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Updated: Mar 10, 2026
Three-dimensional Imaging of Nociceptive Intraepidermal Nerve Fibers in Human Skin Biopsies
Published on: April 29, 2013
Epidermal Nerve Fiber Quantification in Patients With Erythromelalgia
William G Mantyh1, P James B Dyck1, Peter J Dyck1
1Department of Neurology, Mayo Clinic, Rochester, Minnesota.
Erythromelalgia diagnosis does not involve loss of epidermal nerve fiber density (ENFD). However, functional small fiber studies are beneficial for evaluating this condition, as most patients exhibit impaired small fiber function.
Area of Science:
- Neurology
- Dermatology
- Pain Medicine
Background:
- Erythromelalgia is diagnosed clinically by warmth, erythema, and pain in extremities.
- Objective diagnostic methods for erythromelalgia are lacking.
- Small fiber neuropathy can be assessed via epidermal nerve fiber density (ENFD).
Purpose of the Study:
- To investigate if erythromelalgia is associated with reduced ENFD.
- To compare structural small fiber assessment with functional studies.
Main Methods:
- Retrospective analysis of 52 erythromelalgia patients.
- Clinical diagnosis by a dermatologist.
- Epidermal nerve fiber density (ENFD) quantification.
- Functional small fiber testing (autonomic and pain thresholds).
Main Results:
- Only 10% of patients showed reduced ENFD.
- 60% had abnormal sweat test results.
- 42% had abnormal pain thresholds.
- 38% had abnormal autonomic cardiovascular control.
Conclusions:
- Erythromelalgia is not characterized by loss of ENFD, unlike other small fiber neuropathies.
- Most erythromelalgia patients have functional small fiber impairments.
- Functional small fiber testing is recommended for evaluating erythromelalgia.
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