Outcomes of hematopoietic stem cell gene therapy for Wiskott-Aldrich syndrome.

Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder characterized by combined immunodeficiency, eczema, microthrombocytopenia, autoimmunity, and lymphoid malignancies. Gene therapy (GT) to modify autologous CD34+ cells is an emerging alternative treatment with advantages over standard allogeneic hematopoietic stem cell transplantation for patients who lack well-matched donors, avoiding graft-versus-host-disease. We report the outcomes of a phase 1/2 clinical trial in which 5 patients with severe WAS underwent GT using a self-inactivating lentiviral vector expressing the human WAS complementary DNA under the control of a 1.6-kB fragment of the autologous promoter after busulfan and fludarabine conditioning. All patients were alive and well with sustained multilineage vector gene marking (median follow-up: 7.6 years). Clinical improvement of eczema, infections, and bleeding diathesis was universal. Immune function was consistently improved despite subphysiologic levels of transgenic WAS protein expression. Improvements in platelet count and cytoskeletal function in myeloid cells were most prominent in patients with high vector copy number in the transduced product. Two patients with a history of autoimmunity had flares of autoimmunity after GT, despite similar percentages of WAS protein-expressing cells and gene marking to those without autoimmunity. Patients with flares of autoimmunity demonstrated poor numerical recovery of T cells and regulatory T cells (Tregs), interleukin-10-producing regulatory B cells (Bregs), and transitional B cells. Thus, recovery of the Breg compartment, along with Tregs appears to be protective against development of autoimmunity after GT. These results indicate that clinical and laboratory manifestations of WAS are improved with GT with an acceptable safety profile. This trial is registered at clinicaltrials.gov as #NCT01410825.

Higher maternal bread and thiamine intakes are associated with increased infant allergic disease.

BACKGROUND: A mother's diet during pregnancy may influence her infant's immune development. However, as potential interactions between components of our dietary intakes can make any nutritional analysis complex, here we took a multi-component dietary analysis approach. METHODS: Nutritional intake data was collected from 639 pregnant women using a validated semi-quantitative food frequency questionnaire to reflect their dietary intakes during 32-36 weeks of gestation. To investigate their dietary intake pattern, we calculated Dietary Inflammatory Index scores. Maternal consumption of 12 food groups, 20 individual whole foods, and 18 specific nutrient intakes, along with any vitamin and mineral supplementation, were determined. Infant outcomes included eczema, allergen sensitization, and IgE-mediated food allergy. Regression-based analyses with covariates adjustment were applied. RESULTS: Women with higher white bread consumption were more likely to have an infant with doctor-diagnosed eczema (adjusted relative risk [aRR] 1.16; 95% CI 1.08, 1.24; p < .001) and IgE-mediated food allergy (aRR 1.14; 95% CI 1.02, 1.28; p = .02). Higher maternal intakes of fiber-rich bread (aRR 1.14; 95% CI 1.04, 1.25; p = .01) and legumes (aRR 1.11; 95% CI 1.02, 1.21; p = .02) were also associated with infant doctor-diagnosed eczema. Higher maternal thiamine intakes were associated with increased parent-reported infant eczema (aRR 1.08; 95% CI 1.03, 1.12; p < .001). CONCLUSION: In Australia, where bread flour is fortified with thiamine, we identified consistent links between higher maternal thiamine-rich diets and increased risk of infant eczema and food allergy. Our results highlight a need for further investigation of potential effects of high thiamine exposures on immune development, especially in-utero.

Does having siblings really protect against childhood atopic diseases? A total population and within-family analysis.

The association between having older siblings and decreased risk for atopic symptoms is well-established. This has been interpreted as evidence for the microbiota hypothesis, i.e. that increased early-childhood microbial exposure caused by siblings protects from immune hypersensitivities. However, possible confounders of the association have received little attention. We used register data on Finnish cohorts born in 1995-2004 (N = 559,077) to assess medication purchases for atopic diseases: antihistamines, eczema medication, asthma medication and Epinephrine. We modelled the probability of atopic medication purchases at ages 0-15 by birth order controlling for important observed confounders and all unobserved genetic and environmental characteristics shared by siblings in a within-family fixed effects model. We further studied medication purchases among first-borns according to the age difference with younger siblings to assess whether having younger siblings in early childhood is beneficial. Having older siblings was associated with a lower probability of atopic medication purchases. Compared to first-borns, the probability was 10-20% lower among second-borns, 20-40% lower among third-borns, and 30-70% lower among subsequent children, depending on medication type. Confounding accounted for up to 75% of these differences, particularly for asthma and eczema medication, but significant differences by birth order remained across all medication types. Among first-borns, a smaller age difference with younger siblings was related to a lower likelihood of atopic medication use. Our results, based on designs that account for unobserved confounding, show that exposure to siblings in early childhood, protects from atopic diseases, and thus strongly support the microbiota hypothesis.

