{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T04:51:39Z","timestamp":1787979099540,"version":"build-2784847793"},"reference-count":78,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T00:00:00Z","timestamp":1701993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Atopic dermatitis (AD) is a highly prevalent inflammatory skin disorder characterized by episodic exacerbations and remissions. Why the clinically healthy skin of AD patients becomes rapidly inflamed and very pruritic is poorly understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate cowhage\u2010 and histamine\u2010induced itch and skin expression levels of their target receptors in lesional and non\u2010lesional skin of AD, compared to the skin of patients with psoriasis, chronic spontaneous urticaria (CSU) and healthy subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with AD, psoriasis and chronic spontaneous urticaria (CSU) as well as healthy control subjects (HC) (n\u2009=\u200920 each) were assessed for differences in itch parameters, neurogenic flare reaction and local blood flow responses to skin provocations with cowhage and histamine. Skin biopsies from 10\u2009AD, 10 psoriasis,11 CSU and 12 HC were obtained to assess expression of protease\u2010activated receptors 2 and 4 (PAR\u20102, PAR\u20104), histamine H1 and H4 receptors (H1R, H4R), and mast cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Provocation of non\u2010lesional skin of AD patients with cowhage resulted in prolonged itch (<jats:italic>p<\/jats:italic>\u2009=\u20090.020), which was not observed in psoriasis and CSU. Significantly prolonged and more intense cowhage\u2010 and histamine\u2010induced itch (for duration, peak and overall intensity) was also observed in lesional AD skin. Diminished neurogenic flare reaction and blood flow after histamine provocation were shown in AD and psoriasis patients. Non\u2010lesional AD skin along with lesional AD and psoriasis skin showed an increased expression of PAR\u20102 and PAR\u20104, H1R and H4R. Mast cell number was higher in lesional AD and psoriasis skin (<jats:italic>p<\/jats:italic>\u2009=\u20090.006 and <jats:italic>p<\/jats:italic>\u2009=\u20090.006, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The non\u2010lesional skin of AD patients markedly differs from healthy skin in cowhage\u2010induced itch responses and the expression of receptors for proteases and histamine. Proactive therapeutic interventions that downregulate these receptors may prevent episodic exacerbation in AD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.19694","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T14:59:13Z","timestamp":1702047553000},"page":"1089-1100","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Clinically uninvolved but not healthy\u2014The skin of patients with atopic dermatitis is primed for itch and inflammation"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9919-7305","authenticated-orcid":false,"given":"S.","family":"Moon","sequence":"first","affiliation":[{"name":"Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology  Berlin Germany"},{"name":"Institute of Allergology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin 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