From atopic dermatitis to asthma: the atopic march

Division of Allergy and Immunology, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4399, USA.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology (Impact Factor: 2.75). 08/2010; 105(2):99-106; quiz 107-9, 117. DOI: 10.1016/j.anai.2009.10.002
Source: PubMed

ABSTRACT To examine the mechanisms whereby allergen exposure through the epidermis could initiate systemic allergy and predispose individuals to the development of 1 or more atopic diseases via the so-called atopic march.
PubMed databases from 1950 to the present were searched for relevant articles pertaining to epidemiologic and genetic evidence of the progression of the atopic march.
Articles concerning pathophysiologic conditions that link atopic dermatitis, allergic rhinitis, and asthma were examined.
The data suggest that a sequence of atopic manifestations occurs, typically atopic dermatitis in infancy followed by allergic rhinitis and/or asthma in later stages. Reduced filaggrin expression is implicated as a major predisposing factor for atopy in multiple lines of evidence, including genome-wide analysis and microarray investigations. Other gene products have an important role. Cross-sectional and longitudinal studies provide preliminary epidemiologic support for the sequential development of allergic diseases.
The mechanisms by which allergen exposure through the epidermis can initiate systemic allergy and predispose individuals to atopic dermatitis, allergic rhinitis, and asthma have become clearer in recent years. Longitudinal studies of individuals carrying loss-of-function filaggrin gene mutations are needed to further define the risks associated with epidermal barrier dysfunction and potentially identify specific targets for barrier repair and prevention of atopic dermatitis and other atopic disease. The effects of preventive and treatment strategies have been inconsistent across studies, and further research is warranted before any definitive recommendations can be made.

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    ABSTRACT: Little is known about the role of genetic and environmental modifiers in atopic march. To investigate the effects of filaggrin (FLG) P478S polymorphisms and environmental factors on the risk of asthma in a cohort of children with atopic dermatitis (AD). In 2010, 3,246 children from Childhood Environment and Allergic Diseases Cohort Study cohort were recruited. There were 485 children with AD who were invited for further clinical evaluation. Environmental exposures and skin prick tests for allergens were collected at 3 years of age and the development of asthma was determined at 6 years. Multivariate logistic regressions were performed to estimate the association between genetic and environmental factors and the development asthma in children with AD. Of 397 children with AD who completed the follow-up, 97 developed asthma. After controlling for potential confounders, only mite sensitizations (odds ratio 1.89, 95% confidence interval 1.10-3.25) and the FLG TT genotype (odds ratio 2.26, 95% confidence interval 1.33-3.84) were significantly associated with the development of asthma in children with AD. Mite sensitizations and FLG variants had a synergistic effect on the development of asthma. When children with FLG variants were exposed to mite, the risk for asthma was compounded compared with those with FLG variants without mite exposure (odds ratio 3.58, 95% confidence interval 1.81-7.08). Mite sensitization and the FLG TT genotype couldt be associated with the development of atopic march. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
    Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 01/2015; 114(1):52-57. DOI:10.1016/j.anai.2014.10.019 · 2.75 Impact Factor
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    ABSTRACT: Atopic dermatitis (AD) is one of the most common inflammatory allergic diseases with pruritic skin lesions particularly in infancy. It is considered to be the first step of atopic march and has variable disease courses. Many children with AD may resolve their AD symptoms with increasing age and may develop respiratory allergies such as asthma and rhinoconjunctivitis at certain ages. Natural course of AD has been supported by many cross-sectional and longitudinal studies in many countries. In general, atopic dermatitis tends to be more severe and persistent in young children, particularly if they have some risk factors including genetic factors. It appears that approximately 40%-70% of childhood AD will get resolved when they reach the age of 6-7 years. However, it is also observed that over half of the children with AD developed respiratory allergy during late childhood.
    Allergy, asthma & immunology research 03/2015; 7(2):101-5. DOI:10.4168/aair.2015.7.2.101 · 3.08 Impact Factor