Severe atopic dermatitis and multiple allergies as a result of genetic variant in DSG1, case report.

Introduction: DSG1 (Desmoglein 1) is a structural cornerstone of the epidermis, essential for maintaining the skin barrier. Structural or functional alterations in this protein lead to significant cutaneous protection failure. Case Presentation: We present the case of an 18-year-old male with recalcitrant atopic dermatitis and allergic rhinitis. Despite conventional therapy, disease control was not achieved, and the clinical picture was complicated by the development of cold abscesses on the ankles. Immunological screening revealed markedly elevated IgE levels. NGS (Next Generation Sequencing) using an Inborn Errors of Immunity and Cytopenias panel identified a heterozygous pathogenic variant, c.2569C>T (p.Arg857*), in the DSG1 gene. Conclusion: The immunopathological mechanisms underlying DSG1 alterations and their relationship with atopic dermatitis are multifaceted, involving a spectrum of structural epidermal abnormalities and immune dysregulation. Identifying the specific inflammatory endotype is crucial for implementing precision medicine and targeted therapeutic strategies.