BACKGROUND:Paediatric atopic dermatitis (AD) is the most common inflammatory disease of childhood and is closely linked to the subsequent development of food allergy, asthma and rhinitis. There is currently limited insight into the occurrence of AD and allergic comorbidity in early childhood according to gestational maturity. OBJECTIVES:To investigate the occurrence of AD, food allergy, asthma and rhinitis in term and preterm children from birth to age 4-5 years. METHODS:A prospective birth cohort of 389 children (261 term, 128 preterm) was followed from birth to age 4-5 years. Clinical visits were conducted at birth, 2 months, and 12 months, with additional visits for skin signs of AD during the first 2 years. At age 4-5 years, parents completed a structured telephone interview. We compared the prevalence, age at onset, and persistence of AD and allergic comorbidities between preterm and term children using Mann-Whitney U-test and Fisher's exact tests. RESULTS:The overall prevalence of AD was 29.6% at age 2 years and 33.0% at 4-5 years. Preterm children had a lower prevalence of AD (19.2% vs. 39.8%, P < 0.001), later AD onset (median 12.0 vs. 7.5 months, P < 0.01), milder disease severity (median Eczema Area and Severity Index score 1.4 vs. 4.8, P < 0.01) and less persistent AD (11.5% vs. 19.9%, P < 0.001) than term children. Among preterm-born and term-born children, the prevalence of food allergy, asthma and rhinitis at age 4-5 years was 1.6% vs. 3.1%, 20.0% vs. 13.0% and 6.2% vs. 4.6%, respectively. No preterm children with AD (n = 25) developed food allergies within 4-5 years compared with 6.7% among term-born children, whereas asthma prevalence was higher among preterm children with AD (36.0%) compared with term children with AD (17.3%) (P = 0.05). CONCLUSIONS:In this cohort, preterm birth was associated with a lower observed incidence of AD, with later onset and a milder, less persistent disease course. Among children with AD, those born preterm had no food allergy and a higher prevalence of asthma compared with term-born children.

Background: Atopic dermatitis (AD) in high-burden skin areas such as the head-and-neck, the hands, and the genitals is associated with a high disease burden and impaired quality-of-life.Objective: We investigated the prevalence of AD in high-burden skin areas, clinical and demographic characteristics, and association with disease severity in adults with AD.Methods: A cross-sectional survey was sent to 16,718 adults seen with AD (ICD-10, L20.x) at a Danish hospital. Severity was assessed with the Patient-Oriented SCORing Atopic Dermatitis (PO-SCORAD).Results: 7049 completed the survey (42.2% response), and 6716 who reported anatomical site of AD were included. The point prevalence of hand eczema (HE), head-and-neck dermatitis (HND), and genital eczema (GE) increased with AD severity and was 68.7%, 60.0%, and 5.9% in moderate, and 81.7%, 75.6%, and 14.1% in severe AD (P < 0.001). HND and HE patients were primarily women with childhood-onset and more severe AD. GE patients tended to be male, had severe AD, had more atopic comorbidities, and had higher corticosteroid and antibiotic use.Conclusions: AD in high-burden areas is common in adult Danes with AD and characterized by more severe AD and specific patient characteristics. This subgroup warrants recognition as difficult-to-treat, requiring close monitoring and earlier use of advanced systemic therapy.

