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Calcium Pyrophosphate Dihydrate Crystal Deposition Disease


by Lawrence M. Ryan, MD

Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease involves intra-articular and/or extra-articular deposition of CPPD crystals. Manifestations are protean and may be minimal or include intermittent attacks of acute arthritis and a degenerative arthropathy that is often severe. Diagnosis requires identification of CPPD crystals in synovial fluid. Treatment is with intra-articular corticosteroids or oral NSAIDs or colchicine.

CPPD crystal deposition (chondrocalcinosis), whether symptomatic and asymptomatic, becomes more common with age.

The incidence of radiologic (usually asymptomatic) chondrocalcinosis in patients aged 70 is about 3%, reaching nearly 50% in patients aged 90. Asymptomatic chondrocalcinosis is common in the knee, hip, anulus fibrosus, and symphysis pubis. Men and women are affected equally.

Etiology of CPPD Crystal Deposition Disease

The cause of CPPD crystal deposition disease is unknown. Frequent association with other conditions, such as trauma (including surgery), amyloidosis, myxedema, hypomagnesemia, hyperparathyroidism, gout, hemochromatosis, and oldĀ age, suggests that CPPD crystal deposits are secondary to degenerative or metabolic changes in the affected tissues. Some cases are familial, usually transmitted in an autosomal dominant pattern, with complete penetration by age 40. Recent studies indicate that the ANK protein is a central factor in producing excess extracellular pyrophosphate, which promotes CPPD crystal formation. ANK protein is a putative transporter of intracellular pyrophosphate to the extracellular location where CPPD crystals form.

Symptoms and Signs of CPPD Crystal Deposition Disease

Acute, subacute, or chronic arthritis can occur, usually in the knee or other large peripheral joints, which can mimic many other forms of arthritis. Attacks are sometimes similar to gout but are usually less severe. There may be no CPPD crystal deposition disease symptoms between attacks or continuous low-grade symptoms in multiple joints, similar to RA or osteoarthritis. These patterns tend to persist for life.

Diagnosis of CPPD Crystal Deposition Disease

  • Synovial fluid analysis

  • Identification of crystals microscopically

CPPD crystal deposition disease should be suspected in older patients with arthritis, particularly inflammatory arthritis. CPPD crystal deposition disease diagnosis is established by identifying rhomboid- or rod-shaped crystals in synovial fluid that are not birefringent or are weakly positively birefringent on polarized light microscopy. Coincident infectious arthritis must be ruled out by Gram stain and culture. X-rays are indicated if synovial fluid cannot be obtained for analysis; findings of multiple linear or punctate calcification in articular cartilage, especially fibrocartilages, support the diagnosis but do not exclude gout or infection.

Prognosis of CPPD Crystal Deposition Disease

The prognosis for individual attacks is usually excellent. However, chronic arthritis can occur, and severe destructive arthropathy resembling neurogenic arthropathy ( Charcot joints) occasionally occurs.

Treatment of CPPD Crystal Deposition Disease

  • Intra-articular corticosteroids

  • NSAIDs

  • Colchicine maintenance

Symptoms of acute synovial effusion abate with synovial fluid drainage and instillation of a microcrystalline corticosteroid ester suspension into the joint space (eg, 40 mg prednisolone acetate or prednisolone tertiary butylacetate into a knee). Indomethacin, naproxen, or another NSAID given at anti-inflammatory doses often stops acute attacks promptly. Colchicine 0.6 mg po once/day or bid may decrease the number of acute attacks.

Key Points

  • Asymptomatic chondrocalcinosis becomes common with age, particularly in the knee, hip, anulus fibrosus, and symphysis pubis.

  • Arthritis can affect the knee and large peripheral joints and mimic other forms of arthritis.

  • Examine joint fluid for characteristic rhomboid- or rod-shaped crystals in synovial fluid that are not birefringent or are weakly positively birefringent and exclude joint infection.

  • For acute symptoms, treat with an intra-articular corticosteroid or an oral NSAID.

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