What is CPPD (Calcium Pyrophosphate Deposition Disease) and how is it further evaluated?

Calcium Pyrophosphate Deposition Disease (CPPD): Diagnosis and Evaluation

CPPD is a common form of inflammatory arthritis caused by calcium pyrophosphate crystal deposition in joints, requiring diagnosis through synovial fluid analysis for weakly positive birefringent rhomboid-shaped crystals under compensated polarized light microscopy, along with radiographic evidence and evaluation for underlying metabolic disorders. 1

What is CPPD?

CPPD is a crystal-induced arthropathy characterized by:

• Deposition of calcium pyrophosphate (CPP) crystals in joint cartilage (chondrocalcinosis) and surrounding tissues
• Prevalence increases with age (10-15% in ages 65-75, >40% in those over 80) 2
• May present as:
  • Asymptomatic chondrocalcinosis
  • Acute inflammatory arthritis (pseudogout)
  • Chronic arthropathy (pseudorheumatoid, pseudo-osteoarthritis, or pseudoneuropathic joint disease)
  • Deposition in bursae, ligaments, and tendons causing inflammation or ruptures 2

Diagnostic Evaluation

Gold Standard Diagnostic Methods:

• Synovial fluid analysis: Identification of weakly positive birefringent rhomboid-shaped CPP crystals using compensated polarized light microscopy 1
• Radiographic findings: Punctate and linear radiodense areas in fibrocartilage and hyaline cartilage 2
• Ultrasonography: Can detect crystal deposits in cartilage 1

Metabolic Workup:

Patients with CPPD should be evaluated for underlying metabolic disorders, especially with early-onset disease (before age 60) 1:

• Hyperparathyroidism: CPPD patients are 3 times more likely to have primary hyperparathyroidism (OR=3.03,95% CI 1.15 to 8.02) 3
• Hemochromatosis: Particularly important in early-onset disease 1
• Hypomagnesemia: Can predispose to CPPD 3
• Hypophosphatemia: Associated with CPPD 2

Management Approach

Acute Attacks:

1. First-line: Joint aspiration with intra-articular glucocorticoid injection for monoarticular/oligoarticular attacks (SOR: 95%) 1
2. Alternatives when joint aspiration not feasible:
   • NSAIDs (if no contraindications)
   • Colchicine (if NSAIDs contraindicated)
   • Systemic glucocorticoids (if both contraindicated) 1
   • IV methylprednisolone (125 mg) for rapid relief when oral medications are ineffective (NNT=3) 1
   • IM betamethasone (7 mg) as an alternative injectable option 1

Chronic Management:

1. First-line:

   • NSAIDs with gastroprotection
   • Low-dose colchicine (0.5-1.0 mg daily) - NNT of 2 at 4 months for >30% pain reduction 1

2. Second-line:

   • Low-dose corticosteroids 1

3. Third-line:

   • Methotrexate (5-10 mg/week)
   • Hydroxychloroquine (NNT for clinical response of 2,95% CI 1 to 7) 1

4. Refractory cases:

   • IL-1 inhibitors when other anti-inflammatory therapies are ineffective 1
   • Tocilizumab in severe refractory cases 4

Special Considerations

• Elderly patients: Higher risk of toxicity with NSAIDs and colchicine; require careful monitoring 1
• Renal impairment: Increases risk of adverse effects; requires dose adjustment 1
• Disease-modifying treatments: Currently no effective therapy to dissolve CPP crystals or prevent progression of joint destruction 3, 5
• Prophylaxis: Low-dose colchicine may prevent recurrent flares 4
• Magnesium supplementation: May provide clinical benefits (pain reduction) but does not reduce radiographic chondrocalcinosis 3

Treatment Challenges and Future Directions

• Limited high-quality evidence: Few randomized controlled trials available 4
• Need for better disease classification and nomenclature 6
• Research needed on IL-1 inhibitors and methotrexate for chronic CPP crystal inflammatory arthritis 3
• Development of therapies targeting CPP crystal formation and dissolution remains a theoretical possibility 3

By following this systematic approach to diagnosis and management, clinicians can effectively identify and treat CPPD to improve patient outcomes and quality of life.