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This narrative review examines clinical data on the immunomodulatory effects of TCS and recent treatments for atopic dermatitis (AD) in early childhood in the context of atopic comorbidities. While TCS are effective in reducing several markers of inflammation in infants with AD, certain type 2 cytokines, such as interleukin (IL)\u22124, IL-5, and IL-13, remain uncontrolled in the infant stratum corneum, a major source of dysregulated systemic cytokines. A pathomechanism known as remote priming has been identified, wherein allergen-induced antigen-specific immune responses in disrupted skin facilitate allergen-sensitizing immune responses in distant mucosal barrier sites, such as the gut or lung. In the gut, remote priming occurs through the activation of epidermal type 2 innate lymphoid cells (ILC2), which prime gut mast cells and promote food allergies. ILC2s produce IL-5 and IL-13, which remain present in the epidermis with TCS. Consequently, ILC2 cells in the skin of children with AD may remain able to contribute to remote gut priming. Type 2 cytokines also promote immunoglobulin E (IgE) production\u2014a marker of atopic development in children. Over 16 weeks, children aged 6 months to 5 years treated with dupilumab and TCS show a 70% reduction in IgE levels, whereas those treated with TCS alone exhibit a 30% increase in IgE levels. These observations highlight the need for a more comprehensive approach to managing infant AD. Therapies that target inflammation originating from both innate and adaptive effector cells involved in type 2 inflammation may not only alleviate the burden of AD but also disrupt the progression of the atopic march.<\/jats:p>","DOI":"10.1007\/s12016-025-09131-5","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T09:15:05Z","timestamp":1769505305000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Atopic Comorbidities and Topical Steroids in Early Childhood Atopic Dermatitis: Are We Missing a Piece of the Puzzle?"],"prefix":"10.1007","volume":"69","author":[{"given":"Courtney A.","family":"Chau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonya L.","family":"Cyr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruchi","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Lio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"issue":"3","key":"9131_CR1","doi-asserted-by":"publisher","first-page":"237","DOI":"10.4103\/ijd.IJD_169_17","volume":"62","author":"A Das","year":"2017","unstructured":"Das A, Panda S (2017) Use of topical corticosteroids in dermatology: an evidence-based approach. 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The misplaced text in the caption of Figure 1 has been reinstated.","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 February 2026","order":8,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":9,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":10,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1007\/s12016-026-09144-8","URL":"https:\/\/doi.org\/10.1007\/s12016-026-09144-8","order":11,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This research does not involve human participants and\/or animals.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Research Involving Human Participants and\/or Animals"}},{"value":"This research does not involve human participants and informed consent procedures.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"<!--Emphasis Type='Bold' removed-->Informed Consent"}},{"value":"Dr. Sonya L. Cyr is an employee and shareholder of Regeneron Pharmaceuticals Inc.Dr. Ruchi Gupta receives research support from the National Institutes of Health (NIH), Food Allergy Research & Education (FARE), Sunshine Charitable Foundation, Genentech, Novartis, and Abbott Laboratories. She serves as a medical consultant\/advisor for Food Allergy Research & Education (FARE), Genentech, Novartis, OWYN, Kal\u00e9o, Bryn Pharma, Kenvue, ARS Pharmaceuticals, Oracle Life Sciences, and Alpina Biotechnology. Dr. Gupta has ownership interest in Yobee Care, Inc. She is currently employed by Ann & Robert H. Lurie Children\u2019s Hospital of Chicago and is a Professor of Pediatrics & Medicine at Northwestern University Feinberg School of Medicine. Dr. Peter Lio reports being on the speaker\u2019s bureau for AbbVie, Arcutis, Eli Lilly, Galderma, Hyphens Pharma, Incyte, La Roche-Posay\/L\u2019Oreal, Pfizer, Pierre-Fabre Dermatologie, Regeneron\/Sanofi Genzyme, Verrica; reports consulting\/advisory boards for Alphyn Biologics (stock options), AbbVie, Almirall, Amyris, Arcutis, ASLAN, Bristol-Myers Squibb, Burt\u2019s Bees, Castle Biosciences, Codex Labs (stock options), Concerto Biosci (stock options), Dermavant, Eli Lilly, Galderma, Janssen, LEO Pharma, Lipidor, L\u2019Oreal, Merck, Micreos, MyOR Diagnostics, Regeneron\/Sanofi Genzyme, Sibel Health, Skinfix, Suneco Technologies (stock options), Theraplex, UCB, Unilever, Verdant Scientific (stock options), Verrica, Yobee Care (stock options). In addition, Dr. Lio has a patent pending for a Theraplex product with royalties paid and is a Board member and Scientific Advisory Committee Member emeritus of the National Eczema Association.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"3"}}