What is the recommended first‑line treatment for an acute pseudogout flare and the alternatives if NSAIDs are contraindicated?

Pseudogout Treatment

First-Line Treatment for Acute Pseudogout Flare

For an acute pseudogout (calcium pyrophosphate deposition disease) flare, use the same first-line agents recommended for acute gout: NSAIDs, colchicine, or oral corticosteroids, with selection based on renal function, cardiovascular risk, and gastrointestinal comorbidities. 1, 2, 3 Although the evidence provided focuses on gout rather than pseudogout specifically, the inflammatory mechanisms and clinical management are nearly identical, and these agents represent the standard of care for both conditions.

NSAID Therapy (First-Line Option)

• Initiate full-dose NSAID therapy within 24 hours of symptom onset for maximum efficacy 1, 4
• FDA-approved options include naproxen, indomethacin, or sulindac at full anti-inflammatory doses (e.g., naproxen 500 mg twice daily, indomethacin 50 mg three times daily) 3, 4
• Continue at full dose throughout the entire attack until complete resolution—do not reduce the dose early 1, 4
• NSAIDs achieve roughly equivalent efficacy regardless of which specific agent is chosen; the critical factor is rapid initiation 4, 5

Colchicine Therapy (First-Line Option)

• Administer colchicine 1.2 mg immediately, followed by 0.6 mg one hour later (total 1.8 mg in the first hour), then after a 12-hour pause resume 0.6 mg once or twice daily until the attack resolves 3
• This low-dose regimen is only effective if started within 36 hours of symptom onset; efficacy drops sharply beyond this window 3
• The low-dose protocol achieves approximately 42% treatment success versus 17% with placebo, with significantly fewer gastrointestinal adverse effects than older high-dose regimens 3

Corticosteroid Therapy (First-Line Option)

• Oral prednisone 0.5 mg/kg per day (approximately 30–35 mg daily for average adults) for 5–10 days at full dose, then stop abruptly 2
• Alternatively, give full dose for 2–5 days followed by a 7–10 day taper 2
• Corticosteroids demonstrate equivalent efficacy to NSAIDs but with fewer adverse events (27% versus 63% adverse event rate in direct comparison) 2
• Intra-articular corticosteroid injection is highly effective for monoarticular or oligoarticular involvement of accessible large joints (e.g., triamcinolone acetonide 40 mg for the knee, 20–30 mg for the ankle) 2

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Alternatives When NSAIDs Are Contraindicated

Absolute NSAID Contraindications

NSAIDs must be avoided in patients with: 2, 3, 4

• Severe renal impairment (eGFR <30 mL/min), as NSAIDs can precipitate or worsen acute kidney injury
• Active or recent gastrointestinal bleeding
• Severe heart failure or decompensated cardiovascular disease
• Active peptic ulcer disease
• Patients on anticoagulation therapy (relative contraindication requiring careful risk assessment)

Primary Alternative: Oral Corticosteroids

When NSAIDs are contraindicated, oral corticosteroids become the preferred first-line therapy. 2

• Prednisone 30–35 mg daily for 5 days provides rapid symptom control with a favorable safety profile 2
• Corticosteroids are explicitly safer than NSAIDs in patients with renal impairment, cardiovascular disease, heart failure, cirrhosis, or peptic ulcer disease 2
• No dose adjustment is required for renal impairment, making corticosteroids particularly advantageous in this population 2

Secondary Alternative: Colchicine (With Important Caveats)

Colchicine can be used when NSAIDs are contraindicated, but requires careful dose adjustment and has critical drug interactions. 3

• In patients with moderate renal impairment (CrCl 30–80 mL/min), use the standard loading dose (1.2 mg followed by 0.6 mg one hour later) with close monitoring 3
• In severe renal impairment (eGFR <30 mL/min), colchicine should be avoided entirely 3
• Absolute contraindication: patients taking strong CYP3A4 or P-glycoprotein inhibitors (clarithromycin, erythromycin, cyclosporine, ketoconazole, ritonavir), especially when combined with renal or hepatic impairment—this combination can cause fatal toxicity 3

Tertiary Alternative: Intra-articular Corticosteroid Injection

For monoarticular or oligoarticular pseudogout involving one or two large accessible joints, intra-articular corticosteroid injection provides targeted therapy with minimal systemic effects. 2

• Dose varies by joint size: knee 40 mg, ankle 20–30 mg, wrist 10–20 mg triamcinolone acetonide 2
• Can be combined with oral corticosteroids if additional joints require treatment 2

Parenteral Corticosteroids for Patients Unable to Take Oral Medications

Intramuscular triamcinolone acetonide 60 mg is the specifically recommended IM dose for acute flares when oral access is not feasible (e.g., NPO status, surgical conditions, inability to tolerate oral therapy) 2

• Alternative: IV or IM methylprednisolone 0.5–2.0 mg/kg (approximately 40–140 mg for most adults) 2

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Treatment Algorithm

1. Assess timing: Is the patient within 24 hours of symptom onset? (Critical for optimal efficacy) 1, 3

2. Evaluate renal function:

   • eGFR ≥30 mL/min → NSAIDs, colchicine, or corticosteroids are all options 2, 3
   • eGFR <30 mL/min → Avoid NSAIDs and colchicine; use corticosteroids 2, 3

3. Screen for cardiovascular/GI risk:

   • Heart failure, recent MI, or high CV risk → Prefer corticosteroids over NSAIDs 2
   • Active GI bleeding or peptic ulcer → Avoid NSAIDs; use corticosteroids 2
   • On anticoagulation → Prefer corticosteroids over NSAIDs 2

4. Check for drug interactions:

   • Strong CYP3A4/P-gp inhibitors + renal/hepatic impairment → Absolute contraindication to colchicine 3

5. Assess joint involvement:

   • Monoarticular or oligoarticular (1–2 large joints) → Consider intra-articular corticosteroid injection 2
   • Polyarticular (≥4 joints) → Consider combination therapy (e.g., oral corticosteroid + intra-articular injection) 3

6. Select agent:

   • No contraindications → NSAID, colchicine, or oral corticosteroid based on patient preference and prior response 1, 3
   • NSAID contraindicated → Oral corticosteroid (prednisone 30–35 mg daily × 5 days) 2
   • Oral route not feasible → IM triamcinolone 60 mg or IV methylprednisolone 2

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Common Pitfalls to Avoid

• Delaying treatment beyond 24 hours markedly reduces efficacy of all agents 1, 3
• Do not use colchicine after 36 hours from symptom onset—it will not work 3
• Do not attempt dose reduction of colchicine in patients on CYP3A4/P-gp inhibitors—even a single 0.6 mg dose carries unacceptable toxicity risk when these inhibitors are present alongside renal or hepatic impairment 3
• Do not combine NSAIDs with systemic corticosteroids due to synergistic gastrointestinal toxicity 1, 3
• Do not use high-dose prednisone (>10 mg/day) for prolonged periods as prophylaxis 2

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Monitoring 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 diagnosis or switch to a different monotherapy, or add a second agent for severe attacks 2, 3