title: Epidermal innervation morphometry by immunofluorescence and bright-field microscopy.
abstract: We investigated the agreement between simple indirect immunofluorescence (IF) and bright-field immunohistochemistry (BFI) on free-floating sections for intraepidermal nerve fiber density (IENFD) quantification. Fifty-five healthy subjects and 63 patients with probable small fiber neuropathy (SFN) underwent two adjacent skin biopsies at the distal leg processed by IF and BFI technique. Agreement between IENFD pairs obtained by each method was assessed by Bland-Altman testing. The area under the curve of the receiving operating characteristics (ROC) curves was used to compare the discrimination ability. The diagnostic judgment was based on sex and age-adjusted normative values. IF and BFI showed good correlation (r = 0.81), with a ratio of about 2:1 and a mean difference of 5.5 ± 3.0 IENF per millimeter between paired measures, as demonstrated by linear regression and Bland-Altman test analyses. The square root transformation confirmed a Poisson distribution of the data and a fixed bias between IF and BFI measurements. The ROC curves analysis demonstrated a striking overlap between IF and BFI (0.83 and 0.82; p = 0.72). The diagnosis of SFN disagreed in only 6.7% of cases when the judgment was based on a difference of >1 IENF from 5% cut-off value. IF and BFI showed comparable diagnostic efficiency when referred to appropriate normative reference values.
authors: "Salvatore Maugeri" Foundation, Institute of Telese Terme (BN), Telese Terme (BN), Italy.
authors: Maria
authors: M
authors: Nolano
authors: Department of Neurology and Psychiatry, University Sapienza, Rome, Italy.
authors: Antonella
authors: A
authors: Biasiotta
authors: 3rd Neurology Unit and Skin Biopsy, Peripheral Neuropathy and Neuropathic Pain Clinic, IRCCS Foundation "Carlo Besta" Neurological Institute, Milan, Italy.
authors: Raffaella
authors: R
authors: Lombardi
authors: "Salvatore Maugeri" Foundation, Institute of Telese Terme (BN), Telese Terme (BN), Italy.
authors: Vincenzo
authors: V
authors: Provitera
authors: "Salvatore Maugeri" Foundation, Institute of Telese Terme (BN), Telese Terme (BN), Italy.
authors: Annamaria
authors: A
authors: Stancanelli
authors: "Salvatore Maugeri" Foundation, Institute of Telese Terme (BN), Telese Terme (BN), Italy.
authors: Giuseppe
authors: G
authors: Caporaso
authors: Department of Neurosciences, Reproductive Science and Odontostomatology, University Federico II of Naples, Napoli, Italy.
authors: Lucio
authors: L
authors: Santoro
authors: Department of Neurology, Spaarne Hospital, Hoofddorp, The Netherlands.
authors: Ingemar S J
authors: IS
authors: Merkies
authors: Department of Neurology and Psychiatry, University Sapienza, Rome, Italy.
authors: Andrea
authors: A
authors: Truini
authors: 3rd Neurology Unit and Skin Biopsy, Peripheral Neuropathy and Neuropathic Pain Clinic, IRCCS Foundation "Carlo Besta" Neurological Institute, Milan, Italy.
authors: Carla
authors: C
authors: Porretta-Serapiglia
authors: 3rd Neurology Unit and Skin Biopsy, Peripheral Neuropathy and Neuropathic Pain Clinic, IRCCS Foundation "Carlo Besta" Neurological Institute, Milan, Italy.
authors: Daniele
authors: D
authors: Cazzato
authors: 3rd Neurology Unit and Skin Biopsy, Peripheral Neuropathy and Neuropathic Pain Clinic, IRCCS Foundation "Carlo Besta" Neurological Institute, Milan, Italy.
authors: Patrizia
authors: P
authors: Dacci
authors: "Salvatore Maugeri" Foundation, Institute of Telese Terme (BN), Telese Terme (BN), Italy.
authors: Dino F
authors: DF
authors: Vitale
authors: 3rd Neurology Unit and Skin Biopsy, Peripheral Neuropathy and Neuropathic Pain Clinic, IRCCS Foundation "Carlo Besta" Neurological Institute, Milan, Italy.
authors: Giuseppe
authors: G
authors: Lauria
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D004817:Epidermis / Q000294:innervation*; D004916:Erythromelalgia / Q000473:pathology*; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008297:Male; D008853:Microscopy / Q000379:methods*; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology*
keywords: immunofluorescence; immunohistochemistry; intraepidermal nerve fiber; painful neuropathy; skin biopsy