Research Progress in Atopic March

Abstract

The incidence of allergic diseases continues to rise. Cross-sectional and longitudinal studies have indicated that allergic diseases occur in a time-based order: from atopic dermatitis and food allergy in infancy to gradual development into allergic asthma and allergic rhinitis in childhood. This phenomenon is defined as the "atopic march". Some scholars have suggested that the atopic march does not progress completely in a temporal pattern with genetic and environmental factors. Also, the mechanisms underlying the atopic march are incompletely understood. Nevertheless, the concept of the atopic march provides a new perspective for the mechanistic research, prediction, prevention, and treatment of atopic diseases. Here, we review the epidemiology, related diseases, mechanistic studies, and treatment strategies for the atopic march.

Keywords: allergic rhinitis; asthma; atopic dermatitis; atopic march; food allergy.

Figure 1

A possible model of the contribution of skin barrier dysfunction to the atopic march. Allergens (including food allergens and aeroallergens) enter the skin through the damaged skin barrier. Then, they stimulate epithelial cells in the skin to release thymic stromal lymphopoietin (TSLP), interleukin (IL)-25, and IL-33. This action activates some immune cells in the dermis (e.g., basophils, mast cells, DCs, eosinophils, and ILC2) to secrete cytokines, followed by the generation of T-helper type 2 (Th2) cells and immunoglobulin E (IgE) production in local lymph nodes. Th2 cells can secrete more type 2 cytokines (e.g., IL-4) to activate more ILC2 and eosinophils, and IgE can act on mast cells and basophils. This positive feedback causes skin inflammation and atopic dermatitis (AD). Furthermore, IgE, Th2 cells, TSLP, IL-25, and IL-33 might enter the digestive tract and respiratory tract through blood circulation to facilitate the development of allergic asthma (AA), allergic rhinitis (AR), and food allergy if allergens are re-encountered.

Figure 2

The temporal pattern and the possible mechanisms of the atopic march. The temporal pattern of the atopic march is, in general, from atopic dermatitis (AD) and food allergy in infancy to gradual development into allergic asthma (AA) and allergic rhinitis (AR) in childhood. Several mechanisms could underlie the atopic march: skin barrier damage, microbiome alteration, “social” dysfunction of cells and molecules, epigenetic factors, and interference of other predicted genes.