How do you diagnose Calcium Pyrophosphate Deposition (CPPD) disease?

Diagnosis of Calcium Pyrophosphate Deposition (CPPD) Disease

The diagnosis of CPPD requires either synovial fluid analysis demonstrating CPP crystals or imaging evidence of calcium pyrophosphate deposits, with conventional radiography and ultrasound being the recommended first-line imaging modalities. 1

Definitive Diagnostic Test

Arthrocentesis with synovial fluid analysis is the gold standard and should be performed whenever possible to confirm the diagnosis. 2 The identification of CPP crystals under polarized light microscopy provides definitive confirmation. 3 However, imaging has been incorporated into recent diagnostic recommendations when synovial fluid analysis is not feasible or unsuccessful. 1, 2

• Use ultrasound guidance for joint aspiration when anatomical landmarks make the procedure challenging, as this improves success rates and avoids ionizing radiation. 1, 2

Recommended Imaging Modalities

First-Line Imaging

Conventional radiography and ultrasound are the recommended imaging modalities for diagnostic assessment of CPPD. 1

• Conventional radiography detects chondrocalcinosis (calcification of cartilage), though it identifies only about 40% of clinically important CPPD cases. 4
• Ultrasound has superior sensitivity for detecting CPP deposits and can identify three distinct patterns: thin hyperechoic bands parallel to cartilage surface, hyperechoic spots (most common pattern), and hyperechoic nodular or oval deposits. 3
• Fibrocartilage calcifications are more commonly detected than hyaline cartilage calcifications on ultrasound. 3

Axial Involvement

CT is recommended when axial joint involvement is suspected, particularly for crowned dens syndrome (calcification around the odontoid process). 1, 5, 6

Target Sites for Imaging

Both symptomatic areas and disease-specific target sites should be examined, with the knee and wrist being the most common locations. 1

• The knee is the most frequently affected joint both clinically and on imaging. 3
• Other common sites include the wrist, shoulder (glenohumeral and acromioclavicular joints), hips, ankles, and symphysis pubis. 3
• The polyarticular nature of CPPD means multiple joints may be involved even when only one is symptomatic. 4

Mandatory Metabolic Screening

Screen for underlying metabolic conditions in all patients presenting with CPPD before age 60. 2

Essential screening tests include:

• Serum magnesium to detect hypomagnesemia 2
• Iron studies and ferritin to investigate for hemochromatosis, particularly in early-onset disease 2
• Serum calcium and parathyroid hormone to evaluate for hyperparathyroidism 5
• Alkaline phosphatase to screen for hypophosphatasia 5

Medication Review

Identify medications that may precipitate CPPD, particularly loop diuretics like furosemide that cause magnesium depletion. 2

Clinical Phenotype Assessment

Determine the clinical presentation pattern (acute CPP crystal arthritis, chronic CPP crystal inflammatory arthritis, or CPPD with osteoarthritis), as this guides treatment decisions. 2, 5

Critical Diagnostic Pitfalls

Do not rely solely on imaging findings without clinical correlation. 2 Chondrocalcinosis on radiographs is common in elderly patients and may be asymptomatic—the presence of calcification does not automatically indicate CPPD disease. 1, 2, 6

Do not assume the diagnosis without attempting crystal confirmation when possible. 2 Other conditions including gout, septic arthritis, and osteoarthritis can mimic CPPD clinically and radiographically. 1

Do not skip metabolic screening in younger patients (<60 years). 2 Treatable conditions like hemochromatosis and hyperparathyroidism require early identification to prevent systemic complications. 2, 5

Recognize that imaging abnormalities related to crystal deposition may not always correlate with clinical symptoms. 1 Asymptomatic CPPD is common and should not be confused with CPPD disease. 6

When Synovial Fluid Analysis is Not Needed

When characteristic features of CPP crystal deposition are identified on imaging in an appropriate clinical context, synovial fluid analysis may not be required to confirm the diagnosis. 1 However, arthrocentesis should still be attempted when feasible to rule out septic arthritis or coexisting gout, particularly in acute presentations. 1

Serial Imaging

Serial imaging is NOT recommended for monitoring CPPD unless there is unexpected clinical deterioration. 1, 2 Unlike gout, there is no evidence supporting routine follow-up imaging in CPPD. 2