Abstract
Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease in which dry and itchy skin may develop into skin lesions. AD has a strong genetic component, as children from parents with AD have a two-fold increased chance of developing the disease. Genetic risk loci and epigenetic modifications reported in AD mainly locate to genes involved in the immune response and epidermal barrier function. However, AD pathogenesis cannot be fully explained by (epi)genetic factors since environmental triggers such as stress, pollution, microbiota, climate, and allergens also play a crucial role. Alterations of the epidermal barrier in AD, observed at all stages of the disease and which precede the development of overt skin inflammation, manifest as: dry skin; epidermal ultrastructural abnormalities, notably anomalies of the lamellar body cargo system; and abnormal epidermal lipid composition, including shorter fatty acid moieties in several lipid classes, such as ceramides and free fatty acids. Thus, a compelling question is whether AD is primarily a lipid disorder evolving into a chronic inflammatory disease due to genetic susceptibility loci in immunogenic genes. In this review, we focus on lipid abnormalities observed in the epidermis and blood of AD patients and evaluate their primary role in eliciting an inflammatory response.
Highlights
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Atopic dermatitis (AD) is characterized by major aberrations in lipid metabolism (Figure 2), resulting in epidermal barrier impairment and itch and significantly contributing to inflammation via activation of KCs, Langerhans cell (LC), and inflammatory dendritic epidermal cell (IDEC), emphasizing a key role of lipids in AD pathogenesis (Figure 3)
It is pertinent to hypothesize that AD is primarily a disorder of lipid metabolism evolving into an inflammatory disease due to genetic susceptibility in immunogenic genes
Summary
Atopic dermatitis (AD) is the most common inflammatory skin disorder worldwide, with a prevalence of 1–20% in both children and adults (http://isaac.auckland.ac.nz/index. html (accessed on 9 February 2022) [1,2,3,4,5]. Atopic dermatitis (AD) is the most common inflammatory skin disorder worldwide, with a prevalence of 1–20% in both children and adults Html (accessed on 9 February 2022) [1,2,3,4,5]. Food allergies might be concomitant to AD in very young children (https://nationaleczema.org/atopic-dermatitis-and-allergies-connection/ (accessed on 9 February 2022)) [6]. AD is a complex disease whose etiology has not yet been fully deciphered due to its heterogeneity resulting from patient age, ethnicity, and lifestyle factors [7,8,9]. Heterogeneity of AD due to genetic polymorphism extends beyond filaggrin (FLG) loss-of-function mutations, since patients with serine peptidase inhibitor Kazal-type 5 (SPINK5) mutations exhibit a severe AD-like phenotype, as do other patients with inherited disorders [17,18]. Better knowledge of the pathomechanisms common to all endotypes would deliver important information for designing effective pan-therapies
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