Histamine and Skin Barrier: Are Histamine Antagonists Useful for the Prevention or Treatment of Atopic Dermatitis?

Abstract

Atopic Dermatitis (AD), the most common chronic inflammatory skin disease, is characterized by an overactive immune response to a host of environmental allergens and dry, itchy skin. Over the past decade important discoveries have demonstrated that AD develops in part from genetic and/or acquired defects in the skin barrier. Histamine is an aminergic neurotransmitter involved in physiologic and pathologic processes such as pruritus, inflammation, and vascular leak. Enhanced histamine release has been observed in the skin of patients with AD and antihistamines are often prescribed for their sedating and anti-itch properties. Recent evidence suggests that histamine also inhibits the terminal differentiation of keratinocytes and impairs the skin barrier, raising the question whether histamine might play a role in AD barrier impairment. This, coupled with the notion that histamine’s effects mediated through the recently identified histamine receptor H4R, may be important in allergic inflammation, has renewed interest in this mediator in allergic diseases. In this paper we summarize the current knowledge on histamine and histamine receptor antagonists in AD and skin barrier function.

Differential Expression and Function of Bicellular Tight Junctions in Skin and Oral Wound Healing

“…It improves skin wound healing by enhancing basic fibroblast growth factor production, angiogenesis, and macrophage recruitment [21]. Histamine has been previously shown to disrupt epidermal barriers [22,23]. We hypothesized that histamine treatment would alter the permeability of HaCaT and TIGK cells.…”

Histamine and Food Allergy

“…Histamine (2-[4-imidazolyl]-ethylamine) is an aminergic neurotransmitter and involved in abundant physiologic and pathologic processes, like pruritus, inflammation, and vascular leak (De Benedetto et al, 2015;Maintz and Novak, 2007). It is discovered in 1910 by Dale and Laidlaw, in 1932 it was recognized that histamine has biological effects in anaphylactic reaction.…”

“…Therefore, the enzymes do not seem to compete for the histamine, though HNMT has a slightly higher affinity for histamine (kM: 6-13 µmol/L) than does DAO (kM: 20 µmol/L), and they are expressed in some overlapping tissues. Several further enzymes, including monoamine oxidase B (MAO-B) and Aldehyde dehydrogenase (ALDH2), other process the immediate metabolites of histamine for excretion or recycling (De Benedetto et al, 2015;Maintz and Novak, 2007;Gutowska-Owsiak et al, 2014).…”

“…Histamine (2-[4-imidazolyl]-ethylamine), as an aminergic neurotransmitter, is involved in abundant physiologic and pathologic processes, such as, inflammation, pruritus and vascular leak (De Benedetto et al, 2015;Maintz and Novak, 2007). It is synthesised by histidine decarboxylase (HDC) in wide types of immune cells including mast cells, basophils, enterochromaffin cells, T cells, keratinocytes, enterochromaffin-like (ECL) cell of the stomach and the brain.…”

“…Degranulation of mast cell and basophil by several mechanism lead to histamine release. Food allergy is one of these mechanisms (De Benedetto et al, 2015;Maintz and Novak, 2007;Leurs et al, 2011).…”