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Abstract Background Helminths are potent immunomodulators and in their chronic infection state they may protect against allergy‐related disease and atopy. However, they are also known for inducing allergic conditions. This study aimed to assess the association between helminths, atopy and allergic conditions. Methods A total of 461 school children participated in this cross‐sectional study. Data on allergic symptoms and a range of confounding variables was gathered from parents via an interviewer‐led questionnaire. Skin sensitization to house dust mite and cockroaches was analyzed, and a stool sample was collected for helminth analysis. Serum total Immunoglobulin E using enzyme‐linked immunosorbent assay and eosinophil count were also measured. Results Overall sensitivity to both allergens was 2.4%. Self‐reported allergic outcomes in the last 12 months for the 461 participants had been : wheezing 3.7%, asthma 2.2%, eczema 13.2% and hay fever 6.9%. Overall, the prevalence of helminth infection was 11.9% (53/444). A borderline significant association was found between atopy and any allergy symptoms (odds ratio [OR]: 3.32, 95% confidence interval [95% CI: 0.99, 11.1], p = .052). There was no significant association between helminths and atopy (OR: 0.64 [95% CI: 0.29, 1.41], p = .268) and also between helminths and allergic symptoms (OR: 0.64 [95% CI: 0.29, 1.41], p = .268). Bivariate analysis showed keeping an animal in the house increases the risk of atopy while maternal and paternal history of allergy increases the risk of developing allergic symptoms in the children. Conclusion and clinical relevance This study found a non‐significant inverse association between helminths infection and atopy and allergic disorders, likely due to reduced statistical power, resulting in a lower prevalence of atopy and allergic conditions. A high powered longtitudinal study is necessary to explore the casuality and potential therapeutic benefits of helminths for allergic disorders.

Food protein-induced allergic proctocolitis (FPIAP) is a non-IgE-mediated allergic condition that presents with hematochezia in otherwise healthy infants. It is most commonly induced by cow's milk protein via breast milk or formula. The prognosis for FPIAP is generally considered favorable with most infants achieving symptomatic resolution after diet modification. Most infants go on to tolerate the offending foods by 1–3 years of age. Over 8 years at our institution, five patients were identified and noted to have FPIAP to cow's milk during infancy with subsequent development of IgE-mediated allergic reaction to cow's milk and other foods. All five cases developed other atopic disorders (atopic dermatitis in four cases). IgE-mediated cow's milk allergy has persisted beyond the preschool years in at least two patients (currently 8 and 16 years old). For three of the patients, the IgE-mediated reaction to cow's milk was severe with development of anaphylaxis or angioedema. In addition, three patients experienced anaphylaxis or angioedema to allergens other than milk. While FPIAP is a non-IgE-mediated process traditionally thought not to progress past the first year of life, some infants with FPIAP develop severe, persistent IgE-mediated cow's milk allergy. To our knowledge, this is the first detailed clinical description of such patients.

Wan Zhen Janice Ng,1,* James van Hasselt,2,* Bhumika Aggarwal,3 Anand Manoharan4 1School of Biological Sciences, Nanyang Technological University, Singapore, Singapore; 2GSK, Regional Medical Affairs, Bryanston, Gauteng, South Africa; 3Regional Respiratory Medical Affairs, GSK Plc, Singapore, Singapore; 4Infectious Diseases Medical & Scientific Affairs, GSK, Mumbai, India*These authors contributed equally to this workCorrespondence: James van Hasselt, GSK, The Campus, Flushing Meadows, 57 Sloane Street, Bryanston, Gauteng, 2021, South Africa, Tel +27-82-330-8489, Email james.d.van-hasselt@gsk.comBackground: Strong associations between early antibiotic exposure and increased risk of childhood allergies have been established. Antibiotics have the potential to induce microbial dysbiosis that may be linked to allergic conditions. This review examines the limited available evidence on the associations between adult antibiotic use, microbial dysbiosis and atopic conditions.Methods: A systematic literature search was conducted using PubMed and Embase for relevant studies, published between 01– 01– 2000 and 08– 17– 2022. We searched for associations between antibiotic use, microbial dysbiosis, and allergic conditions in adults, defined as over 13 years of age for the purposes of this review.Results: Twenty-one studies were analyzed, with the inclusion of four narrative reviews as scarce relevant literature was found when stricter selection criteria were employed. Relevant studies predominantly focused on asthma. Significant microbial differences were observed in most measures between healthy subjects and subjects with allergic conditions. However, no system-wise and strain-wise associations were evident. Notably, at the phyla level, the Bacillota and Pseudomonadota phyla were associated with asthmatics, while the Actinobacteria phylum was linked to healthy controls. Asthmatics tends to reflect upregulation in the Bacillota and Pseudomonadota phyla in both airway and gut microbiomes.Conclusion: No compelling evidence could be found between adult antibiotic exposure, consequent microbial dysbiosis, and allergic conditions in adults. Our review is limited by scarce literature and therefore remains inconclusive. However, potential implications of antibiotic use impacting on allergic conditions justify additional research and heightened pharmacovigilance in this area.Keywords: atopy, allergic, asthma, microbiome

Introduction: Eosinophilic esophagitis (EoE) is a chronic, allergic inflammatory disease of the esophagus. It has a peak incidence in the 2nd and 3rd decades of life. Despite this, little is known about pregnancy outcomes in patients with EoE. Methods: Using a validated histopathologic and nationwide population-based cohort for the diagnosis of EoE, we examined maternal and fetal outcomes, with preterm birth as the primary outcome, in females with EoE compared to matched controls. Odds ratios (ORs) were calculated using logistic regression. Results: Between 1992 and 2016, we identified 19 females with EoE who gave birth to 23 children (reference births: n = 115). There was 1 (4.3%) preterm birth in the EoE cohort versus 8 (7.0%) in the reference cohort (OR = 0.60; 95% CI = 0.07–5.14). Secondary fetal outcomes included stillbirth, neonatal death, small for gestational age, low birth weight (LBW), and low Apgar score. Of these, LBW (

BackgroundMonogenic conditions that disrupt proper development and/or function of the immune system are termed inborn errors of immunity (IEIs), also known as primary immunodeficiencies. Patients with IEIs often suffer from other manifestations in addition to infection, and allergic inflammation is an increasingly recognized feature of these conditions.MethodsWe performed a retrospective analysis of IEIs presenting with allergic inflammation as reported in the USIDNET registry. Our inclusion criteria comprised of patients with a reported monogenic cause for IEI where reported lab eosinophil and/or IgE values were available for the patient prior to them receiving potentially curative therapy. Patients were excluded if we were unable to determine the defective gene underlying their IEI. Patients were classified as having eosinophilia or elevated IgE when their record included at least 1 eosinophil count or IgE value that was greater than the age stratified upper limit of normal. We compared the proportion of patients with eosinophilia or elevated IgE with the proportion of samples in a reference population that fall above the upper limit of normal (2.5%).ResultsThe query submitted to the USIDNET registry identified 1409 patients meeting inclusion criteria with a monogenic cause for their IEI diagnosis, of which 975 had eosinophil counts and 645 had IgE levels obtained prior to transplantation or gene therapy that were available for analysis. Overall, 18.8% (183/975) of the patients evaluated from the USIDNET registry had eosinophilia and 20.9% (135/645) had an elevated IgE. IEIs caused by defects in 32 genes were found to be significantly associated with eosinophilia and/or an elevated IgE level, spanning 7 of the 10 IEI categories according to the International Union of Immunological Societies classification.ConclusionType 2 inflammation manifesting as eosinophilia or elevated IgE is found in a broad range of IEIs in the USIDNET registry. Our findings suggest that allergic immune dysregulation may be more widespread in IEIs than previously reported.

