Synovial Fluid Analysis in Pseudogout
The definitive finding in synovial fluid analysis of patients with pseudogout is the presence of calcium pyrophosphate dihydrate (CPPD) crystals, which appear as weakly positive birefringent rhomboid-shaped crystals under polarized light microscopy.
Characteristics of CPPD Crystals in Synovial Fluid
Crystal appearance:
- Rhomboid or rod-shaped crystals
- Weakly positive birefringent under compensated polarized light microscopy
- Appear blue when parallel to the slow axis of the red compensator
- Appear yellow when perpendicular to the slow axis 1
Crystal structure:
Other synovial fluid findings:
- Inflammatory characteristics with increased white blood cell count
- Predominance of neutrophils during acute attacks
- Normal or slightly decreased viscosity
- Normal or slightly decreased glucose levels
Diagnostic Approach
Synovial fluid analysis is the gold standard for diagnosing pseudogout. The European League Against Rheumatism (EULAR) recommends routine examination of synovial fluid for CPPD crystals in all undiagnosed inflamed joints 1.
When examining synovial fluid:
- Use compensated polarized light microscopy
- Look specifically for weakly positive birefringent rhomboid-shaped crystals
- Differentiate from monosodium urate (MSU) crystals (seen in gout), which are:
- Needle-shaped
- Strongly negative birefringent
- Appear yellow when parallel to the slow axis of the red compensator
- Appear blue when perpendicular to the slow axis 1
Important Considerations
Coexistence with other conditions: CPPD crystals and MSU crystals can coexist in the same joint, making careful crystal evaluation essential 3
Alternative diagnostic methods: When conventional synovial fluid analysis fails to establish a diagnosis, electron microscopy can be used to identify CPPD crystals 4
Imaging correlation: While synovial fluid analysis is definitive, imaging findings can support the diagnosis:
- Radiography: Chondrocalcinosis (calcification of cartilage), especially in fibrocartilage of wrists, knees, and symphysis pubis 1
- Ultrasound: Shows characteristic "icing" of cartilage (double contour sign) with sensitivity of 83% and specificity of 76% 1
- CT: Can identify chondrocalcinosis and calcification of tendons, ligaments, and joint capsules 1
Quantitative considerations: During acute attacks of pseudogout, synovial fluid typically contains:
- Higher concentration of CPPD crystals per ml of fluid
- Greater total mineral content per joint
- Larger crystal size
- Higher ratio of monoclinic to triclinic CPPD crystals 2
Pitfalls to Avoid
- Misidentifying CPPD as other birefringent materials (calcium oxalate, synthetic steroids, EDTA) 5
- Failing to recognize coexisting crystal types (CPPD and MSU) 3
- Delaying analysis, as crystals may dissolve or change morphology over time
- Missing the diagnosis in unusual locations (e.g., spine, temporomandibular joint) 5, 6
By correctly identifying CPPD crystals in synovial fluid, clinicians can definitively diagnose pseudogout and distinguish it from other crystal arthropathies, particularly gout, which requires different management approaches.