From Skin Barrier Dysfunction to Systemic Impact of Atopic Dermatitis: Implications for a Precision Approach in Dermocosmetics and Medicine

Abstract

Atopic dermatitis (AD) affects up to 20% of children and is considered the starting point of the atopic march with the development of food allergy, asthma, and allergic rhinitis. The heterogeneous phenotype reflects distinct and/or overlapping pathogenetic mechanisms with varying degrees of epidermal barrier disruption, activation of different T cell subsets and dysbiosis of the skin microbiome. Here, we review current evidence suggesting a systemic impact of the cutaneous inflammation in AD together with a higher risk of asthma and other comorbidities, especially in severe and persistent AD. Thus, early therapy of AD to restore the impaired skin barrier, modified microbiome, and target type 2 inflammation, depending on the (endo)phenotype, in a tailored approach is crucial. We discuss what we can learn from the comorbidities and the implications for preventive and therapeutic interventions from precision dermocosmetics to precision medicine. The stratification of AD patients into biomarker-based endotypes for a precision medicine approach offers opportunities for better long-term control of AD with the potential to reduce the systemic impact of a chronic skin inflammation and even prevent or modify the course, not only of AD, but possibly also the comorbidities, depending on the patient's age and disease stage.

Keywords: asthma; atopic dermatitis; atopic march; biologic therapies; comorbidities; dermocosmetics; emollient; immunity; precision medicine; systemic disease.

Figure 1

Atopic dermatitis with risk factors for the development of asthma, and implications for prophylactic and therapeutic intervention. Prophylactic emollients may contribute to the prevention or, at least, delay the early onset of AD within the first year of life. AD with early-onset, severe, and persistent disease course are at a higher risk for asthma. Early intervention and adequate treatment of AD might prevent the progress from mild and transient AD to severe and persistent forms, and in already existing severe AD, might contribute to downregulation of the severity and persistence of AD. This, in turn, might reduce the risk of the development of asthma = 95% Confidence interval, MD= physician diagnosis, mo=months, OR = odds ratio, RR = risk ratio. Effect sizes of risk factors [14,74], and the Asthma Predictive Index (API) estimating the probability of the development of asthma in a child with a history of wheezing [75,76,77], have been adapted from the literature. The Table with the API has been modified and adapted from: JOSÉ A. CASTRO-RODRÍGUEZ , CATHARINE J. HOLBERG, ANNE L. WRIGHT , and FERNANDO D. MARTINEZ/2000/ A Clinical Index to Define Risk of Asthma in Young Children with Recurrent Wheezing/Am J Respir Crit Care Med/Vol 162. pp 1403–1406, 2000. Adapted with permission of the American Thoracic Soci-ety. Copyright © 2022 American Thoracic Society. All rights reserved. The American Journal of Respiratory and Critical Care Medicine is an official journal of the American Thoracic Society. Readers are encouraged to read the entire article for the correct context at https://www.atsjournals.org/doi/full/10.1164/ajrccm.162.4.9912111. The authors, editors, and The American Thoracic Society are not responsible for errors or omissions in adaptations.