What lab test is used to diagnose Calcium Pyrophosphate Dihydrate (CPPD) disease?

Synovial Fluid Analysis is the Definitive Test for Diagnosing CPPD

The gold standard laboratory test for diagnosing calcium pyrophosphate dihydrate (CPPD) disease is synovial fluid analysis with identification of calcium pyrophosphate crystals using polarized light microscopy.

Diagnostic Approach for CPPD

Primary Diagnostic Test

• Synovial fluid analysis is the reference standard for diagnosing CPPD 1
• Identification of calcium pyrophosphate (CPP) crystals in synovial fluid must be performed using one of these microscopy techniques:
  • Light microscopy
  • Compensated polarized light microscopy (preferred method)
  • Phase contrast microscopy

Characteristics of CPP Crystals

• CPP crystals appear as weakly birefringent, rhomboid-shaped crystals
• They typically show weak positive birefringence (unlike the negative birefringence seen in gout)
• CPP crystals can be found both intracellularly and extracellularly in synovial fluid 2

Imaging as Supportive Evidence

According to the 2023 EULAR recommendations 3, imaging can provide supportive evidence but cannot replace synovial fluid analysis:

• Conventional radiography (CR) - shows chondrocalcinosis
• Ultrasound - can detect CPP deposits in fibrocartilage and hyaline cartilage
• CT - useful for axial involvement (e.g., crowned dens syndrome)

Clinical Considerations

When to Perform Synovial Fluid Analysis

• Always attempt arthrocentesis when feasible, especially to rule out other causes of acute arthritis such as septic arthritis 3
• Ultrasound guidance should be used when aspiration based on anatomical landmarks is challenging

Important Caveats

1. CPP crystals are regularly found in synovial fluid from non-inflamed joints of patients with CPPD arthropathy 2
2. Synovial fluid analysis should be performed promptly as crystals may dissolve over time
3. Laboratory personnel must be properly trained in crystal identification
4. Even in the absence of an acute flare, CPP crystals can be identified in affected joints

Associated Conditions to Evaluate

When CPPD is diagnosed, consider screening for associated metabolic conditions 4, 5:

• Hyperparathyroidism
• Hemochromatosis
• Hypomagnesemia
• Hypophosphatasia

Practical Implementation

1. Obtain synovial fluid via arthrocentesis
2. Examine fresh, unfixed fluid within 1-2 hours of collection
3. Use compensated polarized light microscopy when available
4. If polarized microscopy is unavailable, ordinary light microscopy can be used initially 6
5. Document both the presence of crystals and their characteristics

While imaging findings are helpful supportive evidence, they cannot replace direct crystal identification in synovial fluid, which remains the definitive diagnostic test for CPPD disease.