Search

Copyright of Revue Francaise d'Allergologie is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Atopic dermatitis (AD) affects ∼10% of children. Food allergy is a known provoking cause of AD in a subset of affected children. A literature search of PubMed and Medline was conducted to review the epidemiology and pathophysiology of AD, with special focus on the role of food allergy in the development of AD, its management, and its long-term preventive strategies. A literature search of PubMed and Medline was conducted. Food allergens readily provoke AD in ∼35% of patients, as proven through double-blind placebo-controlled food challenge studies. Milk, egg, wheat, soy, and peanut account for 75% of the cases of food-induced AD. However, the positive predictive values of the parental history, skin-prick tests, or serum tests for detecting food-specific IgE are low, making these unsuitable for use as single diagnostic modalities. Therefore, the use of a food challenge test is very helpful in objectively confirming the history or positive tests. Elimination diets are often helpful in challenge-proven cases, but care must be taken to evaluate the nutritional status of the child. There are few effective long-term strategies to prevent the development of food allergen-induced AD. Early onset of AD has been shown to be a risk factor for the development of other allergic diseases, including other food allergy/sensitization, as part of the atopic march. Treatment of other causes of AD, such as barrier dysfunction and cutaneous infection, are of equal importance to food allergen avoidance. Food allergy is an important provoking cause of AD, but it is only relevant in ∼35% of affected individuals. [ABSTRACT FROM AUTHOR]

Background:Childhood atopic dermatitis (AD) is classically accepted as initial finding of atopic march; however, nonatopic cases do not follow this course. The aim of this study was to determine the characteristics and prognosis of AD in childhood in Turkey. Methods:The study included 531 children with AD that presented to pediatric allergy departments in 11 different regions of Turkey. Age at diagnosis, total serum and inhalant-specific immunoglobulin E (IgE) levels and allergen skin prick test results were recorded retrospectively. Clinical characteristics like additional allergic diseases at presentation or during follow-up were recorded as well as duration of follow-up. Results:Mean age at diagnosis was 37.8 ± 36.2 months. Mean IgE level was 318.3 ± 677.8 IU/ml (median 100 IU/ml). Skin prick tests yielded positive results in 47% of children. At presentation, 31.6% of children reported additional allergic disease, while 11.7% developed allergic disease during follow-up. Among all, 46.6% had additional allergic disease at any point. IgE levels were significantly higher in children with additional allergic diseases (p = 0.001). Allergen skin prick test positivity and family history of allergic diseases increased the risk of additional allergic diseases significantly (OR = 3.90, 95% CI = 2.3–6.6 and OR = 1.89, 95% CI = 1.3–2.8, respectively). Conclusions: Allergic sensitization is not present in all cases of AD. Coexistence of additional allergic diseases is not as high as expected but more common in children who have been demonstrated to have atopic sensitization with high IgE levels and allergen skin prick test positivity. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Copyright of Revue Francaise d'Allergologie is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Although children allergic to eggs, milk or wheat in infancy tend to become tolerant by school age, the allergic status of these children at school age has not been well evaluated. To investigate the allergic status of schoolchildren who avoided eggs, milk or wheat because of an immediate-type allergic reaction at <1-yr-old (food avoiders in infancy), we conducted a large-scale questionnaire-based survey of schoolchildren. A questionnaire on allergic diseases was distributed to the parents of 14,669 schoolchildren aged 7 to 15 yr in 30 schools in Kyoto, Japan. Of these, 13,215 responded (response rate, 90.1%). The rate of 7-yr-old children who were food avoiders in infancy was 5.4%. This rate decreased as the current age of the children increased, down to 3% in 15-yr-old children, indicating that food allergy in infancy tended to become more prevalent over the past 8 yr. Although more than 80% became tolerant to these foods by school age, the prevalence of bronchial asthma, atopic dermatitis, allergic rhinitis and allergic conjunctivitis were significantly higher in this group. Moreover, avoidance of other foods (buckwheat, shellfish, fruits and others) at school age was seen at much higher frequencies than in non-food avoiders in infancy (adjusted odds ratio, 7.7; confidence interval, 5.9–10.2). This risk did not differ significantly between those who did and did not develop tolerance to eggs, milk and wheat by 3 yr old. In conclusion, food avoiders in infancy appear to have a higher risk of not only other allergic diseases (‘atopic march’) but also allergy to other foods (‘food allergen march’) at school age, indicating the need for continuous attention to food allergy. [ABSTRACT FROM AUTHOR]

