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Skin blister and skin biopsy to quantify epidermal nerves

A comparative study

From the Departments of Neuroscience (I.G.P.), Neurology (I.G.P., G.W.-C., W.R.K.), and Dermatology (I.G.P.), and Division of Biostatistics (J.S.H.), University of Minnesota,Minneapolis.

Address correspondence and reprint requests to Dr. Ioanna G. Panoutsopoulou, 420 Delaware St, MMC 187, Minneapolis, MN 55455

Background: 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.

Objective: We compared the suction skin blister method to the punch skin biopsy for evaluation of ENFs.

Methods: 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.

Results: 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).

Conclusions: 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.

BMI = body mass index; ENF = epidermal nerve fiber; PBS = phosphate buffered saline.

panou001{at}umn.edu

Editorial, page 1200

e-Pub ahead of print on December 17, 2008, at www.neurology.org.

Supported by the American Legion Brain Sciences Chair, the Juvenile Diabetes Research Foundation, and the RW Goltz Professorship in Dermatology.

Disclosure: Ioanna G. Panoutsopoulou, Gwen Wendelschafer-Crabb, and James S. Hodges report no conflicts of interest. William R. Kennedy holds a patent on the Skin Blister Apparatus and Method.

Received June 13, 2008. Accepted in final form October 13, 2008.

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				Analysis of Epidermal Nerve Fibers: Comparison of Two Techniques Journal Watch Neurology, June 30, 2009; 2009(630): 3 - 3. [Full Text]

				C. M. Klein and P. J. Dyck Skin biopsy for peripheral neuropathy: Is it better to punch or to blister? Neurology, April 7, 2009; 72(14): 1200 - 1201. [Full Text] [PDF]