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Calciphylaxis: Causes, Symptoms and Treatment

Calciphylaxis is a rare, life-threatening condition involving calcium deposits in small blood vessels, leading to painful skin wounds and tissue death.

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Things worth knowing about "Calciphylaxis"

Calciphylaxis is a rare, life-threatening condition involving calcium deposits in small blood vessels, leading to painful skin wounds and tissue death.

What is Calciphylaxis?

Calciphylaxis is a rare and serious medical condition in which calcium deposits form in the walls of small blood vessels (arterioles) in the skin and subcutaneous fat tissue. These deposits cause narrowing or complete blockage of the vessels, depriving surrounding tissue of oxygen. As a result, patients develop intensely painful, poorly healing wounds and tissue necrosis (tissue death), most commonly affecting the legs, abdomen, or buttocks. The condition is also referred to as calcific uremic arteriolopathy, reflecting its close association with kidney failure.

Causes and Risk Factors

The exact cause of calciphylaxis is not yet fully understood. The most important risk factors include:

Chronic kidney disease and dialysis dependency: The majority of affected individuals have advanced kidney failure.
Disturbances in calcium-phosphate metabolism: Elevated blood levels of calcium and phosphate promote deposits in vessel walls.
Secondary hyperparathyroidism: Overactivity of the parathyroid glands increases calcium release into the blood.
Obesity
Diabetes mellitus
Certain medications: Including vitamin K antagonists (e.g. warfarin), systemic corticosteroids, and high-dose calcium or vitamin D supplements.
Female sex

Symptoms

Typical signs of calciphylaxis include:

Severe, intense pain in the skin, often preceding visible skin changes
Bluish, net-like skin discoloration (livedo racemosa)
Hardened nodules beneath the skin
Open, non-healing wounds (ulcers) with black or yellowish tissue
Tissue necrosis, commonly affecting the legs, abdomen, breasts, or buttocks

Diagnosis

Calciphylaxis is often a clinical diagnosis, supported by the following investigations:

Skin biopsy: Tissue sample showing calcium deposits in vessel walls and signs of vascular occlusion under the microscope
Blood tests: Measurement of calcium, phosphate, parathyroid hormone (PTH), albumin, kidney function markers, and coagulation parameters
Imaging: X-rays can reveal vascular calcifications; bone scintigraphy may detect soft tissue deposits

Treatment

Treatment of calciphylaxis is complex and requires an interdisciplinary team including nephrologists, dermatologists, wound care specialists, and other experts. Approaches include:

Conservative and Medical Therapy

Sodium thiosulfate: A medication that increases the solubility of calcium deposits and improves circulation; typically administered intravenously during dialysis sessions.
Adjustment of dialysis: Intensifying dialysis treatment to better control calcium-phosphate balance.
Discontinuation or substitution of medications: Vitamin K antagonists are replaced with alternative anticoagulants where possible.
Vitamin K supplementation: May help inhibit vascular calcification.
Pain management: Effective pain control is a central component of therapy.

Wound Care

Regular professional wound management to prevent infection
Surgical debridement (removal of dead tissue) in severe cases
Hyperbaric oxygen therapy (treatment in a pressurized chamber with pure oxygen) as a supplementary measure

Surgical Therapy

In cases of severe secondary hyperparathyroidism, parathyroidectomy (surgical removal of the parathyroid glands) may be beneficial.

Prognosis

Calciphylaxis is associated with a high mortality rate. Many patients die within months of diagnosis, often due to severe infections (sepsis) arising from skin wounds. However, early diagnosis and consistent, comprehensive treatment can improve outcomes.

References

Nigwekar SU, Thadhani R, Brandenburg VM. Calciphylaxis. New England Journal of Medicine. 2018;378(18):1704-1714.
Kidney Disease: Improving Global Outcomes (KDIGO). KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease'Mineral and Bone Disorder (CKD-MBD). Kidney International Supplements. 2017;7(1):1-59.
Brandenburg VM, Evenepoel P, Floege J, et al. Lack of evidence does not justify neglect: how can we address unmet medical needs in calciphylaxis? Nephrology Dialysis Transplantation. 2016;31(8):1211-1219.

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