Exploring the skin microbiome in atopic dermatitis pathogenesis and disease modification.

Inflammatory skin diseases such as atopic eczema (atopic dermatitis [AD]) affect children and adults globally. In AD, the skin barrier is impaired on multiple levels. Underlying factors include genetic, chemical, immunologic, and microbial components. Increased skin pH in AD is part of the altered microbial microenvironment that promotes overgrowth of the skin microbiome with Staphylococcus aureus. The secretion of virulence factors, such as toxins and proteases, by S aureus further aggravates the skin barrier deficiency and additionally disrupts the balance of an already skewed immune response. Skin commensal bacteria, however, can inhibit the growth and pathogenicity of S aureus through quorum sensing. Therefore, restoring a healthy skin microbiome could contribute to remission induction in AD. This review discusses direct and indirect approaches to targeting the skin microbiome through modulation of the skin pH; UV treatment; and use of prebiotics, probiotics, and postbiotics. Furthermore, exploratory techniques such as skin microbiome transplantation, ozone therapy, and phage therapy are discussed. Finally, we summarize the latest findings on disease and microbiome modification through targeted immunomodulatory systemic treatments and biologics. We believe that targeting the skin microbiome should be considered a crucial component of successful AD treatment in the future.

Early-pregnancy BMI, maternal gestational weight gain, and asthma and allergic diseases in children.

BACKGROUND: Association of early pregnancy body mass index (BMI) and maternal gestational weight gain (GWG), and asthma and allergic disease in children is unclear. METHODS: We analyzed data from 3176 mother-child pairs in a prospective birth cohort study. Maternal anthropometric measurements in the first and last antenatal clinic visits were obtained through post-delivery questionnaires to calculate early pregnancy BMI and maternal GWG. Asthma and allergic diseases in children by the age of 5 years was assessed using a validated questionnaire. Furthermore, serum samples were analyzed for IgE antibodies to eight allergens. We applied Cox proportional hazards and logistic regression analyses to estimate the association of early pregnancy BMI and maternal GWG (as continuous variables and categorized into quarters), and asthma, atopic eczema, atopic sensitization, and allergic rhinitis in children. RESULTS: Neither early pregnancy BMI nor maternal GWG was associated with asthma and allergic disease in children when analyzed as continuous variables. However, compared to the first quarter of GWG (a rate <0.32 kg/week), mothers in the third quarter (rate 0.42-0.52 kg/week) had children with significantly higher odds of developing atopic eczema (adjusted OR 1.49, 95% CI [1.13-1.96]) by 5 years of age. CONCLUSION: Association of early pregnancy BMI and maternal GWG, and asthma and allergic disease in children, is inconsistent. High maternal GWG may be associated with increased odds of atopic eczema.

Dupilumab provides sustained effectiveness on patient-reported outcomes and favorable safety in patients with moderate-to-severe atopic dermatitis: Up to 5-year results from the daily practice BioDay registry.

BACKGROUND: Long-term daily practice data on patient-reported benefits of dupilumab for atopic dermatitis (AD) remains limited. OBJECTIVE: To evaluate patient-reported outcome measures (PROMs) and the safety of dupilumab in patients with moderate-to-severe AD over a follow-up period of up to 5 years. METHODS: Data were extracted from the prospective, multicenter BioDay registry (October 2017-2022) of patients with moderate-to-severe AD treated with dupilumab in daily practice. RESULTS: In total 1223 patients, 1108 adults and 115 pediatric patients were included. After ≥1 year of treatment, mean Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), Numeric rating scale (NRS)-pruritus ranged between 7.8 and 8.7, 3.5 and 4.2, and 2.9 and 3.1 in adults, respectively, whilst these patient-reported outcome measures (PROMs) ranged between 8.9 and 10.9, 4.4 and 6.4, and 3.0 and 3.7 in pediatric patients, respectively. At follow-up, overall work impairment decreased from 40.1% to 16.3% to 13.3% in adults. Furthermore, class I obesity and itch-dominant patients generally had less favorable treatment response. Of all patients, 66.8% reported ≥1 adverse event, with conjunctivitis being the most common (33.7%). LIMITATIONS: The overall percentage of missing values for selected PROMs was 26% in adults and 46% in pediatric patients. CONCLUSION: In addition to favorable safety, dupilumab has demonstrated sustained effectiveness across various PROMs, underscoring the treatment benefits from patients' perspectives.