The nature of the relationship between eczema, asthma, and allergic rhinitis has been controversial. It has been commonly held that these disorders, while sharing genetic and environmental risk factors, are unrelated disorders that may develop sequentially along an atopic pathway. Conversely, the link between eczema and these later-onset respiratory disorders may be causal. This review examines the relationship between eczema, asthma, and allergic rhinitis in the context of the atopic march, the skin barrier, and recent developments in eczema genetics; and we propose that the relationship is causal. We describe a plausible biological pathway with eczema as the first step in a progressive atopic march that over time leads to asthma and/or allergic rhinitis. Such a pathway has implications for our understanding of these disorders and steps that might be made to prevent the development of asthma in particular. We propose that intervention studies in eczema should be conducted to confirm or refute this causal relationship. Such studies may materially improve the quality of life of eczema patients and will have important public health benefits if the interventions lead to a reduction in the burden of asthma. [ABSTRACT FROM AUTHOR]

The atopic march has been studied mostly in White populations, biasing our current paradigms. We sought to define the atopic march in Black and White children and explore mechanisms for racial differences. Utilizing the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children (MPAACH) cohort (n = 601), we assessed longitudinal sensitization, food allergy (FA), allergic rhinitis, risk of asthma development (through the Pediatric Asthma Risk Score), Scoring for Atopic Dermatitis (SCORAD), transepidermal water loss, skin filaggrin (FLG) expression, exposures, and genetic heritability to define AD progression endotypes in Black and White children. White MPAACH children were more likely to be sensitized to aero and food allergens (P =.0001) and over 3 times more likely to develop FA and/or allergic rhinitis (AR) without asthma risk (P <.0001). In contrast, Black children were over 6 times more likely to proceed to high asthma risk without FA, sensitization, or AR (P <.0001). White children had higher lesional and nonlesional transepidermal water loss (both P <.001) as well as decreased nonlesional keratinocyte FLG expression (P =.02). Black children had increased genetic heritability for asthma risk and higher rates of exposures to secondhand smoke and traffic-related air pollution. Black and White children with AD have distinct allergic trajectories defined by different longitudinal endotypes. 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. The observed racial differences are likely due in part to increased genetic heritability for asthma risk and harmful environmental exposures in Black children. Collectively, our findings provide a new paradigm for an atopic march that is inclusive of Black children. [Display omitted] [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is often the initial step in the "atopic march," given that more than half of AD patients with moderate to severe AD develop asthma later in life. Both AD and asthma share a similar "atopy" phenotype that includes T helper type 2 inflammation with eosinophilia and hyper-IgE immunoglobulinemia, but the molecular mechanisms underlying the "atopic march" remain elusive. In the present study, we show that induced expression of thymic stromal lymphopoletin (TSLP) in mouse epidermal keratinocytes upon topical application of MC903 (a low calcemic analogue of vitamin D3) not only triggers AD as we previously reported but also aggravates experimental allergic asthma induced by ovalbumin sensitization and challenge. Our study, which provides a mouse model to study human "atopic march," indicates that keratinocyte-produced TSLP may represent an important factor in the link of atopic dermatitis to asthma. [ABSTRACT FROM AUTHOR]

Background: The atopic march hypothesis suggests that infants with eczema are at increased risk of asthma. Others argue that eczema is not a risk factor for asthma unless there is also sensitization or early wheezing. Objective: To examine the role of infantile eczema as a predictor of risk of childhood asthma, while allowing for the effects of early wheeze, sensitization, and sex, both as independent effects and possible effect modifiers. Methods: A total of 620 infants with a family history of allergic disease was recruited. Eczema and wheeze was prospectively documented to 2 years of age. Sensitization was determined by skin prick tests at 6, 12, and 24 months to 6 common food and inhalant allergens. Interviews were conducted at 6 and 7 years to ascertain current asthma. Results: Sufficiently complete data were available for 403 children. Eczema within the first 2 years of life was clearly associated with an increased risk of childhood asthma in boys (adjusted odds ratio, 2.45; 95% CI, 1.31-4.46) but not in girls (odds ratio, 0.88; 95% CI, 0.43-1.77; P for interaction = .031) even with adjustment for the effects of early allergic sensitization and wheeze. If these relationships are causal, an intervention to prevent eczema in boys might reduce the incidence of childhood asthma by as much as 28%. Conclusion: Eczema in the first 2 years of life is associated with an increased risk of childhood asthma in boys, but there is no evidence of this in girls. [Copyright &y& Elsevier]

