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Competing Interests: Conflicts of interest Dr Brandling-Bennett has served as principal investigator for Lilly. Dr Arkin has received consulting fees from AbbVie, Regeneron, and Verrica. Dr Hebert has received research grants (paid to UTHealth McGovern Medical School) from LEO Pharma, Mayne Pharma, UCB, GSK, Ortho Dermatolgics, Amgen, Arcutis, AbbVie, and Pfizer; has received honoraria from Pfizer, Arcutis, UCB, Verrica, LEO Pharma, Novan, Incyte, Janssen, Mayne Pharma, and Castle Creek Bioscience; and has served on drug safety monitoring boards for Ortho Dermatologics, GSK, and Sanofi Regeneron. Dr Cordoro has served as a member of a scientific steering committee for Celgene. Dr Curran has served as an advisory board member for Novartis, receiving honoraria. Dr Dalrymple has served as an advisory board member for Novartis. Dr Flohr is chief investigator of the UK National Institute for Health Research-funded TREAT (ISRCTN15837754, EudraCT 2,015-002,013-29) and SOFTER (Clinicaltrials.gov: NCT03270566) trials as well as the UK-Irish Atopic Eczema Systemic Therapy Register (A-STAR; ISRCTN11210918) and a principal investigator in the European Union (EU) Horizon 2020-funded BIOMAP Consortium (http://www.biomap-imi.eu/). He also leads the EU Trans-Foods Consortium. His department has received funding from Sanofi-Genzyme and Pfizer for host-microbiome research. Dr Gordon has received personal fees from AbbVie, Almirall, Amgen, BMS, Dermavant, Dermira, Lilly, Janssen, Kyowa Hakko Kirin, LEO Pharma, Novartis, Pfizer, Sun Pharma, and UCB and grants from BMS, Lilly, and UCB. Dr Irvine has received person fees from AbbVie, LEO Pharma, Lilly, Novartis, and Sanofi/Regeneron, and has received a grant from the UK National Institute for Health Research (research arm of the UK Department of Health) as co-principal investigator of a clinical trial comparing MTX with cyclosporine in children with severe atopic dermatitis. Dr Kirkorian has received honoraria from Verrica. Dr Lara-Corrales has served as an advisory board member for Ipsen, LEO Pharma, Lilly, Novartis, Pfizer, and Sanofi Genzyme; as a consultant for AbbVie, Avicanna, Janssen, Johnson & Johnson, Loreal, Pfizer, Pierre Fabre, Sanofi Genzyme, and Valeant; as a speaker for AbbVie, Amgen, Novartis, and Sanofi Genzyme; and has served as a site investigator for AbbVie, Clementia Pharmaceuticals, Janssen, Lilly, and, Mayne Pharma. Dr Jill Lindstrom has received consulting fees from AbbVie, AnaptysBio, Arena Pharmaceuticals, Aristea, Incyte, and Priovant. Dr Amy S. Paller has served as an investigator for AbbVie, Applied Pharma Research, Dermavant, Eli Lilly, Incyte, Janssen, Krystal, Regeneron, and UCB; Consultant for Aegerion Pharma, Azitra, BioCryst, Boehringer-Ingelheim, Bristol Myers Squibb, Castle Creek, Eli Lilly, Janssen, Krystal, LEO Pharma, Novartis, Regeneron, Sanofi/Genzyme, Seanergy, TWI Biotechnology, and UCB, and on the data safety monitoring board for AbbVie, Abeona, Catawba, Galderma, and InMed. Author Begolka has served as an advisory board member for Incyte and Pfizer, and has received a grant from Pfizer. Dr Tom has served as a site investigator for clinical trials for Janssen, Regeneron, Incyte, Pfizer, Dermira, Eli Lilly, and AbbVie, and has been on data safety committees for LEO Pharma. Dr Voorhees has received research grants from AbbVie, Celgene, and Lilly; has served as an advisory board member for BMS, Boehringer Ingelheim, Celgene, Novartis, and UCB; and had received consulting fees from Amgen. Dr Vleugels has received consulting fees from AbbVie, Pfizer, and Priovant. Dr Lee has received consulting fees from AbbVie and Krystal Biotech; served as an investigator for AbbVie, Amryt, Arcutis, BMS, Castle Creek Biosciences, Celgene, Galderma, Incyte, Janssen, Kiniksa, Lilly, Mayne Pharma, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Target Pharma, Trevi Therapeutics, and UCB; and has served as an advisory board member for Lilly, Novartis, Pfizer, and Regeneron. Dr Davies has received a fellow stipend from Pediatric Dermatology Research Alliance (PeDRA). Dr Siegfried has received consulting fees from AbbVie, Boehringer Ingelheim, Incyte, LEO Pharma, Novan, Novartis, Pierre Fabre, Pfizer, Regeneron, Sanofi Genzyme, UCB, and Verrica; has received honoraria from Regeneron, Sanofi Genzyme, and Verrica; has served on data safety monitoring boards for LEO Pharma, Novan, Pfizer, and UCB; participated in contracted research for AI Therapeutics; served as principal investigator for Janssen, and her institution has received fees related to clinical trials from Janssen, Lilly, Pierre Fabre, Regeneron, and Verrica and in support of a 2020-2021 pediatric dermatology fellowship from Pfizer. Dr Chiu, Dr Callen, Dr Castello-Soccio, Dr Co, Author Hanna, Dr Kim, and Dr Reyes have no conflicts of interest to declare.

