What is calcifilaxis?

What is Calciphylaxis?

Calciphylaxis is a rare, life-threatening condition characterized by calcification, fibrosis, and thrombosis of small to medium-sized dermal vessels, resulting in profoundly painful ischemic skin lesions and tissue necrosis, occurring predominantly in patients with end-stage renal disease (ESRD). 1, 2

Pathophysiology

Calciphylaxis represents a severe manifestation of chronic kidney disease-mineral and bone disorder (CKD-MBD), where the bone fails to properly modulate calcium and phosphate levels, leading to metastatic calcification in soft tissues and vascular structures 2. The disease process involves:

• Vascular calcification of dermal vessels leading to ischemic skin ulceration 3
• Thrombosis of affected vessels causing tissue necrosis 1
• Inflammatory component reflected by elevated C-reactive protein levels 1, 2

Clinical Presentation

The hallmark features include:

• Painful, violaceous, mottled skin lesions that progress to necrotic ulcers, typically affecting the extremities 4, 5
• Severe pain that is disproportionate to the appearance of lesions and requires aggressive multimodal analgesia including opioids 1
• Non-healing ulcers with high risk of secondary infection and sepsis 1, 4
• Gangrene of digits that may require amputation 5

Major Risk Factors

Medication-Related (Modifiable)

• Vitamin K antagonists (warfarin) increase risk up to 11-fold, particularly in ESRD patients 2, 3, 6
• Active vitamin D, calcium supplements, and iron should be reconsidered in at-risk patients 6

Disease-Related

• End-stage renal disease on hemodialysis is the primary affected population 1, 4
• Elevated inflammatory markers (C-reactive protein) indicate increased risk 1, 2
• Adynamic bone disease with low PTH levels is a risk factor 2
• Secondary hyperparathyroidism with elevated PTH >500 pg/mL 3, 5

Diagnostic Approach

Laboratory Assessment

• C-reactive protein is the most helpful laboratory test reflecting inflammation and should be measured 2, 3
• Serum calcium and phosphate levels are NOT predictive of outcomes and cannot reliably guide therapy 3
• Calciphylaxis can occur even with normal calcium and phosphate levels 3

Imaging and Biopsy

• Skin biopsy is NOT recommended as standard practice due to variable sensitivity (20-80%) and significant risk of traumatizing vulnerable tissue, potentially triggering additional non-healing ulcers 1, 2, 3
• Radiographic imaging may reveal characteristic calcifications in medium and small blood vessels and soft tissues 5

Prognosis

The prognosis is generally poor with mortality rates up to 50% within 1 year, primarily due to sepsis from infected ulcers. 1, 2, 6 This devastating outcome emphasizes the critical importance of:

• Early recognition of characteristic skin lesions 3
• Prompt multidisciplinary intervention 1, 2
• Advanced care planning and shared decision-making given the high mortality rate 2

Common Pitfalls

• Do not delay treatment waiting for biopsy confirmation, as this risks further tissue damage 2, 3
• Avoid aggressive phosphate-lowering therapy in patients without overt hyperphosphatemia due to safety concerns and limited evidence of benefit 3
• Recognize that normal mineral levels do not exclude the diagnosis 3
• Patients on dialysis with calciphylaxis must avoid vitamin K antagonists for anticoagulation due to significantly increased risk; consider reduced-dose apixaban instead 2, 3