Pseudogout (Calcium Pyrophosphate Dihydrate)



  • 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 = ankylosing spondylitis, osteoarthritis, and vascular calcification
  • Suspect pseudogout with arthritis and 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 with or without additional findings of osteoarthritis)
    • Acute CPPD arthritis (acute onset, self-limiting, synovitis)
      • Knee is affected in >50% of all acute attacks versus MTP in gout.
      • Can be brought on my trauma, medical illness, or surgery (after parathyroidectomy) (1)
    • Chronic CPPD crystal inflammatory arthritis (2)[C]
  • Chronic CPPD crystal deposition may cause a progressive degenerative arthritis in numerous joints; usually large joints; primarily in elderly patients
  • 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



  • Thought to affect 4–7% of adults in Europe and United States; 80% of patients >60 years
  • No gender predominance. Men more likely to present acutely; women more likely to present atypically
  • Chondrocalcinosis present in 1:10 adults age 60 to 75 years,1:3 age >80 years; only a small percentage develop arthropathy.

Etiology and Pathophysiology

  • Arthropathy results from an acute autoinflammatory reaction to CPPD crystals in the synovial cavity.
  • CPPD crystal deposition occurs in three stages:
    • Overproduction of anionic pyrophosphate (PPi) in articular cartilage
    • PPi binds calcium to form CCPD crystals, eliciting an inflammatory response. Neutrophils engulf CPPD crystals, inducing extracellular trap formation.
    • Increased CPPD crystal deposition causes inflammation and damage (3)[C].

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

Risk Factors

Advanced age; joint trauma

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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