The rare calciphylaxis is a pronounced calcification of small and very small skin arteries (arterioles). The disease is usually caused by severe kidney disease and a secondary overproduction of parathyroid hormone in the parathyroid glands caused by nephropathy. Untreated calciphylaxis has a poor prognosis and, in an advanced stage, is usually accompanied by painful, ischemic-related bluish-black necrotic skin areas and ulcerations.
What is calciphylaxis?
The rare calciphylaxis, also known as uremic calcifying arteriolopathy (UCA), affects small and very small arteries and arterioles on certain skin regions and sometimes also on certain organs. The formation and precipitation of calcium phosphate crystals is usually the result of severe kidney disease with renal insufficiency and the resulting hyperparathyroidism.
The crystals settle preferably on the media, the middle wall of the arterioles, and lead to obstruction of the vessels, so that there is a marked deficiency in the supply of oxygen and nutrients in the affected areas of the skin. It formed skin ulcers, inflammation and painful necrosis, which is manifested by bluish-black discoloration.
Calciphylaxis is a typical secondary disease that arises as a result of an underlying disease. In this case, the underlying disease is usually severe nephropathy with clear signs of renal insufficiency. It leads to impaired calcium and phosphate excretion.
The kidneys can no longer convert sufficient amounts of calcidiol, the precursor of vitamin D, into calcitriol, the active form of vitamin D. There is a vitamin D deficiency, which leads to an unchecked synthesis of the parathyroid hormone by the parathyroid glands. The high concentration of parathyroid hormone causes a pathologically high phosphate concentration (hyperphosphataemia) with a simultaneous very low calcium concentration (hypocalcemia) in the blood serum.
The increased amounts of phosphate come from the bones, which – comparable to osteoporosis – increasingly demineralize. The high phosphate concentration in the blood causes a slight acidification (acidosis), which in turn favors the formation and precipitation of calcium phosphate salts in the walls of the arterioles and in the subcutaneous fatty tissue.
In rare cases, calciphylaxis can also result from an overproduction of parathyroid hormone that is not caused by renal insufficiency or from an extreme overdose of vitamin D. Cases have also been reported in which drugs containing warfarin have caused calciphylaxis as an undesirable side effect. Medicines containing warfarin act as vitamin K antagonists and serve, among other things, as anticoagulants.
Symptoms, ailments & signs
The first signs of the disease are rather unspecific. For example, there is severe itching in the affected areas of the skin. As the disease progresses, bluish to bluish-black discolored necrotic areas develop in the insufficiently supplied skin areas, which can lead to severe pain. If necrotic areas form on the fingers, they can also mummify, i.e. dry out, without the dead skin areas loosening. In most cases, calciphylaxis is accompanied by very painful ulcers.
Diagnosis & course
If calciphylaxis is suspected, the diagnosis consists initially in the detection of calcifications in the arterioles and small arteries in the affected skin areas. Evidence can usually be provided radiologically. In cases of doubt, the diagnosis of ischemic processes can be supported by a histological examination. In terms of laboratory chemistry, among other things, the calcium and phosphate values as well as the parathyroid hormone concentration in the serum are conspicuous.
A second direction of diagnosis serves to identify and prove severe nephropathy with renal insufficiency. Because some symptoms of calciphylaxis resemble those of ischemic disease for other reasons, it is important to distinguish it from other diseases in a differential diagnosis. For example, diseases such as peripheral arterial occlusive disease (intermittent claudication) should be excluded.
Possible vascular damage from diabetes mellitus and vascular inflammation due to an autoimmune disease must also be ruled out beforehand as a differential diagnosis. If the main causative factor, hyperparathyroidism, is not treated, the disease has a poor prognosis. The poor prognosis is exacerbated by bacterial superinfections that are frequently observed and which can be resistant to treatment due to ischemia.
In most cases, calciphylaxis is diagnosed late, preventing early treatment of the disease. This is due to the fact that calciphylaxis does not have any particular specific symptoms that can be directly linked to this disease. The affected person suffers from itching, which can develop in different parts of the body.
There is also severe pain in these areas. As a rule, it is the fingers in particular that are affected, so that calciphylaxis leads to considerable restrictions in everyday life. Ulcers form on the fingers, which also reduce the patient’s aesthetics. In addition to these complaints, it is not uncommon for autoimmune diseases that lead to severe infections to occur.
The treatment of calciphylaxis is always causal and aims above all to eliminate the underlying disease. However, it cannot be universally predicted whether a complete cure of the underlying disease is possible. In some cases, amputation of the affected areas is therefore necessary to completely relieve the symptoms. Whether calciphylaxis reduces life expectancy usually also depends on the underlying disease.
