Risk factors and the temporal relationship between atopic dermatitis (AD) and atopic march remain understudied.

Determine risk factors for atopic march in early-onset AD patients and the temporality between AD and atopic march.

We used the MarketScan Research Database for our retrospective cohort analysis from 2010 to 2018, comparing infants diagnosed with AD before age 1 with controls without early-onset AD. Primary outcomes were hazard ratios (HRs) for the development of asthma, allergic rhinitis, and food allergy.

Compared to 55,174 controls, higher proportions of the 27,228 AD patients developed asthma (19.21% vs 8.65%, P < .001), allergic rhinitis (28.27% vs 12.62%, P < .001), food allergy (16.00% vs 2.27%, P < .001), and all atopic triad conditions (10.69% vs 0.71%, P < .001). Among AD patients, higher proportions developed the atopic triad if they were male (HR 1.66, 95% confidence interval [1.45-1.90]), had severe disease (HR 3.16, [2.77-3.60]), or had family atopy history (HR > 3.40, P < .001 for all comparisons). Among AD patients, 20.1% developed allergic rhinitis.

Our study was based on health care claims data.

Early-onset AD is associated with higher rates of developing atopic march conditions compared to controls. Particular attention should be paid toward risk factors and atopic march screening in early-onset AD patients.

Atopic dermatitis is a highly heritable and common inflammatory skin condition affecting children and adults worldwide. Multi-ancestry approaches to atopic dermatitis genetic association studies are poised to boost power to detect genetic signal and identify loci contributing to atopic dermatitis risk. Here, we present a multi-ancestry GWAS meta-analysis of twelve atopic dermatitis cohorts from five ancestral populations totaling 56,146 cases and 602,280 controls. We report 101 genomic loci associated with atopic dermatitis, including 16 loci that have not been previously associated with atopic dermatitis or eczema. Fine-mapping, QTL colocalization, and cell-type enrichment analyses identified genes and cell types implicated in atopic dermatitis pathophysiology. Functional analyses in keratinocytes provide evidence for genes that could play a role in atopic dermatitis through epidermal barrier function. Our study provides insights into the etiology of atopic dermatitis by harnessing multiple genetic and functional approaches to unveil the mechanisms by which atopic dermatitis-associated variants impact genes and cell types.

Advances in sequencing technologies have facilitated the identification of the genes and mechanisms for many inherited skin diseases. Although targeted nucleic acid therapeutics for diseases in other organs have begun to be deployed in patients, the goal of precise therapeutics for skin diseases has not yet been realized. First, we review the current and emerging nucleic acid-based gene-editing and delivery modalities. Next, current and emerging viral and nanoparticle vehicles for the delivery of gene therapies are reviewed. Finally, specific skin diseases that could benefit optimally from nucleic acid therapies are highlighted. By adopting the latest technologies and addressing specific barriers related to skin biology, nucleic acid therapeutics have the potential to revolutionize treatments for patients with skin disease.

Hundreds of genetic associations for asthma have been identified, yet translating these findings into mechanistic insights remains challenging. We leveraged plasma proteomics from the UK Biobank Pharma Proteomics Project (UKB-PPP) to identify biomarkers and effectors of asthma risk or heterogeneity using genetic causal inference approaches. We identified 609 proteins associated with asthma status (269 proteins after controlling for body mass index [BMI] and smoking). Analysis of genetically predicted protein levels identified 70 proteins with putative causal roles in asthma risk, including known drug targets and proteins without prior genetic evidence in asthma (e.g., GCHFR, TDRKH, and CLEC7A). The genetic architecture of causally associated proteins provided evidence for a Toll-like receptor (TLR)1-interleukin (IL)-27 asthma axis. Lastly, we identified evidence of causal relationships between proteins and heterogeneous aspects of asthma biology, including between TSPAN8 and neutrophil counts. These findings illustrate that integrating biobank-scale genetics and plasma proteomics can provide a framework to identify therapeutic targets and mechanisms underlying disease risk and heterogeneity.

Background: The role of gut dysbiosis in the pathophysiology of atopic dermatitis (AD) through immune system (IS) imbalance is a novel line of investigation currently under discussion. This study aimed to characterize compare the composition and functional profile of the gut microbiota (GM) between adults with AD and healthy individuals. Methods: Observational cross-sectional study, where fecal samples from 70 adults (38 patients and 32 controls) were analyzed using metagenomics and bioinformatics. Results: Differences between the GM of patients with AD and healthy individuals were demonstrated. Reduced microbial diversity was found in subjects with AD. Bacterial species with lower abundance primarily belonged to the families Ruminococcaceae, Akkermansiaceae, and Methanobacteriaceae. Several microbial metabolic pathways were found to be decreased in patients with AD, including amino acid biosynthesis, vitamin biosynthesis, fatty acids and lipids biosynthesis, and energy metabolism. Conclusion: Adults with AD exhibited a distinct GM compared to healthy individuals. Changes were demonstrated both compositionally and functionally. Further investigation is mandatory to elucidate the potential link and causal relationship between gut dysbiosis and AD, which may be crucial for a deeper understanding of the disease's pathophysiology and the development of novel therapeutic approaches.