Tapinarof cream 1% once daily: Significant efficacy in the treatment of moderate to severe atopic dermatitis in adults and children down to 2 years of age in the pivotal phase 3 ADORING trials.

BACKGROUND: Tapinarof cream 1% once daily (QD), a topical aryl hydrocarbon receptor agonist, downregulates pro-inflammatory Th2 cytokines, upregulates skin-barrier components, and reduces oxidative stress. OBJECTIVE: To assess tapinarof efficacy and safety in adults and children down to 2 years of age with atopic dermatitis (AD). METHODS: Eight hundred and thirteen patients were randomized to tapinarof or vehicle QD in two 8-week phase 3 trials. RESULTS: The primary efficacy endpoint, Validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 and ≥2-grade improvement from baseline at Week 8, was met with statistical significance in both trials: 45.4% versus 13.9% and 46.4% versus 18.0% (tapinarof vs vehicle; both P < .0001). Significantly superior Eczema Area and Severity Index 75 (EASI75) responses were also observed with tapinarof versus vehicle at Week 8: 55.8% versus 22.9% and 59.1% versus 21.2% (both P < .0001). Rapid improvements in patient-reported pruritus were also significant with tapinarof versus vehicle. Common adverse events (≥5%) of folliculitis, headache, and nasopharyngitis were mostly mild or moderate, with lower discontinuations due to adverse events in the tapinarof groups than with vehicle. LIMITATIONS: Long-term efficacy was not assessed. CONCLUSION: Tapinarof demonstrated highly significant efficacy and favorable safety and tolerability in a diverse population of patients with AD down to 2 years of age.

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.

A machine-learning exploration of the exposome from preconception in early childhood atopic eczema, rhinitis and wheeze development.

BACKGROUND: Most previous research on the environmental epidemiology of childhood atopic eczema, rhinitis and wheeze is limited in the scope of risk factors studied. Our study adopted a machine learning approach to explore the role of the exposome starting already in the preconception phase. METHODS: We performed a combined analysis of two multi-ethnic Asian birth cohorts, the Growing Up in Singapore Towards healthy Outcomes (GUSTO) and the Singapore PREconception Study of long Term maternal and child Outcomes (S-PRESTO) cohorts. Interviewer-administered questionnaires were used to collect information on demography, lifestyle and childhood atopic eczema, rhinitis and wheeze development. Data training was performed using XGBoost, genetic algorithm and logistic regression models, and the top variables with the highest importance were identified. Additive explanation values were identified and inputted into a final multiple logistic regression model. Generalised structural equation modelling with maternal and child blood micronutrients, metabolites and cytokines was performed to explain possible mechanisms. RESULTS: The final study population included 1151 mother-child pairs. Our findings suggest that these childhood diseases are likely programmed in utero by the preconception and pregnancy exposomes through inflammatory pathways. We identified preconception alcohol consumption and maternal depressive symptoms during pregnancy as key modifiable maternal environmental exposures that increased eczema and rhinitis risk. Our mechanistic model suggested that higher maternal blood neopterin and child blood dimethylglycine protected against early childhood wheeze. After birth, early infection was a key driver of atopic eczema and rhinitis development. CONCLUSION: Preconception and antenatal exposomes can programme atopic eczema, rhinitis and wheeze development in utero. Reducing maternal alcohol consumption during preconception and supporting maternal mental health during pregnancy may prevent atopic eczema and rhinitis by promoting an optimal antenatal environment. Our findings suggest a need to include preconception environmental exposures in future research to counter the earliest precursors of disease development in children.

