title: Reduced intraepidermal nerve fibre density in lesional and nonlesional prurigo nodularis skin as a potential sign of subclinical cutaneous neuropathy.
abstract: BACKGROUND
  Prurigo nodularis (PN) is a highly pruritic condition characterized by multiple hyperkeratotic nodules. Previous immunohistochemical studies demonstrated increased numbers of dermal nerve fibres.
  
  
  OBJECTIVE
  Given that the sensation of pruritus is transmitted mainly by thin, unmyelinated epidermal nerves, the aim of our study was to investigate the intraepidermal nerve fibre (IENF) density.
  
  
  METHODS
  Biopsies taken from lesional and nonlesional skin of 53 patients (37 women and 16 men; mean ± SD age 60·6 ± 14·9 years) with PN of diverse origin were immunostained for protein gene product 9·5. According to the guideline of the European Federation of Neurological Societies, the IENF density per millimetre was determined and compared with that in 20 healthy volunteers.
  
  
  RESULTS
  Lesional and uninvolved PN skin biopsies showed significantly decreased IENF density (P < 0·001) regardless of patient age, origin of PN, intensity or quality of pruritus.
  
  
  CONCLUSIONS
  Hypoplasia of epidermal sensory nerves independently of clinical parameters is a new finding in PN and suggests involvement of epidermal nerves in PN pathophysiology. To date, it cannot be ruled out that reduced IENF density is due to repeated scratching. However, the presence of hypoplasia in nonlesional PN skin suggests the presence of a subclinical small fibre neuropathy.
authors.affiliation: Departments of Dermatology Neurology, Competence Center Chronic Pruritus, University Hospital Münster, D-48149 Münster, Germany. sonja.staender@uni-muenster.de
authors.forename: B
authors.initials: B
authors.lastname: Schuhknecht
authors.forename: M
authors.initials: M
authors.lastname: Marziniak
authors.forename: A
authors.initials: A
authors.lastname: Wissel
authors.forename: N Q
authors.initials: NQ
authors.lastname: Phan
authors.forename: D
authors.initials: D
authors.lastname: Pappai
authors.forename: J
authors.initials: J
authors.lastname: Dangelmaier
authors.forename: D
authors.initials: D
authors.lastname: Metze
authors.forename: S
authors.initials: S
authors.lastname: Ständer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D015331:Cohort Studies; D004817:Epidermis / Q000294:innervation*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology*; D009431:Neural Conduction; D015588:Observer Variation; D010523:Peripheral Nervous System Diseases / Q000473:pathology*; D011536:Prurigo / Q000473:pathology*