Atopic dermatitis (AD) is a chronic, recurrent inflammatory skin disorder characterized by dry skin, eczema-like lesions, and severe itching. The multifaceted etiology of AD, which is not yet fully understood, includes genetic predispositions, immune dysfunctions(such as an impaired skin barrier and abnormal immune regulation), imbalances in the skin microbiota, and environmental factors, among others. In the field of AD treatment, the combination of traditional Chinese medicine and modern medicine is becoming an emerging trend. Given the potenzial side effects and reduced efficacy of conventional therapeutic drugs, Chinese herbal medicines offer patients new treatment options because of their unique efficacy and low toxicity. Some saffron extracts derived from saffron and gardenia, such as crocin, crocetin, and safranal, have shown promising potenzial in the treatment of AD. These natural ingredients not only possess anti-inflammatory and immunomodulatory properties similar to those of traditional Chinese medicines but also demonstrate excellent effects in promoting the repair of damaged skin barriers. Therefore, this article reviews the therapeutic potenzial of saffron extract in the treatment of AD, with a special focus on its mechanisms and potenzial interventions, while emphasizing the importance of herbal medicines as alternatives to traditional treatments, providing AD patients with safer and more effective treatment options.

Atopic dermatitis (AD) is the most common inflammatory skin disease in the pediatric age group, affecting 15%-20% of children globally. Initial treatment modes include hydration, occlusive topical medicines, antimicrobial treatment, phototherapy, and systemic immune suppressants in the case of severe to moderate refractory AD. However, there is a lack of head-to-head studies on the choice of topical and systemic therapies for moderate to severe AD in the pediatric age group.

This systematic review aimed to determine the efficacy and safety of topical and systemic treatments for moderate-to-severe AD in the pediatric age group.

A systematic review was performed following the Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines. A search of articles was done from PubMed and Google Scholar from 1975 to 2023.

We found a total of 1114 possible clinical trials. Of these, 68 articles fulfilled the eligibility criteria. Thirty-four articles discussed topical therapies, which included corticosteroids, calcineurin inhibitors, and emollients, and 34 articles were about systemic therapies, consisting of cyclosporine, dupilumab, upadacitinib, thymopentin, omalizumab, antihistamines, probiotics, and others. Out of 68 studies, 41 were randomized controlled trials.

Based on the study results, we conclude that topical steroids and calcineurin inhibitors are effective and safe in mild to moderate pediatric AD. It was also demonstrated that while systemic monotherapy with dupilumab (in age groups younger than 6 months) and JAK inhibitors (like abrocitinib and upadacitinib in those younger than 12 years) is highly effective in rapidly reducing severity scores, their high cost and limited availability restrict their use in countries like India. In such settings, cyclosporine (and sometimes oral prednisolone in tapering doses over 2 weeks) is still recommended as a first-line therapy in severe AD while planning for steroid-sparing agents.

Atopic dermatitis (AD) is a common chronic inflammatory skin condition that significantly impairs patients' quality of life as a result of intense itching and persistent eczematous lesions. Although AD has a multifaceted etiology-including genetic predisposition, environmental triggers, barrier dysfunction, and dysregulated immune responses-interleukin-4 (IL-4) has a recognized central role in its pathogenesis. This narrative review explores the role of IL-4 in the pathophysiology of AD, its contribution to the atopic march, and the therapeutic impact of IL-4 inhibition. IL-4 plays a critical role in skin barrier dysfunction, dysbiosis, pruritus, and inflammation, all of which contribute to the debilitating symptoms of AD. Moreover, IL-4 is implicated in other atopic conditions, such as asthma, allergic rhinitis, and food allergies, underscoring its role beyond AD and its importance in the atopic march. Recent advances in targeted therapies, particularly IL-4/IL-13 signaling inhibitors, have changed AD management. Dupilumab, an IL-4 receptor antagonist, has demonstrated significant efficacy in reducing AD symptoms and enhancing patient outcomes in both children and adults. In addition to symptomatic relief, suppressing IL-4 signaling may also offer potential for disease modification, altering AD's progression and possibly preventing the onset of other atopic conditions. This review highlights the crucial role of IL-4 as a therapeutic target in AD. By understanding the role of IL-4 in AD pathogenesis and exploring the therapeutic implications of targeting IL-4 pathways, this work can contribute to guide future research concerning treatment approaches and also emphasize the need for early and targeted interventions to mitigate disease impact and ultimately improve patient quality of life.

Significant advancements have been made in understanding the cellular and molecular mechanisms of type 2 immunity in allergic diseases such as asthma, allergic rhinitis, chronic rhinosinusitis, eosinophilic esophagitis (EoE), food and drug allergies, and atopic dermatitis (AD). Type 2 immunity has evolved to protect against parasitic diseases and toxins, plays a role in the expulsion of parasites and larvae from inner tissues to the lumen and outside the body, maintains microbe-rich skin and mucosal epithelial barriers and counterbalances the type 1 immune response and its destructive effects. During the development of a type 2 immune response, an innate immune response initiates starting from epithelial cells and innate lymphoid cells (ILCs), including dendritic cells and macrophages, and translates to adaptive T and B-cell immunity, particularly IgE antibody production. Eosinophils, mast cells and basophils have effects on effector functions. Cytokines from ILC2s and CD4+ helper type 2 (Th2) cells, CD8 + T cells, and NK-T cells, along with myeloid cells, including IL-4, IL-5, IL-9, and IL-13, initiate and sustain allergic inflammation via T cell cells, eosinophils, and ILC2s; promote IgE class switching; and open the epithelial barrier. Epithelial cell activation, alarmin release and barrier dysfunction are key in the development of not only allergic diseases but also many other systemic diseases. Recent biologics targeting the pathways and effector functions of IL4/IL13, IL-5, and IgE have shown promising results for almost all ages, although some patients with severe allergic diseases do not respond to these therapies, highlighting the unmet need for a more detailed and personalized approach.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder with significant implications for patient quality of life and a well-documented association with the atopic march. Recent advancements in biomarker research have unveiled critical insights into AD pathogenesis, diagnosis, prognosis, and therapeutic monitoring. This comprehensive review evaluates the utility of emerging biomarkers, including cytokines, chemokines, genetic markers, and microbiome-related components, in understanding the disease mechanisms and stratifying patient care. The role of minimally invasive diagnostic techniques, such as tape stripping and RNA monitoring, is highlighted, offering innovative approaches to pediatric populations. Furthermore, this review explores the biomarkers that predict disease progression, therapeutic response, and comorbidities, including food allergies and asthma. Personalized treatment strategies based on endotype-specific biomarkers are discussed as a future direction for improving clinical outcomes. Despite promising findings, the integration of biomarkers into routine practice necessitates further validation through large-scale studies. This work underscores the transformative potential of biomarker-driven approaches in enhancing the management of AD in children and its associated conditions.

