What is the recommended management of an acute gout flare in an adult, including first‑line anti‑inflammatory therapy and adjustments for comorbid conditions such as renal impairment, peptic ulcer disease, cardiovascular risk, age over 65, and diabetes?

Treatment of Acute Gout Flare

For an acute gout flare, initiate therapy within 24 hours using NSAIDs, colchicine, or corticosteroids as first-line monotherapy, selecting the agent based on renal function, cardiovascular risk, gastrointestinal comorbidities, and drug interactions. 1

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First-Line Treatment Selection Algorithm

Step 1: Assess timing and contraindications

• If symptom onset ≤36 hours and no contraindications exist, colchicine, NSAIDs, or corticosteroids are equally appropriate first-line options. 1
• If symptom onset >36 hours, do not use colchicine—efficacy drops sharply beyond this window; select NSAIDs or corticosteroids instead. 1

Step 2: Apply patient-specific factors to select the optimal agent

Colchicine is preferred when:

• Symptom onset is ≤36 hours (ideally ≤12 hours for maximum benefit). 1
• Renal function is adequate (eGFR ≥30 mL/min). 1
• Patient is not taking strong CYP3A4 or P-glycoprotein inhibitors (clarithromycin, erythromycin, cyclosporine, ketoconazole, ritonavir). 1
• No severe hepatic impairment exists. 1

Dosing: Give 1.2 mg orally once, followed 1 hour later by 0.6 mg (total 1.8 mg over 1 hour). After a 12-hour pause, resume 0.6 mg once or twice daily until the attack resolves. 1 This low-dose regimen achieves ≈42% treatment success versus ≈17% with placebo and produces significantly fewer gastrointestinal adverse effects than high-dose protocols. 1

Corticosteroids are preferred when:

• Severe renal impairment (eGFR <30 mL/min) is present—colchicine and NSAIDs must be avoided. 1, 2
• Cardiovascular disease or heart failure exists—NSAIDs carry unacceptable cardiovascular risk. 2, 3
• Peptic ulcer disease or gastrointestinal bleeding risk is present—NSAIDs are contraindicated. 2, 3
• Cirrhosis or hepatic impairment exists—NSAIDs are contraindicated. 2
• Patient is on anticoagulation—NSAIDs increase bleeding risk. 1
• Age >65 years with multiple comorbidities—corticosteroids are safer than NSAIDs. 4, 5

Dosing: Prescribe prednisone 30–35 mg once daily for 5 days (fixed dose, no taper required for most patients). 2, 3 For severe or polyarticular attacks, use prednisone 0.5 mg/kg/day for 2–5 days followed by a 7–10 day taper to reduce rebound inflammation risk. 2, 3

Alternative routes:

• Intra-articular corticosteroid injection (e.g., triamcinolone acetonide 40 mg for the knee, 20–30 mg for the ankle) is highly effective for monoarticular or oligoarticular gout involving one or two large, accessible joints. 1, 2
• Intramuscular triamcinolone acetonide 60 mg is appropriate when oral administration is not feasible (NPO status, severe vomiting). 1, 2

NSAIDs are preferred when:

• No renal impairment (eGFR ≥60 mL/min), no cardiovascular disease, no peptic ulcer disease, and no anticoagulation exist. 1
• Patient has no contraindications to NSAIDs and prefers this option. 1

Dosing: Use full FDA-approved anti-inflammatory doses (naproxen 500 mg twice daily, indomethacin 50 mg three times daily, or sulindac 200 mg twice daily) and maintain that dose throughout the entire attack until complete resolution. 1 No single NSAID is more effective than others for gout. 1

Caution: NSAIDs with short plasma half-lives (diclofenac, ketoprofen) are preferred in elderly patients if NSAIDs must be used, but corticosteroids remain safer. 4

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Combination Therapy for Severe Attacks

For severe acute gout involving ≥4 joints or multiple large joints, initiate combination therapy:

