Early-onset Atopic Dermatitis Research Articles

The Relationship between Atopic Dermatitis and Food Allergy

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterised by an inadequate skin barrier. This can be caused by a variety of reasons such as hereditary predisposition and immunological dysregulation. AD affects 20% of infants, it is the most common chronic inflammatory skin disease in this group, and 3% of adults. It typically manifests as moderate disease, with two-thirds of people with AD unlikely to develop sensitivity to environmental allergens; nonetheless, there have frequently been connections with atopic diseases, particularly IgE-mediated food allergy (FA). Allergy is confirmed with a food challenge test before restricting this in the diet. Up to one-third of children with early-onset AD experience an atopic march, which is characterised by the later development of atopic disorders including asthma, allergic rhinitis and/or rhinoconjunctivitis, food allergies, and hay fever. As a result, AD and food allergy are linked, and recent research shows that AD develops before food sensitisation, and food allergy relates to atopic dermatitis of varied severity.

Factor associated with food allergy among preschool children with atopic dermatitis, and resolution of atopic dermatitis.

Food allergy (FA) has been reported in one-third of children with moderate-to-severe atopic dermatitis (AD). To identify factor associated with food allergy among preschool children with AD, and to compare AD resolution between preschool children with and without FA. A cross-sectional study using database registry and questionnaire interview was conducted at Siriraj Hospital(Bangkok, Thailand) during 2022, and physician-diagnosed AD children aged ≤ 6 years were enrolled. A total of 110 children (60.9% male, median age: 2.3 years) were included. Of those, 53 and 57 children had AD with and without FA, respectively. Very early-onset AD (≤ 3 months) and moderate-to-severe AD at onset were reported in 43.9% and 26.3% of AD without FA, and in 35.8% and 45.3% of AD with FA, respectively. The most commonly reported FAs were hen's egg, cow's milk, and wheat. Moderate-to-severe AD at onset was found significant associated with FA (aOR: 2.50; p = 0.037). Thirty-one (28.2%) patients experienced completed resolution of AD by 5 years of age. Of those, 19 had AD without FA, and 12 had AD with FA (p = 0.213). The median age at AD resolution was 18 months and 22.5 months in the without and with FA groups, respectively. AD with FA showed a strong trend toward a significantly longer duration to achieving AD resolution after adjusting for onset and severity of AD (aHR: 0.46, p = 0.050). Preschool AD children with FA were found to have significantly greater AD severity at AD onset and a longer duration to AD resolution compared to AD children without FA.

Association between skin barrier development and early-onset atopic dermatitis: A longitudinal birth cohort study

A diagnosis of atopic dermatitis (AD) is common during infancy; however, it is unclear whether differential skin barrier development defines this period and signals disease onset in predisposed individuals. We sought to study (NCT03143504) and assess the feasibility of remote skin testing from birth to monitor skin barrier maturation and model association with an AD diagnosis by age 12 months. Biophysical testing and infrared spectroscopy were conducted at the maternity ward and family home. Tape stripping collected samples for desquamatory protease and natural moisturizing factor analysis. The 4 common European filaggrin risk alleles were screened. A total of 128 infants completed the study, with 20% developing mild disease. Significant changes in permeability barrier function, desquamatory protease activity, and molecular composition assessed spectroscopically were observed longitudinally, but only subtle evidence of differential skin barrier development was noted between infant subgroups. Common filaggrin risk alleles were strongly associated with early-onset disease and conferred a significant reduction in natural moisturizing factor and water content by age 4 weeks. Accounting for a family history of atopy, these parameters alongside a greater lipid/protein ratio and reduced chymotrypsin-like activity at birth were associated with AD. Measured in ambient conditions, transepidermal water loss did not signal disease risk at any stage. Skin barrier dysfunction lacked an acquired modality but was considered proportional to cohort severity and suggests that a portfolio of tests used in a community setting has the potential to improve current AD risk evaluations from birth.

In utero or early-in-life exposure to antibiotics and the riskof childhood atopic dermatitis, a population-based cohort study.