Dermavant Sciences has announced that the US FDA has accepted its supplemental new drug application (sNDA) for tapinarof cream 1% for the treatment of atopic dermatitis (AD) in adults and children aged 2 years and older. The FDA's decision is based on data from the ADORING phase 3 clinical trials, an open-label pharmacokinetics trial, and an interim analysis of a phase 3 extension trial. Tapinarof cream is a non-steroidal treatment option that has shown efficacy in improving AD symptoms, with minimal adverse events reported. The FDA's decision is an important step towards providing a new treatment option for patients with AD. [Extracted from the article]

A study published in Digestive Diseases & Sciences explores the relationship between vitamin D levels and eosinophilic esophagitis (EoE), a type of chronic food allergy. The study found that patients with EoE had lower levels of vitamin D compared to controls, although they were not deficient. While there was no direct relationship between vitamin D levels and markers of EoE disease activity, there was a suggestion of lower vitamin D levels in patients with fibrosis. The study suggests that vitamin D supplementation may be beneficial for patients with EoE, but further research is needed to fully understand the relationship between vitamin D and the disease. [Extracted from the article]

This article provides an overview of the role of the skin microbiome in atopic dermatitis (AD) and explores the potential benefits of using microbiome-containing moisturizers for AD management. It emphasizes the importance of maintaining microbial balance in AD therapies and suggests further research is needed to determine the effectiveness of these products. The article also mentions the use of probiotics and prebiotics in AD treatment, as well as the potential of balneotherapy in optimizing microbial diversity and reducing the severity of AD lesions. Overall, it offers valuable insights into the current understanding of the skin microbiome in AD and its implications for treatment. [Extracted from the article]

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder of the esophagus. EoE shares a common pathogenetic mechanism with other chronic disorders pertaining to the type 2 inflammatory spectrum, such as atopic dermatitis (AD), allergic rhinitis (AR), asthma, and chronic rhinosinusitis with nasal polyps (CRSwNP). The recent advancements in EoE pathogenesis understanding have unveiled new molecular targets implied within the “atopic march” picture as well as specific to EoE. These discoveries have led to the clinical evaluation of several novel drugs (monoclonal antibodies and immune modulators), specifically aimed at the modulation of Th2 inflammation. In this comprehensive review, we have focused on the subtle mechanisms of type 2 inflammatory disorders, highlighting the similarities and differences with EoE, taking a deeper look into the evolving field of biologic therapies, already approved or under current investigation.

Atopic diseases, including atopic dermatitis (AD) and allergic asthma (AA), are characterized by complex immune responses involving various T cells subsets and their cytokine profiles. It is assumed that single nucleotide polymorphisms (SNPs) in the Vitamin D receptor (VDR) gene and the Vitamin D-binding protein (GC) gene are related to the action of Vitamin D and, consequently, play a role in regulating the immune response. However, there is not enough data to unequivocally support the hypothesis about the relationship between T cells profile and VDR or GC SNPs. Two hundred sixty-six subjects (aged > 18 years) were involved in the study: 100 patients with mild or moderate AD, 85 patients with mild or moderate AA, and 81 healthy individuals. Blood cell counts were determined by standard methods. Flow cytometric analysis was used to evaluate CD4+ T-helper (Th) cell subtypes: Th2, Th1, Th17, and T regulatory (Treg) cells in peripheral blood. Measurements of cytokines, total immunoglobulin E (IgE), and Vitamin D levels in serum were evaluated by ELISA. Significantly higher levels of Th1, Th2, and Th17 cells, along with lower levels of Tregs, were found in patients with atopic diseases compared to healthy individuals. Additionally, higher serum levels of interleukin (IL) 5, IL-17A, and transforming growth factor-β1 (TGF-β1), as well as lower levels of IL-10, were observed in patients with atopic diseases than in control. The study established associations between VDR SNPs and immune profiles: the AA genotype of rs731236 was associated with increased Th2 and Th17 cells and a higher Th1/Th2 ratio; the GG genotype of rs731236 was linked to decreased serum IL-10 and TGF-β1 levels; and the TT genotype of rs11168293 was associated with increased IL-10 levels. Additionally, the GG genotype of GC gene SNP rs4588 was associated with reduced Th2 and Th17 lymphocytes, while the TT genotype of rs4588 was linked to decreased IL-10 levels. Furthermore, the CC genotype of rs7041 was associated with higher levels of Th2, Th17, IL-10, and IL-35, as well as reduced levels of TGF-β1, while the GG genotype of rs3733359 was associated with reduced IL-10 levels. In conclusion, our study demonstrates that the Vitamin D receptor gene single nucleotide polymorphisms rs731236 and rs11168293, along with polymorphisms in the Vitamin D-binding protein gene (rs4588, rs7041, rs3733359), are significantly associated with variations in T cell profiles in atopy. These variations may play a crucial role in promoting inflammation and provide insight into the genetic factors contributing to the pathogenesis of atopy.

(1) Background: Food allergy (FA) is an immune-mediated hypersensitivity to foods, significantly contributing to childhood morbidity and mortality. This study aimed to assess the prevalence, characteristics, and influencing factors of parent-reported FAs among children in Saudi Arabia. (2) Methods: This cross-sectional study utilized a validated parental questionnaire distributed across all regions of Saudi Arabia. Data from 2130 participants were collected and analyzed using SPSS v. 26 and Prism software v. 10.3.0. (3) Results: Parent-reported FA prevalence was 15.2%. Egg was the most common allergen (6.2%), followed by tree nuts (4.1%), peanuts (4.0%), milk (3.8%), and sesame (3.2%). Significant geographical variations were observed, with the western region having the highest burden (p < 0.001). Older children had higher rates of shellfish and fish allergies. Parental allergies and co-existing asthma/drug allergies were positively associated with childhood FAs. (4) Conclusions: This study highlights a substantial burden of parent-reported FAs in Saudi Arabia, with regional variations in food allergen distribution. Parental allergies and co-existing allergic conditions may influence FA risk.

Black, Latinx, and Indigenous people in the United States experience a disproportionate burden of asthma and atopic dermatitis. The study of these disease disparities has focused on proximal socioenvironmental exposures and on the biomechanistic (including genetic) differences between racial and ethnic groups. Although biomedical research in allergy and immunology stands to benefit from the inclusion of diverse study populations, the narrow focus on biologic mechanisms disregards the complexity of interactions across biologic and structural factors, including the effects of structural racism. Structural racism is the totality of ways in which society fosters discrimination by creating and reinforcing inequitable systems through intentional policies and practices sanctioned by government and institutions. It is embedded across multiple levels, including the economic, educational, health care, and judicial systems, which are manifested in inequity in the physical and social environment. In this review, we present a conceptual framework and pull from the literature to demonstrate how structural racism is a root cause of atopic disease disparities by way of residential segregation, socioeconomic position, and mass incarceration, which may lead to aberrations in the innate and adaptive immune response and the augmentation of physiologic stress responses, contributing to a disproportionate disease burden for racial and ethnic populations.

