45. | Manual of Rheumatology and Outpatient Orthopedic Disorders (LB Spiral Manuals)

Chapter 38 Pseudogout (Calcium Pyrophosphate Dihydrate Crystal Arthropathy)

Manual of Rheumatology and Outpatient Orthopedic Disorders

Chapter 38 Pseudogout (Calcium Pyrophosphate Dihydrate Crystal Arthropathy)

Theodore R. Fields and Nicholas P. Scarpa

Pathogenesis
History
Physical examination
Laboratory studies
Differential diagnosis
Treatment
Prophylaxis
Prognosis

Pseudogout is an inflammatory arthropathy, with acute and chronic forms, caused by the deposition of calcium pyrophosphate dihydrate (CPPD) crystals in synovial structures. Chondrocalcinosis (calcified cartilage seen on radiographs), found in the majority of pseudogout patients , was first recognized in 1957 by Zitnan and Sitaj. McCarty in 1962 defined the relationship of intrasynovial CPPD crystals to chondrocalcinosis. The prevalence of pseudogout is not known. However, 8% of all people older than 60 years have radiographic evidence of chondrocalcinosis. The prevalence of chondrocalcinosis increases with age to involve as many as 28% of the population in the ninth decade . The mode of inheritance of CPPD is unsettled. However, an autosomal dominant pattern has been described in some populations in which disease begins in early adulthood , progresses rapidly , and is polyarticular.

I. Pathogenesis. Aging, osteoarthritis , genetic defects, and certain metabolic disorders are thought to induce abnormalities in cartilage that enhance deposition of CPPD crystals. Crystals are shed into the joint and undergo phagocytosis by leukocytes. The release lysosomal enzymes results in an acute inflammatory response. If inflammation persists, the cellular infiltrate of the synovium changes to a mononuclear pattern with fibroblastic proliferation in the chronic form of the disease.

Diseases associated with CPPD include hyperparathyroidism, hemochromatosis, hypophosphatasia, hypomagnesemia, gout, neuropathic arthropathy, and osteoarthritis. The association of CPPD with hypothyroidism is controversial . Diabetes has been shown not to be linked with pseudogout.

Osteoarthritis and chondrocalcinosis are both common disorders, and their exact relationship has not been established. It is possible that chrondrocalcinosis is a disease marker for certain cartilage changes in osteoarthritis.

II. History. CPPD deposition syndromes occur in the following clinical patterns:

Acute pseudogout. Acute monarthritis occurs in nearly 25% of patients with CPPD. Elderly women are afflicted more often then men. The knee is the most commonly involved joint. Ankle, wrist, and shoulder involvement is also common, and acromioclavicular pseudogout has been described. Attacks are usually self-limited, lasting several days to several weeks. Surgical procedures, especially parathyroidectomy, and severe medical illness may precipitate acute pseudogout attacks.
Chronic pseudogout
1. Pseudo-rheumatoid arthritis. This chronic polyarticular inflammation occurs in up to 5% of patients with CPPD deposition. In some patients, prominent symptoms of fatigue, malaise, and morning stiffness may also develop, making the distinction from rheumatoid arthritis difficult.
2. Atypical osteoarthritis, the most common pattern of CPDD arthropathy, tends to be distinguished from true osteoarthritis by the involvement of the wrists and metacarpophalangeal joints. Flexion contractures and periarticular tendinous involvement also occur in this subgroup of patients. Formation of osteophytes occurs, but it is not as exuberant as that seen with true osteoarthritis.
Asymptomatic chondrocalcinosis refers to the radiographic finding of calcified cartilage in patients without joint complaints. It is very common in the eighth decade and later.
Pseudoneuropathic joints. The deposition of CPPD crystals in the presence of destructive arthropathy, as seen in Charcot's joints, has been described. This is usually a chronic relapsing arthropathy with a female predominance of 14:1 and associated with tendon ruptures, especially at the shoulder joints.

III. Physical examination

Articular features. Signs of inflammation are prominent, particularly in the knees, hips, and wrists. Involvement of the small joints of the hands and feet is less common.
Extraarticular features. Signs of other diseases associated with CPPD arthropathy may be present, such as skin pigmentation and the hepatomegaly of hemochromatosis or the band keratopathy and muscle weakness of hyperparathyroidism.

