CPPD

CPPD
    • Clinical Presentations CPPD NEJM 2016
      • Asymptomatic or Presymptomatic CPPD
      • Acute CPP Arthritis 
      • Chronic CPP Arthritis (Shoulder, Knee, Wrist)
      • Pseudo RA (less symmetrical than RA)
      • Pseudo-Neurotrophic or Charcot's Arthropathy
      • Spinal (The crowned dens syndrome)
      • Tumoral deposits in tissue 
    • Familial CPPD - CCAL2 locus on chromosome 5p causing gain of ANKH protein, and CCAL1 locus on chromosome 8 a gain-of-function mutation in the TNFRSF11B (osteoprotegerin) gene) CPPD NEJM 2016
    • Usually associated with following Metabolic Disease CPPD NEJM 2016
      • Hyper: 
        • Hyperparathyroidism (alters Ca metabolism, but association is more complex as persists even after correction)
        • Familial hypocalciuric hypercalcemia (increased Ca)
        • Hemochromatosis (inhibitory action of Iron on Pyrophosphotase, or high level of PTH in cartilage ?? )
      • Hypo: 
        • Hypothyroidism, 
        • Hypophosphatasia, 
        • Hypomagnesemia (Mg increases solubility of CPP crystals, and also  acts as cofactor for pyrophosphotase)
          • Gitlemans variant of Barters syndrome 
        • Alkaline phosphatase deficiency (causes high ePP)
      • Medicines: Loop diuretics, pamidronate, intrarticular hyarulonic acid, GM-CSF prep
    • Pathogenesis: CPP Deposition in the pericellular matrix of cartilage is the first step. 
  • CCP crystals deposit exclusively in articular hyaline cartilage, and fibrocartilage, and at site of chondroin metaplasia including in the synovium.
  • PPi generation: from ATP and other nucleoside triphophosphate by ectoenzyme ectonucleotide PP / phosphodiesterase 1 (ENPP1)
  • PPi transport: iATP to eATP by ANKH 
  • PPi degradation: PPi to Pi by TNAP (ectoenzyme tissue non-specific ALP (alkaline phosphatase) 
  • Then, CCP crystals form when eg Magnesium is low which normally surpasses CCP crystal formation 


  • Calcium Pyrophosphate Deposition Disease NEJM 2016
  • Basic Calcium Phosphate Deposition Disease:
    • Can lead to highly destructive inflammatory arthritis (Milwaukee shoulder)







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