Background: It is commonly believed that the majority of infants and young children with early atopic eczema will develop asthma in later childhood. This belief is mainly based on cross-sectional population studies. Recent evidence suggests a more complex relationship between early eczema and asthma. Objective: This systematic review was conducted to assess the risk of developing asthma in children with atopic eczema during the first 4 years of life. Methods: A sensitive search was performed to identify all prospective cohort studies on the topic. By pooling the eligible reports, we calculated the risk of developing asthma at 6 years of age or older in children with atopic eczema in the first 4 years of life. Results: Thirteen prospective cohort studies were included, with 4 representing birth cohort studies and 9 representing eczema cohort studies. The pooled odds ratio for the risk of asthma after eczema, compared with children without eczema, in birth cohort studies was 2.14 (95% CI, 1.67-2.75). The prevalence of asthma at the age of 6 years in eczema cohort studies was 35.8% (95% CI, 32.2% to 39.9%) for inpatients and 29.5% (95% CI, 28.2% to 32.7%) for a combined group of inpatients and outpatients. Conclusion: Although there is an increased risk of developing asthma after eczema in early childhood, only 1 in every 3 children with eczema develops asthma during later childhood. This is lower than previously assumed. Clinical implications: Our results may have important consequences for counseling patients with atopic eczema and their parents. [Copyright &y& Elsevier]

Background: Childhood eczema often precedes the development of asthma and allergic rhinitis in the so-called atopic march. Recently, 2 loss-of-function mutations in the gene encoding the epidermal barrier protein filaggrin were reported to be predisposing factors for eczema and concomitant asthma, suggesting a possible role in disease transition. Objective: We aimed to assess the importance of filaggrin loss-of-function mutations in the susceptibility to eczema and associated clinical phenotypes. Methods: The filaggrin mutations were genotyped and tested for association with allergic disorders in 2 large European populations including 1092 children with eczema. Results: Highly significant association of the filaggrin null mutations with eczema and concomitant asthma was replicated. Moreover, we found that these mutations predispose to asthma, allergic rhinitis, and allergic sensitization only in the presence of eczema. We show that the presence of 2 filaggrin null alleles is an independent risk factor for asthma in children with eczema, and that the 2 investigated mutations account for about 11% of eczema cases in the German population. Conclusion: These results lend strong support to the role of filaggrin in the pathogenesis of eczema and in the subsequent progression along the atopic march. The fact that previous expression of eczema is a prerequisite for the manifestation of allergic airways disease and specific sensitization highlights the importance of the epidermal barrier in the pathogenesis of these disorders. Clinical implications: Our results suggest that the maintenance and repair of the epidermal barrier in infants with eczema may prevent the subsequent development of allergic airways disease. [Copyright &y& Elsevier]

Recent studies have shown that the pH of exhaled breath condensate (EBC) could be predictive of asthma exacerbation. Moreover, it has been documented that both allergic rhinitis and atopic dermatitis constitute risk factors for the occurrence of asthma in a progression of disease known as atopic march. The aim of our study was to establish if condensate pH could be used as a valuable mean of monitoring of asthma in atopic children. We studied 34 atopic children with acute asthma, 70 with stable asthma, 35 children with allergic rhinitis, and 17 with atopic dermatitis. Thirty healthy children were used as controls. All children underwent skin prick tests and lung function tests. Exhaled breath condensate samples were collected with a condensing device and de-aerated with argon. The pH of EBC was measured using a pH meter. Children with acute asthma were treated with inhaled steroids and bronchodilators. We found that the pH of condensate in patients with acute asthma was lower than that of patients with stable asthma, rhinitis, and controls (7.25 vs. 7.32, p < 0.05; 7.25 vs. 7.48, p < 0.02; 7.25 vs. 7.78, p < 0.0001, respectively). Patients with stable asthma, rhinitis, and eczema had also lower pH than that of controls (7.32, 7.48, and 7.44 vs. 7.78; p < 0.0001, p < 0.006, p < 0.04, respectively). Patients with acute asthma normalized their pH after treatment (7.82 vs. 7.25; p < 0.0001). Finally, patients with acute asthma showed a positive correlation between pH and lung functional parameters (forced expiratory volume in 1 s; r = 0.39, p = 0.04). Our study shows that EBC pH measurement may be a promising marker for assessing airway inflammation and monitoring response to anti-inflammatory treatment in asthmatic children. Furthermore, we report the first evidence of airways acidification in children with allergic rhinitis and atopic dermatitis. Therefore, EBC pH assessment may be useful in the evaluation of progression of the atopic march toward the development of asthma later in life. Further studies are recommended in order to confirm this indication. [ABSTRACT FROM AUTHOR]