Atopic dermatitis (AD) is a common inflammatory disease of the skin that begins early in life and can be lifelong. The purpose of our study was to evaluate whether fetal exposure and/or early-life exposure of a child to antibiotics increases the risk of early-onset AD. We hypothesize that antibiotic exposure in utero or early in life (e.g. first 90 days) increases the likelihood that children developAD. Utilizing a large, prospectively collected electronic medical records database, we studied the association of antibiotic exposure received in utero or very early in life and the relative risk of onset of AD in a population-based cohort study. Associations were estimated using proportional hazards models as hazard ratios (HRs) with 95% confidence intervals (CIs). The risk of AD in childhood was increased after in utero or early-life antibiotic exposure. For any in utero antibiotic exposure the HR (CI) was 1.38 (1.36-1.39). However, penicillin demonstrated the strongest association with AD for both in utero exposure [1.43 (1.41-1.44)] and for childhood exposure [1.81 (1.79-1.82)]. HRs were higher in children born to mothers without AD than in those with AD pointing to effect modification by maternal AD status. Children born to mothers exposed to antibiotics while in utero had, depending on the mother's history of AD, approximately a 20-40% increased risk of developing AD. Depending on the antibiotic, children who received antibiotics early in life had a 40-80% increased risk of developing AD. Our study supports and refines the association between incident AD and antibiotic administration. It also adds population-based support to therapeutic attempts to treat AD by modifying the skin microbiome.

Birth mode is associated with development of atopic dermatitis in infancy and early childhood.

Birth by caesarean section (CS) is associated with development of allergic diseases, but its role in the development of atopic dermatitis (AD) is less convincing. Our primary aim was to determine if birth mode was associated with AD in 3-year-olds and secondarily to determine if birth mode was associated with early onset and/or persistent AD in the first 3 years of life. We included 2129 mother-child pairs from the Scandinavian population-based prospective PreventADALL cohort with information on birth mode including vaginal birth, either traditional (81.3%) or in water (4.0%), and CS before (6.3%) and after (8.5%) onset of labor. We defined early onset AD as eczema at 3 months and AD diagnosis by 3 years of age. Persistent AD was defined as eczema both in the first year and at 3 years of age, together with an AD diagnosis by 3 years of age. AD was diagnosed at 3, 6, 12, 24, and/or 36 months in 531 children (25%). Compared to vaginal delivery, CS was overall associated with increased odds of AD by 3 years of age, with adjusted odds ratio (95% confidence interval) of 1.33 (1.02-1.74), and higher odds of early onset AD (1.63, 1.06-2.48). The highest odds for early onset AD were observed in infants born by CS after onset of labor (1.83, 1.09-3.07). Birth mode was not associated with persistent AD. CS was associated with increased odds of AD by 3 years of age, particularly in infants presenting with eczema at 3 months of age.

Autosomal Dominant STAT6 Gain of Function Causes Severe Atopy Associated with Lymphoma.

The transcription factor STAT6 (Signal Transducer and Activator of Transcription 6) is a key regulator of Th2 (T-helper 2) mediated allergic inflammation via the IL-4 (interleukin-4) JAK (Janus kinase)/STAT signalling pathway. We identified a novel heterozygous germline mutation STAT6 c.1255G > C, p.D419H leading to overactivity of IL-4 JAK/STAT signalling pathway, in a kindred affected by early-onset atopic dermatitis, food allergy, eosinophilic asthma, anaphylaxis and follicular lymphoma. STAT6 D419H expression and functional activity were compared with wild type STAT6 in transduced HEK293T cells and to healthy control primary skin fibroblasts and peripheral blood mononuclear cells (PBMC). We observed consistently higher STAT6 levels at baseline and higher STAT6 and phosphorylated STAT6 following IL-4 stimulation in D419H cell lines and primary cells compared to wild type controls. The pSTAT6/STAT6 ratios were unchanged between D419H and control cells suggesting that elevated pSTAT6 levels resulted from higher total basal STAT6 expression. The selective JAK1/JAK2 inhibitor ruxolitinib reduced pSTAT6 levels in D419H HEK293T cells and patient PBMC. Nuclear staining demonstrated increased STAT6 in patient fibroblasts at baseline and both STAT6 and pSTAT6 after IL-4 stimulation. We also observed higher transcriptional upregulation of downstream genes (XBP1 and EPAS1) in patient PBMC. Our study confirms STAT6 gain of function (GOF) as a novel monogenetic cause of early onset atopic disease. The clinical association of lymphoma in our kindred, along with previous data linking somatic STAT6 D419H mutations to follicular lymphoma suggest that patients with STAT6 GOF disease may be at higher risk of lymphomagenesis.245 words.

Breakthrough evidence based on the dual allergen exposure hypothesis-both skin intervention and oral intervention.

