Calciphylaxis in Stage 3 Chronic Kidney Disease on Apixaban Successfully Treated With Sodium Thiosulfate

A Case Report

Faria Ali, MD; Tarvinder Matharu, MD; R. Venkata Nagesh, MD; Elizabeth Gordon Spratt, MD; Ben J. Friedman, MD, FAAD

Disclosures

Wounds. 2020;32(9):E42-E49. 

In This Article

Abstract and Introduction

Abstract

Introduction: Calciphylaxis is a serious condition that often occurs in patients with end-stage renal failure undergoing hemodialysis, with potential comorbidities of hyperparathyroidism and chronic kidney disease (CKD). It is a result of progressive calcification in small- and medium-sized arteries. Causing ischemia in multiple organs and skin ulcers, calciphylaxis has a poor prognosis. No definitive therapeutic or diagnostic guideline exists to prevent the devastating consequences of calciphylaxis. Association of warfarin with calciphylaxis has been reported in the literature, but, to the authors' knowledge, there are no literature reports of patients with CKD who were not on dialysis or warfarin developing calciphylaxis.

Objective: The authors report an unusual case of calciphylaxis in a patient with stage 3 CKD who was not on dialysis, warfarin, or insulin.

Case Report: A 72-year-old female with a history of type 2 diabetes mellitus, who was not taking subcutaneous insulin and had stage 3 CKD, was diagnosed with calciphylaxis by skin biopsy. She was treated with intravenous sodium thiosulfate twice weekly for 2 months with complete resolution of skin lesions.

Conclusions: This case illustrates that early diagnosis, intervention, and a multidisciplinary approach are of utmost importance in the management of calciphylaxis. Sodium thiosulfate, when used in the correct setting, can improve prognosis in patients. Serious consideration should be given to sodium thiosulfate as a practical measure of treatment.

Introduction

Calciphylaxis, or calcific uremic arteriolopathy, is a rare, life-threatening disease characterized by vascular calcifications. Among patients with end-stage renal disease (ESRD) who are on chronic hemodialysis, the incidence of calciphylaxis is 3.5 new cases per 1000 patient-years.[1] Implying a systemic anaphylactic or hypersensitivity reaction, the term calciphylaxis is actually a misnomer.[2] Calciphylaxis is commonly seen in patients with ESRD.[3,4] It also is reported in patients who do not have ESRD,[3,4] such as those with acute kidney injury (AKI),[5] recipients of kidney transplants,[6] and, rarely, patients with normal kidney function.[3,4,7,8]

It is characterized by microvascular occlusion of arterioles in subcutaneous adipose tissue and dermis, resulting in painful, indurated, and necrotic nodules.[3,9] A compromise in blood supply to the skin frequently manifests as livedo and reticulate (netlike) areas of erythema.[9] Dusky discoloration of the skin is a red flag for impending necrosis.[9] Initial lesions can quickly escalate to malodourous, stellate ulcers with black eschars,[10,11] which can lead to sepsis and death.[7,12,13] Hallmark histologic features include fibrointimal hyperplasia, calcification, thrombosis of microvessels, dermal-epidermal separation, necrotic adipose and epidermal tissue, extravascular calcifications, and dermal endothelial cell proliferation.[14,15]

Patients who are nonuremic (normal renal function or earlier stages of chronic kidney disease [CKD]) have a better prognosis, with a 1-year mortality of 25% to 40%.[7,8] In comparison, patients with ESRD have a 1-year mortality of 45% to 80%;[3,16,17] this may be attributed to the differences in coexisting comorbidities and the variation in location of lesions. In the literature, 50% of patients without ESRD have central lesions (ie, areas rich in adipose tissue including the breasts, abdominal pannus, thighs, and buttocks)[7,12] compared with 70% to 80% of patients with ESRD who have central distribution.[12,16] Patients with central lesions have been noted to have a higher body mass index (BMI), are more likely to be female,[16] and have a higher risk of death.[18] The presence of ulcerated (late) lesions is a poor prognostic indicator and decreases the 6-month survival rate to 20%.[17] The average age at the time of diagnosis ranges between 50 and 70 years old.[3,4,12,19] Risk factors include diabetes mellitus (DM), obesity, dependence on dialysis for more than 2 years, hepatobiliary disease, elevated alkaline phosphatase, hypoalbuminemia, thrombophilia (eg, protein C deficiency, lupus anticoagulant, antithrombin deficiency), vitamin K deficiency, and female sex.[1,7,8,16,19–23] Administration of recombinant parathyroid hormone (PTH)[20] and primary hyperparathyroidism[7] are additional risk factors in patients who are nonuremic. Warfarin, a vitamin K antagonist, predisposes individuals to develop calciphylaxis and increases mortality among these patients.[16,19,24–26]

Calciphylaxis is underrecognized, which can further jeopardize the health of patients with urgent, unmet clinical needs.[27] Once the diagnosis has been established, prognosis is usually poor, with survival estimated at less than 1 year.[3,16,17]

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