We challenge 3 prevailing concepts in understanding atopic dermatitis using data from epidemiologic studies. First, we show that although atopy is associated with atopic dermatitis to some degree, its importance is not likely to be a simple cause-and-effect relationship, especially at a population level. Our epidemiologic data do not exclude a contributory role for IgE-mediated immunologic processes, especially in those with existing and severe disease. Second, evidence is presented that does not support a straightforward inverse relationship between infections and atopic dermatitis risk. A link, if present, is likely to be more complex, depending critically on the timing and type of infectious exposure. Third, recent evidence suggests that the risk of subsequent childhood asthma is not increased in children with early atopic dermatitis who are not also early wheezers, suggesting a comanifestation of phenotypes rather than a progressive atopic march. Collectively, these observations underline the importance of epidemiologic studies conducted at a population level to gain a more balanced understanding of the enigma of atopic dermatitis. [Copyright &y& Elsevier]

Food allergy (FA) is rapidly increasing in industrialised countries. In France out of a population of 62 millions, 3 millions are suffering from allergic diseases (5%). FA may be defined as an adverse reaction to food proteins mostly IgE mediated but also non-IgE mediated. FA represents 4% of allergic hypersensitivities and has increased more rapidly than asthma during these past ten years, due to the profound changes in eating habits, consumption of new exotic foods and progress in food technology. Prevalence which means the study of the number of cases (old and new) of diseases in a fixed population is varying with different countries. Questionnaires are used to search FA, and double blind oral challenges are still considered as the gold standard procedures. The results obtained in Great Britain, Holland and France vary from 2 to 4%. FA is more frequent in childhood. Its incidence is estimated at 5 to 10% in children under eight years, whereas it may affect 3% of adults. In children five food common allergens are responsible of 82% of FA: hen''s egg, peanut, cow''s milk, mustard and fish. Peanut, the main food allergen after three years of age, is the most frequent cause of anaphylaxis. Allergy to cow''s milk represents more than 1% up to 30 months. Chronologically, FA affects the gastrointestinal tract, the skin and the respiratory system, which all together define “the Atopic March”. [Copyright &y& Elsevier]

Starting from the "Hygiene Hypothesis" to the "Microflora hypothesis" we provided an overview of the symbiotic and dynamic equilibrium between microbiota and the immune system, focusing on the role of dysbiosis in atopic march, particularly on allergic rhinitis. The advent of deep sequencing technologies and metabolomics allowed us to better characterize the microbiota diversity between individuals and body sites. Each body site, with its own specific environmental niches, shapes the microbiota conditioning colonization and its metabolic functionalities. The analysis of the metabolic pathways provides a mechanistic explanation of the remote mode of communication with systems, organs, and microflora of other body sites, including the ecosystem of the upper respiratory tract. This axis may have a role in the development of respiratory allergic disease. Notably, the microbiota is significant in the development and maintenance of barrier function; influences hematopoiesis and innate immunity; and shows its critical roles in Th1, Th2, and Treg production, which are necessary to maintain immunological balance and promote tolerance, taking part in every single step of the inflammatory cascade. These are microbial biotherapy foundations, starting from probiotics up to postbiotics and parabiotics, in a still-ongoing process. When considering the various determinants that can shape microbiota, there are several factors to consider: genetic factors, environment, mode of delivery, exposure to antibiotics, and other allergy-unrelated diseases. These factors hinder the engraftment of probiotic strains but may be upgradable with postbiotic and parabiotic administration directly on molecular targets. Supplementation with postbiotics and parabiotics could represent a very exciting perspective of treatment, bypassing probiotic limitations. At present, this avenue remains theoretical and to be explored, but it will certainly be a fascinating path to follow.

Atopic eczema is the most common chronic inflammatory skin disease of early childhood and is often the first manifestation of atopic march. Therefore, one challenge is to identify the risk factors associated with atopic eczema that may also be predictors of atopic disease progression. The aim of this study was to investigate the association of SNPs in hornerin (HRNR) and filaggrin-2 (FLG2) genes with childhood atopic eczema, as well as other atopic phenotypes. Genotyping for HRNR and FLG2 was performed in 188 children younger than 2 years of age, previously screened for the FLG null mutations, and followed at yearly intervals until the age of 6. We demonstrated that risk variants of HRNR rs877776[C] and FLG2 rs12568784[T] were associated with atopic eczema, allergic sensitization, and susceptibility to the complex phenotype-asthma plus eczema. These effects seem to be supplementary to the well-known associations for FLG mutations and may be modulated by gene-gene interactions. Additionally, in children with eczema, these genetic variants may also be considered, along with FLG mutations, as predictive biomarkers for eczema-associated asthma. In conclusion, our results indicate that genetic variants in the epidermal differentiation complex gene could contribute to the pathogenesis of atopic eczema and progression to subsequent allergic disease.