BACKGROUND:Identification of clinical signs and biomarkers predicting the onset of paediatric atopic dermatitis (AD) is important for disease prevention strategies. Hyperlinear palms, a minor Hanifin & Rajka criterion, are characterized by an increased number and depth of skin creases and have been associated with both filaggrin gene (FLG) mutations and AD. OBJECTIVES:To investigate whether distinct palmar phenotypes in infancy are associated with AD in early childhood. METHODS:In total, 300 term and 150 preterm newborns were followed clinically for possible AD onset until 2 years. The palm of the hand was photographed at 2 months of age for later blinded clinical assessment. FLG mutations were analysed in buccal cells. Skin tape strips were collected at 2 months of age and analysed for immune and skin barrier biomarkers. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated for the risk of AD development. RESULTS:Hyperlinear palms at 2 months of age were diagnosed in 14.3% (35/245) of the children. The presence of hyperlinear palms was associated with increased occurrence of AD within 1 year (HR 2.82; 95% CI: [1.59-5.00]; p = 0.0004) and 2 years of age (HR 2.40; 95% CI: [1.39-4.13]; p = 0.002), which remained after adjustment for FLG mutation status within 1 year (aHR: 2.13; 95% CI: [1.08-4.20]; p = 0.03) and within 2 years of age (aHR: 1.79; 95% CI: [0.94-3.38]; p = 0.08). Having both hyperlinear palms and elevated TARC/CCL17 at 2 months of age was further associated with increased AD occurrence within 2 years of age among children born to term (HR 5.66; 95% CI: [1.74-18.41]; p = 0.004). CONCLUSIONS:Hyperlinear palms at 2 months of age are associated with paediatric AD within the first year of life. Our study indicates that the presence of type 2 inflammation at 2 months of age further increases the occurrence of AD.

BACKGROUND:Atopic dermatitis (AD) is driven by a complex interplay of skin barrier dysfunction and immune dysregulation, including a significant T-cell-mediated immune response. The thymus is the key organ of T cell receptor gene rearrangement and T-cell maturation in early life. This study investigated whether infant thymus size is associated with incident AD during the first 2 years of life. METHODS:Three hundred term newborns were followed clinically from birth until 2 years of age. Trans-sternal ultrasound scans of the thymus were performed at birth, 2 months, and 12 months. The thymic index was calculated and dichotomized at ≥ 90th percentile. Skin tape strips from the dorsal hand were analyzed for immune biomarkers. Hazard ratios (HR) with 95% confidence intervals (95% CI) were calculated for AD risk and early-onset AD. Multivariate analyses (aHR) were adjusted for sex, weight, height, breastfeeding, FLG mutation, and parental atopy. RESULTS:Of the 300 enrolled children, 290 (97%) were eligible for analyses. The 2-year cumulative prevalence of AD was 34.1% (95% CI: 28.7%-39.6%). A higher thymic index at 2 months was associated with increased AD risk during the first 2 years of life (HR: 3.51; 95% CI: [1.73-7.12]; p < 0.001), (aHR: 6.32; 95% CI: [2.81-14.20]; p < 0.001) and increased early-onset AD before 6 months (HR: 2.95; 95% CI: [1.29-6.76]; p = 0.01), (aHR: 5.35; 95% CI: [2.05-13.90]; p < 0.001). A moderate correlation between thymic index and EASI (Eczema Area and Severity Index) was observed at 2 months of age (r = 0.39). CONCLUSION:Our findings indicate that increased thymic activity and T-cell development may be associated with a higher risk of AD onset, suggesting a potential role of early-life T-cell maturation in disease pathogenesis.

Background:Environmental factors play a role in the pathogenesis of complex traits including atopic eczema (AE) and a greater understanding of gene-environment interactions (G*E) is needed to define pathomechanisms for disease prevention. We analysed data from 16 European studies to test for interaction between the 24 most significant AE-associated loci identified from genome-wide association studies and 18 early-life environmental factors. We tested for replication using a further 10 studies and in vitro modelling to independently assess findings. Results:The discovery analysis showed suggestive evidence for interaction (p<0.05) between 7 environmental factors (antibiotic use, cat ownership, dog ownership, breastfeeding, elder sibling, smoking and washing practices) and at least one established variant for AE, 14 interactions in total (maxN=25,339). In replication analysis (maxN=252,040) dog exposure*rs10214237 (on chromosome 5p13.2 near IL7R) was nominally significant (ORinteraction=0.91 [0.83-0.99] P=0.025), with a risk effect of the T allele observed only in those not exposed to dogs. A similar interaction with rs10214237 was observed for siblings in the discovery analysis (ORinteraction=0.84[0.75-0.94] P=0.003), but replication analysis was under-powered ORinteraction=1.09[0.82-1.46]). Rs10214237 homozygous risk genotype is associated with lower IL-7R expression in human keratinocytes, and dog exposure modelled in vitro showed a differential response according to rs10214237 genotype. Conclusions:Interaction analysis and functional assessment provide evidence that early-life dog exposure may modify the genetic effect of rs10214237 on AE via IL7R, supporting observational epidemiology showing a protective effect for dog ownership. The lack of evidence for other G*E studied here implies that only weak effects are likely to occur.

