Calciphylaxis
Encyclopedia
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.
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.
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. In certain patients, anti-nuclear antibody may play a role.
There is no specific treatment. Of the treatments that exist, none is internationally recognised as the standard of care. An acceptable treatment could include:
(ie, infection of blood with bacteria; sepsis can be life-threatening) in some patients. Overall, the clinical prognosis remains poor.
Severe forms of calciphylaxis may cause diastolic heart failure from cardiac calcification, called heart of stone.
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
necrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
. 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
Calcification
Calcification is the process in which calcium salts build up in soft tissue, causing it to harden. Calcifications may be classified on whether there is mineral balance or not, and the location of the calcification.-Causes:...
. Similar extraskeletal calcifications are observed in some patients with hypercalcaemic states, including patients with milk alkali syndrome, sarcoidosis, primary hyperparathyroidism
Hyperparathyroidism
Hyperparathyroidism is overactivity of the parathyroid glands resulting in excess production of parathyroid hormone . The parathyroid hormone regulates calcium and phosphate levels and helps to maintain these levels...
, and hypervitaminosis D.
Symptoms
Calciphylaxis is characterised by- systemic medial calcification of the arteries, ie calcification of tunica mediaTunica mediaThe tunica media is the middle layer of an artery or vein.-Artery:It is made up of smooth muscle cells and elastic tissue...
. Unlike other forms of vascular calcifications (eg, intimal, medial, valvular), calciphylaxis is characterised also by - small vessel mural calcification with or without endovascular fibrosis, extravascular calcification and vascular thrombosis, leading to tissue ischaemia (including skin ischaemia and, hence, skin necrosisNecrosisNecrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
).
Cause
The cause is not known. It does not seem to be an immune type reaction. In other words, calciphylaxis is not a hypersensitivityHypersensitivity
Hypersensitivity refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. These reactions may be damaging, uncomfortable, or occasionally fatal. Hypersensitivity reactions require a pre-sensitized state of the host. The four-group classification...
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 . 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. In certain patients, anti-nuclear antibody may play a role.
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:
- DialysisDialysisIn medicine, dialysis is a process for removing waste and excess water from the blood, and is primarily used to provide an artificial replacement for lost kidney function in people with renal failure...
(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, cinacalcetCinacalcetCinacalcet is a drug that acts as a calcimimetic by allosteric activation of the calcium-sensing receptor that is expressed in various human organ tissues. It is sold by Amgen under the trade name Sensipar in North America and Australia and as Mimpara in Europe...
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 immunosuppressionImmunosuppressionImmunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...
. 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 sepsisSepsis
Sepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...
(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.
External links
- DermNet NZ: Calciphylaxis
- Calciphylaxis Registry
- German Calciphylaxis Registry: www.calciphylaxie.de