Atopic march refers to the phenomenon wherein the occurrence of asthma and food allergy tends to increase after atopic dermatitis. The mechanism underlying the progression of allergic inflammation from the skin to gastrointestinal (GI) tract and airways has still remained elusive. Impaired skin barrier was proposed as a risk factor for allergic sensitization. Claudin-1 protein forms tight junctions and is highly expressed in the epithelium of the skin, airways, and GI tract, thus, the downregulation of claudin-1 expression level caused by CLDN-1 gene polymorphism can mediate common dysregulation of epithelial barrier function in these organs, potentially leading to allergic sensitization at various sites. Importantly, in patients with atopic dermatitis, asthma, and food allergy, claudin-1 expression level was significantly downregulated in the skin, bronchial and intestinal epithelium, respectively. Knockdown of claudin-1 expression level in mouse models of atopic dermatitis and allergic asthma exacerbated allergic inflammation, proving that downregulation of claudin-1 expression level contributes to the pathogenesis of allergic diseases. Therefore, we hypothesized that the tight junction dysfunction mediated by downregulation of claudin-1 expression level contributes to atopic march. Further validation with clinical data from patients with atopic march or mouse models of atopic march is needed. If this hypothesis can be fully confirmed, impaired claudin-1 expression level may be a risk factor and likely a diagnostic marker for atopic march. Claudin-1 may serve as a valuable target to slowdown or block the progression of atopic march., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xia, Cao, Zheng and Chen.)

Atopic dermatitis (AD) affects up to 20% of children and is considered the starting point of the atopic march with the development of food allergy, asthma, and allergic rhinitis. The heterogeneous phenotype reflects distinct and/or overlapping pathogenetic mechanisms with varying degrees of epidermal barrier disruption, activation of different T cell subsets and dysbiosis of the skin microbiome. Here, we review current evidence suggesting a systemic impact of the cutaneous inflammation in AD together with a higher risk of asthma and other comorbidities, especially in severe and persistent AD. Thus, early therapy of AD to restore the impaired skin barrier, modified microbiome, and target type 2 inflammation, depending on the (endo)phenotype, in a tailored approach is crucial. We discuss what we can learn from the comorbidities and the implications for preventive and therapeutic interventions from precision dermocosmetics to precision medicine. The stratification of AD patients into biomarker-based endotypes for a precision medicine approach offers opportunities for better long-term control of AD with the potential to reduce the systemic impact of a chronic skin inflammation and even prevent or modify the course, not only of AD, but possibly also the comorbidities, depending on the patient's age and disease stage.

In the present study, a subject of atopic dermatitis (AD) is exposed progressively to allergic rhinitis (AR) and asthma (AS), which is defined as atopic march (AM). However, both the targets and compounds against AM are still largely unknown. Hence, we investigated the overlapping targets related directly to the occurrence and development of AD, AR, and AS through public databases (DisGeNET, and OMIM). The final overlapping targets were considered as key targets of AM, which were visualized by a Venn diagram. The protein-protein interaction (PPI) network was constructed using R package software. We retrieved the association between targets and ligands via scientific journals, and the ligands were filtered by physicochemical properties. Lastly, we performed a molecular docking test (MDT) to identify the significant ligand on each target. A total of 229 overlapping targets were considered as AM causal elements, and 210 out of them were interconnected with each other. We adopted 65 targets representing the top 30% highest in degree centrality among 210 targets. Then, we obtained 20 targets representing the top 30% greatest in betweenness centrality among 65 targets. The network analysis unveiled key targets against AM, and the MDT confirmed the affinity between significant compounds and targets. In this study, we described the significance of the eight uppermost targets (CCL2, CTLA4, CXCL8, ICAM1, IL10, IL17A, IL1B, and IL2) and eight ligands (Bindarit, CTLA-4 inhibitor, Danirixin, A-205804, AX-24 HCl, Y-320, T-5224, and Apilimod) against AM, providing a scientific basis for further experiments.

The progression of allergic diseases with the development of atopic dermatitis and food allergy in infancy and subsequent asthma and allergic rhinitis in the later childhood is known as 'atopic march'. There have been many arguments in favour of and against this concept. This article reviews the latest epidemiology, immunological mechanisms and translational implications in clinical practice and research, which is relevant to the dermatologists. The role of skin as a site of initiation and the potential for interventions on skin that may prevent subsequent allergic diseases is also highlighted., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Journal of Dermatology.)