BACKGROUND:Multiple environmental and genetic factors play a role in the pathogenesis of atopic eczema (AE). We aimed to investigate gene-environment interactions (G × E) to improve understanding of the pathophysiology. METHODS:We analysed data from 16 European studies to test for interaction between the 24 most significant AE-associated loci identified from genome-wide association studies and 18 early-life environmental factors. We tested for replication using a further 10 studies and in vitro modeling to independently assess findings. RESULTS:The discovery analysis (including 25,339 individuals) showed suggestive evidence for interaction (p < 0.05) between seven environmental factors (antibiotic use, cat ownership, dog ownership, breastfeeding, elder sibling, smoking and washing practices) and at least one established variant for AE, 14 interactions in total. In the replication analysis (254,532 individuals) dog exposure × rs10214237 (on chromosome 5p13.2 near IL7R) was nominally significant (ORinteraction = 0.91 [0.83-0.99] p = 0.025), with a risk effect of the T allele observed only in those not exposed to dogs. A similar interaction with rs10214237 was observed for siblings in the discovery analysis (ORinteraction = 0.84 [0.75-0.94] p = 0.003), but replication analysis was under-powered (ORinteraction = 1.09 [0.82-1.46]). rs10214237 homozygous risk genotype is associated with lower IL-7R expression in human keratinocytes, and dog exposure modelled in vitro showed a differential response according to rs10214237 genotype. CONCLUSION:Interaction analysis and functional assessment provide preliminary evidence that early-life dog exposure may modify the genetic effect of rs10214237 on AE via IL7R, supporting observational epidemiology showing a protective effect for dog ownership. The lack of evidence for other G × E studied here implies only weak effects are likely to occur.

BACKGROUND:Skin tape-strips and biopsies are widely used methods for investigating the skin in atopic dermatitis (AD). Biopsies are more commonly used but can cause scarring and pain, whereas tape-strips are noninvasive but sample less tissue. The study evaluated the performance of skin tape-strips and biopsies for studying AD. METHODS:Whole-transcriptome RNA-sequencing was performed on paired tape-strips and biopsies collected from lesional and non-lesional skin from AD patients (n = 7) and non-AD controls (n = 5). RNA yield, mapping efficiency, and differentially expressed genes (DEGs) for the two methods (tape-strip/biopsy) and presence of AD (AD/non-AD) were compared. RESULTS:Tape-strips demonstrated a lower RNA yield (22 vs. 4596 ng) and mapping efficiency to known genes (28% vs. 93%) than biopsies. Gene-expression profiles of paired tape-strips and biopsies demonstrated a medium correlation (R2 = 0.431). Tape-strips and biopsies demonstrated systematic differences in measured expression levels of 6483 genes across both AD and non-AD samples. Tape-strips preferentially detected many itch (CCL3/CCL4/OSM) and immune-response (CXCL8/IL4/IL5/IL22) genes as well as markers of epidermal dendritic cells (CD1a/CD207), while certain cytokines (IL18/IL37), skin-barrier genes (KRT2/FLG2), and dermal fibroblasts markers (COL1A/COL3A) were preferentially detected by biopsies. Tape-strips identified more DEGs between AD and non-AD (3157 DEGs) then biopsies (44 DEGs). Tape-strips also detected higher levels of bacterial mRNA than biopsies. CONCLUSIONS:This study concludes that tape-strips and biopsies each demonstrate respective advantages for measuring gene-expression changes in AD. Thus, the specific skin layers and genes of interest should be considered before selecting either method.

