The skin barrier and microbiome in infantile atopic dermatitis development: can skin care prevent onset?

Atopic dermatitis (AD), a prevalent Th2-dominant skin disease, involves complex genetic and environmental factors, including mutations in the Filaggrin gene and dysbiosis of skin microbiota characterized by an increased abundance of Staphylococcus aureus. Our recent findings emphasize the pivotal role of the skin barrier's integrity and microbial composition in infantile AD and allergic diseases. Early skin dysbiosis predisposes infants to AD, suggesting targeted skincare practices as a preventive strategy. The effects of skincare interventions, particularly the application of moisturizers with the appropriate molar concentration of ceramides, cholesterol, and fatty acids, play a crucial role in restoring the skin barrier. Notably, our study revealed that appropriate skincare can reduce Streptococcus abundance while supporting Cutibacterium acnes presence, thus directly linking skincare practices to microbial modulation in neonatal skin. Despite the mixed outcomes of previous Randomized Controlled Trials on the efficacy of moisturizers in AD prevention, our research points to the potential of skincare intervention as a primary preventive method against AD by minimizing the impact of genetic and environmental factors. Furthermore, our research supports the notion that early aggressive management of eczema may reduce the incidence of food allergies, highlighting the necessity for multifaceted prevention strategies that address both the skin barrier and immune sensitization. By focusing on repairing the skin barrier and adjusting the skin's microbiome from birth, we propose a novel perspective on preventing infantile AD and allergic diseases, opening new avenues for future studies and practices in allergy prevention.

Using a survey, analyzing the current situation of allergic March in elementary and junior high school students of oyama and tochigi cities, Japan.

BACKGROUND: Over the past few decades, allergic diseases have become more prevalent and impact around 20% of the global population. There is clinical significance of allergic march as it places a burden on the quality of life of children and their families. OBJECTIVES: To assess the current situation of allergy conditions experienced by children attending elementary and junior high schools in Oyama and Tochigi cities, Japan. METHODS: A letter was sent to parents informing them about an opt-in online survey concerning children's allergies along with a weblink and a QR code. A video explained the survey process and informed parents that their replies could not be retracted. Parents who had watched the explanation video and answered yes to participating were considered to have provided consent for the survey. RESULTS: A total of 2038 valid replies were gathered. Allergic Rhinitis was the most commonly diagnosed allergy, followed by Asthma, Food Allergy, and Atopic Dermatitis. Around 70% of the children were affected by the allergies, of whom half had been affected by multiple allergies. Most children affected by Atopic Dermatitis, Food Allergy or Asthma were affected by other allergies. Atopic Dermatitis and Food Allergy were mostly diagnosed before Asthma and Allergic Rhinitis. CONCLUSIONS: Children who are diagnosed with either Atopic Dermatitis or a Food Allergy will likely be affected by other allergies later in life. Allergic march perpetuated an earlier peak diagnosis incident rate for allergic rhinitis. Allergic Rhinitis can occur independently from other allergies compared to Atopic Dermatitis, Food Allergy and Asthma.

The Multiple Trajectories of the Allergic March.

The allergic march comprises the sequential appearance of a series of allergic comorbidities. However, variability in the onset and progression of allergic diseases generates a heterogeneous scenario that does not follow a linear and single trajectory. Almost half of the pediatric population presents at least 1 allergy symptom. However, only 4%-6% present multimorbidity, with several allergic diseases co-occurring. It has recently been shown that although they share etiological mechanisms and risk factors, allergic diseases arise independently. In most cases, progression is not consecutive, or at least not the same in all patients. TH2-mediated inflammation, epithelial barrier dysfunction, and genetic predisposition play a fundamental role in the etiology of allergic diseases, on which the interaction with the exposome acts decisively. Therefore, studying diseases from an omics point of view is essential when attempting to describe the various trajectories of allergic progression and to propose effective interventions to prevent multimorbidity. In this narrative review, we provide an overview of the current perception of the allergic march, including clinical observations, omics data, risk factors, and measures aimed at modifying its course or even preventing its onset.

