Description

• 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

Epidemiology

Prevalence

• 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].

Genetics
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