Abstract
Inborn errors of immunity (IEI) encompass a broad spectrum of immunodeficiency disorders characterized by variability in genetic background, individual immunophenotype, and clinical manifestations with organ-specific immunopathology and immune dysregulation in the form of atopy, autoimmunity, polyclonal lymphoproliferation, and malignancy. With the ever-expanding insight in the pathophysiology of IEI, atopy may be perceived as an integral part and even a hallmark of IEI diseases. This review is aimed at gathering, delineating, and summarizing the immunogenetic underpinnings of IEI diseases accompanied by atopic dermatitis. Particular emphasis is laid on syndromes connected with atopy, such as hyper-IgE syndromes, Omenn syndrome, immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome, Netherton syndrome, Wiskott-Aldrich syndrome, and atypical complete DiGeorge syndrome. Therefore, atopic dermatitis proved not to be a sole disease, but rather a warning sign of multiple pediatric monogenic immunodeficiency disorders. Surpassing from the era of clinical and immunological diagnosis to the era of immunogenetics and the integrated "omics" approach highlighted the complex and heterogeneous immunopathology of atopic dermatitis. It also paved the way for patient-tailored immunotherapies with monoclonal antibodies and small molecules targeted at suppressing atopic inflammatory processes and improving disease-associated outcomes.