Background: Atopic dermatitis (AD) is associated with immune dysregulation, but epidemiologic data on the pattern of autoimmune comorbidity in people with AD are limited., Objective: We sought to determine the risk of autoimmune conditions in people newly diagnosed with AD., Methods: Retrospective cohort analysis (January 2009 to December 2018), using the UK-based Oxford-Royal College of General Practitioners Research and Surveillance Centre primary care database. We compared baseline prevalence and incidence after diagnosis of autoimmune conditions in 173,709 children and adults with new-onset AD and 694,836 age-, sex-, and general practitioner practice-matched controls. Outcomes were a composite of any autoimmune condition (Crohn disease, ulcerative colitis, celiac disease, pernicious anemia, type 1 diabetes, autoimmune hypothyroidism, Graves disease, psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, Sjögren syndrome, vitiligo, alopecia areata, and multiple sclerosis) and each individual autoimmune condition., Results: Preexisting autoimmune conditions were more common in people diagnosed with AD compared to controls (composite 5.8% vs 4.3%). Excluding people with preexisting autoimmune disease, there was an association between AD and incidence of new-onset autoimmune disease (composite adjusted hazard ratio [aHR] 1.28; 95% confidence interval [CI] 1.23-1.34). Risk was highest for more severe AD (aHR 1.99; 95% CI 1.77-2.23) than moderate AD (aHR 1.33; 95% CI 1.19-1.49) or mild AD (aHR 1.22; 95% CI 1.16-1.28). People with AD were at significantly increased risk of developing psoriatic arthritis, Sjögren syndrome, Crohn disease, vitiligo, alopecia areata, pernicious anemia, ulcerative colitis, rheumatoid arthritis, and hypothyroidism (aHR range 1.17-2.06), but not other autoimmune conditions., Conclusion: People with AD have an increased risk of multiple autoimmune conditions, especially those with more severe AD., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Food allergy is thought to develop through transcutaneous sensitization, especially in the presence of skin barrier impairment and inflammation. Regular moisturizer application to infant skin could potentially promote transcutaneous sensitization and the development of food allergy., Objectives: We tested this hypothesis in the Enquiring About Tolerance (EAT) study population., Methods: The EAT study was a population-based randomized clinical trial conducted from January 15, 2008, to August 31, 2015, and recruited 1303 exclusively breastfed 3-month-old infants and their families from England and Wales. At enrollment at 3 months, families completed a questionnaire that included questions about frequency and type of moisturizer applied, use of corticosteroid creams, and parental report of dry skin or eczema. Infants were examined for visible eczema at the enrollment visit., Results: A statistically significant dose-response relationship was observed between parent-reported moisturization frequency at 3 months of age and the subsequent development of food allergy. Each additional moisturization per week was associated with an adjusted odds ratio of 1.20 (95% CI, 1.13-1.27; P < .0005) for developing food allergy. For infants with no visible eczema at the enrollment visit, the corresponding adjusted odds ratio was 1.18 (95% CI, 1.07-1.30; P = .001) and for those with eczema at the enrollment visit, 1.20 (95% CI, 1.11-1.31; P < .0005). Moisturizer frequency showed similar dose-response relationships with the development of both food and aeroallergen sensitization at 36 months., Conclusions: These findings support the notion that regular application of moisturizers to the skin of young infants may promote the development of food allergy through transcutaneous sensitization., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The gut microbiota potentially plays an important role in the immunologic education of the host during early infancy., Objective: We sought to determine how the infant gut microbiota evolve during infancy, particularly in relation to hygiene-related environmental factors, atopic disorders, and a randomized introduction of allergenic solids., Methods: A total of 1303 exclusively breast-fed infants were enrolled in a dietary randomized controlled trial (Enquiring About Tolerance study) from 3 months of age. In this nested longitudinal study, fecal samples were collected at baseline, with additional sampling of selected cases and controls at 6 and 12 months to study the evolution of their gut microbiota, using 16S ribosomal RNA gene-targeted amplicon sequencing., Results: In the 288 baseline samples from exclusively breast-fed infant at 3 months, the gut microbiota was highly heterogeneous, forming 3 distinct clusters: Bifidobacterium-rich, Bacteroides-rich, and Escherichia/Shigella-rich. Mode of delivery