BACKGROUND: Intraepidermal nerve fiber density (IENFD) is considered a good diagnostic tool for small fiber neuropathy (SFN). OBJECTIVES: 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 '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 (κ values '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. CONCLUSION: This study provides clinically applicable distal intraepidermal nerve fiber density normative values, showing age-and sex-related differences.

adult, aged, article, bright field microscopy, construct validity, controlled study, female, groups by age, human, human tissue, interrater reliability, intraepidermal nerve fiber density, intrarater reliability, major clinical study, male, neuropathy, priority journal, quality of life, sarcoidosis, sensory analysis, sex difference, skin biopsy, structured questionnaire,
Erasmus MC: University Medical Center Rotterdam

Bakkers, M, Merkies, I.S.J, Lauria, G, Devigili, G, Penza, P, Lombardi, R, … Faber, C.G. (2009). Intraepidermal nerve fiber density and its application in sarcoidosis. Neurology, 73(14), 1142–1148. doi:10.1212/WNL.0b013e3181bacf05