Atopic dermatitis: allergic dermatitis or neuroimmune dermatitis?

Abstract

Advances in knowledge of neurocellulars relations have provided new directions in the understanding and treatment of numerous conditions, including atopic dermatitis. It is known that emotional, physical, chemical or biological stimuli can generate more accentuated responses in atopic patients than in non-atopic individuals; however, the complex network of control covered by these influences, especially by neuropeptides and neurotrophins, and their genetic relations, still keep secrets to be revealed. Itching and airway hyperresponsiveness, the main aspects of atopy, are associated with disruption of the neurosensory network activity. Increased epidermal innervation and production of neurotrophins, neuropeptides, cytokines and proteases, in addition to their relations with the sensory receptors in an epidermis with poor lipid mantle, are the aspects currently covered for understanding atopic dermatitis.

Figure 1

Nerves marked in green (PGP 9.5). A: Lesional epidermis: presence of nerves (marked in green with PGP 9.5). Dermoepidermal limit enhanced by adding a discontinued white line. B: Non-lesional epidermis: nerves evidenced only in the dermis

Figure 2

Skin / nerve bidirectional circuit: nerve fibers scheme contacting directly basal keratinocytes. The release of neuropeptides stimulates the proliferation of basal cells. When they multiply, they develop NGF, which is autocrine for these, and by retrograde pathway, runs through the axons, reaches the neuron bodies and stimulates their tropism and production of neuropeptides

Figure 3

A: Healthy control. B: Atopic dermatitis: before PUVA. C: Atopic dermatitis: after PUVA

Figure 4

Atopic lesions. Evaluation of animals before and after semaphorin topical application

Figure 5

A: Presence of sema phorin 3A (marked in green) in the normal skin (1) and in atopic lesions before (2) and after (3) PUVA. B: Presence of NGF (marked in green) in non-atopic skin (1) and atopic lesions before (2) and after (3) PUVA

Figure 6

Mechanism of neurogenic inflammation formation. Stimuli (physical, chemical or biological) that promote the neuropeptides release, including substance P (SP), attract and degranulate mast cells, stimulate adhesion of platelets, release of histamine and 5HT, vasodilation and plasma outlet with formation of an urticarial papule

Figure 7

A: Nerve touching mast cells in AD. B: Sensory nerves in AD (marked in green)

Figure 8

Nasal mucosa (atopic rhinitis). Neural response in D normal mucosa (A) and in allergic rhinitis (B) after physical stimulation (touch with monofilament). Immunoreactive nerve fibers (PGP 9.5) viewed individually in the control group (arrow) or in groups (arrow). Few fibers in the control group (C). Fibers present in glands and mucosal vasculature with rhinitis (D)