Early-onset atopic dermatitis increases the risk of food allergies, suggesting that transcutaneous sensitization may occur through inflamed skin. Regarding food allergy causation, the dual allergen exposure hypothesis proposes that oral-route allergen exposure leads to immune tolerance, whereas allergen exposure via the inflamed skin causes food allergy. This hypothesis implies that it is important to induce oral immune tolerance and prevent allergic food sensitization through the skin. In this review, we focus on the breakthrough evidence based on the dual allergen exposure hypothesis-both skin intervention and oral intervention for food allergy prevention.

Enhanced early skin treatment for atopic dermatitis in infants reduces food allergy

Early-onset atopic dermatitis is a strong risk factor for food allergy, suggesting that early effective treatment may prevent transcutaneous sensitization. This study tested whether enhanced treatment of atopic dermatitis to clinically affected and unaffected skin is more effective in preventing hen's egg allergy than reactive treatment to clinically affected skin only. This was a multicenter, parallel-group, open-label, assessor-blind, randomized controlled trial (PACI [Prevention of Allergy via Cutaneous Intervention] study). This study enrolled infants 7-13 weeks old with atopic dermatitis and randomly assigned infants in a 1:1 ratio to enhanced early skin treatment or conventional reactive treatment using topical corticosteroids (TCSs). The primary outcome was the proportion of immediate hen's egg allergy confirmed by oral food challenge at 28 weeks of age. This study enrolled 650 infants and analyzed 640 infants (enhanced [n= 318] or conventional [n= 322] treatment). Enhanced treatment significantly reduced hen's egg allergy compared with the conventional treatment (31.4% vs 41.9%, P= .0028; risk difference: -10.5%, upper bound of a 1-sided CI: -3.0%), while it lowered body weight (mean difference: -422 g, 95% CI: -553 to -292 g) and height (mean difference: -0.8 cm, 95% CI: -1.22 to -0.33 cm) at 28 weeks of age. This study highlighted the potential of well-controlled atopic dermatitis management as a component of a hen's egg allergy prevention strategy. The enhanced treatment protocol of this trial should be modified before it can be considered as an approach to prevent hen's egg allergy in daily practice to avoid the adverse effects of TCSs. After remission induction by TCSs, maintenance therapy with lower potency TCSs or other topical therapies might be considered as alternative proactive treatments to overcome the safety concerns of TCSs.

MRNAs in skin surface lipids unveiled atopic dermatitis at one month.

The molecular pathogenesis of atopic dermatitis (AD), presenting skin barrier dysfunction and abnormal inflammations around 1-2 months is unreported. We aimed to examine the molecular pathogenesis of very early-onset AD by skin surface lipid-RNA (SSL-RNA) using a non-invasive technology in infants aged 1 and 2 months from a prospective cohort. We collected sebum by oil-blotting film of infants aged 1 and 2 months and analyzed RNAs in their sebum. We diagnosed AD according to the United Kingdom Working Party's criteria. Infants with AD aged one month showed lower expression of genes related to various lipid metabolism and synthesis, antimicrobial peptides, tight junctions, desmosomes, and keratinization. They also had higher expression of several genes involved in Th2-, Th17-, and Th22-type immune responses and lower expression of negative regulators of inflammation. In addition, gene expressions related to innate immunity were higher in AD infants. Infants aged one month with neonatal acne and diagnosed with AD aged two months already had gene expression patterns similar to AD aged one month in terms of redox, lipid synthesis, metabolism, and barrier-related gene expression. We identified molecular changes in barrier function and inflammatory markers that characterize the pathophysiology of AD in infants aged one month. We also revealed that neonatal acne at one month could predict the subsequent development of AD by sebum transcriptome data.

Iatrogenic Contact Dermatitis in a Patient with Atopic Dermatitis

: The relationship between atopic and allergic contact dermatitis is often discussed, especially in children. The damaged skin barrier in atopic patients can make the skin more permeable to exogenous agents and increase the risk of triggering contact dermatitis. Topical treatment of atopic dermatitis is associated with skin sensitization to several drugs, including antiseptics, emollients, and topical corticosteroids. The early onset of atopic dermatitis, as in the case reported here, the severity of the disease, and IgE-mediated sensitization are identified as the main risk factors associated with sensitization to topical treatments for atopic dermatitis. We report a two-year-old child with a previous diagnosis of atopic dermatitis, whose condition was aggravated by inadequate medical treatment.

