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New Directions in Understanding Atopic March Starting from Atopic Dermatitis.

ABSTRACT: 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.

SUBMITTER: Maiello N

PROVIDER: S-EPMC9029734 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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New Directions in Understanding Atopic March Starting from Atopic Dermatitis.

Maiello Nunzia N Comberiati Pasquale P Giannetti Arianna A Ricci Giampaolo G Carello Rossella R Galli Elena E

Children (Basel, Switzerland) 20220323 4

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 understandin ...[more]

PMID: 35455494

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Longitudinal atopic dermatitis endotypes: An atopic march paradigm that includes Black children.

Project description:BackgroundThe atopic march has been studied mostly in White populations, biasing our current paradigms.ObjectiveWe sought to define the atopic march in Black and White children and explore mechanisms for racial differences.MethodsUtilizing 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.ResultsWhite 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.ConclusionsBlack 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.

| S-EPMC9275099 | biostudies-literature

<i>TSLP</i> Polymorphisms in Atopic Dermatitis and Atopic March in Koreans.

Project description:BackgroundAtopic march (AM) is the progression from atopic dermatitis (AD) to allergic rhinitis and asthma. The development of AD is as high as 20% in children worldwide and continues to increase. AD seems to be caused by both genetic and environmental factors. Recently, polymorphisms of the thymic stromal lymphopoietin (TSLP) gene associated with allergic disorders were reported in ethnic groups from various countries.ObjectiveIdentification of TSLP polymorphisms in Koreans with AD or AM.MethodsWhole-exome sequencing was performed in 20 AD and 20 AM patients.ResultsNine single nucleotide polymorphisms (SNPs) of TSLP were detected (rs191607411, rs3806933, rs2289276, rs2289277, rs2289278, rs139817258, rs11466749, rs11466750, rs10073816). These SNPs have been correlated with susceptibility to allergic diseases in ethnic groups from China, Japan, Turkey, and Costa Rica in previous studies. Remarkably, one of 20 patients in the AD group lacked all SNPs, compared to six of 20 patients in the AM group. Odds ratios showed that Korean patients without the nine TSLP variants had an 8.14 times higher risk of moving from AD to AM. Two haplotype blocks were validated in 60 AD and 59 AM patients using Sanger sequencing. The haplotype blocks (rs3806933 and rs2289276) and (rs11466749 and rs11466750) were in high linkage disequilibrium, respectively (D'=0.97, D'=1).ConclusionThe increase of major allele frequency of respective nine TSLP variants may enhance the risk of AM. These data will contribute to improved genetic surveillance system in the early diagnosis technology of allergic disease.

| S-EPMC7992469 | biostudies-literature

Mechanisms by Which Atopic Dermatitis Predisposes to Food Allergy and the Atopic March.

Project description:The Atopic march denotes the progression from atopic dermatitis (AD) to the development of other allergic disorders such as immunoglobulin (Ig) E-mediated food allergy, allergic rhinitis and asthma in later childhood. There is increasing evidence from prospective birth cohort studies that early-onset AD is a risk factor for other allergic diseases or is found in strong association with them. Animal studies now provide mechanistic insights into the pathways that may be responsible for triggering the progression from the skin barrier dysfunction seen in AD to epicutaneous sensitization, food allergy and allergic airway disorders. Recent large randomized controlled trials have demonstrated the efficacy of early interventions targeted at AD and food allergy prevention. These show great promise for research into future strategies aimed at prevention of the atopic march.

| S-EPMC6267189 | biostudies-literature

Microarray result of human skin derived from normal, atopic dermatitis and atopic march patients

Project description:The patho-mechanism of atopic dermatitis showing systemic involvement may be explained by Th17-related cytokines induced by FABP5 through systemic sensitization to a major allergen of a house dust mite.

2020-03-05 | GSE146352 | GEO

Current understanding of epigenetics in atopic dermatitis.