Prenatal risk factors of indoor environment and incidence of childhood eczema in the Japan Environment and Children's Study.

The quality of indoor environment is a risk factor for early childhood eczema and atopic dermatitis; however, its influence during pregnancy on childhood eczema in Japan has not been investigated. In this study, we aimed to determine the indoor environmental factors that are associated with eczema in children up to 3 years of age, using national birth cohort data from the Japan Environment and Children's Study (JECS). Information on indoor environments and eczema symptoms until 3 years of age was collected using self-administered questionnaires to the mothers. A total of 71,883 and 58,639 mother-child pairs at 1.5- and 3-years-old, respectively, were included in the former analyses. To account for prenatal indoor risk factors, 17,568 (1.5-years-old) and 7063 (3-years-old) children without indoor mold and/or ETS exposure were included in the final analysis. A higher mold index, gas heater use, parquet flooring use, and frequent insecticide use showed significantly increased risks for childhood eczema up to 3 years of age. These associations were consistent after stratification analysis among children whose parents did not have a history of allergies. The updated WHO guidelines on indoor air quality should be implemented based on recent findings regarding the effects of prenatal exposure to indoor dampness on health effects of children further in life, including asthma, respiratory effects, eczema, and other immunological effects.

Contact sensitisation pattern of patients with eczema at the face and neck region: A retrospective study in Kuala Lumpur.

INTRODUCTION: Allergic contact dermatitis (ACD) involving the face and neck region (FNR) is not uncommon. We aimed to determine the sensitisation pattern among patients with dermatitis involving FNR who underwent skin patch tests between 2016 and 2022. MATERIALS AND METHODS: This is a 7-year retrospective review on contact sensitisation patterns in patients with dermatitis over the FNR who underwent skin patch tests between 2016 and 2022 in the Department of Dermatology Hospital Kuala Lumpur. RESULTS: There were 291 patients (female-to-male ratio of 7.8:1; mean age of 34.1 ± 14.0 years) with dermatitis at the FNR who underwent patch tests. The majority (n = 116,39.9%) were aged between 20 and 29 years. About 8% were below 19 years of age. Nearly 50% had dermatitis over the perioral region, 8.6% at the periorbital area and 50.6% at the other parts of the face and neck region. The clinical diagnoses included contact dermatitis (n = 145, 49.8%), cheilitis (n = 81, 27.8%), endogenous eczema (n = 28, 9.6%) and others. All were tested with European baseline series, with 91.4% and 77.0% tested with extended series, and own products, respectively. About 70.1% were sensitised to at least one allergen. The most common sensitizing allergen was nickel sulfate (34.0%), followed by cobalt chloride (11.7%), fragrance mix (10.7%), methylchloroisothiazolinone/ methylisothiazolinone (8.9%), and formaldehyde (8.9%). Clinical relevance was documented in 58.8% of them. CONCLUSION: Contact sensitisation was detected in about 70% of patients with dermatitis at the FNR who were patchtested. Nickel, cobalt chloride and fragrance mix were the most common sensitising allergens in these patients.

Association between Polyunsaturated Fatty Acid Intake and Eczema in Children and Adolescents.

