Crystal Arthropathies



  • Accumulation of precipitated crystals in and around joint spaces causing acute or chronic symptoms
  • Monosodium urate crystals (gout) most common; others include calcium pyrophosphate dihydrate (CPPD-pseudogout), basic calcium phosphate (BCP) crystals (calcium hydroxyapatite and calcium oxalate); lipid and immunoglobulin crystals (rare)
  • Intra-articular crystals initiate an immune response and neutrophil phagocytosis with the subsequent release inflammatory factors.
  • Joint aspiration is the gold-standard for diagnosis.
  • Uncontrolled disease may lead to chronic joint changes and disability.
  • Most treatments are aimed at decreasing crystal-induced inflammation.



  • Gout: 4% of U.S. adults >20 years with lifetime incidence of gout, men > women (1)
  • CPPD (pseudogout), hydroxyapatite, and calcium oxalate, men = women (2)


  • Highest prevalence of gout is 7% in men >65 years (3).
  • Prevalence of other crystal arthropathies not well defined

Etiology and Pathophysiology

  • High levels of crystal-forming molecules precipitate in synovium and synovial fluid.
  • Inflammatory response is initiated, attracting neutrophils to the synovial tissues.
  • Subsequent phagocytosis of crystals releases cascade of additional inflammatory factors (IL-1β).
  • Gout: hyperuricemia prerequisite to monosodium urate crystal formation
  • CPPD: excessive local production of extracellular inorganic pyrophosphate from chondrocytes
  • BCP/hydroxyapatite: normal part of bone metabolism, crystallization seen in associated tissue damage associated with elderly joints
  • Calcium oxalate: crystallization in patients with hyperoxalemia or end-stage renal disease


  • Genetics play a role in hyperuricemia and familial CPPD disease.
  • Clinical application of genetic studies limited

Risk Factors

  • Age >40 years (gout); age >60 years (CPPD)
  • Dehydration, alcohol consumption, obesity (gout)
  • Chronic renal disease
  • Underlying arthritic disease, joint trauma
  • Parathyroid disease
  • Calcium, phosphorus, or magnesium derangements

Commonly Associated Conditions

  • CPPD (also called chondrocalcinosis)
    • Mostly idiopathic
    • Hereditary CPPD
    • Hyperparathyroidism
    • Hemochromatosis
    • Hypophosphatasia
    • Hypomagnesemia
  • BCP/hydroxyapatite
    • Tissue damage
    • Parathyroid, calcium, or phosphorus disorders
  • Calcium oxalate
    • Excessive ascorbic acid intake
    • Renal failure

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