A Randomized, Double-Blind, Placebo-Controlled, Multicenter, 16-Week Trial to Evaluate the Efficacy and Safety of FB-401 in Children, Adolescents, and Adult Subjects (Ages 2 Years and Older) with Mild-to-Moderate Atopic Dermatitis.

BACKGROUND: Atopic dermatitis is a common chronic, relapsing, and remitting inflammatory skin disorder associated with cutaneous dysbiosis. Current treatment options often fail to adequately control the disease and have unfavorable safety profiles. There is a need for new options that address these treatment shortcomings. OBJECTIVE: The aim of the study was to evaluate the efficacy, safety, and tolerability of FB-401, a live therapeutic product of 3 strains of Roseomonas mucosa, compared to matching placebo applied topically 3 times per week to participants ages ≥2 years of age with mild-to-moderate atopic dermatitis. METHODS: A randomized, double-blind, placebo-controlled, parallel-group study was conducted. The primary outcome was the proportion of participants with 50% improvement in Eczema Area and Severity Index score from baseline at week 16. 154 subjects aged 2 or older with a clinical diagnosis of atopic dermatitis as defined by Hanifin and Rajka criteria with mild or moderate severity were randomized 1:1 via interactive web response system to FB-401 or placebo. RESULTS: The proportion of subjects who achieved the primary outcome was similar between both treatment groups, with no significant treatment group differences observed at any post-baseline visit. The number of treatment-emergent adverse events and the number of subjects with at least one were similar across treatment groups. One serious adverse event not related to treatment was reported. No treatment-emergent adverse events led to treatment discontinuation or study discontinuation. CONCLUSIONS: FB-401 showed an acceptable safety profile but failed to prove superior to placebo in treating children and adults with mild-to-moderate atopic dermatitis.

Risk of incident venous thromboembolism in patients with atopic dermatitis: systematic analysis of the literature and meta-analysis.

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease. While various inflammatory conditions have been linked to venous thromboembolism (VTE), the risk of VTE among patients with AD remains unclear. We sought to systematically review and meta-analyze population-based studies to determine the association between AD and incident VTE. A systematic review was performed of published studies in PubMed, Web of Science, Embase and Cochrane library from their inception to 27 May 2024. At least two reviewers conducted title/abstract, full-text review and data extraction. Cohort studies examining the association of AD with incident VTE were included. Quality of evidence was assessed using the Newcastle-Ottawa Scale. Six cohort studies, encompassing a total of 10,186,861 participants, were included. The meta-analysis revealed a significantly increased risk for incident VTE among AD patients (pooled hazard ratio (HR), 1.10; 95% CI, 1.00-1.21), with an incidence rate of VTE at 3.35 events per 1000 patient-years. Individual outcome analyses suggested that AD was associated with higher risks of deep vein thrombosis (pooled HR, 1.15; 95% CI, 1.04-1.27) but not pulmonary embolism (pooled HR, 0.99; 95% CI, 0.87-1.13). This systematic review and meta-analysis indicated an increased risk of incident VTE among patients with AD. Future studies are necessary to elucidate the underlying pathophysiology of the association between AD and VTE.

Response to Biologic Therapy in Skin of Colour Participants With Moderate-to-Severe Psoriasis and Atopic Dermatitis: A Systematic Review.

