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Calciphylaxis

What is Calciphylaxis?

Calciphylaxis is a life-threatening condition that occurs due to calcium deposition in small blood vessels in the skin and the fatty layer under the skin. This calcification causes the occlusion of these small blood vessels which reduces blood supply, and therefore oxygen supply, to the skin, and eventually causing painful skin ulcers due to necrosis or death of the skin cells, blood clots, and infections. Lower extremities are most frequently affected. Calciphylaxis most commonly occurs in individuals with pre-existing end-stage kidney failure who are on dialysis, however, it can also occur in individuals with any underlying kidney disease. 

Calciphylaxis is highly debilitating and associated with high mortality. About half of the affected individuals survive a year after diagnosis. Treatment options are wound care, surgical debridement (removal of affected tissues), as well as medications such as sodium thiosulfate, and bisphosphonates.

 

 

Synonyms

  • Calcific uremic arteriolopathy
  • Metastatic calcinosis cutis
  • Necrotizing panniculitis
  • Calcifying panniculitis

Calciphylaxis is a life-threatening condition that occurs due to calcium deposition in small blood vessels in the skin and the fatty layer under the skin. This calcification causes the occlusion of these small blood vessels which reduces blood supply, and therefore oxygen supply, to the skin, and eventually causing painful skin ulcers due to necrosis or death of the skin cells, blood clots, and infections. Lower extremities are most frequently affected. Calciphylaxis most commonly occurs in individuals with pre-existing end-stage kidney failure who are on dialysis, however, it can also occur in individuals with any underlying kidney disease. 

Calciphylaxis is highly debilitating and associated with high mortality. About half of the affected individuals survive a year after diagnosis. Treatment options are wound care, surgical debridement (removal of affected tissues), as well as medications such as sodium thiosulfate, and bisphosphonates.

 

Acknowledgement of Calciphylaxis has not been added yet.

Calciphylaxis is estimated to present in about 35 per 10,000 individuals on hemodialysis* in the United States and in about 4 per 10,000 individuals on hemodialysis in Europe. Females are affected more than males.

Calciphylaxis can also occur in individuals who are not on dialysis or do not have any kidney disease, however, the prevalence is much lower in this population. 

 

*Hemodialysis is a treatment used to filter wastes and water from the blood in the absence of healthy and functioning kidneys which would normally do so.

 

Name Abbreviation
Calcific uremic arteriolopathy Calciphylaxis
Metastatic calcinosis cutis Calciphylaxis
Necrotizing panniculitis Calciphylaxis
Calcifying panniculitis Calciphylaxis

The cause of calciphylaxis is unknown. However, it is believed that a combination of phosphate and calcium metabolism impairment and blood clotting factor defects may be involved in the disease process. Clotting factors are proteins that are involved in forming blood clots and stopping bleeding. Calciphylaxis is often associated with what is known as a hypercoagulable state, meaning that blood clots form more often than they normally do. Calciphylaxis is associated with long-term elevation in blood phosphate levels and parathyroid hormone which is involved in calcium and phosphate metabolism. Calcium metabolism imbalance leads to calcium deposition in small blood vessels which causes blood vessel narrowing and the hypercoagulability leads to blood clot formation and the complete occlusion of the blood vessels. As a result, the area of the skin supplied by the blocked blood vessels dies which leads to ulcerations.

 

Calciphylaxis most commonly, but not exclusively, occurs in individuals with an underlying end-stage kidney failure on dialysis. Other factors such as poorly controlled hyperparathyroidism (increased parathyroid hormone levels), diabetes, obesity, certain medications such as warfarin (a blood thinner), calcium-binding agents, and corticosteroids (a class of anti-inflammatory drugs) can increase the risk of calciphylaxis. Uremia is another risk factor for calciphylaxis. Uremia is the toxic accumulation of substances that are normally excreted in the urine such as urea, calcium, and phosphate.

There are several factors that inhibit calcification in blood vessel walls. In a majority of calciphylaxis cases, these factors are deficient. Some of these factors are vitamin K-dependent. Therefore, processes that lead to vitamin K deficiency can lower the production of these factors, For example, warfarin inhibits vitamin K recycling and this might be why warfarin therapy increases the risk of calciphylaxis. In addition, high doses of active vitamin D administration can downregulate another important calcification inhibitor and increase the risk of calciphylaxis. There is some preliminary evidence that certain variations in the vitamin D receptor gene may be associated with an increased risk of calciphylaxis. 

In non-dialysis patients, prednisone (a corticosteroid) use seems to be a strong risk factor. Other risk factors in this population are chronic inflammatory conditions such as systemic lupus erythematosus, ulcerative colitis, and rheumatoid arthritis.

 

Calciphylaxis often starts with painful, symmetrical, violet-colored, net-like discolorations that can develop in painful nodules or plaques. Plaques are red, warm, tender, and present as palpable regions of thickened skin (induration). These nodules may develop into non-healing ulcers and open wounds with a hard, dark crust. These ulcers are very prone to recurrent infections. The most commonly affected areas are legs and feet, inner thigh, buttocks, and abdomen.

The most consistent feature of calciphylaxis is severe pain, out of proportion with the skin involvement. Pain may even present before skin lesions. The exact cause of this pain is unknown but it’s believed to be due to a lack of oxygen supply (ischemic pain) and potentially nerve damage in the area (neuropathic pain).

 

Calciphylaxis is suspected in individuals who have end-stage kidney disease and painful nodules or plaques in the layers under the skin or non-healing skin ulcers in the regions associated with calciphylaxis. The presence of other risk factors such as warfarin use, vitamin K deficiency, elevated parathyroid hormone, obesity, and elevated calcium and phosphate levels increase suspicion.