was the major discriminating factor. Increased Clostridium sensu stricto relative abundance at 3 months was associated with presence of atopic dermatitis on examination at age 3 and 12 months. From the selected cases and controls with longitudinal samples (n = 70), transition to Bacteroides-rich communities and influx of adult-specific microbes were observed during the first year of life. The introduction of allergenic solids promoted a significant increase in Shannon diversity and representation of specific microbes, such as genera belonging to Prevotellaceae and Proteobacteria (eg, Escherichia/Shigella), as compared with infants recommended to exclusively breast-feed., Conclusions: Specific gut microbiota characteristics of samples from 3-month-old breast-fed infants were associated with cesarean birth, and greater Clostridium sensu stricto abundance was associated with atopic dermatitis. The randomized introduction of allergenic solids from age 3 months alongside breast-feeding was associated with differential dynamics of maturation of the gut microbial communities., (Copyright © 2020. Published by Elsevier Inc.)

Background: The Enquiring About Tolerance (EAT) study examined whether the early introduction of 6 allergenic foods from 3 months of age in exclusively breastfed infants prevented the development of food allergy. The intervention was effective in the per-protocol analysis for allergy to 1 or more foods and for egg and peanut individually, but only 42% of early introduction group (EIG) children met the per-protocol criteria., Objective: We sought to identify which factors were responsible for nonadherence in the EAT study., Methods: Factors influencing adherence within the key early introduction period in the EIG (up to 6 months of age) were divided into enrollment and postenrollment factors, and their association with nonadherence was explored., Results: In an adjusted analysis, at enrollment, increased maternal age, nonwhite ethnicity, and lower maternal quality of life were independently and significantly associated with overall nonadherence in the EIG. Enrollment eczema and enrollment serum allergen-specific IgE sensitization to 1 or more foods (≥0.1 kU/L) were not related to overall nonadherence. After enrollment, 2 factors were significantly related to EIG overall nonadherence: parent-reported IgE-type symptoms with infant allergenic food consumption by 6 months of age and reported feeding difficulties by 4 months of age., Conclusion: If early introduction of allergenic foods were to be considered a strategy to prevent food allergy, families of nonwhite ethnicity, those with older mothers, and those with infants with reported feeding difficulties or early-onset eczema would benefit from support to promote early and sustained consumption., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The Enquiring About Tolerance (EAT) study was a randomized trial of the early introduction of allergenic solids into the infant diet from 3 months of age. The intervention effect did not reach statistical significance in the intention-to-treat analysis of the primary outcome., Objective: We sought to determine whether infants at high risk of developing a food allergy benefited from early introduction., Methods: A secondary intention-to-treat analysis was performed of 3 groups: nonwhite infants; infants with visible eczema at enrollment, with severity determined by SCORAD; and infants with enrollment food sensitization (specific IgE ≥0.1 kU/L)., Results: Among infants with sensitization to 1 or more foods at enrollment (≥0.1 kU/L), early introduction group (EIG) infants developed significantly less food allergy to 1 or more foods than standard introduction group (SIG) infants (SIG, 34.2%; EIG, 19.2%; P = .03), and among infants with sensitization to egg at enrollment, EIG infants developed less egg allergy (SIG, 48.6%; EIG, 20.0%; P = .01). Similarly, among infants with moderate SCORAD (15-<40) at enrollment, EIG infants developed significantly less food allergy to 1 or more foods (SIG, 46.7%; EIG, 22.6%; P = .048) and less egg allergy (SIG, 43.3%; EIG, 16.1%; P = .02)., Conclusion: Early introduction was effective in preventing the development of food allergy in specific groups of infants at high risk of developing food allergy: those sensitized to egg or to any food at enrollment and those with eczema of increasing severity at enrollment. This efficacy occurred despite low adherence to the early introduction regimen. This has significant implications for the new national infant feeding recommendations that are emerging around the world., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The early introduction group participants of the Enquiring About Tolerance study were asked to undertake a proscriptive regimen of early introduction and sustained consumption of 6 allergenic foods. It