BACKGROUND:Despite previous attempts to classify atopic dermatitis (AD) into subtypes (e.g. extrinsic vs. intrinsic), there is a need to better understand specific phenotypes in adulthood. OBJECTIVES:To identify, using machine learning (ML), adult AD phenotypes. METHODS:We used unsupervised cluster analysis to identify AD phenotypes by analysing different responses to predetermined variables (age of disease onset, severity, itch and skin pain intensity, flare frequency, anatomical location, presence and/or severity of current comorbidities) in adults with AD from the Danish Skin Cohort. RESULTS:The unsupervised cluster analysis resulted in five clusters where AD severity most clearly differed. We classified them as 'mild', 'mild-to-moderate', 'moderate', 'severe' and 'very severe'. The severity of multiple predetermined patient-reported outcomes was positively associated with AD, including an increased number of flare-ups and increased flare-up duration and disease severity. However, an increased severity of rhinitis and mental health burden was also found for the mild-to-moderate phenotype. CONCLUSIONS:ML confirmed the use of disease severity for the categorization of phenotypes, and our cluster analysis provided novel detailed information about how flare patterns and duration are associated with AD disease severity.

It is currently unknown whether alterations in the skin microbiome exist before development of atopic dermatitis (AD). In this prospective Danish birth cohort of 300 children, we examined whether skin microbiome alterations during the first 2 months of life were associated with an increased risk of AD in the first 2 years and its severity after adjustment for environmental factors and selected skin chemokine and natural moisturizing factor levels. We found no overall association between the skin microbiome at birth and age 2 months and AD during the first 2 years of life. However, when restricting the analysis to children with at least one parent with atopy, a lower alpha diversity at age 2 months was associated with an increased risk of AD (adjusted hazard ratio = 1.7, 95% confidence interval = 1.1-2.6). We observed a stronger association in children where both parents had atopy (adjusted hazard ratio = 4.4, 95% confidence interval = 1.1-18.2). The putative pathogenic role of changes in the skin microbiome on AD risk remains uncertain but may play a role in those with an atopic predisposition.

Dupilumab, a monoclonal antibody targeting IL-4/IL-13 signalling, was the first targeted therapy approved for treatment of moderate-to-severe atopic dermatitis (AD) by the US Food and Drug Administration and European Medical Agency.1 Dupilumab induces rapid improvement of signs and symptoms of AD in majority of patients with a mean percentage improvement of clinical severity scores of 69.6% in real-life studies.1 The main reason for dupilumab discontinuation is development of ocular side effects.2 Several ocular side effects have been reported including conjunctivitis, blepharitis, keratitis, dry eye disease and conjunctival fibrosis. According to a systematic review and meta-analysis, the most common side effect to dupilumab therapy is conjunctivitis reported in 26.1% of AD patients treated with dupilumab.1 However, irrespective of treatment with dupilumab, conjunctivitis is common in patients with AD with a life-time prevalence of 66%.3 Hence, it has been speculated whether conjunctivitis during dupilumab treatment is a result of worsening of already prevalent conjunctivitis or de novo development.2 At present, real-world studies on safety of dupilumab have been limited by retrospective design and/or lack of thorough ophthalmologic assessment of ocular surface disease prior to treatment initiation.2 The work by Costedoat et al.4 represents the first larger, prospective study that includes a systematic, standardized ophthalmologic assessment prior to and following 16 weeks of dupilumab therapy in moderate-to-severe AD patients and is therefore pivotal in differentiating between dupilumab-exacerbated and dupilumab-induced ocular surface disease with primary focus on conjunctivitis. This multicentre study included 181 adult AD patients of which 27 had conjunctivitis at treatment initiation. Dupilumab-induced conjunctivitis was defined as either worsening of pre-existing conjunctivitis or de novo development of conjunctivitis and was observed in 34 patients after 16 weeks of dupilumab therapy. Of these, 32 patients were classified as having de novo conjunctivitis while two patients experienced worsening of pre-existing conjunctivitis. Thus, the results indicated de novo development as the most common nature of dupilumab-induced conjunctivitis. However, at treatment initiation and all follow-up visits, patients were examined by an ophthalmologist; hence, it is possible that prescriptions have prevented development and exacerbation of pre-existing conjunctivitis thereby limiting the interpretation of the results. Patients with dupilumab-induced conjunctivitis were significantly more likely to develop blepharitis compared to patients without dupilumab-induced conjunctivitis, and 30 patients had concomitant blepharitis defined as blepharoconjunctivitis. Contrary to findings of previous studies, neither AD severity, current or previous conjunctivitis or presence of atopic comorbidities were associated with an increased risk of dupilumab-induced conjunctivitis,1, 2 while head-and-neck dermatitis, erythroderma and dry eye syndrome were identified as risk factors of dupilumab-induced conjunctivitis. With respect to other potential ocular side effects, neither keratitis, dry eye syndrome or conjunctival fibrosis increased in prevalence following dupilumab therapy indicating that these diseases may be linked to the natural course of AD and not dupilumab therapy. The finding that dry eye syndrome increased the risk of dupilumab-induced conjunctivitis is interesting since depletion of goblet cells and subsequent decrease in mucin production and tear instability has been proposed as a potential mechanism for this side effect.2, 5 However, the underlying pathophysiology of dupilumab-induced conjunctivitis has still not been established, and several potential mechanisms have been proposed such as increased colonization with demodex mites resulting in Th17 activation, increase in eosinophils and increase in conjunctivitis promoting ligands such as OX40L.1, 2 Interestingly, dupilumab-induced conjunctivitis seems to be caused by a unique interplay between AD disease mechanisms and dupilumab therapy since this side effect is rarely reported in patients with asthma, chronic rhinosinusitis or eosinophilic oesophagitis treated with dupilumab.1, 2 Overall, the study by Costedoat et al. provides some important new findings of dupilumab-induced conjunctivitis by showing that de novo development is the primary origin of this side effect. Although the results must be confirmed in larger studies, they emphasize that current or previous conjunctivitis should not be a contraindication for receiving dupilumab therapy while presence of head-and-neck dermatitis, erythroderma and dry eye syndrome might increase the risk of conjunctivitis if treated with dupilumab. Future studies should focus on establishing the pathophysiological mechanisms underlying dupilumab-induced conjunctivitis in order to promote a systematic approach for prevention and management of this frequent side effect in patients with AD. C.M.O.: Industrial postdoc at Leo Pharma and Bispebjerg hospital. A.S.H.: None. Data sharing not applicable.

