What is the next step for treating pseudogout (calcium pyrophosphate deposition disease) that does not respond to colchicine (anti-inflammatory medication)?

Management of Pseudogout That Does Not Respond to Colchicine

For pseudogout (calcium pyrophosphate deposition disease) that does not respond to colchicine, the next step should be treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids, depending on patient-specific factors and comorbidities. 1

Treatment Options After Colchicine Failure

NSAIDs

• First-line alternative when colchicine fails
• Use full anti-inflammatory doses until the attack resolves
• Consider patient's renal function, cardiovascular risk, and gastrointestinal history
• Examples include naproxen, diclofenac, or indomethacin at anti-inflammatory doses

Corticosteroids

• Excellent alternative, especially when NSAIDs are contraindicated
• Administration options:
  • Intra-articular injection: Preferred for involvement of 1-2 large joints 1
  • Systemic oral: Prednisone or prednisolone at 0.5 mg/kg/day for 5-10 days 2
  • Parenteral: Intramuscular triamcinolone acetonide (60 mg) or intravenous methylprednisolone 1

ACTH (Adrenocorticotropic Hormone)

• Can be considered when NSAIDs and colchicine are contraindicated
• Administered parenterally (40-80 units intravenously, intramuscularly, or subcutaneously) 1
• Evidence suggests it may be effective for acute CPP crystal arthritis 1

Treatment Selection Algorithm

1. Assess patient comorbidities:

   • Renal impairment → Avoid NSAIDs, prefer corticosteroids
   • Cardiovascular disease → Avoid NSAIDs, prefer corticosteroids
   • Diabetes/uncontrolled hypertension → Prefer NSAIDs over corticosteroids
   • GI issues/history of ulcers → Avoid NSAIDs, prefer corticosteroids

2. Assess joint involvement:

   • 1-2 large joints → Consider intra-articular corticosteroid injection
   • Polyarticular involvement → Systemic therapy (oral NSAIDs or corticosteroids)

3. For severe attacks:

   • Consider combination therapy (e.g., NSAIDs plus corticosteroids) 1

Special Considerations

Elderly Patients

• Use extreme caution with NSAIDs due to increased risk of adverse effects
• Short-acting NSAIDs (diclofenac, ketoprofen) are preferred if NSAIDs must be used 3
• Corticosteroids (intra-articular or systemic) are often safer options 3

Prophylaxis for Recurrent Attacks

• Low-dose colchicine (0.6 mg once or twice daily) may be effective for preventing recurrent attacks 1
• If colchicine fails for prophylaxis, consider low-dose NSAIDs with gastroprotection 1

Investigational Options

• Methotrexate has shown promise in small uncontrolled studies for difficult cases 4
• IL-1 inhibitors (anakinra, canakinumab) may be considered in refractory cases, though evidence is limited and primarily extrapolated from gout studies 1, 5

Monitoring and Follow-up

• Assess response within 24-48 hours of initiating new therapy
• Inadequate response is defined as <20% improvement in pain within 24 hours or <50% improvement after 24 hours 1
• If no response to the alternative treatment, consider combination therapy or reassess diagnosis

Remember that unlike gout, pseudogout has less robust evidence for specific treatments, and management approaches are often extrapolated from gout treatment guidelines. The European League Against Rheumatism (EULAR) provides specific recommendations for calcium pyrophosphate deposition disease management that should guide treatment decisions 1.