INTRODUCTION: Eczema is a common allergic skin condition among children and adolescents, and polyunsaturated fatty acids (PUFAs) are a kind of fatty acid which were reported to be associated with reduced risk of eczema. Previous studies explored different types of PUFAs with various age groups of children and adolescents, and the influence of confounding factors such as medicine use was not considered. In the present study, we aimed to identify the associations between PUFAs and the risk of eczema in children and adolescents. These findings of our study might help better understand the associations between PUFAs and eczema. METHODS: This cross-sectional study collected the data of 2,560 children and adolescents aged 6-19 years from National Health and Nutrition Examination Surveys (NHANES) between 2005 and 2006. Total PUFA, omega-3 (n-3), including octadecatrienoic acid/18:3, octadecatrienoic acid/18:4, eicosapentaenoic acid/20:5, docosapentaenoic acid/22:5, and docosahexaenoic acid/22:6, omega-6 (n-6), including octadecatrienoic acid/18:2 and eicosatetraenoic acid/20:4, total n-3 intake, total n-6 intake, and n-3/n-6 were main variables in this study. Univariate logistic regression was applied for identifying potential confounders for eczema. Univariate and multivariate logistic regression analysis were conducted to explore the associations between PUFAs and eczema. Subgroup analysis was performed on subjects with different ages, and patients complicated with other allergic diseases, allergy, and medicine use or not. RESULTS: In total, there were 252 (9.8%) subjects who had eczema. After adjusting for confounding factors including age, race, poverty to income ratio (PIR), medicine use, hay fever, sinus infection, body mass index (BMI), serum total immunoglobulin E (IgE) antibody, and IgE, we observed that eicosatetraenoic acid/20:4 (OR = 0.17, 95% CI: 0.04-0.68) and total n-3 (OR = 0.88, 95% CI: 0.77-0.99) were linked with decreased risk of eczema in children and adolescents. Eicosatetraenoic acid/20:4 was correlated with decreased risk of eczema in participants without hay fever (OR = 0.82, 95% CI: 0.70-0.97) and medicine use (OR = 0.80, 95% CI: 0.68-0.94) or with allergy (OR = 0.75, 95% CI: 0.59-0.94). Total n-3 intake was associated with a reduced risk of eczema with the adjusted OR of 0.84, 95% CI: 0.72-0.98) in participants without hay fever. In those without sinus infection, octadecatrienoic acid/18:4 was linked with decreased risk of eczema (OR = 0.83, 95% CI: 0.69-0.99). CONCLUSION: N-3 and eicosatetraenoic acid/20:4 might be associated with the risk of eczema in children and adolescents.

Exploration of associations between occupational exposures and current adult eczema.

OBJECTIVES: There is a scarcity of evidence on occupational exposures that may increase eczema in adults. We aimed to investigate potential associations between occupational exposures and eczema in middle-aged adults. METHODS: A lifetime work history calendar was collected from the Tasmanian Longitudinal Health Study participants when they were at age 53. Their work history was collated with the occupational asthma-specific job exposure matrix to define ever-exposure and cumulative exposure unit-years since no eczema job exposure matrix is available. Eczema was determined using the report of flexural rash that was coming and going for at least 6 months in the last 12 months. Skin prick tests were used to further subgroup eczema and atopic eczema (AE) or non-AE (NAE). Logistic and multinomial regression models were used to investigate the associations. RESULTS: Eczema prevalence was 9.1%. Current occupational exposure to animals (adjusted OR, aOR=3.06 (95% CI 1.43 to 6.58)), storage mites (aOR=2.96 (95% CI 1.38 to 6.34)) and endotoxin (aOR=1.95 (95% CI 1.04 to 3.64)) were associated with increased risk of current eczema. Furthermore, increased odds of NAE were associated with current exposure to animals (aOR=5.60 (95% CI 1.45 to 21.7)) and storage mites (aOR=5.63 (95% CI 1.45 to 21.9)). Current exposures to isocyanates (aOR=5.27 (95% CI 1.17 to 23.7)) and acrylates (aOR=8.41 (95% CI 1.60 to 44.3)) were associated with AE. There was no evidence of associations between cumulative exposures and eczema prevalence. Cumulative exposure to metalworking fluids (aOR=1.10 (95% CI 1.01 to 1.22)) was associated with NAE and acrylates (aOR=1.24 (95% CI 1.04 to 1.46)) with AE. CONCLUSIONS: In this exploratory assessment, multiple occupational exposures were associated with current eczema in middle-aged adults. Raising awareness and limiting these exposures during an individual's productive working life will likely have various health benefits, including reducing eczema prevalence.

Maternal dietary patterns during pregnancy and the risk of infantile eczema during the first year of life: a cohort study in northeast China.

