What is the appropriate workup and treatment for a patient with gout?

Workup and Treatment of Gout

Diagnostic Workup

The diagnosis of gout is confirmed by identifying monosodium urate crystals in synovial fluid from the affected joint, though clinical criteria from the American College of Rheumatology can be used when joint aspiration is not feasible. 1

Key Diagnostic Steps:

• Joint aspiration with synovial fluid analysis is the gold standard—look for needle-shaped, negatively birefringent monosodium urate crystals under polarized light microscopy 1
• Serum uric acid level should be measured, though normal levels do not exclude acute gout (uric acid may be normal or low during acute flares) 2
• Assess for tophi on physical examination (ears, fingers, elbows, Achilles tendons) 2
• Evaluate renal function (creatinine clearance) before initiating any treatment, as this determines medication choices and dosing 2
• Screen for cardiovascular disease, heart failure, peptic ulcer disease, and liver disease as these affect treatment selection 3

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Acute Gout Flare Management

For acute gout flares, initiate treatment with colchicine, NSAIDs, or oral corticosteroids within 24 hours of symptom onset—these are equally effective first-line options, with selection based on renal function, gastrointestinal risk, and cardiovascular comorbidities. 2, 3

Treatment Algorithm Based on Severity:

Mild to Moderate Flare (pain ≤6/10, involving 1-3 small joints or 1-2 large joints):

Choose ONE of the following monotherapy options: 3

Option 1: Low-Dose Colchicine (Preferred if started early)

• 1.2 mg immediately, followed by 0.6 mg one hour later (total 1.8 mg over first hour) 2, 4
• Then 0.6 mg once or twice daily until flare resolves (typically 3-5 days) 2, 4
• Must start within 36 hours of symptom onset for effectiveness 2, 4
• Do NOT use high-dose colchicine—it provides no additional benefit but dramatically increases gastrointestinal toxicity 4

Option 2: NSAIDs at Full Anti-inflammatory Dose

• Naproxen, indomethacin, or sulindac at FDA-approved doses until complete resolution 2, 3
• Continue at full dose throughout the attack rather than early dose reduction 4, 3
• No single NSAID is superior to others 3

Option 3: Oral Corticosteroids

• Prednisone 30-35 mg daily (or 0.5 mg/kg/day) for 3-5 days, then stop or taper over 7-10 days 2, 3, 5
• Preferred in patients with renal disease, heart failure, cirrhosis, or cardiovascular disease 3

Severe Flare (pain ≥7/10, polyarticular involvement ≥4 joints, or multiple large joints):

Use combination therapy: 4, 3

• Colchicine + NSAIDs (most common combination) 4
• Oral corticosteroids + colchicine 3
• Intra-articular corticosteroids + any oral agent (for accessible large joints) 3
• AVOID combining NSAIDs with systemic corticosteroids due to synergistic gastrointestinal toxicity 2

Monoarticular Gout in Accessible Large Joint:

• Intra-articular corticosteroid injection is highly effective and avoids systemic drug exposure 2, 5

Patients Unable to Take Oral Medications:

• Intramuscular, intravenous, or intra-articular glucocorticoids are strongly recommended over IL-1 inhibitors or ACTH 2

Adjuvant Therapy:

• Topical ice is conditionally recommended as adjuvant treatment 2

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Special Population Dosing Adjustments

Renal Impairment:

Mild to Moderate Renal Impairment (CrCl 30-80 mL/min):

• Colchicine: Standard acute dosing (1.2 mg then 0.6 mg one hour later), but monitor closely for adverse effects 4, 6
• NSAIDs: Use with extreme caution; corticosteroids are safer 3, 5

Severe Renal Impairment (CrCl <30 mL/min):

• Colchicine: Standard acute dose acceptable, but repeat treatment course no more than once every 2 weeks 6
• NSAIDs: Contraindicated 3
• Corticosteroids are the preferred treatment 5

Dialysis Patients:

• Colchicine: Single dose of 0.6 mg only; do not repeat more than once every 2 weeks 6
• Oral prednisone 30-35 mg/day for 3-5 days is the safest option 5

