Calciphylaxis

Calciphylaxis is a syndrome of vascular calcification, thrombosis and skin necrosis. It is seen almost exclusively in patients with Stage 5 chronic kidney disease. It results in chronic non-healing wounds and is usually fatal. 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.

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 a hypersensitivity reaction (i.e., allergic reaction) leading to sudden local calcification. Clearly, additional factors are involved in calciphylaxis. It is also known as calcific uraemic arteriolopathy; however, the disease is not limited to patients with kidney failure.

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 without end-stage renal disease, an entity called as non-uremic calciphylaxis by Nigwekar et al ^[1]. Non-uremic calciphylaxis has been observed in patients with primary hyperthyroidism, breast cancer (treated with chemotherapy), liver cirrhosis (due to alcohol abuse), cholangiocarcinoma, Crohn's disease, rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE).

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 supported 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.^[2] In certain patients, anti-nuclear antibody may play a role. ^[3]

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
• Clot-Dissolving Agents (Tissue Plasminogen Activator)
• Hyperbaric Oxygen
• Maggot Larval Debridement
• Adequate pain control
• Correction of the underlying plasma calcium and phosphorus abnormalities (lowering the Ca x P product below 55 mg2/dL2)
• Sodium Thiosulfate
• 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.

Whom to contact

The correct person to ask questions about calciphylaxis is a dermatologist (skin specialist) or a nephrologist (kidney specialist) who is familiar with the condition.

Heart of stone

Severe forms of calciphylaxis may cause diastolic heart failure from cardiac calcification, called heart of stone.^[4]

See also

• List of cutaneous conditions

External links

• Weenig RH (2008). "Pathogenesis of calciphylaxis: Hans Selye to nuclear factor kappa-B". J. Am. Acad. Dermatol. 58 (3): 458–71. doi:10.1016/j.jaad.2007.12.006. PMID 18206262. 
• Weenig RH, Sewell LD, Davis MD, McCarthy JT, Pittelkow MR (2007). "Calciphylaxis: natural history, risk factor analysis, and outcome". J. Am. Acad. Dermatol. 56 (4): 569–79. doi:10.1016/j.jaad.2006.08.065. PMID 17141359. 
• Li JZ, Huen W (2007). "Images in clinical medicine. Calciphylaxis with arterial calcification". N. Engl. J. Med. 357 (13): 1326. doi:10.1056/NEJMicm060859. PMID 17898102. http://content.nejm.org/cgi/content/full/357/13/1326. 
• DermNet NZ: Calciphylaxis
• Calciphylaxis Registry
• German Calciphylaxis Registry: www.calciphylaxie.de

References