BACKGROUND: There are few studies on the relationship between diet during pregnancy and infantile eczema and the conclusions are inconsistent. The aim of the present study was to explore the impact of dietary patterns during pregnancy on infantile eczema. METHODS: A total of 495 mother-child pairs from a prospective cohort in Shenyang, China was recruited. Information on maternal dietary intake during pregnancy was assessed with a validated self-administered food frequency questionnaire. The data of infantile eczema was assessed using a structured questionnaire. Factor analysis to derive dietary patterns. The relationship between the dietary pattern and infantile eczema was examined by the logistic regression analysis. RESULTS: The cumulative incidence of eczema in 6 months and 12 months in northeast China was 45.7% and 57.8%, respectively. Three dietary patterns were identified. There was a tendency for an expose-response relationship between the maternal high-protein dietary pattern during pregnancy and the risk of infantile eczema within 12 months (P for trend = 0.023): the adjusted odds ratio (95% confidence interval) in the Q1, Q2, Q3, Q4 were 1.00 (reference), 1.63 (0.96-2.76), 1.81 (1.06-3.06), and 1.87 (1.09-3.20), respectively. No association between Western and plant-based patterns during pregnancy and infantile eczema within 12 months was found. Infantile eczema within 6 months was not associated with any of the three dietary patterns. CONCLUSION: The maternal high-protein pattern during pregnancy may be a risk factor for infantile eczema during the first year of life.

Timing of introduction to solid food, eczema and wheezing in later childhood: a longitudinal cohort study.

BACKGROUND: The timing of introduction to solid food has been associated with eczema and wheezing in childhood. Our aim was to determine whether differences persist within the recommended 4 to 6 month age range. METHODS: A longitudinal cohort study with repeated measures was conducted among children from birth to 10 years of age who were participating in the TARGet Kids! practice based research network in Toronto, Canada. The primary exposure was the timing of introduction to infant cereal as the first solid food. The primary outcome was eczema and the secondary outcome was wheezing collected by parent report using the validated International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Multinomial generalized estimating equations were used and effect modification by family history of asthma and breastfeeding duration were explored. RESULTS: Of the 7843 children included, the mean (standard deviation) age of introduction to infant cereal was 5.7 (1.9) months. There was evidence for family history of asthma and breastfeeding duration to be effect modifiers in the eczema (P = 0.04) and wheezing (P = 0.05) models. Introduction to infant cereal at 4 vs. 6 months of age was associated with higher odds of eczema (OR 1.62; 95% CI: 1.12, 2.35; P = 0.01) among children without a family history of asthma who were not breastfeeding when solid foods were introduced. Introduction to infant cereal at 4 vs. 6 months of age was associated with a higher odds of wheezing (OR 1.31; 95% CI: 1.13, 1.52; P < .001) among children without a family history of asthma who were breastfeeding when solid foods were introduced. There was little evidence of an association among the remaining strata for either outcome. CONCLUSION: The findings of this study support recommendations to introduce solid food around 6 months of age.

Aetiology of occupational hand eczema in hairdressers: Tackling the complexity of exposure combinations to identify patterns associated with increased risk of hand eczema.

INTRODUCTION: Hairdressers are exposed to wet work and manifold allergens at work, rendering exposure complex and the aetiology of occupational hand eczema (OHE) often multifactorial in this occupational group. OBJECTIVES: To identify exposure patterns associated with increased risk of hand eczema in hairdressers. METHODS: All hairdressers graduating from 2004 to 2007 and 2015 to 2018 received a questionnaire in 2009 and 2020, respectively. Current exposures (with or without regular glove use) and OHE were self-reported, and their association examined. Patterns of exposure were identified by latent class analysis (LCA). RESULTS: A total response of 39.9% (668/1675) was obtained. Six exposure profiles (#1-6) were identified by LCA across 11 tasks performed with or without gloves as well as deep conditioning, that is, 23 task items. Compared to profile #1 with the lowest OHE risk (reference) an increased risk of current OHE were seen in profile #4 [adjusted odds ratio [aOR] 6.5, 95% confidence interval [CI] 1.5-44.8 and #6 (aOR 39.4, 95%CI 6.1-362.8)] in logistic regression analysis. Profile #1 and #6 had performed the same tasks, but in profile #6 regular glove use was performed in 9.1% (1/ 11) of tasks compared to 72.7% (8/11) of tasks in profile #1 (p = 0.002). CONCLUSION: Although occupational exposures in hairdressing are complex, meaningful patterns associated with a wide range of OHE risk can be identified by LCA. The increase of OHE risk seems predominantly to be due to poor compliance with protective gloves. LCA could be applied to further fields of complex (skin) exposures.

