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Altman K, Shinohara M. Demographics, Comorbid Conditions, and Outcomes of Patients With Nonuremic Calciphylaxis. JAMA Dermatol. 2019;155(2):251–252. doi:10.1001/jamadermatol.2018.4937
Calciphylaxis (calcific uremic arteriolopathy) is a rare, potentially life-threatening condition in which vascular calcification produces ulcerative skin lesions. Calciphylaxis was first described in patients with end-stage renal disease receiving dialysis, with an annual incidence of 35 cases per 10 000 patients in the United States.1 Calciphylaxis has also been observed in patients without renal disease, and the condition is termed nonuremic calciphylaxis (NUC). The most common underlying conditions associated with NUC are hyperparathyroidism, malignant neoplasm, alcoholic liver disease, and autoimmune disorders.2 In addition, exposure to some medications, such as corticosteroids, may increase the risk of NUC, possibly by affecting the receptor activator of nuclear factor-κB, receptor activator of nuclear factor-κB ligand, or osteoprotegerin, which are involved in regulation of extraskeletal calcification.3 With this knowledge, we sought to investigate the demographics, comorbid conditions, and outcomes of patients with NUC at the University of Washington hospitals and to compare this information with prior published findings.
We reviewed patients’ electronic medical records at the University of Washington hospital system, searching for the term “calciphylaxis” in the body of a pathology report or diagnostic line from 2000 to 2017. The pathology reports and the patients’ medical records were reviewed to determine if the pathology was consistent with calciphylaxis. Additionally, medical histories were reviewed to determine if the patients had renal disease to categorize the condition as uremic calciphylaxis or NUC. The University of Washington institutional review board approved this study. Patient written informed consent was not required.
We identified 81 cases of calciphylaxis. Of these cases, 16 patients (20%) had NUC. The patients with NUC ranged in age from 22 to 87 years, and 15 of 16 patients (94%) were women. All patients had ulceration. Skin biopsy specimens tested positive for calciphylaxis in 10 of 16 patients. Results were equivocal in 6 biopsy specimens; however, a consulting dermatologist determined that the results from these specimens were compatible with calciphylaxis, and there was no other clear diagnosis based on pathology findings. In the group of patients with NUC, 8 (50%) had received warfarin, while 2 (13%) had been treated with heparin. Three patients (19%) had systemic lupus or antiphospholipid syndrome and were also receiving warfarin. Two patients (13%) had diabetes and 1 (6%) had secondary hyperparathyroidism (Table).
The most common treatments initiated in the NUC cohort were intravenous sodium thiosulfate 3 times per week (63%, n = 10), cinacalcet (6%, n = 1), and antibiotics (50%, n = 8). At the time of our analysis, 75% of patients (n = 12) with NUC were alive, with survival ranging from 1 to 14 years after diagnosis.
Although the number of cases of NUC in the study is small, the condition affected a high percentage of women receiving anticoagulation therapy, adding further support to the body of evidence that sex and anticoagulant use are 2 important risk factors for NUC. Warfarin, in particular, has been hypothesized to promote NUC by inhibiting vitamin K–dependent carboxylation of matrix Gla protein, decreasing inhibition of local calcification.4
The estimated 1-year survival rate for all patients with calciphylaxis has previously been reported as 45.8%5; and patients with ulceration fare worse, with an estimated 80% mortality.6 Patients in the present study had a high survival rate (75%) despite the fact that all patients had ulceration. One possible reason for this improved survival rate is the frequent use of sodium thiosulfate, with 63% of patients (n = 10) in our analysis receiving this form of therapy. This finding contrasts with the 48% survival rate previously reported among NUC patients2; notably, none of these patients received sodium thiosulfate, suggesting a possible benefit associated with sodium thiosulfate therapy for NUC.
A limitation of the study is that only patients who had a skin biopsy were included. The diagnosis of calciphylaxis is often made on clinical grounds, particularly in the setting of end-stage renal disease, and a skin biopsy is not always performed.
Accepted for Publication: November 7, 2018.
Corresponding Author: Katherine Altman, DO, MS, 1959 NE Pacific St, Seattle, WA 98195 (firstname.lastname@example.org).
Published Online: January 2, 2019. doi:10.1001/jamadermatol.2018.4937
Author Contributions: Dr Altman had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Shinohara.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Altman.
Critical revision of the manuscript for important intellectual content: Shinohara.
Statistical analysis: Altman.
Study supervision: Shinohara.
Conflict of Interest Disclosures: None reported.