Atopic March Research Articles

Atopic dermatitis and its relation to food allergy.

To present the most recent evidence on atopic dermatitis and its relation to food allergy. Atopic dermatitis is a chronic inflammatory disorder of the skin characterized by impaired skin barrier because of multifactorial causes including genetic factors, immune dysregulation, and skin microbiome dysbiosis. Infants with temporary skin barrier disruption and/or persistent atopic dermatitis are particularly at risk of developing food allergy (during the so-called atopic march), with up to half of patients demonstrating positive food-specific IgE and one-third of severe cases of atopic dermatitis having positive symptoms on oral food challenge. A high proportion of children with atopic dermatitis exhibit asymptomatic sensitization to foods, and skin testing to identify potential food triggers is not recommended unless the patient has a history suggestive of food allergy and/or moderate-to-severe atopic dermatitis unresponsive to optimal topical care. Indeed, indiscriminate testing can lead to a high proportion of false-positive tests and harmful dietary evictions. Promising strategies to prevent food allergy in children with atopic dermatitis include early skincare with emollients and treatment with topical steroid, and early introduction of highly allergenic foods. Further studies are required to identify risk factors for atopic dermatitis to help prevent the development of food allergy in this high-risk population.

The atopic march and Staphylococcus aureus colonization are associated with fall birth

The atopic march and Staphylococcus aureus colonization are associated with fall birth

Origins of allergic disease: Maternal and early childhood factors

The incidence of allergic diseases has increased during the past 2 decades. 1 DeKruyff R.H. Zhang W. Nadeau K.C. Leung D.Y.M. Wills-Karp M. Summary of the Keystone Symposium “Origins of allergic disease: microbial, epithelial and immune interactions,” March 24-27, Tahoe City, California. J Allergy Clin Immunol. 2020; 145: 1072-1081.e1 Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar The study of the origins of allergy is important to understand the mechanisms of allergy development and to produce interventions to treat or prevent allergic diseases. The term atopic march is used to describe the progression of allergic disease development, beginning with atopic dermatitis (AD) and progressing to food allergy (FA), asthma, and allergic rhinitis. Although it is necessary to focus on early childhood factors, the prenatal environment must also be considered. In particular, factors that contribute to epithelial barrier disruption in the skin, lungs, and gut play a role in the type 2 inflammation associated with allergic diseases. Pollution, other environmental irritants, food chemicals, and allergens are areas of focus that drive allergy development in utero into early childhood.

Polygenic risk score for atopic dermatitis in the Canadian population

Atopic dermatitis (AD) is characterized by a damaged skin barrier that allows allergens to penetrate the body, leading to sensitization and a higher risk of developing food allergies (relative risk [RR], 33.79), asthma (RR, 7.04), and/or rhinitis (RR, 11.75), all features of the atopic march.1 Recent evidence has shown that the atopic march can be modified in high-risk infants with early interventions directed at reestablishing and/or maintaining skin barrier function with intense use of simple emollients, and introducing food allergens early into the diet.2, 3, 4, 5 Although these constitute examples of low-intensity, high-impact interventions for health care systems, their successful and indiscriminate implementation in the whole population is neither feasible nor realistic. In this context, building a predictive tool to identify children at high risk of developing moderate to severe AD (MSAD) would allow targeted interventions with maximized impact. In this study, a polygenic risk score (PRS) with an area under the curve (AUC) of 88% and explaining 37% of MSAD variance was established for the Canadian population.

Epicutaneous sensitization in the development of food allergy: What is the evidence and how can this be prevented?

There is increasing evidence regarding the importance of allergic sensitization through the skin. In this review, we provide an overview of the atopic march and immune mechanism underlying the sensitization and effector phase of food allergy. We present experimental models and human data that support the concept of epicutaneous sensitization and how this forms one half of the dual-allergen exposure hypothesis. We discuss specific important elements in the skin (FLG and other skin barrier gene mutations, Langerhans cells, type 2 innate lymphoid cells, IL-33, TSLP) that have important roles in the development of allergic responses as well as the body of evidence on environmental allergen exposure and how this can sensitize an individual. Given the link between skin barrier impairment, atopic dermatitis, food allergy, allergic asthma, and allergic rhinitis, it is logical that restoring the skin barrier and prevention or treating atopic dermatitis would have beneficial effects on prevention of related allergic diseases, particularly food allergy. We present the experimental and human studies that have evaluated this approach and discuss various factors which may influence the success of these approaches, such as the type of emollient chosen for the intervention, the role of managing skin inflammation, and differences between primary and secondary prevention of atopic dermatitis to achieve the desired outcome.