was envisaged that this might be challenging, and early introduction group families were presented with an open-text question to express any problems they were experiencing with the regimen in recurring online questionnaires., Objective: We sought to analyze these open-text questionnaire responses with the aim of identifying challenges associated with the introduction and regular consumption of allergenic foods., Methods: Three combinations of interim questionnaire responses were selected for analysis, representing the early period (4, 5, and 6 months), middle period (8 and 12 months), and late period (24 and 36 months) of participation in the Enquiring About Tolerance study. Responses were assigned a code to describe their content and subsequently grouped into themes to portray key messages. A thematic content analysis allowed for conversion of qualitative codes into quantitative summaries., Results: Three main challenges to allergenic food consumption were identified. First, some children refused the allergenic food, causing a sense of defeat among caregivers. Second, caregivers were concerned that allergenic foods might be causing a reaction, triggering a need for reassurance. Third, practical problems associated with the regimen compromised caregivers' capacity to persist., Conclusion: Understanding the challenges experienced with allergenic food introduction and sustained consumption is the necessary precursor to developing specific communication and support strategies that could be used by caregivers, practitioners, policymakers, and key stakeholders to address these problems., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Interleukin (IL)-13 plays a key role in type 2 inflammation and is an emerging pathogenic mediator in atopic dermatitis (AD)., Objective: We investigated the efficacy and safety of lebrikizumab, an IL-13 monoclonal antibody, as an add-on to topical corticosteroid (TCS) treatment., Methods: A randomized, placebo-controlled, double-blind, phase 2 study. Adults with moderate-to-severe AD were required to use TCS twice daily and then randomized (1:1:1:1) to lebrikizumab 125 mg single dose, lebrikizumab 250 mg single dose, lebrikizumab 125 mg every 4 weeks for 12 weeks, or placebo every 4 weeks for 12 weeks, after a 2-week TCS run-in. The primary endpoint was percentage of patients achieving Eczema Area and Severity Index (EASI)-50 at week 12., Results: In total, 209 patients received the study drug. At week 12, significantly more patients achieved EASI-50 with lebrikizumab 125 mg every 4 weeks (82.4%; P = .026) than placebo every 4 weeks (62.3%); patients receiving a single dose of lebrikizumab showed no statistically significant improvements in EASI-50 compared with placebo. Adverse events were similar between groups (66.7% all lebrikizumab vs 66.0% placebo) and mostly mild or moderate., Limitations: Protocol-mandated twice daily TCS treatment limits our understanding of the efficacy of lebrikizumab as a monotherapy. The short study duration did not enable long-term efficacy or safety evaluations., Conclusion: When combined with TCS, lebrikizumab 125 mg taken every 4 weeks led to a significant improvement and was well tolerated in patients with moderate-to-severe AD., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Although most patients with atopic dermatitis (AD) are effectively managed with topical medication, a significant minority require systemic therapy. Guidelines for decision making about advancement to systemic therapy are lacking., Objective: To guide those considering use of systemic therapy in AD and provide a framework for evaluation before making this therapeutic decision with the patient., Methods: A subgroup of the International Eczema Council determined aspects to consider before prescribing systemic therapy. Topics were assigned to expert reviewers who performed a topic-specific literature review, referred to guidelines when available, and provided interpretation and expert opinion., Results: We recommend a systematic and holistic approach to assess patients with severe signs and symptoms of AD and impact on quality of life before systemic therapy. Steps taken before commencing systemic therapy include considering alternate or concomitant diagnoses, avoiding trigger factors, optimizing topical therapy, ensuring adequate patient/caregiver education, treating coexistent infection, assessing the impact on quality of life, and considering phototherapy., Limitations: Our work is a consensus statement, not a systematic review., Conclusion: The decision to start systemic medication should include assessment of severity and quality of life while considering the individual's general health status, psychologic needs, and personal attitudes toward systemic therapies., (Copyright © 2017 American Academy of Dermatology, Inc. All rights reserved.)

