Skin blister and skin biopsy to quantify epidermal nerves

Abstract

Skin biopsy is an important procedure for the diagnosis of peripheral neuropathy. The main indicators of unmyelinated nerve involvement are decreased density and abnormal morphology of epidermal nerve fibers (ENFs). The suction skin blister is an alternative, less invasive method to visualize and quantify ENFs. The blister roof provides an integrated bird's eye view of all ENFs within one tissue specimen. We compared the suction skin blister method to the punch skin biopsy for evaluation of ENFs. Twenty-five volunteers, 35 to 62 years old, without symptoms or history of peripheral neuropathy, and normal by neurologic examination and nerve conduction tests, were studied. One 3 mm punch biopsy and two 3 mm suction blister specimens were collected from the right foot and calf. Comparison between blister and biopsy ENF density was assessed by repeated measures analysis of covariance, accounting for age, gender, and specimen's location. The epidermal roof of the suction skin blister permitted detailed analyses of ENF density, morphology, and distribution across the epidermis and observation of ENF branching pattern. No systematic differences of ENF density were found between skin blisters and biopsies (p = 0.29) or between pairs of blisters from the same location (p = 0.15). ENF density was lower for older subjects (p < 0.01). The suction skin blister method has potential as a diagnostic tool to investigate small fiber neuropathies. It is a minimally invasive and reliable technique, comparable to skin biopsy for determining epidermal nerve fiber density.