Atopic diseases are continuously growing in terms of worldwide prevalence even in infants and children, starting very early during infancy with atopic dermatitis (AD), followed by allergic rhinitis and asthma later in life [1], in the clinical pipeline known as the “atopic march” [2]. Their cause is not fully revealed, yet, but their increased global prevalence, particularly concerning AD, is not to be due to genetics alone, but can be attributable to an interplay with evolving environmental exposures, at least in predisposed individuals [3].
Notably, environmental agents, including pollutants and allergens, are associated with an increasing prevalence of the disease. Other environmental players, such as tobacco exposure, microbes, diet, nutrients, together with genetic variants, including filaggrin mutations, could lead to the deficiency of the skin barrier and the immune system, overall, paving the way for AD onset already early during life [4].
Quite surprisingly, atopic disorders [5], and in particular AD, were found to be somewhat associated with a number of psychiatric conditions, also starting during childhood [6, 7], among which autism spectrum disorders (ASD) are probably the best known and most prevalent worldwide.
Somewhat similarly to AD, also ASD pathogenesis is still unclear, but also in this case mounting evidence supports the hypothesis for a significant gene-environment interaction in its etiology [8].
A recent study on this topic attempted at making clarity based on population data from 5 countries (Denmark, Finland, Israel, Sweden and Western Australia). The authors found the heritability of ASD to be around 80%, with the variation in ASD occurrence mostly due to inherited genetic influences, and no evidence for related maternal effects [9]. Interestingly, the prevalence of AD in children living in Western countries is rising in a similar manner when compared to ASD, with hypothesised bidirectional association between them, suggesting a shared pathogenesis underlying the two, apparently far, conditions [1]. Several hypotheses were raised about a possible common pathway between the two disorders, including the dysregulation of common microRNAs, such as miR-146 and miR-155 [10], the co-existence of higher concentrations of pro-inflammatory cytokines in both atopic and neuropsychiatric disorders [11], or the action of overexpressed inflammatory mediators released during atopic responses that could have affected neural circuitry in genetically susceptible children [12].
More specifically, genetic variants in Stat6, pivotal element in the regulation of Th2 immune response, are known to be associated with atopy. But Stat6 is also found to be largely expressed in the central nervous system and to play a key role in the pathogenesis of some neuropsychiatric conditions, including ADHD, in turn largely co-morbid to ASD [6]. This, still indirect, possible association has further fostered the hypothesis for a somewhat connection between atopy and neuropsychiatric, or neurodevelopmental disorders.
Nevertheless, in this complex and quite puzzled framework, two of the largest population-based longitudinal studies published to date hypothesised a role for AD as an early precursor for ASD [13, 14]. According to the authors, toddlers affected from AD as young as 3 years old are at higher risk of developing ASD or ADHD later during childhood, especially in presence of other atopic comorbidities such as allergic rhinitis, allergic conjunctivitis, and asthma. Lee et al. [13] hypothesised a role for AD as a trigger for an immunological cascade comprising mast cells activation, in turn inducing the release of pro-inflammatory cytokines, mostly IL-6, whose levels were seen to be elevated in ASD patients and to modulate the autistic-like behaviour in animal models [15]. Such elevated cytokine levels found in ASD patients can bring to damage to the blood–brain barrier, in turn playing a key role in the etiopathogenesis of ASD and other neuropsychiatric conditions.
Both AD and ASD are actually under the magnifying glass of clinical research in the respective medical fields (allergology/immunology and pediatric neuropsychiatry, respectively) due to their increasing prevalence and to the attention of physicians and pharmaceutical industry. However, despite this fact, until a few years ago, the scientific literature experienced a lack of uniform correlation analyses between their respective prevalence in a significant number of nations from all over the world, except some isolated attempts to follow the prevalence trend of the two conditions longitudinally in a given country [16,17,18]. This, apparently strange phenomenon, was possibly due to a lack of standardization in clinical criteria that might have prevented researchers from carrying out such analysis in a reliable fashion.
Fortunately, in more recent times, larger databases have been published, therefore allowing for more exhaustive comparisons between the data pertaining the two conditions. Indeed, a big amount of countries are now included within uniform data collection reported online (https://worldpopulationreview.com/country-rankings/autism-rates-by-country) or in scientific literature [19] for both conditions, making the analysis less complicated than before.