Background: There is a paucity of literature to direct physicians in the prescribing of immunomodulators for patients with severe atopic dermatitis (AD)., Objective: To survey systemic agent prescribing practices for severe childhood AD among clinicians in the United States and Canada., Methods: The TREatment of severe Atopic dermatitis in children Taskforce (TREAT), US&CANADA, a project of the Pediatric Dermatology Research Alliance (PeDRA), developed an online multiple-response survey to assess clinical practice, gather demographic information and details of systemic agent selection, and identify barriers to their use in patients with recalcitrant pediatric AD., Results: In total, 133 of 290 members (45.9%) of the Society for Pediatric Dermatology completed the survey, and 115 of 133 (86.5%) used systemic treatment for severe pediatric AD. First-line drugs of choice were cyclosporine (45.2%), methotrexate (29.6%), and mycophenolate mofetil (13.0%). The most commonly used second-line agents were methotrexate (31.3%) and mycophenolate mofetil (30.4%); azathioprine was the most commonly cited third-line agent. The main factors that discouraged use of systemic agents were side-effect profiles (82.6%) and perceived risks of long-term toxicity (81.7%)., Limitations: Investigation of the sequence of systemic medications or combination systemic therapy was limited. Recall bias may have affected the results., Conclusion: Great variation exists in prescribing practices among American and Canadian physicians using systemic agents for treatment of pediatric AD., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease. There are no standardized methods for capturing long-term control of AD., Objective: We sought to identify how long-term control has been captured in published randomized controlled trials (RCTs). Results will initiate consensus discussions on how best to measure long-term control in the core outcome set for AD., Methods: We conducted a systematic review of RCTs of AD treatments published between 2000 and 2013, with a follow-up period of 3 months or longer, at least 1 outcome measure recorded at 3 or more time points, full article available, and published in English., Results: In all, 101 of 353 RCTs were eligible. Methods to capture long-term control included: repeated measurement of AD outcomes (92 RCTs; 91%), use of AD medication (29 RCTs; 28.7%), and AD flares/remissions (26 RCTs; 25.7%). Repeated measurements of AD outcomes were typically collected 3 to 5 times during a trial, but analysis methods often failed to make best use of the data. Time to first flare was most commonly used for trials including flare data (21/52). Medication use was recorded based on quantity, potency, and frequency of application., Limitations: We included RCT data only., Conclusion: This review illustrates the difficulties in measuring long-term control, and points to the need for improved harmonization of outcomes., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Domestic water hardness and chlorine have been suggested as important risk factors for atopic dermatitis (AD)., Objective: We sought to examine the link between domestic water calcium carbonate (CaCO3) and chlorine concentrations, skin barrier dysfunction (increased transepidermal water loss), and AD in infancy., Methods: We recruited 1303 three-month-old infants from the general population and gathered data on domestic water CaCO3 (in milligrams per liter) and chlorine (Cl2; in milligrams per liter) concentrations from local water suppliers. At enrollment, infants were examined for AD and screened for filaggrin (FLG) skin barrier gene mutation status. Transepidermal water loss was measured on unaffected forearm skin., Results: CaCO3 and chlorine levels were strongly correlated. A hybrid variable of greater than and less than median levels of CaCO3 and total chlorine was constructed: a baseline group of low CaCO3/low total chlorine (CaL/ClL), high CaCO3/low total chlorine (CaH/ClL), low CaCO3/high total chlorine (CaL/ClH) and high CaCO3/high total chlorine (CaH/ClH). Visible AD was more common in all 3 groups versus the baseline group: adjusted odds ratio (AOR) of 1.87 (95% CI, 1.25-2.80; P = .002) for the CaH/ClL group, AOR of 1.46 (95% CI, 0.97-2.21; P = .07) for the CaL/ClH, and AOR of 1.61 (95% CI, 1.09-2.38; P = .02) for the CaH/ClH group. The effect estimates were greater in children carrying FLG mutations, but formal interaction testing between water quality groups and filaggrin status was not statistically significant., Conclusions: High domestic water CaCO3 levels are associated with an increased risk of AD in infancy. The influence of increased total chlorine levels remains uncertain. An intervention trial is required to see whether installation of a domestic device to decrease CaCO3 levels around the time of birth can reduce this risk., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The influence of early exposure to allergenic foods on the subsequent development of food allergy remains