Calciphylaxis, also known as Calcific Ureamic Arteriolopathy, is a rare but serious and devastating condition which manifests as subcutaneous vascular calcification and cutaneous necrosis (small blood vessels of the fat tissue and the skin).
Calciphylaxis is a disorder of arterial calcification in subcutaneous tissues leading to severe ischemia and tissue necrosis. It usually occurs in chronic kidney disease patients on maintenance hemodialysis. Although the pathogenesis is unknown, there are factors present in the uremic patient that predispose to this condition, such as secondary hyperparathyroidism and chronic inflammation. Severe infection accounts for its high mortality rate. Treatment focuses on early recognition, and prevention of hypercalcemia, hyperphosphatemia, and elevated calcium x phosphorus product.
Calciphylaxis most often occurs on the lower limb especially in fatty areas. Lesions on the trunk, abdomen, buttocks or thighs, appear to be more dangerous than lesions on the lower legs and feet.
Calciphylaxis begins as surface purple-coloured mottling of the skin (retiform purpura) then bleeding occurs within the affected area. There may be blood-filled blisters. The skin goes black in the centre of star-shaped (stellate) purple lesions. The skin cells die because of lack of blood supply (dry gangrene). This causes deep and often extensive ulcers. It may cause serious infections that can lead to death.
This condition mainly occurs in dialysis patients with serious renal disorders. The exact prevalence statistics is not known. However, experts believe that 1 out of every 1000 to 1500 patients with chronic renal disorders develop Ischemic Necrosis Skin-Muscles in a year.
Causes
The cause of calciphylaxis is not properly understood. Calcification blocks small blood vessels deep in the skin, resulting in spreading skin necrosis (tissue death).
Small blood vessels become blocked with blood clots, which leads to the black painful necrotic areas. It is thought that the clots occur because of calfication within the walls of the blood vessels.
In chronic renal failure, it is often associated with a condition known as secondary hyperparathyroidism. The damaged kidneys don’t excrete phosphate properly, which results in a build up of phosphate in the blood, which combines with calcium. Vitamin-D levels are reduced because of the kidney failure and reduced absorption through the gut. The bones become resistant to parathyroid hormone. The parathyroid glands therefore increase in size and produce more hormone increasing the amount of calcium circulating in the blood.
Calciphylaxis can occur in those with high or normal levels of serum calcium and phosphate, with or without vitamin D replacement, in dialysed patients and less often in those who have not yet commenced dialysis or in those who have received a renal transplant. It is more common in women than in men, in obese patients compared to those of normal weight, and in patients who have been taking corticosteroids or other immunosuppressive medicines.
Calciphylaxis can also occur in patients with normal kidney function, in the presence of hypercoagulability states. These may include liver disease, diabetes and treatment with warfarin. High levels of matrix metalloproteinases have been described and one theory suggests chemically altered elastin protein allows deposition of calcium on small vessels.
Some causes include aluminum toxicity, coagulation abnormalities, and iron dextran infusion.
Who is at risk?
- Race – Although the disease may affect persons of any race, it appears to be more prevalent in whites.
- Sex – Females are affected more often than males, with a female-to-male ratio of approximately 3:1. Females also appear to be more commonly affected with nonuremic calciphylaxis.
- Age – Calciphylaxis has been reported in individuals ranging in age from 6 months to 83 years. From a large series of patients, a mean patient age of 48 years (±16 y) has been calculated. Individuals seemingly more predisposed are younger patients who have had a longer duration of renal replacement therapy.