The Multiple Trajectories of the Allergic March

The allergic march comprises the sequential appearance of a series of allergic comorbidities. However, variability in the onset and progression of allergic diseases generates a heterogeneous scenario that does not follow a linear and single trajectory. Almost half of the pediatric population presents at least 1 allergy symptom. However, only 4%-6% present multimorbidity, with several allergic diseases co-occurring. It has recently been shown that although they share etiological mechanisms and risk factors, allergic diseases arise independently. In most cases, progression is not consecutive, or at least not the same in all patients. TH2-mediated inflammation, epithelial barrier dysfunction, and genetic predisposition play a fundamental role in the etiology of allergic diseases, on which the interaction with the exposome acts decisively. Therefore, studying diseases from an omics point of view is essential when attempting to describe the various trajectories of allergic progression and to propose effective interventions to prevent multimorbidity. In this narrative review, we provide an overview of the current perception of the allergic march, including clinical observations, omics data, risk factors, and measures aimed at modifying its course or even preventing its onset. (AU)

La marcha alérgica ha dado respuesta durante mucho tiempo a un escenario de aparición secuencial de diferentes comorbilidades alérgicas. Sin embargo, la variabilidad en la aparición y progresión de las diferentes enfermedades alérgicas dibuja un escenario heterogéneo que no responde a una trayectoria lineal y única. Aunque en la actualidad casi la mitad de la población infantil presenta al menos un síntoma de alergia, tan solo un 4-6% presenta multimorbilidad, coexistiendo varias entidades alérgicas. Recientemente se ha demostrado que, aunque compartiendo mecanismos etiológicos y factores de riesgo, estas enfermedades alérgicas surgen de manera independiente y que, en la mayoría de los casos, no se observa una progresión consecutiva, o al menos, no la misma en todos los pacientes. La inflamación mediada por células T helper de tipo 2 (Th2), la disfunción de la barrera epitelial y la predisposición genética juegan un papel fundamental en la etiología de estas enfermedades, sobre los que actúan de manera determinante la interacción con el exposoma. Por ello, el estudio de las enfermedades, desde un punto de vista de las ómicas, es fundamental para describir las diferentes trayectorias de la marcha alérgica y proponer intervenciones eficaces para evitar escenarios de multimorbilidad. En esta revisión narrativa se incluye una descripción general de la percepción actual de la marcha alérgica, incluidas observaciones clínicas, datos ómicos, factores de riesgo y medidas preventivas propuestas para modificar su curso o incluso prevenir su aparición. (AU)

A different starting line for allergic march: food protein-induced allergic proctocolitis.

OBJECTIVE: The aim of this study is to investigate the long-term prognosis of food protein--induced allergic proctocolitis (FPIAP) patients, the risk of developing both allergic and gastrointestinal diseases, and to evaluate whether it leads to allergic march. METHODS: A total of 149 children who were diagnosed with FPIAP and developed tolerance at least 5 years prior to the study and 41 children (with no history of food allergy) as a control group were enrolled. Both groups were re-evaluated for allergic diseases as well as gastrointestinal disorders. RESULTS: The mean age of diagnosis for the FPIAP group was 4.2 ± 3.0 months, while the mean age of tolerance was 13.9 ± 7.7 months. The mean age of both FPIAP and control groups at the last visit was 101.6 ± 24.4 and 96.3 ± 24.1 months, respectively (P = 0.213). At the final evaluation of both groups, the comorbid allergic disease was significantly higher in the FPIAP group (P < 0.001). There was no significant difference between the two groups in terms of functional gastrointestinal disorders (FGIDs), eosinophilic gastrointestinal diseases, and inflammatory bowel disease (P = 0.198, 0.579, and 0.579, respectively).In the FPIAP group, the allergic disease was significantly higher at the final visit in patients with comorbid allergic disease at diagnosis (P < 0.001). In the FPIAP group, FGID was significantly higher in the group that developed allergic diseases in the future, compared to the group that did not develop allergic diseases in the future (P = 0.034). The proportion of both FGID and allergic diseases was significantly higher in subjects that developed tolerance at >18 months, compared to subjects that developed tolerance at >18 months (P < 0.001 and <0.001, respectively). CONCLUSIONS: Patients with FPIAP may develop allergic diseases as well as FGID in the long term.

Allergic March in Children: The Significance of Precision Allergy Molecular Diagnosis (PAMD@) in Predicting Atopy Development and Planning Allergen-Specific Immunotherapy.

The allergic march is a progression of naturally occurring symptoms whose nature changes with age. The classic allergic march typically begins in infancy and manifests in the form of atopic dermatitis and food allergy. As immune tolerance develops over time, these conditions may resolve by the age of 3-5 years; however, they may evolve into allergic rhinitis and bronchial asthma. Traditional diagnostic assessments, such as skin prick testing or serum allergen-specific immunoglobulin E (sIgE) level testing, are conducted to introduce effective treatment. Recent years saw the emergence of precision allergy molecular diagnosis (PAMD@), which assesses sIgE against allergenic molecules. This new technology helps more accurately evaluate the patient's allergy profile, which helps create more precise dietary specifications and personalize allergen-specific immunotherapy. This review presents possible predictions regarding the allergic march and the means of controlling it based on PAMD@ results.

