What are the clinical features of the different subtypes of Calcium Pyrophosphate Deposition (CPPD) disease?

Clinical Features of CPPD Disease Subtypes

CPPD disease presents with four distinct clinical phenotypes that require different management approaches: asymptomatic chondrocalcinosis, acute CPP crystal arthritis, chronic CPP inflammatory arthritis, and osteoarthritis with CPPD. 1, 2

Asymptomatic Chondrocalcinosis

• Radiographic finding only without clinical symptoms - typically an age-related incidental finding in the normal population that requires no treatment 1, 3
• Prevalence increases dramatically after age 70 years, with overall prevalence of 13% across all age groups 1
• Crystals deposited in fibrocartilage and hyaline cartilage without triggering inflammatory response 2

Acute CPP Crystal Arthritis (Pseudogout)

• Sudden onset of severe pain, swelling, and tenderness with overlying erythema, typically affecting a single large joint 2
• Most commonly involves the knee, wrist, shoulder, and hip in descending order of frequency 2
• Episodes are extremely painful and require rapid symptom relief as the primary management objective 1
• Can occasionally affect ligaments, tendons, bursae, bone, and spine 2
• Crowned dens syndrome: CPPD of the atlanto-occipital joint causing periodic acute cervico-occipital pain with fever, neck stiffness, and elevated inflammatory markers 2
• Attacks may be triggered by acute illness, surgery, or trauma 4

Chronic CPP Inflammatory Arthritis

• Persistent joint swelling, morning stiffness, pain, and elevated ESR/CRP mimicking rheumatoid arthritis 2
• Can be misdiagnosed as seronegative rheumatoid arthritis - prevalence of 3.9% among patients initially diagnosed with seronegative RA, rising to 7.0% in patients ≥60 years 5
• Characterized by chronic symptoms and functional impairment of varying severity 1
• Does not develop typical RA-like erosions on follow-up, which helps distinguish it from true RA 5
• Typical radiographic patterns include chondrocalcinosis of triangular fibrocartilage (100%), knee (53%), metacarpophalangeal joints (41%), and scapholunate advanced collapse (29%) 5

Osteoarthritis with CPPD

• Joint degeneration with radiographic chondrocalcinosis and CPP crystal deposition 1, 2
• The causal relationship remains unclear - crystals may directly contribute to OA pathogenesis or result from joint degeneration 2
• Management objectives and treatment options are identical to OA without CPPD 3
• Associated with chronic symptoms and functional impairment 1

Key Diagnostic Considerations

• Synovial fluid analysis is the reference standard: CPP crystals appear as rhomboid-shaped with weak positive birefringence under compensated polarized light microscopy, though this pattern only occurs in ~20% of samples 2, 6
• Non-polarized light microscopy should be used initially to screen based on characteristic crystal morphology 2
• Conventional radiography demonstrates chondrocalcinosis in fibrocartilage (triangular fibrocartilage of wrist, menisci of knee, symphysis pubis) 2, 5
• Evaluate for associated conditions in patients <60 years: hyperparathyroidism, hemochromatosis, hypomagnesemia, hypophosphatasia, and familial hypocalciuric hypercalcemia 3

Critical Pitfalls to Avoid

• Do not assume all polyarticular inflammatory arthritis in elderly patients is rheumatoid arthritis - consider CPPD, especially with wrist involvement and absence of typical RA erosions 5
• Do not overlook crowned dens syndrome in patients with acute neck pain and fever - this can mimic meningitis or cervical spine infection 2
• Do not assume chondrocalcinosis always causes symptoms - asymptomatic radiographic findings are common and require no intervention 1, 3