Atopic dermatitis (AD) and food allergy (FA) share similar type 2 inflammation and commonly co-occur, but the precise proportion of AD patients with FA and vice versa, as well as the effect of AD disease severity on the strength of this association remains uncertain. The aim of this comprehensive systematic review and meta-analysis was to determine the prevalence and bidirectional associations of AD with food sensitivity (FS), FA and challenge-proven food allergy (CPFA). We searched PubMed and EMBASE and three independent reviewers performed title/abstract and full-text review and data extraction. Overall, 557 articles (n = 225,568 individuals with AD, n = 1,128,322 reference individuals; n = 1,357,793 individuals with FS, FA or CPFA, n = 1,244,596 reference individuals) were included in quantitative analyses. The overall pooled prevalence of FS, FA and CPFA in individuals with AD were 48.4% (95% confidence interval: 43.7-53.2), 32.7% (28.8-36.6) and 40.7% (34.1-47.5) respectively. AD prevalence among individuals with FS, FA and CPFA were 51.2% (46.3-56.2), 45.3% (41.4-49.3) and 54.9% (47.0-62.8) respectively. Children with AD had higher pooled FS (49.8% (44.4-55.1)) and FA (31.4% (26.9-36.1)) prevalences than adults with AD (28.6% (13.4-46.8) and 24.1% (12.1-38.7) respectively). Prevalences of FS and FA numerically increased with AD severity. FS, FA and CPFA are common comorbidities of AD and are closely related. Physicians should be attentive to this relationship to optimize management and treatment strategies in patients.

