What is calciphylaxis and how is it treated?

Calciphylaxis: Diagnosis and Management

Calciphylaxis is a rare but life-threatening condition characterized by vascular calcification leading to ischemic skin ulceration, primarily affecting patients with chronic kidney disease, especially those on dialysis. 1, 2

Clinical Presentation and Pathophysiology

• Calciphylaxis presents as painful, violaceous, mottled lesions of the extremities and/or trunk that progress to skin and subcutaneous tissue necrosis, non-healing ulcers, and gangrene 3
• The condition involves calcium deposition in dermal and adipose microvasculature, leading to vascular calcification, thrombosis, and subsequent tissue ischemia 1, 4
• Mortality rates can reach up to 50% within one year, with sepsis being a common cause of death 5, 3

Diagnosis

• C-reactive protein is the most helpful laboratory test for diagnosing calciphylaxis, as it reflects the inflammatory component of the condition 1, 2
• Serum calcium and phosphate levels are not predictive of outcomes in calciphylaxis and cannot be reliably used for diagnosis or guiding therapy 1, 2
• Skin biopsy has significant limitations with variable sensitivity (20-80%) and risks traumatizing vulnerable tissue, potentially triggering additional non-healing ulcers 1, 2
• The diagnosis is primarily clinical, based on characteristic painful skin lesions in patients with risk factors 2, 6

Risk Factors

• End-stage renal disease is the most common underlying condition 2, 4
• High doses of active vitamin D derivatives increase risk 1
• Vitamin K antagonists (particularly warfarin) increase risk up to 11-fold 1, 2
• Other risk factors include inflammation (elevated C-reactive protein), hypoalbuminemia, and disturbances in calcium-phosphate metabolism 1, 7

Treatment Approach

First-Line Interventions

• Sodium thiosulfate is recommended as first-line therapy at dosages of 12.5–25 g/session, 2–3 times/week, for 3–6 months 2
• Discontinue medications that may contribute to calciphylaxis development, including:
  • Warfarin and other vitamin K antagonists 2, 5
  • Active vitamin D derivatives 5
  • Calcium supplements 5
  • Iron supplements 5
• Limit exposure to excess calcium and phosphate 2
• Aggressive wound care and pain management are essential components of treatment 6

Advanced Therapeutic Options

• Consider parathyroidectomy in patients with elevated PTH levels (>500 pg/mL) 2, 3
• Magnesium supplementation (magnesium oxide or hydroxide) may help prevent phosphate-induced vascular calcification 2
• SNF472 (Hexaphosphate Phytate) is an emerging therapy showing promise in clinical trials with improvements in wound healing and reduced hospitalizations 1, 2

Monitoring and Follow-up

• Regular monitoring of wound healing and inflammatory markers (C-reactive protein) is essential 2
• Ongoing vascular surveillance to assess for progression of calcification 2
• Multidisciplinary care involving nephrology, dermatology, wound care specialists, and palliative care is recommended for optimal management 4

Prognosis and Pitfalls

• Prognosis is poor, with high mortality rates even with appropriate treatment 3, 6
• Early recognition and intervention may improve outcomes 3
• Avoid aggressive phosphate-lowering therapy in patients without overt hyperphosphatemia 2
• Be aware that calciphylaxis can occur even with normal calcium and phosphate levels 2
• The disease is often underrecognized, leading to delayed diagnosis and treatment 7