title: Intraepidermal nerve fiber density and its application in sarcoidosis.
abstract: BACKGROUND
  Intraepidermal nerve fiber density (IENFD) is considered a good diagnostic tool for small fiber neuropathy (SFN).
  
  
  OBJECTIVE
  To assess stratified normative values for IENFD and determine the reliability and validity of IENFD in sarcoidosis.
  
  
  METHODS
  IENFD was assessed in 188 healthy volunteers and 72 patients with sarcoidosis (n = 58 with SFN symptoms, n = 14 without SFN symptoms). Healthy controls were stratified (for age and sex), resulting in 6 age groups (20-29, 30-39, ... up to > or = 70 years) containing at least 15 men and 15 women. A skin biopsy was taken in each participant 10 cm above the lateral malleolus and analyzed in accordance with the international guidelines using bright-field microscopy. Interobserver/intraobserver reliability of IENFD was examined. In the patients, a symptoms inventory questionnaire (SIQ; assessing SFN symptoms) and the Vickrey Peripheral Neuropathy Quality-of-Life Instrument-97 (PNQoL-97) were assessed to examine the discriminative ability of normative IENFD values.
  
  
  RESULTS
  There was a significant age-dependent decrease of IENFD values in healthy controls, with lower densities in men compared with women. Good interobserver/intraobserver reliability scores were obtained (kappa values > or = 0.90). A total of 21 patients with sarcoidosis had a reduced IENFD score (< 5th percentile; 19 [32.8%] in patients with SFN symptoms, 2 [14.3%] in patients without SFN symptoms). The validity of the normative IENFD values was demonstrated by distinguishing between the SIQ scores and various PNQoL-97 values for the different patient groups.
  
  
  CONCLUSIONS
  This study provides clinically applicable distal intraepidermal nerve fiber density normative values, showing age- and sex-related differences.
authors.affiliation: Department of Neurology, Maastricht University Medical Centre, PO Box 5800, 6202 AZ, Maastricht, The Netherlands. m.bakkers@mumc.nl
authors.forename: M
authors.initials: M
authors.lastname: Bakkers
authors.forename: I S J
authors.initials: IS
authors.lastname: Merkies
authors.forename: G
authors.initials: G
authors.lastname: Lauria
authors.forename: G
authors.initials: G
authors.lastname: Devigili
authors.forename: P
authors.initials: P
authors.lastname: Penza
authors.forename: R
authors.initials: R
authors.lastname: Lombardi
authors.forename: M C E
authors.initials: MC
authors.lastname: Hermans
authors.forename: S I
authors.initials: SI
authors.lastname: van Nes
authors.forename: M
authors.initials: M
authors.lastname: De Baets
authors.forename: C G
authors.initials: CG
authors.lastname: Faber
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001706:Biopsy; D016022:Case-Control Studies; D004817:Epidermis / Q000294:innervation*; D005260:Female; D006801:Humans; D008297:Male; D008853:Microscopy; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology*; D010523:Peripheral Nervous System Diseases / Q000209:etiology* / Q000473:pathology*; D011788:Quality of Life; D015203:Reproducibility of Results; D012507:Sarcoidosis / Q000150:complications* / Q000473:pathology; D012737:Sex Factors; D011795:Surveys and Questionnaires