calcium pyrophosphate dihydrate (cppd) deposition disease
TRANSCRIPT
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
• Hereditary/familial
• Idiopathic
• Associated with metabolic abnormality
• Post-traumatic
Familial CPPD Deposition Disease
• 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
• Hyperparathyroidism
• Hypomagnesemia
• Hypophosphatasia
• Hemochromatosis
• Hypothyroidism
Other Factors Associated with CPPD Deposition Disease
• 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 DiseaseClinical Features
• Pseudogout
• Osteoarthritis variant
• Pseudo-RA
• Lanthanic (asymptomatic)
Pseudogout
• 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
• 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
• Knee articular cartilage & menisci
• Triangular fibrocartilage of the wrist
• Symphsis pubis
• Hip acetabular labrum
CPPD Deposition Disease Radiographic Findings
• 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!