What is CPPD Arthropathy?
CPPD arthropathy is a crystal-induced joint disease caused by the deposition of calcium pyrophosphate dihydrate crystals in articular and periarticular tissues, leading to inflammation and joint damage with highly variable clinical presentations ranging from asymptomatic radiographic findings to severe destructive arthritis. 1
Pathophysiology
The disease develops when elevated inorganic pyrophosphate levels in cartilage lead to CPP crystal formation and deposition, with no current treatment available to prevent crystal formation or enhance their dissolution, fundamentally limiting management to symptomatic control rather than disease modification. 2
Interleukin-1 (IL-1) plays a central role in the inflammatory response when CPP crystals trigger joint inflammation. 2
Magnesium deficiency promotes crystal formation, as magnesium normally solubilizes CPP crystals and inhibits their nucleation. 2
Clinical Presentations
CPPD presents with a spectrum of clinical phenotypes: 3, 4
Asymptomatic chondrocalcinosis: Radiographic calcium deposits in cartilage without symptoms, particularly common in elderly patients and requiring no treatment. 3
Acute CPP crystal arthritis (pseudogout): Sudden-onset severe inflammatory attacks mimicking gout, with rapid onset of sharp pain and joint swelling. 4, 5
Chronic CPP inflammatory arthritis: Persistent inflammatory arthritis resembling rheumatoid arthritis. 4
Osteoarthritis with CPPD: Degenerative changes with superimposed crystal deposition, potentially accelerating joint destruction. 3
Destructive arthropathy: Severe joint destruction resembling neuropathic joint disease. 4
Epidemiology
The prevalence of radiographic chondrocalcinosis is approximately 13% across all age groups but increases dramatically with age, reaching 10-15% in patients aged 65-75 years and exceeding 40% in those over 80 years old. 3, 4
Diagnosis is quite challenging due to variable clinical presentation and difficulty attributing symptoms to CPPD versus concomitant conditions. 1
Associated Metabolic Conditions
Early-onset disease (before age 60) requires evaluation for underlying metabolic conditions, particularly: 4
- Primary hyperparathyroidism (3-fold increased risk, OR=3.03). 2
- Hemochromatosis. 2, 4
- Hypomagnesemia. 2, 4
- Hypophosphatasia. 3
Diagnostic Approach
Definitive diagnosis requires synovial fluid analysis demonstrating positively birefringent CPPD crystals visualized by compensated polarized light microscopy. 4
Conventional radiography remains a key diagnostic modality, showing punctate and linear radiodense areas in fibrocartilage and hyaline cartilage (chondrocalcinosis). 3, 4
Ultrasound and CT can detect crystal deposits, with CT being particularly useful for axial joints such as crowned dens syndrome. 2
Management Principles
The primary goal is symptomatic control of inflammation and prevention of acute attacks, as no disease-modifying treatments exist to reduce articular calcification or crystal burden. 2, 6
Acute Attacks
- NSAIDs, corticosteroids (intra-articular or systemic), and colchicine are effective for acute CPP arthritis. 6
- Anakinra (IL-1 receptor antagonist) can be used when other treatments fail. 6
Chronic Disease
- NSAIDs and/or colchicine as first-line therapy. 6
- Hydroxychloroquine showed clinical response (NNT=2) in chronic inflammatory arthritis. 2
- Low-dose weekly methotrexate may be valuable for severe refractory disease. 2
- Tocilizumab can be used in refractory cases. 6
Prophylaxis
- Colchicine can prevent recurrent flares. 6
- Magnesium supplementation has shown symptom improvement but no reduction in radiographic calcification. 7
Key Clinical Pitfall
Unlike gout, there are no agents available that decrease the crystal burden or prevent CPP crystal formation, making CPPD management fundamentally different and limited to symptomatic control. 2, 6, 8