At least three different calcium-containing crystals are now known to deposit in joints and to be associated with a variety of patterns of arthritis in much the same way as urate crystals cause the various features of gouty arthritis. Calcium pyrophosphate and occasionally calcium oxalate produce linear or punctuate calcifications in menisci and articular cartilage that can be readily seen on roentgenograms. These calcifications are termed chondrocalcinosis. Both these crystals and calcium apatite can also deposit diffusely in synoviurn and periarticular tissues, giving a soft tissue pattern on roentgenograms. X-rays may not show obvious calcifications when crystals are relatively few. Definitive diagnosis is made only by aspiration of synovial fluid for identification of the crystal type.

CALCIUM PYROPHOSPHATE DIHYDRATE (CPPD) CRYSTAL DEPOSITION DISEASE (Pseudogout Syndrome)

This is defined by the identification of rod- or rhomboidshaped 2- to 25-[L long, weakly positively birefringent crystals in synovial fluid or articular tissue. This is a common cause of arthritis; it is most frequent in the elderly. Up to 27 per cent of nursing home patients in their 80's have x-ray evidence of chondrocalcinosis on this basis. Familial cases have been described in populations of various ethnic origins. Both sexes are affected.

The cause of CPPD crystal deposition is not established, but local overproduction of pyrophosphate related to excessive activity of nucleoside triphosphate pyrophosphohydrolase, deficiency of phosphatases, and local connective tissue changes are probably important. CPPD crystals deposit only in joints and adjacent tendons or bursae, where they produce hernatoxyphilic clumps replacing the normal tissue. Virtually any joint can be involved, but knees, wrists, and second and third metacarpophalangeal joints are most common so that chronic cases can be confused with rheumatoid arthritis. Acute bouts of crystal-induced arthritis at one or more joints can mimic gout and lead to "pseudogout." CPPD crystal deposition often complicates osteoarthritis; these crystals were seen in 42 per cent of osteoarthritic knee effusions in one series. Whether crystals contribute to cartilage degeneration in osteoarthritis is not yet clear. Occasional severe arthritis mimics the destruction seen in neuropathic joints. Radiographic evidence of calcification can be present in some cases for years without inducing any symptoms. Others may have crystals in joint fluid with osteoarthritis-like x-ray changes but no visible chondrocalcinosis. Synovial effusions are generally inflammatory with leukocyte counts up to 100,000 per cu mm and with 80 to 90 per cent neutrophils during acute attacks. Between attacks crystals can be seen in clear, noninflammatory joint effusions.

CPPD crystal deposition can be an important clue to a number of associated diseases, many of which have specific treatments that can control systemic features if not the arthropathy. Associated diseases include hyperparathyroidism, hemochromatosis, myxedema, ochronosis, hypophosphatasia, hypomagnesemia, and perhaps acromegaly and Wilson's disease. CPPD crystal deposition may complicate other advanced arthritides such as gout and rheumatoid arthritis.

Treatment of inflammatory episodes with thorough aspiration and use of nonsteroidal anti-inflammatory agents is generally successful. Intra-articular steroid injections may provide relief in refractory involvement of individual joints. Intravenous colchicine may also be helpful. Recent studies show that chronic therapy with 0.6 to 1.2 mg colchicine per day can greatly decrease the frequency of acute attacks. Otherwise the prognosis is for slow progression. Joint replacement has been successful when needed

APATITE CRYSTAL DEPOSITION DISEASE

Individual apatite crystals can be seen only by electron microscopy (EM), but clumps of these crystals appear as 2- to 15-VL shiny (but not generally birefringent) globules that can suggest the diagnosis. Apatite crystal deposition and crystalinduced inflammation are common findings in bursitis and periarthritis, Apatite also occurs in some otherwise unexplained acute arthritis and, like CPPD, is common in osteoarthritic joint effusions. Most joints or bursae can be involved, with more common sites including shoulders, hips, knees, and digits. Joint or periarticular inflammation can be acute or chronic. An extremely destructive arthritis has been noted especially at shoulders ("Milwaukee shoulder"), hips, and knees. X-rays can also show soft tissue calcifications with or without bony erosions. Definitive diagnosis of the crystal type is only by EM with electron probe elemental analysis, x-ray diffraction, or infrared spectroscopy. Other basic calcium phosphates such as octacalcium phosphate can be seen along with the apatite. Synovial or bursal effusions can have many or few leukocytes. Serum studies are generally normal except that phosphate levels are often elevated in renal dialysis patients who are at high risk of apatite deposition.

Apatite deposition can also be associated with scleroderma and the other connective tissue diseases and with high-dose vitamin D therapy. In most instances the cause of soft tissue apatite deposition is not known. Treatment for acute arthritis or periarthritis is with nonsteroidal anti-inflammatory agents or colchicine. Aspiration of crystals and local injection with depot corticosteroids can also be effective.

OXALATE CRYSTAL DEPOSITION DISEASE

Calcium oxalate deposition can occur in joints along with other tissues of renal failure patients on chronic hemodialysis, producing x-ray evidence of soft tissue calcification and chondrocalcinosis. Acute or chronic joint effusions with intracellular crystals can be seen. Diagnosis is made by identification of typical bipyramidal crystals. When less characteristic crystals are seen, other techniques as described under apatite deposition can be used. There is some recent suggestion that vitamin C may potentiate oxalate deposition so this might be avoided.