Morphometry of dermal nerve fibers in human skin

Neuromuscular Diseases Unit, IRCCS Foundation, Carlo Besta Neurological Institute, Via Celoria, 11, 20133, Milan, Italy.
Neurology (Impact Factor: 8.29). 07/2011; 77(3):242-9. DOI: 10.1212/WNL.0b013e318225ab51
Source: PubMed


We aimed to assess the innervation density of dermal nerves in human skin biopsies by bright-field immunohistochemistry.
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-μm 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/mm2) 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.
Patients showed significantly lower DNFL (1.96 mm ± 0.96 SD), DNFL/mm (0.65 ± 0.29 SD), and DNFL/mm2 (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/mm2 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/mm2. 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).
We provided a reliable method to quantify the innervation density of dermal nerves that might improve the diagnostic yield of skin biopsy.

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Available from: Giuseppe Lauria, May 19, 2014
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    • "Indeed, in about 12% of patients with complaints of SFN, IENF density can be normal (Devigili et al., 2008). We have recently standardized a new method to determine the innervation of the dermis in human skin by measuring the overall length of the fibers, that proved to be reliable in terms of diagnostic yield in patients with pure SFN (Lauria et al., 2011). Other studies are warranted to demonstrate that dermal nerve morphometry can increase the value of skin biopsy in diagnosing patients with neuropathy. "
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