Morphometry of dermal nerve fibers in human skin.

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-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. RESULTS: 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). CONCLUSIONS: We provided a reliable method to quantify the innervation density of dermal nerves that might improve the diagnostic yield of skin biopsy.

Intraepidermal nerve fiber density and its application in sarcoidosis.

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 > or = 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 (kappa values > or = 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.

Neumomediastino espontáneo asociado al consumo de drogas inhalantes / Spontaneous pneumomediastinum as a complication of inhalant drug use

El neumomediastino es una entidad descripta por Hamman en 1939 y cuya patogenia fue establecida por Macklin en 1944(1). Se define por la presencia de aire en el mediastino y el carácter de espontáneo se lo otorga la ausencia de vinculación con otras patologías asociadas. Es una enfermedad benigna, infrecuente, autolimitada y que puede asociarse a neumotórax. Este trabajo presenta dos casos de neumomediastino espontáneo, sin neumotórax, en los cuales se destaca la concomitancia de inhalación de cocaína y pasta base de cocaína.