What is CPPD (Calcium Pyrophosphate Deposition Disease)?
CPPD is a metabolic arthropathy caused by the formation and deposition of calcium pyrophosphate (CPP) crystals in joint cartilage and periarticular tissues, leading to inflammation and joint destruction that can only be managed symptomatically since no treatment exists to prevent crystal formation or enhance their dissolution. 1
Disease Mechanism
Elevated inorganic pyrophosphate levels in cartilage drive CPP crystal formation and deposition, fundamentally distinguishing CPPD from gout where urate-lowering therapy can dissolve crystals—this means CPPD management is restricted to symptomatic control rather than disease modification. 1, 2
CPP crystals accumulate primarily in fibrocartilage and hyaline cartilage of joints, appearing as punctate and linear radiodense areas on X-rays (chondrocalcinosis). 2, 3
Interleukin-1 (IL-1) drives the inflammatory cascade when crystals are shed into the joint space, explaining why IL-1 inhibitors are being investigated as potential treatments. 1, 2
Clinical Presentations
CPPD manifests in several distinct patterns:
Asymptomatic chondrocalcinosis: Radiographic calcium deposits without symptoms, particularly common in elderly patients with prevalence of 10-15% in ages 65-75 and over 40% in those over 80. 1, 3
Acute CPP crystal arthritis (pseudogout): Severe acute inflammatory attacks mimicking gout, treated with NSAIDs, corticosteroids (intra-articular or systemic), or colchicine. 3, 4
Chronic CPP inflammatory arthritis: Can mimic rheumatoid arthritis (pseudorheumatoid), osteoarthritis (pseudo-osteoarthritis), or neuropathic joint disease. 3, 5
Crowned dens syndrome: Crystal deposition in axial joints, particularly well-visualized on CT imaging. 1
Metabolic Associations Requiring Evaluation
Early-onset disease (before age 60) mandates screening for underlying metabolic conditions, particularly:
Hemochromatosis: Requires specific treatment and is a critical association in early-onset CPPD. 6, 3
Primary hyperparathyroidism: Associated with 3-fold increased CPPD risk (OR=3.03). 1
Hypomagnesemia: Magnesium normally solubilizes CPP crystals and inhibits their nucleation—deficiency promotes crystal formation and can be precipitated by medications like furosemide. 1, 2
Hypophosphatemia: Another metabolic condition that can promote chondrocalcinosis. 3
Diagnosis
Gold standard: Identification of positively birefringent CPP crystals in synovial fluid using compensated polarized light microscopy. 3, 7
Imaging: X-rays show chondrocalcinosis; ultrasound and CT can detect crystal deposits, with CT particularly useful for axial joints. 1, 3
Treatment Approach
Since no disease-modifying treatments exist, management follows this hierarchy:
For acute attacks:
- NSAIDs, intra-articular or systemic corticosteroids (use small amounts if prolonged), or colchicine are first-line. 3, 4
- Anakinra (IL-1 receptor antagonist) for refractory acute flares. 4
For prevention of recurrent attacks:
- Low-dose colchicine prophylaxis is effective. 3, 4
- Magnesium supplementation has shown symptom improvement but no reduction in radiographic calcification. 6, 3
For chronic inflammatory arthritis:
- Start with NSAIDs and/or colchicine. 4
- Hydroxychloroquine showed clinical response with NNT=2 for chronic inflammatory arthritis. 1
- Low-dose weekly methotrexate may be valuable for severe refractory disease. 1, 3
- Low-dose glucocorticoids or tocilizumab for refractory cases. 4
Critical Pitfall
The most important caveat is that unlike gout, CPPD cannot be cured or have its crystal burden reduced—all therapy is purely symptomatic control of inflammation. 1, 2, 8 This fundamental limitation must be communicated to patients to set appropriate expectations.