Calcific uremic arteriolopathy (calciphylaxis) is a rare and devastating disease which can develop in end-stage renal disease patients. Media calcification induces thrombi of small and medium-sized vessels in the dermis and subcutaneous tissue. It is associated with high morbidity and mortality (up to 80%) likely due to infections of necrotic skin resulting in sepsis. We report here the use of rheopheresis as adjuvant treatment of calciphylaxis to improve tissue oxygenation and cutaneous scarring.
A 71-year-old woman under hemodialysis for diabetic nephropathy presented with septic shock due to necrotic lesions of the thigh and abdomen. Calciphylaxis was histologically proven. After resuscitation, calciphylaxis treatment was based on increasing hemodialysis intensity, lowering circulating P x Ca product, nutritional support, intravenous sodium thiosulfate (25g three times a week) and vitamin K implementation, in addition to local wound care. Hyperbaric oxygen therapy could not be performed as the patient suffered from claustrophobia. Despite two months of intensive therapy the cutaneous lesions worsened. As agreed with the patient, we decided to add double filtration rheopheresis (Plasma separator Plasmaflo OP-05W; Rheofilter AR-200; Asahi Kasei Medical, Tokyo, Japan) to each hemodialysis session. One week after start of therapy the patient’s pain had decreased. Over the following two weeks we observed more granulation and less necrotic tissue. In total, 24 sessions were performed without side effects. Each session treated 5L of plasma and was completed by perfusion of 25g of albumin. Mean changes of α2-macroglobulin, fibrinogen and cholesterol plasma concentration before and after rheopheresis were 81±10.7%, 74±10% and 70.5±13.5%, respectively. Rheopheresis was stopped after 10 weeks of treatment with no calciphylaxis relapse. Whole cicatrization of the skin was obtained six weeks later.
Rheopheresis has been studied in microcirculation disorders of the retina (age-related macular degeneration), skin (peripheral arterial disease) and ear (sudden hearing loss). Its concept is based on the Fåhraeus-Lindqvist effect. Double filtration rheopheresis eliminates LDL particles and high molecular weight proteins (α2-macroglobulin, IgM), decreases plasma viscosity and thereby improves hemorheology and microcirculation. Ischemia during calciphylaxis is due to two mechanisms: 1) the reduction in the diameter of luminal vessels by phospho-calcic deposits and micro thrombi, and 2) raised inflammatory proteins which increase blood viscosity. In our case report rheopheresis was proposed not as a treatment for calciphylaxis etiologies itself (phospho-calcic deposits), but for its microvascular impact. The first clinical benefit for our patient was reduction of pain, suggesting optimum oxygenation of tissue as early as the third treatment. The second benefit was initiation of the cutaneous scarring process which was not achieved with previous treatments.
In conclusion, we think that rheopheresis could be used as an adjuvant treatment for severe calciphylaxis to further cutaneous scarring and limit infection-associated disease.