Does calciphylaxis cause skin itching?

Does Calciphylaxis Cause Skin Itching?

Yes, calciphylaxis can cause significant skin itching (pruritus) as part of its clinical manifestation, particularly in the early stages before skin lesions become fully necrotic. 1

Understanding Calciphylaxis and Its Symptoms

Calciphylaxis is a rare and life-threatening complication primarily associated with chronic kidney disease-mineral and bone disorder (CKD-MBD), particularly in patients with end-stage renal disease. It involves the following pathological processes:

• Calcium-phosphate deposition in small blood vessels
• Medial calcification of arterioles
• Intimal fibrosis
• Thrombotic occlusion leading to tissue ischemia and necrosis

Clinical Presentation Sequence:

1. Early stage: Painful, pruritic skin with violaceous, mottled appearance
2. Progressive stage: Development of non-healing ulcers and necrotic tissue
3. Advanced stage: Gangrene, particularly of digits, with high risk of sepsis

Relationship Between Calciphylaxis and Pruritus

Pruritus in calciphylaxis occurs through several mechanisms:

• Direct tissue irritation from calcium-phosphate crystal deposition
• Inflammatory response to vascular calcification
• Uremic pruritus in patients with underlying kidney disease
• Secondary hyperparathyroidism which itself can cause pruritus

According to the KDIGO guidelines, severe pruritus is specifically mentioned as one of the clinical manifestations that can occur in calciphylaxis patients 1. In fact, severe intractable pruritus is listed as one of the indications for parathyroidectomy in patients with calciphylaxis and hyperparathyroidism 1.

Diagnostic Considerations

When evaluating a patient with unexplained pruritus and risk factors for calciphylaxis:

• Look for characteristic painful, violaceous skin lesions, often on lower extremities, buttocks, or abdomen
• Check calcium-phosphate product (values >70-80 mg/dl raise concern)
• Evaluate parathyroid hormone levels (often significantly elevated)
• Consider skin biopsy, though this carries risks:
  • 30% have inadequate sampling
  • Variable sensitivity (20-80%)
  • Risk of triggering additional non-healing ulcers 1

Management Approach for Calciphylaxis with Pruritus

1. Address underlying calcium-phosphate metabolism:

   • Normalize calcium and phosphate levels through intensive hemodialysis
   • Consider parathyroidectomy for severe hyperparathyroidism 1, 2

2. Wound care and pain management:

   • Diligent wound care and frequent debridement
   • Multimodal pain control

3. Specific treatments that may help with associated pruritus:

   • SNF472 (hexaphosphate phytate) has shown promise in the CALCIPHYX trial, with improvements in wound healing and reduction in pain 1
   • Avoid vitamin K antagonists which increase risk of calciphylaxis 1

Important Caveats and Pitfalls

• Don't mistake for simple uremic pruritus: While patients with kidney disease commonly experience pruritus, the presence of painful, violaceous skin lesions should raise suspicion for calciphylaxis
• Early recognition is crucial: Calciphylaxis carries high mortality (up to 93% in some series) 3
• Multidisciplinary approach is essential: Involvement of nephrology, dermatology, vascular surgery, endocrinology, and wound care specialists improves outcomes 4, 5
• Don't delay treatment: Early parathyroidectomy in appropriate patients can dramatically improve pain, pruritus and ulcer healing 2

Calciphylaxis-associated pruritus can be particularly distressing for patients and may precede the development of more severe skin manifestations. Recognizing this symptom early may contribute to faster diagnosis and improved outcomes in this high-mortality condition.