Toll-like receptors (TLR), the key players of the innate immune system, contribute to the pathogenesis of atopic dermatitis (AD) through multiple pathways. TLRs play a crucial role in delaying barrier repair, promoting Th2-mediated dermatitis, shifting the response toward Th1 in the chronic phase, and contributing to the establishment of the itch-scratch cycle, as well as mediating the effects of UV radiation. The dysregulation of proinflammatory and immunomodulatory effects of TLRs can be attributed to their ligand structures, receptor heterodimerization, the relative frequency of each TLR, interactions with other receptors/signalling pathways, cytokine milieu, and genetic polymorphisms. Current AD treatments like vitamin-D analogs, tacrolimus, and cyclosporine partially work through TLR modulation. Direct TLR stimulation using different compounds has shown therapeutic benefits in preclinical studies. However, significant challenges exist, including off-target effects due to ubiquitous TLR expression and complex roles in immune responses. Future directions include CRISPR-based gene editing to understand TLR functions, development of specific TLR modulators for targeted therapy, and machine learning applications to predict drug responses and identify novel ligands. Patient heterogeneity, including the presence or absence of polymorphisms, variations in TLR expression levels, and differences in immune responses, underscores the need for personalized therapeutic approaches.

Background: Systemic advanced therapies, including biologic drugs and Janus kinase (JAK) inhibitors, have revolutionized atopic dermatitis management. The increasing number of available options for such complex diseases demands careful treatment selection for each patient, considering numerous variables. Comparative analyses of these treatment modalities in the real world are still limited. Only a faithful basal characterization would enable posterior meaningful and accurate comparisons of the efficacy and safety profiles of these groups of drugs. This communication focuses on describing and comparing the baseline demographics and comorbidities of patients with atopic dermatitis currently treated with biologic therapies versus JAK inhibitors in our setting. Methods: We conducted an observational, descriptive, and ambispective study across three hospitals covering a population of over 500,000 inhabitants from January 2019 to December 2024. Baseline demographic data, anthropometric measures, lifestyle factors, cardiovascular risk factors, and comorbidities were analyzed using descriptive and inferential statistics. Additionally, basal severity and effectivity over time have also been compared. Results: A total of 150 patients were analyzed. A total of 102 had received biological therapies (dupilumab or tralokinumab), whereas 48 patients had received JAK inhibitors (upadacitinib, baricitinib, or abrocitinib). Ages ranged from 11 to 76 years. The overall cohort had a mean age of 35.87 ± 14.37 years and a male predominance (male-to-female ratio 1.63:1). Hypertension was more prevalent in the JAK inhibitors group (p = 0.0175), yet other cardiovascular risk factors, body measurements, atopic and non-atopic comorbidities, and disease severity were comparable across both groups. Conclusions: This study helped to characterize the baseline characteristics of patients treated with advanced systemic therapies in a real-world clinical setting. It pointed to just slight differences between the profiles of patients treated with biologics versus JAK inhibitors. This homogeneity in baseline characteristics sets the ground for further future comparisons of treatment outcomes in this cohort as potential confounding factors related to group imbalances are minimized.

Allergic and autoimmune disorders are characterised by dysregulation of the immune responses to otherwise inert environmental substances and autoantigens, leading to inflammation and tissue damage. Their incidence has constantly increased in the last decades, and their co-occurrence defies current standards in patient care. For years, allergy and autoimmunity have been considered opposite conditions, with IgE and Th2 lymphocytes cascade driving canonical allergic manifestations and Th1/Th17-related pathways accounting for autoimmunity. Conversely, growing evidence suggests that these conditions not only share some common inciting triggers but also are subtended by overlapping pathogenic pathways. Permissive genetic backgrounds, along with epithelial barrier damage and changes in the microbiome, are now appreciated as common risk factors for both allergy and autoimmunity. Eosinophils and mast cells, along with autoreactive IgE, are emerging players in triggering and sustaining autoimmunity, while pharmacological modulation of B cells and Th17 responses has provided novel clues to the pathophysiology of allergy. By combining clinical and therapeutic evidence with data from mechanistic studies, this review provides a state-of-the-art update on the complex interplay between allergy and autoimmunity, deconstructing old dichotomic paradigms and offering potential clues for future research.

