BL 02-25-14 9-10AM Crystal Anthropathies-CPDD

Question 1

Calcium Pyrophosphate Dihydrate Deposition Disease (CPDD) defn.

Answer 1

= type of arthritis associated w/ release of calcium pyrophosphate dihydrate (CPPD) crystals into joint space & chondrocalcinosis (calcified joint cartilage)

Question 2

Pseudogout

Answer 2

= acute episodic arthritis due to CPPD crystals

Question 3

Clinical Features of CPDD/Pseudogout

Answer 3

= sudden onset of severe pain, swelling, warmth, and redness of usually a large joint

• most often the knee
• less frequently, wrist & ankle
• 1st MTP is rarely involved (unlike in gout)

Question 4

Epidemiology of CPDD/Pseudogout & Chondrocalcinosis

Answer 4

• predominantly in the elderly (50% over 84 yo)

Associated with:

• metabolic diseases (hyperparathyroidism, hemochromatosis)
• aging
• concurrent osteoarthritis
• rare familial forms

In younger pts, risk factors are joint trauma/surgery

Question 5

Pathology of CPDD/Pseudogout

Answer 5

• Examine fresh synovial fluid for CPPD crystals
• rhomboid-shaped & positively birefringent (blue when parallel to axis of red compensator) on polarizing microscopy

Synovial fluid is inflammatory (2,000-80,000 leukocytes/mm3) w/ predominance of neutrophils.

Peripheral blood WBC & ESR may be increased during acute attacks.

Serum Ca, phosphorus, & Fe studies helpful in search for associated metabolic causes of CPDD.

Question 6

Pathophysiology of CPDD/Pseudogout – A. Abnormal pyrophosphate (PPi) metabolism

Answer 6

1. PPi = product of nucleoside triphosphates (NTP) metabolism, esp. from articular chondrocytes
2. Elevated synovial fluid PPi in CPDD & OA
3. Increased extracellular PPi precipitate w/Ca
   - –> CPPD crystals in mid-zonal cartilage layers around chondrocytes.

Question 7

Reasons for elevation of synovial fluid PPi levels in CPDD & Osteoarthritis

Answer 7

• most likely from chondrocyte surface enzyme, NTP pyrophosphohydrolase (hydrolyzes phosphodiesterase 1 bond generating NMP & PPi)

Overexpresion or Mutation of ank gene (ANKH) that produces a transmembrane PPi transporter protein in chondrocytes
—> could promote CPPD crystal formation & deposition by allowing excess intracellular PPi egress from chondrocytes

Question 8

Pathophysiology of CPDD/Pseudogout – B. “Crystal shedding” hypothesis:

Answer 8

1. CPPD crystals do not form in synovial fluid by spontaneous precipitation of supersaturated solutions (unlike MSU crystals in gout)
2. CPPD crystals are released into synovial fluids by a “shedding phenomenon” of pre-formed crystals in cartilage matrix

Question 9

Pathophysiology of CPDD/Pseudogout – Inflammatory response

Answer 9

Similar to inflammatory response to MSU crystals

Question 10

Treatment of CPDD/Pseudogout

Answer 10

• Anti-inflammatory drugs to treat acute pseudogout (as in gout)
• Unlike gout, NO way to remove CPPD crystals from joints or to retard further disease progression