By Aletha Tippett MD

Calciphylaxis involves ischemic wounds that occur almost exclusively in patients undergoing hemodialysis. It is a syndrome of vascular calcification, thrombosis and skin necrosis. It results in chronic non-healing wounds and is usually fatal. Calciphylaxis is a rare but serious disease.

Calciphylaxis most commonly occurs in patients with end-stage renal disease who are on hemodialysis or who have recently received a renal (kidney) transplant. Yet calciphylaxis does not occur only in end-stage renal disease patients. When reported in patients without end-stage renal disease, it is called non-uremic calciphylaxis by Nigwekar et al.¹ Non-uremic calciphylaxis has been observed in patients with primary hyperthyroidism, breast cancer (treated with chemotherapy), liver cirrhosis (due to alcohol abuse), cholangiocarcinoma, Crohn's disease, rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE).

There is no diagnostic test for calciphylaxis. The diagnosis is a clinical one. The characteristic lesions are the ischemic skin lesions (usually with areas of skin necrosis). The necrotic skin lesions (i.e. the dying or already dead skin areas) typically appear initially as violaceous (dark bluish purple) lesions and/or completely black leathery lesions. They can be extensive. They are very painful. The suspected diagnosis can be supported by a skin biopsy. It shows arterial calcification and occlusion in the absence of vasculitis. Sometimes a bone scan can show increased tracer accumulation in the soft tissues.² In certain patients, anti-nuclear antibody may play a role.³

The optimal treatment is prevention. Rigorous and continuous control of phosphate and calcium balance is the most likely option to avoid the metabolic changes which may lead to calciphylaxis. However, it is not clear what, if any, calcium and phosphate levels contribute to calciphylaxis. There is no specific treatment. Of the treatments that exist, none is internationally recognized as the standard of care. Treatments that have been tried include:

• Dialysis (the number of sessions may be increased)
• Intensive wound care
• Clot-dissolving agents (tissue plasminogen activator)
• Hyperbaric oxygen⁴
• Maggot larval debridement
• Adequate pain control
• Correction of the underlying plasma calcium and phosphorus abnormalities (lowering the Ca x P product below 55 mg2/dL2)
• Sodium thiosulfate
• Avoiding (further) local tissue trauma (including avoiding all subcutaneous injections, and all not-absolutely-necessary infusions and transfusions); avoid adhesives on the skin
• Urgent parathyroidectomy: The efficacy of this measure remains uncertain although calciphylaxis is associated with frank hyperparathyroidism. Urgent parathyroidectomy may benefit those patients who have uncontrollable plasma calcium and phosphorus concentrations despite dialysis. Also, cinacalcet can be used and may serve as an alternative to parathyroidectomy. The trade name of cinacalcet is Sensipar or Mimpara.
• Patients who receive kidney transplants also receive immunosuppression, which is believed to increase risk of calciphylaxis. Considering lowering the dose of or discontinuing the use of immunosuppressive drugs in renal transplant patients who continue to have persistent or progressive calciphylactic skin lesions can contribute to an acceptable treatment of calciphylaxis.

In our clinic we have treated a number of cases of calciphylaxis. The first step is always to control the pain. We use a lidocaine containing hydrogel dressing on the wounds and provide adequate oral pain medications. Sometimes we also use electrical stimulation to stimulate circulation and increased oxygenation. In general we have had success with healing of many of the lesions. We have tried sodium thiosulfate once, but the results were equivocal.

Treating calciphylaxis is almost an oxymoron, but if you can control the pain that will be wonderfully helpful for the patient. Work with the patient’s nephrologist as possible. Perhaps they can help with the Ca and P balance, and may be able to infuse sodium thiosulfate. Just remember the patient has a serious problem with a lot of pain and needs your compassion and help.

Sources
1. Nigwekar SU, Wolf M, Sterns RH, Hix JK. Calciphylaxis from nonuremic causes: a systematic review. Clin J Am Soc Nephrol. 2008 Jul;3(4):1139-43. Epub 2008 Apr 16
2. Araya CE, Fennell RS, Neiberger RE, Dharnidharka VR (2006). "Sodium thiosulfate treatment for calcific uremic arteriolopathy in children and young adults". Clin J Am Soc Nephrol 1 (6): 1161–6. doi:10.2215/CJN.01520506. PMID 17699342. 
3. Anti-nuclear antibody: a potential predictor of calciphylaxis in non-dialysis patients. Rashid RM, Hauck M, Lasley M. J Eur Acad Dermatol Venereol. 2008 Nov;22(10):1247-8. Epub 2008 Apr 15.
4. Edsell ME, Bailey M, Joe K, Millar I (2008). "Hyperbaric oxygen therapy in the treatment of skin ulcers due to calcific uraemic arteriolopathy: experience from an Australian hyperbaric unit.". Diving and Hyperbaric Medicine (South Pacific Underwater Medicine Society) 38 (3): 139–44. Retrieved 2013-04-02.

About The Author
Aletha Tippett MD is a family medicine and wound care expert, founder and president of the Hope of Healing Foundation®, family physician, and international speaker on wound care.

The views and opinions expressed in this blog are solely those of the author, and do not represent the views of WoundSource, Kestrel Health Information, Inc., its affiliates, or subsidiary companies.