Calcium Pyrophosphate Dihydrate (CPPD) Deposition Disease

CALCIUM PYROPHOSPHATE DIHYDRATE
(CPPD) DEPOSITION DISEASE
Susan Knowles, MD, FACP, FACR
Definitions
• Chondrocalcinosis – cartilage calcification
• CPPD deposition disease – degenerative
arthritis associated with CPPD crystal
deposition
• Pseudogout – acute inflammatory arthritis
attack due to CPPD crystals
Etiology
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Hereditary/familial
Idiopathic
Associated with metabolic abnormality
Post-traumatic
Familial CPPD Deposition Disease
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Autosomal dominant
Early onset
Variable severity
ANKH gene
– Transmembrane protein, transports inorganic
pyrophosphate out of the cell
• Other genetic associations:
– Gitelman’s & Bartter’s
– Hemochromatosis & Wilson’s
Metabolic Conditions associated with
CPPD Deposition Disease
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Hyperparathyroidism
Hypomagnesemia
Hypophosphatasia
Hemochromatosis
Hypothyroidism
Other Factors Associated with
CPPD Deposition Disease
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Age
Previous joint surgery
Osteoarthritis
Trauma
Pathogenesis
• Overproduction of extracellular inorganic pyrophosphate
(PPi)
– Enhanced activity of ATP pyrophosphohydrolase & 5’
nucleotidase (ATP  adenosine + pyrophosphate)
– Elevated PPi in synovial fluid
– Chondrocytes produce more PPi than normal and OA
chondrocytes
– PPi combines with calcium to form crystals
• Inflammatory response to CPPD crystals, similar to gout
• Phagocytosis of crystals, cytokine release, lysosomal
enzymes, matrix metalloproteases
CPPD Deposition Disease
Clinical Features
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Pseudogout
Osteoarthritis variant
Pseudo-RA
Lanthanic (asymptomatic)
Pseudogout
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Acute inflammatory arthritis
Self limited attacks, longer lasting than gout
One or more joints
Wrist, knee, MCPs
– Ankle, shoulder, ligamentum flavum/cervical spine
• Elderly: 80% pts > 60yrs
• Fever, leukocytosis, elevated ESR, acute phase
reactants
• Synovial fluid: 5,000-100,000 WBC
CPPD Deposition Disease
Osteoarthritis Variant
• Unusually severe OA
• Odd distribution, wrists, MCPs, shoulders,
elbows, ankles, spine
• Chronic symptoms with superimposed acute
attacks
• May be significantly under-recognized
CPPD Deposition Disease Pseudo-RA
Variant
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5% patients
Polyarticular inflammatory arthritis
Symmetric distribution
Wrists, MCPs
Other Presentations
• Lanthanic: Chondrocalcinosis without
symptomatic arthritis
• Neuropathic arthropathy
• Tophaceous CPPD crystal deposits – nerve
compression
• 30% patient undergoing surgery for spinal
stenosis had CPPD crystal deposits in
ligamenta flava
CPPD Deposition Disease Diagnosis
• Often clinical + radiologic diagnosis
• Definitive diagnosis = demonstration of
crystals in synovial fluid
– Rhomboid crystals with weakly positive
birefingence
• Synovial fluid analysis:
– Crystals
– Inflammatory (mean WBC 12,000-24,000)
• Labs: Ca2+, Phos, Mg+, alk phos,
transferrin saturation, ferritin, PTH, TSH
CPPD Deposition Disease Radiographic
Findings
• Punctate &/or linear radiodense deposits in
cartilage
– Hyaline or fibrocartilage
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Knee articular cartilage & menisci
Triangular fibrocartilage of the wrist
Symphsis pubis
Hip acetabular labrum
CPPD Deposition Disease Radiographic
Findings
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Joint space narrowing
Squaring of MCP heads
Subchondral cysts
Hooklike osteophytes (Hemochromatosis)
CPPD Deposition Disease Radiographs
CPPD Deposition Disease Radiographs
CPPD Deposition Disease Radiographs
Crowned Dens Syndrome
CPPD Deposition Disease Treatment
• Acute attacks:
– NSAIDs, systemic steroids, intra-articular steroids
• Prophylaxis & Chronic Treatment:
– ? Colchicine
– ? Plaquenil (hydroxychloroquine)
– ? Methotrexate
Questions?
Thank you!