From the Guidelines
Diagnosing calciphylaxis is a complex process that cannot rely solely on skin biopsy due to its low sensitivity and specificity, and instead, a comprehensive clinical assessment is necessary. According to the most recent study published in 2025 in the journal Kidney International 1, skin biopsy is unable to reliably diagnose calciphylaxis due to the lack of established features or validated histologic diagnostic criteria, and the use of standard staining methods alone is not specific. Additionally, skin biopsy can traumatize vulnerable tissue and may trigger additional nonhealing ulcers.
The diagnosis of calciphylaxis should involve recognizing characteristic painful, violaceous, netlike skin lesions that often progress to necrotic ulcers, typically on adipose-rich areas like the abdomen, thighs, and buttocks. Laboratory tests, such as calcium, phosphorus, parathyroid hormone, and albumin levels, can help assess mineral metabolism abnormalities, but serum calcium and phosphate levels are not predictive of outcomes and cannot be used for guiding therapy 1.
Some key points to consider when diagnosing calciphylaxis include:
- Limiting exposure to excess calcium and phosphate is regarded as important in managing this severe disorder 1
- Calcification inducers, such as high doses of active vitamin D derivatives, or lack of inhibitors, such as vitamin K antagonism or deficiency, inflammation, have been identified as potential risk factors for the development of calciphylaxis 1
- Use of vitamin K antagonists for anticoagulation in patients undergoing dialysis is associated with an up to 11-fold increased risk of developing calciphylaxis 1
- Maintaining a high index of suspicion, particularly in patients with end-stage renal disease or other risk factors like obesity, female gender, or warfarin use, is crucial for early diagnosis and treatment.
Given the high mortality rates associated with calciphylaxis, primarily due to sepsis from infected wounds, early diagnosis and treatment are essential. While awaiting further diagnostic results, initiating treatment may be necessary in highly suspicious cases, including wound care, pain management, normalization of calcium-phosphate metabolism, and sodium thiosulfate therapy 1.
From the Research
Diagnosis of Calciphylaxis
The diagnosis of calciphylaxis can be complicated due to the lack of conclusive serologic, radiographic, or visual signs 2. However, several methods can be used to diagnose calciphylaxis, including:
- Skin biopsy: A biopsy of the calciphylaxis ulcer can reveal calcium deposits lining the vascular intima 3
- Radiographic features: Tissue calcification may also be seen on plain radiographs 3
- Clinical features: Painful skin ulceration and necrosis are characteristic of calciphylaxis 4, 5
- Risk factors: Identifying risk factors such as hyperparathyroidism, chronic renal impairment, and disturbances in calcium-phosphate metabolism can raise suspicion of calciphylaxis 3, 4, 5
Diagnostic Criteria
Diagnostic criteria for calciphylaxis have been proposed to facilitate recognition of the disease 5. These criteria include:
- Painful skin ulceration
- Necrosis
- Risk factors such as hyperparathyroidism, chronic renal impairment, and disturbances in calcium-phosphate metabolism
Limitations of Diagnosis
It is essential to note that negative results from skin biopsy and radiographic features do not necessarily exclude the diagnosis of calciphylaxis 4. A high index of suspicion and careful evaluation of clinical features and risk factors are necessary to diagnose calciphylaxis accurately.