This document summarizes calciphylaxis, a rare and life-threatening condition where calcium deposits in small blood vessels of subcutaneous tissue and skin. It predominantly affects those with end-stage renal disease or kidney failure and can cause painful skin lesions. Risk factors include obesity, diabetes, long-term dialysis, and high calcium or phosphate levels. While prognosis is generally poor with most patients surviving less than a year, sodium thiosulfate may help resolve or improve lesions in some cases, though more research is still needed on effective treatments.

1. Calciphylaxis
(Calcific uremic arteriolopathy)
A Review – June 28, 2018
Matthew Fabiszak, D.O., PGY2

2. https://www.calciphylaxis.net/eu/what-is-calciphylaxis/

3. Introduction
• Rare, life-threatening syndrome of vascular calcification
• Occlusion of microvessels in the subcutaneous adipose tissue and dermis
which results in ischemic skin lesions
• Prognosis is generally poor (survival < 1 year)
• Typically affects ESRD patients
• But, can occur in the setting of AKI, early CKD, renal transplant, and even
normal renal function
• Ongoing pain, anorexia, insomnia, and depression compromise
quality of life
• Sepsis originating from the wounds is the most common cause of
death

4. Risk Factors
• Obesity
• Diabetes mellitus
• Female sex
• Dialysis for more than 2 years
• The use of warfarin, increases the risk of calciphylaxis by a factor of 3
to 13 (due to vitamin K antagonism)
• Elevations in phosphate and calcium levels increase the risk of
subsequent calciphylaxis in patients undergoing dialysis

5. Clinical Manifestations
• The pain of calciphylaxis is somatic and may precede skin lesions
• May fluctuate in intensity
• Frequently accompanied by tactile hyperesthesia
• Skin manifestations:
• Induration
• Plaques
• Nodules
• Livedo
• Purpura
• Lesions tend to have a central distribution in ESRD compared to those
without kidney disease

7. Pathogenesis

8. Diagnosis
• Elevations in serum calcium or phosphate levels are not specific
• Skin biopsy is the standard method for confirmation of clinically suspected
calciphylaxis
• The role in practice is debated, given the risk of provoking new, nonhealing ulcers
and infection
• A biopsy is not needed for a patient with ESRD and the classic presentation of a painful
necrotic ulcer covered with a black eschar.
• Biopsy should be strongly considered if a patient has early, atypical lesions or if
calciphylaxis is suspected in a patient without ESRD.
• A biopsy is contraindicated for acral, penile, or infected lesions.
• Although imaging studies (e.g., plain radiography, mammography, or
nuclear bone scanning) are not routinely recommended for the diagnosis,
they may support the diagnosis when a biopsy is inconclusive or
contraindicated.

9. Are there any approved pharmacotherapeutic
agents for the treatment of calciphylaxis?
• Currently there is no approved therapy for calciphylaxis
• Sodium thiosulfate - antioxidant and vasodilatory properties, also inhibits
adipocyte calcification, blocking the ability of adipocytes to induce calcification of
vascular smooth-muscle cells
• In a study involving 53 hemodialysis-dependent patients with calciphylaxis who were treated
with intravenous sodium thiosulfate (three times per week [with each dialysis session] for
approximately 3 months), calciphylaxis completely resolved in 26% of the patients, and 19%
had marked improvement in skin lesions.
• In another study, involving 27 patients being treated with dialysis, complete remission was
observed in 52% of the patients and partial remission in 19% after treatment with
intravenous sodium thiosulfate.
• Lack of a control group and the retrospective nature of the study preclude definitive conclusions
regarding the effectiveness of sodium thiosulfate.
• Although successful use of sodium thiosulfate for the treatment of calciphylaxis
was first reported more than a decade ago, only now are to ongoing trials
investigating its safety and efficacy.

10. References
• Images (slide 6): Article:
https://www.nejm.org/doi/full/10.1056/NEJMra1505292?utm_medi
um=referral&utm_source=r360#