Calciphylaxis

Calciphylaxis, also known as calcific uremic arteriolopathy, is a rare but life-threatening disorder characterized by calcification and thrombosis of small- and medium-sized cutaneous vessels, leading to painful skin ischemia and necrosis. It most often affects people with end-stage kidney disease on dialysis, but nonuremic calciphylaxis can occur in individuals without advanced kidney disease.

The pathogenesis involves disturbances in calcium-phosphate metabolism with medial vascular calcification and subsequent thrombosis of dermal vessels, resulting in tissue ischemia and necrosis. Risk factors include advanced kidney disease with elevated phosphate and parathyroid hormone levels, female sex, obesity, diabetes, malnutrition, and exposure to vitamin K antagonists such as warfarin. Inflammatory and prothrombotic states may contribute to disease development.

Clinical presentation typically begins with very painful, violaceous, mottled patches on the thighs, abdomen, or legs that progress to retiform purpura, ulceration, and necrosis. Wounds are prone to infection, and sepsis is a leading cause of death in affected patients.

Diagnosis is primarily clinical, supported by imaging and laboratory findings. Biopsy can confirm calcification and thrombosis in small vessels but carries a risk of impaired wound healing and should be weighed against potential benefits. Laboratory studies often show elevated calcium-phosphate product and secondary hyperparathyroidism. Imaging such as plain radiographs or CT may reveal vascular calcifications; nuclear medicine scans can show characteristic soft tissue uptake.

Management requires a multidisciplinary approach focused on hurting progression, wound care, and infection prevention. Interventions include correcting mineral metabolism with non-calcium-containing phosphate binders, limiting calcium intake and calcium-containing dialysate, and addressing hyperparathyroidism with calcimimetics or parathyroidectomy if indicated. Warfarin should be avoided when possible; sodium thiosulfate therapy has shown benefit in some cases. Additional treatments such as aggressive wound care, analgesia, and, in select cases, hyperbaric oxygen may be used. The prognosis is poor, with high mortality often related to sepsis from infected wounds.