Infections and Exposure to Antibiotics May Affect the Development of Late-onset Rather than Early-onset Atopic Dermatitis.

Infections and Exposure to Antibiotics May Affect the Development of Late-onset Rather than Early-onset Atopic Dermatitis.

Increasing Severity of Early-onset Atopic Dermatitis, but Not Late-onset, Associates With Development of Aeroallergen Sensitization and Allergic Rhinitis in Childhood

To investigate if there is an association between severity and time of onset of atopic dermatitis and the later development of aeroallergen sensitization or allergic rhinitis.The study included 368 children from the Copenhagan Prospective Studies on Asthma in Childhood (COPSAC) at-risk mother-child cohort. Inclusion criteria included children born between August 1998 and December 2001 to mothers with a history of asthma. The study population was followed from birth until 12 years of age.The study was a single-center, prospective trial. Study participants had planned clinic visits, arranged acute care visits for allergy-related flare ups, and were examined by a COPSAC research physician with dermatology training. Atopic dermatitis was diagnosed according to Hanifin and Rajka criteria and severity was scored using the SCORAD index. Aeroallergen sensitization assessment was conducted via specific-IgE (sIgE) levels at age 6 and 12 years, and sensitization was defined as ≥0.35 kUA/L. Allergic rhinitis assessment at age 7 and 12 years was conducted via parental interview on history of symptoms and congruence with allergy testing (positive sIgE or skin prick test).At 6 years of age, aeroallergen sensitization was noted in 29 of 84 (35%) children with early onset atopic dermatitis versus 45 of 207 (22%) children without. At 12 years of age, aeroallergen sensitization was noted in 48 of 89 (54%) children with early onset atopic dermatitis versus 92 of 215 (43%) children without. Among children with early onset atopic dermatitis and aeroallergen sensitization, a 1 point increase in SCORAD had an odds ratio (OR) = 1.08 (1.03–1.14), P < .01 at 6 years and OR = 1.08 (1.03–1.14), P < .01 at 12 years. In contrast, in children with late onset atopic dermatitis, SCORAD had no significant association with aeroallergen sensitization. In children with early onset atopic dermatitis, allergic rhinitis was noted in 17 of 83 (20%) children at 7 years of age, whereas at 12 years of age it was noted in 38 of 98 (38%) children. The same could be seen with severity of SCORAD and association with development of allergic rhinitis. Additionally, these observations had a stronger association in children with filaggrin mutation. Adjusting for sex, older siblings, parental allergic rhinitis, breastfeeding, and smoking did not significantly alter results.More severe early onset atopic dermatitis was found to be associated with aeroallergen sensitization and allergic rhinitis.Atopic dermatitis is a very common childhood disorder and this study demonstrates that earlier and better control of atopic dermatitis may prevent the development of allergic rhinitis. This suggests that an infant’s skin barrier may be more permeable to aeroallergen penetration and/or that early onset versus late onset atopic dermatitis represent different endotypes. This study emphasizes the need for eczema control in atopic infants.URL: www.pediatrics.org/cgi/doi/10.1542/peds.10.1111/all.15108

Treatment Patterns of Atopic Dermatitis Medication in 0-10-Year-Olds: A Nationwide Prescription-Based Study.

IntroductionThe literature on treatment patterns for paediatric atopic dermatitis (AD) is scarce and is rarely based on real-world data. Using national registers, we sought to establish up-to-date, population-based prevalence estimates, predictors of risk and disease burden and a comprehensive overview of treatment patterns and course for paediatric patients with AD.MethodsDispensed prescriptions for the entire Norwegian child population aged 0–10 years from 2014 to 2020 were analysed.ResultsThere were 176,458 paediatric patients with AD. Of these, 99.2% received topical corticosteroids, 5.1% received topical calcineurin inhibitors, 37.1% received potent topical corticosteroids and 2.1% received systemic corticosteroids. Of the 59,335 live births in Norway (2014), 14,385 [24.8%; 95% confidence interval (CI) 24.5–25.1] paediatric patients were treated for AD before the age of 6 years, and of these, only 934 (6.5%; 95% CI 6.1–6.9) received medication annually for 5 years or more. Compared with girls, 17.9% (95% CI 6.5–27.9) more boys were treated for at least 5 years, receiving 6.4% (95% CI 1.2–11.3) more potent topical corticosteroids and 12.4% (95% CI 6.5–18.0) more were treated for skin infections. Compared with patients with late-onset treatment, 18.9% (95% CI 7.5–29.0) more paediatric patients with early-onset treatment were still receiving treatment at 5 years of age, 15.7% (95% CI 7.1–23.4) more paediatric patients received potent topical corticosteroids and 44.4% (95% CI 36.5–51.2) more paediatric patients were treated for skin infections.ConclusionMost paediatric patients were treated for a mild disease for a limited period. Although the prevalence of AD is higher at a younger age, these paediatric patients were the least likely to receive potent topical corticosteroids. Male sex and early-onset AD are associated with and are potential predictors of long-term treatment and treatment of potent topical corticosteroids, antihistamines and skin infections, which may have clinical utility for personalised prognosis, healthcare planning and future AD prevention trials.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-022-00754-6.

