Calciphylaxis Treatment & Management

Updated: Aug 02, 2018
  • Author: Julia R Nunley, MD; Chief Editor: Dirk M Elston, MD  more...
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Treatment

Medical Care

Therapy is multifaceted and includes medical and surgical intervention. [42, 43] Aggravating conditions should be addressed, and trigger factors should be eliminated. This may mean the discontinuation of parenteral iron therapy, calcium supplementation, and vitamin D supplementation. Although frequently implicated as a trigger some studies suggest that patients may benefit from systemic glucocorticoids early on, unless ulcerated lesions are present. Early use of sodium thiosulfate should be considered. [44, 45]

In patients with an elevated calcium-phosphate product, serum calcium and phosphate concentrations must be brought to low-normal levels as quickly and safely as possible. [46, 47] Conservative therapy should be tried first, with dietary alteration, use of noncalcium, nonaluminum phosphate binders and low-calcium bath dialysis. [48] Some benefit may be achieved with increasing the frequency or duration of dialysis sessions.

Calcimimetics such as cinacalcet hydrochloride may be beneficial in cases of hyperparathyroidism. [49, 50, 51] These agents increase the sensitivity of the calcium receptors to available calcium, thereby decreasing PTH secretion. Studies have shown efficacy in decreasing PTH, calcium, and phosphate levels. Reports of successful treatment with these agents as adjunctive therapy for calciphylaxis are emerging. [52, 53]

Bisphosphonates (eg, pamidronate, [54, 55] etridronate [56] ) increase osteoprotegerin production and inhibit arterial calcification. Case reports suggest these may be helpful in some cases of calciphylaxis, even without changing calcium or phosphate levels. [52, 57, 58, 59] Parathyroidectomy should be considered if conservative management fails, but only if hyperparathyroidism is present.

Marked improvement of calciphylaxis has now been reported with the use of intravenous sodium thiosulfate. Sodium thiosulfate is a potent antioxidant, and it also increases the solubility of calcium deposits. Success has been reported in uremic and nonuremic calciphylaxis. [8, 52, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69]

Calciphylaxis therapy with sodium thiosulfate is off-label usage, but reports of success are mounting. A study of 14 patients suggests that several factors may impact patient outcome. [70] Earlier intervention and/or a higher total dose of sodium thiosulfate may be more effective. More obese patients and patients on long-term renal replacement therapy did not fair as well. Success was recently reported in a nonuremic patient treated with intravenous sodium thiosulfate. [71] A multimodality approach using sodium thiosulfate, cinacalcet, and sevelamer has also been used. [72]

Sodium thiosulfate has been administered intravenously, intralesionally, topically, and intraperitoneally, and it has been used in both adults and children. [73]  Intravenous doses have varied from 5-75 g after or during hemodialysis in adults. The most commonly reported dose has been 25 g after each dialysis. Some have used weight-based dosing (especially in children) at using 12 g/1.7 m2. Infusion times vary from 30-60 minutes. Although generally well tolerated, adverse effects have include nausea with emesis and the development of an anion gap metabolic acidosis that can be managed by altering the bicarbonate level of the dialysate. Symptomatic relief and clinical improvement may occur within 2 weeks. See the Anion Gap calculator.

Early data suggest that intralesional sodium thiosulfate may also be an option. [74]

Patients should be monitored for the potential development of a metabolic acidosis. Oral sodium thiosulfate has also been reported to suppress calciphylaxis, although or absorption may be poor. A 2 M (molar) solution can be prepared with 74.4 g in 150 mL free water; 2.6 g can be given orally daily or 3 times a week. Dose is limited by diarrhea.

Judicious use of antibiotics may be advantageous. Additionally, in some cases, hyperbaric oxygen may be beneficial to promote wound healing. [75, 76]

Conditions of hypercoagulability should be sought and addressed. Patients with documented conditions of hypercoagulability may benefit from proper and adequate anticoagulation. [77] Successful treatment of calciphylaxis with low-dose tissue plasminogen activator has been reported. [78] Laboratory evaluation of the reported patient demonstrated low antithrombin III antigen and activity, as well as low protein C antigen and activity prior to intervention with tissue plasminogen activator therapy. However, the role of anticoagulation in all cases of calciphylaxis is controversial. Random prophylactic use of warfarin or heparin is probably not indicated because precipitation of calciphylaxis has occurred with indiscriminate use. [79, 80] In addition, most patients with ESRD have a prolonged bleeding time due to the uremic condition, and anticoagulation or tissue plasmogen activator therapy should be approached cautiously. Nonetheless, in the setting of thrombotic occlusion and cutaneous ischemia, restoration of blood flow is critical. [15]

Pain management is also crucially important. [81] Consultation with pain-management specialists may be necessary.

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Surgical Care

Aggressive wound care and debridement of necrotic tissue may be necessary to avoid wound infection and sepsis. [6] However, some advise against debridement. Currently, there is no consensus on wound management. [17] The decision to debride, and to what extent, depends on the patient's overall health and the clinical picture.

Use of a vacuum-assisted closure device has been successful in several cases of calciphylaxis after extensive debridement and prior to skin grafting. [82]

Total or subtotal parathyroidectomy with autotransplantation may be of therapeutic benefit. [6, 48, 83, 84, 85]  Small case studies have demonstrated some benefit; however, other larger retrospective studies have shown no significant difference in survival. [17] Decisions should be made on a case-to-case basis.

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Consultations

Consult a surgeon regarding wound debridement and possible parathyroidectomy. Consult a dietitian regarding dietary alterations. Consider consulting a pain-management specialist.

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Diet

Patients with abnormalities in calcium and phosphate homeostasis need to be referred to a dietitian well versed in the dietary needs and restrictions of patients with ESRD. Special consideration should be given to phosphate restriction.

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Activity

The patient's activity may be greatly hampered by the pain and the ulceration of calciphylaxis lesions. Patients are generally hospitalized in intensive care units during the acute illness.

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