The usefulness of quantifying intraepidermal nerve fibers density in the diagnostic of diabetic peripheral neuropathy: a cross-sectional study

Background: Distal symmetric polyneuropathy (DSPN) is the most common complication of type 2 diabetes mellitus (T2DM) and the most common form of peripheral neuropathy. DSPN increases the risk of foot ulceration up to sevenfold, and is a significant risk factor in more than 60 % of the amputations of the lower limbs in patients with T2DM. The aims of our study were to evaluate the difference in the density of intraepidermal nerve fibers (IENF) in patients with respectively without DSPN, to evaluate the strength of the relationship between the symptomatology of the DSPN and IENF density and to define a cutoff value of the IENF density for the diagnosis of DSPN. Methods: We enrolled, according to a consecutive, population-based method, 36 patients with T2DM admitted in our Clinic. For all patients, we measured HbA1c, lipid profile, body mass index and we assessed the presence and severity of DSPN using the evaluation of clinical symptoms, nerve conduction velocity and IENF density quantification. Results: The presence of neuropathy was significantly associated with a decreased density of IENF for both the proximal (11.6 vs. 14.9 fibers/mm; p = 0.014) and the distal biopsies (7.2 vs. 8.6 fibers/mm; p = 0.020). The optimal threshold value of IENF density (the point with the maximum sum of specificity and sensitivity), according to our model, was 10.1 fibers/mm. Conclusions: Skin biopsy followed by IENF density quantification is a valid, reliable tool for the diagnosis of DSPN.