Pseudogout (Calcium Pyrophosphate Dihydrate)

Pseudogout (Calcium Pyrophosphate Dihydrate) is a topic covered in the 5-Minute Clinical Consult.

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  • Autoinflammatory disease triggered by calcium pyrophosphate dihydrate (CPPD) crystal deposition within joints
  • One of many diseases associated with pathologic deposition of crystal; mineralization and ossification
    • CPPD crystal deposition = chondrocalcinosis (calcification of hyaline or fibrocartilage), pseudogout, and pyrophosphate arthropathy
    • Monosodium urate crystal deposition = gout
    • Hydroxyapatite deposition associated with ankylosing spondylitis, osteoarthritis, and vascular calcification
  • Suspect pseudogout in arthritis cases with a pattern of joint involvement inconsistent with degenerative joint disease (e.g., metacarpophalangeal joints, wrists).
  • Clinical presentation is broad:
    • Asymptomatic CPPD (incidentally identified on radiograph by chondrocalcinosis with or without additional findings of osteoarthritis)
    • Acute CPPD arthritis (acute onset, self-limiting, synovitis)
    • Chronic CPPD crystal inflammatory arthritis (1)[C]
  • Chronic CPPD crystal deposition may cause a progressive degenerative arthritis in numerous joints:
    • Primarily affects the elderly
    • Usually involves large joints
  • Symptom onset is usually insidious.
  • Definitive diagnosis requires the identification of CPPD crystals in synovial fluid.
  • System(s) affected: endocrine/metabolic; musculoskeletal
  • Synonyms: pseudogout; CPPD; pyrophosphate arthropathy; chondrocalcinosis—when calcification visibly seen within tissues on imaging


  • Predominant age: 80% of patients >60 years
  • No gender predominance. Men more likely to present acutely; women more likely to present atypically
  • Prevalence varies by method of identification (chondrocalcinosis on radiograph vs. CPPD crystals in synovial fluid).
  • Chondrocalcinosis is present in 1:10 adults age 60 to 75 years and 1:3 by >80 years; however, only a small percentage develop arthropathy.
  • 20–43% prevalence of CPPD crystals in synovial fluid of osteoarthritic joints at time of joint replacement

Etiology and Pathophysiology

  • Arthropathy results from an acute autoinflammatory reaction to CPPD crystals in the synovial cavity.
  • CPPD crystal deposition occurs in three stages:
    • CPPD crystals first develop in the pericellular matrix of the articular cartilage via overproduction of anionic pyrophosphate (PPi).
    • PPi binds calcium to form CPPD crystals that are released from cartilage surface eliciting an inflammatory response. Neutrophils engulf CPPD crystals, inducing extracellular trap formation.
    • Increased CPPD crystal deposition in and around cartilage causes inflammation and damage. Cartilage degeneration is accelerated through mechanical wear and tear of the joint (2)[C].

Uncommonly seen in familial pattern with autosomal dominant inheritance (<1% of patients); most cases are sporadic. Mutation in ANKH gene increases risk for calcium crystal formation.

Risk Factors

  • Advanced age
  • Joint trauma
  • CPPD may occur as a complication in patients hospitalized for other medical and surgical illnesses.

General Prevention

Colchicine 0.6 mg BID may be used prophylactically to reduce frequency of episodes in recurrent CPPD.

Commonly Associated Conditions

  • Gout
  • Hyperparathyroidism
  • Amyloidosis
  • Hemochromatosis; ochronosis
  • Hypothyroidism
  • Wilson disease
  • Hypomagnesemia
  • Familial hypocalciuric hypercalcemia
  • X-linked hypophosphatemic rickets
  • Acromegaly

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