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

• 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!