Calciphylaxis

In the Rapid Review series, I briefly review the key points of a clinical review paper (which often extends to multiple papers because I can’t help myself). The topic this time: Calciphylaxis

The papers: 

Nigwekar SU, Thadhani R, Brandenburg VM. Calciphylaxis. N Engl J Med. 2018 May 3;378(18):1704-1714. doi: 10.1056/NEJMra1505292. PMID: 29719190

Chewcharat A, Nigwekar SU. Ten tips on how to deal with calciphylaxis patients. Clin Kidney J. 2025 Apr 9;18(4):sfaf098. doi: 10.1093/ckj/sfaf098. PMID: 40600068

Scola N, Kreuter A. Calciphylaxis: a severe complication of renal disease. CMAJ. 2011 Nov 8;183(16):1882. doi: 10.1503/cmaj.110046. Epub 2011 Aug 15. PMID: 21844101

What is it?

Calciphylaxis is a disease usually seen in patients with end-stage renal disease, characterized by painful ischemic necrotic skin lesions. The actual pathophysiology is not perfectly understood, but it involves microvascular calcification and thrombosis.

How common is it?

It is pretty rare. You will see about 5 cases per 1,000 hemodialysis patient-years.

How is it diagnosed?

Calciphylaxis is considered a clinical diagnosis. Although biopsies can be used to rule out alternative diagnoses, they should be used judiciously, as the biopsy has a high risk of poor healing and infection. 

The diagnosis should be considered when patients with end-stage kidney disease present with painful or non-healing skin lesions.

How is it treated?

Calciphylaxis is a chronic condition that will require a team to manage, including close involvement of the patient’s nephrologist, a wound care team, potentially plastic surgery and/or dermatology, and also possibly palliative care. It is not a condition we will be able to definitely manage in the emergency department, so a huge part of our job will be organizing this team.

Good wound care is essential to the management, focused on debridement of devitalized tissue to reduce infection risk and negative pressure wound dressings. Hyperbaric oxygen has been suggested, and makes some sense, without any clinical evidence of benefit. 

Supportive care and optimization of comorbidities are essential. Patients will require correction of metabolic derangements, especially calcium and phosphate. Optimizing nutrition might help.

In terms of acute management in the emergency department, a major focus is going to be analgesia. Pain is often severe, and opioids are commonly required. Looking for and treating secondary infections is also important. 

There are no specific therapies. Warfarin use is associated with a higher risk of calciphylaxis, and so it might be discontinued, although I would leave that decision to their nephrologist. Sodium thiosulfate is sometimes recommended. There is not currently any good evidence, but there are RCTs underway. (Eg NCT03150420)

This is a severely painful condition that occurs in patients with a life limiting medical diagnosis. Consider early involvement of palliative care.

What is the prognosis?

Patients with calciphylaxis have very significant morbidity and mortality. Mortality at 1 year exceeds 50%. The most common cause of death is sepsis, often originating from the wounds, emphasizing the importance of good wound care and infection control.