What is the investigation for calciphylaxis?

Diagnostic Investigation for Calciphylaxis

The diagnostic investigation for calciphylaxis should include C-reactive protein measurement as the primary laboratory test, imaging studies to detect vascular calcification, and careful consideration of skin biopsy due to its limitations and risks. 1, 2

Laboratory Testing

• C-reactive protein is the most helpful laboratory test for diagnosing calciphylaxis as it reflects the inflammatory component of the condition 1, 2
• Complete blood count with differential and other inflammatory markers should be measured to assess systemic inflammation 2
• Calcium, phosphate, alkaline phosphatase, 25-hydroxy-vitamin D, parathyroid hormone levels, and renal function tests should be included in the initial evaluation 1, 3
• Serum calcium and phosphate levels alone are not predictive of outcomes in calciphylaxis and cannot reliably guide therapy, as calciphylaxis can occur even with normal levels 2, 3
• Bone turnover markers may be considered but cannot reliably differentiate between high and low bone turnover in calciphylaxis patients 4

Imaging Studies

• Radiological imaging should be performed of the affected body part to detect vascular calcification 5, 6
• Multiple imaging modalities can detect vascular calcification:
  • Plain radiographs can identify calcification as fine as 0.1 to 0.3 mm 6
  • Mammography can detect calcification of 0.1 to 0.2 mm 6
  • Computed tomography can identify calcification of 0.1 to 0.2 mm 6
• Findings of superficial vascular calcifications on imaging studies are sensitive for the diagnosis of calciphylaxis 5

Skin Biopsy Considerations

• Skin biopsy has significant limitations with variable sensitivity (20-80%) and no established validated histologic diagnostic criteria 1, 2
• There is a risk of traumatizing vulnerable tissue, potentially triggering additional non-healing ulcers 2, 3
• When performed, histopathology typically shows calcification of small-caliber arteries or arterioles 6
• Inadequate sampling occurs in approximately 30% of biopsies 2

Bone Biopsy Evaluation

• Bone biopsy should be considered to determine the underlying bone disorder (high vs. low bone turnover), as this is essential for directed treatment 4
• Laboratory tests alone cannot reliably differentiate between high and low bone turnover in calciphylaxis patients 4
• Knowledge of bone status is crucial before initiating specific therapies that alter bone metabolism 4

Additional Assessments

• Evaluation for risk factors should include:
  • History of vitamin K antagonist use (increases risk up to 11-fold) 1, 3
  • Assessment for adynamic bone disease with low PTH levels 1
  • Evaluation for inflammation 1, 2
• Regular monitoring should include:
  • Wound healing assessment 3
  • Inflammatory markers (C-reactive protein) 2, 3
  • Vascular surveillance for calcification progression 3

Diagnostic Pitfalls to Avoid

• Relying solely on calcium and phosphate levels for diagnosis, as calciphylaxis can occur with normal levels 2, 3
• Performing skin biopsy without considering the risks of traumatizing vulnerable tissue 2
• Initiating treatment without understanding the underlying bone disorder 4
• Failing to evaluate for vitamin K antagonist use, which significantly increases risk 1, 3