Hand eczema in glove-wearing patients.

BACKGROUND: Allergic contact dermatitis to gloves is mostly induced by rubber accelerators. The European baseline series (EBS) appears insufficient to detect glove allergy. Since 2017, it is recommended to use the European rubber series (ERS) and to test the patients' own gloves. OBJECTIVES: To investigate the clinical profile of glove-wearing patients with hand eczema (HE) and to evaluate their sensitisation profile to glove allergens and the value of testing the patients' own gloves. METHODS: We conducted a French multicentre study of patients evaluated for HE between 2018 and 2020 and tested with the EBS, the ERS and their own gloves in patch tests and semi-open (SO) tests. RESULTS: A total of 279 patients were included; 32.6% of patients had positive tests to their own gloves or to glove allergens. Almost 45% of the sensitisations to glove allergens were detected only by the ERS. Among the patients tested both in patch tests and SO tests with their own gloves with positive results, 28% had positive SO tests only. Polyvinylchloride (PVC) gloves were positive in four patients. CONCLUSION: Our series confirms the need to test the ERS. All the patients' gloves must also be tested including PVC gloves. SO tests with gloves are useful as a complement to patch tests.

Prevalence and risk factors for hand eczema among professional hospital cleaners in Denmark: A cross-sectional questionnaire-based study.

BACKGROUND: Professional cleaners are commonly affected by hand eczema (HE) due to wet work and exposure to cleaning products in the work environment. OBJECTIVE: To investigate (1) the prevalence of HE in a group of professional hospital cleaners, (2) the association of HE with various comorbidities and self-reported signs/symptoms of skin lesions and (3) the association of HE with various occupational and personal risk factors in the same population. METHODS: A cross-sectional questionnaire-based study including all cleaners working in three hospitals in Denmark. The questionnaire was composed of 35 questions. Prevalence is reported using proportions with 95% confidence intervals and compared using difference of proportions and Fisher's exact test. RESULTS: A total of 122 out of 180 cleaners (response rate = 68%) participated in this study. The self-reported lifetime prevalence of HE among the cleaners was 30.3%, while the 1-year prevalence was 18.9%. HE was significantly associated with a history of atopic diseases. There was a significant correlation between having HE, and self-reported redness and itch of the hands in the last 12 months, as well as the use of hydrochloric acid ≥4 days/week during the last 12 months. Logistic regression analysis found HE significantly associated with washing hands ≥20 times during a working day and a history of atopic dermatitis. CONCLUSION: Cleaners are at an elevated risk of developing HE. More focus on education/information regarding the prevention and treatment of HE is necessary for the cleaning profession. Self-reported redness and itching of the hands may be a useful prediction of HE in cleaners.

New Perspectives in the Management of Chronic Hand Eczema: Lessons from Pathogenesis.

Chronic hand eczema (CHE) is a common inflammatory skin condition that significantly impacts the quality of life. From work-related disabilities to social embarrassment, pain, and financial costs, the burden on society is substantial. Managing this condition presents challenges such as long-term treatment, poor patient compliance, therapy side effects, and economic feasibility. As a result, significant efforts have been made in this field in recent years. Specifically, the broader understanding of CHE pathogenesis has led to the development of new drugs, both topical and systemic. The aim of this narrative review is to summarize the current available data on hand eczema pathophysiology and explore the resulting developments in drugs for its treatment. A comprehensive search on PubMed and the other main scientific databases was conducted using keywords related to CHE and its pathogenesis. The most relevant pathways targeted by therapies include the JAK-STAT cascade, IL-4, and IL-13 axis, phosphodiesterase 4 enzyme, and chemo-attractant cytokines. In the near future, physicians will have a plethora of therapeutic alternatives. Consequently, they should be well-trained not only in how to use these alternatives but also how to combine these treatments to address the ongoing challenges related to efficacy, tolerability, and safety.

Sex-specific developmental trajectories of eczema from infancy to age 26 years: A birth cohort study.

