What is the first-line treatment for an acute pseudogout attack of the knee?

Pseudogout Knee Treatment

For an acute pseudogout attack of the knee, first-line treatment is joint aspiration followed by intra-articular corticosteroid injection, or alternatively, oral NSAIDs at full anti-inflammatory doses, oral colchicine (low-dose regimen), or systemic corticosteroids—with the choice guided by renal function, cardiovascular risk, and comorbidities. 1

First-Line Treatment Options

The 2011 EULAR guidelines establish that acute CPP crystal arthritis (pseudogout) is extremely painful and requires rapid symptom relief. 1 Treatment selection must be individualized based on patient age, comorbidities, and risk factors, particularly because pseudogout predominantly affects older patients. 1

Intra-articular Corticosteroid Injection (Preferred for Monoarticular Knee Involvement)

• Joint aspiration with or without intra-articular injection of long-acting glucocorticosteroids is very commonly used for monoarticular or oligoarticular attacks, though evidence is extrapolated from gout studies rather than pseudogout-specific trials. 1
• This approach provides targeted local control with minimal systemic effects and is particularly valuable in elderly patients with multiple comorbidities. 1
• Standard precautions for glucocorticoid injection should be applied. 1

Oral NSAIDs

• NSAIDs at full anti-inflammatory doses are effective when started promptly, with evidence primarily extrapolated from gout treatment studies. 1, 2
• Continue the full dose throughout the entire attack until complete resolution; do not taper early. 1
• NSAIDs should be avoided in patients with chronic kidney disease, congestive heart failure, peptic ulcer disease, or cirrhosis due to high risk of gastrointestinal bleeding, cardiovascular events, and renal impairment—particularly problematic in older patients who often have chronic renal impairment and comorbidity. 1, 2

Oral Colchicine

• Low-dose colchicine (0.5 mg three to four times daily, with or without a 1 mg loading dose) is recommended based on expert opinion, as the traditional high-dose regimen (1 mg loading followed by 0.5 mg every 2 hours) causes marked side effects in 100% of patients. 1
• Evidence for colchicine efficacy in pseudogout is extrapolated from gout studies, where it effectively relieves acute crystal synovitis. 1
• Colchicine is contraindicated in severe renal impairment (GFR <30 mL/min) and in patients receiving strong P-glycoprotein or CYP3A4 inhibitors (e.g., clarithromycin, cyclosporine, ketoconazole, ritonavir, verapamil). 3
• The length of treatment depends on symptom relief and side effects, with diarrhea being the most common adverse event. 1

Systemic Corticosteroids

• Systemic corticosteroids are particularly useful in older patients with comorbidities and contraindications to NSAIDs or colchicine. 1
• Oral prednisone 30–35 mg daily for 3–5 days is an effective regimen. 2
• Small amounts should be used if prolonged treatment is required. 1

Adjunctive Non-Pharmacologic Measures

• Ice or cool packs and temporary rest are strongly supported by evidence from other causes of acute synovitis, including gout, though no RCT evidence exists specifically for pseudogout. 1

Treatment Algorithm for Acute Pseudogout of the Knee

1. If monoarticular knee involvement with accessible joint: Perform joint aspiration to confirm diagnosis (positively birefringent CPPD crystals on compensated polarized light microscopy) and inject intra-articular corticosteroid. 1, 4

2. If systemic treatment is preferred or multiple joints involved:

   • Check renal function first: If GFR <30 mL/min, use systemic corticosteroids only; avoid NSAIDs and colchicine. 1, 3
   • Assess cardiovascular and GI risk: If heart failure, cirrhosis, or peptic ulcer disease present, use systemic corticosteroids; avoid NSAIDs. 1, 2
   • Review medication list: If patient is on strong CYP3A4/P-gp inhibitors, avoid colchicine; use NSAIDs or corticosteroids. 3
   • If no contraindications exist: Choose between full-dose NSAIDs, low-dose colchicine, or oral corticosteroids based on patient tolerance and preference. 1, 2

Common Pitfalls to Avoid

• Do not use the obsolete high-dose colchicine regimen (0.5 mg every 2 hours until relief or toxicity), as it causes severe diarrhea in most patients without additional benefit. 1, 3
• Do not use intravenous colchicine, as this route is no longer used in most countries due to high risk of serious toxicity and even fatality. 1
• Do not prescribe NSAIDs in elderly patients with renal impairment without careful consideration of the risk-benefit ratio, as side effects greatly restrict their use in this population. 1
• Do not assume pseudogout treatment is identical to gout treatment—while many principles are extrapolated, pseudogout lacks the same level of RCT evidence and has no equivalent to urate-lowering therapy for long-term prevention. 1, 5

Long-Term Considerations

• There is no known drug that can prevent progression of joint destruction in CPPD disease, so treatment remains primarily symptomatic. 4
• Colchicine can be effective in recurring pseudogout when used prophylactically, and magnesium supplementation may have a role in prevention. 4
• Screen for underlying metabolic conditions (hyperparathyroidism, hemochromatosis, hypomagnesemia, hypophosphatemia) in patients with early-onset disease (before age 60), as these can promote or cause chondrocalcinosis. 4, 6, 7