Project description:Atopic dermatitis (AD) is an inflammatory skin disorder affecting up to 20% of the paediatric population worldwide. AD patients commonly exhibit dry skin and pruritus and are at a higher risk for developing asthma as well as allergic rhinitis. Filaggrin loss-of-function variants are the most widely replicated genetic risk factor among >40 genes associated with AD susceptibility. The prevalence of AD has tripled in the past 30 years in industrial countries around the world. This urgent public health issue has prompted the field to more thoroughly investigate the mechanisms that underlie AD pathogenesis amidst environmental exposures. Epigenetics is the study of heritable, yet reversible, modifications to the genome that affect gene expression. The past decade has seen an emergence of exciting studies identifying a role for epigenetic regulation associated with AD and at the interface of environmental factors. Such epigenetic studies have been empowered by sequencing technologies and human genome variation and epigenome maps. miRNAs that post-transcriptionally modify gene expression and circRNAs have also been discovered to be associated with AD. Here, we review our current understanding of epigenetics associated with atopic dermatitis. We discuss studies identifying distinct DNA methylation changes in keratinocytes and T cells, eQTLs as DNA methylation switches that impact gene expression, and histone modification changes associated with AD-related microbial dysbiosis. We further highlight the need for integrative and collaborative analyses to elucidate the impact of these epigenetic findings as potential drivers for AD pathogenesis and the translation of this new knowledge to develop newer targeted treatments.

| S-EPMC8361700 | biostudies-literature

Effect of topical emollient on the development of atopic dermatitis and atopic march in a mice model

Project description:To investigate the effect of emollient on atopic march in a murine model of chronic atopic dermatitis (AD). Mice were divided into 3 groups and treated with topical calcipotriol and ovalbumin alone or with a linoleic acid-ceramide-containing emollient. After 28 days, clinical, histological, and transcriptomic analyses were performed in skin lesions, lung and serum. Calcipotriol combined with ovalbumin induced a typical AD model with concomitant increased expression of Th2 and basophil-related genes in the lung. Compared to AD group, emollient group: 1) Skin: clinical severity and inflammatory cell infiltration were significantly reduced and transcriptomic analysis revealed significant downregulation of AD-related genes (286 of 1450 differentially expressed genes (DEGs)) including those related to innate inflammation (S100a8/a9, Il1b, Defb3/6, Mmp12), chemokines (Cxcl1/3, Ccl3/4) and barrier (Krt2/6b/80, Serpinb12, Lce3e, Sprr2). DEGs down-regulated by emollient were enriched in mitochondrial OXPHOS-related pathways, while up-regulated DEGs were mainly enriched in axon guidance, tight junctions, as shown by KEGG analyses. 2) Serum: total IgE and TSLP levels were significantly decreased, and IL-4 levels showed a decreasing tendency. 3) Lung: 187 of 275 upregulated DEGs were significantly downregulated in lung tissue including genes involved in cytokine and cytokine receptor interaction (Cxcl2/Cxcr2, Ccl2/3, Csf3r, etc.) and basophil activation (Mcpt8, Cd200r3, Ms4a2). Thus, topical emollient not only reduces skin inflammation and maintain skin barrier homeostasis by inhibiting the mitochondrial respiratory chain, but also limits systemic inflammation by decreasing TSLP and IgE levels. Moreover, it reduces respiratory chemokine production and basophil infiltration and activation, providing a molecular basis for blocking the atopic march.

2023-03-29 | GSE222019 | GEO

Online education improves pediatric residents' understanding of atopic dermatitis.

Project description:Background/objectivesPediatricians manage skin conditions such as atopic dermatitis (AD) but report that their dermatologic training is inadequate. Online modules may enhance medical education when sufficient didactic or clinical teaching experiences are lacking. We assessed whether an online module about AD improved pediatric residents' knowledge and changed their clinical management of AD.MethodsTarget and control cohorts of pediatric residents from two institutions were recruited. Target subjects took a 30-question test about AD early in their residency, reviewed the online module, and repeated the test 6 months and 1 year later. The control subjects, who had 1 year of clinical experience but had not reviewed the online module, also took the test. The mean percentage of correct answers was calculated and compared using two-sided, two-sample independent t tests and repeated-measures analysis of variance. For a subset of participants, clinical documentation from AD encounters was reviewed and 13 practice behaviors were compared using the Fisher exact test.ResultsTwenty-five subjects in the target cohort and 29 subjects in the control cohort completed the study. The target cohort improved from 18.0 ± 3.2 to 23.4 ± 3.4 correctly answered questions over 1 year (P < .001). This final value was greater than that of the control cohort (20.7 ± 4.5; P = .01). Meaningful differences in practice behaviors were not seen.ConclusionPediatric residents who reviewed an online module about AD demonstrated statistically significant improvement in disease-specific knowledge over time and had statistically significantly higher scores than controls. Online dermatology education may effectively supplement traditional clinical teaching.