INTRODUCTION:Lesional skin of atopic dermatitis (AD) is often colonised by Staphylococcus aureus and the bacterial abundance increases during a flare. However, the role of S. aureus and the skin microbiome in the pathogenesis of AD, including its influence on the dysfunctional skin barrier and immune response, remains to be elucidated. In this study, the temporal relationship between alterations in the skin barrier function, inflammation and microbiome is examined in adults with AD.METHODS AND ANALYSIS:This clinical study consists of 81 adult patients with AD, as defined by the Hanifin and Rajka criteria, and 41 age and sex-matched controls. The objectives are to examine alterations in the skin microbiome, skin barrier and immune response during (1) an untreated AD flare, (2) an AD flare treated with topical corticosteroids (TCS), (3) an AD flare treated with systemic dicloxacillin/placebo and TCS or (4) cutaneous exposure to either autologous S. aureus, staphylococcal enterotoxin B or a vehicle. Skin biopsies, tape strips, skin and nasal swabs are collected and analysed using RNA sequencing, multiplex immunoassays, liquid chromatography-mass spectrometry and 16S rDNA. Blood samples are analysed for filaggrin gene mutations and leucocyte gene expression.ETHICS AND DISSEMINATION:The scientific Ethical Committee of the Capital Region in Denmark (phases I and II: H-20011047, phases III and IV: H-21079287), the local data protection agency (phases I and II: P-2020-165, phases III and IV: P-2022-250) and the Danish Medicines Agency (phases III and IV: EudraCT 2021-006883-25, ClinicalTrials.gov: NCT05578482) have approved the studies. Participants will give written informed consent prior to study initiation. The study is conducted in accordance with the Helsinki Declaration. Outcomes will be presented at national and international conferences and in international peer-reviewed publications.TRIAL REGISTRATION NUMBER:NCT05578482, EudraCT 2021-006883-2.

Contact dermatitis because of use of diabetes devices is frequent in individuals with type 1 diabetes (TD1), especially in the pediatric age group, but the putative role of a constitutional impaired skin barrier in persons with TD1 is unclear. This study examined the skin barrier function by the measurement of natural moisturizing factor and free cytokines collected through skin tape strips, as well as biophysical markers and the skin microbiome, in persons with TD1 than to age- and sex-matched healthy controls. All measurements were done in nonlesional skin. We found that the skin barrier function was similar in children and adolescents with TD1 than to controls but found that the beta-diversity of skin microbiome at the buttock differed between the two groups. We conclude that individuals with TD1 have normal skin barrier function, and that the increased occurrence of contact dermatitis following pump and sensor use is explained by exogenous factors.

Atopic dermatitis (AD) is a common disease that is associated with atopic and nonatopic comorbidities. There has been a growing interest in this area of AD, because presence or risk of comorbidities can in many ways impact the management of patients with AD. Thus, some treatments for AD may improve its comorbidities as well, whereas others may increase their risk. In this review article, we discuss various comorbidities of AD mostly on the basis of the results of recent multiple systematic reviews and meta-analyses to update readers about this rapidly developing area of dermatology. We emphasize the important information provided by studies presenting both relative risk and absolute risk, and show that AD is associated with, among others, atopic comorbidities such as asthma, rhinitis, and food allergy, nonatopic comorbidities such as ocular, psychiatric, infectious, endocrine, autoimmune, and cardiovascular diseases, and certain cancers. Clinicians need to be aware of these and be cognizant about positive and negative effects of existing and new treatments for AD. (J Allergy Clin Immunol 2023;151:1155-62.)

Background Staphylococcus aureus may worsen already established atopic dermatitis (AD), but its primary role in the aetiopathogenesis and severity of AD is unclear. Objectives To compare the prevalence of S. aureus colonization in early infancy in children who developed AD during the first 2 years of life with children who did not. Methods In this prospective birth cohort study, which included 450 infants, we analysed bacterial swabs collected from cheek skin at 0 and 2 months of age. The development of AD, and its severity, was diagnosed by a physician and monitored prospectively for 2 years. Information on parental atopy, filaggrin gene mutation status and use of antibiotics and emollients was included in the analyses. Results At birth, the occurrence of S. aureus colonization was similar in infants who developed subsequent AD and those who did not. At 2 months of age, S. aureus colonization was more common in children who later developed AD (adjusted hazard ratio 1.97, 95% confidence interval 1.21-3.19; P = 0.006). No association was found between S. aureus colonization and AD severity or age at onset. Conclusions It remains unknown whether colonization with S. aureus may directly increase the risk of AD, or whether it should be considered as secondary to skin barrier impairment or a skewed immune activity, but according to our findings, S. aureus colonization is more commonly increased at 2 months of age in children who later developed AD.

