Assessment of Intraepidermal Nerve Fiber using Skin Biopsy in Diabetic Polyneuropathy

ABSTRACT

BACKGROUND: Immunohistochemical staining of skin for panaxonal marker, protein gene product 9.5 (PGP 9.5), has recently emerged as a useful diagnostic procedure for the assessment of small nerve fibers. The first aim of our study is to quantify the intraepidermal nerve fibers (IEDNF) and to investigate the histological changes of IEDNF in diabetic patents. And the second is to evaluate whether IEDNF has the correlation with the clinical, electrophysiological and biological parameters. METHODS: Skin biopsy specimens were obtained at the distal leg and proximal thigh from twelve type 2 diabetes mellitus patients having the symptoms of peripheral polyneuropathy. Fixed sections were stained using PGP 9.5, and the number of intraepidermal nerve fibers at each site was compared with those of fifteen normal healthy volunteers. We analyzed the correlation of IEDNF density with the clinical history, neuropathic symptom score (NSS), severity of diabetes (serum glucose, HbA1C), and nerve conduction studies. RESULTS: The number of IEDNF in diabetic patients was 3.0 per millimeter at the distal leg and 12.7 per millimeter at the proximal thigh compared with 15.3 per millimeter and 23.3 per millimeter in normal control respectively. Some specimen showed a morphological change of axons such as axonal swelling. The IEDNF density was not correlated with the duration of disease, biological or electrophysiological parameters but correlated with the clinical neuropathic symptom score. CONCLUSIONS: The IEDNF density is reduced in all the diabetic patients, more severely at the distal extremity. We suggest skin biopsy can provide the quantification as well as the objective evidence for the small fiber involvement of diabetic neuropathy.