There has been a call to action to enhance representation of non-white individuals in dermatology clinical trials. Investigations in differential response to treatment across populations are limited, particularly in conditions of commonality, impact, distinct presentation, and diagnosis in non-white participants, such as atopic dermatitis and psoriasis. This systematic review summarized and identified if biologic treatment outcomes in moderate-to-severe atopic dermatitis and psoriasis varied in skin of colour (SOC) participants in phase 3 trials. MEDLINE, COCHRANE, and EMBASE databases were used to conduct the search following PROSPERO registration. Following screening of 3209 articles, 11 studies were collected with 1781 SOC participants with a mean age of 40.99 ± 6.3 years (range: 30.6-51.6 years). Male participants accounted for 76.9% (n = 1370/1781) of the sample, and Chinese, Japanese, Taiwanese, and Korean participants accounted for 64.3%, 24.2%, 4.5%, and 3.4% of participants, respectively. Participants with atopic dermatitis were treated with dupilumab (n = 216/388) and participants with psoriasis were treated with adalimumab (n = 313/1393), bimekizumab (n = 62/1393), ixekizumab (n = 13/1393), secukinumab (n = 117/1393), and ustekinumab (n = 289/1393). No significant SOC population-based outcomes were found across treatment groups. However, differences in baseline characteristics or comorbidities were found, suggesting race or ethnic background should be considered when treatment is prescribed in psoriasis or atopic dermatitis. Although no significant SOC participant differential response to treatment were found, large-scale randomized controlled trials investigating comparable treatment outcomes and stratifying results by SOC population in atopic dermatitis and psoriasis are warranted to confirm these findings.

Allergen immunotherapy for atopic dermatitis: Systematic review and meta-analysis of benefits and harms.

BACKGROUND: Atopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli such as allergens, irritants, and microbes. The role of environmental allergens (aeroallergens) in triggering AD remains unclear. OBJECTIVE: We systematically synthesized evidence regarding the benefits and harms of allergen immunotherapy (AIT) for AD. METHODS: As part of the 2022 American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters AD Guideline update, we searched the MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Global Resource for Eczema Trials, and Web of Science databases from inception to December 2021 for randomized controlled trials comparing subcutaneous immunotherapy (SCIT), sublingual immunotherapy (SLIT), and/or no AIT (placebo or standard care) for guideline panel-defined patient-important outcomes: AD severity, itch, AD-related quality of life (QoL), flares, and adverse events. Raters independently screened, extracted data, and assessed risk of bias in duplicate. We synthesized intervention effects using frequentist and Bayesian random-effects models. The GRADE approach determined the quality of evidence. RESULTS: Twenty-three randomized controlled trials including 1957 adult and pediatric patients sensitized primarily to house dust mite showed that add-on SCIT and SLIT have similar relative and absolute effects and likely result in important improvements in AD severity, defined as a 50% reduction in SCORing Atopic Dermatitis (risk ratio [95% confidence interval] 1.53 [1.31-1.78]; 26% vs 40%, absolute difference 14%) and QoL, defined as an improvement in Dermatology Life Quality Index by 4 points or more (risk ratio [95% confidence interval] 1.44 [1.03-2.01]; 39% vs 56%, absolute difference 17%; both outcomes moderate certainty). Both routes of AIT increased adverse events (risk ratio [95% confidence interval] 1.61 [1.44-1.79]; 66% with SCIT vs 41% with placebo; 13% with SLIT vs 8% with placebo; high certainty). AIT's effect on sleep disturbance and eczema flares was very uncertain. Subgroup and sensitivity analyses were consistent with the main findings. CONCLUSIONS: SCIT and SLIT to aeroallergens, particularly house dust mite, can similarly and importantly improve AD severity and QoL. SCIT increases adverse effects more than SLIT. These findings support a multidisciplinary and shared decision-making approach to optimally managing AD.

