Clinical Pearls & Morning Reports
Published May 2, 2018
Calciphylaxis is a rare, life-threatening syndrome of vascular calcification characterized by occlusion of microvessels in the subcutaneous adipose tissue and dermis that results in intensely painful, ischemic skin lesions. Sepsis originating from the resultant wounds is considered the most common cause of death. Read the latest Review Article here.
Q: What are some of the risk factors for calciphylaxis?
A: The disorder, which is underrecognized, typically affects patients with end-stage renal disease (ESRD). Calciphylaxis also occurs in patients with earlier stages of chronic kidney disease, acute kidney injury, or prior receipt of a kidney transplant, and in rare cases, it occurs in patients with normal kidney function. Approximately 60 to 70% of patients with calciphylaxis are women. Risk factors for calciphylaxis include obesity, diabetes mellitus, female sex, and dependence on dialysis for more than 2 years. Elevations in phosphate and calcium levels increase the risk of subsequent calciphylaxis in patients undergoing dialysis. The use of warfarin, a vitamin K antagonist, increases the risk of calciphylaxis by a factor of 3 to 13.
Q: What are some of the clinical manifestations of calciphylaxis?
A: Calciphylaxis causes painful skin lesions. The initial skin manifestations may include induration, plaques, nodules, livedo, or purpura. A dusky discoloration of the skin indicates an area of imminent necrosis. Because an arteriole supplies a 1-to-3-cm conical area of microvasculature in a funnel shape, there are frequently reticulate (netlike) areas of erythema and livedo. Patients typically have multiple, bilateral lesions, with surrounding skin showing a leatherlike texture. The initial lesions rapidly progress to stellate, malodorous ulcers with black eschars. The presence of ulcerated (late) lesions reduces the 6-month survival rate to 20%.
A: Clinical suspicion is important for an early diagnosis. Elevations in serum calcium or phosphate levels are not specific. Skin biopsy is the standard method for confirmation of clinically suspected calciphylaxis; however, its role in practice is debated, given the risk of provoking new, nonhealing ulcers and infection. A biopsy is not needed for a patient with ESRD and the classic presentation of a painful necrotic ulcer covered with a black eschar. However, a biopsy should be strongly considered if a patient has early, atypical lesions or if calciphylaxis is suspected in a patient without ESRD. A biopsy is contraindicated for acral, penile, or infected lesions. Although imaging studies (e.g., plain radiography, mammography, or nuclear bone scanning) are not routinely recommended for the diagnosis, they may support the diagnosis when a biopsy is inconclusive or contraindicated.
A: Although there is no approved therapy for calciphylaxis, several approaches may be effective. Sodium thiosulfate is an agent with antioxidant and vasodilatory properties that also inhibits adipocyte calcification and blocks the ability of adipocytes to induce calcification of vascular smooth-muscle cells. In a study involving 53 hemodialysis-dependent patients with calciphylaxis who were treated with intravenous sodium thiosulfate (three times per week [with each dialysis session] for approximately 3 months), calciphylaxis completely resolved in 26% of the patients, and 19% had marked improvement in skin lesions. In another study, involving 27 patients being treated with dialysis, complete remission was observed in 52% of the patients and partial remission in 19% after treatment with intravenous sodium thiosulfate. Lack of a control group and the retrospective nature of the study preclude definitive conclusions regarding the effectiveness of sodium thiosulfate. Although successful use of sodium thiosulfate for the treatment of calciphylaxis was first reported more than a decade ago, only now are to ongoing trials investigating its safety and efficacy.