Calcium pyrophosphate deposition (CPPD) disease is a crystalline inflammatory arthritis seen primarily in individuals over age 60. It results from the deposition of calcium pyrophosphate dihydrate (CPP) crystals within articular cartilage. While it is typically idiopathic, it may also be caused by joint damage, various metabolic abnormalities, or a genetic predisposition. CPPD disease can be asymptomatic or manifest with acute or chronic symptoms. Pseudogout refers to acute CPP crystal arthritis, which typically presents as sporadic flares of monoarticular synovitis affecting a large joint and can last for much longer than a typical gout flare. Chronic CPP crystal arthritis has many clinical phenotypes, the most common of which resembles severe osteoarthritis. Identification of CPP crystals on synovial fluid analysis or on imaging in a patient with typical symptoms confirms the diagnosis. Treatment is primarily symptomatic and consists of antiinflammatory medications (including intraarticular and systemic glucocorticoids, colchicine, and NSAIDs). There is currently no specific treatment targeted at CPP crystals.
- The primary (idiopathic) form is most common, with age as a major risk factor. 
- Secondary forms 
Acute CPP crystal arthritis (pseudogout)
- Clinical features
Features that differ from acute gout
- Longer duration of acute attacks
- Possible systemic symptoms 
- Triggers: can occur spontaneously or be triggered by joint trauma/surgery or acute illness 
Pseudogout refers to the acute, not chronic, form of CPPD disease.
Chronic CPP crystal arthritis
- Osteoarthritis-like presentation (osteoarthritis with CPPD; pseudo-osteoarthritis) ; 
- Rheumatoid arthritis-like presentation (chronic CPP crystal inflammatory arthritis)
- Less common phenotypes
There are currently no validated diagnostic criteria for CPPD disease. Diagnosis is based on the identification of CPP crystals on synovial fluid analysis and/or the presence of cartilage calcification on imaging in a patient with suggestive symptoms. 
Arthrocentesis and synovial fluid analysis (SFA) 
- The most accurate diagnostic method, but crystals can often be difficult to identify. 
- Expected findings
Polarized light microscopy (with a red filter) appearance of CPP crystals
- Rhomboid-shaped crystals that are weakly positively
- Crystals appear blue when their optical axis is oriented parallel to the polarizer.
- Crystals appear yellow when their axis is perpendicular to the polarizer.
- Cell count: WBC > 2000/μL with > 50% neutrophils 
- See also “ .”
- Polarized light microscopy (with a red filter) appearance of CPP crystals
X-ray of the affected joint(s)
- Chondrocalcinosis: calcification of cartilage in the affected joints 
- Appears as radiodense shadows within the cartilage
- Types of cartilage involved:
- Sensitivity: ∼ 40% (i.e., x-ray may appear normal) 
- Ultrasound of the affected joint(s)
- Other modalities 
- Serum uric acid
- Tests to rule out differential diagnoses of inflammatory arthritis: e.g., CBC, rheumatoid factor, anti-CCP antibodies
- Evaluate for underlying metabolic disorders if appropriate : e.g., obtain serum levels of iron, transferrin, ferritin, calcium, magnesium, PTH, and alkaline phosphatase 
- Other inflammatory arthritides, e.g.:
- Septic arthritis (in patients with acute CPPD): See “Interpretation of synovial fluid analysis.”
- Osteoarthritis and erosive osteoarthritis
The differential diagnoses listed here are not exhaustive.
- All patients: Treat any underlying condition (e.g., hyperparathyroidism, hemochromatosis).
- Asymptomatic patients: no further treatment required
- Acute CPP crystal arthritis (pseudogout): Symptomatic therapeutic options in order of preference include the following. 
Chronic CPP crystal arthritis 
- Same antiinflammatory therapies as above
- Sometimes in combination
- Prophylaxis: Consider low-dose colchicine to decrease the frequency of acute attacks.