Rare calciphylaxis is a marked calcification of small and minute skin arteries (arterioles). The condition is usually caused by severe kidney disease and secondary nephropathy-induced overproduction of parathyroid hormone in the parathyroid glands. Untreated calciphylaxis has a poor prognosis and is usually accompanied by painful ischemic bluish-black necrotic skin patches and ulceration in advanced stages.
What is calciphylaxis?
Rare calciphylaxis, also known by the purposeful name uremic calcifying arteriolopathy (UCA), affects small and minute arteries and arterioles in certain skin regions and sometimes in certain organs. The formation and precipitation of calcium–phosphate crystals usually occurs due to severe kidney disease with renal insufficiency and hyperparathyroidism caused by this disease. The crystals are deposited preferably on the media, the middle wall of the arterioles, and lead to obstructions of the vessels, so that there is a marked reduction in the supply of oxygen and nutrients in the affected areas of the skin. Skin ulcers, inflammation, and painful necrosis form, which are noticeable by bluish-black discoloration.
Causes
Calciphylaxis represents a typical secondary disease that develops as a consequence 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 kidney can no longer convert calcidiol, the precursor of vitamin D, into calcitriol, the active form of vitamin D, to a sufficient extent. This results in vitamin D deficiency, which leads to unrestrained synthesis of parathyroid hormone by the parathyroid glands. The high concentration of parathyroid hormone causes a pathologically high concentration of phosphate (hyperphosphatemia) with a simultaneously very low concentration of calcium (hypocalcemia) in the blood serum. The increased amounts of phosphate originate from the bones, which become increasingly demineralized as a result – comparable to osteoporosis. The high phosphate concentration in the blood causes a slight acidification (acidosis), which in turn promotes 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 overproduction of parathyroid hormone not caused by renal insufficiency, or from extreme overdose of vitamin D. Cases have also been reported in which warfarin-containing drugs have caused calciphylaxis as an adverse side effect. Drugs containing warfarin act as vitamin K antagonists and serve as anticoagulants, among other functions.
Symptoms, complaints, and signs
The first signs of the disease are rather nonspecific. For example, there is severe itching in affected areas of the skin. As the disease progresses, bluish to bluish-black necrotic areas develop in the deficient skin areas, which can lead to severe pain. If necrotic areas form on the fingers, they may also mummify, i.e. dry up, without the dead skin areas becoming detached. In most cases, calciphylaxis is accompanied by very painful ulcers.
Diagnosis and course
When calciphylaxis is suspected, the diagnosis consists first of all in the detection of calcifications of the arterioles and small arteries in the affected skin areas. The evidence can usually be obtained radiologically. In doubtful cases, the diagnosis of ischemic processes can be substantiated by histological examination. Laboratory findings include conspicuous calcium and phosphate levels and serum parathyroid hormone concentrations. A second diagnostic direction is used to detect and demonstrate severe nephropathy with renal insufficiency. Because some symptoms of calciphylaxis also resemble those of ischemic disease from other causes, differential diagnostic differentiation from other diseases is important. For example, conditions such as peripheral arterial occlusive disease (shin disease) should be able to be ruled out. Possible vascular damage due to diabetes mellitus and vascular inflammation due to an autoimmune disease should also be excluded beforehand as differential diagnoses.If the main causative factor, hyperparathyroidism is not treated, the disease is associated with a poor prognosis. The poor prognosis is exacerbated by frequently observed bacterial superinfections, which may prove resistant to treatment because of ischemia.
Complications
In most cases, calciphylaxis is diagnosed at a late stage, so early treatment of this disease is not possible. This occurs from the fact that in calciphylaxis there are no particular specific symptoms that could be directly associated with this disease. The affected person suffers from itching, which can develop in different parts of the body. Furthermore, severe pain also occurs in these areas. As a rule, it is mainly the fingers that are affected, so that calciphylaxis leads to considerable restrictions in everyday life. Ulcers form on the fingers, which also reduce the aesthetics of the patient. It is not uncommon for autoimmune diseases to occur in addition to these complaints, leading to severe infections. The treatment of calciphylaxis is always causal, aiming first of all at the elimination of the underlying disease. However, it cannot be universally predicted whether a complete cure of the underlying disease is possible. In some cases, therefore, amputation of the affected areas is necessary to completely alleviate the symptoms. Whether life expectancy is reduced by calciphylaxis also usually depends on the underlying disease.