| S-EPMC5777881 | biostudies-literature

Itch in Atopic Dermatitis - What Is New?

Project description:Atopic dermatitis (AD) is among the most frequent inflammatory skin diseases in humans, affecting up to 20% of children and 10% of adults in higher income countries. Chronic pruritus is a disease-defining symptom of AD, representing the most burdensome symptom for patients. Severe chronic pruritus causes significant sleep disturbances and impaired quality of life, as well as increased anxiety, depression and suicidal behavior. Until recently, skin care, topical corticosteroids, and calcineurin-inhibitors were primarily used to treat mild to moderate AD, while phototherapy and immunosuppressive agents such as corticosteroids, cyclosporine, and methotrexate were used to treat patients with moderate to severe AD. The potential short- and long-term adverse events associated with these treatments or their insufficient therapeutic efficacy limited their use in controlling pruritus and eczema in AD patients over longer periods of time. As our understanding of AD pathophysiology has improved and new systemic and topical treatments have appeared on the market, targeting specific cytokines, receptors, or their intracellular signaling, a new era in atopic dermatitis and pruritus therapy has begun. This review highlights new developments in AD treatment, placing a specific focus on their anti-pruritic effects.

| S-EPMC8137993 | biostudies-literature

What's New in Topicals for Atopic Dermatitis?

Project description:Atopic dermatitis (AD) is a chronic inflammatory skin condition that can have tremendous impact on quality of life for affected children and adults. First-line therapy for acute management of AD includes topical therapies such as corticosteroids, calcineurin inhibitors, and, more recently, the phosphodiesterase inhibitor crisaborole. Topical agents have remained the mainstay therapy for decades; however, there has been a longstanding need for topical therapies with high efficacy and low risk of adverse effects with long-term use. Given the ongoing advances in understanding the pathogenesis of AD, there are novel targets for pharmacological intervention. We are now in an unprecedented time with more than 40 topical treatments in the pipeline for AD in addition to many developments and treatments on the horizon. This review summarizes selected therapeutic topical agents in later phases of development that target various aspects in the pathogenesis of AD such as Janus kinase inhibition (ruxolitinib and delgocitinib), phosphodiesterase-4 inhibition (roflumilast and difamilast), aryl hydrocarbon modulation (tapinarof), and modulation of the microbiome. We also review novel targeted therapies that are in early phase clinical trials, including AMTX-100, BEN-2293, and PRN473. Preliminary findings on efficacy and tolerability of most of these agents are promising, but further studies are warranted to evaluate the long-term safety and efficacy of these novel agents against the current standard of care.

| S-EPMC9464760 | biostudies-literature

New Biologics for the Treatment of Atopic Dermatitis: Analysis of Efficacy, Safety, and Paradoxical Atopic Dermatitis Acceleration.

Project description:Atopic dermatitis (AD) is a chronic, inflammatory skin disease with an eczematous rash and itching. Due to undesired adverse effects of traditional systemic treatment, there is still an unmet need for safe and effective long-term therapy for refractory AD. As our understanding of the pathogenesis underlying AD grows, novel treatments targeting specific molecules have been developed. Here, we discuss the efficacy and safety profiles of these drugs in recent clinical trials. Among their adverse effects, of particular note is AD acceleration. Although there is still debate about whether certain adverse reactions can be said to be paradoxical adverse events (PAEs), a wide range of PAEs have been reported during biological treatment for chronic immune-mediated diseases. Close surveillance of novel biologics is crucial to detect new undescribed paradoxical reactions and to shed light on the convoluted pathogenesis of AD.

| S-EPMC8181104 | biostudies-literature

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