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      Use of H-1 Antihistamine in Dermatology: More than Itch and Urticaria Control: A Systematic Review

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          Abstract

          H-1 antihistamines are commonly used in dermatological practice for itch and urticaria control. The widespread expression of H-1 receptor on different cells in the skin and various biologic functions of H-1 antihistamines indicate the possible treatment potentials of H-1 antihistamines in dermatology. A literature search was performed on PubMed and Embase, targeting articles reporting use of antihistamine for purposes other than itch and urticaria control in dermatological practice. Several off-label usages of antihistamines were identified, including alopecia, acne, Darier disease, eosinophilic dermatoses, paraneoplastic dermatoses, psoriasis, lichen nitidus, radiation dermatitis, skin dysesthesia, and cutaneous malignancies. Additional benefits were observed when H-1 antihistamines were used either alone or in combination with other therapeutic modalities. Although various novel uses of H-1 antihistamines have been uncovered, the evidence level of most included studies is weak. Further randomized control trials are warranted to better evaluate the efficacy and dosage of H-1 antihistamine for dermatological disorders.

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          Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia.

          Testosterone is necessary for the development of male pattern baldness, known as androgenetic alopecia (AGA); yet, the mechanisms for decreased hair growth in this disorder are unclear. We show that prostaglandin D(2) synthase (PTGDS) is elevated at the mRNA and protein levels in bald scalp compared to haired scalp of men with AGA. The product of PTGDS enzyme activity, prostaglandin D(2) (PGD(2)), is similarly elevated in bald scalp. During normal follicle cycling in mice, Ptgds and PGD(2) levels increase immediately preceding the regression phase, suggesting an inhibitory effect on hair growth. We show that PGD(2) inhibits hair growth in explanted human hair follicles and when applied topically to mice. Hair growth inhibition requires the PGD(2) receptor G protein (heterotrimeric guanine nucleotide)-coupled receptor 44 (GPR44), but not the PGD(2) receptor 1 (PTGDR). Furthermore, we find that a transgenic mouse, K14-Ptgs2, which targets prostaglandin-endoperoxide synthase 2 expression to the skin, demonstrates elevated levels of PGD(2) in the skin and develops alopecia, follicular miniaturization, and sebaceous gland hyperplasia, which are all hallmarks of human AGA. These results define PGD(2) as an inhibitor of hair growth in AGA and suggest the PGD(2)-GPR44 pathway as a potential target for treatment.
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            Mast cells activated by SARS-CoV-2 release histamine which increases IL-1 levels causing cytokine storm and inflammatory reaction in COVID-19.

            SARS-CoV-2 virus is an infectious agent commonly found in certain mammalian animal species and today also in humans. SARS-CoV-2, can cause a pandemic infection with severe acute lung injury respiratory distress syndrome in patients with COVID-19, that can lead to patient death across all ages. The pathology associated with pandemic infection is linked to an over-response of immune cells, including virus-activated macrophages and mast cells (MCs). The local inflammatory response in the lung that occurs after exposure to SARS-CoV-2 is due to a complex network of activated inflammatory innate immune cells and structural lung cells such as bronchial epithelial cells, endothelial cells and fibroblasts. Bronchial epithelial cells and fibroblasts activated by SARS-CoV-2 can result in the up-regulation of pro-inflammatory cytokines and induction of MC differentiation. In addition, endothelial cells which control leukocyte traffic through the expression of adhesion molecules are also able to amplify leukocyte activation by generating interleukin (IL)-1, IL-6 and CXC chemokines. In this pathologic environment, the activation of mast cells (MCs) causes the release of histamine, proteases, cytokines, chemokines and arachidonic acid compounds, such as prostaglandin D2 and leukotrienes, all of which are involved in the inflammatory network. Histamine is stored endogenously within the secretory granules of MCs and is released into the vessels after cell stimulation. Histamine is involved in the expression of chemokine IL-8 and cytokine IL-6, an effect that can be inhibited by histamine receptor antagonists. IL-1 is a pleiotropic cytokine that is mainly active in inflammation and immunity. Alveolar macrophages activated by SARS-CoV-2 through the TLR produce IL-1 which stimulates MCs to produce IL-6. IL-1 in combination with IL-6 leads to excessive inflammation which can be lethal. In an interesting study published several years ago (by E. Vannier et al., 1993), it was found that histamine as well as IL-1 are implicated in the pathogenesis of pulmonary inflammatory reaction, after micorganism immune cell activation. IL-1 in combination with histamine can cause a strong increase of IL-1 levels and, consequently, a higher degree of inflammation. However, it has been reported that histamine alone has no effect on IL-1 production. Furthermore, histamine enhances IL-1-induced IL-6 gene expression and protein synthesis via H2 receptors in peripheral monocytes. Therefore, since MCs are large producers of histamine in inflammatory reactions, this vasoactive amine, by increasing the production of IL-1, can amplify the inflammatory process in the lung infected with SARS-CoV-2. Here, we have proposed for the first time an emerging role for histamine released by MCs which in combination with IL-1 can cause an increase in lung inflammation induced by the viral infection SARS-CoV-2.
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              Similar itch and nociceptive sensations evoked by punctate cutaneous application of capsaicin, histamine and cowhage.