• Colchicine + NSAID (if no contraindications to either agent). 1
• Oral corticosteroids + colchicine (synergistic anti-inflammatory effects). 1, 3
• Intra-articular steroids + any oral modality (for accessible large joints plus systemic involvement). 1, 3

Do not combine NSAIDs with systemic corticosteroids—synergistic gastrointestinal toxicity risk. 1

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Critical Adjustments for Comorbid Conditions

Renal Impairment

• Mild to moderate (eGFR 30–59 mL/min): Colchicine can be used at standard dosing (1.2 mg followed by 0.6 mg 1 hour later) with close monitoring for adverse effects. 1 NSAIDs should be used with extreme caution. 1
• Severe (eGFR <30 mL/min): Avoid colchicine and NSAIDs entirely. Use prednisone 30–35 mg daily for 5 days as the safest first-line option; no dose adjustment is required. 1, 2, 3
• Patients with renal impairment taking strong CYP3A4/P-glycoprotein inhibitors: Absolute contraindication to colchicine—fatal toxicity can occur. 1 Use corticosteroids instead. 1

Peptic Ulcer Disease

• Avoid NSAIDs. Use colchicine (if renal function permits) or corticosteroids. 1, 6
• If NSAIDs are unavoidable, co-prescribe a proton pump inhibitor. 2

Cardiovascular Disease or Heart Failure

• Avoid NSAIDs—they increase cardiovascular event risk and worsen heart failure. 7, 5
• Colchicine is safe and may reduce myocardial infarction risk. 7
• Short-duration, low-dose corticosteroids (prednisone 30–35 mg for 5 days) are efficacious and may be safe. 7, 5

Age >65 Years

• Corticosteroids are safer than NSAIDs in elderly patients due to reduced gastrointestinal, renal, and cardiovascular toxicity. 4, 5
• Colchicine is poorly tolerated in the elderly—avoid if possible. 4
• Intra-articular or systemic corticosteroids are increasingly used for acute gouty flares in aged patients with medical disorders contraindicating NSAID therapy. 4

Diabetes

• Short-term corticosteroids can elevate blood glucose significantly—monitor glucose closely and adjust diabetic medications proactively. 2, 3
• Colchicine or NSAIDs (if no contraindications) may be preferred to avoid hyperglycemia. 1

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Common Pitfalls and How to Avoid Them

• Delaying treatment beyond 24 hours markedly reduces efficacy of any acute therapy. 1 Educate patients on the "pill in the pocket" approach to self-medicate at the first warning symptoms. 1
• Do not attempt dose reduction of colchicine as a "compromise" in patients with renal impairment plus CYP3A4/P-glycoprotein inhibitors—even a single 0.6 mg dose carries unacceptable toxicity risk. 1
• Do not discontinue ongoing urate-lowering therapy (allopurinol, febuxostat) during an acute flare—continuation helps maintain serum urate control and does not worsen the attack. 1
• Do not use high-dose colchicine regimens (>1.8 mg in the first hour)—they provide no additional benefit but substantially increase gastrointestinal toxicity. 1
• Do not use NSAIDs in patients with severe renal impairment, heart failure, or cirrhosis—risk of acute kidney injury and cardiovascular complications. 1, 4, 5

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Monitoring Response and Inadequate Response

• Define inadequate response as <20% improvement in pain within 24 hours or <50% improvement at ≥24 hours after initiating therapy. 2
• If inadequate response occurs: Consider alternative diagnoses, switch to another monotherapy, or add a second agent (combination therapy). 2

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Prophylaxis During Urate-Lowering Therapy Initiation

• When initiating or adjusting urate-lowering therapy, provide anti-inflammatory prophylaxis for at least 6 months (or 3 months after achieving target serum urate if no tophi are present). 1
• First-line prophylaxis: Low-dose colchicine 0.6 mg once or twice daily. 1
• Second-line prophylaxis (if colchicine contraindicated): Low-dose prednisone <10 mg/day or low-dose NSAID with proton pump inhibitor. 1, 3
• Do not use high-dose prednisone (>10 mg/day) for prophylaxis—inappropriate and carries significant long-term risks. 2, 3