Critical Drug Interactions:

Colchicine is absolutely contraindicated with strong CYP3A4 or P-glycoprotein inhibitors (clarithromycin, erythromycin, cyclosporine, ketoconazole, ritonavir) in patients with renal or hepatic impairment—this combination can cause fatal toxicity 4, 6

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Long-Term Urate-Lowering Therapy (ULT)

Initiate ULT in all patients with:

• ≥2 gout flares per year 2
• Presence of tophi 2
• Chronic kidney disease 2
• History of urolithiasis 2
• Young age at presentation (<40 years) 2
• Very high serum uric acid (>8.0 mg/dL or 480 μmol/L) 2

Target Serum Uric Acid:

• Maintain serum uric acid <6 mg/dL (360 μmol/L) lifelong 2, 5
• For severe gout with tophi or chronic arthropathy, target <5 mg/dL (300 μmol/L) until complete crystal dissolution 2
• Do not maintain serum uric acid <3 mg/dL long-term 2

First-Line ULT:

Allopurinol (First-Line in Normal Renal Function):

• Start at 100 mg/day 2
• Increase by 100 mg every 2-4 weeks until serum uric acid target is reached 2
• In renal impairment, adjust maximum dose to creatinine clearance 2

If Allopurinol Fails or Not Tolerated:

• Switch to febuxostat 2
• Add or switch to a uricosuric agent (probenecid, benzbromarone) 2

Refractory Severe Tophaceous Gout:

• Switch to pegloticase if XOI and uricosurics have failed AND patient has frequent flares (≥2/year) or nonresolving tophi 2
• Do NOT use pegloticase if flares are infrequent (<2/year) and no tophi present—harms and costs outweigh benefits 2

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Prophylaxis During ULT Initiation

All patients starting or adjusting ULT must receive anti-inflammatory prophylaxis to prevent acute flares. 3, 1

First-Line Prophylaxis Options:

• Low-dose colchicine 0.6 mg once or twice daily 3, 1
• Low-dose NSAID with proton pump inhibitor (if colchicine not tolerated) 3
• Low-dose prednisone (<10 mg/day) as second-line 3

Duration of Prophylaxis:

• At least 6 months 3, 1
• OR 3 months after achieving target serum uric acid if no tophi present 3
• OR 6 months after achieving target serum uric acid if tophi present 3

Special Considerations:

• Do NOT stop existing ULT during an acute flare 3
• Do NOT initiate new ULT during an acute flare—wait until flare resolves 3
• Febuxostat clinical trials included mandatory colchicine or NSAID prophylaxis, demonstrating this is standard of care 4

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Lifestyle Modifications

All patients with gout should receive counseling on modifiable risk factors: 2

Dietary Recommendations:

• Weight loss if overweight 2
• Avoid alcohol (especially beer and spirits) 2
• Avoid sugar-sweetened drinks and foods high in fructose 2
• Limit excessive intake of meat and seafood 2
• Encourage low-fat dairy products 2
• Encourage regular physical activity 2
• Coffee and cherry consumption may reduce gout risk 2

Medication Adjustments:

• Discontinue loop or thiazide diuretics if possible 2
• Consider losartan for hypertension (increases urinary uric acid excretion) 2
• Consider calcium channel blockers for hypertension 2
• Consider statin or fenofibrate for hyperlipidemia 2

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Common Pitfalls to Avoid

• Do NOT delay treatment waiting for diagnostic confirmation—early treatment within 24 hours is more important than definitive diagnosis 3
• Do NOT use high-dose colchicine regimens—they increase toxicity without improving efficacy 4, 3
• Do NOT preferentially use indomethacin—it has no efficacy advantage over other NSAIDs and potentially more adverse effects 3
• Do NOT combine NSAIDs with systemic corticosteroids due to synergistic GI toxicity 2
• Do NOT give colchicine to patients on strong CYP3A4/P-glycoprotein inhibitors with renal or hepatic impairment 4, 6
• Do NOT start colchicine treatment beyond 36 hours after symptom onset—effectiveness drops significantly 2, 4
• Do NOT initiate new ULT during an acute flare 3