Allergic phenotype identified on allergen testing is associated with proton pump inhibitor nonresponse in eosinophilic esophagitis.

BACKGROUND AND AIM: Food/environmental allergens have been associated with eosinophilic esophagitis (EoE); however, the correlation between allergy profiles and disease responsiveness to proton pump inhibitor (PPI) therapy remains unclear. We aimed to assess the association between food/environmental allergies identified on allergen testing and histologic response to PPI in patients with treatment-naive EoE. METHODS: Adults with newly diagnosed EoE who underwent formal testing for food/environmental allergies at a tertiary center were included. All patients underwent twice-daily PPI for 8 weeks with subsequent repeat endoscopy and biopsy to assess histologic response. Patients with <15 eosinophils/hpf on post-PPI mucosal biopsies were classified as responders (PPI-r-EoE), while those with ≥15 eosinophils/hpf were nonresponders (PPI-nr-EoE). RESULTS: Sixty-one patients met inclusion criteria (21 PPI-r-EoE vs 40 PPI-nr-EoE). Demographic, clinical, and endoscopic finding variables were similar between groups. Positive food allergen test was more prevalent among PPI-nr-EoE patients (82.5% vs 42.9%, P = 0.003). On multivariable analysis, positive food allergen testing remained an independent predictor for PPI nonresponse (aOR 0.15, CI: 0.04-0.58, P = 0.0006). Positive environmental allergen testing was highly prevalent, with no significant differences between groups (77.5% vs 95.2%, P = 0.14). However, higher number of positive environmental allergens (23.3% [≥5 allergens] vs 73.3% [<5 allergens], P = 0.003) and specific aeroallergens correlated with PPI-nr-EoE. CONCLUSION: Positive food allergy testing and increased environmental allergens predicted lower likelihood of histologic response to PPI in EoE. Our findings support an allergic phenotype of EoE that may less likely respond to PPI therapy. Formal allergen testing may play a role in therapy selection and tailored management in EoE.

Aeroallergens in Atopic Dermatitis and Chronic Urticaria.

PURPOSE OF REVIEW: While aeroallergens are a well-established trigger of asthma and allergic rhinitis, their role in allergic skin diseases such as atopic dermatitis and chronic urticaria remains controversial. This paper reviews the pathophysiology and clinical evidence for aeroallergens in these allergic skin diseases and summarizes current strategies for evaluation and management. RECENT FINDINGS: Current evidence implicates aeroallergens as triggers of cutaneous reactions in atopic dermatitis. Direct skin contact is the likely route of trigger. Aeroallergens may also trigger chronic urticaria, though mechanistic studies are limited. These allergens may cross the skin barrier and directly trigger neurons to release substance P, resulting in mast cell degranulation and dumping of histamine and prostaglandin D2. Many studies link aeroallergen sensitization to chronic urticaria, and case reports suggest the utility of avoidance strategies. The role of aeroallergens as a trigger is clear in atopic dermatitis and becoming emergent in chronic urticaria. Skin prick testing or serum-specific immunoglobulin E testing may be used to determine sensitivities. Management at this time centers on avoidance, and further studies are necessary to evaluate the efficacy of aeroallergen immunotherapy for both conditions.

Skin Testing Is Useful in Assessing Aeroallergen Sensitization in IgE Deficient Patients with Environmental Allergy-Like Symptoms.

BACKGROUND: The value of aeroallergen skin testing is not known in IgE deficient individuals (IgE<2.5 kU/L). OBJECTIVE: To investigate the utility of skin prick (SPT), intradermal skin testing (IDST) and measuring serum specific IgE (ssIgE) in IgE deficient patients presenting with environmental allergy-like symptoms. METHODS: Individuals with IgE deficiency who had both SPT and IDST performed between 2010 to 2020 were matched (age and gender) to three different groups of non-IgE deficient patients with IgE≥2.5 kU/L (normal IgE [2.5 ≤ IgE<100], high IgE [100≤IgE<1000] and very high IgE levels [≥1000 kU/L]) who also had skin testing performed for evaluation of environmental allergy-like symptoms. RESULTS: Among 34 IgE deficient patients who completed SPT and IDST, 52.9% (18/34) had at least one positive skin test (4 ± 3 positive tests/patient), compared with 91.2% in those with normal, 94.1% with high or 97.1% with very high IgE levels (p < 0.01). In contrast, only one of the IgE deficient patients had detectable ssIgE, while ssIgE levels were significantly higher in all other IgE subgroups. Allergic immunotherapy was prescribed for 22.2% of the IgE-deficient patients with positive skin tests, similar to those with normal (2/31, 6.5%, p = 0.21), high IgE (9/32, 28.1%, p = 0.25) and very high IgE levels (8/33, 23.5%, p = 0.07), with similar efficacy in their symptoms control. CONCLUSION: Individuals with IgE deficiency may present with environmental allergy-like symptoms. A combination of SPT and IDST is useful for diagnosing aeroallergen sensitizations in these patients, indicating the presence of skin mast cell-bound IgE in some of these individuals, despite very low serum IgE levels. Further studies are needed to assess the exact significance of positive skin tests and the benefits of immunotherapy in this group.