              Itch evoked by cowhage or histamine is reduced or blocked by capsaicin desensitization, suggesting that pruriceptive neurons are capsaicin-sensitive. Topical capsaicin can evoke both nociceptive sensations and itch, whereas intradermal injection of capsaicin evokes only burning pain. To dissociate the pruritic and nociceptive sensory effects caused by the chemical activation of sensory neurons, chemicals were applied in a punctiform manner to the skin of the forearm using individual, heat-inactivated cowhage spicules treated with various concentrations of capsaicin (1-200 mg/ml) or histamine (0.01-100 mg/ml). Perceived intensities of itch, pricking/stinging and burning were obtained every 30 s using the general version of the Labeled Magnitude Scale and compared with ratings evoked by individual native cowhage spicules. Similar to cowhage, capsaicin and histamine spicules reliably evoked sensations of itch in a dose-dependent manner which were most often accompanied by pricking/stinging and to a lesser extent burning. Spicules containing 200 mg/ml capsaicin or 10 mg/ml histamine yielded peak magnitudes and durations of sensations comparable to those elicited by cowhage. Each type of spicule also produced comparable areas of dysesthesias (enhanced mechanically evoked itch or pain) and/or skin reactions (wheal and/or flare) in surrounding skin, though inconsistently. The incidence of flare was greater in response to histamine than to capsaicin or cowhage. These results suggest the possibility that capsaicin, histamine and cowhage activate common peripheral or central neural mechanisms that mediate pruritic sensations and associated dysesthesias.
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                Author and article information

                Contributors
                allen17570@gmail.com
                tftsai@yahoo.com
                Journal
                Dermatol Ther (Heidelb)
                Dermatol Ther (Heidelb)
                Dermatology and Therapy
                Springer Healthcare (Cheshire )
                2193-8210
                2190-9172
                12 April 2021
                12 April 2021
                June 2021
                : 11
                : 3
                : 719-732
                Affiliations
                GRID grid.412094.a, ISNI 0000 0004 0572 7815, Department of Dermatology, , National Taiwan University Hospital, ; Taipei, Taiwan
                Author information
                https://orcid.org/0000-0002-9740-9720
                http://orcid.org/0000-0002-1498-1474
                Article
                524
                10.1007/s13555-021-00524-w
                8163952
                33846906
                e32c8336-e89e-410f-ab08-dbbbfee705a2
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 27 February 2021
                Categories
                Review
                Custom metadata
                © The Author(s) 2021

                Dermatology
                anti-inflammation,dermatology,h-1 antihistamines,off-label usages,pleiotropic effects
                Dermatology
                anti-inflammation, dermatology, h-1 antihistamines, off-label usages, pleiotropic effects

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