Introduction. Pediatric asthma is predominantly atopic, but no data are found on atopy in obese asthmatic child in the literature. In addition, the increased obesity rates, sensitization to airborne allergens are a risk factor for asthma. Objective. To determine whether elevation of body mass index (BMI) was associated with asthma severity or with sensitization to inhalation allergens in adolescents in the wilaya of Constantine. Material and methods. This was a prospective, descriptive and cross-sectional study, carried out during the 2017-2018 school year, on 104 asthmatic adolescents, aged between 13 and 14, in schools in Constantine. The weight status of the patients was assessed using the 2012 thresholds of the International Obesity Task Force (IOTF), and a BMI ≥ 25 kg/m2 defined overweight or obesity. Asthmatics obese and non-obese groups were compared for the prevalence of severe asthma and sensitization using the Chi-square test, at the 95% confidence interval. Results. Twenty-five per cent of asthmatics were overweight or obese with an average BMI of 28,20±3,80. Asthma symptoms were persistent in 66%, and uncontrolled in 40% of cases. Almost 70% of the population were atopic, and 50% were poly-sensitized. Sensitization occurred in both groups with a significant positive ratio (p=0.03). No association was observed between obesity and prevalence of severe asthma (p=0.5), or poly-sensitizations. Conclusion. The quarter of adolescents is overweight or obese, and tends to present an atopy. However, no positive association is found between obesity and prevalence of severe asthma symptoms. Further prospective studies are needed for a better understanding of this obese asthmatics group. [Résumé Introduction. L’asthme pédiatrique est majoritairement atopique, mais aucune donnée n’existe sur l’atopie de l’enfant asthmatique obèse dans la littérature. En outre, l’élévation du taux d’obésité, la sensibilisation aux pneumallergènes sont un facteur de risque pour l’asthme. Objectif. Déterminer si l’élévation de l’indice de masse corporelle (IMC) est associée à la sévérité de l’asthme ou à la sensibilisation aux pneumallergènes, chez des adolescents asthmatiques dans la wilaya de Constantine. Matériel et méthodes. Une étude prospective, descriptive et transversale est réalisée durant l’année scolaire 2017-2018, et a porté sur 104 adolescents asthmatiques, âgés entre 13 et 14 ans, au sein des établissements scolaires de Constantine. Le statut pondéral des malades a été évalué en utilisant les seuils de l’International Obesity Task Force (IOTF), avec un indice de masse corporelle (IMC) ≥ 25 kg/m² définissant le surpoids ou l’obésité. Des groupes d’asthmatiques obèses et non obèses ont été comparés afin de noter la prévalence de l’asthme sévère et la sensibilisation en utilisant le test de Chi-deux à l’intervalle de confiance de 95 %. Résultats. Un quart des asthmatiques étaient en surpoids ou obèses avec un IMC moyen de 28,20±3,80. Les symptômes d’asthme étaient persistants chez 66%, et non contrôlés chez 40% des cas. Près de 70% de la population était atopique et 50 % étaient polysensibilisés. La sensibilisation s’est produite dans les deux groupes avec un rapport positif significatif (p=0,03). Aucune association n’est observée entre l’obésité et la prévalence de l’asthme sévère ou les poly-sensibilisations. Conclusion. Le quart des adolescents sont en surpoids ou obèses et ont tendance à présenter une atopie. Cependant, aucune association n’est notée entre l’obésité et la prévalence des symptômes sévères d’asthme. D’autres études prospectives sont nécessaires pour une meilleure compréhension du groupe d’asthmatiques obèses.]

The prevalence and severity of allergic diseases have increased over the last 30 years. Understanding the mechanisms responsible for these diseases is a major challenge in current allergology, as it is crucial for the transition towards precision medicine, which encompasses predictive, preventive, and personalized strategies. The urge to identify predictive biomarkers of allergy at early stages of life is crucial, especially in the context of major allergic diseases such as food allergy and atopic dermatitis. Identifying these biomarkers could enhance our understanding of the immature immune responses, improve allergy handling at early ages and pave the way for preventive and therapeutic approaches. This minireview aims to explore the relevance of three biomarker categories (proteome, microbiome, and metabolome) in early life. First, levels of some proteins emerge as potential indicators of mucosal health and metabolic status in certain allergic diseases. Second, bacterial taxonomy provides insight into the composition of the microbiota through high-throughput sequencing methods. Finally, metabolites, representing the end products of bacterial and host metabolic activity, serve as early indicators of changes in microbiota and host metabolism. This information could help to develop an extensive identification of biomarkers in AD and FA and their potential in translational personalized medicine in early life.

Allergy is a conundrum lacking satisfactory answers despite its global prevalence. Traditional systems of medicine may contain sustainable and effective solutions for the same. For mainstreaming them, an evaluation based on the system's own methods is inevitable rather than symptom-based correlations. Atopy is a novel entity in Ayurveda, but the methods of tripartite delineation (disease pattern, disease targets and influencing factors) of novel diseases and multifactorial approach to diagnosis and management in Ayurveda can bring about comprehensiveness in collection and categorization of data regarding the entity. This in turn can make the prediction, prevention and management of the same more precise, effective and sustainable. The article provides a template for the application of Ayurvedic biological framework in the diagnosis and management of novel diseases, with special reference to childhood allergic disorders.

Introduction: Measuring soluble interleukin-2 receptor (sIL-2R) might be useful for diagnosis and monitoring of immune-mediated diseases. The study investigated factors associated with serum sIL-2R concentrations in adults. Methods: Serum sIL-2R concentrations were measured in 1499 randomly selected individuals (44.6% male, median age 52 years, range 18–91 years). Lifestyle factors (alcohol consumption, smoking, and physical activity) were assessed by questionnaire. Body mass index and data defining metabolic syndrome were measured in all participants. Atopy was defined by skin tests to aeroallergens. Results: Serum sIL-2R concentrations displayed wide variation (2.5–97.5 percentile range, 209–950 U/mL). A total of 230 (15.3%) individuals showed values higher than the standard reference range (158–623 U/mL). After adjusting for covariates, sIL-2R concentrations increased with age, particularly after 65 years. Serum sIL-2R concentrations were higher in males than in females, were higher in smokers than in never smokers, and were higher in atopic than in non-atopic individuals. Serum sIL-2R concentrations were positively associated with metabolic syndrome, particularly with abdominal obesity, and with a history of ischemic heart disease. Light alcohol drinkers showed lower sIL-2R concentrations than abstainers. Conclusion: Aging, sex, lifestyle factors, atopy, metabolic abnormalities, and ischemic heart disease might influence serum sIL-2R concentrations in adults.