Background: Atopic march (AM), a unique characteristic of allergic diseases, refers to the sequential progression of atopic dermatitis (AD) in infants to allergic asthma and allergic rhinitis in children and young adults, respectively. Although there are several studies on AM, the establishment of an AM murine model to expand our understanding of the underlying mechanism and to identify the potential biomarkers is yet to be achieved. In this study, an improved murine model was established by applying a method to minimize skin irritation in inducing AD, and it was used to perform integrated analyses to discover candidate biomarkers., Methods: To induce atopic dermatitis, 2,4-dinitrochlorobenzene (DNCB) was applied to the ear skin once a week, and this was continued for 5 weeks. From the second application of DNCB, Dermatophagoides pteronyssinus (Dp) extract was applied topically 2 days after each DNCB application; this was continued for 4 weeks. Dp sensitization and intranasal challenges were then performed for 4 weeks to develop conditions mimicking AM., Results: Exacerbated airway inflammation and allergic responses observed in the AM-induced group suggested successful AM development in our model. Two-dimensional gel electrophoresis (2-DE) and mass spectrometry analysis identified 753 candidate proteins from 124 2-DE spots differentially expressed among the experimental groups. Functional analyses, such as Gene Ontology (GO) annotation and protein-protein interaction (PPI) analysis were conducted to investigate the relationship among the candidate proteins. Seventy-two GO terms were significant between the two groups; heat shock protein 8 (Hspa8) was found to be included in six of the top 10 GO terms. Hspa8 scored high on the PPI parameters as well., Conclusion: We established an improved murine model for AM and proposed Hspa8 as a candidate biomarker for AM., Competing Interests: The authors declare that they have no competing interests., (© 2022 Jeong et al.)

Recent evidence showed that the postulated linear progression of the atopic march, from atopic dermatitis to food and respiratory allergies, does not capture the heterogeneity of allergic phenotypes, which are influenced by complex interactions between environmental, genetic, and psychosocial factors. Indeed, multiple atopic trajectories are possible in addition to the classic atopic march. Nevertheless, atopic dermatitis is often the first manifestation of an atopic march. Improved understanding of atopic dermatitis pathogenesis is warranted as this could represent a turning point in the prevention of atopic march. In this review, we outline the recent findings on the pathogenetic mechanisms leading to atopic dermatitis that could be targeted by intervention strategies for the prevention of atopic march.

Abstract Background Children often develop allergies that may or not persist into adulthood. Although the different allergic symptoms over time have been well documented, the underlying pattern of sensitization to various proteins and subsequent allergy development is unexplored. The aim was to study the sensitization pattern to allergen components over time from infancy to adulthood in a group of infants with heredity for allergic diseases. Methods IgE profiles were monitored in a group of 67 children from 6 months to 18 years using a microarray chip (ImmunoCAP® ISAC) containing 103 allergen components derived from 47 allergen sources. The chip IgE profile was compared with clinical history, skin prick test results and diagnoses (atopic dermatitis, asthma and allergic rhinoconjunctivitis) at each time point for each child. Results IgE profiles were unique for each child and showed broad agreement with the results of skin prick tests and doctors’ diagnoses. In addition, close examination of the IgE profiles often revealed early indication of subsequent allergies. IgE profiles also facilitated the examination of cross-reactivity contra co-sensitization, thereby greatly enhancing the possibility for managing patients. Conclusion This explorative description indicates that sensitization pattern to allergen components differs over time as well as among allergic individuals when examined with microarray technology.