Could FeNO Predict Asthma in Patients with House Dust Mites Allergic Rhinitis?

Background and Objectives: The evolution of allergic rhinitis to asthma is a part of “atopic march”. The aim of this study was to analyze possible predictive markers for asthma occurrence in patients with allergic rhinitis to house dust mites (HDM). Materials and Methods: Fifty-eight patients with persistent allergic rhinitis (PAR) were included. The clinical, biological evaluation and fractionated exhaled nitric oxide (FeNO) measurement were performed at enrolment. The patients were clinically evaluated after one year to determine asthma occurrence. Results: The severity of rhinitis symptoms, levels of total immunoglobulin E (IgE), ICAM-1, VCAM-1, E-selectin and IL-6, but not IL-8 and TNF-α were higher in patients with allergic rhinitis who developed asthma compared to non-asthmatics, but the differences were not significant to considered them as predictive factors for asthma occurrence. The risk of asthma was independently influenced by patients aged over 30 years ((OR-3.74; CI95% 0.86–16.31; p = 0.07), a duration of allergic rhinitis over 12 months ((OR-4.20; CI95% 0.88–20; p = 0.07) and a basal FeNO over 28 parts per billion (pbb) ((OR-18.68; CI95% 3.79–92.05; p < 0.001). Conclusion: Clinical and biological parameters may predict asthma occurrence in patients with persistent allergic rhinitis to HDM. Adult patients with a longer duration of rhinitis symptoms and a high level of FeNO have a greater risk to develop asthma.

Biomarker prediction of pediatric atopic dermatitis severity

Abstract Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects 25% of children and 1–3% of adults worldwide, and has increased 2- to 3-fold over the past several decades. The pathogenesis of AD may result from complex interactions between environmental and genetic factors, barrier defects and immune dysregulation resulting in epidermal hyperplasia and increased penetration of allergens and microbial pathogens. Although most cases of AD are transient, and AD is often thought of as the first step of the atopic march, some AD patients have active disease throughout life. In this study, we analyzed a population of infants that were at high risk for atopic disease and sampled serum, analyzed peripheral blood mononuclear cells, and clinical parameters upon entry (mean age 10.3 months) and five years later. We tested 161 serum analytes using a combination of single-plex, multiplex, Olink, and Quanterix assays. Broadly, the concentration of many analytes fell over time, while SDF and sCD40L concentration increased at the later time point. Several analytes correlated with AD severity as assessed by SCORAD, and most significantly, IL-13 and MCP-4 correlated with SCORAD at both time points. Subsets of cytokines were significantly correlated with each other, consistent with early disease skewing toward type 2 immune response, and two subsets were correlated with percentages of NKT cells or Th2 cells in the peripheral blood. Importantly, forward selection modeling identified 33 infant serum analytes that could be used to predict AD severity five years later (r2=0.85, p=0.042). This dataset will likely have predictive value for AD persistence past infancy and will be useful in further defining the pathogenesis of atopic disease.

Events in Normal Skin Promote Early-Life Atopic Dermatitis—The MPAACH Cohort

Nonlesional skin in atopic dermatitis (AD) is abnormal, but the pathobiology of lesional and nonlesional skin and the definition of endotypes are poorly understood. To define lesional and nonlesional endotypes of AD by building the first US-based early-life prospective cohort of children with AD, the Mechanisms of Progression from AD to Asthma in Children cohort. We assessed lesional and nonlesional skin transepidermal water loss, filaggrin (FLG) and alarmin (S100A8, S100A9) expression, staphylococcal colonization, and patterns of aeroallergen and food sensitization to define nonlesional and lesional phenotypes and endotypes. Pathophysiologic changes were present in lesional and nonlesional skin and were associated with SCORing for Atopic Dermatitis. Nonlesional skin had features characteristic of diseased skin including low FLG and high alarmin expression, and increased colonization with Staphylococcus aureus. In a multivariate model, nonlesional, but not lesional, FLG expression was associated with the development of cosensitization and moderate to severe AD. Lesional skin was characterized by further deficits in FLG expression (P < .001), but alarmin expression was the same as observed in nonlesional skin. This study reveals that events in the nonlesional, not the lesional, skin promote the subsequent development of AD severity and cosensitization, which is a key risk factor for allergic comorbidities. Collectively, these data suggest the presence of a subclinical eczema endotype that may predispose to the development of allergic disease in the absence of overt eczema. This may represent a new definition of the atopic march that starts with skin barrier dysfunction rather than eczema.

