111 Neurological Abnormalities in Alopecia Areata

M. Toyoda, M. Nakamura, T. Makino, and M. Morohashi. Dept. of Dermatology, Toyama Medical and Pharmaceutical University, Toyama, Japan

Much clinical evidence suggests that the nervous system can influence the course of alopecia areata (AA). Although it is probable that components of the nervous system are involved at various stages in the pathogenesis of AA, there has been little substantial evidence of specific participation of neurogenic factors in that disease process. To examine neurological abnormalities in the lesional skin as well as in the peripheral blood from patients with AA, we examined characteristic expression of neuropeptides and those degrading enzymes in the lesional skin, and plasma levels of neuropeptides and nerve growth factor in AA. In addition, correlation of these neurological factors with the histopathology such as mast cells and with the immunophysiology such as cytokine profiles in AA was statistically evaluated. Imunohistochemical studies of the central hair loss areas of patients with AA revealed that rich innervation by substance P (SP)- containing nerve fibers in affected hair follicles, strong expression of neutral endopeptidase in hair follicles and lack of immunoreactivity for angiotensin-converting enzyme in perifollicular vascular endothelia. Further, intense expression of endothelial-leukocyte adhesion molecule-1 (ELAM-1) on vessels and many degranulating mast cells were observed adjacent to affected hair follicles in AA. Plasma levels of both SP and nerve growth factor were significantly higher in patients with multiple patchy type of AA than in controls as well as in another types of AA including alopecia totalis or universalis. In multiple patchy type of AA, significant correlation was observed between plasma levels of SP and serum levels of nerve growth factor, interleukin (IL)-1, IL-4, IL-6, interferon-gamma and soluble ELAM-1, and between plasma levels of nerve growth factor and the number of mast cells, serum levels of SP, IL-4, IL-10, soluble ELAM-1 and soluble vascular cell adhesion molecule. These data represent the first reported evidence of multiple aspects of neurological abnormalities in AA and suggest the involvement of neurogenic factors in the pathogenesis of AA, probably through an interaction with inflammatory cells, proinflammatory cytokines and cell adhesion molecules.