Abstract Background Early wheezing and asthma are relevant health problems in the tropics. Mite sensitization is an important risk factor, but the roles of others, inherent in poverty, are unknown. We designed a birth-cohort study in Cartagena (Colombia) to investigate genetic and environmental risk factors for asthma and atopy, considering as particular features perennial exposure to mites, parasite infections and poor living conditions. Methods Pregnant women representative of the low-income suburbs of the city were randomly screened for eligibility at delivery; 326 mother-infant pairs were included at baseline and biological samples were collected from birth to 24 months for immunological testing, molecular genetics and gene expression analysis. Pre and post-natal information was collected using questionnaires. Results 94% of families were from the poorest communes of the city, 40% lacked sewage and 11% tap-water. Intestinal parasites were found as early as 3 months; by the second year, 37.9% of children have had parasites and 5.22% detectable eggs of Ascaris lumbricoides in stools (Median 3458 epg, IQR 975-9256). The prevalence of "wheezing ever" was 17.5% at 6 months, 31.1% at 12 months and 38.3% at 24 months; and recurrent wheezing (3 or more episodes) 7.1% at 12 months and 14.2% at 24 months. Maternal rhinitis [aOR 3.03 (95%CI 1.60-5.74), p = 0.001] and male gender [aOR 2.09 (95%CI 1.09 - 4.01), p = 0.026], increased risk for wheezing at 6 months. At 24 months, maternal asthma was the main predisposing factor for wheezing [aOR 3.65 (95%CI 1.23-10.8), p = 0.01]. Clinical symptoms of milk/egg allergy or other food-induced allergies were scarce (1.8%) and no case of atopic eczema was observed. Conclusions Wheezing is the most frequent phenotype during the first 24 months of life and is strongly associated with maternal asthma. At 24 months, the natural history of allergic symptoms is different to the "atopic march" described in some industrialized countries. This cohort is representative of socially deprived urban areas of underdeveloped tropical countries. The collection of biological samples, data on exposure and defined phenotypes, will contribute to understand the gene/environment interactions leading to allergy inception and evolution.

Background: While numerous genetic loci associated with atopic dermatitis (AD) have been discovered, to date, work leveraging the combined burden of AD risk variants across the genome to predict disease risk has been limited., Objectives: This study aims to determine whether polygenic risk scores (PRSs) relying on genetic determinants for AD provide useful predictions for disease occurrence and severity. It also explicitly tests the value of including genome-wide association studies of related allergic phenotypes and known FLG loss-of-function (LOF) variants., Methods: AD PRSs were constructed for 1619 European American individuals from the Atopic Dermatitis Research Network using an AD training dataset and an atopic training dataset including AD, childhood onset asthma, and general allergy. Additionally, whole genome sequencing data were used to explore genetic scoring specific to FLG LOF mutations., Results: Genetic scores derived from the AD-only genome-wide association studies were predictive of AD cases (PRS AD : odds ratio [OR], 1.70; 95% CI, 1.49-1.93). Accuracy was first improved when PRSs were built off the larger atopy genome-wide association studies (PRS AD+ : OR, 2.16; 95% CI, 1.89-2.47) and further improved when including FLG LOF mutations (PRS AD++ : OR, 3.23; 95% CI, 2.57-4.07). Importantly, while all 3 PRSs correlated with AD severity, the best prediction was from PRS AD++ , which distinguished individuals with severe AD from control subjects with OR of 3.86 (95% CI, 2.77-5.36)., Conclusions: This study demonstrates how PRSs for AD that include genetic determinants across atopic phenotypes and FLG LOF variants may be a promising tool for identifying individuals at high risk for developing disease and specifically severe disease., (Copyright © 2021. Published by Elsevier Inc.)

Atopic diseases are multifactorial chronic disturbances which may evolve one into another and have overlapping pathogenetic mechanisms. Atopic dermatitis is in most cases the first step towards the development of the atopic march and represents a major socio-economic burden in the industrialized countries. The treatment of atopic diseases is often long-lasting and in some cases with lower effectiveness than expected.In order to prevent the development of the atopic march, the links between the atopic diseases have to be understood. The aim of this review is to present some major points outlining the link between atopic dermatitis and asthma, through a research in the medical literature from recent years.Stratifying patient populations according to the clinical phenotype of their disease and according to specific measurable values (biomarkers) can help to establish the main etiopathogenetic mechanisms of the disease in these populations. This will add predictive value for the evolution of the disease, and will allow the use and research of more targeted therapy in order to stop this evolution and comorbidities., (© 2021. The Author(s).)

