What is the recommended workup and management for pseudogout (Calcium Pyrophosphate Deposition Disease)?

Workup for Pseudogout (CPPD)

The workup for pseudogout centers on synovial fluid analysis to identify calcium pyrophosphate crystals under compensated polarized light microscopy, combined with imaging to detect chondrocalcinosis, and metabolic screening for underlying conditions in patients under 60 years of age. 1

Diagnostic Approach

Synovial Fluid Analysis (Gold Standard)

• Arthrocentesis is the definitive diagnostic test and should be performed whenever possible to secure the diagnosis 1
• Examine synovial fluid under compensated polarized light microscopy to identify positively birefringent calcium pyrophosphate dihydrate crystals 2, 3
• Use ultrasound guidance for joint aspiration when anatomical landmarks make the procedure challenging, as this improves success rates and avoids ionizing radiation 1
• If conventional light microscopy fails to identify crystals but clinical suspicion remains high, electron microscopy can establish the diagnosis 4

Imaging Studies

Conventional Radiography (First-Line Imaging)

• Obtain plain radiographs of affected joints to identify punctate and linear radiodense areas in fibrocartilage and hyaline cartilage (chondrocalcinosis) 2
• The 2023 EULAR guidelines emphasize that imaging has been incorporated into recent diagnostic recommendations for CPPD 1

Advanced Imaging (When Needed)

• Ultrasound, CT, or MRI may be used for diagnostic purposes, though the 2023 EULAR recommendations note that serial imaging is NOT recommended for monitoring CPPD unless there is unexpected clinical deterioration 1
• Unlike gout, there is no evidence supporting routine follow-up imaging in CPPD 1

Metabolic Workup

Screen for Underlying Conditions in Early-Onset Disease

• For patients presenting before age 60, mandatory screening includes: 2
  • Serum calcium and parathyroid hormone (to detect hyperparathyroidism)
  • Iron studies including ferritin and transferrin saturation (to detect hemochromatosis)
  • Serum magnesium (to detect hypomagnesemia)
  • Serum phosphate (to detect hypophosphatemia)
• The Annals of the Rheumatic Diseases specifically emphasizes that early-onset disease requires investigation for hemochromatosis 5

Medication Review

• Identify medications that may precipitate CPPD, particularly loop diuretics like furosemide that cause magnesium depletion 6, 7

Clinical Phenotype Assessment

Determine the Clinical Presentation Pattern 2

• Acute CPP crystal arthritis (pseudogout attacks)
• Chronic CPP crystal inflammatory arthritis (pseudo-rheumatoid pattern)
• Osteoarthritis with CPPD (pseudo-osteoarthritis)
• Asymptomatic chondrocalcinosis (incidental finding)

This classification guides treatment decisions, as management differs substantially between acute attacks requiring rapid symptom relief versus chronic disease requiring long-term symptom control 1

Key Diagnostic Pitfalls

• Do not rely solely on imaging: Chondrocalcinosis on radiographs is common in elderly patients (>40% in those over 80) and may be asymptomatic 2
• Do not assume the diagnosis without crystal confirmation when possible: Other conditions can mimic CPPD clinically and radiographically 1
• Do not skip metabolic screening in younger patients: Treatable conditions like hemochromatosis require early identification 5, 2

Monitoring Recommendations

Serial imaging is NOT recommended for routine CPPD monitoring unless there is rapid symptom progression or concern for an additional diagnosis 1. This contrasts sharply with gout, where imaging can track crystal burden and predict flares. The fundamental difference is that unlike urate crystals, there are currently no treatments to prevent CPP crystal formation or enhance dissolution 6.