Calciphylaxis.

Abstract

The phenomenon of calciphylaxis is rare, but potentially fatal. It has been recognised for a long time in patients with chronic renal failure with secondary hyperparathyroidism. Disturbed calcium and phosphate metabolism can result in painful necrosis of skin, subcutaneous tissue and acral gangrene. Appearance of the lesions is distinctive but the pathogenesis remains uncertain. The beneficial effects of parathyroidectomy are controversial. However, correction of hyperphosphataemia or occasionally hypercalcaemia is imperative. Fulminant sepsis as a consequence of secondary infection of necrotic and gangrenous tissue is a frequent cause of patient morbidity and mortality.

(Postgrad Med J 2001;77:557-561)

Keywords: calciphylaxis; calcium-phosphate product; secondary hyperparathyroidism; chronic renal failure

The syndrome of calciphylaxis is ischaemic ulceration of skin due to metastatic calcification of subcutaneous tissue and small arteries occurring as a consequence of hyperparathyroidism in uraemic patients (box 1). Bryant and White first recorded the occurrence of calciphylaxis in uraemia in 1898 in Guy's Hospital Reports. Selye in 1962 coined the term calciphylaxis for acute local calcification of various organs and equated this to a hypersensitivity reaction. This is inappropriate, as there is no relation to IgE type 1 mediated allergy. He induced extensive soft tissue calcification in rats that were previously sensitised by high doses of vitamin D analogues or parathyroid hormone, by local injection of irritants designated as challengers. [1-10] These experimental conditions were not comparable with the clinical situations in the context of the absence of uraemic milieu and ischaemic necrosis from medial calcification and intimal hyperplasia of small arteries. Hence the suitability of the term was doubtful . [4,5,10-12] However, the term calcinosis fails to distinguish secondary calcification in a necrotic tissue from ischaemic tissue necrosis due to arterial calcification. [12] Hafner et al in 1995 termed this phenomenon as uraemic small artery disease to characterise skin necrosis and acral gangrene consequent to medial calcification and intimal hyperplasia in arteries of subcutaneous tissue and those of hands and feet. [5,10]

Pathogenic factors

Pathogenesis remains speculative. [13] Chronic renal failure, hyperparathyroidism, and a high phosphate diet act as sensitising agents resulting in a high calcium-phosphate product (Ca x P; normal range 4.2-5.6 [mmol.sup.2]/[l.sup.2]) with resultant precipitation of Ca-P crystals. [14] This results in diffuse calcification of the media and internal elastic lamina of small to medium sized arteries and arterioles with intimal proliferation and rarely arterial occlusion causing tissue necrosis. This entity was given the term calcinosis cutis to signify vascular calcification with ischaemic epidermolysis as seen in patients with chronic renal failure on haemodialysis. [15-17] Other triggering events include intravenous iron dextran and albumin infusion, low serum albumin, corticosteroids, immunosuppression, trauma, subcutaneous injections in obese patients, and protein C and S deficiencies causing hypercoagulability and subsequent thrombosis. [8,12,16,18-25] Obesity has recently been established as a risk factor primarily due to large deposits of adipose tissue that may be associated with reduction of local blood flow. [9,18,23,25,26] Diabetics with chronic renal failure are especially prone to develop acral necrosis partly due to extensive vascular calcifications. …