When should you see a doctor?
If severe itching and other symptoms of calciphylaxis are noticed, a visit to the doctor is recommended. If the typical bluish-black skin changes are noticed, this must be clarified immediately. Severe pain, dryness and dead skin areas indicate that the calcification is already far advanced – in this case, the nearest hospital should be visited immediately to have the symptoms clarified. Calcyphylaxis can be reliably detected using the known diagnostic methods. Subsequently, a targeted treatment is possible. Since amputation of the affected limb is sometimes the only option if treatment is delayed, the disease must be diagnosed as early as possible and then treated promptly. Patients with an existing nephropathy or a hormone disorder are particularly at risk. Calcification of the arteries also seems to occur repeatedly after taking certain drugs containing warfarin. Anyone belonging to these risk groups should consult their family doctor at the first signs of calcyphylaxis. Other contacts include specialists in arteriosclerosis and necrosis and emergency medical services.
Treatment and therapy
One of the most important therapeutic measures is to overcome hyperparathyroidism. The parathyroid hormone concentration must be restored to a level within the normal range to eliminate the main trigger of the disease. Calcium-free phosphate binders are suitable for rapid reduction of calcium and phosphate concentrations. In some cases – especially in dialysis patients – reduction of blood levels can be achieved via dialysis. If drug treatments do not show sustained success, partial removal of the four parathyroid glands responsible for homeostatic regulation of calcium balance may 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 respond sufficiently strongly to homeostatic stimuli to reduce parathyroid hormone secretion. In addition to therapeutic measures to normalize calcium and phosphate balance, treatments of the affected skin areas are usually necessary. Due to the ischemia, there is a risk of bacterial infections, which are difficult to treat because, for example, systemically acting antibiotics have only limited effect due to the ischemia. In severe cases, the only option is surgical removal of the affected tissue. In extreme cases, this may require amputation of a limb.
Outlook and prognosis
The prognosis of calciphylaxis is very unfavorable. The disease is associated with serious complications. In addition, the patient’s life expectancy is significantly reduced. Mortality is markedly high in this disease, reaching 80%.The poor outlook is due to the fact that various internal organs are involved in the disease. Their ability to function is severely limited by calciphylaxis. Only just under half of all patients survive the first year after diagnosis. In a large number of cases, patients requiring dialysis suffer septic as well as cardiovascular complications resulting in death. Sufferers are at increased risk of bacterial superinfection, which the organism is usually unable to cope with. Multiple organ failure results in the patient’s demise. If calciphylaxis is detected at an early stage, it is possible to lower the calcium level in the body. This prevents the progress of calcification and reduces the risk factors for deterioration of the health condition. If the doctors manage to stop the overproduction of parathyroid hormone at the same time, the prospects of alleviating the symptoms improve. Nevertheless, the prospects of cure depend on the extent of the underlying disease present. In the case of chronic renal insufficiency, the prognosis worsens considerably. In addition, the body can no longer cope with a wound infection due to the weakened state of health.
Prevention
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. Therefore, keeping the kidneys healthy can be considered the most important preventive measure. Above all, it must be ensured that the kidneys can activate sufficient vitamin D by converting calcidiol, the inactive precursor of vitamin D, into calcitriol, the bioactive vitamin D. Since dialysis patients and those suffering from diabetes mellitus are at increased risk, it is recommended that they pay increased attention to initial possible symptoms.
What you can do yourself
Calciphylaxis affects the kidney in its function. Inevitably, vitamin D deficiency occurs in the body. Self-help is feasible only with a lot of discipline and should be done only with a therapy plan tailored to everyday life. The symptom also interferes with the parathyroid glands, causing a high concentration of phosphate to be released while calcium absorption is curbed. Therefore, it is imperative to maintain a low-salt balanced diet containing vitamin D and calcium. Since the autoimmune system is affected in parallel and the susceptibility to infections increases, the 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 discontinued. As long as the kidneys are still doing their work independently, patients should carefully follow the advice on how to help themselves in order to delay the threat of dialysis. This is particularly true for diabetes mellitus patients suffering from calciphylaxis. In the worst case, they are threatened with the death of isolated areas of skin and joints, resulting in amputation. Due to the physical changes and pain, depression often develops, which can hardly be overcome by self-help. Affected individuals should not be afraid to seek psychological support.