Introduction: Obesity can complicate IgE-mediated allergic diseases. In the present study, we aimed to investigate the ability of obesity-related concentrations of leptin to modulate the in vitro effector and regulatory Fel d1-specific CD4+ T-cell subsets in patients allergic to cat, considered the third most common cause of respiratory allergy in humans. Methods: For this study, plasma and peripheral blood mononuclear cells (PBMC) from 30 cat-allergic patients with mild, moderate and severe respiratory symptoms were obtained. The PBMC cultures were stimulated with Fel d1 antigen (10 µg/mL) in the presence or absence of obesity-related leptin dose (50 hg/mL). After 6 days, the levels of cytokines and IgE in the supernatants were evaluated by multiplex and ELISA, respectively. The frequency of different nonfollicular (CXCR5-) and follicular (CXCR5+) Fel d1-specific CD4+ T cell subsets was determined by flow cytometry. The plasma levels of leptin and IgE anti-cat titers were evaluated by ELISA and ImmunoCAP, respectively. Results and conclusions: Fel d1 induced both IgE production and release of cytokines related to Th2, Th9 and Th17 cell phenotypes. Feld1 wasmore efficient in increasing the frequency of TFHIL-21-cells positive for IL-4, IL-5 and IL-13 than TFHIL-21+ cell subsets. Leptin favored the expansion Th2-like and Th9-like cells and TFHIL-21-cells positive for IL-4, IL-5 and IL-13, but reduced the proportion of conventional (Treg/Tr-1) and follicular (TFR) regulatory CD4+ T-cell subsets expressing or not CD39 marker. Finally, many of the imbalances between Fel d1-specific CD4+ T-cells were also correlated with plasma leptin and anti-Fel d1 IgE titers. In summary, hyperleptinemia should negatively impact on the severity of cat allergies by favoring the expansion of pathogenic Fel d1-specific CD4+ T-cell phenotypes and damaging the functional status of regulatory CD4+ T-cell subsets. [ABSTRACT FROM AUTHOR]

Background: Considering the cross-regulation of Th1 and Th2 responses, we hypothesised that atopic diseases (Th2) inhibit the protective Th1 immune response to Mycobacterium leprae and exacerbates leprosy. Objective: In this study, we aimed to evaluate the association between leprosy and atopic diseases. Methods: To evaluate the association of atopic diseases with leprosy, we conducted a case-control study that included leprosy patients (n = 333) and their household contacts (n = 93). The questionnaire from the International Study of Asthma and Allergies in Childhood, which is validated in several countries for epidemiological diagnosis of atopic diseases, was applied to determine the occurrence of atopic diseases, allergic rhinitis, asthma, and atopic dermatitis among leprosy patients and the household contacts. Results: Considering clinical and epidemiological data, among the leprosy group 51.6% (n = 172) were determined to have at least one atopic disease, while atopy was observed less frequently at 40.86% among household contacts (n = 38). When two or more atopic diseases were assessed, the frequency was significantly higher among the leprosy patients than in the household contacts (21.9% vs. 11.8%; P-value = 0.03). Likewise, the frequency of asthma was significantly higher among leprosy patients (21%) than in the household contacts (10.8%; P-value = 0.02). Thus, our analyses revealed an association of atopic diseases with leprosy, with a significant linear increase in the occurrence of leprosy with an increase in the number of atopic diseases (P-value = 0.01). Limitation: Due to the difficulties in recruiting household contacts that have prolonged contact with patients, but are not genetically related to the patient, the household contacts group is smaller than the leprosy patient group. Conclusion: The data reveal an association between atopic diseases and leprosy outcomes. This knowledge could improve the treatment of leprosy patients with co-incident atopic diseases. [ABSTRACT FROM AUTHOR]

Background: Allergic bronchopulmonary aspergillosis (ABPA) develops in the presence or absence of asthma, either atopic or nonatopic. We have tried to explore the essential components in the pathogenesis of the disease, which are either consistent and variable according to the presence and type of asthma. Methods: Non‐cystic fibrosis ABPA cases satisfying Asano's criteria were extracted from a prospective registry of ABPA and related diseases in Japan between 2013 and 2023. According to the type of preceding asthma, ABPA was classified into three groups: ABPA sans asthma (no preceding asthma), ABPA with atopic asthma, and ABPA with nonatopic asthma. Exploratory and confirmatory factor analyses were performed to identify the components that determined the clinical characteristics of ABPA. Results: Among 106 cases of ABPA, 25 patients (24%) had ABPA sans asthma, whereas 57 (54%) and 24 (23%) had ABPA with atopic and nonatopic asthma, respectively. Factor analysis identified three components: allergic, eosinophilic, and fungal. Patients with atopic asthma showed the highest scores for the allergic component (p <.001), defined by total and allergen‐specific IgE titers and lung opacities, and the lowest scores for the fungal component defined by the presence of specific precipitin/IgG or positive culture for A. fumigatus. Eosinophilic components, including peripheral blood eosinophil counts and presence of mucus plugs/high attenuation mucus in the bronchi, were consistent among the three groups. Conclusion: The eosinophilic component of ABPA is considered as the cardinal feature of ABPA regardless of the presence of preceding asthma or atopic predisposition. [ABSTRACT FROM AUTHOR]

Our knowledge of biology and mast cell (MC) function, as well as disorders associated with the pathologic activation of MCs, has evolved over the last few decades. Anaphylaxis, mast cell activation syndrome (MCAS), and mastocytosis are interrelated yet distinct conditions within the spectrum of mast cell activation disorders. Nevertheless, all three conditions can co-exist in one and the same patient, as pathologic MC activation is the key finding in all three. When mediator release is excessive and involves multiple systems, anaphylaxis and MCAS may occur. Furthermore, mastocytosis is a clonal disorder of MCs and often presents with anaphylaxis and MCAS. Nevertheless, in some cases, even the proliferative and accumulative features of MCs in mastocytosis can account for symptoms and disease progression. In each case, diagnosis can be only made when the diagnostic consensus criteria are fulfilled. The current article aims to provide a concise clinical update and pinpoint the main difficulties in diagnosing these puzzling disorders of MCs in medical practice. [ABSTRACT FROM AUTHOR]

Keratoconus appears to be a rare corneal disease with a prevalence previously estimated at 1:2000. The aim of our study was to investigate the prevalence of keratoconus in a large German cohort and to evaluate possible associated factors. Method: In the population-based, prospective, monocentric cohort study, Gutenberg Health Study, 12,423 subjects aged 40–80 years were examined at the 5-year follow-up. Subjects underwent a detailed medical history and a general and ophthalmologic examination including Scheimpflug imaging. Keratoconus diagnosis was performed in two steps: all subjects with conspicuous TKC analysis of corneal tomography were included in further grading. Prevalence and 95% confidence intervals were calculated. Logistic regression analysis was carried out to investigate association with age, sex, BMI, thyroid hormone, smoking, diabetes, arterial hypertension, atopy, allergy, steroid use, sleep apnea, asthma, and depression. Results: Of 10,419 subjects, 75 eyes of 51 subjects were classified as having keratoconus. The prevalence for keratoconus in the German cohort was 0.49% (1:204; 95% CI: 0.36–0.64%) and was approximately equally distributed across the age decades. No gender predisposition could be demonstrated. Logistic regression showed no association between keratoconus and age, sex, BMI, thyroid hormone, smoking, diabetes, arterial hypertension, atopy, allergy, steroid use, sleep apnea, asthma, and depression in our sample. Conclusion: The prevalence of keratoconus disease in a mainly Caucasian population is approximately tenfold higher than previously reported in the literature using latest technologies (Scheimpflug imaging). Contrary to previous assumptions, we did not find associations with sex, existing atopy, thyroid dysfunction, diabetes, smoking, and depression. [ABSTRACT FROM AUTHOR]

This article discusses two studies that explore the relationship between DNA methylation and asthma development, as well as prenatal vitamin D levels and childhood asthma. The first study found that DNA methylation in newborns is linked to the development of asthma in adolescence, with specific CpG sites potentially serving as biomarkers for different types of asthma. The second study found that higher levels of vitamin D during pregnancy are associated with a reduced risk of childhood asthma. Both studies emphasize the importance of understanding these factors in the development of asthma and suggest further avenues for research. [Extracted from the article]

