The Evaluation of Intraepidermal Nerve Fiber Density in Skin Biopsy – Normative Data

Summary

Introduction:
At present, evaluation of intraepidermal nerve fiber density (IENFD) from skin bio­psies represents one of the most important methods for diagnosing neuropathic pain and sensory neuropathies, particularly in small-fiber neuropathy patients. The aim of the study was to analyze the effects physiological variables may have on IENFD values and to establish valid IENFD normal limits for distal calf region. Furthermore, we evaluated the IENFD values from anterolateral proximal thigh samples in a pilot study with a small group of healthy individuals.

Patients and methods:
Skin biopsies from the distal calf were obtained from a group of 74 healthy individuals (39 men, 35 women, age: median 54.5 years, range 27–84 years). IENFD was established in all the samples using the indirect immunofluorescence method. The effect of age and gender on IENFD values was evaluated and age-stratified normal values were derived in subgroups of patients aged 20–40, 40–60 and 60+ years. In addition, IENFD values obtained from proximal thigh skin biopsies of 14 individuals were compared to the distal samples.

Results:
Significant age-related decrease in IENFD values and non-significant trend to higher IENFD values in women were found in distal skin biopsy samples. Lower normal limits in the respective age subgroups were set at 5.5–5.1–1.9 fi­bers per 1 mm in men and 6.1–5.2–3.1, respectively, in women. Compared to the distal samples, proximal IENFD values were significantly higher.

Conclusion:
In a group of healthy volunteers, a significant effect of age and non-significant trend towards an effect of gender on IENFD values was found. Therefore, age-stratified and gender-specific normal values should be used when evaluating IENFD in distal skin biopsy samples. Comparison of these findings to proximal thigh samples confirms significant proximo-distal gradient of IENFD values.

Key words:
skin biopsy – intraepidermal nerve fiber density – normative values – healthy individuals – age stratification