Study protocol: assessing SleeP IN infants with early-onset atopic Dermatitis by Longitudinal Evaluation (The SPINDLE study)

BackgroundAtopic dermatitis (AD) is the most common chronic inflammatory skin condition in childhood. Most (50-60%) children with AD report sleep disturbance, which is secondary to itch, dry skin, inflammation, and abnormal circadian rhythm. Sleep is essential for brain development, learning, and growth. Sleep disruption in early life is associated with cognitive and psychological dysfunction in later life. The aim of this study is to describe in detail the sleep architecture of infants with early-onset atopic dermatitis (AD), compared to controls, by using EEG polysomnography, sleep actigraphy, and parental reporting.MethodsThis observational study will recruit six- to eight-month old infants with moderate to severe AD and age-matched control infants who do not have AD. At six-eight months diurnal sleep electroencephalography and polysomnography will be performed in our research center. Nocturnal sleep actigraphy will be performed at home for five consecutive nights at six-eight months and 12 months. Between six and 12 months, monthly questionnaires will capture data on quantitative sleep and parental sleep. Skin barrier and immune profiles will be captured at six-eight and 12 months. AD will be assessed using standardized severity assessment tools and treated according to protocol. A neurodevelopmental assessment will be performed at 18 months to assess cognition and behaviour. An estimated sample size of 50 participants in each group is required to power the primary outcome of disturbed macrostructure of sleep and secondary outcomes of disturbed microstructure of sleep, and disturbed parental sleep, assuming an attrition rate of 60%. Potential confounding factors which will be controlled for in the data analysis will include parental educational level, parental depression, feeding practice, and number of siblings.DiscussionThis study will provide a rich analysis of sleep in infants with AD in the first year of life using detailed electroencephalography, novel actigraphy techniques, and longitudinal parent-reported data. It may provide guidance on the optimal treatment of AD to prevent or reduce sleep disruption.Trial registrationclinicaltrials.govNCT05031754, retrospectively registered on September 2nd, 2021.

Differences in Occurrence, Risk Factors and Severity of Early-onset Atopic Dermatitis among Preterm and Term Children.

This prospective birth cohort followed 150 preterm and 300 term newborns during the first year of life to assess possible differences in risk factors, age at onset, anatomical location, and severity of atopic dermatitis. Atopic dermatitis was diagnosed clinically, and severity was assessed using Eczema Area Severity Index (EASI). DNA was analysed for filaggrin gene mutations. Parents were asked about environmental exposures and emollient use. Atopic dermatitis during the first year of life was observed in 21.2% of children and was more common in term children compared with preterm children (26.7% vs 11.7%, p < 0.001), with lower age of onset (4 vs 6 months, p < 0.05) and more severe disease at onset (EASI: 4.8 vs 0.4, p < 0.0005). Environmental risk factors for atopic dermatitis were essentially similar for preterm and term born children, apart from winter and autumn births. Filaggrin gene mutations were less common in preterm than term children (4.1% vs 9.2%, p = 0.06).

Atopic march in children with early-onset atopic dermatitis: A retrospective study

