Correlation between clinical and pathological features of cutaneous calciphylaxis

Abstract

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.

Fig 1. Patient selection criteria.

Fig 2. Representative images of skin lesions with various clinical and histological features.

(A): Clinical image of an ulcer with black eschar and irregular violaceous border and surrounding erythema. (B): Non-ulcerated calciphylaxis lesions with plaque morphology and surrounding retiform purpura. (C): Erythematous lesions of calciphylaxis. (D): Histopathology of cutaneous calciphylaxis demonstrating ulceration, marked dermal necrosis, fibrointimal hyperplasia of a calcified medium sized vessel and subcutaneous fat necrosis with foci of acute inflammation (hematoxylin & eosin, 40x original magnification). (E): A von Kossa stain reveals presence of stippled peri-eccrine calcification (von Kossa stain, 600x original magnification). Panel F: Intravascular thrombosis in the deep dermis (hematoxylin & eosin stain, 200x original magnification).

Fig 3. Distribution of study cohort according to the Mayo Clinic criteria [4], for likelihood of calciphylaxis diagnosis.