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Disorders of skin barrier and primary immunodeficiencies are severe early onset and sometimes life-threatening genodermatoses. Comel-Netherton syndrome, peeling skin syndrome type B, SAM syndrome, ectodermal dysplasia, Dubowitz syndrome, hyperimmunoglobulin E syndromes, 22q11.2 deletion syndrome, Wiskott-Aldrich syndrome, IPEX syndrome and Omenn syndrome are all disorders presenting with eczema and may look like atopic dermatitis, thereby postponing the correct diagnosis and treatment. Knowledge of specific clinical features is crucial to differentiate from atopic dermatitis. In this article we will give an overview of rare skin diseases that are frequently misdiagnosed as atopic dermatitis, highlighting warning signs which are helpful in early detection of such complex disorders.