uncertain., Objective: We sought to determine the feasibility of the early introduction of multiple allergenic foods to exclusively breast-fed infants from 3 months of age and the effect on breastfeeding performance., Methods: We performed a randomized controlled trial. The early introduction group (EIG) continued breastfeeding with sequential introduction of 6 allergenic foods: cow's milk, peanut, hard-boiled hen's egg, sesame, whitefish (cod), and wheat; the standard introduction group followed the UK infant feeding recommendations of exclusive breastfeeding for around 6 months with no introduction of allergenic foods before 6 months of age., Results: One thousand three hundred three infants were enrolled. By 5 months of age, the median frequency of consumption of all 6 foods was 2 to 3 times per week for every food in the EIG and no consumption for every food in the standard introduction group (P < .001 for every comparison). By 6 months of age, nonintroduction of the allergenic foods in the EIG was less than 5% for each of the 6 foods. Achievement of the stringent per-protocol consumption target for the EIG proved more difficult (42% of evaluable EIG participants). Breastfeeding rates in both groups significantly exceeded UK government data for equivalent mothers (P < .001 at 6 and at 9 months of age)., Conclusion: Early introduction, before 6 months of age, of at least some amount of multiple allergenic foods appears achievable and did not affect breastfeeding. This has important implications for the evaluation of food allergy prevention strategies., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The association between atopic dermatitis (AD) and food allergy (FA) is not fully understood, although a causal relationship has been suggested. This has important implications for prevention and treatment., Objective: We aimed to review the association between AD and FA, the effect of FA on AD severity, chronicity, and age of onset, and the temporal relationship between the two., Methods: Medline and Embase were systematically searched from inception to November 2014 for studies investigating both AD and FA., Results: Sixty-six studies were identified. Eighteen were population-based, 8 used high-risk cohorts, and the rest comprised patients with either established AD or FA. In population-based studies, the likelihood of food sensitization was up to 6 times higher in patients with AD versus healthy control subjects at 3 months of age (odds ratio, 6.18; 95% CI, 2.94-12.98; P < .001). Other population-based studies reported that up to 53% of subjects with AD were food sensitized, and up to 15% demonstrated signs of FA on challenge. Meanwhile, studies including only patients with established AD have reported food sensitization prevalences up to 66%, with challenge-proven FA prevalences reaching up to 81%. Sixteen studies suggested that FA is associated with a more severe AD phenotype. Six studies indicated that AD of earlier onset or increased persistence is particularly associated with FA. Finally, one study found that AD preceded the development of FA., Conclusions: This systematic review confirms a strong and dose-dependent association between AD, food sensitization, and FA. AD of increased severity and chronicity is particularly associated with FA. There is also evidence that AD precedes the development of food sensitization and allergy, in keeping with a causal relationship., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The association between allergic sensitization and eczema has been debated for years., Objective: We sought to determine and compare the strength of the association between allergen skin sensitization and eczema in both developing and industrialized countries., Methods: Twenty-eight thousand five hundred ninety-one randomly selected 8- to 12-year-old schoolchildren in 20 countries were physically examined for flexural eczema and received skin prick testing to Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat hair, Alternaria tenuis, mixed tree and grass pollen, and allergens of local relevance., Results: The age- and sex-adjusted odds ratios (ORs) for a positive association between flexural eczema and atopy ranged between 0.74 (95% CI, 0.31-1.81) and 4.53 (95% CI, 1.72-11.93), with a significantly stronger association in affluent compared with nonaffluent countries (combined age- and sex-adjusted OR(affluent) = 2.69 [95% CI, 2.31-3.13] and OR(nonaffluent) = 1.17 [95% CI, 0.81-1.70]). The combined population attributable fraction for atopy in flexural eczema was 27.9% for affluent and 1.2% for nonaffluent-country centers. Correlating gross national per-capita income with either ORs or population attributable fractions for atopy in flexural eczema confirmed a highly significant positive association (P = .006 and P < .001, respectively)., Conclusions: The association between atopy and flexural eczema is weak and more variable than previously suggested, and the strength of this association is positively linked to gross national income.

