The role of the histamine H₄ receptor in atopic dermatitis and psoriasis

Abstract

Atopic dermatitis (AD) and psoriasis are common skin diseases with a high negative impact on patients' quality of life. Both diseases are mediated by a pro‐inflammatory infiltrate consisting of several cell types, such as T‐cells, antigen‐presenting cells and granulocytes and display disturbed keratinocyte differentiation. Given the fact that histamine levels are also highly elevated in inflamed skin, it is likely that histamine plays a relevant role in disease pathology. However, antagonists blocking histamine H1 receptor or H2 receptors are largely ineffective in reducing chronic symptoms in AD and psoriasis. Over the last years, much research has been undertaken to shed light into the mode of action of the most recently discovered histamine H4 receptor. This research has shown that H4 receptor antagonists display antipruritic and anti‐inflammatory effects not only in mouse models but also in first human clinical trials, and therefore, H4 receptors might present a novel therapeutic target. In this review, we summarize the effects of the H4 receptors on different cell types, mouse models and clinical studies in regard to AD and psoriasis respectively. Linked Articles This article is part of a themed section on New Uses for 21st Century. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.3/issuetoc

Pathophysiological Role of Histamine H4 Receptor in Cancer: Therapeutic Implications

“…A recent phase 2a clinical trial was carried out with the selective H4R antagonist ZPL-3893787, administered orally in patients with moderate to severe atopic dermatitis. This compound further reinforced the antipruritic and anti-inflammatory effects of H4R antagonists (Werfel et al, 2018; Schaper-Gerhardt et al, 2019).…”

ETFAD/EADV Eczema task force 2020 position paper on diagnosis and treatment of atopic dermatitis in adults and children

“…135 Ongoing studies focus on the blockade of alternative histamine receptors such as H4RA, which may be more important in AD. 136,137 In conclusion, there is not enough randomized control trial evidence to demonstrate the efficacy of topical antihistamines, including doxepin in the treatment of itch in AD.…”

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“…Histamine is a pleiotropic mediator that is present in elevated concentrations in human skin in inflammatory skin diseases such as psoriasis (Krogstad, Lonnroth, Larson, & Wallin, 1997) or atopic dermatitis (Ruzicka & Gluck, 1983) mediating its effect through four G‐protein coupled receptors (Schaper‐Gerhardt et al, 2018).…”