A different starting line for allergic march: food protein-induced allergic proctocolitis

Objective: The aim of this study is to investigate the long-term prognosis of food protein--induced allergic proctocolitis (FPIAP) patients, the risk of developing both allergic and gastrointestinal diseases, and to evaluate whether it leads to allergic march. Methods: A total of 149 children who were diagnosed with FPIAP and developed tolerance at least 5 years prior to the study and 41 children (with no history of food allergy) as a control group were enrolled. Both groups were re-evaluated for allergic diseases as well as gastrointestinal disorders. Results: The mean age of diagnosis for the FPIAP group was 4.2 ± 3.0 months, while the mean age of tolerance was 13.9 ± 7.7 months. The mean age of both FPIAP and control groups at the last visit was 101.6 ± 24.4 and 96.3 ± 24.1 months, respectively (P = 0.213). At the final evaluation of both groups, the comorbid allergic disease was significantly higher in the FPIAP group (P < 0.001). There was no significant difference between the two groups in terms of functional gastrointestinal disorders (FGIDs), eosinophilic gastrointestinal diseases, and inflammatory bowel disease (P = 0.198, 0.579, and 0.579, respectively). In the FPIAP group, the allergic disease was significantly higher at the final visit in patients with comorbid allergic disease at diagnosis (P < 0.001). In the FPIAP group, FGID was significantly higher in the group that developed allergic diseases in the future, compared to the group that did not develop allergic diseases in the future (P = 0.034). The proportion of both FGID and allergic diseases was significantly higher in subjects that developed tolerance at >18 months, compared to subjects that developed tolerance at >18 months (P < 0.001 and <0.001, respectively). Conclusions: Patients with FPIAP may develop allergic diseases as well as FGID in the long term (AU)

Atopic March: Dermatologic Perspectives.

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.

Genetic polymorphism of ADAM17 and decreased bilirubin levels are associated with allergic march in the Korean population.

BACKGROUND: The "allergic march" refers to changes in the frequency and intensity of allergic diseases with age. Classically, the allergic march begins with atopic dermatitis in infancy and leads to asthma and rhinitis as it continues. There are many factors that induce the allergic march; however, TNF-α may play an important role in inducing inflammation. Therefore, the therapeutic potential of TNF alpha-targeting agents is being considered for allergic march treatment. METHODS: We performed a correlation study to determine whether genetic polymorphisms of ADAM17 and clinical serum values between allergic and normal groups affect disease development by using the cohort data of the Korean genome epidemiologic research project. Gene association study was performed using PLINK version 1.07 ( http://pngu.mgh.harvard.edu/-purcell/plink ) and other statistical analysis was performed using PASW Statistics (version 18.0, SPSS Inc. Chicago, IL, USA). RESULTS: ADAM17 (also called TNF-α converting enzyme or TACE) showed a statistically significant association with the allergic march. The 13 and 8 SNPs in ADAM17 were significantly associated with asthma and allergies, respectively. Among them, on average, SNP of rs6432011 showed the greatest statistical correlation with asthma (P = 0.00041, OR = 1.95, 95% CI 1.35-2.82) and allergies (P = 0.02918, OR = 1.35, 95% CI 1.03-1.78). The effect of SNPs in ADAM17 on transcription factor binding was confirmed using RegulomeDB. The six SNPs are located in the genomic expression quantitative trait loci (eQTL) region and can affect transcription factor binding and gene expression. In clinical serum analysis, bilirubin levels were significantly decreased in the allergic group. The multivariate logistic regression analysis revealed that the low-bilirubin groups indicated a 3.22-fold increase in the prevalence of asthma compared with the high-bilirubin group. CONCLUSIONS: The ADAM17 gene and low bilirubin levels are associated with the allergic march in the Korean population, which can provide new guidelines for managing this disease progression phenomena.

Unsupervised modeling and genome-wide association identify novel features of allergic march trajectories.