Atopy is defined as a predisposition to hypersensitivity reactions against a range of antigens. It is characterized by the activation of CD4+ T helper type 2 (Th2) cells and an increased production of immunoglobulin E (IgE). The most common atopic conditions are atopic dermatitis, asthma, allergic rhinitis, food allergies, and atopic ocular diseases. Atopic keratoconjunctivitis (AKC) is a chronic, bilateral inflammatory condition affecting the ocular surface, frequently occurring in conjunction with atopic dermatitis. It is not uncommon for patients to present with multiple conditions simultaneously or in a sequential manner. A comprehensive understanding of the underlying mechanisms of atopic diseases is essential for the effective clinical evaluation and treatment. Recent research has underscored the pivotal role of the microbiota in the pathogenesis of atopic dermatitis and atopic eye diseases, with alterations in microbial composition (dysbiosis) being linked to a spectrum of atopic conditions. Probiotics are currently being investigated as a potential treatment option for restoring microbial balance and alleviating disease symptoms. This review examines the relationship between atopic dermatitis, atopic keratoconjunctivitis, and the microbiota, evaluating the current evidence and exploring the potential of probiotics as a novel therapeutic approach.

FLG and FLG2 proteins are expressed in the outer layers of the epidermis, where they are vital in epidermal differentiation and skin barrier formation. Filaggrinopathies involving dysfunctions in these proteins are associated with a spectrum of phenotypic presentations, from monogenic to multifactorial conditions. This review examines biosynthesis and function of FLG and FLG2 proteins and evaluates their molecular pathogenesis in filaggrinopathies. Moreover, genotype-phenotype correlations are assessed, emphasizing genetic diagnosis complexities and diverse immune dysregulation patterns. Finally, it examines ongoing immunotherapeutic approaches by targeting different cytokines as promising treatment options for filaggrinopathies management.

Atopic dermatitis (AD) is mainly driven by type 2 inflammation and often treated with topical agents. Studies comparing differences in biomarkers between these treatments are lacking.

The aim of this study was to evaluate the effects of topical betamethasone 17-valerate 0.1% and tacrolimus 0.1% ointment on skin barrier function and inflammatory biomarkers in skin and blood in adults with AD.

In this randomized parallel-group double-blind double-dummy active-comparator study design, 36 adults with AD were treated with either whole-body topical corticosteroid (betamethasone ointment 0.1% plus placebo once daily, n = 18) or calcineurin inhibitor (tacrolimus ointment 0.1% twice daily, n = 18). At baseline, after 2 weeks of daily treatment and after further 4 weeks of twice-weekly maintenance treatment, we evaluated AD severity, levels of natural moisturizing factor (NMF) and cytokines in the skin and blood and characterized circulating T cells.

Mean AD severity at baseline corresponded to moderate disease and decreased significantly in both groups. Levels of NMF increased significantly in the tacrolimus group after 2 weeks of treatment (p = 0.002) and tended to increase more than betamethasone at week 6 (p = 0.06). Most skin cytokines decreased with both treatments. However, IL-8, IL-18, IL-22, IP-10, MDC, MMP-9 and TARC were significantly more decreased with betamethasone than tacrolimus after 2 weeks, while after 6 weeks this was only the case for IL-8 and MMP-9. Approximate half of the systemic cytokines decreased significantly with both treatments, but betamethasone decreased MDC significantly more after 2 weeks of treatment. T-cell characterization analyses indicated slight differences in the expression and activation of T cells between groups.

Topical treatment of AD with betamethasone and tacrolimus ointment effectively reduced disease severity, cutaneous and systemic inflammatory markers. Betamethasone was more effective in decreasing inflammation, but tacrolimus improved skin hydration (NMF levels) more than betamethasone.

Dupilumab is a monoclonal antibody targeting interleukin-4 and interleukin-13, approved for the treatment of multiple T2 diseases and more recently for Eosinophilic Esophagitis (EoE). EoE is a chronic T2 inflammatory disease, believed to be a member of the "atopic march", due to multiple similarities with other atopic diseases, ranging from epidemiology to genetics and pathophysiology. Although often co-existing in the same patient, these diseases are still treated as separated entities by different specialists, resulting in polypharmacy and chronic use of steroids. Thus, a shared-decision approach by a multidisciplinary team composed of different specialists might improve clinical management and outcomes. Yet, prospective data on the effectiveness of dupilumab as a single agent for multiple T2 inflammatory diseases are lacking, since only few case reports and small studies have been published so far reporting outcomes in patients affected by multiple T2 diseases. The purpose of this review is to illustrate the rationale and clinical evidence supporting the possibility of using dupilumab as a single therapeutic agent in those patients affected by multiple T2 diseases in addition to EoE.

Neutrophils are short-lived cells of the innate immune system and represent 50-70% of the circulating leucocytes. Their primary role is antimicrobial defence which they accomplish through rapid migration to sites of inflammation followed by phagocytosis, degranulation, and the release of neutrophil extracellular traps (NETosis). While previously considered terminally differentiated cells, they have been shown to have great adaptability and to play a role in conditions ranging from cancer to autoimmunity. This review focuses on their role in allergic disease. In particular: their role as potential amplifiers of type 1 hypersensitivity reactions leading to anaphylaxis; their involvement in alternative pathways of food and drug allergy; their role in allergic rhinitis and asthma and neutrophil dysfunction in atopic dermatitis. The use of potential biomarkers and therapeutic targets is also discussed with a view to guiding future research.

Studies have identified increased risks of pregnancy complications in expectant mothers with atopic dermatitis (AD). However, the associations between maternal AD and adverse pregnancy or offspring outcomes in Asians remain unexplored. Our aim was to investigate the relationship between maternal AD and adverse pregnancy and offspring outcomes in Taiwan.

