title: Skin blister and skin biopsy to quantify epidermal nerves: a comparative study.
abstract: 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.
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA. panou001@umn.edu
authors.forename: Ioanna G
authors.initials: IG
authors.lastname: Panoutsopoulou
authors.forename: Gwen
authors.initials: G
authors.lastname: Wendelschafer-Crabb
authors.forename: James S
authors.initials: JS
authors.lastname: Hodges
authors.forename: William R
authors.initials: WR
authors.lastname: Kennedy
mesh_terms: D000328:Adult; D000375:Aging / Q000502:physiology; D001706:Biopsy / Q000379:methods*; D002452:Cell Count; D004817:Epidermis / Q000294:innervation* / Q000473:pathology*; D005260:Female; D005528:Foot; D006801:Humans; D007866:Leg; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009412:Nerve Fibers / Q000502:physiology; D010525:Peripheral Nerves / Q000473:pathology*; D010523:Peripheral Nervous System Diseases / Q000473:pathology*; D015203:Reproducibility of Results; D012867:Skin / Q000294:innervation* / Q000473:pathology*