Efficacy of the curcumin to ameliorate ovalbumin induced atopic dermatitis and progression of atopic march in mice

Atopic dermatitis (AD) is a chronic pruritic skin inflammatory condition which arises due to skin barrier disruption and immune dysregulation. Curcumin has been widely exploited in the treatment of various skin‐related pathologies due to its pharmacologic effects. The present study was designed to investigate the beneficial effect of curcumin in the amelioration of ovalbumin (OVA)‐induced atopic dermatitis and ensuing atopic march. AD was induced in female Balb/c mice by epicutaneous application of OVA at the back skin site for 1 week followed by a resting period of two‐weeks and same protocol was repeated thrice. Curcumin treatment was given either intraperitoneally or topically in two separate groups of animals. Curcumin was administered intraperitoneally at different doses during the last sensitization phase for a period of 7 days. Topical application of curcumin at a dose of 10 mg/kg was done for a period of 14 days during the second resting period. Skin tissues were examined for histologic changes, Th2 cytokines and the oxidative stress markers. Systemic curcumin administration ameliorated the onset of AD‐like lesions and significantly improved the dermal destruction in mice upon OVA exposure. Curcumin reduced the levels of various inflammatory mediators such as Th2 promoting cytokines (TSLP and IL‐33), Th2 cytokines (IL‐4, IL‐5, IL‐13 and IL‐31) and also downregulated the activation/expression of Stat‐6 and GATA‐3. Next, when curcumin preparation was applied topically, it shows a remarkable efficacy in restoration of the histo‐architecture of the skin suggesting that the phytochemical based ointment(s) can offer a newer treatment option for AD and associated atopic march. Finally, curcumin blocked the OVA initiated progression of AD towards asthma as evident by the reduced number of BALF inflammatory cells and suppressed expression of Th2 cytokines in the lung tissue upon aerosolized exposure of the allergen to the AD mice. Overall, our findings demonstrate for the first time that curcumin has the efficacy to ameliorate AD and halt the progression of associated atopic march.Support or Funding InformationFinancial support from Department of Biotechnology, Government of India [BT/PR17968/MED/122/33/2016]; University Grants Commission, New Delhi, India [UGC‐SAP] and [UGC‐BSR‐SRF]

Exposure to diisononyl phthalate promotes atopic march by activating of NF-κB and p38 MAPK

What factors and underlying mechanisms influence the occurrence of the atopic march remain unclear. Recent studies suggest that exposure to diisononyl phthalate (DINP) might be associated with the occurrence of atopic dermatitis (AD) and asthma. However, little is known about the role of DINP exposure in the atopic march. In this study, we investigated the effect of DINP exposure on the progression from AD to asthma, and explored the potential mechanisms. We built an atopic march mouse model from AD to asthma, by exposure to DINP and sensitization with OVA. Pyrrolidine dithiocarbamate and SB203580 were used to block NF-κB and p38 MAPK respectively, to explore the possible molecular mechanisms. The data showed that DINP aggravated airway remodeling and airway hyperresponsiveness (AhR) in the progression from AD to asthma, induced a sharp increase in IL-33, IgE, Th2 and Th17 cytokines, and resulted in an increase in the expression of thymic stromal lymphopoietin (TSLP) and in the number of inflammatory cells. Blocking NF-κB inhibited AD-like lesions, and the production of IL-33 and TSLP in the progression of AD, while alleviating airway remodeling, AhR, and the expression of Th2 and Th17 cytokines in both the progression of AD and the asthmatic phenotype. Blocking p38 MAPK in the progression of asthma, inhibited airway remodeling, AhR, and the expression of Th2 and Th17 cytokines. The results demonstrated that exposure to DINP enhanced the immune response to memory CD4+ T helper cells through the NF-κB and p38 MAPK signaling pathways, leading to an aggravation of the atopic march.

