๐ ็ธฝ็ฎ้ ๏ฝ ๐ ่ฑๆๅๆ๏ผๆฌ็ฏ๏ผ ๏ฝ ๐ ๅฎๆด็ฟป่ญฏ ๏ฝ โญ ็ฒพ่ฏ็ญ่จ
Calciphylaxis
Synonyms:๏ก Calcific arteriolopathy ๏ก Calcific uremic arteriolopathy
The cutaneous manifestations of calciphylaxis are reviewed in Chaptersย 50 and 106. This section focuses on the mechanisms that underlie the associated thrombotic vasculopathy. While calcification in vessels or peri-eccrine areas within the subcutis is considered the gold standard for the diagnosis of cutaneous calciphylaxis, identical calcification has been demonstrated in normal skin in ~40% of patients with end-stage and chronic renal disease without calciphylaxis as well as in 18% of a small sample of control patients without renal disease under-going elective surgery.
In one study, patients whose skin biopsies fulfilled the histologic criteria for calciphylaxis also had areas of thrombosis within vessels without evidence of calcification. This raised the question of whether calcification is a driver of occlusion, an incidental factor, or a consequence of an underlying vascular dysfunction distinct from calcification (subcutaneous thrombotic vasculopathy). More recently, at least half of patients with uremic and non-uremic calciphylaxis were found to have lupus anticoagulant, offering an explanation for vascular dysfunction.
The elevated calcium ร phosphate product, association of calciphylaxis with administration of vitamin D, and calciphylaxis in individuals without chronic kidney disease treated with teriparatide (PTH agonist for osteoporosis), suggests that calcium plays a triggering or synergistic role in this disease. Vitamin K is thought, at least in part, to play a role in the pathogenesis of the vascular calcification. There are two forms of vitamin K: (1) K1 (phylloquinone), stored primarily in the liver, is an essential cofactor for synthesis of the procoagulant factors II, VII, IX, and X as well as the anticoagulant proteins C and S; and (2) K2 (metaquinone), stored primarily in vessels and bones, is essential for carboxylation of multiple inhibitors of vascular calcification, especially Gas6 (growth arrest-specific 6) and MGP (matrix Gla) proteins. Chronic renal disease leads to depletion of vascular stores of vitamin K2, resulting in accelerated atherogenesis with arterial calcification and presumably increases the risk of cutaneous vessel calcification. This may also explain why warfarin is associated with a greater risk of calciphylaxis, as warfarin or other vitamin K antagonists further interfere with impaired K2-dependent carboxylation of Gas6 and matrix Gla proteins.