This retrospective cohort study collected data from Taiwan's National Health Insurance Research Database and the Taiwan Maternal and Child Health Database between 2003 and 2019. We recruited 15,495 AD mothers and 77,475 non-AD mothers, as well as 19,173 children born to AD mothers and 95,865 children born to non-AD mothers, using propensity score matching. Pregnancy and offspring outcomes were compared in the maternal and offspring cohorts, respectively.

AD mothers had higher risks of threatened abortion, preeclampsia/eclampsia, premature rupture of membranes, threatened preterm labor, fetal growth restriction, antepartum hemorrhage, postpartum hemorrhage, anemia, surgical complications, infections, pulmonary events, and renal events, with adjusted hazard ratios of 1.09-1.71. Children born to AD mothers had increased risks of AD, allergic rhinitis, asthma, alopecia areata, and attention deficit hyperactivity disorder, with adjusted hazard ratios of 1.05-2.29.

There is a significant association between maternal AD and adverse pregnancy and offspring outcomes in Taiwan.

Background/Objectives: Research on the relationship between gut microbiota (GM) and atopic dermatitis (AD) has seen a growing interest in recent years. The aim of this systematic review was to determine whether differences exist between the GM of adults with AD and that of healthy adults (gut dysbiosis). Methods: We conducted a systematic review based on the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The search was performed using PubMed, EMBASE, and Web of Science. Observational and interventional studies were analyzed. Results: Although the studies showed heterogeneous results, some distinguishing characteristics were found in the intestinal microbial composition of adults with dermatitis. Even though no significant differences in diversity were found between healthy and affected adults, certain microorganisms, such as Bacteroidales, Enterobacteriaceae, and Clostridium (perfringens), were more characteristic of the fecal microbiota in adults with AD. Healthy individuals exhibited lower abundances of aerobic bacteria and higher abundances of short-chain fatty acid-producing species and polyamines. Clinical trials showed that the consumption of probiotics (Bifidobacterium and/or Lactobacillus), fecal microbiota transplants, and balneotherapy modified the fecal microbiota composition of participants and were associated with significant improvements in disease management. Conclusions: In anticipation of forthcoming clinical trials, it is essential to conduct meta-analyses that comprehensively evaluate the effectiveness and safety of interventions designed to modify intestinal flora in the context of AD. Preliminary evidence suggests that certain interventions may enhance adult AD management.

The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide. It attributes their onset to a functionally impaired epithelial barrier triggered by the toxicity of the exposed substances, associated with microbial dysbiosis, immune system activation, and inflammation. Diseases encompassed by the epithelial barrier theory share common features such as an increased prevalence after the 1960s or 2000s that cannot (solely) be accounted for by the emergence of improved diagnostic methods. Other common traits include epithelial barrier defects, microbial dysbiosis with loss of commensals and colonization of opportunistic pathogens, and circulating inflammatory cells and cytokines. In addition, practically unrelated diseases that fulfill these criteria have started to emerge as multimorbidities during the last decades. Here, we provide a comprehensive overview of diseases encompassed by the epithelial barrier theory and discuss evidence and similarities for their epidemiology, genetic susceptibility, epithelial barrier dysfunction, microbial dysbiosis, and tissue inflammation.

Atopic dermatitis is highly heterogeneous with respect to pathogenesis, clinical manifestations, and treatment response. There is evidence that ancestry and skin type each contribute to this heterogeneity, indicating the need to improve understanding of disease mechanisms in diverse populations. Methods to integrate multiomics studies have been well-described, but this review focuses on the importance and the strategies needed to integrate data across different ancestral groups, focusing, because of data availability, on Asian and European populations. Skin scientists and clinicians will each benefit from an understanding of how the multiple complimentary layers of omics data may inform future clinical management, from insight into disease pathogenesis and treatment targets.

Exposure to toxic substances, introduced into our daily lives during industrialization and modernization, can disrupt the epithelial barriers in the skin, respiratory, and gastrointestinal systems, leading to microbial dysbiosis and inflammation. Athletes and physically active individuals are at increased risk of exposure to agents that damage the epithelial barriers and microbiome, and their extreme physical exercise exerts stress on many organs, resulting in tissue damage and inflammation. Epithelial barrier-damaging substances include surfactants and enzymes in cleaning products, laundry and dishwasher detergents, chlorine in swimming pools, microplastics, air pollutants such as ozone, particulate matter, and diesel exhaust. Athletes' high-calorie diet often relies on processed foods that may contain food emulsifiers and other additives that may cause epithelial barrier dysfunction and microbial dysbiosis. The type of the material used in the sport equipment and clothing and their extensive exposure may increase the inflammatory effects. Excessive travel-related stress, sleep disturbances and different food and microbe exposure may represent additional factors. Here, we review the detrimental impact of toxic agents on epithelial barriers and microbiome; bring a new perspective on the factors affecting the health and performance of athletes and physically active individuals.