Background: T helper type 2 (Th2), Th17, and regulatory T cells (Tregs) play essential roles in the pathogenesis and control of allergic rhinitis (AR). Fexofenadine and budesonide are first-line treatments for AR. This study aimed to investigate the effect of co-treatment with fexofenadine and budesonide on the expression of Th2, Th17, and Treg-specific transcription factors (GATA-binding protein 3 [GATA-3], RAR-related orphan receptor gamma [RORγt], and forkhead box P3 [FoxP3], respectively) in AR patients. Methods: In this study, 29 AR patients were co-treated with fexofenadine and budesonide for 1 month. Blood was collected from AR patients before and after 1 month of treatment. The gene expression levels of GATA-3, RORγt, and FoxP3 transcription factors in blood samples were measured. In addition, serum immunoglobulin E (IgE) levels and eosinophil percentages in blood samples were determined. Findings: The expression level of FoxP3 increased significantly after treatment compared with that before treatment (P <.001). In contrast, GATA-3 and RORγt expression levels did not show any noticeable changes. In addition, the percentage of peripheral blood eosinophils significantly decreased (P <.01). Serum IgE levels decreased compared with those before treatment, but the difference was not statistically significant. Furthermore, the clinical symptoms of the patients improved compared with those before treatment. Conclusion: Our results showed that combined treatment with fexofenadine and budesonide increased the expression level of the FoxP3 gene, decreased the percentage of peripheral blood eosinophils, and improved the clinical symptoms of AR patients. This regimen appears to improve disease symptoms, at least in part by increasing the Treg population and decreasing the eosinophil population. [ABSTRACT FROM AUTHOR]

Human epigenetic variation is associated with both environmental exposures and allergic diseases and can potentially serve as a biomarker connecting climate change with allergy and airway diseases. In this narrative review, we summarize recent human epigenetic studies examining exposure to temperature, precipitation, extreme weather events, and malnutrition to discuss findings as they relate to allergic and airway diseases. Temperature has been the most widely studied exposure, with the studies implicating both short-term and long-term exposures with epigenetic alterations and epigenetic aging. Few studies have examined natural disasters or extreme weather events. The studies available have reported differential DNA methylation of multiple genes and pathways, some of which were previously associated with asthma or allergy. Few studies have integrated climate-related events, epigenetic biomarkers, and allergic disease together. Prospective longitudinal studies are needed along with the collection of target tissues beyond blood samples, such as nasal and skin cells. Finally, global collaboration to increase diverse representation of study participants, particularly those most affected by climate injustice, as well as strengthen replication, validation, and harmonization of measurements will be needed to elucidate the impacts of climate change on the human epigenome. [ABSTRACT FROM AUTHOR]

(1) Background: "Brittle Asthma" was considered an asthma clinical phenotype and deemed to be life-threatening in the early 2000s; then, this definition disappeared. The purpose of this review is to examine what has historically been referred to as this term and see whether it may be applied to modern clinical practice, thus acquiring fresh relevance and meaning. (2) Methods: A non-systematic search of the literature was conducted using both MeSH and free-text phrases. No limitations on the research design or type of publication were applied. (3) Results: Reliable data regarding "Brittle Asthma" are lacking due to the paucity of current data and the few studies available. After a few years of reworking, it was divided into two sub-classes: one characterized by a wide PEF variability despite high-dose therapy and the other by sudden acute attacks in otherwise apparently normal airway functions or well-controlled asthma. Their characteristics were hardly defined because of their low prevalence. Data regarding risk factors, atopy, mechanisms, and treatments were analyzed. (4) Conclusions: Over time, different terminology has been introduced to define asthma severity and control. It would be worth investigating whether the term "Brittle Asthma" previously used may be helpful to find new hints to stratify patients and improve disease management. [ABSTRACT FROM AUTHOR]

Background: Food allergy (FA) is an increasing health problem in children. Previous studies have reported conflicting results about the diagnostic value of atopy patch test in food allergies. The aim of the present study was to investigate the accuracy of atopy patch test in identifying non-IgE-mediated gastrointestinal FA to pasteurized/homogenized cow›s milk, heated raw cow›s milk, white and yolk egg, soy, wheat, walnut, sesame, pistachio, almond, peanut, date and cumin which are popular food ingredients in southern Iran. Methods: This study was performed on children with gastrointestinal allergic problems who were not improved after at least 4 weeks of cow’s milk protein elimination. Atopy patch test (APT) was performed and the elimination diet was considered according to positive skin results and after resolving symptoms, introduction of each accused food was done sequentially. Results: Fifty tree children under 7 years old with mean age of 19.6 months underwent APT and the results were verified by open oral food challenge (OFC). Sensitivity in the range of 59%-95%, specificity of 80.7-92.8%, positive predictive values of 75-96.4% and negative predictive value of 23%-80.7% were calculated depending on the type of food. Compared to the heated raw cow’s milk, the pasteurized/homogenized cow’s milk reaction was significant. Conclusion: APT can be included in the diagnostic workup of non-IgE-mediated GI allergy because it is safe and has great accuracy. However, several aspects require further investigation especially to enable the standardization of the technique. We should be aware of the allergenicity of our foods due to processing and geographic region. [ABSTRACT FROM AUTHOR]

In previous pre-clinical studies, we examined the contribution of interleukin 4 receptor (IL4R) signaling in the progression and metastasis of colorectal cancer (CRC). Aberrant activation of this receptor can result in atopic diseases such as asthma. We hypothesized that further evidence for the contribution of excessive IL4R being associated with CRC progression could be seen in medical records, and specifically that chronic asthma patients were more likely to be diagnosed with metastatic CRC. To test this hypothesis, we took advantage of the Synthetic Derivative, a resource developed at Vanderbilt University Medical Center that hosts de-identified data taken from the electronic medical record. We developed search protocols that produced retrospective cohorts of invasive CRC patients and cancer-free equivalents. In comparing 787 metastatic CRC patients to 238 non-metastatic patients, we actually found significantly fewer asthmatics went on to develop metastatic CRC (P=0.0381). By comparing these groups together against 1197 cancer-free patients, even fewer asthmatic patients would develop invasive CRC (P<0.0001). While these results are clearly in opposition to our original hypothesis, they still support a link between chronic asthma and metastatic CRC development. One intriguing possibility, that will be examined in the future, is whether treatment for chronic asthma may be responsible for the reduction in metastatic cancer. [ABSTRACT FROM AUTHOR]

Introduction: Eotaxin-1/CCL11 is a pivotal chemokine crucial for eosinophil homing to the lungs of asthmatic patients. Recent studies also suggest that CCL11 is involved in the aging process, as it is upregulated in elderly, and correlated with shorter telomere length in leukocytes from asthmatic children. Despite its potential pro-aging effects, the precise contribution of CCL11 and the underlying mechanisms involved in the promotion of cellular senescence remains unclear. Therefore, the primary goal of this study was to explore the role of CCL11 on senescence development and the signaling pathways activated by this chemokine in lung fibroblasts. Methods: To investigate the targets potentially modulated by CCL11, we performed an in silico analysis using PseudoCell. We validated in vitro the activation of these targets in the human lung fibroblast cell line MRC-5 following rhCCL11 exposure. Finally, we performed differential gene expression analysis in human airway epithelial cells of asthmatic patients to assess CCL11 signaling and activation of additional senescent markers. Results: Our study revealed that eotaxin-1/CCL11 promote reactive oxygen secretion (ROS) production in lung fibroblasts, accompanied by increased activation of the DNA damage response (DDR) and p-TP53 and gH2AX. These modifications were accompanied by cellular senescence promotion and increased secretion of senescence-associated secretory phenotype inflammatory cytokines IL-6 and IL-8. Furthermore, our data show that airway epithelial lung cells from atopic asthmatic patients overexpress CCL11 along with aging markers such as CDKN2A (p16INK4a) and SERPINE1. Discussion: These findings provide new insights into the mechanisms underlying the pro-aging effects of CCL11 in the lungs of asthmatic patients. Understanding the role of CCL11 on senescence development may have important implications for the treatment of age-related lung diseases, such as asthma. [ABSTRACT FROM AUTHOR]