BackgroundAtopic march is a term that describes the progression of atopic disorders, from atopic dermatitis in young infants and toddlers to allergic rhinitis and asthma in later childhood. The aim of this study was to elucidate the course of allergic diseases between 3-7 years of age in patients with atopic dermatitis in the first 2 years of life. MethodsA total of 211 children have been analyzed in this retrospective study. The atopic dermatitis group consisted of 119 children diagnosed with atopic dermatitis between the ages of 0–2 in 2013 and the control group consisted of 92 children aged 0-3 months who had a hearing test for screening in the same year. The diagnoses of wheezing, atopic dermatitis, and allergic rhinitis in both groups below 2 years old and between 3-7 years old were examined from the hospital database and government e-health service. ResultsThe frequency of at least one wheezing attack (28.6% vs. 29.3%), at least three wheezing attacks (15.1% vs. 9.8%) and allergic rhinitis (22.7% vs. 22.8%) were not significantly different between atopic dermatitis and control groups in children between 3 and 7 years old. However, in the atopic dermatitis group, the frequency of at least one wheezing attack (42.6% vs. 19.4%, P=0.006), at least three wheezing attacks (25.6% vs. 8.3%, P=0.011), and allergic rhinitis (38.3% vs. 12.5%, P=0.001) were significantly higher in children with food sensitization than individuals without food sensitization. ConclusionThis study showed that the later allergic respiratory diseases in children with early-onset atopic dermatitis were associated with food sensitization regardless of early wheezing, and the persistence of atopic dermatitis was associated with multiple food sensitizations.

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Dupilumab has proven to be an effective treatment for patients with moderate-to-severe atopic dermatitis (AD) in clinical trials. However, real-world experience with dupilumab in a broader population is limited. The study population comprised adult patients with moderate-to-severe AD, defined as an Eczema Area Severity Index (EASI) score of 24 or higher, treated with dupilumab at 10 Italian teaching hospitals. We analyzed physician-reported outcome measures (EASI), patient-reported outcome measures (pruritus and sleep score, Dermatology Life Quality Index [DLQI]), and serological markers (IgE and eosinophil count) after 16 weeks. We enrolled 543 patients with moderate-to-severe AD. Two patients (0.4%) discontinued treatment. The median (IQR) change from baseline to 16 weeks of treatment in the EASI score was -87.5 (22.0) (P<.001). The EASI-50, EASI-75, and EASI-90 response rates were 98.1%, 81.5%, and 50.8% after 16 weeks. At 16 weeks, 93.0% of the patients had achieved a 4-point or higher improvement in DLQI from baseline. During treatment with dupilumab, 12.2% of the patients developed conjunctivitis, and total IgE decreased significantly (P<.001). Interestingly, in the multivariate logistic regression model, the risk of developing dupilumab-related conjunctivitis was associated with early onset of AD (OR, 2.25; 95%CI, 1.07-4.70; P=.03) and presence of eosinophilia (OR, 1.91; 95%CI, 1.05-3.39; P=.03). This is the broadest real-life study in AD patients treated with dupilumab to date. We observed more significant improvements induced by dupilumab in adult patients with moderate-to-severe AD than those reported in clinical trials.

Circulating Epithelial Cell Cytokines Are Associated With Early-Onset Atopic Dermatitis.

Circulating Epithelial Cell Cytokines Are Associated With Early-Onset Atopic Dermatitis.

Disease characteristics, comorbidities, treatment patterns and quality of life impact in children

Disease characteristics, comorbidities, treatment patterns and quality of life impact in children <12 years old with atopic dermatitis: Interim results from the PEDISTAD Real-World Registry

Atopic Dermatitis With Coexisting Food Allergy in Early Life Is Associated With Childhood Asthma.

PurposeAtopic dermatitis (AD) and food allergy (FA) are associated with respiratory comorbidities, in the concept of ‘atopic march.’ However, children with AD and a coexisting FA have various disease courses, and the mechanism of atopic march remains unclear. In this study, we investigated whether the phenotype of AD with coexisting FA in early life affected asthma or allergic rhinitis (AR) in school children.MethodsA total of 1,579 children from the Panel Study on Korean Children (PSKC) cohort were followed-up in 2013. The participants diagnosed with AD in this cohort were classified by the age of AD onset and persistence as well as FA history. We compared the presence of comorbidities—asthma and rhinitis—among different AD phenotypes.ResultsAsthma and AR with current symptoms within 12 months at age 6–8 years were associated with early-onset persistent AD phenotype, regardless of coexisting FA. AD with FA conferred a higher risk of recent wheezing at 8 years of age than AD without FA (adjusted odds ratio, 8.09; 95% confidence interval, 2.54–25.76). Children with early-onset persistent AD with FA manifested a distinctive trajectory with a higher prevalence of wheezing and AR at age 5–8 years than those without AD.ConclusionsAD with FA in early life is strongly associated with asthma and AR in school children, and the early-onset persistent AD with FA had a strong additive effect on the risk of asthma at school age. Classifying AD phenotypes regarding FA in early life will help predict and prevent asthma and AR in school children.