Calcium pyrophosphate disease

Introduction

Calcium pyrophosphate dihydrate crystal deposition disease is a relatively common arthritic disorder that occurs most often in elderly patients. It may manifest clinically as attacks of acute arthritis associated with the intra-articular deposition of calcium pyrophosphate

dihydrate crystals (pseudogout syndrome). Roentgenographic features

Include^[1]

• articular chondrocalcinosis (calcification of hyaline or fibrous articular cartilage or both)
• capsular or periarticular calcific deposits or both
• pyrophosphate arthropathy, a progressive, destructive, accelerated form of osteoarthritis with distinctive roentgenographic findings

Deposition of calcium pyrophosphate (CPP) crystals in and on cartilaginous surfaces can provoke acute inflammatory arthritis that is clinically similar to acute gout. Calcium pyrophosphate deposition (CPPD) is less well characterized than gout, but four subgroups are described:

• asymptomatic CPPD
• acute CPP crystal arthritis
• chronic CPP crystal inflammatory arthritis
• osteoarthritis with CPPD.^[2]

Epidemiology

CPPD primarily affects the elderly, and prior joint damage is a significant risk factor. The risk for cartilage calcification (chondrocalcinosis) doubles for every decade past 60 years, and nearly half of patients in their late 80s have CPPD. For younger patients with CPPD, consideration of contributory metabolic disease is warranted.

• Hyperparathyroidism
• hemochromatosis
• Hypophosphatasia
•  hypomagnesemia

Clinical Manifestations

• Episodes of pseudogout involved a single joint in 25 patients
• Two joints in 16
• three or more joints in 9

. The knee and wrist joints were the most commonly affected. The arthritis was characterized

by a sudden onset of pain and swelling, associated with tenderness and variable degrees of warmth, redness and effusion. It was the first attack of pseudogout for 20

patients; the remaining 30 had had one or more previous attacks. In 35 patients the attacks occurred during the course of another illness for which the patient was already hospitalized.^[3]

The spectrum of articular manifestations ranges from acute attacks of inflammatory arthritis

("pseudogout" or type "A" arjhritis according to McCarty's classification to calcification of fibrous or hyaline cartilage or both (chondrocalcinosis), capsular and periarticular calcifications, and a

progressive, destructive type of osteoarthritis designated pyrophosphate

arthropathy" (corresponding to McCarty's type "C" pseudoosteoarthritis and type "F" pseudoneuropathic joints.

Asymptomatic Calcium Pyrophosphate Deposition

Asymptomatic CPPD occurs with radiographic changes in the absence of clinical symptoms. Cartilage calcification appears as a linear opacity below the surface of articular cartilage. It most commonly occurs in (descending order):^[4]

• knees
• wrists (triangular fibrocartilage)
• pelvis (pubis symphysis)
• metacarpophalangeal (MCP) joints Asymptomatic CPPD is common in the elderly and in osteoarthritic joints, and it may be a precursor of osteoarthritis with CPPD

Acute Calcium Pyrophosphate Crystal Arthritis

Arthritis (pseudogout) typically presents as a monoarticular inflammatory arthritis, characterized by sudden onset of swelling, pain, loss of function, tenderness, and warmth of the affected joint, usually a knee or wrist. Similar to acute gout, attacks may be provoked by systemic insults such as major surgery or acute illness. Attacks are usually milder than those of gout, but if untreated can persist for months. Definitive diagnosis requires identification of CPP crystals (along with leukocytes) in synovial fluid; in contrast to uric acid crystals, the CPP crystals are rhomboid shaped and positively birefringent under polarized light. Radiographic evidence of cartilage calcification in elderly patients with acute monoarticular arthritis is suggestive but not diagnostic of acute CPP crystal arthritis.^[5]

Chronic Calcium Pyrophosphate Arthropathy

Chronic calcium pyrophosphate arthropathy may be present as two patterns:

• chronic calcium pyrophosphate (CPP) crystal inflammatory arthritis
• Chronic CPP crystal inflammatory arthritis is a polyarthritis involving the wrists and MCP joints (“pseudo–rheumatoid arthritis”); it is rare and difficult to treat.^[6]

Osteoarthritis with calcium pyrophosphate deposition (CPPD).

Osteoarthritis with CPPD manifests as typical osteoarthritic findings involving joints not commonly associated with osteoarthritis (such as shoulders or MCP joints); radiographic CPPD often precedes the onset of osteoarthritis, suggesting a causal role for the CPP.^[7]

Causes

Although most cases are idiopathic, there are familial forms and the condition has been observed in coincidence with other metabolic disorders. An association between pseudogout

attacks and both primary hyperparathyroidism and idiopathic

hemochromatosis has been well documented. Among our 50 patients we found three cases of

primary hyperparathyroidism (a frequency of 6%, which corresponds with that reported in other series and one case of idiopathic hemochromatosis. It is therefore important to screen patients with pseudogout for unsuspected metabolic disorders.^[8]