Calciphylaxis

Calciphylaxis is a syndrome of vascular calcification and skin necrosis. It is seen almost exclusively in patients with end stage renal disease. It results in chronic non-healing wounds and requires parathyroidectomy and hyperbaric therapy. Calciphylaxis is a rare but serious disease.

Calciphylaxis is one type of extraskeletal calcification. Similar extraskeletal calcifications are observed in some patients with hypercalcaemic states, including patients with milk alkali syndrome, sarcoidosis, primary hyperparathyroidism, and hypervitaminosis D.

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Symptoms

Calciphylaxis is characterised by

1. systemic medial calcification of the arteries, ie calcification of tunica media. Unlike other forms of vascular calcifications (eg, intimal, medial, valvular), calciphylaxis is characterised also by
2. small vessel mural calcification with or without endovascular fibrosis, extravascular calcification and vascular thrombosis, leading to tissue ischaemia (including skin ischaemia and, hence, skin necrosis).

Cause

The cause is not known. It does not seem to be an immune type reaction. In other words, calciphylaxis is not only a hypersensitivity reaction (= allergic reaction) leading to sudden local calcification. Clearly, additional factors are involved in calciphylaxis. It possibly could be described as calcific uraemic arteriolopathy.

Who is affected?

Calciphylaxis most commonly occurs in patients with end-stage renal disease who are on haemodialysis or who have recently received a renal transplant (= kidney transplant). Yet, calciphylaxis does not occur only in end-stage renal disease patients. It also has been reported in patients with breast cancer (treated with chemotherapy), liver cirrhosis (due to alcohol abuse), cholangiocarcinoma, Crohn's disease, rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) (including SLE patients with or without chronic renal disease).

Diagnosis

There is no diagnostic test for calciphylaxis. The diagnosis is a clinical one. The characteristic lesions are the ischaemic skin lesions (usually with areas of skin necrosis). The necrotic skin lesions (ie, the dying or already dead skin areas) typically appear as violaceous (dark bluish purple) lesions and/or completely black leathery lesions. They can be extensive. The suspected diagnosis can be confirmed by a skin biopsy. It shows arterial calcification and occlusion in the absence of vasculitis. Sometimes the bone scintigraphy can show increased tracer accumulation in the soft tissues.^[1]

Treatment

The optimal treatment is prevention. Rigorous and continuous control of phosphate and calcium balance most probably will avoid the metabolic changes which may lead to calciphylaxis.

There is no specific treatment. Of the treatments that exist, none is internationally recognised as the standard of care. An acceptable treatment could include:

• Dialysis (the number of sessions may be increased)
• Intensive wound care
• Adequate pain control
• Correction of the underlying plasma calcium and phosphorus abnormalities (lowering the Ca x P product below 55 mg2/dL2)
• Avoiding (further) local tissue trauma (including avoiding all subcutaneous injections, and all not-absolutely-necessary infusions and transfusions)
• Urgent parathyroidectomy: ???. The efficacy of this measure remains uncertain although calciphylaxis is associated with frank hyperparathyroidism. Urgent parathyroidectomy may benefit those patients who have uncontrollable plasma calcium and phosphorus concentrations despite dialysis. Also, cinacalcet can be used and may serve as an alternative to parathyroidectomy. The trade name of cinacalcet is Sensipar or Mimpara.
• Patients who receive kidney transplants also receive immunosuppression. Considering lowering the dose of or discontinuing the use of immunosuppressive drugs in renal transplant patients who continue to have persistent or progressive calciphylactic skin lesions can contribute to an acceptable treatment of calciphylaxis.

Response to treatment

Unfortunately, response to treatment is not guaranteed. Also, the necrotic skin areas may get infected, and this then may lead to sepsis (ie, infection of blood with bacteria; sepsis can be life-threatening) in some patients. Overall, the clinical prognosis remains poor.

Who to contact?

The correct person to ask questions about calciphylaxis is a nephrology fellow or a professor of nephrology.

Heart of stone

Severe forms of calciphylaxis may cause diastolic heart failure from cardiac calcification, called heart of stone.^[2]

References

1. ^ Clin J Am Soc Nephrol. 2006 Nov;1(6):1161-6. Epub 2006 Aug 30[1]
2. ^ [www.mayoclinicproceedings.com/pdf%2F8103%2F8103mi1.pdf Heart of Stone] - CINDY W. T OM, MD,ANDDEEPAKR. TALREJA, MD. Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, Minn