Investigating Distinct Skin Microbial Communities and Skin Metabolome Profiles in Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder influenced by genetic predisposition, environmental factors, immune dysregulation, and skin barrier dysfunction. The skin microbiome and metabolome play crucial roles in modulating the skin's immune environment and integrity. However, their specific contributions to AD remain unclear. We aimed to investigate the distinct skin microbial communities and skin metabolic compounds in AD patients compared to healthy controls (HCs). Seven patients with AD patients and seven HCs were enrolled, from whom skin samples were obtained for examination. The study involved 16S rRNA metagenomic sequencing and bioinformatics analysis as well as the use of gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) to detect metabolites associated with AD in the skin. We observed significant differences in microbial diversity between lesional and non-lesional skin of AD patients and HCs. Staphylococcus overgrowth was prominent in AD lesions, while Cutibacterium levels were decreased. Metabolomic analysis revealed elevated levels of several metabolites, including hypoxanthine and glycerol-3-phosphate in AD lesions, indicating perturbations in purine metabolism and energy production pathways. Moreover, we found a positive correlation between hypoxanthine and glycerol-3-phosphate and clinical severity of AD and Staphylococcus overgrowth. These findings suggest potential biomarkers for monitoring AD severity. Further research is needed to elucidate the causal relationships between microbial dysbiosis, metabolic alterations, and AD progression, paving the way for targeted therapeutic interventions.

S3 Guideline Atopic dermatitis: Part 1 - General aspects, topical and non-drug therapies, special patient groups.

This S3 guideline was created based on the European S3 guideline, with special consideration of the medical conditions in the German-speaking region and incorporating additions from the previous German-language version. The interdisciplinary guideline commission consisted of representatives from the German Dermatological Society, the Professional Association of German Dermatologists, the Austrian Society of Dermatology and Venereology, the Swiss Society of Dermatology and Venereology, the German Society for Allergology and Clinical Immunology, the German Society for Pediatric and Adolescent Medicine, the Professional Association of Pediatricians and Adolescent Medicine, the Society for Pediatric Allergology and Environmental Medicine, the German Society for Pediatric Rehabilitation and Prevention, the German Society for Psychosomatic Medicine and Medical Psychotherapy, the German Network for Health Services Research, the German Eczema Association and the German Allergy and Asthma Association. This first part of the guideline focuses on the definition and diagnostic aspects of atopic dermatitis (AD), addressing topical therapy as well as non-pharmacological treatment approaches such as UV therapy, psychoeducational therapy, dietary interventions for AD, allergen immunotherapy for AD, and complementary medicine. This part of the guideline also covers specific aspects of AD in children and adolescents, during pregnancy and lactation, and in the context of family planning. Additionally, it addresses occupational aspects of AD and highlights the perspective of the patients. The second part of the guideline, published separately, addresses the systemic therapy of AD.

Characteristics of atopic dermatitis patients using complementary and alternative medicine: A literature review.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease. Due to the burden of the disease, some patients try complementary and alternative medicine (CAM). OBJECTIVE: To identify characteristics associated with CAM use in children and adults with AD. METHODS: We conducted a literature review in accordance with the PRISMA international guidelines for literature reviews and meta-analyses. A systematic search was performed in the PubMed database. Qualitative and quantitative analyses using a χ2 test were performed to compare characteristics between CAM users and non-users. A p-value of <0.05 was considered statistically significant. RESULTS: Out of 514 articles retrieved, 12 studies were included, giving a total of 2240 patients. Our statistical analysis identified an association between CAM use and rhino-conjunctivitis (p = 0.015 in children, p = 0.041 in adults), topical corticosteroid use (p = 0.042 in children, p = 0.008 in adults), and daily application of moisturizing cream (p = 0.002 in children, p < 0.001 in adults). Gender did not affect the decision to use CAM (p > 0.05). In studies, a higher number of affected eczema sites (p < 0.001), prior use of more than two conventional treatments (p = 0.047), and food avoidance diets (p = 0.016) were predictive of CAM use in children. In adults, a younger age (p < 0.05), higher education level (p = 0.043), and lower age at AD onset (p = 0.004) were related to CAM use. DISCUSSION: To our knowledge, this is the first literature review focusing on socio-demographic and disease determinants related to CAM use among AD patients. The lack of homogeneity in measuring tools makes it difficult to compare and synthesize the studies.

Associations between Atopic Dermatitis and Behavior Difficulties in Children.

