Morphometry of dermal nerve fibers in human skin

G. Lauria*, D. Cazzato, C. Porretta-Serapiglia, J. Casanova-Molla, M. Taiana, P. Penza, Raffaella Lombardi, C. G. Faber, Ingemar S. J. Merkies

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Objective: We aimed to assess the innervation density of dermal nerves in human skin biopsies by bright-field immunohistochemistry. Methods: The size of dermal area where nerve length was quantified was validated in 30 skin biopsy sections (5 controls and 5 patients with small-fiber neuropathy [SFN]). It was obtained dividing an area of 200-mu m depth from the dermal-epidermal junction into 4 equal portions. The length of dermal nerves (DNFL) was measured into 150 sections (25 controls and 25 patients with SFN) and values per millimeter of epidermis (DNFL/mm) and dermal area (DNFL/mm(2)) were obtained. Age-and gender-matched normative values of intraepidermal nerve fiber (IENF) density were used as gold standard to calculate the performance of dermal nerve morphometry. Results: Patients showed significantly lower DNFL (1.96 mm +/- 0.96 SD), DNFL/mm (0.65 +/- 0.29 SD), and DNFL/mm(2) (3.75 +/- 1.7 SD) than controls (DNFL 3.52 mm +/- 1.31 SD, 5th percentile 2.05; DNFL/mm 1.25 +/- 0.39, 5th percentile 0.71; DNFL/mm(2) 7.07 +/- 2.41 SD, 5th percentile 3.95). Sensitivity, specificity, and percentage of individuals correctly classified were 75.8%, 73.9%, and 74.8% for DNFL, 75%, 80%, and 77.7% for DNFL/mm, and 75.8%, 80.2%, and 78.1% for DNFL/mm(2). Receiver operator characteristic area analysis confirmed the excellent discrimination (0.8-0.9) between patients and controls. Dermal nerve morphometry significantly correlated with IENF density. Spearman rank correlation demonstrated good agreement for interobserver analysis (0.87-0.89), and between DNFL and IENF densities (0.71-0.73; p <0.0001). Conclusions: We provided a reliable method to quantify the innervation density of dermal nerves that might improve the diagnostic yield of skin biopsy. Neurology (R) 2011;77:242-249
Original languageEnglish
Pages (from-to)242-249
Issue number3
Publication statusPublished - Jul 2011

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