Disease relevance of Calciphylaxis

• CONCLUSION: These findings suggest that hypercoagulability due to functional protein C deficiency may contribute to thrombosis, resulting in skin necrosis and digital gangrene in systemic calciphylaxis [1].
• We describe a case of chronic renal failure with severe secondary HPT in which the patient developed calciphylaxis 4 days after the appearance of a psoriatic flare [2].
• Thrombosis and protein C deficiency have been implicated in the pathophysiology of calciphylaxis [3].
• The amino bisphosphonate ibandronate prevents calciphylaxis in the rat at doses that inhibit bone resorption [4].
• However, given the lack of significant toxicity, as well as a dramatic clinical improvement, we feel that sodium thiosulfate may have an important adjunctive role in the treatment of calciphylaxis in dialysis patients [5].

High impact information on Calciphylaxis

• Intraarticular calciphylaxis with cartilage and synovial calcification was produced in rabbits by oral administration of a single dose of dehydrotachysterol followed by an intraarticular injection of ferrous chloride [6].
• Although most calciphylaxis patients have abnormalities of the calcium:phosphate axis or elevated levels of parathyroid hormone, these abnormalities do not appear to be fundamental to the pathophysiology of the disorder, and the etiology of calciphylaxis remains unclear [7].
• PURPOSE: To determine if the natural anticoagulant protein C plays a role in the pathogenesis of systemic calciphylaxis, a syndrome characterized by extensive vascular and soft tissue calcification and skin necrosis, which is similar to that seen in warfarin-induced skin necrosis [1].
• However, OPN and MGP were expressed at sites of calcification within atherosclerotic lesions and in microvessels in calciphylaxis, suggesting that calcification in different sized vessels may occur by a common mechanism [8].
• TSP-1 and COMP were also detected in areas of microcalcification in atherosclerotic lesions and TSP-1 was detected adjacent to areas of calcification in calciphylaxis [8].

Chemical compound and disease context of Calciphylaxis

• Rapid resolution of calciphylaxis with intravenous sodium thiosulfate and continuous venovenous haemofiltration using low calcium replacement fluid: case report [9].
• Calcergy and calciphylaxis: timed appearance of gamma-carboxyglutamic acid and osteocalcin in mineral deposits [10].
• The amount of non-collagenous proteins is increased greatly during the pathological calcification of rat skin experimentally induced by dihydrotachysterol (DHT) and Ovalbumin (topical cutaneous calciphylaxis) [11].
• Polyurethane calcium and phosphate levels and morphological changes due to calciphylaxis were compared with those of control rat subdermal explants in 60-day studies [12].
• Rapid improvement of calciphylaxis after intravenous pamidronate therapy in a patient with chronic renal failure [13].

Biological context of Calciphylaxis

• Body mass index, diabetes, blood pressure, aluminum, and higher dosage of erythropoietin and iron dextran were not independent predictors of calciphylaxis [14].
• A brief review of the molecular biology of vascular calcification supports the concept that warfarin administration may exacerbate the calcific process, particularly in the setting of hyperphosphatemia, as has been reported in patients with calciphylaxis [15].
• Parathyroidectomy promotes wound healing and prolongs survival in patients with calciphylaxis from secondary hyperparathyroidism [16].
• CONCLUSION: Although hyperparathyroidism and imbalance of calcium-phosphorus homeostasis are paramount for calciphylaxis to occur, other mechanisms must be involved because the disease manifests itself in only a minority of ESRD patients [17].

Anatomical context of Calciphylaxis

• Review of the literature revealed 7 other cases of calciphylaxis due to primary hyperparathyroidism and showed that prompt surgical removal of the autonomous parathyroid gland lesion results in clinical recovery of calciphylactic skin lesions [18].
• In contrast to atherosclerosis, BMP-4 in calciphylaxis cannot be found in vascular media, but in intradermal cells at the border of arterioles and hair follicles [19].

Gene context of Calciphylaxis

• We present the first case of calciphylaxis occurring in a patient with both normal renal function and parathyroid hormone level and discuss the possible aetiological role of chemotherapy-induced functional protein C and protein S deficiency [20].
• Protein malnutrition increases the likelihood of calciphylaxis, as does warfarin use and hypercoagulable states, such as protein C and/or protein S deficiency [21].
• METHODS: We present a case of a 26-year-old woman with end-stage renal disease taking intramuscular injections of erythropoietin in whom systemic calciphylaxis subsequently developed [22].
• However, protein C activity was significantly reduced as measured by chromogenic (p less than 0.01) or anticoagulant assays (p less than 0.01) in patients with calciphylaxis compared with the other three groups [1].
• The syndrome has been reviewed in the renal, dermatologic, and surgical literature under the term calciphylaxis, which describes a postulated pathogenetic mechanism whereby sensitization to an endogenous or exogenous substance (such as parathyroid hormone) predisposes to calcium deposition after exposure to a challenging agent [23].

Analytical, diagnostic and therapeutic context of Calciphylaxis

• Therefore, patients with secondary hyperparathyroidism and signs/symptoms of calciphylaxis should be referred promptly for consideration of parathyroidectomy [16].
• The calcification-prone state, known as calciphylaxis, was induced in 4-week old rats by oral administration of a vitamin-D analog, dihydrotachysterol [12].
• Calciphylaxis in a chronic hemodialysis patient with protein S deficiency [24].
• This clinical picture, previously named "calciphylaxis" should come into the differential diagnosis of systemic vasculitis in a uraemic patient with hyperparathyroidism [25].

References