Molecular Mechanisms in Seborrheic Dermatitis—Systematic Review

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-lipid axis. Increasing molecular evidence indicates that SD is associated with both systemic and cutaneous abnormalities, including elevated β-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-control 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-barrier-lipid 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.