BACKGROUND: Eczema is a common inflammatory skin disease with varying developmental trajectories/patterns that are influenced by different risk factors. The aim of this study was to investigate eczema development from infancy to early adulthood by identifying distinct developmental trajectories that describe disease patterns over time and evaluate the role of prenatal and early-life risk factors. METHODS: The Isle of Wight Birth Cohort (n = 1456) was prospectively assessed at birth, 1, 2, 4, 10, 18 and 26 years. In all assessments, eczema was defined as chronic or chronically relapsing itchy dermatitis lasting >6 weeks with characteristic morphology and distribution in the past 12 months. Developmental trajectories of eczema between 1 or 2 and 26 years were identified separately for males and females by applying semiparametric mixture models. Associations were assessed by applying a modified Poisson regression to estimate adjusted risk ratios (aRR) and 95% confidence intervals (CI). RESULTS: In both males and females, the following eczema developmental trajectories were identified: unaffected/transient (males: 77.7% vs. females: 73.0%), mid-onset late-resolving (males: 7.8% vs. females: 4.4%), late-onset (males: 5.2% vs. females: 9.5%) and early-onset persistent (males: 9.3% vs. females: 5.4%). In females, an additional trajectory was identified as follows: early-onset early-resolving (7.7%). Among males, filaggrin gene (FLG) variants (aRR = 2.45, 95% CI: 1.34-4.46) and paternal eczema (2.66, 1.39-5.08) were associated with the early-onset persistent trajectory. Among females, maternal eczema (2.84, 1.42-5.70) and high birthweight (2.25, 1.08-4.69) were associated with the early-onset persistent trajectory. CONCLUSIONS: Four and five trajectories represented eczema development among males and females, respectively, with different predisposing risk factors. Our results indicate that males and females may experience a different course of eczema.

Establishing subclasses of childhood eczema, their risk factors and prognosis.

BACKGROUND: The heterogeneity of development and progression of eczema suggests multiple underlying subclasses for which aetiology and prognosis may vary. A better understanding may provide a comprehensive overview of eczema development and progression in childhood. Thus, we aimed to determine longitudinal eczema subclasses based on assessments and identify their associations with risk factors and allergic outcomes. METHODS: A total of 619 participants with a family history of allergic disease were assessed at 24 time-points from birth to 12 years. At each time, eczema was defined as the report of current rash treated with topical steroid-based preparations. Longitudinal latent class analysis was used to determine eczema subclasses. Subsequent analyses using regression models assessed the associations between eczema subclasses and potential risk factors and allergic outcomes at 18- and 25-year follow-ups (eczema, allergic rhinitis, asthma and allergic sensitization). RESULTS: We identified five eczema subclasses 'early-onset persistent', 'early-onset resolving', 'mid-onset persistent', 'mid-onset resolving' and 'minimal eczema'. Filaggrin null mutations were associated with the early-onset persistent (OR = 2.58 [1.09-6.08]) and mid-onset persistent class (OR = 2.58 [1.32-5.06]). Compared with 'minimal eczema', participants from early-onset persistent class had higher odds of eczema (OR = 11.8 [5.20-26.6]) and allergic rhinitis (OR = 3.13 [1.43-6.85]) at 18 and at 25 years eczema (OR = 9.37 [3.17-27.65]), allergic rhinitis (OR = 3.26 [1.07-9.93]) and asthma (OR = 2.91 [1.14-7.43]). Likewise, mid-onset persistent class had higher odds of eczema (OR = 2.59 [1.31-5.14]), allergic rhinitis (OR = 1.70 [1.00-2.89]) and asthma (OR = 2.00 [1.10-3.63]) at 18 and at 25 years eczema (OR = 6.75 [3.11-14-65]), allergic rhinitis (OR = 2.74 [1.28-5.88]) and asthma (OR = 2.50 [1.25-5.00]). Allergic and food sensitization in early life was more common in those in the persistent eczema subclasses. CONCLUSION: We identified five distinct eczema subclasses. These classes were differentially associated with risk factors, suggesting differences in aetiology, and also with the development of allergic outcomes, highlighting their potential to identify high-risk groups for close monitoring and intervention.

Impaired skin barrier and allergic sensitization in early infancy.