Background: Geohelminth infection and poor hygiene may be protective against allergic sensitization., Objective: To determine whether current helminth infection is associated with a reduced prevalence of allergen skin test sensitization in a Southeast Asian population of children with a high prevalence of hookworm infection., Methods: A total of 1742 Vietnamese schoolchildren were invited to take part in a cross-sectional survey. Allergen skin sensitization to house dust mites (Dermatophagoides pteronyssinus and Dermatophagoides farinae) and American cockroach (Periplaneta americana) were measured and stool samples for qualitative and quantitative geohelminth estimation collected., Results: A total of 1601 children age 6 to 18 participated. Sensitization to dust mites was present in 14.4% and to cockroach in 27.6% of children. In a mutually adjusted model, the risk of sensitization to dust mites was reduced in those with higher hookworm burden (adjusted odds ratio [OR] for 350+ vs no eggs per gram, 0.61; 95% CI, 0.39-0.96) and with Ascaris infection (adjusted OR, 0.28; 0.10-0.78), and increased in those using flush toilets (adjusted OR for flush toilet vs none/bush/pit, 2.51; 1.00-6.28). In contrast, sensitization to cockroach was not independently related to geohelminth infection but was increased in those regularly drinking piped or well water rather than from a stream (adjusted OR, 1.33; 1.02-1.75)., Conclusion: Geohelminth infection, sanitation, and water supply influence the risk of allergic sensitization in Vietnamese children. This is consistent with a protective effect against allergy by geohelminth or other gastrointestinal infection., Clinical Implications: If the inverse relationship between geohelminth infection, poor sanitation, and allergic sensitization proves to be causal, drugs derived from parasite products may help to alleviate clinical allergic disease.

We challenge 3 prevailing concepts in understanding atopic dermatitis using data from epidemiologic studies. First, we show that although atopy is associated with atopic dermatitis to some degree, its importance is not likely to be a simple cause-and-effect relationship, especially at a population level. Our epidemiologic data do not exclude a contributory role for IgE-mediated immunologic processes, especially in those with existing and severe disease. Second, evidence is presented that does not support a straightforward inverse relationship between infections and atopic dermatitis risk. A link, if present, is likely to be more complex, depending critically on the timing and type of infectious exposure. Third, recent evidence suggests that the risk of subsequent childhood asthma is not increased in children with early atopic dermatitis who are not also early wheezers, suggesting a co-manifestation of phenotypes rather than a progressive atopic march. Collectively, these observations underline the importance of epidemiologic studies conducted at a population level to gain a more balanced understanding of the enigma of atopic dermatitis.

Background: The extent to which the phenotype of atopic dermatitis (AD) is truly atopic has been the subject of much debate., Objective: We sought to systematically evaluate the evidence for the value of measurement of IgE antibodies in diagnosing AD and whether knowledge of IgE sensitization increases clinical diagnostic and predictive ability., Methods: We searched Medline from its inception until September 2003. Only studies that measured atopy as either skin prick test positivity or IgE-antibody sensitization to environmental allergens were included within a descriptive analysis. Because the small number of studies of adequate quality did not allow a formal meta-analysis, we assigned strength of evidence according to predefined quality criteria and ranked studies accordingly., Results: Inclusion of atopy as part of the diagnostic criteria for AD did not enhance the criteria's sensitivity and specificity in relation to the clinical phenotype of AD. The strength of association between atopy and AD varied significantly between hospital studies (47% to 75%; n=14 studies) and was stronger in hospital than in community populations (7.4% to 78%; n=13 studies). Whereas study quality did not have an effect on atopy prevalence in hospital populations, low atopy prevalences in community surveys were seen in less rigidly conducted studies. AD severity was positively associated with the number of positive skin prick test responses or IgE-antibody levels in 7 of 8 studies that measured both. Only one study suggested that IgE-specific sensitization to hen's egg is associated with subsequent development of AD, and 2 studies found that allergen-specific IgE sensitization in patients with AD is a prognostic marker for allergic airway disease in later life. Atopy-associated AD might also have a worse long-term prognosis than AD that is not associated with atopy., Conclusion: Although atopy is clearly associated with AD, the role of IgE sensitization in AD needs further study. Current evidence suggests that up to two thirds of persons with AD are not atopic, which implies that continued use of the term atopic dermatitis is problematic. Longitudinal studies are needed to compare the treatment response and prognosis of IgE-associated and non-IgE-associated AD., (Copyright 2004 American Academy of Allergy, Asthma and Immunology)