Immunohistochemical study of epidermal nerve fibres in involved and uninvolved psoriatic skin using confocal laser scanning microscopy

Abstract

Psoriasis is a typical hyperproliferative epidermal disease whose aetiopathogenesis is still to be defined. One of the most likely hypotheses is that it has a neurogenic origin correlated with an altered release of some neuropeptides by sensitive cutaneous nerves via antidromic pathways. As there are conflicting reports about the existence of cutaneous nerve alterations in psoriasis, we carried out an immunolocalization study using the protein gene product 9.5 as a marker for neuronal structures observed by confocal laser scanning microscopy in order to determine the pattern of sensory nerves in psoriatic skin. The investigation was carried out on cutaneous biopsies taken from involved (mature and long-established lesions) and uninvolved skin of ten patients with extensive chronic plaque psoriasis. In uninvolved psoriatic skin a significant decrease in epidermal nerve fibres was found, a further decrease was observed in mature lesions and almost a complete lack of epidermal nerve fibres in long-established psoriatic lesions. The reduction in epidermal nerve fibres and the consequent loss of relationship between these nerve structures and the skin immunocompetent cells (antigen-presenting cells, Langerhans cells, keratinocytes) might be a factor of fundamental importance in the self-maintenance of the disease.

Neuronal Control of Skin Function: The Skin as a Neuroimmunoendocrine Organ

“…With the use of electron microscopy (336), confocal laser scan microscopy (671), and immunohistochemistry (809), it is possible to demonstrate that the epidermis is also innervated by a three-dimensional network of unmyelinated C fibers with free-branching endings that arise in the dermis and their basement membrane apposed to epidermal cells such as keratinocytes, melanocytes, Langerhans cells, and Merkel cells, respectively. Increased epidermal innervation has been described in skin lesions of various inflammatory skin diseases (379,383,633,640,761,809), wound repair (234), skin cancer (232, 447,552,567,765), epithelial hyperplasia (702), after exposure to ultraviolet (UV) light, or during psoralen UVA therapy (525,785).…”

Role of neurturin in spontaneous itch and increased nonpeptidergic intraepidermal fiber density in a mouse model of psoriasis

“…Epidermal hyperinnervation by itch-signaling fibers is considered to be one cause of chronic itch [32], and increased epidermal nerve density has been frequently reported in humans with chronic itch conditions, including psoriasis [12; 18; 29–32], with some exceptions [19; 24]. Nociceptive fibers are expressed throughout the epidermis and often categorized as peptidergic or nonpeptidergic fibers [7].…”

Unexpected diminished innervation of epidermis and dermoepidermal junction in lichen amyloidosus

“…Values are expressed as pixel intensity per unit area. et al10 suggested a role for increased nerve density in the itch of psoriasis, Pergolizzi et al11 observed a reduced nerve density in this disorder.…”