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Updated: Jan 19, 2026

Three-dimensional Imaging of Nociceptive Intraepidermal Nerve Fibers in Human Skin Biopsies
Published on: April 29, 2013
Evaluation of small nerve fiber dysfunction in type 2 diabetes
Linnéa Ekman1, Soley Thrainsdottir2,3, Elisabet Englund4
1Department of Hand Surgery, Skåne University Hospital, Malmö, Sweden.
Intraepidermal nerve fiber density (IENFD) correlates with peripheral neuropathy measures in elderly men. Lower IENFD indicates increased neuropathy prevalence, suggesting its utility in diagnosing nerve damage.
Area of Science:
- Neurology
- Histopathology
- Diabetology
Background:
- Peripheral neuropathy is a common complication of diabetes.
- Assessing small nerve fibers in the skin is crucial for diagnosis.
- Limited data exists on the correlation between intraepidermal nerve fiber density (IENFD) and clinical neuropathy measures in different glucose tolerance groups.
Purpose of the Study:
- To investigate the relationship between intraepidermal nerve fiber density (IENFD) and clinical neuropathy assessments.
- To compare IENFD across elderly men with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes (T2DM).
Main Methods:
- Skin biopsies from the distal leg of 86 men (71-77 years) were analyzed for IENFD using immunohistochemistry (PGP 9.5).
- IENFD was correlated with neurophysiological tests (nerve conduction study, quantitative sensory testing) and clinical scores (Total Neuropathy Score).
Main Results:
- Absent intraepidermal nerve fibers (IENF) were observed in 21% of T2DM and 7% of IGT subjects.
- IENFD showed weak negative correlations with HbA1c and Total Neuropathy Score.
- Positive correlations were found between IENFD and sural nerve amplitude and conduction velocity.
Conclusions:
- Decreasing IENFD is associated with a higher prevalence of neuropathy signs.
- The presented technique for evaluating IENFD in histopathological sections is valuable for neuropathy detection.
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