Neuronal Theory
Neuronal elements were originally thought to have a role in vitiligo through catecholamine released from epidermal nerve endings which might be cytotoxic to melanocytes or by autonomic dysfunction producing pigment cell destruction [203, 204]. Clinical pointers towards neural involvement included the distribution along blaschkoid lines in segmental vitligo, and the occasional observation of a true dermatomal appearance, e.g. in the trigeminal areas [167, 204].
Ultrastructurally vitiligo skin shows degeneration of fine cutaneous nerves in 42% of cases, with Schwann cells showing thickened basement membrane in 75% of instances and axonal damage in a half [203, 205]. Changes in neuropeptides, notably neuropeptide Y, are evident at the margins of vitiligo patches [205]. This led to the postulation that neuropeptides, potentially neuropeptide Y, which has effects on the immune system through receptors located on several immunologically active cells including T cells, NK cells, dendritic cells, granulocytes, and macrophages, released from nerve ending release next to melanocytes, could provoke a local immune reaction and melanocyte destruction [206, 207]. Treg cells, seen as central to melanocyte destruction in vitiligo, can be induced by vasoactive intestinal polypeptide, and can alter the Th1/cytotoxic T cell (Tc)1 balance that is skewed in vitiligo [208]. Hence, the neural and neuro-endocrine systems, neuropeptides and neurotransmitters, interacting with the immune systems, need to be taken into account in the
causation of vitiligo [209].