{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:37:29Z","timestamp":1791877049317,"version":"4.3.4"},"reference-count":24,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Seborrheic dermatitis (SD) is a chronic inflammatory skin disorder with a multifactorial pathogenesis involving immune dysregulation, oxidative stress, neuroendocrine signaling, and alterations of the epidermal barrier\u2013lipid axis. Increasing molecular evidence indicates that SD is associated with both systemic and cutaneous abnormalities, including elevated \u03b2-endorphin levels, disturbed redox homeostasis, enhanced lipid peroxidation, dysregulated cytokine signaling, and genetic and epigenetic susceptibility factors. This systematic review was conducted in accordance with PRISMA guidelines. Comprehensive literature searches of PubMed, Scopus, and Web of Science identified eight studies that met the inclusion criteria. The included investigations comprised clinical case\u2013control studies, genetic and epigenetic analyses, and multi-omics profiling of human blood and skin samples. Collectively, the findings demonstrate consistent systemic oxidative and neuroendocrine alterations alongside pronounced local immune activation characterized by Th1- and Th17-skewed responses, cytokine and stress-ligand upregulation, and activation of inflammatory signaling pathways. Genetic association signals and disease-specific microRNA profiles further implicate post-transcriptional regulation of immune and keratinocyte-related pathways in SD pathogenesis. Moreover, multi-omics studies revealed coordinated immune activation accompanied by impaired epidermal barrier function and altered lipid metabolism, supporting a dysregulated immune\u2013barrier\u2013lipid axis. Overall, SD emerges as a disorder driven by interconnected systemic and cutaneous molecular mechanisms. The identified pathways may represent promising directions for future biomarker research and targeted therapeutic development rather than established diagnostic or treatment strategies.<\/jats:p>","DOI":"10.3390\/ijms27062799","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T15:38:01Z","timestamp":1773934681000},"page":"2799","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Molecular Mechanisms in Seborrheic Dermatitis\u2014Systematic Review"],"prefix":"10.3390","volume":"27","author":[{"given":"Sofiia","family":"Khimuk","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Wroclaw Medical University, 50-367 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastazja","family":"Andrusiewicz","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Wroclaw Medical University, 50-367 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Mijas","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Wroclaw Medical University, 50-367 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1717-4280","authenticated-orcid":false,"given":"Danuta","family":"Nowicka","sequence":"additional","affiliation":[{"name":"University Centre of General Dermatology and Oncodermatology, Faculty of Medicine, Wroclaw Medical University, 50-556 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1111\/exd.14091","article-title":"An update on the microbiology, immunology and genetics of seborrheic dermatitis","volume":"29","author":"Adalsteinsson","year":"2020","journal-title":"Exp. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Trivi\u00f1o, F.J.N., Amador, J.P.V., and Ruiz, I.R. (2025). Seborrheic Dermatitis Revisited: Pathophysiology, Diagnosis, and Emerging Therapies\u2014A Narrative Review. Biomedicines, 13.","DOI":"10.3390\/biomedicines13102458"},{"key":"ref_3","first-page":"5S","article-title":"Current Understanding of Seborrheic Dermatitis: Epidemiology, Burden of Disease, and Pathophysiology","volume":"29","author":"Turchin","year":"2025","journal-title":"J. Cutan. Med. Surg."},{"key":"ref_4","first-page":"10","article-title":"Seborrheic Dermatitis and Dandruff: A Comprehensive Review","volume":"3","author":"Borda","year":"2015","journal-title":"J. Clin. Investig. Dermatol."},{"key":"ref_5","first-page":"24","article-title":"Seborrheic Dermatitis in Skin of Color: Clinical Considerations","volume":"18","author":"Elgash","year":"2019","journal-title":"J. Drugs Dermatol."},{"key":"ref_6","first-page":"e70335","article-title":"Ocular Manifestations in Seborrheic Dermatitis Epidemiology, Clinical Features, and Management: A Comprehensive Review","volume":"16","author":"Alofi","year":"2024","journal-title":"Cureus"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.clindermatol.2013.01.001","article-title":"Seborrheic dermatitis: Etiology, risk factors, and treatments: Facts and controversies","volume":"31","author":"Dessinioti","year":"2013","journal-title":"Clin. