Calciphylaxis Treatment & Management

  • Author: Julia R Nunley, MD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Jun 24, 2011
 

Medical Care

Therapy is multifaceted and includes medical and surgical intervention.[32, 33] 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.

Serum calcium and phosphate concentrations must be brought to low-normal levels as quickly and safely as possible.[34, 35] Conservative therapy should be tried first, with dietary alteration, use of noncalcium, nonaluminum phosphate binders and low-calcium bath dialysis.[36] 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.[37, 38, 39] 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.[40, 41] Also see the clinical guideline summary, Cinacalcet for the treatment of secondary hyperparathyroidism in patients with end-stage renal disease on maintenance dialysis therapy.

Bisphosphonates (eg, pamidronate,[42, 43] etridronate[44] ) 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.[40, 45, 46] 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.[6, 40, 47, 48, 49, 50, 51, 52, 53, 54, 55]

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.[56] 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.

Sodium thiosulfate has been administered both intravenously and intraperitoneally, and it has been used in both adults and children. 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.

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.[57, 58]

Conditions of hypercoagulability should be sought and addressed. Patients with documented conditions of hypercoagulability may benefit from proper and adequate anticoagulation. Successful treatment of calciphylaxis with low-dose tissue plasminogen activator has been reported.[59] 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.[60] 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.

Pain management is also crucially important.[61] 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.[4] 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.[62]

Total or subtotal parathyroidectomy with autotransplantation has been shown to be of therapeutic benefit to many, but not all, individuals.[4, 36, 63, 64, 65] Only a few studies have been able to demonstrate a decrease in the mortality rate in patients who undergo parathyroidectomy; however, it should be considered when levels are very high. Hyperparathyroidism may recur after surgery.

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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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Contributor Information and Disclosures
Author

Julia R Nunley, MD  Professor, Program Director, Dermatology Residency, Department of Dermatology, Virginia Commonwealth University Medical Center

Julia R Nunley, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, American Society of Nephrology, International Society of Nephrology, Medical Dermatology Society, Medical Society of Virginia, National Kidney Foundation, Phi Beta Kappa, and Women's Dermatologic Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Smeena Khan, MD  Private Practice, Adult and Pediatric Dermatology Associates

Smeena Khan, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

Richard P Vinson, MD  Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association

Disclosure: Nothing to disclose.

Jeffrey Meffert, MD  Assistant Clinical Professor of Dermatology, University of Texas School of Medicine at San Antonio

Jeffrey Meffert, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Association of Military Dermatologists, and Texas Dermatological Society

Disclosure: Nothing to disclose.

Joel M Gelfand, MD, MSCE  Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania

Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology

Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds Investigator; Genentech Grant/research funds investigator; Centocor Consulting fee Consulting; Abbott Grant/research funds investigator; Abbott Consulting fee Consulting; Novartis investigator; Pfizer Grant/research funds investigator; Celgene Consulting fee DMC Chair; NIAMS and NHLBI Grant/research funds investigator

Chief Editor

Dirk M Elston, MD  Director, Department of Dermatology, Geisinger Medical Center

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

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Several lesions of calciphylaxis that occurred on the lower extremity of a patient undergoing dialysis. These lesions developed in areas of livedo reticularis and followed the path of the vasculature.
An isolated lesion of calciphylaxis manifesting as an enlarging necrotic plaque on the lower extremity of a patient undergoing dialysis. The stellate purpuric morphology can be appreciated surrounding the area of necrosis.
Calciphylaxis may manifest as rapidly progressive, diffuse and extensive, cutaneous necrosis, as is seen in this patient with chronic renal failure. Bullae may also be seen as a rare manifestation of calciphylaxis.
Radiologic findings of a hand in a patient with calciphylaxis. Extensive calcification of the radial and ulnar arteries is readily visible.
Histologically, calcification of the blood vessels, as well as the subcutis, can be seen in calciphylaxis.
Demonstrated here is the characteristic circumferential medial calcific deposit in an arteriole with subintimal edema. Histologic images courtesy of Steve A. McClain, MD, Department of Dermatology SUNY-Stony Brook.
This image shows circumferential medial calcific deposits obliterating the external elastica of an arteriole. Histologic images courtesy of Steve A. McClain, MD, Department of Dermatology SUNY-Stony Brook.
 
 
 
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