Introduction:
Calciphylaxis is a sparsely understood and highly fatal condition. It occurs due to the deposition of calcium in the vessels, especially the arterioles (small blood vessels), resulting in obstruction of the microvasculature. The obstruction of blood vessels causes severe ischemia and necrosis of the skin at the site. The term calciphylaxis was coined by Selye in 1962, who highlighted the pathophysiology of this condition.
What Is Calciphylaxis?
Calciphylaxis, which is now referred to as calcific uremic arteriolopathy (CUA),is a painful condition occurring mostly as a complication of chronic renal failure. It has a complex clinical presentation due to the calcific changes in the vascular and dermal layers of the skin. These calcific changes result in various abnormalities such as:
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Abnormal thickening of the innermost layer of the arterial wall.
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Inflammation of the skin.
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Fibrosis of the blood vessel and obliteration.
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Calcium deposits in the medial layer of the arterial wall.
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Obstruction leads to ischemia and necrosis of the dermal, sub-dermal, and fatty tissues.
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Painful skin ulcerations.
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Increased suppression of calcification inhibitors.
What Is the Pathophysiology of CUA in Renal Failure?
Calcific uremic arteriolopathy commonly occurs as a complication of renal failure, especially in patients undergoing hemodialysis. In chronic renal failure, there is impaired kidney function resulting in decreased vitamin D synthesis and calcium reabsorption and causing the excretion of phosphate. This, in return, promotes bone remodeling resulting in increased serum calcium levels and facilitating microvascular calcification (deposition of calcium). Suppression in the levels of circulating inhibitors of calcification in renal failure is believed to trigger microvascular calcification.
What Are the Clinical Manifestations of Calciphylaxis?
Clinical manifestations of calciphylaxis include:
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Extreme pain and tenderness in the affected area.
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Presence of intensely painful and palpable nodules under the skin with marked spots of purplish discoloration of the skin.
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Nodules might later develop into blisters which progressively develop into blackened areas of slough over the surface of the skin, eventually leading to a non-healing ulcer formation.
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Once the adipose layer of the skin gets affected, the skin and the underlying tissues become necrosed and ulcerated, which can be fatal to the patients.
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The skin lesions initially begin in the lower extremities. But they are believed to occur more frequently in fatty tissues such as the abdomen, thigh region, trunk, and genital region. The calcification is extensive and spreads across the entire body.
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The calcification of the medial layer of the arterial wall not only occurs in the skin but also affects the internal organs, muscles, and nerve fibers.
What Are the Complications of CUA?
The complications of calcific uremic arteriolopathy range from moderate intervention in the quality of life to death. A few possible complications seen in patients with CUA are:
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Presence of large non-healing ulcers and gangrene of the skin.
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Lesions in the peripheral body parts may fail to heal and can lead to amputation.
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Non-healing wounds may result in sepsis, causing infections of the blood.
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Microvascular calcification of the internal organs may lead to internal bleeding and multiple organ failure.
How Is the CUA Diagnosed?
The healthcare provider usually diagnoses this condition based on the clinical condition, symptoms, and physical examination of the patient. The doctor will thoroughly assess the skin, looking for any changes. This will also include a detailed history taking and questioning about the previous medical history. Diagnosis of this condition can be challenging for the healthcare provider, but if not done at the right time can lead to serious consequences for the patient. The doctor performs various tests to confirm the diagnosis, such as
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Skin biopsy: Skin biopsy is one of the standard tools in diagnosing calciphylaxis. A punch biopsy is preferred over an excisional biopsy, even though an adequate amount of tissue is not obtained. A telescopic punch biopsy is performed where a sample of skin and tissue are taken most conservatively and sent to the microscopic laboratory for analysis. However, this procedure might raise the concern about instigating a new ulcer that might not heal, and a biopsy might be unnecessary in severe cases.
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Various metabolic parameters are obtained through laboratory analysis to assess kidney function, such as:
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Serum phosphate, calcium, and alkaline phosphatase levels.
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Parathyroid hormone level.
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Blood clotting factors.
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Serum creatinine level.
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Blood urea nitrogen level.
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Radiological imaging studies: As bone scintigraphy (bone scan) are non-invasive and useful in detecting soft tissue microcalcification. The bone scan is 97 % positive in detecting abnormal calcium deposits and displays the actual extent of the disease. It is also used in monitoring the progress of the treatment.
How Is Calciphylaxis Treated?
Treatment of calciphylaxis involves a multidisciplinary approach such as;
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Wound management.
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Use of antibiotics.
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Alteration of biochemical abnormalities.
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Avoiding trauma to the skin.
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Use of sodium thiosulfate.
Wound management:
The best possible wound management and prevention of further infection are most necessary while managing calciphylaxis. Debridement of the necrotic tissue will facilitate proper wound healing. Maggot debridement therapy has also been shown to be successful in wound management of calciphylaxis. Pain management is also very important in extremely painful lesions. Opioid analgesics such as Fentanyl are preferred.
Hyperbaric oxygen (HBO):
Hyperbaric oxygen therapy has been shown to be beneficial in several cases of calciphylaxis. The patient is placed inside an air-tight chamber. It involves the patient breathing 100 % O2 (oxygen) at a pressure greater than normal, and this therapy has been thought to promote wound healing.
Alteration of biochemical abnormalities:
In patients with elevated serum calcium and phosphate levels, steps should be taken to reduce calcium and phosphorus levels. Discontinuing calcium and vitamin D supplements is necessary. Alterations in the duration and frequency of dialysis sessions are beneficial.
Sodium thiosulfate:
Recent studies evaluated the response of patients with calcific uremic arteriolopathy to the treatment for sodium thiosulphate (STS), and the majority of the patients showed improvement after STS. They are administered through the intravenous route, topical route, and intraperitoneal route. They are usually recommended at the dose of 25 grams intravenously three times a week. Common side effects are nausea, vomiting, and diarrhea.
Antibiotics:
Use of antibiotics in patients with infections.
Diet:
It is equally important to monitor the diet and nutrition of patients with calciphylaxis to prevent malnutrition.
Conclusion:
Calcific uremic arteriolopathy is a debilitating condition disrupting the quality of life and is often seen as a complication of renal failure. Though the cause of this condition is still quite unknown, identifying the risk factors and diagnosis plays a huge role in the outcome of patients. Even with the early diagnosis, multiple disciplinary treatment approaches, and various management options, calciphylaxis is considered to be a fatal condition with a high mortality rate.