BACKGROUND: The allergic march refers to the natural history of allergic conditions during infancy and childhood. However, population-level disease incidence patterns do not necessarily reflect the development of allergic disease in individuals. A better understanding of the factors that predispose to different allergic trajectories is needed. OBJECTIVE: Our aim was to determine the demographic and genetic features that are associated with the major allergic march trajectories. METHODS: Presence or absence of common allergic conditions (atopic dermatitis [AD], IgE-mediated food allergy [IgE-FA], asthma, and allergic rhinitis [AR]) was ascertained in a pediatric primary care birth cohort of 158,510 subjects. Hierarchic clustering and decision tree modeling were used to associate demographic features with allergic outcomes. Genome-wide association study was used to test for risk loci associated with specific allergic trajectories. RESULTS: We found an association between self-identified black race and progression from AD to asthma. Conversely, Asian or Pacific Islander race was associated with progression from AD to IgE-mediated food allergy, and white race was associated with progression from AD to AR. Genome-wide association study of trajectory groups identified risk loci associated with progression from AD to asthma (rs60242841) and from AD to AR (rs9565267, rs151041509, and rs78171803). Consistent with our epidemiologic associations, rs60242841 was more common in individuals of African ancestry than in individuals of European ancestry, whereas rs9565267 and rs151041509 were more common in individuals of European ancestry than in individuals of African ancestry. CONCLUSION: We have identified novel associations between race and progression along distinct allergic trajectories. Ancestral genetic differences may contribute to these associations. These results uncover important health disparities, refine the concept of the allergic march, and represent a step toward developing individualized medical approaches for these conditions.

Dietary Prevention of Atopic March in Pediatric Subjects With Cow's Milk Allergy.

Cow's milk allergy (CMA) is one of the most prevalent food allergies and the most expensive allergic diseases in the pediatric age. There is no cure for CMA, and actual disease management is based on strict avoidance of cow milk protein-containing foods, access to rescue medication, and use of substitutive formulas. Early-life CMA could be one of the first steps of the "allergic march" (AM), leading to the occurrence of other atopic manifestations later in the life, including asthma and oculorhinitis, with subsequent further increase of costs for health care systems and families of affected children. In the last years, diet is emerged as a relevant strategy to prevent allergic diseases through, at least in part, epigenetic modulation of immune system. We provide an overview of studies that investigate the potential role of different dietary strategies in preventing the AM in pediatric patients with CMA.

Asthma/Rhinitis (The United Airway) and Allergy: Chicken or Egg; Which Comes First?

While allergy, asthma and rhinitis do not inevitably co-exist, there are strong associations. Not all those with asthma are allergic, rhinitis may exist without asthma, and allergy commonly exists in the absence of asthma and/or rhinitis. This is likely due to the separate gene/environment interactions which influence susceptibility to allergic sensitization and allergic airway diseases. Allergic sensitization, particularly to foods, and eczema commonly manifest early in infancy, and not infrequently are followed by the development of allergic rhinitis and ultimately asthma. This has become known as the "allergic march". However, many infants with eczema never develop asthma or rhinitis, and both the latter conditions can evolve without prior eczema or food allergy. Understanding the mechanisms underlying the ontogeny of allergic sensitization and allergic disease will facilitate rational approaches to the prevention and management of asthma and allergic rhinitis. Furthermore, a range of new, so-called biological, therapeutic approaches, targeting specific allergy-promoting and pro-inflammatory molecules, are now in clinical trials or have been recently approved for use by regulatory authorities and could have a major impact on disease prevention and control in the future. Understanding basic mechanisms will be essential to the employment of such medications. This review will explain the concept of the united airway (rhinitis/asthma) and associations with allergy. It will incorporate understanding of the role of genes and environment in relation to the distinct but interacting origins of allergy and rhinitis/asthma. Understanding the patho-physiological differences and varying therapeutic requirements in patients with asthma, with or without rhinitis, and with or without associated allergy, will aid the planning of a personalized evidence-based management strategy.

Atopic dermatitis. Interdisciplinary diagnostic and therapeutic recommendations of the Polish Dermatological Society, Polish Society of Allergology, Polish Pediatric Society and Polish Society of Family Medicine. Part I. Prophylaxis, topical treatment and phototherapy.

Atopic dermatitis is a chronic and recurrent inflammatory dermatosis with concomitant intensive pruritus, and is diagnosed both in children and adults. Atopic dermatitis-patients are predisposed to have bacterial, viral and fungal skin infections; they also suffer from an increased risk of developing food allergies (especially, at an infantile age), allergic rhinitis, or bronchial asthma (a so-called atopic march). Currently, an increasing atopic dermatitis incidence constitutes a serious medical problem that regards not only dermatology and allergology, but also paediatrics, and family medicine. The basis for atopic dermatitis treatment and prophylaxis is restoration of epidermal barrier functions by means of tailored emollients. Atopic dermatitis therapies should effectively eliminate clinical symptoms of the disease, prevent exacerbations as well as complications, and improve patients' quality of life.