Atopic diseases, including atopic dermatitis (AD), food allergy (FA), asthma, and allergic rhinitis (AR) are closely related to inflammatory diseases involving different body sites (i.e. the skin, airway, and digestive tract) with characteristic features including specific IgE to allergens (so-called "atopy") and Th2 cell-mediated inflammation. It has been recognized that AD often precedes the development of other atopic diseases. The progression from AD during infancy to FA or asthma/AR in later childhood is referred to as the "atopic march" (AM). Clinical, genetic, and experimental studies have provided evidence that allergen sensitization occurring through AD skin could be the origin of the AM. Here, we provide an updated review focusing on the role of the skin in the AM, from genetic mutations and environmental factors associated with epidermal barrier dysfunction in AD and the AM to immunological mechanisms for skin sensitization, particularly recent progress on the function of key cytokines produced by epidermal keratinocytes or by immune cells infiltrating the skin during AD. We also highlight the importance of developing strategies that target AD skin to prevent and attenuate the AM.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder associated with significant morbidity, including pruritus, recurrent skin lesions, and immune dysregulation. This study aimed to investigate the antioxidative and anti-AD effects of peptides derived from hydrolyzed Sebastes schlegelii (Korea rockfish) tail by-products. Hydrolysates were prepared using various enzymes, including Alcalase, Flavourzyme, Neutrase, and Protamex. Among them, Protamex hydrolysates demonstrated the highest ABTS radical scavenging activity with an RC50 value of 69.69 ± 0.41 µg/mL. Peptides were further isolated from the Protamex hydrolysate using dialysis, fast protein liquid chromatography (FPLC), and high-performance liquid chromatography (HPLC). The most active peptide, STPO-B-II, exhibited a single peak and was identified as a sequence of Glu-Leu-Ala-Lys-Thr-Trp-His-Asp-Met-Lys, designated as MP003. In vivo experiments were conducted using a 2,4-dinitrochlorbenzene (DNCB)-induced AD model in NC/Nga mice. The isolated peptide, MP003, showed significantly reduced AD symptoms, including erythema, lichenification, and collagen deposition. Additionally, MP003 decreased epidermal and dermal thickness, eosinophil, and mast cell infiltration and downregulated the expression of pro-inflammatory cytokines IL-1β, IL-6, and IgE in serum and skin tissues. These findings suggest that peptides derived from Sebastes schlegelii tail by-products may serve as potential therapeutic agents for AD.

Idiopathic anaphylaxis (IA) is a severe allergic reaction without identifiable external triggers, presenting significant challenges in diagnosis and management. However, growing evidence suggests that many cases classified as idiopathic may actually be driven by cofactors such as exercise, hormonal fluctuations, medications, or hidden allergens. This mini-review explores the evolving understanding of IA, highlighting the role of these cofactors in triggering or amplifying anaphylactic reactions. It emphasizes how advances in diagnostic tools, including component-resolved diagnostics, are helping to identify previously undetected allergens, leading to more accurate diagnoses and reducing the prevalence of true idiopathic cases. As our knowledge of anaphylaxis and its underlying mechanisms deepens, the need for comprehensive evaluations that account for cofactor involvement becomes increasingly clear. Continued research in this area is essential to improve patient outcomes and better manage this complex condition.

Atopic dermatitis (AD) is a complex immune-mediated abnormality of the skin characterized by impaired barrier function, eczematous dermatitis, chronic pruritus and itch. The immunological response in AD is mediated by a Th2-dominated immune response in the early acute phase followed by a Th1/ Th2 mixed immune response in the chronic phase. AD is the first step of the "atopic march" that progresses into food allergy, allergic rhinitis, and asthma. Different models are indispensable for studying AD pathogenesis and for designing pre-clinical studies for therapeutic discovery. They reflect the characteristic morphological features of typical human AD with regard to epidermal thickening, hyperkeratosis, acanthosis, and spongiosis and help understand the immunopathogenesis of the disease with respect to IgE levels and cellular infiltration of eosinophils, mast cells, and lymphocytes. Although it is difficult to replicate all human AD clinical features in a model, several AD in vivo models comprising spontaneous, induced, transgenic, and humanized and in vitro models, including 2D, co-culture, and 3D, have been described previously. However, several questions remain regarding whether these models satisfactorily reflect the complexity of human AD. Therefore, this review comprehensively highlights the diversity of currently available models and provides insights into the selection of suitable models based on research questions. It also summarizes the diverse mechanisms associated with each model, which may be valuable for better study design to test new therapeutic options.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by persistent itching. Conventional treatments for AD include topical corticosteroids and calcineurin inhibitors, but there are emerging therapies targeting the JAK-TYK2 pathway that are promising for the treatment of AD.

This review comprehensively explores the pathogenesis, triggers, clinical manifestations, and conventional treatment options for AD. In addition, we discuss novel therapeutic agents targeting alternative signaling pathways, with a focus on clinical trials evaluating tyrosine kinase 2 (TYK2) inhibitors, including systemic and topical agents. We also provide a detailed assessment of ICP-332 efficacy, safety, and potential adverse effects in moderate-to-severe AD.

Janus kinase inhibitors that have been recently approved have shown promise for the treatment of AD, especially for patients with severe phenotypes. Preliminary findings from randomized controlled trials suggest that TYK2 inhibitors exhibit rapid efficacy and acceptable safety in the management of AD; however, additional investigations, including long-term trials, are warranted to fully understand their efficacy and safety profile.

The epidermal barrier acts as a defense against external agents as well as helps to maintain body homeostasis. Polynucleotides (PN), exogenous DNA fragments, promote wound repair through their stimulatory and anti-inflammatory effects. Recent findings indicate a synergistic effect of PN and hyaluronic acid (HA) combinations in regulating inflammation and promoting cell proliferation. This study aims to elucidate the effects of PN and HA on repairing the epidermal barrier following its disruption by tape stripping (TS) in a mouse model.

After disrupting the epidermal barrier using TS, a formulation containing PN (14 mg/mL) and HA (6 mg/mL) was applied. Trans-epidermal water loss (TEWL) was measured at 0, 3, 6, 24, 48, and 72 h. Mice were euthanized after the final application at 72 h, and tissue samples were analyzed for epidermal/dermal thickness, neutrophil infiltration, and filaggrin expression.