Background and Objectives: There has been increasing evidence that atopic dermatitis (AD) is associated with behavioral difficulties (BDs). There is currently a lack of evidence of how the severity of the disease determines BDs and what additional factors may contribute to their manifestation. The aim is to determine what kind of BDs occur in children with AD compared to healthy children and to find out what additional factors may contribute to the development of BDs in AD patients. Materials and Methods: This is a cross-sectional, prospective study with the application of a risk assessment instrument for behavior difficulties (Child Behavior Checklist, CBCL 6/18) in pediatric patients with AD and healthy controls (6-17 years) between 1 January 2020 and 31 December 2022. For statistical comparison, mainly Wilcoxon-Mann-Whitney and Student's t-test were used, considering a significance level of 5%. Results: This study included a total of 101 children: 48% with AD, 52% non-AD. The mean age was 10 ± 2.7 years for AD, and10.5 ± 3.1 years for the control patients. AD patients had higher internal behavior scale scores and T-scores (6.6 ± 6.4 vs. 9.6 ± 6.9 and 47.9 ± 9.5 vs. 52.3 ± 10.2, p = 0.01), anxiety/depression scale score and T-score (2.8 ± 2.7 vs. 4.3 ± 3.5 and 47.7 ± 8.4 vs. 52.5 ± 11, p = 0.02), and somatic problems scale score and T-score (2.1 ± 2.3 vs. 3.5 ± 3 and 47.6 ± 8.5 vs. 52.7 ± 10.9, p = 0.005). Patients with severe AD had sleep disturbance and itching scores higher than those with mild-moderate AD (5.4 ± 2.6 vs. 2.4 ± 2.2, p = 0.000 and 6.6 ± 2.4 vs. 4 ± 2.8, p = 0.001). The mean morning serum cortisol concentration was lower in AD patients compared to controls (252.91 ± 304.34 vs. 351.55 ± 126.09 nmol/L, p = 0.047). Conclusions: Children with AD present a higher risk of BDs than healthy controls. Patients with severe AD experience more sleep disturbances and a greater intensity of itching compared to mild-moderate AD. The occurrence of BDs was not related to serum cortisol levels. The cortisol level, severity, age, gender, duration of illness, intensity of pruritus, and sleep disturbance did not affect the development of BDs.

Two-sample Mendelian randomization analysis of causal relationship between eczema and autoimmune diseases. / åŒæ ·æœ¬å­Ÿå¾·å°”éšæœºåŒ–åˆ†æžæ¹¿ç–¹ä¸Žè‡ªèº«å ç–«æ€§ç–¾ç— ä¹‹é—´çš„å› æžœå ³ç³»ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: The causal relationship between eczema and autoimmune diseases has not been previously reported. This study aims to evaluate the causal relationship between eczema and autoimmune diseases. METHODS: The two-sample Mendelian randomization (MR) method was used to assess the causal effect of eczema on autoimmune diseases. Summary data from the Genome-Wide Association Study Catalog (GWAS) were obtained from the Integrative Epidemiology Unit (IEU) database. For eczema and autoimmune diseases, genetic instrument variants (GIVs) were identified according to the significant difference (P<5×10-8). Causal effect estimates were generated using the inverse-variance weighted (IVW) method. MR Egger, maximum likelihood, MR-PRESSO, and MR-RAPS methods were used for alternative analyses. Sensitivity tests, including heterogeneity, horizontal pleiotropy, and leave-one-out analyses, were performed. Finally, reverse causality was assessed. RESULTS: Genetic susceptibility to eczema was associated with an increased risk of Crohn's disease (OR=1.444, 95% CI 1.199 to 1.738, P<0.001) and ulcerative colitis (OR=1.002, 95% CI 1.001 to 1.003, P=0.002). However, no causal relationship was found for the other 6 autoimmune diseases, including systemic lupus erythematosus (SLE) (OR=0.932, P=0.401), bullous pemphigoid (BP) (OR=1.191, P=0.642), vitiligo (OR=1.000, P=0.327), multiple sclerosis (MS) (OR=1.000, P=0.965), ankylosing spondylitis (AS) (OR=1.001, P=0.121), rheumatoid arthritis (RA) (OR=1.000, P=0.460). Additionally, no reverse causal relationship was found between autoimmune diseases and eczema. CONCLUSIONS: Eczema is associated with an increased risk of Crohn's disease and ulcerative colitis. No causal relationship is found between eczema and SLE, MS, AS, RA, BP, or vitiligo.