BACKGROUND: Factors predicting allergic sensitization in the first 6 months of life are poorly understood. We aimed to determine whether eczema, dry skin, and high transepidermal water loss (TEWL) at 3 months were associated with allergic sensitization at 6 months of age and, secondarily, to establish whether these characteristics predicted sensitization from 3 to 6 months of age. METHODS: At 3 months of age, 1,994 infants from the population-based PreventADALL birth cohort in Norway and Sweden were assessed for eczema and dry skin on the cheeks and/or extensors; impaired skin barrier function, defined as TEWL in the upper quartile (>9.4 g/m2 /h), and allergen-specific IgE levels <0.1 kUA /L, available in 830. At 6 months, we assessed allergic sensitization to any food (egg, cow's milk, peanut, wheat, soy) or inhalant (birch, timothy grass, dog, and cat) allergen by a skin prick test wheal diameter ≥2 mm larger than negative control. RESULTS: Any sensitization was found in 198 of the 1,994 infants (9.9%), the majority to food allergens (n = 177, 8.9%). Eczema, dry skin, and high TEWL at 3 months increased the risk of sensitization at 6 months; adjusted odds ratios 4.20 (95% CI 2.93-6.04), 2.09 (95% CI 1.51-2.90) and 3.67 (95% CI 2.58-5.22), respectively. Eczema predicted sensitization with 55.6% sensitivity and 68.1% specificity; dry skin with 65.3% sensitivity and 57.3% specificity; and high TEWL with 61.7% sensitivity and 78.1% specificity. CONCLUSION: Eczema, dry skin, and high TEWL at 3 months predicted allergic sensitization at 6 months of age.

Trajectories of asthma and allergy symptoms from childhood to adulthood.

BACKGROUND: Phenotypes of asthma and allergic diseases are mainly studied separately for children and adults. To explore the role of adolescence and young adulthood, we investigated symptom trajectories at the transition from childhood into adulthood. METHODS: Latent class analysis (LCA) was conducted in a population initially recruited for the German arm of Phase II of the International Study of Asthma and Allergies in Childhood and followed-up three times until their early 30s (N=2267). Indicators included in LCA were 12-month prevalences of symptoms of wheeze, rhinoconjunctivitis, and eczema. Latent classes were further characterised regarding important traits such as skin prick tests. Logistic regression models were used to investigate associations with environmental determinants such as smoking and occupational exposures. RESULTS: Six latent classes were identified: an asymptomatic one as well as three with single and two with co-occurring symptoms. All trajectories essentially established between baseline assessment at around 10 years and the first follow-up at around 17 years. Probabilities for symptoms increased from childhood to adolescence, especially for wheeze-related latent classes, while they remained constant in adulthood. Wheeze-related latent classes were also positively associated with exposures during adolescence (e.g. active smoking). CONCLUSION: Distinct trajectories of asthma and allergy symptoms establish from childhood through adolescence and stabilize during early adulthood. This pattern was most notable in wheeze-related latent classes which also showed the strongest positive associations with environmental exposures in adolescence/young adulthood. Therefore, not only childhood but also adolescence is relevant for disease development and offers considerable potential for prevention and health promotion.

The association between domestic hard water and eczema in adults from the UK Biobank cohort study.

BACKGROUND: Eczema is a chronic inflammatory skin disease. Domestic water with high mineral content (hard water) is a risk factor for eczema in children, but this association has not been assessed in adults. OBJECTIVES: To examine the association between domestic hard water supply and eczema prevalence and incidence in adults aged 40-69 years and the contextual effect in eczema outcomes by postcode in adults in the UK. METHODS: We used data from the UK Biobank study collected in 2006-10 (baseline) and 2013-14 (follow-up). Eczema prevalence at baseline (2006-10) and at follow-up (2013-14) and incidence (new onset between baseline and follow-up) were determined from the touchscreen questionnaires and nurse-led interviews. Domestic hard water information was obtained in 2005 and 2013 from the local water supply companies in England, Wales and Scotland as CaCO3 concentrations. We fitted multilevel logistic regression models with random intercepts for postcode areas to examine the effect of domestic hard water on eczema outcomes, and we measured components of variance. RESULTS: In total, 306 531 participants with a mean age of 57 years nested across 7642 postcodes were included in the baseline analysis, and 31 036 participants nested across 3695 postcodes were included in the follow-up analysis. We observed an increase in the odds of eczema at baseline [odds ratio (OR) 1·02, 95% confidence interval (CI) 1·01-1·04] per 50 mg L-1 of CaCO3 increase. Furthermore, exposure to domestic hard water (> 200 mg L-1 of CaCO3 ) was associated with increased odds of prevalent eczema at baseline (OR 1·12, 95% CI 1·04-1·22). Moreover, there was a significant linear trend (P < 0·001) in which increasing levels of hard water increased eczema prevalence risk. No association was observed with incident eczema or eczema at follow-up. The intraclass correlation coefficient for postcode was 1·6% (95% CI 0·7-3·4), which remained unexplained by area-level socioeconomic measures. CONCLUSIONS: Increasing levels of domestic hard water, as measured by CaCO3 concentrations, were associated with an increased prevalence of eczema in adults but not increased incidence. Ongoing efforts to reduce hard water exposure may have a beneficial effect in reducing the burden of eczema in adults. Further research is needed to explore area-level factors that may lead to eczema. What is already known about this topic? Hard water is formed when minerals are dissolved in water from filtration through sedimentary rocks. Several studies have reported a higher prevalence of eczema in areas with hard water. However, all studies on this topic have assessed this in infants and school-aged children, while this association has not been explored in adults. What does this study add? Our findings suggest that exposure to higher concentrations of domestic hard water is associated with an increase in eczema prevalence in adults aged 40-69 years. Ongoing efforts to reduce hard water exposure may have a beneficial effect in reducing eczema prevalence in adults.