Fatty-Acid-Binding Protein 5 Induces Th17 Polarization in Atopic Dermatitis Patients with Atopic March

Background: While incidence of patients with atopic dermatitis (AD) with atopic march (AM) showing respiratory allergy is steadily rising, the pathomachanism is still unclear. Methods: To explore the mechanism of AM, RNA microarray, flow cytometry, quantitative real-time polymerase chain reaction, and immunofluorescence staining were performed to compare the skin, lungs, and T cells from two groups; patients and mice with AD and AM versus AD without AM. We also co-cultured dendritic cells and CD4+ T cells with various Dermatophagoides farinae allergen fractions. Cytokine levels were evaluated using enzyme-linked immunosorbent assay. Findings: Fatty-acid-binding protein 5 (FABP5) was more highly expressed in AM patients and Th17-related genes were also strongly associated with AM patients. Correspondingly, FABP5 knockdown significantly decreased Th17-inducing cytokines in keratinocytes and IL-17A in T cells from AM patients. Further confirmation was done by using AM mice models compared to those without AM. Der f 1, a major D. farinae allergen, increased FABP5 and IL-17A expression in T cells from AM patients. Higher serum FABP5 levels from AM patients were positively correlated with serum IL-17A levels. Interpretation: FABP5 expression, possibly enhanced by higher epicutaneous and respiratory sensitization to Der f 1, may directly promote Th17 responses in AD patients with AM. Funding Statement: This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science and ICT; No. NRF-2017R1A2B4009568), grants of the Korean Health Technology R&D Project, Ministry for Health, Welfare & Family Affairs, and the Republic of Korea (HI13C0010, HI14C1324, HI14C1799). Declaration of Interests: The authors state no conflict of interest. Ethics Approval Statement: Informed consent was obtained from all subjects, and the protocols were approved by the Institutional Review Board (no. 4-2013-0624). All animal procedures were approved by the Institutional Animal Care and Use Committee of the Department of Laboratory Animal Resources, Yonsei Biomedical Research Institute, Yonsei University College of Medicine (IACUC No. 2016-0007).

Maternal Nutritional Status and Development of Atopic Dermatitis in Their Offspring.

Atopic dermatitis (AD) is the leading chronic skin inflammatory disease and the initial manifestation of atopic march. Available evidence supports the notion that primary prevention early in life leads to a decreased incidence of AD, thus possibly decreasing the subsequent occurrence of atopic march. Nutritional status is essential to a proper functioning immune system and is valued for its important role in AD. Essential nutrients, which include carbohydrates, proteins, lipids, vitamins, and minerals, are transferred from the mother to the fetus through the placenta during gestation. Various nutrients, such as polyunsaturated fatty acids (PUFAs) and vitamin D, were studied in relation to maternal status and offspring allergy. However, no strong evidence indicates that a single nutrient or food in mothers' diet significantly affects the risk of childhood AD. In the light of current evidence, mothers should not either increase nor avoid consuming these nutrients to prevent or ameliorate allergic diseases in their offspring. Each essential nutrient has an important role in fetal development, and current government recommendations suggest specific intake amounts for pregnant women. This review discusses evidence on how various nutrients, including lipids (monounsaturated fatty acids, PUFAs, saturated fatty acids, and short-chain fatty acids), carbohydrates (oligosaccharides and polysaccharides), proteins, vitamins (A,B, C, D, and E), and trace minerals (magnesium, iron, zinc, copper, selenium, and strontium) in maternal status are associated with the development of AD and their possible mechanisms.

Halting the March: Primary Prevention of Atopic Dermatitis and Food Allergies

Atopic dermatitis (AD) is one of the most common inflammatory skin conditions, affecting 15% to 30% of children and 2% to 10% of adults. Population-based studies suggest that having AD is associated with subsequent development of other atopic diseases, in what is known as the "atopic march." We will provide an overview of studies that investigate primary prevention strategies for the first 2 diseases in the march, namely, AD and food allergies (FA). These strategies include emollients, breastfeeding, microbial exposures, probiotics, vitamin D and UV light, water hardness, and immunotherapy. Some studies, including randomized controlled trials on emollients and microbial supplementation, have found encouraging results; however, the evidence remains limited and contradictory. With regard to breastfeeding, microbial and lifestyle exposures, vitamin D and UV light, water hardness, and immunotherapy, the lack of randomized controlled trials makes it difficult to draw definitive conclusions. Current American Academy of Pediatrics guidelines support the idea that breastfeeding for 3 to 4 months can decrease AD incidence in children less than 2 years old. Recommendations regarding a direct relationship between breastfeeding on FA, however, cannot be made because of insufficient data. Regarding microbial supplementation, most guidelines do not recommend probiotics or prebiotics for the purpose of preventing allergic diseases because of limited evidence. Before definitive conclusions can be made regarding these interventions, more well-designed, longitudinal, and randomized controlled trials, particularly in at-risk populations, are required.

