Pseudogout (CPPD Disease)
Acute crystal arthritis from calcium pyrophosphate deposition; classic site is the knee with chondrocalcinosis.
Also known as: pseudogout, CPPD, calcium pyrophosphate, chondrocalcinosis
Overview
Inflammatory arthritis caused by deposition of calcium pyrophosphate dihydrate (CPP) crystals in articular cartilage and periarticular tissues. Encompasses asymptomatic chondrocalcinosis, acute CPP crystal arthritis (classic 'pseudogout'), chronic CPP crystal inflammatory arthritis, and osteoarthritis with CPPD.
Epidemiology
Prevalence rises sharply with age; chondrocalcinosis present on imaging in ~10% of adults over 60 and >30% over 80. Equal sex distribution.
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Risk factors
- Advanced age (most common)
- Osteoarthritis (often coexists)
- Hyperparathyroidism
- Hemochromatosis
- Hypomagnesemia, hypophosphatasia
- Familial chondrocalcinosis (ANKH gene mutations)
- Acute medical illness, surgery, trauma (common provocations)
Pathophysiology
Abnormal cartilage matrix metabolism increases extracellular pyrophosphate, which precipitates with calcium to form CPP crystals in articular and fibrocartilage. Released crystals activate the NLRP3 inflammasome, producing acute neutrophilic synovitis similar to gout.
Clinical presentation
Symptoms
- Acute monoarticular or oligoarticular swelling, pain, and warmth — most often knee or wrist
- Onset over hours to a day; often precipitated by surgery, trauma, or acute medical illness
- Less severe than typical gout but can be incapacitating
- Chronic forms: insidious polyarticular arthritis mimicking RA or OA
Signs / physical exam
- Warm, swollen joint with effusion
- Reduced range of motion
- Low-grade fever possible
- Pseudo-RA pattern: symmetric small-joint synovitis (MCP 2, 3 often involved with hook-like osteophytes if also hemochromatosis)
Differential diagnosis
- Gout — Negatively birefringent needle-shaped MSU crystals; first MTP classic
- Septic arthritis — Fever, immunocompromise; coexists with CPPD; arthrocentesis with Gram stain/culture mandatory
- Osteoarthritis — Chronic, non-inflammatory; may coexist with CPPD (especially knees and wrists)
- Rheumatoid arthritis — Symmetric polyarticular MCP/PIP/wrist; positive RF/CCP
- Hemarthrosis — Trauma or anticoagulation; bloody arthrocentesis fluid
Diagnostic workup
Diagnostic criteria
ACR/EULAR 2023 classification criteria for CPPD use clinical features + imaging + crystal identification.
Labs
- Arthrocentesis with polarized microscopy — rhomboid or rod-shaped, POSITIVELY birefringent CPP crystals; inflammatory fluid
- Gram stain and culture to exclude septic arthritis
- Screen for underlying metabolic disease in patients <55 or with polyarticular CPPD:
- • Calcium, PTH, magnesium, phosphorus, alkaline phosphatase
- • Iron studies and ferritin (hemochromatosis)
- • TSH
- CBC, ESR/CRP often elevated during attack
Imaging
- Plain radiographs — linear calcification within hyaline or fibrocartilage (chondrocalcinosis), classically in knee menisci, triangular fibrocartilage complex of wrist, symphysis pubis
- Ultrasound — hyperechoic deposits within cartilage
- DECT — less established than for gout
Diagnostic algorithm
| Feature | Pseudogout (CPPD) |
|---|---|
| Crystal | Calcium pyrophosphate dihydrate |
| Shape | Rhomboid or rod-shaped |
| Birefringence | Positive (BLUE when parallel to compensator) |
| Typical joints | Knee (most common), wrist (TFCC), MCP, shoulder, symphysis pubis |
| Radiograph clue | Chondrocalcinosis — linear calcification in cartilage |
| Workup if young/polyarticular | Ca, PTH, Mg, ferritin/iron studies, alkaline phosphatase, TSH |
| Acute therapy | Intra-articular steroid, NSAIDs, colchicine, oral steroids |
| Chronic prevention | Low-dose colchicine; treat underlying metabolic cause |
Complications
- Recurrent acute attacks
- Chronic destructive arthropathy of knee, shoulder ('Milwaukee shoulder' with BCP and CPP crystals)
- Secondary OA with characteristic distribution (wrist radiocarpal, MCP, patellofemoral)
- Spinal involvement: crowned dens syndrome — acute neck pain, fever, elevated CRP from CPPD at C1-C2 (mimics meningitis or GCA)
PANCE pearls
- Patients <55 with CPPD warrant a workup for hemochromatosis, hyperparathyroidism, and hypomagnesemia.
- Crowned dens syndrome (CPPD around the odontoid) causes acute neck pain + fever and can mimic meningitis — CT shows calcification.
- Chondrocalcinosis on knee or wrist radiographs supports the diagnosis but is not pathognomonic.
- Always perform Gram stain and culture on the aspirate — septic arthritis can coexist with crystals.
References
- ACR/EULAR 2023 — 2023 ACR/EULAR Classification Criteria for Calcium Pyrophosphate Deposition Disease (Abhishek et al., Arthritis Rheumatol 2023)
- EULAR 2011 — EULAR Recommendations for Calcium Pyrophosphate Deposition (Zhang et al., Ann Rheum Dis 2011)
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