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 Disease Clinical 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!