The link between atopic dermatitis and asthma- immunological imbalance and beyond

Yaneva and Darlenski Asthma Research and Practice (2021) 7:16 https://doi.org/10.1186/s40733-021-00082-0 Open Access REVIEW The link between atopic dermatitis and asthma‑ immunological imbalance and beyond Martina Yaneva1* and Razvigor Darlenski1,2 Abstract Atopic diseases are multifactorial chronic disturbances which may evolve one into another and have overlapping pathogenetic mechanisms. Atopic dermatitis is in most cases the first step towards the development of the atopic march and represents a major socio-economic burden in the industrialized countries. The treatment of atopic diseases is often long-lasting and in some cases with lower effectiveness than expected. In order to prevent the development of the atopic march, the links between the atopic diseases have to be understood. The aim of this review is to present some major points outlining the link between atopic dermatitis and asthma, through a research in the medical literature from recent years. Stratifying patient populations according to the clinical phenotype of their disease and according to specific measurable values (biomarkers) can help to establish the main etiopathogenetic mechanisms of the disease in these populations. This will add predictive value for the evolution of the disease, and will allow the use and research of more targeted therapy in order to stop this evolution and comorbidities. Keywords: Atopy, Atopic march, Comorbidities, Asthma, Endotypes, Phenotypes Background Atopic dermatitis (AD), or atopic eczema, is the most common chronic inflammatory disorder [1] which according to the World Health Organization (WHO) affects more than 230 million people worldwide, and is the fourth leading cause of non-fatal disability [2]. AD currently affects between 15 and 20% of the children and between 1 and 10% of the adult population. [3]. Asthma is a long-term condition affecting both children and adults. Around 300 million people worldwide have asthma and it is estimated that by 2025 another 100 million will be affected [4]. Atopic asthma is the most common form of asthma, from which 70–90% of the children and 50% of the adult patients are affected. [5]. Disrupted skin barrier, genetics, allergic sensitization, elevated IgE levels, microbiome, Th2 immunity, environmental triggers are familiar concepts all of which are somehow connected, and their connection outline the concept of atopy and the development of the atopic march. The aim of this review is to define the main links between atopic dermatitis (AD) and asthma. Through an investigation of the medical literature we will try to present the current understanding of the atopic march and its comorbidities beyond the immunological imbalance concept. *Correspondence: 1 Department of Dermatology and Venereology, Acibadem City Clinic, Sofia, Bulgaria Full list of author information is available at the end of the article © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Yaneva and Darlenski Asthma Research and Practice (2021) 7:16 Search methodology A systematic literature review was conducted using the online PubMed MEDLINE database. The keywords included “asthma”, “atopic dermatitis”, “atopy”, “skin microbiome”, “atopic march”, “comorbidities”,” skin barrier”. Studies and reviews published in English were included. Non-English articles, animal studies and in vitro experiments were excluded. The oldest article reviewed was published in 1989 and the newest in 2021. Atopic march AD is associated with food allergy (FA), asthma, and allergic rhinitis (AR), with or without the occurrence of elevated IgE- levels [6]. This gradual transition of one atopic disease into another in an almost specific age range is known as atopic march. AD is considered the first step as disrupted skin barrier, inflammation and bacterial dysbiosis [7] lead to sensitization required for the development of other atopic diseases [8]. However, AD can follow asthma and AR. FA develops early in life, it can precede or follow the AD, and may in some cases be the first sign of the atopic march. FA often occurs before the appearance of AR or asthma [9, 10]. Dysfunctional skin barrier in AD could lead to food sensitization or FA could accompany AD. Either way food sensitization could be a marker for AD severity, an endotype, which could suggest more probable transition to other atopic comorbidities (asthma and AR) [11]. In the classical evolution of the atopic march allergic asthma is the result of hyperreactivity of the airways- an immunological reaction part of a cascade which has started earlier in life. The individual had been initially sensitized through the skin. Many studies have shown that the development of asthma in AD patients is more common, although the exact causative factors are not yet clear. In a study conducted by Pourpak et al. [12] the prevalence of asthma in patients with AD was 27,5%. The exact pathogenesis of asthma and AD is not entirely understood. Both diseases are associated with chronic inflammation. In asthma patients cytokines and other inflammatory mediators are found in bronchial washings. Both diseases can be IgE- mediated which suggests genetic predisposition as atopy refers to the familial tendency to produce Ig-E. Imbalance in the Th1/ Th2 ratio is associated with higher production of IgE in atopic patients. By producing Il-2 and Il-13, Th2 cells promote the production of IgE by B-cells in response to antigen trigger. This leads to hyperreactive response of the airways in asthma patients and in skin inflammation in AD patients. Mast cells have major role in an allergic and inflammatory disorders [13]. The many similarities between AD and asthma in terms of pathogenesis and Page 2 of 8 immunological imbalance, often leads us to consider each disease in the context of the other. A Canadian study, published in 2018 found that AD increased the risk of asthma in children at the age of 3 years only if AD was accompanied by se (...truncated)