The effect of an educational program for pregnant women to prevent allergic diseases in infants: study protocol for a randomized controlled trial.

BACKGROUND: Allergic diseases in infants have dramatically increased in developed countries during the past few decades. To date, extensive research has been done on risk factors for allergies in infancy, and preventive measures against them. However, the effect of the primary approach to preventing infantile allergy is still limited. The aim of this trial is to evaluate whether prenatal education interventions, including the latest public research results on allergic diseases, prevent the onset of infant allergies. METHODS/DESIGN: We designed a randomized controlled, two-arm (standard prenatal education vs our education), parallel-group, assessor-blind trial. A sample of 120 pregnant women will be recruited at Chiba Aiyu-kai Kinen Hospital and allocation is by computer-generated randomization. Pregnant women in the intervention arm participate in the childbirth education program established by the specialist and a pediatric allergy educator. The program was developed based on evidences supporting interventions on primary prevention, which are suggested to be beneficial to infantile allergies in recent studies. The primary objective of the study is to determine whether it is possible to establish effective behaviors for allergy prevention in early infancy in the children of pregnant women who participate in an educational program developed by pediatric allergy specialists. Four months after birth, their behaviors will be compared against those of pregnant women who did not participate in the program. DISCUSSION: Allergies are common in many individuals worldwide, and can be present from babyhood through the person's lifetime. One of the strong points of this study is that it should provide pregnant women with accumulated information on preventive knowledge against allergy, that can be effective in some cases, and that women can apply a combination of these behaviors before and after pregnancy. The results of our program will be publicized to help change the behaviors of mothers, and, if the program is effective, for preventing allergies in infants, it will be disclosed worldwide as a new preventive strategy for allergy in infants. TRIAL REGISTRATION: UMIN-CTR, ID: UMIN000034730 Retrospectively registered on 1 December 2018.

Epigenome-wide association study reveals methylation pathways associated with childhood allergic sensitization.

Epigenetic mechanisms integrate both genetic variability and environmental exposures. However, comprehensive epigenome-wide analysis has not been performed across major childhood allergic phenotypes. We examined the association of epigenome-wide DNA methylation in mid-childhood peripheral blood (Illumina HumanMethyl450K) with mid-childhood atopic sensitization, environmental/inhalant and food allergen sensitization in 739 children in two birth cohorts (Project Viva-Boston, and the Generation R Study-Rotterdam). We performed covariate-adjusted epigenome-wide association meta-analysis and employed pathway and regional analyses of results. Seven-hundred and five methylation sites (505 genes) were significantly cross-sectionally associated with mid-childhood atopic sensitization, 1411 (905 genes) for environmental and 45 (36 genes) for food allergen sensitization (FDR<0.05). We observed differential methylation across multiple genes for all three phenotypes, including genes implicated previously in innate immunity (DICER1), eosinophilic esophagitis and sinusitis (SIGLEC8), the atopic march (AP5B1) and asthma (EPX, IL4, IL5RA, PRG2, SIGLEC8, CLU). In addition, most of the associated methylation marks for all three phenotypes occur in putative transcription factor binding motifs. Pathway analysis identified multiple methylation sites associated with atopic sensitization and environmental allergen sensitization located in/near genes involved in asthma, mTOR signaling, and inositol phosphate metabolism. We identified multiple differentially methylated regions associated with atopic sensitization (8 regions) and environmental allergen sensitization (26 regions). A number of nominally significant methylation sites in the cord blood analysis were epigenome-wide significant in the mid-childhood analysis, and we observed significant methylation - time interactions among a subset of sites examined. Our findings provide insights into epigenetic regulatory pathways as markers of childhood allergic sensitization.

Non-IgE-mediated gastrointestinal allergies-Do they have a place in a new model of the Allergic March.