When should you go to the doctor?
If severe itching and other symptoms of calciphylaxis are noticed, a doctor is recommended. If the typical bluish-black skin changes are noticed, this must be clarified immediately. Severe pain, drying out and dead skin areas indicate that the calcification is already well advanced – in this case the nearest hospital should be visited immediately to have the complaints clarified. Calcyphylaxis can be reliably detected using the known diagnostic methods.
Targeted treatment is then possible. Since treatment that is too late sometimes only involves amputation of the affected limb, the disease must be diagnosed as early as possible and then treated immediately. Patients with existing nephropathy or hormonal disorders are particularly at risk. Even after taking certain medications containing warfarin, calcification of the arteries seems to occur again and again. Anyone who belongs to these risk groups should consult their family doctor at the first signs of calcyphylaxis. Other contact persons are specialists in arteriosclerosis and necrosis as well as the medical emergency service.
Treatment & Therapy
One of the most important therapeutic measures is to overcome hyperparathyroidism. Parathyroid hormone levels must be returned to levels within the normal range in order to eliminate the main causative factor of the disease. Calcium-free phosphate binders are suitable for rapidly lowering the calcium and phosphate concentration. In some cases – especially with dialysis patients – the blood values can be reduced through dialysis.
If drug treatments do not show lasting success, partial removal of the four parathyroid glands, which are responsible for the homeostatic regulation of the calcium balance, can be considered in exceptional cases. This is particularly indicated when the parathyroid glands, which are usually located near the two poles of the thyroid gland, are greatly enlarged and no longer react sufficiently strongly to homeostatic impulses to reduce parathyroid hormone secretion.
In addition to the therapeutic measures to normalize the calcium and phosphate balance, treatments of the affected skin areas are usually necessary. Because of the ischemia, there is a risk of bacterial infections which are difficult to treat because, for example, systemically acting antibiotics have only a limited effect because of the ischemia.
In severe cases, all that remains is surgical removal of the affected tissue. In extreme cases, this may require amputation of a limb.
Outlook & forecast
The prognosis for calciphylaxis is very poor. The disease is fraught with serious complications. In addition, the life expectancy of the patient is significantly reduced. The mortality rate from this disease is extremely high and is 80%.
The bad outlook is due to the fact that various internal organs are involved in the disease. Their functionality is severely restricted by calciphylaxis. Just under half of all patients survive the first year after diagnosis. The dialysis patients suffer in a large number of cases septic as well as cardiovascular complications resulting in death. Sick people are exposed to an increased risk of bacterial superinfection, which the organism can usually not cope with. By a multiple organ failure occurs on the death of the patient.
If calciphylaxis is detected early, there is an opportunity to lower the calcium level in the body. This prevents the progress of calcification and reduces the risk factors for a deterioration in the state of health. If the doctors manage to stop the overproduction of parathyroid hormone at the same time, the chances of relief from the symptoms improve.
The chances of recovery still depend on the extent of the underlying disease. With chronic kidney failure, the prognosis worsens considerably. In addition, the body can no longer cope with a wound infection due to the weakened health condition.
Because calciphylaxis is a secondary disease that is the result of one or more underlying diseases, preventive measures must always aim to avoid the underlying diseases. Keeping the kidneys healthy can therefore be seen as the most important preventive measure.
Above all, it must be ensured that the kidneys can activate enough vitamin D by converting calcidiol, the inactive precursor of vitamin D, into calcitriol, the bioactive vitamin D. Since dialysis patients and people suffering from diabetes mellitus are at greater risk, it is advisable for them to pay more attention to the first possible symptoms.
You can do that yourself
Calciphylaxis impairs the functioning of the kidneys. Vitamin D deficiency inevitably occurs in the body. Self-help can only be carried out with a lot of discipline and should only take place with a therapy plan tailored to everyday life.
The symptom also disturbs the parathyroid glands, releasing a high concentration of phosphate while reducing calcium absorption. Therefore, it is essential to maintain a balanced, low-salt vitamin D and calcium-containing diet. Since the autoimmune system is affected at the same time and the susceptibility to infection increases, a low-fat and vitamin-rich diet is decisive. In addition, at least three liters should be drunk and bad habits such as smoking, alcohol and drug abuse should be abandoned.
As long as the kidneys are still doing their work independently, those affected should carefully follow the advice on self-help in order to postpone an impending dialysis. This applies even more to diabetes mellitus patients suffering from calciphylaxis. In the worst case, you are threatened with death of isolated skin and joint areas, resulting in amputation. The physical changes and pain often lead to depression that can hardly be dealt with in self-help. Those affected should not be afraid to seek psychological support.