Purpose: To report indications and clinical outcomes of corneal grafts ≤ 5.5 mm in diameter ("mini-KP") in a German tertiary referral center. Methods: Patients who had undergone mini-KP to treat corneal ulcers with or without perforation between 2011 and 2018 at the Department of Ophthalmology, University of Düsseldorf, Germany, were identified from the local keratoplasty registry. All patient records were reviewed for age, gender, laterality, systemic and ophthalmological diseases, etiology of the corneal ulcerative disease, pre- and postoperative visual acuity over a follow-up time of up to 12 months, graft size, postoperative complications and the need for and timing of further corneal interventions. Results: 37 eyes of 37 patients (male: n = 20; female: n = 17) with a mean age (± standard deviation) at presentation of 70 ± 18.8 years (range: 22–92 years) were identified. Most common etiologies were neurotrophic keratopathy (n = 15), dysfunctional tear syndrome (n = 9) and atopic keratoconjunctivitis (9). Mean graft diameter was 4.51 ± 0.63 mm (range: 3-5.5 mm). 23/37 eyes (62%) required no further intervention in the acute phase. 14/37 patients (38%) required secondary corneal intervention, due to complications. One-year graft survival was 78.4%. One eye had to be eviscerated due to recurrent corneal ulceration and endophthalmitis. 36 of 37 eyes were preserved. We found a highly significant correlation between type 2 diabetes and the development of postoperative complications (r =.46; p =.005). Corrected distance visual acuity (CDVA) improved from 1.42 ± 0.75 logMAR to 0.9 ± 0.65 logMAR postoperatively (t (23) = 5.76; p <.001). Conclusion: Mini-KP can be used successfully in eyes with advanced corneal ulcers due to various infectious and noninfectious etiologies to restore tectonic stability in the long-term and with moderate visual gains. [ABSTRACT FROM AUTHOR]

Background: Current management of food protein-induced enterocolitis syndrome (FPIES) involves strict avoidance of the offending food for 12–18 months, followed by oral food challenge (OFC) under physician supervision. OFCs are resource-intensive and there is a lack of a universal standardized protocol for FPIES. Prolonged avoidance may increase the risk of IgE-mediated allergy, particularly in atopic patients. Food ladders have shown success in promoting accelerated tolerance in patients with IgE-mediated allergy. Our case series evaluated the safety of use of the Canadian Egg Ladder in patients with mild-to-moderate FPIES to egg. Methods: From May 2020 to November 2021, patients with mild-to-moderate FPIES to egg, defined as no history of lethargy or intravenous fluid administration, were started on the Canadian Egg Ladder. Instructions for advancing up the ladder were identical to using the Canadian Egg Ladder in patients with IgE-mediated allergy. Patients were followed every 3–6 months, at which time information was collected regarding progression up the ladder, symptoms while on treatment and interventions required. Treating allergists completed a survey to capture baseline demographic characteristics and prior tolerance to egg. Descriptive statistics were analyzed using MS Excel. Results: Twenty-one patients with mild-to-moderate FPIES were started on the Canadian Egg Ladder. Median age at initiation of the ladder was 10 months (IQR, 9–11). Nineteen (90.5%) patients completed the ladder, tolerating a serving size amount of cooked egg, over a median duration of 7 month (IQR, 4–9 months). Four patients (19.0%) had mild symptoms including vomiting (9.5%), pallor (9.5%), belching (4.8%), irritability (4.8%) and small spit up (4.8%). In three of the four patients, symptoms were the result of accidental exposure to a higher step of the ladder. There were no reports of lethargy. No patients required health care presentation or intravenous fluid administration. No patients discontinued the ladder. Conclusions: The Canadian Egg Ladder can safely guide the dietary advancement of egg-containing foods in patients with mild-to-moderate FPIES to egg, without the need for prolonged avoidance and resource-intensive OFCs. [ABSTRACT FROM AUTHOR]

Atopic dermatitis represents a non-infectious, multifactorial inflammatory and chronic dermatosis. Pruritus is the main symptom. The pathophysiology of atopic dermatitis is very complex and includes genetic disorders, a defect in the epidermal barrier, an altered immune response and a disruption of the skin's microbial balance, all of which damage the epidermis, causing itchy skin lesions. The prevalence varies, but it is generally present in 30% of children, and 85% of cases manifest before the age of 5. The triad of atopic diseases consists of atopic dermatitis, allergic rhinitis and asthma. A retrospective analysis of the documentation of the children who were treated at the Pediatric Clinic of the University Clinical Center Niš from 2018 to 2019 focused on anamnestic data, clinical manifestations, and laboratory parameters obtained from the medical records of the subjects. The total number of examined children was 40, among them, 21 were male and 19 female. They were divided into 3 age groups, from 2 months to 7 years. Anamnestic data indicate a connection between AD and other disorders of atopic diseases, allergic rhinitis, asthma, respiratory infections, and milk allergies. [ABSTRACT FROM AUTHOR]

Subphenotypes of asthma may be determined by age onset and atopic status. We sought to characterize early or late onset atopic asthma with fungal or non-fungal sensitization (AAFS or AANFS) and non-atopic asthma (NAA) in children and adults in the Severe Asthma Research Program (SARP). SARP is an ongoing project involving well-phenotyped patients with mild to severe asthma. Phenotypic comparisons were performed using Kruskal-Wallis or chi-square test. Genetic association analyses were performed using logistic or linear regression. Airway hyper-responsiveness, total serum IgE levels, and T2 biomarkers showed an increasing trend from NAA to AANFS and then to AAFS. Children and adults with early onset asthma had greater % of AAFS than adults with late onset asthma (46% and 40% vs. 32%; P < 0.00001). In children, AAFS and AANFS had lower % predicted FEV1 (86% and 91% vs. 97%) and greater % of patients with severe asthma than NAA (61% and 59% vs. 43%). In adults with early or late onset asthma, NAA had greater % of patients with severe asthma than AANFS and AAFS (61% vs. 40% and 37% or 56% vs. 44% and 49%). The G allele of rs2872507 in GSDMB had higher frequency in AAFS than AANFS and NAA (0.63 vs. 0.55 and 0.55), and associated with earlier age onset and asthma severity. Early or late onset AAFS, AANFS, and NAA have shared and distinct phenotypic characteristics in children and adults. AAFS is a complex disorder involving genetic susceptibility and environmental factors. [ABSTRACT FROM AUTHOR]

