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Atopic Dermatitis and Respiratory Allergy: What Is the Link

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Atopic Dermatitis and Respiratory Allergy: What Is the Link Curr Derm Rep (2015) 4:221–227 DOI 10.1007/s13671-015-0121-6 ATOPIC DERMATITIS (C FLOHR, SECTION EDITOR) Atopic Dermatitis and Respiratory Allergy: What is the Link Danielle C. M. Belgrave1,2 & Angela Simpson1 & Iain E. Buchan2 & Adnan Custovic1 Published online: 28 September 2015 # Springer Science+Business Media New York 2015 Abstract Understanding the aetiology and progression of Introduction atopic dermatitis and respiratory allergy may elucidate early preventative and management strategies aimed towards reduc- Understanding the aetiology and progression of atopic derma- ing the global burden of asthma and allergic disease. In this titis and respiratory allergy may elucidate early preventative article, we review the current opinion concerning the link and management strategies aimed towards reducing the global between atopic dermatitis and the subsequent progression of burden of asthma and allergic disease [1, 2]. There is increas- respiratory allergies during childhood and into early adoles- ing interest in determining the causes of atopic dermatitis and cence. Advances in machine learning and statistical method- respiratory allergies, especially in the light of the increasing ology have facilitated the discovery of more refined defini- prevalence and economic burden associated with these condi- tions of phenotypes for identifying biomarkers. Understand- tions. Globally, up to 20 % of children suffer from atopic ing the role of atopic dermatitis in the development of respi- dermatitis [3]. According to the 2014 Global Asthma Report, ratory allergy may ultimately allow us to determine more ef- it is estimated that 334 million people have asthma with 14 % fective treatment strategies, thus reducing the patient and eco- of the world’s children and 8.6 % of young adults exhibiting nomic burden associated with these conditions. asthma symptoms [4]. Allergic rhinitis has a maximum global prevalence of 40 %. In the UK alone, the yearly financial burden of these three conditions is over £2.5 billion per year Keywords Atopic dermatitis . Respiratory allergy . Asthma . [3, 5–7]. It is hoped that research into underpinning the causal Stratified and personalised medicine strategies . Statistical mechanisms of atopic dermatitis and respiratory allergy can machine learning . Biomarker identification . Dermatology . help to ameliorate the global burden of these conditions. Review To date, the majority of research in understanding the link between atopic dermatitis and respiratory allergy has focused on establishing causal mechanisms via the existence of the supposed Batopic march^ of allergic symptoms. The term Batopic march^ refers to the temporal progression of symp- toms during childhood from atopic dermatitis to asthma to • – This article is part of the Topical Collection on Atopic Dermatitis allergic rhinitis [2, 8, 9 , 10 14]. This hypothesis is based on the observation that clinical signs of atopic dermatitis often * Danielle C. M. Belgrave occur earlier in life and often asthma and allergic rhinitis occur [email protected] later on in life. This observation has widely led to the conclu- sion that atopic dermatitis is a causal Bentry point^ for subse- quent asthma and allergic rhinitis [13]. Consequently, it has 1 Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, University of Manchester and University been suggested that effective management of atopic dermatitis Hospital of South Manchester, Manchester, UK could deter the progression of the atopic march, therefore 2 Centre for Health Informatics, Institute of Population Health, preventing or at least reducing the subsequent development University of Manchester, Manchester, UK of asthma and allergic rhinitis. This conceptual framework has 222 Curr Derm Rep (2015) 4:221–227 been the basis for studies aiming to prevent the development early adolescence. When considering respiratory allergies, of airway inflammation and asthma in children who were we will focus on asthma and rhinitis which are commonly deemed to be at risk by virtue of having atopic dermatitis described as allergic conditions. Indeed, the purpose of under- and a family history of atopic disease [15•]. However, there standing allergic disease progression is with the view of de- is no evidence that targeting children with atopic dermatitis veloping targeted, personalised treatment and management with an intervention designed to modify the progression to- strategies. Understanding the role of atopic dermatitis in the wards asthma is effective [16]. development of respiratory allergy may ultimately allow us to The hypothesis of the atopic march as an explanation of the determine more effective