What laboratory tests are recommended for diagnosing pseudogout?

Laboratory Tests for Pseudogout

The definitive diagnosis of pseudogout requires synovial fluid aspiration with identification of calcium pyrophosphate dihydrate (CPPD) crystals under compensated polarized light microscopy, which should be performed on all suspected cases. 1, 2

Essential Diagnostic Laboratory Tests

Synovial Fluid Analysis (Gold Standard)

• Joint aspiration with polarized light microscopy is mandatory to identify CPPD crystals, which appear as rhomboid-shaped, weakly positively birefringent crystals (in contrast to the needle-shaped, negatively birefringent monosodium urate crystals of gout) 1, 2
• Synovial fluid white blood cell count should be obtained, as pseudogout can produce markedly elevated counts (65,000-100,000/mm³ with 93-100% polymorphonuclear cells), which may mimic septic arthritis 3
• Gram stain and culture must always be performed even when CPPD crystals are identified, as crystal arthropathy and septic arthritis can coexist 3

Serum Laboratory Tests to Identify Underlying Causes

• Serum calcium and parathyroid hormone (PTH) to screen for primary hyperparathyroidism, which is associated with pseudogout in approximately 3.8% of cases 4
• Serum creatinine and blood urea nitrogen (BUN) to evaluate for chronic renal failure, as pseudogout occurs more frequently in this population (3.7% overall incidence, increasing to 15.8% in patients over age 60) 2
• Serum magnesium, phosphate, alkaline phosphatase, and thyroid function tests to identify other metabolic disorders associated with CPPD deposition 4

Imaging Studies (Complementary, Not Laboratory Tests)

While not laboratory tests per se, imaging is critical for diagnosis:

• Plain radiographs are the initial imaging method (rated 9/9 by ACR) and show characteristic chondrocalcinosis in fibrocartilage (triangular fibrocartilage of wrists, menisci of knees, symphysis pubis) and hyaline cartilage 5
• Ultrasound and CT may be appropriate (rated 5/9) for detecting chondrocalcinosis and calcification of tendons, ligaments, and joint capsules 5

Critical Diagnostic Algorithm

1. Aspirate the affected joint immediately when acute inflammatory arthritis is present 1, 2
2. Examine synovial fluid under compensated polarized light microscopy for CPPD crystals 1, 2
3. Send synovial fluid for cell count, Gram stain, and culture to exclude septic arthritis 3
4. Order serum calcium, PTH, creatinine, and BUN to identify underlying metabolic causes 2, 4
5. Obtain plain radiographs of the affected joint and typical sites (wrists, knees) to identify chondrocalcinosis 5

Common Pitfalls to Avoid

• Do not assume infection is excluded based on crystal identification alone—the synovial fluid white blood cell count in pseudogout can reach 100,000/mm³, mimicking septic arthritis, and both conditions can coexist 3
• Do not overlook hyperparathyroidism screening—pseudogout may be the presenting feature of primary hyperparathyroidism or occur acutely after parathyroidectomy when calcium levels drop 4
• Do not dismiss pseudogout in younger patients with renal failure—while typically a disease of older adults, pseudogout can occur in younger patients (as young as age 39) with chronic renal failure 2
• Do not rely on radiographic chondrocalcinosis alone—crystal identification in synovial fluid remains the gold standard, as radiographs may be normal in acute attacks 1