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However, the skin transcriptomic profiling of PN arising from atopic dermatitis (AD), so\u2010called atopic PN (APN), remains unclear. We sought to explore the cutaneous transcriptome of APN with severe pruritus and compare it with classic AD. RNA sequencing was performed on the lesional skin from 13 APN to 11 AD patients with severe pruritus (itch numerical rating scale score\u2009\u2265\u20097) and normal skin from 11 healthy subjects. Quantitative real\u2010time polymerase chain reaction and immunochemistry were used for validation. We detected 1085 and 1984 differentially expressed genes (DEGs) in lesional APN skin and lesional AD skin versus normal skin, respectively. In total, 142 itch\/inflammation\u2010related DEGs were identified. Itch\/inflammation\u2010related DEGs, such as IL\u20106, IL\u201010, IL\u201013, oncostatin M, and IL\u20104 receptor, had elevated gene transcript levels in both diseases. The itch\/inflammation\u2010related DEGs that increased only in APN were mainly neuroactive molecules, while many inflammatory mediators such as T helper 22\u2010related genes were found to be increased only in AD. Both disorders showed mixed Th1\/Th2\/Th17 polarisation and impaired skin barrier. In contrast to AD, M1\/M2 macrophage activation, tumor necrosis factor production, fibrosis, revascularization and neural dysregulation are unique features of APN. The study findings broaden our understanding of the pathogenesis underlying APN, which provides insights into novel pathogenesis with potential therapeutic implications.<\/jats:p>","DOI":"10.1111\/exd.14678","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T08:18:32Z","timestamp":1663834712000},"page":"30-40","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["<scp>RNA<\/scp> sequencing reveals the transcriptome profile of the atopic prurigo nodularis with severe itching"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6524-5058","authenticated-orcid":false,"given":"Yixin","family":"Shao","sequence":"first","affiliation":[{"name":"Department of Dermatology, Huashan Hospital Fudan University  Shanghai 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