IV. Laboratory studies

Biochemical. There are no known specific biochemical abnormalities of pseudogout itself. The chemical abnormalities noted in other diseases associated with the development of pseudogout may, however, be present. These values include low serum levels of magnesium and phosphate in addition to elevated levels of calcium, ferritin, and uric acid. Low thyroxine levels are not any longer believed to be related to pseudogout.
Synovial fluid. Study of aspirated joint fluid is required to confirm the diagnosis. The white blood cell count ranges from 3,000 to 50,000, with 70% or more neutrophils. No organisms are present on Gram's stain . Results of cultures are negative. CPPD crystals can be identified with compensated polarized microscopy. CPPD crystals are rhomboid-shaped and exhibit weakly positive birefringence. These crystals can also be seen on light microscopy with use of alizarin red S stain.
Radiographs. Chondrocalcinosis can be demonstrated in approximately 75% of pseudogout patients. Fibrocartilage sites that are most likely to demonstrate chondrocalcinosis include knee menisci, the symphysis pubis, and the triangular cartilage of the wrist. Chondrocalcinosis appears as linear or punctate radiographic densities within cartilage. Subchondral bone cysts and hooklike osteophytes of metacarpophalangeal joints may also be observed .

V. Differential diagnosis

Disorders resembling acute pseudogout
1. Gout. The only absolute method of distinction is the characterization of crystals in synovial fluid. However, the simultaneous existence of both gout (monosodium urate crystals) and pseudogout (CPPD) can occur.
2. Septic arthritis. The finding of prominent systemic signs of infection, when present, may offer a clue to the diagnosis; aspiration of synovial fluid with Gram's stain and appropriate cultures are essential.
3. Hydroxyapatite crystal deposition disease may produce synovitis or tendinitis. Crystals may be seen with electron microscopy but not with routine polarizing microscopy. Therefore, the diagnosis must be made clinically. This disorder tends to develop in patients with calcifications of the shoulder area and patients on hemodialysis. In young, premenopausal women, goutlike inflammation of the first metatarsophalangeal joint, or pseudopodagra, may be caused by CPPD crystals.
4. Other causes of monarthritis, including osteoarthritis and neuropathic arthropathy, are reviewed in Chapter 9.
Metabolic disorders associated with syndromes of calcium pyrophosphate dihydrate deposition include hyperparathyroidism, hemochromatosis, ochronosis, gout, hypomagnesemia, Wilson's disease, and hypophosphatasia. Other associations include aging, osteoarthritis, neuropathic joints, trauma, and septic arthritis.

VI. Treatment. In the acute attacks of pseudogout, a combination of joint aspiration and drug therapy is very beneficial. The affected joint should be mobilized quickly so that patients do not suffer complications from prolonged joint inactivity.

Joint aspiration alone removes a significant quantity of inciting crystals and chemical mediators, thereby often allowing the synovitis to subside. In those with protracted courses, intraarticular injection of a long-acting corticosteroid preparation is usually beneficial.
Antiinflammatory drugs
1. Indomethacin (50 mg every 8 hours with tapering doses during 5 days) is usually effective.
2. Other nonsteroidal antiinflammatory drugs (NSAIDs), such as naproxen and sulindac, have efficacy similar to that of indomethacin and are often better tolerated in the elderly than is indomethacin.
Chronic pseudogout can be managed with NSAIDs and periodic intraarticular corticosteroid injections. Any associated diseases such as hemochromatosis and hyperparathyroidism should be managed appropriately, but treatment of the underlying disease may not prevent the recurrent attacks of arthropathy.

VII. Prophylaxis. Some evidence favors long- term prophylaxis with oral colchicine (0.6 mg PO twice daily) for patients with recurrent acute attacks. Several letters to the editor suggest a benefit of hydroxychloroquine, in doses similar to those used for rheumatoid arthritis, in preventing pseudogout flares.

VIII. Prognosis. Pseudogout itself has no known effect on life expectancy; associated diseases carry their own prognoses. Joint symptoms can be controlled by the treatment regimens outlined in section VI. Patients with associated osteoarthritis may eventually require prosthetic joints if symptoms and disability become chronic and severe.

Bibliography

Chaisson CE, et al. Lack of association between thyroid status and chondrocalcinosis or osteoarthritis: the Framingham osteoarthritis study. J Rheumatol 1996;23:711.

Ellman MH, Brown NL, Porat AP. Laboratory investigations in pseudogout patients and controls. J Rheumatol 1980;7:77.

McCarty DJ, ed. Conference on pseudogout and pyrophosphate metabolism. Arthritis Rheum 1976;19:275.

Utsinger PD, Zvaifler NJ, Resnick D. Calcium pyrophosphate dihydrate deposition disease without chondrocalcinosis. J Rheumatol 1975;2:258.

Books@Ovid
Copyright 2000 by Lippincott Williams & Wilkins
Stephen A. Paget, M.D., Allan Gibofsky, M.D., J.D. and John F. Beary, III, M.D.
Manual of Rheumatology and Outpatient Orthopedic Disorders

-->