 

In individuals with end-stage kidney disease, the presence of characteristic skin lesions may be sufficient to confirm the diagnosis. However, additional tests may be required if the skin findings are atypical or if there is suspicion in an individual without any advanced kidney disease. 

A skin biopsy is a procedure often done by a dermatologist or a surgeon in which a piece of the skin lesion is removed and analyzed to determine whether there is any calcification.

Imaging studies are typically not used for the diagnosis of calciphylaxis, although there is evidence for the utility of bone scans to identify calcified regions in the skin.

 

Treatment of calciphylaxis first focuses on the prevention of vascular calcification. If vascular calcification has already occurred, the goal of treatment is reversing that process to reduce the amount of occlusion of the blood vessels and improve blood supply to the affected areas. Lastly, pain management and wound care are critical in individuals with painful skin lesions and ulcers. 

Although not all individuals with calciphylaxis have hyperphosphatemia and hypercalcemia, controlling blood phosphate and calcium levels may be helpful in preventing or slowing vascular calcification. This can be achieved by increasing phosphate and calcium removal during dialysis for individuals who are already receiving dialysis as well as restricting the consumption of calcium and phosphate-rich foods. Non-calcium-based phosphate binders may also help control phosphate levels.

 

There is controversial evidence suggesting that the surgical removal of parathyroid glands can confer some benefit in individuals who have an overactive parathyroid gland (hyperparathyroidism), and therefore, produce too much parathyroid hormone. Parathyroid hormone increases calcium levels in the blood when the perceived concentration of calcium is below a certain level. There is no evidence suggesting that this procedure is helpful in individuals with normal levels of parathyroid hormone. Parathyroid hormone levels can also be lowered by using medications that mimic calcium, tricking the body into believing that blood calcium levels are higher than they actually are, and therefore, suppressing the production of parathyroid hormone.


 

Wound Care

Wound care involves wound bed management including controlling the moisture and using appropriate dressings if needed, antibiotic therapy to prevent infection, and in some cases, surgical debridement. Surgical debridement is a procedure in which skin wounds are cleaned, and the thickened skin, infected areas, and the dead tissue are removed. This is particularly important for infected skin to prevent the spread of infection.

Hyperbaric oxygen therapy (HOT) is another technique for wound care. It involves breathing 100% oxygen at a pressure higher than atmospheric pressure. This technique improves the amount of oxygen that reaches the tissue in the affected areas which stimulates the formation of new blood vessels. There is some evidence that HOT may be helpful in the treatment of skin ulcers in calciphylaxis.

 

Sodium thiosulfate

Sodium thiosulfate is commonly used for the treatment of calciphylaxis, although the mechanism of action is not well-understood. It is believed that sodium thiosulfate works as a calcium chelator, meaning that it binds calcium and removes it from blood vessels, and therefore, decalcifying them. In addition, it is also believed that sodium thiosulfate relaxes the blood vessels, increasing their diameter, which makes it easier for blood to pass through in occluded regions. It appears that the use of sodium thiosulfates leads to pain relief and reduction in skin lesions.

 

Other treatments

Although the use of vitamin K for the treatment of calciphylaxis is not well-supported by evidence, it is possible that it may slow the calcification process in the blood vessels. It is also important to assess the risks and benefits of prescribing agents that can increase the rate of calcification such as warfarin and vitamin A.

 

Calciphylaxis is typically a fatal disease with about half of the affected individuals surviving one year after diagnosis. The presentation of skin ulcers increases the risk of death with infection being the main cause of death in these individuals. Individuals without any kidney diseases still have a high rate of death, but lower than those who are on dialysis. In addition, individuals with skin involvement around the abdomen, buttocks, thighs, and legs have a slightly higher rate of death than those with skin involvement in the feet, toes, and hands. 

 

Tips or Suggestions of Calciphylaxis has not been added yet.

Bhambri A, Del Rosso JQ. Calciphylaxis: a review. J Clin Aesthet Dermatol. 2008;1(2):38-41.

 

Chang, John J. MD Calciphylaxis: Diagnosis, Pathogenesis, and Treatment, Advances in Skin & Wound Care: May 2019 - Volume 32 - Issue 5 - p 205-215 doi: 10.1097/01.ASW.0000554443.14002.13 

 

Gaisne, R., Péré, M., Menoyo, V. et al. Calciphylaxis epidemiology, risk factors, treatment and survival among French chronic kidney disease patients: a case-control study. BMC Nephrol 21, 63 (2020). https://doi.org/10.1186/s12882-020-01722-y

 

Mathur RV, Shortland JR, El Nahas AMCalciphylaxisPostgraduate Medical Journal 2001;77:557-561.

 

Nigwekar SU, Thadhani R, Brandenburg VM. Calciphylaxis. New England Journal of Medicine. 2018; 378:1704-1714. DOI: 10.1056/NEJMra1505292

 

Udomkarnjananun S, Kongnatthasate K, Praditpornsilpa K, Eiam-Ong S, Jaber BL, Susantitaphong P. Treatment of Calciphylaxis in CKD: A Systematic Review and Meta-analysis. Kidney Int Rep. 2018;4(2):231-244. Published 2018 Oct 9. doi:10.1016/j.ekir.2018.10.002

 

Community Details Update Created by RareshareTeam
Last updated 30 Jun 2021, 01:43 AM

Posted by RareshareTeam
30 Jun 2021, 01:43 AM

Hi everyone,

The Calciphylaxis community details have been updated. We added more information about the cause, prevalence, symptoms, diagnosis, and treatment. Hopefully, you find it helpful. 

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Visit sanfordresearch.org/CoRDS to enroll.

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Created by RareshareTeam | Last updated 30 Jun 2021, 01:43 AM


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