The rise in food allergy has been described as the "second wave" of the allergy epidemic, with some developed countries reporting a prevalence of 10% of challenge-proven food allergies. Recognition of the Allergic March has played a crucial role in identifying causality in allergic conditions, linking atopic dermatitis to food allergy and food allergy to other atopic disorders, thereby highlighting opportunities in prevention and the importance of early intervention. This publication will establish the value of weaving the less well-understood, non-IgE-mediated food allergy into the Allergic March and mapping its progression through childhood and its associated co-morbidities. The proposed non-IgE-mediated Allergic March highlights the concomitant presentation of gastrointestinal symptoms and atopic dermatitis as early presenting symptoms in confirmed non-IgE-mediated allergies and the later development of atopic co-morbidities, including asthma and allergic rhinitis, similar to the IgE-mediated Allergic March. This publication highlights recent observations of a link between non-IgE-mediated food allergy in early childhood and functional gastrointestinal disorders in later life and also the reported occurrence of extra-intestinal manifestations at later ages. Although significant limitations exist in regard to the proposed evolution of the Allergic March model, the authors hope that this publication will influence the management of non-IgE-mediated gastrointestinal allergies and inform future research and interventions.

Higher Polygenetic Predisposition for Asthma in Cow's Milk Allergic Children.

Cow's milk allergy (CMA) is an early-onset allergy of which the underlying genetic factors remain largely undiscovered. CMA has been found to co-occur with other allergies and immunological hypersensitivity disorders, suggesting a shared genetic etiology. We aimed to (1) investigate and (2) validate whether CMA children carry a higher genetic susceptibility for other immunological hypersensitivity disorders using polygenic risk score analysis (PRS) and prospective phenotypic data. Twenty-two CMA patients of the Dutch EuroPrevall birth cohort study and 307 reference subjects were genotyped using single nucleotide polymorphism (SNP) array. Differentially genetic susceptibility was estimated using PRS, based on multiple P-value thresholds for SNP inclusion of previously reported genome-wide association studies (GWAS) on asthma, autism spectrum disorder, atopic dermatitis, inflammatory bowel disease and rheumatoid arthritis. These associations were validated with prospective data outcomes during a six-year follow-up in 19 patients. We observed robust and significantly higher PRSs of asthma in CMA children compared to the reference set. Association analyses using the prospective data indicated significant higher PRSs in former CMA patients suffering from asthma and related traits. Our results suggest a shared genetic etiology between CMA and asthma and a considerable predictive sensitivity potential for subsequent onset of asthma which indicates a potential use for early clinical asthma intervention programs.

Eosinophilic Esophagitis Is a Late Manifestation of the Allergic March.

BACKGROUND: The allergic march describes the natural history of allergic conditions as they develop during childhood. Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease that can be triggered by specific foods. Despite its allergic pathophysiology, the epidemiologic relationship between EoE and established members of the allergic march is unknown. OBJECTIVE: We sought to determine whether EoE meets epidemiologic criteria for being considered a member of the allergic march. METHODS: Using a primary care birth cohort of 130,435 children, we determined the natural histories of atopic dermatitis (AD), IgE-mediated food allergy (IgE-FA), asthma, EoE, and allergic rhinitis (AR) in individual patients. We then performed case-control analyses to establish the extent that existing allergic conditions influence the rate of subsequent EoE diagnosis. RESULTS: A total of 139 children developed EoE during the observation period (prevalence of 0.11%). The peak age of EoE diagnosis was 2.6 years, as compared with 0.3 years, 1 year, 1.1 years, and 2.1 years for AD, IgE-FA, asthma, and AR, respectively. The presence of AD (hazard ratio [HR] 3.2, 95% confidence interval [CI] 2.2-4.6), IgE-FA (HR 9.1, 95% CI 6.5-12.6), and asthma (HR 1.9, 95% CI 1.3-2.7) was independently and cumulatively associated with subsequent EoE diagnosis. The presence of AR was associated with subsequent EoE diagnosis (HR 2.8, 95% CI 2.0-3.9), and the presence of EoE was associated with subsequent AR diagnosis (HR 2.5, 95% CI 1.7-3.5). CONCLUSIONS: Allergic comorbidities are positively associated with EoE diagnosis. Together, our findings suggest that EoE is a late manifestation of the allergic march.

SLIT's Prevention of the Allergic March.

PURPOSE OF REVIEW: The progression of atopic disorders from atopic dermatitis in infants to allergic rhinitis and asthma in children, adolescents, and adults defines the allergy march. Allergen immunotherapy is the only causal treatment altering the immunological mechanism underlying the allergic diseases. The sublingual administration route is more acceptable than the subcutaneous one in pediatric age. RECENT FINDINGS: Several studies show the efficacy and safety profile of sublingual immunotherapy (SLIT) for the treatment of respiratory allergy diseases, but few data are available on its effect of primary and secondary prevention of allergic disease. The purpose of this manuscript is to review the latest studies addressing the effect of SLIT on the development of new sensitizations in not sensitized or already sensitized patients and progression of the allergy march.