SAN FRANCISCO – New discoveries could change the way antihistamines are used from a predominantly systemic to a topical approach, according to an article from the San Francisco VAMC and the University of California in San Francisco.
The report, published this year in the Journal of Investigative Dermatology, noted that systemic antagonists of the histamine type 1 and 2 receptors (H1/2r) are widely used as anti-pruritics and central sedatives but demonstrate only modest anti-inflammatory activity.1
Because many inflammatory dermatoses result from defects in cutaneous barrier function, and because keratinocytes express both Hr1 and Hr2, researchers hypothesized that H1/2r antagonists might be more effective if they were used topically to treat inflammatory dermatoses.
They found that topical H1/2r antagonists additively enhanced permeability barrier homeostasis in normal mouse skin by the following mechanisms: (i) stimulation of epidermal differentiation, leading to thickened cornified envelopes; and (ii) enhanced epidermal lipid synthesis and secretion. As barrier homeostasis was enhanced to a comparable extent in mast cell-deficient mice, with no further improvement following application of topical H1/2r antagonists, H1/2r antagonists likely oppose mast cell-derived histamines.
In fact, topical H1/2r agonists aggravated, whereas H1/2r antagonists improved, inflammation and/or barrier function in four immunologically diverse, disease models in mice, characterized by either inflammation alone (acute irritant contact dermatitis, acute allergic contact dermatitis) or by prominent barrier abnormalities (subacute allergic contact dermatitis, atopic dermatitis).
“The apparent ability of topical H1r/2r antagonists to target epidermal H1/2r could translate into increased efficacy in the treatment of inflammatory dermatoses, likely due to decreased inflammation and enhanced barrier function,” according to study authors, who added, “These results could shift current paradigms of antihistamine utilization from a predominantly systemic to a topical approach.”
1. Lin TK, Man MQ, Santiago JL, Park K, Roelandt T, Oda Y, Hupe M, Crumrine D, Lee HJ, Gschwandtner M, Thyssen JP, Trullas C, Tschachler E, Feingold KR, Elias PM. Topical antihistamines display potent anti-inflammatory activity linked in part to enhanced permeability barrier function. J Invest Dermatol. 2013 Feb;133(2):469-78. doi: 0.1038/jid.2012.335. Epub 2012 Sep 27. PubMed PMID:23014339; PubMed Central PMCID: PMC3532566.
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