Last updated: December 2023
Also known as… Calcific Uraemic Arteriolopathy
What is calciphylaxis?
Calciphylaxis is a rare and serious disorder, characterised by ischemia and necrosis of the skin and fatty tissue.
Who gets calciphylaxis?
Calciphylaxis is usually seen in individuals on treatment for severe kidney disease – typically on dialysis for end stage renal failure (ESRF), and more often in those on peritoneal dialysis over haemodialysis.
However, calciphylaxis is not exclusive to ESRF individuals on dialysis, and can also occur in kidney transplant recipients and rarely in individuals with normal kidney function.
What causes calciphylaxis?
While the cause of calciphylaxis remains unknown, it is thought to be due to reduced blood flow in the small arteries (arterioles), due to abnormal calcium deposition (calcification) in a circumferential fashion, most commonly in the intima and internal elastic lamina (the two innermost layers of the arteriole). Other causes that may trigger the development of calciphylaxis, include:
- Medications, such as warfarin, iron, corticosteroids, vitamin D and calcium supplements
- Chronic Inflammatory Conditions, such as Crohn’s Disease, connective tissue disorders, diabetes, obesity, malignancy and liver cirrhosis
- Clotting Disorders, such as hypercoagulable states, protein C and S deficiency, antiphospholipid syndrome
What does calciphylaxis look like?
The appearance of calciphylaxis depends on the time of presentation. Areas most affected are the lower limbs and abdomen, especially fatty areas such as the thighs and buttocks.
In the early stages, calciphylaxis usually starts as dusky purple-pink, painful (tender), plaque like lesions under the skin (subcutaneous nodules), representing areas of diminished blood supply (ischemia). An early cardinal sign is pain out of proportion to clinical findings. These early subcutaneous plaques and nodules can progress to deeper concavities (ulcers) with black overlying tissue (dry gangrene). In advanced stages, dead tissue (necrotic eschar) from inadequate blood supply (infarction) predominates.
Early changes can give a mottled appearance on the skin similar to another condition known as livedo reticularis.
Calciphylaxis can also involve the upper extremities, with lesions on the fingers occurring in some individuals.
How is calciphylaxis diagnosed?
Calciphylaxis is usually diagnosed clinically. A skin biopsy – deep telescoping punch or excisional biopsy to capture the subcutis – from the lesion margin may aid or confirm diagnosis.
There are no specific blood tests for calciphylaxis. In some individuals, increases in phosphate, calcium, calcium x phosphate product or parathyroid hormone (PTH) levels may be observed, although these are not always present.
An X-ray of the affected body area may show evidence of vascular calcification within the skin. Bone scintigraphy and non-contrast CT may also identify areas dense in vascular calcification.
How is calciphylaxis treated?
Treatment options will vary depending on the individual and their needs. It will often involve a multi-faceted approach to target the cause and improve outcomes.
Expert wound care, monitoring for secondary infection, optimal pain relief (analgesia), and meticulous attention to minimise repetitive tissue trauma is universal. Cessation of medication predisposing to calciphylaxis is recommended, if possible.
Intravenous sodium thiosulfate may be used (this helps to remove the deposited calcium). Individuals with renal failure may need some adjustments in their medication to control abnormal calcium and/or phosphate levels.
In some individuals, oxygen therapy (hyperbaric oxygen or high-flow oxygen therapy) as part of a multi-faceted approach may demonstrate benefit.
Some individuals may also benefit from surgical removal of any damaged tissue.
What is the likely outcome of calciphylaxis?
The mortality rate of patients with calciphylaxis and end stage renal failure is reported to be between 60%-80%, and often a result of secondary infection and sepsis.1 Combined distal and proximal involvement, along with penile involvement, portends a worse prognosis.