Associations between Body Mass Index Trajectories in the first two years of life and Allergic Rhinitis, Eczema and Food Allergy outcomes up to early adulthood.

BACKGROUND: Early life body mass index (BMI) trajectories influence the risk of asthma at 18 years of age. However, it is unclear if these are also associated with other allergic diseases. OBJECTIVES: We investigated the associations between BMI trajectories and subsequent allergic rhinitis, eczema and food sensitisation/allergies. METHODS: Parent-reported anthropometric data were collected 18 times in the first two years of life from a cohort of 620 participants in a high-risk cohort. Group-based trajectory modelling was applied to develop BMI trajectories. Associations between trajectories and allergic rhinitis, eczema and food sensitisation at 6, 12 and 18 years of age were assessed using logistic regression models. Potential effect modifications by parental allergic disease, sex and allocated infant formula were assessed. RESULTS: We identified five BMI trajectories: average, below average, persistently low, early low and catch up, and persistently high. None showed an association with allergic rhinitis. In participants with maternal allergic rhinitis, 'early-low and catch-up' (OR = 2.83;95%CI 1.34-5.96, Pint  = 0.05) and 'below average' trajectories (OR = 2.39; 1.18-7.23, Pint  = 0.02) were associated with allergic rhinitis at 18 years of age compared with the average trajectory. No associations were observed with eczema or food sensitisation. CONCLUSION: Infants with early-low and catch-up, or below average BMI growth, were at increased risk of allergic rhinitis at 18 years if they had a mother with allergic rhinitis. These results require replication, but suggest that interactions between poor intrauterine growth, failure to thrive and maternal allergies may influence the risk of allergic rhinitis.

Prenatal occupational disinfectant exposure and childhood allergies: the Japan Environment and Children's study.

BACKGROUND: Disinfectants are widely used in the medical field, particularly recently because of the coronavirus pandemic, which has led to an increase in their use by both medical professionals and the general population. The objective of this study was to examine whether occupational disinfectant use during pregnancy was associated with the development of allergic disease in offspring at 3 years. METHODS: We used data from 78 915 mother/child pairs who participated in the Japan Environment and Children's Study, which is a prospective birth cohort recruited between January 2011 and March 2014. We examined the associations between maternal disinfectant use during pregnancy and allergic diseases (asthma, eczema and food allergies) in children after adjustment for covariates including maternal postnatal return to work when the child was 1 year old by multivariate logistic regression. RESULTS: Compared with those who never used disinfectants, participants who used disinfectant every day had a significantly higher risk of asthma in their offspring (adjusted OR 1.18, 95% CI 1.05 to 1.33 for 1-6 times a week; adjusted OR 1.26, 95% CI 1.05 to 1.52 for every day). The associations between disinfectant exposure and eczema were similar to those of asthma (adjusted OR 1.16, 95% CI 1.02 to 1.31 for 1-6 times a week; adjusted OR 1.29, 95% CI 1.06 to 1.57 for every day). We found a significant exposure-dependent relationship (p for trend <0.01). There were no significant associations between disinfectant use and food allergies. CONCLUSION: Disinfectant use by pregnant women may be a risk factor for asthma and eczema in offspring. As disinfectants are an effective tool in the prevention of infectious diseases, replication of this study and further research into the mechanisms are warranted.