From IBS to ME – The dysbiotic march hypothesis

Irritable bowel syndrome (IBS) is often associated with other unexplained complaints like chronic fatigue syndrome (CFS), fibromyalgia and myalgic encephalopathy (ME). The pathogenesis of the relationship is unknown. Intestinal dysbiosis may be a common abnormality, but based on 1100 consecutive IBS patients examined over a nine years period, we hypothesize that the development of the disease, often from IBS to ME, actually manifests a “dysbiotic march”. In analogy with “the atopic march” in allergic diseases, we suggest “a dysbiotic march” in IBS; initiated by extensive use of antibiotics during childhood, often before school age. Various abdominal complaints including IBS may develop soon thereafter, while systemic symptom like CFS, fibromyalgia and ME may appear years later.

Belinostat resolves skin barrier defects in atopic dermatitis by targeting the dysregulated miR-335:SOX6 axis

Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Skin barrier defects contribute to disease initiation and development; however, underlying mechanisms remain elusive. To understand the underlying cause of barrier defect, we investigated aberrant expression of specific microRNAs (miRNAs) in AD. Delineating the molecular mechanism of dysregulated miRNA network, we focused on identification of specific drugs that can modulate miRNA expression and repair the defective barrier in AD. A screen for differentially expressed miRNAs between healthy skin and AD lesional skin resulted in the identification of miR-335 as the most consistently downregulated miRNA in AD. Using in silico prediction combined with experimental validation, we characterized downstream miR-335 targets and elucidated the molecular pathways by which this microRNA maintains epidermal homeostasis in healthy skin. miR-335 was identified as a potent inducer of keratinocyte differentiation; it exerts this effect by directly repressing SOX6. By recruiting SMARCA complex components, SOX6 suppresses epidermal differentiation and epigenetically silences critical genes involved in keratinocyte differentiation. In AD lesional skin, miR-335 expression is aberrantly lost. SOX6 is abnormally expressed throughout the epidermis, where it impairs skin barrier development. We demonstrate that miR-335 is epigenetically regulated by histone deacetylases; a screen for suitable histone deacetylase inhibitors identified belinostat as a candidate drug that can restore epidermal miR-335 expression and rescue the defective skin barrier in AD. Belinostat is of clinical significance not only as a candidate drug for AD treatment, but also as a potential means of stopping the atopic march and further progression of this systemic allergic disease.

The Atopic March and Staphylococcus Aureus Colonization are Associated with Fall Birth

The Atopic March and Staphylococcus Aureus Colonization are Associated with Fall Birth

House dust mite-specific immunotherapy alters the natural course of atopic march.

Allergen immunotherapy (AIT) is an effective treatment for patients with allergic diseases; it has been shown to modify the underlying cause of the disease. The house dust mite (HDM) is a major perennial allergen source and a significant cause of allergic-related diseases such as allergic rhinitis, asthma, and atopic dermatitis. HDM allergen is an important factor in the pathogenesis of allergic diseases. Sensitization to HDM allergen often occurs early in life and appears to play an important role in the progression from allergic rhinitis to asthma in children. The role of HDM AIT results in immunologic tolerance, provides an alternative option for treating HDM allergy through targeting the mechanisms of allergic reaction, and creates a long-term benefit. There are two forms of testing for aeroallergen, either detect by skin testing or by in vitro IgE assays. Both subcutaneous immunotherapy and sublingual immunotherapy are effective in the treatment of allergic diseases. In the future, new forms of allergen extracts can help improve safety and efficacy of AIT. Novel approaches to immunotherapy currently being explored include the use of adjuvants, allergen-derived peptides, modified recombinant allergen vaccines, and gene-specific immunotherapy.

Deserters on the atopic march: Risk factors, immune profile and clinical outcomes of food sensitized-tolerant infants.

