Are allergic multimorbidities and IgE polysensitization associated with the persistence or re‐occurrence of foetal type 2 signalling? The MeDALL hypothesis

Abstract

Allergic diseases [asthma, rhinitis and atopic dermatitis (AD)] are complex. They are associated with allergen‐specific IgE and nonallergic mechanisms that may coexist in the same patient. In addition, these diseases tend to cluster and patients present concomitant or consecutive diseases (multimorbidity). IgE sensitization should be considered as a quantitative trait. Important clinical and immunological differences exist between mono‐ and polysensitized subjects. Multimorbidities of allergic diseases share common causal mechanisms that are only partly IgE‐mediated. Persistence of allergic diseases over time is associated with multimorbidity and/or IgE polysensitization. The importance of the family history of allergy may decrease with age. This review puts forward the hypothesis that allergic multimorbidities and IgE polysensitization are associated and related to the persistence or re‐occurrence of foetal type 2 signalling. Asthma, rhinitis and AD are manifestations of a common systemic immune imbalance (mesodermal origin) with specific patterns of remodelling (ectodermal or endodermal origin). This study proposes a new classification of IgE‐mediated allergic diseases that allows the definition of novel phenotypes to (i) better understand genetic and epigenetic mechanisms, (ii) better stratify allergic preschool children for prognosis and (iii) propose novel strategies of treatment and prevention.

Association of Polysensitization, Allergic Multimorbidity, and Allergy Severity: A Cross-Sectional Study of School Children

“…However, we found that the agreement between allergic multimorbidity and polysensitization was poor. This discordance could be because allergic diseases share common causal mechanisms with allergen-specific IgE (30-50%) [2,6,7], nonallergic mechanisms [1], and other factors, such as non-IgE mechanisms and the environment [2,36], which contribute to the development of allergic multimorbidity. Allergic multimorbidity has distinct clinical phenotypes compared to single diseases [10,14,37].…”

“…Despite the recent focus on the clustering of aeroallergens that have similar sensitization effects in children [1,5], the association of allergic disease severity with polysensitization remains relatively understudied [16,34,38]. Polysensitization is significantly associated with a poor quality of life in patients with allergic rhinitis [17] and intermittent asthma [19], and with higher asthmatic symptom scores for dyspnea, wheezing, and cough [13].…”

“…The prevalence of allergic multimorbidity is more common than expected due to genetics [1] or based on shared or nonshared environmental exposures [2]. Previous research examined the prevalence and sequential progression of allergic comorbidities (asthma, rhinitis, and eczema) [3,4], and recommended that these should not be regarded as separate diseases [2].…”

“…There is a strong association between IgE sensitization and allergic diseases [1,5], but the attributable risk is only 30-50% [2,6,7]. The presence, severity, and number of factors associated with IgE sensitization are important indicators for diagnosing [8,9,10] and predicting the progression of allergic diseases [11].…”

European Symposium on Precision Medicine in Allergy and Airways Diseases: Report of the European Union Parliament Symposium (October 14, 2015)

“…• The action plan is based on o New scientific data are emerging allowing prediction and prevention (23).…”