[Children with atopic eczema and their environment]. / L'enfant atteint d'eczéma atopique et son environnement.

Taking an interest in the environment of a child suffering from eczema means understanding the word "environment" in the broadest possible sense: the child's lifestyle, family, social and cultural environment. By taking all these aspects into account, we can optimize the effectiveness of treatments, and avoid the multiple problems and comorbidities associated with moderate and severe eczema. It's up to caregivers to be vigilant about this, and to reposition the right gestures by spotting errors right from the start, even in the case of mild eczema. The best way to respond to this challenge, i.e. to help parents understand, is to draw on the principles of therapeutic patient education.

Emollients for preventing atopic eczema: Cost-effectiveness analysis of the BEEP trial.

BACKGROUND: Recent discoveries have led to the suggestion that enhancing skin barrier from birth might prevent eczema and food allergy. OBJECTIVE: To determine the cost-effectiveness of daily all-over-body application of emollient during the first year of life for preventing atopic eczema in high-risk children at 2 years from a health service perspective. We also considered a 5-year time horizon as a sensitivity analysis. METHODS: A within-trial economic evaluation using data on health resource use and quality of life captured as part of the BEEP trial alongside the trial data. Parents/carers of 1394 infants born to families at high risk of atopic disease were randomised 1:1 to the emollient group, which were advised to apply emollient (Doublebase Gel or Diprobase Cream) to their child at least once daily to the whole body during the first year of life or usual care. Both groups received advice on general skin care. The main economic outcomes were incremental cost-effectiveness ratio (ICER), defined as incremental cost per percentage decrease in risk of eczema in the primary cost-effectiveness analysis. Secondary analysis, undertaken as a cost-utility analysis, reports incremental cost per Quality-Adjusted Life Year (QALY) where child utility was elicited using the proxy CHU-9D at 2 years. RESULTS: At 2 years, the adjusted incremental cost was £87.45 (95% CI -54.31, 229.27) per participant, whilst the adjusted proportion without eczema was 0.0164 (95% CI -0.0329, 0.0656). The ICER was £5337 per percentage decrease in risk of eczema. Adjusted incremental QALYs were very slightly improved in the emollient group, 0.0010 (95% CI -0.0069, 0.0089). At 5 years, adjusted incremental costs were lower for the emollient group, -£106.89 (95% CI -354.66, 140.88) and the proportion without eczema was -0.0329 (95% CI -0.0659, 0.0002). The 5-year ICER was £3201 per percentage decrease in risk of eczema. However, when inpatient costs due to wheezing were excluded, incremental costs were lower and incremental effects greater in the usual care group. CONCLUSIONS: In line with effectiveness endpoints, advice given in the BEEP trial to apply daily emollient during infancy for eczema prevention in high-risk children does not appear cost-effective.

Dupilumab-associated ocular adverse events are predicted by low tear break-up time and correlate with high IL-33 tear concentrations in patients with atopic dermatitis.