Certain conditions in addition to renal failure are associated with accelerated calcium deposition in soft tissues –
- Long-term obesity
- Recent and sudden weight loss
- Malnutrition
- Infusion of medications such as iron dextran
- Remote and/or recent use of immunosuppressive agents, especially corticosteroids
- Liver disease
- Diabetes mellitus and insulin injections
- Use of vitamin D and calcium-based phosphate binders
- Elevated aluminum levels
- Concomitant vascular disease
- Concurrent use of warfarin anticoagulation: Current data suggest that warfarin therapy may lower protein C concentrations, leading to a procoagulant condition in the calcified vessel. Warfarin may also inhibit carboxylation of matrix Gla protein, an important inhibitor of calcification, thus promoting calcification
Symptoms
Patients of this condition suffer from various health problems and skin disorders due to the development of painful ulcers. The condition is characterized by –
- Multiple organ failures
- Certain skin infections
- Continuous burning and itching sensations
- Bleeding from the area primarily involved
- Several red or purple lesions on the abdomen, trunk, buttock and thigh
- Systemic medial calcification of arteries (such as the tunica media)
- Calcification of the small vessel walls (endovascular fibrosis may or may not be present)
- Possible development of fluid-filled lesions
- Tissue ischemia, which leads to cell necrosis
Complications
The disease can lead to several serious complications, unless treated properly. The common complications include ulceration and pain in different areas on the skin as well as blood infection. A patient may also undergo severe lung calcification. The lesions may turn fatal due to multi-organ failure and infection.
Treatment
Medications – Drugs that help to reduce the calcium deposits are often prescribed by a physician. He or she also evaluates all the medicines used by a patient to check if any of those medicines are responsible for triggering the lesions.
- Corticosteroids and iron medications are among these precipitating factors.
- Doctors may also modify the dosage of any vitamin D and calcium supplements.
- Cinacalcet (Sensipar) is sometimes prescribed for controlling the parathyroid hormone (PTH) level of a sufferer.
- Sodium thiosulfate is another medicine which is commonly used in this treatment.
- Medications may also be prescribed for improving the calcium and phosphorus balance in the body.
Surgery – In some cases, a hyperactive parathyroid gland (hyperparathyroidism) produces excessive amounts of PTH thus leading to abnormalities in calcium metabolism. In such cases, surgery is recommended for partial or complete removal of the patient’s parathyroid glands.
Dialysis – At times a doctor may change the dialysis prescription if an affected individual is on kidney dialysis. The frequency of dialysis and the medications used by the patient are generally changed for this treatment.
Intensive Wound Care – The initial stage of the treatment is intensive care of the wounds. In some cases, the tissues damaged by the condition require surgical removal (debridement). Sometimes, other procedures including wet dressings and whirlpool treatments are also used for removing the damaged tissues. Antibiotic treatment is necessary to prevent and treat wound infections. A doctor may prescribe certain medications for pain management
Hyperbaric oxygen therapy may be recommended by a doctor for increasing the oxygen flow to the affected regions. Sometimes, a low-dose TPA (tissue plasminogen activator) may also be used for dissolving the blood clots occurring in the small blood vessels of skin. Blood thinning medications can help prevent the formation of additional blood clots.
Intralesional Sodium Thiosulfate for the Treatment of Calciphylaxis – Intralesional sodium thiosulfate may be an effective and well-tolerated treatment for localized calciphylaxis. This treatment for calciphylaxis has aimed at removing potential triggers and providing local wound care. the successful use of intravenous (IV) sodium thiosulfate in the treatment of calciphylaxis. Since then, several studies have supported the use of this medication; however, its application may be limited by adverse effects, such as gastrointestinal upset, metabolic acidosis, and sodium overload.
Alternative Treatment (Not Found)
Reference –
http://www.hxbenefit.com/calciphylaxis.html
http://emedicine.medscape.com/article/1095481-clinical#b4
http://www.rightdiagnosis.com/c/calciphylaxis/treatments.htm
http://www.nature.com/ki/journal/v60/n1/full/4492404a.html
http://www.mayoclinic.org/diseases-conditions/calciphylaxis/basics/definition/con-20034283
http://www.dermnetnz.org/systemic/calciphylaxis.html
http://emedicine.medscape.com/article/1095481-overview