Background: The high‐frequency ultrasonographic appearance of skin of dogs with atopic dermatitis (cAD) has not been described. Objectives: To compare high‐frequency ultrasonographic findings among lesional, macroscopically nonlesional skin of dogs with cAD, and the macroscopically nonlesional skin of healthy dogs. Additionally, to determine whether there is any correlation between the ultrasonographic findings in lesional skin and local Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI‐04) or its domains (erythema, lichenification, excoriations/alopecia). As a secondary aim, six cAD dogs were re‐evaluated after management intervention. Animals: Twenty dogs with cAD (six were re‐examined after treatment) and six healthy dogs. Materials and Methods: In all dogs, ultrasonographic examination was performed on the same 10 skin sites, using a 50 MHz transducer. Wrinkling of skin surface, presence/width of subepidermal low echogenic band, hypoechogenicity of dermis and thickness of the skin were evaluated and scored/measured blindly. Results: Dermal hypoechogenicity was more common and severe in lesional compared to macroscopically nonlesional skin of dogs with cAD. In lesional skin, presence/severity of wrinkling of skin surface and of dermal hypoechogenicity were positively correlated with presence/severity of lichenification, while severity of dermal hypoechogenicity was positively correlated with local CADESI‐04. A positive correlation between the change in skin thickness and the change in the severity of erythema during treatment was noted. Conclusions and Clinical Relevance: High‐frequency ultrasound biomicroscopy may be useful for the evaluation of skin of dogs with cAD and for evaluating the progression of skin lesions during treatment. [ABSTRACT FROM AUTHOR]

Allergic airway diseases such as allergic rhinitis (AR) affects more than 400 million individuals worldwide and afflicts substantial health and economic morbidity.[1] AR is strongly associated with a Type 2 response, characterized by the cytokines IL-5, IL-4, and IL-13. Thus, the severity of eosinophilic airway allergies such as AR seems to be driven by an activated terminally differentiated CD161 SP + sp Th2 subset that is able to secrete a complex set of inflammatory cytokines. Eosinophilic allergic rhinitis is strongly associated with the CD45RBlo subset of CD161+ Th2 cells that secretes IL-2, IL-3, IL-4, IL-5, IL-9, and IL-13 Scatterplots showing (D) proportion of CD161+ Th2 and (E) CD45RB expression on CD161+ Th2 comparison between non-AR and AR individuals. [Extracted from the article]

How does allergen immunotherapy-induced tolerance improve the airway epithelial barrier function: A mechanistical-driven hypothesis Abbreviations AA allergic asthma AIT allergen immunotherapy AR allergic rhinitis DBPC double-blind, placebo-controlled HDM house dust mite ICS inhaled corticosteroids IFN interferon INS intranasal corticosteroids LABA long-acting beta-agonists NNT number needed to treat PAR protease-activated-receptor SABA short-acting beta-agonists TLR toll-like receptor In recent years, there has been a growing emphasis on understanding the critical importance of the epithelial barrier and exploring various mechanisms that contribute to the onset and progression of allergic, autoimmune, and neurodegenerative disorders. In the GRAZAX® asthma prevention (GAP) trial, children treated with the SQ grass SLIT tablet had a significantly reduced risk of developing asthma symptoms and to use asthma medication.[5] This was, surprisingly, not only observed in summer during grass pollen exposure but also during winter without grass pollen exposure. [Extracted from the article]

Introduction: Frequent dietary patterns for fast food diets are suggested to be a risk factor for atopic disease development. Excessive dietary fats in fast foods are postulated to promote low-grade chronic inflammation. However, no studies in Asia have yet to characterize the dietary pattern for high-fat foods with atopic diseases. Thus, this study aims to assess the association between dietary fats with the prevalence of atopic diseases in an allergic cohort. Methods: Through an investigator-administered questionnaire that follows the International Study of Asthma and Allergies in Childhood (ISAAC) protocol, we evaluated the eating habits, lifestyle behaviours, sociodemographics, and atopic symptoms, and history among 11,494 young Chinese adults in Singapore and Malaysia. A skin prick test (SPT) for common house dust mites was also conducted to determine the atopic (allergic) status. We identified 1,550 atopic dermatitis (AD), 1,301 allergic asthma (AS), and 3,757 allergic rhinitis (AR) atopic cases. We derived a novel dietary index, Diet Quality based on Total Fat Amount (DQTFA), to examine the association between eating patterns for estimated total fat amount with various atopic outcomes. Results: There was a preponderance of subjects having positive SPT reaction (69.0%) with the prevalence of AR being the highest (32.7%), then AD (13.5%), and AS (11.3%). Additionally, there is a significantly higher proportion of subjects with an atopy background and atopic diseases consume diets with a high estimated mean fat amount. The adherence to a dietary pattern of the higher estimated total fat amount was shown to be strongly associated with all atopic diseases and exhibited dose-dependent responses in the univariate analysis. These associations remained significant even with the adjustments for age, gender, body mass index, use of alcohol, sedentary lifestyles, and physical activity. A dietary pattern for high-fat amount is more strongly associated with AS (adjusted odds ratio [AOR]: 1.524; 95% confidence interval [CI]: 1.216–1.725; p < 0.001) and AR (AOR: 1.294; 95% CI: 1.107–1.512; p < 0.001) compared to AD (AOR: 1.278; 95% CI: 1.049–1.559; p < 0.05). Finally, it was shown that having either one of the atopic comorbidities was strongly associated with a dietary pattern of high-fat amounts (AOR: 1.360; 95% CI: 1.161–1.594; p < 0.001). Conclusion: Our findings altogether provide initial evidence that the dietary pattern of a diet high in fat amount is associated with an increased risk of atopy and atopic diseases in young Chinese adults in Singapore and Malaysia. Balancing the consumption of dietary fats and changing personal dietary habits by choosing foods of the lower fat amount may reduce the associated odds of atopic diseases. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is on the increase worldwide. In Africa, 40% of cases are associated with tropical endemic limbo-conjunctivitis (TELC). Its predominance in early childhood has a major impact on the quality of life of children and their parents, leading to absenteeism from school and work. The aim of this study was to assess the particularities of AD associated with TELC in Dakar. Materials and Methods: This was a cross-sectional, multicenter study with prospective data collection over a six-month period, conducted at dermatology and ophthalmology departments in Dakar. All patients treated for atopic dermatitis with or without TELC were included in the study. Data entry and analysis were performed with SPSS 18. Results: From the study, 97 cases of atopic dermatitis were identified. Among these, 49 had AD associated with TELC. The sex ratio was 1.18 (36 boys and 13 girls). The mean age of patients was ten years. The age range between 5 and 10 years was more represented. There was atopy equivalent to allergic rhinitis in 44 cases, asthma in 16 cases, allergic conjunctivitis in 14 cases, and food allergy in 20 cases. 31 cases of AD were mild, 16 moderate, and 2 severe according to SCORAD. Patients were in stage I in 26 cases and in stage II in 13 cases according to Diallo’s TECL classification. All patients were managed by dermatologists and ophthalmologists. Aeroallergen prick tests were performed in thirty cases. Tests were positive for house dust mites in 23 cases (92%), animal dander in 11 cases (44%), molds in 7 cases (28%), and pollens in 2 cases (8%). Dermatophagoides pteronyssinus and farinae were the most common aeroallergens. Patch tests were positive for potassium dichromate in 4 cases, cobalt in 4 cases, nickel in 3 cases, and lanolin in 4 cases. Conclusion: AD associated with TECL remains common in tropical environments. They share common aggravating environmental factors, notably hypersensitivity to aeroallergens and a predominance in early childhood. The major impact on functional prognosis makes therapeutic education and multidisciplinary management of patients essential. [ABSTRACT FROM AUTHOR]

