A new paradigm for the Atopic March

Published: October 18, 2021

For nearly two decades, the “atopic march” concept, which describes the sequential development of atopic dermatitis (AD), food allergy (FA), asthma, and allergic rhinitis (AR) has served as a guiding principle, however, a recent NIH workshop concluded that only about 3% of children follow the traditional atopic march. Further, studies of the atopic march have been almost exclusively conducted in White populations and need to be expanded to include other racial and ethnic groups. Black children have a higher prevalence of asthma and increased rates of asthma morbidity and mortality than White children, which has been documented for decades, and this disparity persists as the child ages even when controlling for socioeconomic status. Despite these disparities, studies focused on understanding the trajectories of allergic disorders in childhood have been conducted almost exclusively in White populations, so our current paradigms of the atopic march are inherently biased toward White children. The Mechanisms of Progression of Atopic Dermatitis (AD) to Asthma in CHildren (MPAACH) cohort was designed to meet this need. MPAACH includes 65% Black children and is one of the only early life cohorts that adequately represents this historically underrepresented and understudied population.

In a study recently published in The Journal of Allergy and Clinical Immunology (JACI), Biagini et al. provide a foundation for a new atopic march paradigm that includes Black and White children. They follow 601 Black and White children participating in MPAACH cohort and define longitudinal endotypes of AD by integrating clinical and allergen sensitization data with molecular data regarding skin barrier function. They then go on to explore the mechanisms including genetics and environmental exposures that underlie differences in atopic march trajectories by race. All children in MPAACH are followed prospectively with annual visits where they undergo a physical examination including determination of eczema severity, skin prick testing to 11 aeroallergens and 13 foods, skin barrier assessments, and biospecimens (skin tape strips, blood, contact agar plates, stool, nasal swabs) and questionnaires are collected. In this study, they assessed longitudinal sensitization, FA, AR, risk of asthma development (through the Pediatric Asthma Risk Score), SCORAD, transepidermal water loss (TEWL), skin filaggrin (FLG) expression, environmental exposures and genetic heritability to define AD progression endotypes in Black and White children.

The authors found that Black children exhibit higher asthma risk despite a more intact skin barrier, and less sensitization, FA and AR.  White children have less asthma risk, despite a more dysfunctional skin barrier, and more FA, AR and sensitization. When they examined endotypic factors underlying the progressor phenotypes, Black children had increased parental history of AD and asthma, higher genetic heritability, and increased environmental exposures to air pollutants, but they did not have increased barrier dysfunction and they had less sensitization. In contrast, the endotypic factors underlying progression in the White children were decreased skin barrier quality and function, evident by increased TEWL and decreased keratinocyte FLG expression, increased sensitization to food and aero allergens, and increased pet ownership.

These data collectively support that progression of allergic disease is multi-faceted and differs by race. Black children in MPAACH do not follow the traditional atopic march; rather they are most likely to progress straight to high risk of asthma rather than develop sensitization, FA or AR. The Black children suffer disproportionately from air pollution, have increased genetic heritability of asthma and do not have exposure to pets in the home that confer protection from allergic disease development, culminating in development of asthma. In contrast, White MPAACH children suffer from a poor skin barrier that allows allergen penetration and subsequent sensitization, leading to the development of primarily FA and AR. Their data support that the traditional atopic march largely does not exist in Black children and provide a foundation for a new atopic march paradigm that includes Black children.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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