treatment strategies, thus reducing causal link between atopic dermatitis and respiratory allergies the patient and economic burden associated with these may be erroneously based on evidence on a population level conditions. without taking into account the profile of symptoms at the individual level. Using an epidemiological approach based Atopic Dermatitis and Respiratory Allergy: How are they on the prevalence of allergic diseases on a population level, Linked? Current Understanding in the Literature we observe that atopic dermatitis has an increased prevalence in early life across the population followed by an increase in Several studies have hypothesised that the presence of atopic the prevalence of asthma with a subsequent increase in the dermatitis within the first 2 years of life predicts subsequent prevalence of allergic rhinitis (Fig. 1a). Such an approach asthma followed by rhinitis in later childhood [8, 9•, 10–14, hinders a deeper understanding of the progression of symp- 15•]. In the mid-twentieth century, this triad of symptoms was toms at an individual level and determining whether such a first hypothesised to be causally linked via the mechanism of progression of symptoms is indeed observed within individ- the allergic or atopic march [17]. Later, at the beginning of the uals with an increased risk of atopic dermatitis in early life. twenty-first century, with the increase in epidemiological stud- Studies conducted investigating genetic and other biological ies, publications dealing with asthma and allergic diseases markers of atopic dermatitis and other allergic diseases have gave evidence at a population level to suggest a causal link raised the question as to whether atopic dermatitis is a cause of between atopic dermatitis and subsequent asthma and allergic the subsequent development of asthma and allergic rhinitis or rhinitis. whether the presence of atopic dermatitis in early life is a Most of the studies which associated early-life atopic der- consequence of distinct syndromes with different pathophys- matitis with an increased risk of subsequent asthma and aller- iological mechanisms for the subsequent development of re- gic rhinitis used cross-sectional statistical analysis techniques spiratory allergy [13]. which do not take into account the temporal development of This article focuses on reviewing our current understanding symptoms at a within-individual level [8, 11, 17–24]. The of the link between atopic dermatitis and the subsequent pro- atopic march hypothesis has been criticised as an oversimpli- gression of respiratory allergies during childhood and into fication of what happens to the disease profile on an individual A B Fig. 1 Illustration showing that the atopic march may be the result of an eight distinct profiles of co-occurrence of eczema, wheeze and rhinitis (b) ecological fallacy whereby the profiles of atopic dermatitis (eczema) [32•]. Data is derived from joint profiles of the Avon Longitudinal Study wheeze and rhinitis follow a profile similar to the atopic march when of Parents and Children (ALSPAC) and Manchester Asthma and Allergy looking at prevalence at a population level (a)[32•]. However, when Study (MAAS) we disaggregate profiles of symptoms at an individual level, we identify Curr Derm Rep (2015) 4:221–227 223 level [25–28], and some studies have suggested that among may have been an oversimplification of the profile that exists patients there is heterogeneity in the chronology of the devel- on an individual level with different atopic dermatitis pheno- opment of symptoms [28–30, 31•, 32•, 33]. Children with types having significantly different risks of subsequent devel- early atopic dermatitis who later develop asthma and rhinitis opment of asthma and allergic rhinitis. may belong to a distinct phenotype, rather than represent the In a recent study [32•], we jointly modelled longitudinal typical progression of atopic diseases within the general pop- data from two independent population-based birth cohorts: ulation [28, 30]. Despite apparent clear temporal association The Avon Longitudinal Study of Parents and Children linking atopic dermatitis with progression to asthma and aller- (ALSPAC) Cohort and the Manchester Asthma and Allergy gic rhinitis, there is no definitive proof that atopic march is Study (MAAS) Cohort. The aim of this study was to investi- causal or that atopic dermatitis is causal for the subsequent gate whether the atopic march profile which is observed on a development of asthma and rhinitis [31•]. As there is little population level can be observed on a within-individual level. novelty in the conclusions and statistical-epidemiological This study consisted of atopic dermatitis, wheeze and rhinitis methods used to assess whether atopic dermatitis is causally data from both cohorts which was collected from
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