We observed a significant reduction in TEWL in the PN+HA group compared to that in the control group (20.8 ± 0.5 vs. 43.7 ± 0.5 g/m2h at 72 h, p < 0.05), indicating an improvement in barrier function. Histological evaluation showed decreased epidermal and dermal thickening in the PN+HA group compared to that in the control group (epidermal: 29.4 ± 2.2 vs. 57.9 ± 3.5 μm; dermal: 464.8 ± 25.9 vs. 825.9 ± 44.8 μm, both p < 0.05). Additionally, neutrophil infiltration in the dermis was significantly reduced, and filaggrin protein levels were significantly higher in the PN+HA group compared to those in the control group (4.8 ± 0.4 vs. 21.1 ± 3.3 for neutrophils; 0.84 ± 0.04 vs. 0.42 ± 0.03 for filaggrin, both p < 0.05).

These results suggest that PN+HA may be an effective therapeutic strategy for repairing skin barrier damage.

The skin is the largest immunologic organ in the body and contains immune cells that play a role in both food allergen sensitization and desensitization. The dual allergen exposure hypothesis posits that sensitization to food allergens may occur with cutaneous exposure on inflamed skin, eg, atopic dermatitis, but early oral consumption generally leads to tolerance. However, only one-third of children with atopic dermatitis develop a food allergy, suggesting that there is a more complex mechanism for allergen sensitization. Emerging evidence suggests that the outcome of cutaneous allergen exposure is context-dependent and largely influenced by the state of the skin barrier with healthy skin promoting natural tolerance. Current research supports the ability to induce desensitization through repeated application of allergens to the skin, known as epicutaneous immunotherapy. Preclinical research with an occlusive patch has demonstrated a significantly reduced T-helper cell type 2-driven immunologic response when applied to intact, uninflamed skin and induction of a unique population of regulatory T cells that express a broader range of homing receptors, which may be able to maintain sustained protection. In clinical studies of children aged 1 through 11 years with a peanut allergy, epicutaneous immunotherapy with an occlusive patch led to significant desensitization with no major differences in efficacy or safety between children with and without atopic dermatitis. These data begin to answer the conundrum of how allergens that are applied to the skin can lead to both sensitization and desensitization, and future studies should enable us to optimize the power of the skin as a complex immunologic organ to treat allergic, autoimmune, and autoinflammatory disorders.

Background: Mutations in filaggrin (FLG), the gene that codes for the skin barrier protein, have been shown to be associated with atopic dermatitis (AD). Objective: The objectives of this study were to determine the effects of genetic counseling and parental education on infants at a high risk of AD. Methods: We enrolled 7521 newborns in Taiwan from January 1, 2016, to March 30, 2020, and all of them received genetic testing encompassing 20 known FLG mutations. The genetic counseling and AD prevention and care team consisted of pediatricians, dermatologists, social workers, and genetic counselors. The counseling was arranged for at least 30 minutes within 45 days after delivery. Results: A total of 2963 high-risk infants (39.4%) were identified. Homozygous c.1432C>T was the most commonly identified mutation. A total of 418 neonates' parents were stratified into counseling and noncounseling groups, where the effect of parental education was evaluated. The genetically stratified parental education program was effective in preventing AD development by 63.3% in high-risk infants before 12 months of life (P < 0.0001). Conclusion: Genetic stratification and parental education are effective in preventing the development of AD in high-risk infants before 12 months of life.

Staphylococcus aureus acts both as a colonizing commensal bacterium and invasive pathogen. Nasal colonization is associated with an increased risk of infection caused by the identical strain. In patients with atopic dermatitis (AD), the degree of S. aureus colonization is associated with the severity of the disease. Here, we comparatively analyzed the in vivo transcriptional profile of S. aureus colonizing the nose and non-diseased skin (non-lesional skin) as opposed to the diseased skin (lesional skin-defined here as infection) of 12 patients with AD. The transcriptional profile during the asymptomatic colonization of the nose closely resembled that of the lesional skin samples for many of the genes studied, with an elevated expression of the genes encoding adhesion-related proteins and proteases. In addition, the genes that modify and remodel the cell wall and encode proteins that facilitate immune evasion showed increased transcriptional activity. Notably, in a subgroup of patients, the global virulence regulator Agr (accessory gene regulator) and downstream target genes were inactive during nasal colonization but upregulated in the lesional and non-lesional skin samples. Taken together, our results demonstrate a colonization-like transcriptional profile on diseased skin and suggest a role for the peptide quorum sensing system Agr during the transition from asymptomatic nasal colonization to skin colonization/infection.

The skin microbiota, with its millions of bacteria, fungi, and viruses, plays a key role in balancing the health of the skin and scalp. Its continuous exposure to potentially harmful stressors can lead to abnormalities such as local dysbiosis, altered barrier function, pathobiont overabundance, and infections often sustained by multidrug-resistant bacteria. These factors contribute to skin impairment, deregulation of immune response, and chronic inflammation, with local and systemic consequences. In this scenario, according to the needs of the bio-circular-green economy model, novel harmless strategies, both for regulating the diverse epidermal infectious and inflammatory processes and for preserving or restoring the host skin eubiosis and barrier selectivity, are requested. Vitis vinifera L. leaves and their derived extracts are rich in plant secondary metabolites, such as polyphenols, with antioxidant, anti-inflammatory, antimicrobial, and immunomodulatory properties that can be further exploited through microbe-driven fermentation processes. On this premise, this literature review aims to provide an informative summary of the most updated evidence on their interactions with skin commensals and pathogens and on their ability to manage inflammatory conditions and restore microbial biodiversity. The emerging research showcases the potential novel beneficial ingredients for addressing various skincare concerns and advancing the cosmeceutics field as well.