Dupilumab, blocking IL-4 and IL-13 signals, improves atopic dermatitis and Quality of Life but might be also associated with the occurrence of ocular adverse events (OAEs). The main objective of our prospective study was to characterize the cytokine and chemokine profile in the tear fluid of dupilumab-treated patients with moderate-to- severe atopic dermatitis and to identify biomarkers predicting the occurrence of ocular adverse events. Patients with moderate-to-severe AD underwent dermatological and ophthalmological evaluation at the baseline (T0) and week 16 or at the time of an eventual ocular adverse events (T1). A multiplex immunoassay measuring multiple cytokines and chemokines in the tear fluid extracted during ocular examination at both T0 and T1 was performed. Thirty-nine patients with moderate-to-severe AD and treated with dupilumab were included in the study. Baseline tear fluid levels revealed a significantly higher concentration of type 2 cytokines and chemokines in AD patients than healthy controls. The occurrence of ocular adverse events during dupilumab therapy was associated with a significant increase of IL-33 tear fluid levels and a significantly lower tear break-up time, this latter also identified as predictive factor. Our findings suggest that the ophthalmological examination should be considered a valid support to identify patients at risk of developing OAEs and to provide their appropriate management.

Maternal fish oil and/or probiotics intervention: Allergic diseases in children up to two years old.

BACKGROUND: As n-3 long-chain polyunsaturated fatty acids and probiotics possess immunomodulatory properties, theoretically they could lower the risk of allergic diseases. But their effects remain controversial. We aimed to study the effects of fish oil and probiotics separately or in combination from early pregnancy onwards to lower the risk of allergic diseases in the infants. METHODS: In this double-blind trial, women (n = 439) in early pregnancies were randomized into four intervention groups: fish oil + placebo, probiotics + placebo, fish oil + probiotics, and placebo + placebo. Fish oil (1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid) and probiotic (Lacticaseibacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 1010 colony-forming units each) supplements were provided for daily consumption from randomization up to 6 months postpartum. All analyses were adjusted with pet ownership. RESULTS: No difference between the infants in the four intervention groups were found regarding physician-diagnosed food allergy, atopic eczema, or atopy at the age of 12 or 24 months (all p > .05). The probiotic intervention was associated with lower odds of recurrent wheezing at 24 months (OR 0.39, 95% CI 0.18-0.84, p = .017), but not at 12 months. CONCLUSIONS: The use of fish oil and/or probiotics from early pregnancy onwards did not lower the odds of childhood allergic diseases or atopy, with the exception of the probiotic intervention which decreased the risk of recurrent wheezing when the infants were two years old. This suggests that the incidence of asthma could also decrease later in childhood and thus these outcomes need to be clarified in further investigations.

Smoke exposure and childhood atopic eczema and food allergy: A systematic review and meta-analysis.

BACKGROUND: There is no consensus on the effect of timing and type of smoke exposure on early allergy development. This study aimed to determine the relationship between early eczema or food allergy/hypersensitivity development in children by firstly investigating the effect of smoke exposure across critical development periods and secondly by analyzing effects of parental atcive or passive smoking. METHODS: Four databases (PubMed, Web of Science, Scopus and Embase) were searched in May 2022 and assessed by two independent reviewers. Case-control, cross-sectional or cohort studies reporting on smoke exposure from preconception to postnatal periods and atopic eczema, food allergy and/or hypersensitivity outcomes by age 3 years were included. The Newcastle-Ottawa Scale was used to assess study quality. Random effects model was used to estimate the pooled risk ratios. RESULTS: From 1689 identified records, 32 studies with nearly 190,000 subjects were included. Parental smoking during preconception, pregnancy and postnatal periods was generally not associated with the risk of eczema, food allergy and food sensitisation development by age 3 years. Maternal active smoking during pregnancy was negatively associated with self-reported doctor diagnosis of eczema (RR = 0.87, 95% CI 0.77-0.98; I2 = 50.56) and maternal passive smoking during pregnancy was positively associated with clinician assessment of eczema in one study (RR = 1.38; 95% CI 1.06-1.79). CONCLUSION: Our findings highlighted the importance of in utero programming in early-life allergy development. Despite the weak evidence, our results suggest pregnant women should minimise their contact with second-hand smoke to prevent offspring eczema development. There is a need for greater utilisation of objective allergy assessments in future studies.