Expression of neuropeptide-degrading enzymes in alopecia areata: an immunohistochemical study

Background Much clinical evidence suggests that the nervous system, includi ng psychological factors, can influence the course of alopecia areata (AA). However, there has been little substantial evidence of specific participat ion of cutaneous neurogenic factors in the disease process. Objectives As previous studies have demonstrated that stress elicits the re lease of the neuropeptide substance P (SP) from peripheral nerves and that some patients with AA show prominent SP expression in nerves surrounding th eir hair follicles, we aimed to evaluate the role of SP in AA. Methods We used immunohistochemistry to examine the expression of SP and SP -degrading enzymes in scalp biopsies from patients with AA and from healthy controls. Results Affected hair follicles in the centre of the areas of hair loss of patients with AA were richly innervated by SP-staining nerve fibres. Strong expression of the SP-degrading enzyme, neutral endopeptidase (NEP), was ob served in hair follicles not only in the acute progressive phase of AA but also in the chronic stable phase. Expression of NEP in hair follicles from the margins of areas of hair loss was stronger than in normal controls, but was weaker than in the centre of the areas of hair loss. In addition, endo thelial immunoreactivity for angiotensin-converting enzyme (also capable of degrading SP) was not observed in the centre of the areas of hair loss, wh ich was in significant contrast to normal controls as well as to the margin s of areas of hair loss where it was expressed. Further, intense expression of endothelial leucocyte adhesion molecule-1 on vessels and many degranula ting mast cells was observed adjacent to affected hair follicles in AA, in admixture with dense lymphocytic inflammation. Conclusions These findings suggest that SP is endogenously released by derm al nerve fibres around hair follicles and that it may play an important par t in epithelial-mesenchymal-neuroectodermal interactions in AA. This study reveals that SP and its degrading enzymes are involved in the pathogenesis of AA, which in turn might explain the pathological significance of neuroge nic and psychogenic aspects in the disease process.