The transcription factor STAT6 (Signal Transducer and Activator of Transcription 6) is a key regulator of Th2 (T-helper 2) mediated allergic inflammation via the IL-4 (interleukin-4) JAK (Janus kinase)/STAT signalling pathway. We identified a novel heterozygous germline mutation STAT6 c.1255G > C, p.D419H leading to overactivity of IL-4 JAK/STAT signalling pathway, in a kindred affected by early-onset atopic dermatitis, food allergy, eosinophilic asthma, anaphylaxis and follicular lymphoma. STAT6 D419H expression and functional activity were compared with wild type STAT6 in transduced HEK293T cells and to healthy control primary skin fibroblasts and peripheral blood mononuclear cells (PBMC). We observed consistently higher STAT6 levels at baseline and higher STAT6 and phosphorylated STAT6 following IL-4 stimulation in D419H cell lines and primary cells compared to wild type controls. The pSTAT6/STAT6 ratios were unchanged between D419H and control cells suggesting that elevated pSTAT6 levels resulted from higher total basal STAT6 expression. The selective JAK1/JAK2 inhibitor ruxolitinib reduced pSTAT6 levels in D419H HEK293T cells and patient PBMC. Nuclear staining demonstrated increased STAT6 in patient fibroblasts at baseline and both STAT6 and pSTAT6 after IL-4 stimulation. We also observed higher transcriptional upregulation of downstream genes (XBP1 and EPAS1) in patient PBMC. Our study confirms STAT6 gain of function (GOF) as a novel monogenetic cause of early onset atopic disease. The clinical association of lymphoma in our kindred, along with previous data linking somatic STAT6 D419H mutations to follicular lymphoma suggest that patients with STAT6 GOF disease may be at higher risk of lymphomagenesis. 245 words. [ABSTRACT FROM AUTHOR]

Patients with autosomal dominant (AD) hyper-IgE syndrome (HIES) suffer from a constellation of manifestations including recurrent bacterial and fungal infections, severe atopy, and skeletal abnormalities. This condition is typically caused by monoallelic dominant-negative (DN) STAT3 variants. In 2020, we described 12 patients from eight kindreds with DN IL6ST variants resulting in a new form of AD HIES. These variants encoded truncated GP130 receptors, with intact extracellular and transmembrane domains, but lacking the intracellular recycling motif and the four STAT3-binding residues, resulting in an inability to recycle and activate STAT3. We report here two new DN variants of IL6ST in three unrelated families with HIES-AD. The biochemical and clinical impacts of these variants are different from those of the previously reported variants. The p.(Ser731Valfs*8) variant, identified in seven patients from two families, lacks the recycling motif and all the STAT3-binding residues, but its levels on the cell surface are only slightly increased and it underlies mild biological phenotypes with variable clinical expressivity. The p.(Arg768*) variant, identified in a single patient, lacks the recycling motif and the three most distal STAT3-binding residues. This variant accumulates at the cell surface and underlies severe biological and clinical phenotypes. The p.(Ser731Valfs*8) variant shows that a DN GP130 expressed at near normal levels on the cell surface can underlie heterogeneous clinical presentations, ranging from mild to severe. The p.(Arg768*) variant demonstrates that a truncated GP130 protein retaining one STAT3-binding residue can underlie severe HIES. [ABSTRACT FROM AUTHOR]

Expression quantitative trait methylation (eQTM) analyses uncover associations between DNA methylation markers and gene expression. Most eQTM analyses of complex diseases have focused on cis- eQTM pairs (within 1 megabase). This study sought to identify cis- and trans- methylation markers associated with gene expression in airway epithelium from youth with and without atopic asthma. In this study, the investigators conducted both cis- and trans -eQTM analyses in nasal (airway) epithelial samples from 158 Puerto Rican youth with atopic asthma and 100 control subjects without atopy or asthma. The investigators then attempted to replicate their findings in nasal epithelial samples from 2 studies of children, while also examining whether their results in nasal epithelium overlap with those from an eQTM analysis in white blood cells from the Puerto Rican subjects. This study identified 9,108 cis -eQTM pairs and 2,131,500 trans -eQTM pairs. Trans -associations were significantly enriched for transcription factor and microRNA target genes. Furthermore, significant cytosine-phosphate-guanine sites (CpGs) were differentially methylated in atopic asthma and significant genes were enriched for genes differentially expressed in atopic asthma. In this study, 50.7% to 62.6% of cis- and trans- eQTM pairs identified in Puerto Rican youth were replicated in 2 smaller cohorts at false discovery rate–adjusted P <.1. Replicated genes in the trans -eQTM analysis included biologically plausible asthma-susceptibility genes (eg, HDC , NLRP3, ITGAE, CDH26, and CST1) and are enriched in immune pathways. Studying both cis - and trans -epigenetic regulation of airway epithelial gene expression can identify potential causal and regulatory pathways or networks for childhood asthma. Trans -eQTM CpGs may regulate gene expression in airway epithelium through effects on transcription factor and microRNA target genes. [ABSTRACT FROM AUTHOR]

Background: In cases of atopy, IgE antibodies are formed in reaction to certain environmental factors like house dust mites, pollen, or even food allergens. Some studies have shown an association between atopic diseases and keratoconus. This study aims to determine the prevalence of atopy and its associated factors among keratoconus patients.Materials and Methods: A cross-sectional study was conducted among the Jazan population attending ophthalmology clinics regardless of their sex. Data collection started in August 2020 and finished in mid-June 2021. The sample was selected using the convenience sampling technique, and the total sample size was 83 participants. Data were collected via a questionnaire-based interview that contained 46 questions in the Arabic language. The data collected were analyzed using SPSS software.Results: Family history is the leading predisposing factor for keratoconus (P < 0.001). Also, eye rubbing was a significant (P < 0.015) trigger for keratoconus. However, other factors, including demographic factors such as gender and atopic conditions, did not have any significant association.Conclusion: A combination of genetic and environmental factors is the leading cause of the development of keratoconus; however, family history is the most influential factor, followed by eye rubbing. [ABSTRACT FROM AUTHOR]

Introduction: Cow's milk allergy (CMA) is a common complication and one of the most common food allergies in infants, and it is estimated that this disease affects 2-3% of children under five years old. Objectives: This study investigated the factors associated with developing immune tolerance in children with CMA in Gorgan. Patients and Methods: In this cross-sectional study, 50 children with CMA referred to the asthma and allergy clinic of Taleghani Hospital in Gorgan during 2019-2020 were investigated. Multiple logistic regression was applied to measure odds ratios (ORs) and 95% confidence intervals (CIs) of the associations between the selected factors and tolerance to cow's milk. Results: The results suggested that factors including standard delivery (P = 0.024, OR=4.03, 95% CI: 1.20-13.53) and breastfeeding in the first month of birth (P = 0.003, OR=6.73, 95% CI:1.94-23.36), and gastrointestinal symptoms (P = 0.026, OR=3.78, 95% CI: 1.17-12.19) were associated with immune tolerance to CMA. Younger age of starting complementary feeding (P < 0.001, OR=0.070, 95% CI:0.02-0.30), younger age of starting cow's milk feeding (P = 0.003, OR=0.520, 95% CI: 0.32-0.83), skin symptoms (P = 0.012, OR=0.211, 95% CI: 0.06-0.71) and respiratory symptoms (P = 0.013, OR=0.219, 95% CI:0.07-0.72) were associated with allergy persistence. Conclusion: The findings of our study demonstrated natural childbirth, breastfeeding, and gastrointestinal symptoms, including bloody stools, are factors related to immune tolerance in children with CMA. The findings showed that decreasing the onset of complementary feeding, reducing the age of cow's milk feeding, and clinical manifestations of respiratory and skin are associated with persistent CMA in children. [ABSTRACT FROM AUTHOR]