How to manage calcifilaxis of the penis with normal serum calcium levels?

Management of Penile Calciphylaxis with Normal Serum Calcium Levels

Penile calciphylaxis should be treated with sodium thiosulfate, aggressive wound care, and management of calcium-phosphate metabolism even when serum calcium levels are normal, as this rare condition has a mortality rate of up to 69% within 6 months.

Understanding Penile Calciphylaxis with Normal Calcium Levels

Calciphylaxis (calcific uremic arteriolopathy) is a rare and life-threatening condition characterized by vascular calcification, thrombosis, and skin necrosis. When it affects the penis, mortality rates are particularly high. Although calciphylaxis is typically associated with abnormal calcium-phosphate metabolism in end-stage renal disease, it can occur with normal serum calcium levels due to:

• Local tissue factors promoting calcification
• Calcium-phosphate product elevation (even with normal calcium)
• Deficiency of calcification inhibitors
• Underlying vascular disease

Diagnostic Approach

1. Clinical assessment:

   • Evaluate painful, necrotic lesions on the penis
   • Document progression and response to previous treatments
   • Look for signs of infection (purulence, foul odor)

2. Laboratory evaluation:

   • Calcium-phosphate product (target <55 mg²/dL²) 1
   • Serum phosphorus (target <6 mg/dL for CKD patients) 1
   • Intact PTH levels (target 150-300 pg/mL for dialysis patients) 2
   • 25-hydroxyvitamin D levels (target >30 ng/ml) 3

3. Imaging:

   • CT scan to detect vascular calcification
   • Consider 99Tc-Sestamibi scan if hyperparathyroidism is suspected 3

4. Tissue diagnosis:

   • Skin biopsy showing medial calcification of small and medium arteries
   • Note: Biopsy carries risk of poor wound healing and should be performed only if diagnosis is uncertain 3, 4

Treatment Algorithm

Immediate Interventions:

1. Sodium thiosulfate therapy:

   • Intravenous administration 25g three times weekly during dialysis 1
   • First-line therapy shown to successfully treat penile calciphylaxis 1

2. Wound management:

   • Aggressive local wound care with debridement of necrotic tissue
   • Appropriate antimicrobial therapy for infected wounds
   • Pain management

3. Calcium-phosphate metabolism optimization:

   • Maintain serum phosphorus <6 mg/dL 1
   • Keep calcium-phosphate product <55 mg²/dL² 1
   • Use non-calcium-based phosphate binders if phosphate is elevated

Additional Therapeutic Measures:

1. Dialysis optimization:

   • Intensify dialysis regimen to improve clearance
   • Consider low calcium dialysate if calcium levels rise

2. Surgical intervention:

   • For limited lesions: conservative management with local wound care
   • For extensive lesions or progressive disease: partial or complete penectomy may be necessary 1, 4

3. Vitamin K supplementation:

   • Consider vitamin K supplementation as deficiency may contribute to vascular calcification 3

4. SNF472 (hexaphosphate phytate):

   • Consider in refractory cases as it has shown promise in calciphylaxis treatment 3
   • Demonstrated improvements in wound healing and reduced mortality in clinical trials

Monitoring and Follow-up

• Weekly assessment of wound healing
• Regular monitoring of calcium, phosphorus, and PTH levels
• Evaluate calcium-phosphate product with each laboratory check
• Monitor for signs of systemic infection

Special Considerations

• Even with normal calcium levels, the calcium-phosphate product may be elevated due to hyperphosphatemia 1
• Vitamin D analogs should be used cautiously as they may increase calcium and phosphorus levels 3
• Avoid vitamin K antagonists (warfarin) as they increase the risk of calciphylaxis by up to 11-fold 3
• Consider parathyroidectomy only if PTH levels are significantly elevated (>500 pg/mL) 3

Prognosis and Pitfalls

• Penile calciphylaxis carries a mortality rate of approximately 69% within 6 months 1
• Early diagnosis and aggressive multimodal treatment are essential for improved outcomes
• Failure to address calcium-phosphate metabolism, even with normal calcium levels, may lead to treatment failure
• Wound infection is a common complication and requires vigilant monitoring and prompt intervention