Trajectories of allergic diseases in children: Destination unknown?

The trajectories of allergic diseases represent one of the most currently debated topics both when referred to childhood and likewise adulthood. Data from cohorts show their heterogeneity as well as the key role of genetic and environmental factors. More insight has been recently provided in the pathophysiological mechanisms underlying the development and amplification of T2 (hyper)inflammation. Recent data support the hypothesis of associated allergic diseases (multimorbidity) reflecting, at a given time and in given organ(s)/tissue(s), the expression of the same favorable predisposition. In particular, the impairment of the epithelial barrier, especially in subjects genetically predisposed, and the dysregulation of the host's microbiome promote the onset of allergic diseases and multimorbidity, their persistence and/or severity. These findings challenge the classical theory of the atopic march with a temporal sequence characterized by the transition from one disease (eczema) to another (food allergy, airway allergic diseases). A better understanding of the diversity of disease trajectories and the underpinning mechanisms is crucial for prevention and identification of children at risk of a "unfavorable trajectory" (early intervention, i.e., early primary or secondary prevention), for a personalized therapeutic approach based on identification of specific endotypes, and, therefore, addressing specific pathophysiological pathways (treat to target strategies). In the perspective of the so-called "remission" and "treatment-induced-remission", the whole spectrum of the long-term consequences of the disease(s) including their treatment has to be considered. The concept of disease modifying treatment able to interfere with their trajectories and overall long-term induced morbidity is emerging.