Modernization and Westernization in industrialized and developing nations is associated with a substantial increase in chronic noncommunicable diseases. This transformation has far-reaching effects on lifestyles, impacting areas such as economics, politics, social life, and culture, all of which, in turn, have diverse influences on public health. Loss of contact with nature, alternations in the microbiota, processed food consumption, exposure to environmental pollutants including chemicals, increased stress and decreased physical activity jointly result in increases in the frequency of inflammatory disorders including allergies and many autoimmune and neuropsychiatric diseases. This review aims to investigate the relationship between Western lifestyle and inflammatory disorders.

Several hypotheses have been put forth trying to explain the observed increases in these diseases, such as 'Hygiene Hypothesis', 'Old Friends', and 'Biodiversity and Dysbiosis'. The recently introduced 'Epithelial Barrier Theory' incorporates these former hypotheses and suggests that toxic substances in cleaning agents, laundry and dishwasher detergents, shampoos, toothpastes, as well as microplastic, packaged food and air pollution damage the epithelium of our skin, lungs and gastrointestinal system. Epithelial barrier disruption leads to decreased biodiversity of the microbiome and the development of opportunistic pathogen colonization, which upon interaction with the immune system, initiates local and systemic inflammation. Gaining a deeper comprehension of the interplay between the environment, microbiome and the immune system provides the data to assist with legally regulating the usage of toxic substances, to enable nontoxic alternatives and to mitigate these environmental challenges essential for fostering a harmonious and healthy global environment.

Despite major progress in the treatment of autoimmune diseases in the past two decades, most therapies do not cure disease and can be associated with increased risk of infection through broad suppression of the immune system. However, advances in understanding the causes of autoimmune disease and clinical data from novel therapeutic modalities such as chimeric antigen receptor T cell therapies provide evidence that it may be possible to re-establish immune homeostasis and, potentially, prolong remission or even cure autoimmune diseases. Here, we propose a 'sequential immunotherapy' framework for immune system modulation to help achieve this ambitious goal. This framework encompasses three steps: controlling inflammation; resetting the immune system through elimination of pathogenic immune memory cells; and promoting and maintaining immune homeostasis via immune regulatory agents and tissue repair. We discuss existing drugs and those in development for each of the three steps. We also highlight the importance of causal human biology in identifying and prioritizing novel immunotherapeutic strategies as well as informing their application in specific patient subsets, enabling precision medicine approaches that have the potential to transform clinical care.

The pathogenesis of atopic dermatitis (AD) is multifactorial, involving a dynamic interplay between genetic susceptibility, skin-barrier dysfunction, microbiome alterations, and immune dysregulation, whereas food allergy (FA) arises from the interplay of transcutaneous sensitization to food allergens and failure in the induction of oral tolerance. Skin epicutaneous sensitization is commonly involved in the development of AD and FA. Although clinical trials have been conducted to prevent AD or FA by applications of emollients on the skin after birth, the results are not consistent. For more effective preventive strategies, reliable biomarkers are required to identify high-risk individuals. Skin tape stripping (STS) is a non-invasive technique for identifying these biomarkers in the skin. By analyzing the stratum corneum collected via STS, researchers can gain molecular or cellular insights into the early pathogenesis and potential progression of AD and FA. This review aims to elucidate the critical aspects of AD and FA, underlying their pathogenesis, early manifestations, and STS's potential as a tool for identifying predictive non-invasive biomarkers in infants prior to onset of clinical disease.

Atopic dermatitis (AD) is a highly heritable and common inflammatory skin condition affecting children and adults worldwide. Multi-ancestry approaches to AD genetic association studies are poised to boost power to detect genetic signal and identify ancestry-specific loci contributing to AD risk. Here, we present a multi-ancestry GWAS meta-analysis of twelve AD cohorts from five ancestral populations totaling 56,146 cases and 602,280 controls. We report 101 genomic loci associated with AD, including 15 loci that have not been previously associated with AD or eczema. Fine-mapping, QTL colocalization, and cell-type enrichment analyses identified genes and cell types implicated in AD pathophysiology. Functional analyses in keratinocytes provide evidence for genes that could play a role in AD through epidermal barrier function. Our study provides new insights into the etiology of AD by harnessing multiple genetic and functional approaches to unveil the mechanisms by which AD-associated variants impact genes and cell types.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by itching, epidermal barrier dysfunction, and an unbalanced inflammatory reaction. AD pathophysiology involves a dysregulated immune response driven by T helper-2 cells. Many factors, including reactive oxygen species (ROS), are involved in AD pathogenesis by causing cellular damage and inflammation resulting in skin barrier dysfunction. This narrative review aims to provide a comprehensive overview of the role of natural molecules and antioxidant compounds, highlighting their potential therapeutic value in AD prevention and management. They include vitamin D, vitamin E, pyridoxine, Vitamin C, carotenoids, and melatonin. Some studies report a statistically significant association between antioxidant levels and improvement in AD, however, there are conflicting results in which antioxidant supplementation, especially Vitamin D, did not result in improvement in AD. Therefore, the clinical efficacy of these dietary nutritional factors in the treatment of AD needs to be further evaluated in clinical trials. Meanwhile, antioxidants can be incorporated into the management of AD patients in a personalized manner, tailored to the severity of the disease, comorbidities, and individual needs.