Atopic diathesis encompassing atopic dermatitis (AD), allergic rhinoconjunctivitis, food allergy, eosinophilic esophagitis, and asthma is a widely prevalent condition with a broad heterogeneity in clinical course, age of onset, and lifespan persistence. A primary event in AD is the commonly inherited epidermal barrier dysfunction. Together with the host-microbiome interactions, barrier defect and allergen exposure modulate both innate and adaptive immunity, thus triggering and maintaining the inflammatory response. Microbiome diversity, together with the host's contact with nonpathogenic microbes in childhood, is a prerequisite for functional maturation of the immune system, which is in part mediated by microbiome-induced epigenetic changes. Yet, whether microbiome alterations are the result or the reason for barrier impairment and inflammatory response of the host is unclear. Exposure to locally prevalent microbial species could contribute to further modification of the disease course. The objective of this review is to reveal the link between changes in the skin microbiota, barrier dysfunction, and inflammation in AD. Addressing unmet needs includes determining the genetic background of AD susceptibility; the epigenetic modifications induced by the microbiota and other environmental factors; the role of globally diverse provoking factors; and the implementation of personalized, phenotype-specific therapies such as a epidermal barrier restoration in infancy and microbiota modulation via systemic or topical interventions, all of which open gaps for future research., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objectives: To compare the impact of different formulas on the occurrence of other atopic manifestations and the time of immune tolerance acquisition.Study Design: In a 36-month prospective cohort study, the occurrence of other atopic manifestations (eczema, urticaria, asthma, and rhinoconjunctivitis) and the time of immune tolerance acquisition were comparatively evaluated in immunoglobulin E-mediated children with cow's milk allergy (CMA) treated with extensively hydrolyzed casein formula containing the probiotic L. rhamnosus GG (EHCF + LGG), rice hydrolyzed formula, soy formula, extensively hydrolyzed whey formula (EHWF), or amino acid-based formula.Results: In total, 365 subjects were enrolled into the study, 73 per formula cohort. The incidence of atopic manifestations was 0.22 (Bonferroni-corrected 95% CI 0.09-0.34) in the EHCF + LGG cohort; 0.52 (0.37-0.67) in the rice hydrolyzed formula cohort; 0.58 (0.43-0.72) in the soy formula cohort; 0.51 (0.36-0.66) in the EHWF cohort; and 0.77 (0.64-0.89) in the amino acid-based formula cohort. The incidence of atopic manifestations in the rice hydrolyzed formula, soy formula, EHWF, and amino acid-based formula cohorts vs the EHCF + LGG cohort was always greater than the prespecified absolute difference of 0.25 at an alpha-level of 0.0125, with corresponding risk ratios of 2.37 (1.46-3.86, P < .001) for rice hydrolyzed formula vs EHCF + LGG; 2.62 (1.63-4.22, P < .001) for soy formula vs EHCF + LGG; 2.31 (1.42-3.77, P < .001) for EHWF vs EHCF + LGG; and 3.50 (2.23-5.49, P < .001) for amino acid-based formula vs EHCF + LGG. The 36-month immune tolerance acquisition rate was greater in the EHCF + LGG cohort.Conclusions: The use of EHCF + LGG for CMA treatment is associated with lower incidence of atopic manifestations and greater rate of immune tolerance acquisition. [ABSTRACT FROM AUTHOR]

The incidence of allergic diseases is increasing, and research on their epidemiology, pathophysiology, and the prevention of onset is urgently needed. The onset of allergic disease begins in infancy with atopic dermatitis and food allergy and develops into allergic asthma and allergic rhinitis in childhood; the process is defined as "atopic march". Atopic march is caused by multiple immunological pathways, including allergen exposure, environmental pollutants, skin barrier dysfunction, type 2 inflammation, and oxidative stress, which promote the progression of atopic march. Using recent evidence, herein, we explain the involvement of allergic inflammatory conditions and oxidative stress in the process of atopic march, its epidemiology, and methods for prevention of onset.

Purpose: The pathological process of atopic dermatitis (AD) progressing into other types of allergic diseases such as asthma and allergic rhinitis during the first several years of life is often referred to as the atopic march. Although the phenomenon of atopic march has been recognized for decades, how asthma stems from AD is still not fully understood, confounding a universal strategy to effectively protect people from the atopic march., Methods: We established experimental atopic march mice by first inducing allergic dermatitis with 0.5% fluorescein isothiocyante (FITC) applied to the skin, followed by an ovalbumin (OVA) airway challenge. In addition, by examining serum immunoglobulin (Ig) concentrations, airway cytokines, the levels of oxidative stress markers, histopathological changes in lung tissue and airway hyperresponsiveness (AHR), we were able to validate the successful establishment of the model. Furthermore, by detecting the attenuating effects of melatonin (MT) and the levels of oxidative stress in the atopic march mice, we explored the potential molecular mechanisms involved in the development of atopic march., Results: By successfully establishing an experimental atopic march mouse model, we were able to demonstrate that overproduction of oxidative stress in the lung significantly up-regulated the activation of nuclear factor-κB (NF-κB) signaling pathways causing thymic stromal lymphopoietin (TSLP) release, which further promotes the development of atopic march., Conclusions: To mitigate the development of the atopic march, antioxidants such as MT may be imperative to inhibit NF-κB activation in the lung, especially after the onset of AD., (© 2021 The Author(s).)

Copyright of Revue Francaise d'Allergologie is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)