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1001\/jamadermatol.2024.1987","article-title":"The Global Prevalence of Seborrheic Dermatitis: A Systematic Review and Meta-Analysis","volume":"160","author":"Polaskey","year":"2024","journal-title":"JAMA Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1146\/annurev-micro-040820-010114","article-title":"Malassezia: A Commensal, Pathogen, and Mutualist of Human and Animal Skin","volume":"76","author":"Ianiri","year":"2022","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_10","first-page":"65","article-title":"Malassezia virulence factors and their role in dermatological disorders","volume":"31","author":"Kurniadi","year":"2022","journal-title":"Acta Dermatovenerol. Alp. Pannonica Adriat."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Georgescu, S.R., Mitran, C.I., Mitran, M.I., Matei, C., Popa, G.L., Erel, O., and Tampa, M. (2022). Thiol-Disulfide Homeostasis in Skin Diseases. J. Clin. Med., 11.","DOI":"10.3390\/jcm11061507"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"McKenzie, J., Brennan, S., Ryan, R., Thomson, H., Johnston, R., and Thomas, J. (2019). Defining the criteria for including studies and how they will be grouped for the synthesis. Cochrane Handbook for Systematic Reviews of Interventions, John Wiley & Sons, Ltd.. Chapter 3.","DOI":"10.1002\/9781119536604.ch3"},{"key":"ref_14","unstructured":"Joanna Briggs Institute (JBI) (2026, February 20). Critical Appraisal Tools for Use in JBI Systematic Reviews. Available online: https:\/\/jbi.global\/critical-appraisal-tools."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"704","DOI":"10.15584\/ejcem.2023.4.3","article-title":"Plasma level of beta endorphin in seborrheic dermatitis patients","volume":"21","author":"Vysochanska","year":"2023","journal-title":"Eur. J. Clin. Exp. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"12","DOI":"10.4103\/sjmms.sjmms_50_19","article-title":"Dynamic Thiol\/Disulfide Balance in Patients with Seborrheic Dermatitis: A Case-Control Study","volume":"8","author":"Emre","year":"2020","journal-title":"Saudi J. Med. Med. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e06621","DOI":"10.1016\/j.heliyon.2021.e06621","article-title":"Altered serum elements, antioxidants, MDA, and immunoglobulins are associated with an increased risk of seborrheic dermatitis","volume":"7","author":"Jahan","year":"2021","journal-title":"Heliyon"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Shen, N., Chen, W., Hu, L., Huang, J., and Dong, Q. (2025). Scalp seborrheic dermatitis demonstrates a skewing of Th1 activation: A proteomic study in lesional skin. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1638710"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/j.jid.2017.11.020","article-title":"The Genetics of Seborrheic Dermatitis: A Candidate Gene Approach and Pilot Genome-Wide Association Study","volume":"138","author":"Sanders","year":"2018","journal-title":"J. Investig. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"21241","DOI":"10.1038\/s41598-022-24383-3","article-title":"Differential microRNA profiles in elderly males with seborrheic dermatitis","volume":"12","author":"Kim","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/j.jaad.2025.01.082","article-title":"Tape-strip profiling identifies unique immune and lipid dysregulation in patients with seborrheic dermatitis","volume":"92","author":"Ungar","year":"2025","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"149441","DOI":"10.1016\/j.gene.2025.149441","article-title":"Exploring the relationship and diagnostic targets of seborrheic dermatitis and scalp psoriasis based on multi-omics integration analysis","volume":"957","author":"Yang","year":"2025","journal-title":"Gene"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"v+vii+1","DOI":"10.1007\/978-3-642-19683-6_1","article-title":"Sensing the environment: Regulation of local and global homeostasis by the skin\u2019s neuroendocrine system","volume":"212","author":"Slominski","year":"2012","journal-title":"Adv. Anat. Embryol. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1001\/jama.2024.4899","article-title":"Chronic Pruritus: A Review","volume":"331","author":"Butler","year":"2024","journal-title":"JAMA"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/6\/2799\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T15:39:47Z","timestamp":1773934787000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/6\/2799"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,19]]},"references-count":24,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ijms27062799"],"URL":"https:\/\/doi.org\/10.3390\/ijms27062799","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,19]]}}}