A few studies have investigated the antecedents and outcomes of infants who demonstrate IgE sensitization to foods that they clinically tolerate. Improved understanding of this sensitized-tolerant phenotype may inform strategies for the prevention of food allergy. In an Australian birth cohort (n=1074), assembled using an unselected antenatal sampling frame, participants were categorized as nonsensitized (NS), sensitizedtolerant (ST), or food allergic (FA) based on skin prick testing and food challenge at 12months of age. Environmental exposures were recorded throughout. Cord blood regulatory T-cell populations were measured at birth. Subsequent childhood allergic disease was assessed by parent report, clinical examination, and repeat skin prick testing. The covariates of interest varied between NS (n=698), ST (n=27), and FA (n=61) groups as follows, suggesting that across these measures, the ST group was more similar to the NS than the FA group: family history of eczema NS 44.6%, ST. 44.6%, FA 65.6%; pet ownership at 12months: NS 71.5%, ST 81.5%, FA 45.8%; eczema during the first 12months: NS 19%, ST 32%, FA 64%; and aeroallergen sensitization at 4years: NS 19.1%, ST 28.6%, FA 44.4%. At birth, a higher proportion of activated regulatory T cells was associated with ST (OR=2.89, 95% CI 1.03-8.16, P=.045). Food-sensitized-tolerance in infancy appears to be associated with a similar pattern of exposures, immunity, and outcomes to nonsensitized infants. In addition, we found some evidence that an elevated proportion of activated regulatory T cells at birth was specific to the sensitized-tolerant infants, which may be relevant to suppression of clinical disease.

The Roadmap From Allergic Rhinitis to Asthma

Upper and lower airways display some common characteristic described as a holistic model. Because rhinitis may proceed asthma, it is imperative to understand the mechanisms and risk factors responsible for the progression from rhinitis to asthma. Subclinical lower airway abnormalities have been observed in patients with rhinitis without asthma. Recent evidence indicates that these patients may have an increased risk of developing asthma. Environmental and genetic factors can contribute to enhance this possibility. The treatments of rhinitis have also been shown to be beneficial to the lower airway, and therefore potentially modify the natural evolution of the atopic march. Lower airway disease is a good predictor for the roadmap from rhinitis to asthma. The shared genetic link and environmental factors could be essential for this progression. Albeit treatment of rhinitis has a beneficial effect on lower airway defects, their role to prevent the progression to asthma remains yet to be confirmed.

Intrauterine growth restriction induces skin inflammation, increases TSLP and impairs epidermal barrier function.

Intrauterine growth restriction (IUGR) and low birth weight are risk factors for childhood asthma. Atopic march describes the progression from early dermatitis to asthma during life. Since inflammatory signaling is linked to increased airway resistance and lung remodeling in rats after IUGR, we queried if these findings are related to skin inflammatory response. Firstly, we induced IUGR in Wistar rats by isocaloric protein restriction during gestation. IUGR rats showed lower body weight at postnatal day 1 (P1), catch-up growth at P21, and similar body weight like controls at P90. At P1 and P90, mRNA of inflammatory as well as fibrotic markers and number of skin immune cells (macrophages) were increased after IUGR. Skin thymic stromal lymphopoietin (TSLP) mRNA at P1 and serum TSLP at P1 and P21 were elevated in IUGR. Moreover, IUGR impaired transepidermal water loss at P21 and P90. IUGR induced higher. Secondly, the increase of TEWL after Oxazolone treatment as a model of atopic dermatitis (AD) was greater in IUGR than in Co. Our data demonstrate an early inflammatory skin response, which is linked to persistent macrophage infiltration in the skin and impaired epidermal barrier function after IUGR. These findings coupled with elevated TSLP could underlie atopic diseases in rats after IUGR. KEY MESSAGES: • The present study shows that IUGR increases macrophage infiltration and induces an inflammatory and fibrotic gene expression pattern in the skin of newborn rats. • Early postnatal inflammatory response in the skin after IUGR is followed by impaired epidermal barrier function later in life. • IUGR aggravates transepidermal water loss in an experimental atopic dermatitis model, possibly through elevated TSLP in skin and serum. • Early anti-inflammatory treatment and targeting TSLP signaling could offer novel avenues for early prevention of atopic disorders and late asthma in high-risk infants.