Loss of filaggrin and abnormal keratinocyte differentiation allows for a more permissive skin environment that promotes entry of irritants, allergens, and microbes that may evoke immune responses, which then further promote progressive weakening of the epidermal barrier, a phenomenon prominent in chronic skin diseases, such as AD, and an emerging concept in autoimmune skin disease, such as cutaneous lupus erythematosus (CLE) (32). This evidence concerns the gene FLG and Alzheimer disease.