Background: It is unknown whether skin biomarkers collected in infancy can predict the onset of atopic dermatitis (AD) and be used in future prevention trials to identify children at risk.Objectives: This study sought to examine whether skin biomarkers can predict AD during the first 2 years of life.Methods: This study enrolled 300 term and 150 preterm children at birth and followed for AD until the age of 2 years. Skin tape strips were collected at 0 to 3 days and 2 months of age and analyzed for selected immune and barrier biomarkers. Hazard ratio (HR) with 95% confidence interval (CI) using Cox regression was calculated for the risk of AD.Results: The 2-year prevalence of AD was 34.6% (99 of 286) and 21.2% (25 of 118) among term and preterm children, respectively. Skin biomarkers collected at birth did not predict AD. Elevated thymus-and activation-regulated chemokine/C-C motif chemokine ligand 17 -levels collected at 2 months of age increased the overall risk of AD (HR: 2.11; 95% CI: 1.36-3.26; P = .0008) and moderate-to-severe AD (HR: 4.97; 95% CI: 2.09-11.80; P = .0003). IL-8 and IL-18 predicted moderate-to-severe AD. Low filaggrin degradation product levels increased the risk of AD (HR: 2.04; 95% CI: 1.32-3.15; P = .001). Elevated biomarker levels at 2 months predicted AD at other skin sites and many months after collection.Conclusions: This study showed that noninvasively collected skin biomarkers of barrier and immune pathways can precede the onset of AD. (J Allergy Clin Immunol 2023;151:1550-7.)

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 dermatitis is a common inflammatory skin disease that might lead to severe and persistent disease during infancy. Atopic dermatitis is associated with poor school performance, psychiatric disease, and allergic comorbidities. 1 Rønnstad ATM Halling-Overgaard AS Hamann CR Skov L Egeberg A Thyssen JP Association of atopic dermatitis with depression, anxiety, and suicidal ideation in children and adults: a systematic review and meta-analysis. J Am Acad Dermatol. 2018; 79: 448-456 Summary Full Text Full Text PDF PubMed Google Scholar , 2 Schmidt SAJ Mailhac A Darvalics B et al. Association between atopic dermatitis and educational attainment in Denmark. JAMA Dermatol. 2021; 157: 1-9 Crossref Scopus (2) Google Scholar , 3 Paller AS Spergel JM Mina-Osorio P Irvine AD The atopic march and atopic multimorbidity: many trajectories, many pathways. J Allergy Clin Immunol. 2019; 143: 46-55 Summary Full Text Full Text PDF PubMed Scopus (149) Google Scholar If atopic dermatitis is inadequately controlled with emollient use and topical anti-inflammatory therapies, systemic medications including ciclosporin, azathioprine, and methotrexate can be used to treat children with moderate-to-severe disease. However, systemic therapies are rarely used in children because the natural disease course often leads to spontaneous improvement, and because their use requires continuous blood monitoring and is associated with tolerance issues and modest efficacy. 4 Elsgaard S Danielsen AK Thyssen JP Deleuran M Vestergaard C Drug survival of systemic immunosuppressive treatments for atopic dermatitis in a long-term pediatric cohort. Int J Womens Dermatol. 2021; 7: 708-715 Crossref PubMed Scopus (1) Google Scholar Moreover, oral medication can be challenging to use in children. Accordingly, there is a need for systemic therapies that are efficacious and have a favourable safety profile. Dupilumab in children aged 6 months to younger than 6 years with uncontrolled atopic dermatitis: a randomised, double-blind, placebo-controlled, phase 3 trialDupilumab significantly improved atopic dermatitis signs and symptoms versus placebo in children younger than 6 years. Dupilumab was well tolerated and showed an acceptable safety profile, similar to results in older children and adults. Full-Text PDF