A number of cells,
chemotactic factors, and inflammatory mediators are implicated in the complex mechanisms underlying crystal-mediated
inflammation.
Interleukin-8, released from mononuclear cells that have been exposed to
urate and other crystals, is a potent
chemotaxin and activator of neutrophils. Experimental and clinical observations suggest that joint movements, local biomechanical factors, and previous joint damage may play a role in influencing the intensity of microcrystalline
synovitis and the distribution of articular and periarticular crystal deposits in both
calcium pyrophosphate dihydrate crystal deposition disease and
gout. There are rare reports of extra-articular
calcium pyrophosphate dihydrate crystal deposition in tendons, bursae, dura mater, and ligamentum flavum (with radiculomyelopathy) and of massive "tumoral," tophuslike, periarticular
calcium pyrophosphate dihydrate crystal deposits. Synovial fluid levels of
ATP, the main substrate for
nucleoside triphosphate pyrophosphohydrolase ectoenzyme, which cleaves
ATP-releasing inorganic
pyrophosphate, are higher in patients with
calcium pyrophosphate dihydrate crystal deposition disease than in those with other
arthritides, and the levels correlate with inorganic
pyrophosphate concentrations. Further reports of acute calcific
periarthritis of the first metatarsophalangeal joint (
hydroxyapatite pseudopodagra) in young women have been described. The mitogenic response of fibroblasts to stimulation with basic
calcium phosphate crystals is accompanied by induction and secretion of
collagenase and neutral
proteases, implicating a role for the crystals in the pathogenesis of both synovial proliferation and joint damage in chronic basic
calcium phosphate crystal-associated
arthropathy. Subcutaneous
cholesterol crystal deposition with tophus formation is extremely rare and has been described in a patient with scleroderma and
calcinosis cutis.