Intraepidermal nerve fiber density and its application in sarcoidosis

Area of Science:

• Neurology
• Dermatology
• Pathology

Background:

• Intraepidermal nerve fiber density (IENFD) is a key diagnostic marker for small fiber neuropathy (SFN).
• Establishing reliable normative values for IENFD is essential for accurate diagnosis.
• Sarcoidosis can affect peripheral nerves, necessitating evaluation of diagnostic tools in this population.

Purpose of the Study:

• To determine stratified normative values for distal intraepidermal nerve fiber density (IENFD).
• To assess the reliability and validity of IENFD measurements in patients with sarcoidosis.
• To investigate the influence of age and sex on IENFD in a healthy population.

Main Methods:

• IENFD was measured in 188 healthy volunteers and 72 sarcoidosis patients using skin biopsies analyzed by bright-field microscopy.
• Healthy controls were stratified by age and sex to establish normative ranges.
• Reliability was assessed via interobserver and intraobserver analyses; validity was examined using symptom inventories and quality-of-life questionnaires in patients.

Main Results:

• A significant age-dependent decrease in IENFD was observed in healthy individuals, with lower values in men compared to women.
• High interobserver and intraobserver reliability (kappa values ≥ 0.90) were achieved for IENFD measurements.
• Reduced IENFD was found in 32.8% of sarcoidosis patients with SFN symptoms and 14.3% without symptoms, demonstrating the diagnostic utility.

Conclusions:

• Clinically applicable normative values for distal IENFD have been established, accounting for age and sex variations.
• IENFD measurements demonstrate good reliability and validity for diagnosing small fiber neuropathy, including in sarcoidosis.
• These normative values enhance the diagnostic capability of IENFD in clinical practice, particularly for peripheral neuropathies.