Date Published: June 13, 2019
Publisher: Public Library of Science
Author(s): Puja Dutta, Kristine M. Chaudet, Rosalynn M. Nazarian, Daniela Kroshinsky, Sagar U. Nigwekar, Elena Aikawa.
Calciphylaxis is a rare and life-threatening disease that classically manifests with painful skin lesions. It occurs mainly in patients with end-stage renal disease (ESRD) treated with dialysis, has poor outcomes, and has no FDA-approved treatment. Our cohort study aims to examine the clinical and pathological features of calciphylaxis and investigates the correlation between cutaneous clinical manifestations and histopathological findings. Data from 70 calciphylaxis patients who were evaluated at the Massachusetts General Hospital between January 2014 and April 2018 were collected from the institutional electronic database. The median age was 58 years (interquartile range [IQR]: 49–69 years), 60% were women, and 73% were of white race. Most (74%) patients reported severe pain at the time of calciphylaxis diagnosis with a median pain intensity score of 8/10 (IQR: 6–10) on a 0–10 pain scale. The median time from symptom onset to clinical diagnosis was 9 weeks (IQR: 6–16 weeks). The majority (87%) of patients presented with open necrotic wounds (advanced stage lesion) at the time of diagnosis. Common cutaneous clinical features included ulceration (79%), induration (57%), and erythema (41%), while common pathological features included cutaneous microvascular calcification (86%) and necrosis (73%). The presence of fibrin thrombi in skin biopsies was associated with pain severity (p = 0.04). The stage of a skin lesion positively correlated with the presence of necrosis on histological analyses (p = 0.02). These findings have implications for improving understanding of calciphylaxis origins and for developing novel treatments.
Calciphylaxis, or calcific uremic arteriolopathy, is a rare and devastating disease characterized by calcification of microvessels in the subcutaneous adipose tissue, causing painful, ischemic skin lesions [1,2]. Patients with calciphylaxis have poor clinical outcomes, with the one-year mortality rate estimated at more than 50% . The exact pathogenesis of calciphylaxis is poorly understood, and there are no FDA-approved therapies for calciphylaxis [1,4].
Table 1 provides a summary of demographic and clinical characteristics. The median age of patients at the time of diagnosis of calciphylaxis was 58 years (IQR: 49–69 years). Most patients were female (60%) and had ESRD (83%). Obesity and diabetes mellitus were present in 56% and 61% of study patients, respectively. Almost half of the patient cohort (47%) was on warfarin at the time of diagnosis of calciphylaxis. Most patients (74%) reported severe pain at the time of diagnosis, with the median pain score being 8 (IQR: 6–10) on a 0–10 pain scale. The median time from the onset of symptoms of calciphylaxis to the diagnosis was 9 weeks (IQR: 6–16 weeks). Tactile hyperesthesia was reported in 36% of patients. Neuropathic pain was reported in 27% of patients. Two of 70 study patients (3%) reported local skin trauma from injections of heparin and insulin prior to the development of calciphylaxis.
Our study identifies associations between cutaneous clinical features and histopathological findings in calciphylaxis patients. The presence of fibrin thrombi in skin biopsies was associated with pain severity and the stage of a skin lesion positively correlated with the presence of necrosis on histological analyses. Furthermore, microvascular calcification was found to be eight times more common in patients with ulcerated lesions than in those without.