystals produces the acute symptoms of joint swelling, pain, and tenderness 1
• Risk factors include obesity, hypertension, alcohol intake (especially beer), diuretic use, high-fructose foods/drinks, and impaired renal function 1

First-Line Treatment for Acute Attacks

Corticosteroids should be considered first-line therapy for acute gout in patients without contraindications because they are safer, equally effective as NSAIDs, and low-cost. 1, 2

Treatment Options (All Equally Effective):

Corticosteroids:

• Prednisolone 35 mg daily for 5 days 1, 2
• Alternative: Prednisone 0.5 mg/kg/day for 5-10 days at full dose then stop, or 2-5 days at full dose followed by 7-10 day taper 2
• Preferred in patients with renal impairment, heart failure, cirrhosis, or peptic ulcer disease 2, 3
• Avoid in patients with diabetes (NSAIDs or colchicine preferred), systemic fungal infections, or uncontrolled hyperglycemia 1, 2
• Adverse effects with short-term use: dysphoria, mood disorders, elevated glucose, immune suppression, fluid retention 1

NSAIDs:

• Use full FDA-approved anti-inflammatory doses 2
• FDA-approved options: naproxen, indomethacin, sulindac 2
• Indomethacin has no proven superiority over other NSAIDs despite traditional preference 1, 2
• Contraindicated in renal disease, heart failure, cirrhosis, or peptic ulcer disease 1, 2
• Adverse effects: dyspepsia, gastrointestinal bleeding, ulcers, perforations 1

Colchicine:

• Low-dose regimen: 1.2 mg followed by 0.6 mg one hour later 1, 2
• This low-dose regimen is equally effective as higher doses with significantly fewer gastrointestinal side effects 1, 2
• Most effective when started within 12 hours of symptom onset 3, 4
• More expensive than corticosteroids or NSAIDs 1
• Contraindicated in renal or hepatic impairment when using potent CYP3A4 or P-glycoprotein inhibitors 1
• Adverse effects: diarrhea, nausea, vomiting, cramps, abdominal pain 1

Treatment Algorithm Based on Severity

For mild to moderate pain (≤6/10) with limited joint involvement:

• Monotherapy with any first-line agent is appropriate 2

For severe pain (≥7/10) or polyarticular involvement:

• Combination therapy is recommended 2, 4
• Effective combinations: colchicine plus NSAIDs, oral corticosteroids plus colchicine, or intra-articular steroids with any other modality 2, 4

For single joint involvement:

• Intra-articular corticosteroid injection is highly effective 2, 3, 4

Critical Timing Principles

Initiate treatment within 24 hours of symptom onset for optimal outcomes. 2, 3, 4

• Delaying treatment beyond 24 hours significantly reduces effectiveness 4
• Educate patients to self-medicate at first warning symptoms ("pill in the pocket" approach) 4
• Pain relief typically begins within 1 hour with naproxen and within 30 minutes with naproxen sodium 5

Management During Acute Attacks

Continue established urate-lowering therapy without interruption during acute attacks. 2, 3, 4

• Discontinuing urate-lowering therapy during flares is a common pitfall that should be avoided 4
• Topical ice application is recommended as an adjunctive measure 4

When NOT to Initiate Long-Term Urate-Lowering Therapy

Do not initiate long-term urate-lowering therapy after a first gout attack or in patients with infrequent attacks (<2 per year). 1, 3

• Urate-lowering therapy does not reduce acute gout attacks in the first 6 months 1
• Reserve for patients with recurrent attacks, tophi, urate arthropathy, or renal stones 3, 4

Indications for Long-Term Urate-Lowering Therapy

Initiate urate-lowering therapy in patients with recurrent gout flares (≥2 per year), tophi, radiographic changes, or renal stones. 3, 4

Starting Urate-Lowering Therapy:

Allopurinol:

• Start with 100 mg daily 3, 6
• Increase by 100 mg at weekly intervals until serum urate <6 mg/dL is achieved 3, 6
• Maximum dose: 800 mg daily 6
• Adjust dose based on renal function: with creatinine clearance 10-20 mL/min use 200 mg daily; <10 mL/min use ≤100 mg daily 6
• Target serum urate: <6 mg/dL 3, 4

Febuxostat:

• Alternative xanthine oxidase inhibitor, clinically equivalent to allopurinol 1
• Higher cost than allopurinol 1
• Common adverse effects: abdominal pain, diarrhea, musculoskeletal pain 1

Mandatory Prophylaxis When Starting Urate-Lowering Therapy

Prophylactic therapy with low-dose colchicine or low-dose NSAIDs is essential when initiating urate-lowering therapy to prevent acute flares. 1, 3, 4

• Continue prophylaxis for at least 6 months, or 3 months after achieving target serum urate if no tophi present 4
• If tophi present, continue for 6 months after achieving target serum urate 4
• Inadequate duration of prophylaxis leads to breakthrough flares and poor medication adherence 4
• Prophylactic options: low-dose colchicine (0.5-1 mg/day), low-dose NSAIDs with gastroprotection, or low-dose prednisone 3, 4

Management of Inadequate Response

Consider inadequate response if <20% improvement in pain within 24 hours or <50% improvement after 24 hours of therapy. 4

• Switch to another monotherapy or add a second recommended agent 4
• For severe refractory attacks, IL-1 inhibitors (anakinra or canakinumab) may be considered, though off-label 4

Special Population Considerations

Renal impairment:

• Corticosteroids are safer than NSAIDs or colchicine 2, 3, 4
• Adjust allopurinol dose based on creatinine clearance 3, 6

Hepatic impairment:

• Consider colchicine dose reduction and monitor closely 3

NPO patients:

• For 1-2 affected joints: intra-articular corticosteroid injection 4
• For multiple joints: IV/IM methylprednisolone (0.5-2.0 mg/kg) or subcutaneous ACTH (25-40 IU) 4

Common Pitfalls to Avoid

• Never use high-dose colchicine regimens - they cause significant gastrointestinal side effects with no additional benefit 1, 4
• Never discontinue urate-lowering therapy during acute flares 4
• Never delay treatment beyond 24 hours - effectiveness decreases significantly 4
• Never start urate-lowering therapy without prophylaxis - this leads to breakthrough flares 4
• Never use NSAIDs in heart failure, peptic ulcer disease, or significant renal disease 4
• Check for drug interactions with colchicine, particularly with strong P-glycoprotein and/or CYP3A4 inhibitors (cyclosporine, clarithromycin) 4

Non-Pharmacologic Measures

• Weight loss for obese patients 3, 4
• Avoid alcoholic drinks, especially beer 1, 3, 4
• Avoid beverages sweetened with high-fructose corn syrup 1, 4
• Limit purine-rich foods (organ meats, shellfish) 3
• Encourage consumption of vegetables and low-fat dairy products 3
• Maintain fluid intake sufficient to yield daily urinary output of at least 2 liters 6