Allergies, Allergic Comorbidities and the Home Environment in Pediatric Asthma in Southern Florida.

Background: Environmental exposure is critical in sensitization to environmental allergens and pediatric asthma morbidity, especially in tropical climates where children are perennially exposed to bioaerosols, such as pollen and mold spores, and endotoxins. Objective: This cross-sectional study examines the association of allergies, associated allergic comorbidities, and the home environment separately and synergistically in pediatric asthma, including in asthma prevalence, severity of asthma, and undiagnosed asthma, in South Florida. Methods: An online survey was administered to the parents of children attending two of the University of Miami pediatric clinics from June to October 2016. Descriptive, factor, and multivariate regression analyses were used to analyze the data. Results: Of 163 children, 22% (36) children had physician-diagnosed asthma; 10% and 32% had allergic rhinitis diagnosis and rhinitis symptoms, respectively, in the past. The allergy diagnosis age was 2.3 years higher than the asthma diagnosis age (p < 0.01). Children with ≥ 2 allergies were 12.8 times more likely to have physician-diagnosed asthma than those without allergies (p < 0.01). Children with allergies and allergic rhinitis were 4.3 (p < 0.05) times more likely to have asthma, and those with asthma were 15 (p < 0.05) times more likely to have an asthma attack than those without known allergies and allergic rhinitis. Conclusion: Allergies and associated comorbidities are risk factors of asthma, asthma persistence, and multiple allergies exacerbate their effects. Early screening for allergies and treatment are warranted to manage asthma. Since the home environment plays an important role in sensitization to allergens, further research is needed to assess home-environment-mediated allergic conditions in the onset and persistence of asthma.

Otolaryngologists Practice Pattern on Oral Allergy Syndrome.

BACKGROUND: Oral allergy syndrome is a unique type of food allergy caused by cross-sensitivity between inhalant allergens and food allergens. Despite its significant prevalence and potentially serious outcome, the knowledge base and practice patterns on OAS are not well known among otolaryngologists. Our study is designed to understand the practice patterns of otolaryngologists in screening, testing, and treating OAS through a web-based survey. METHODS: Three thousand otolaryngologists were randomly selected from a membership list of the American Academy of Otolaryngology - Head and Neck Surgery. A survey was designed to include demographic questions and questions about OAS understanding, screening, and management. Surveys were sent to selected otolaryngologists via mail. Responses were de-identified and analyzed using SPSS. RESULTS: Out of the 50 survey responses, 46 reported treating environmental allergy in their practices. Twenty eight out of 46 reported knowing about OAS (60.9%). Fifteen out of the 28 physicians screened for OAS (53.6%). Out of the responders who knew about OAS, 12 (42.9%) reported diagnosing under 5 cases in the past year, 7 (25%) diagnosed 5 to 10 cases, and 7 (25%) reported diagnosed more than 10 cases in the past year. Eleven (39.3%) reported ordering component allergy testing for food allergies. Twenty six (92.9%) reported using avoidance, 18 (64.3%) prescribed oral antihistamine medications, 14 (50%) prescribed epi-pen, and 19 (67.9%) desensitized patients to environmental allergies as a treatment for OAS. 26 (93%) reported using more than one of the listed treatments. 10 (36%) reported using all four methods. CONCLUSION: Only 60.9% of the responders had a knowledge of OAS. Only 53.6% of those screened for OAS. Current treatment for OAS includes avoidance of allergens, desensitization of environmental allergens, prescription of oral antihistamine and epi-pen. Nearly everyone (93%) reported using more than one treatment method.

Epigenome-wide association study reveals methylation pathways associated with childhood allergic sensitization.

Epigenetic mechanisms integrate both genetic variability and environmental exposures. However, comprehensive epigenome-wide analysis has not been performed across major childhood allergic phenotypes. We examined the association of epigenome-wide DNA methylation in mid-childhood peripheral blood (Illumina HumanMethyl450K) with mid-childhood atopic sensitization, environmental/inhalant and food allergen sensitization in 739 children in two birth cohorts (Project Viva-Boston, and the Generation R Study-Rotterdam). We performed covariate-adjusted epigenome-wide association meta-analysis and employed pathway and regional analyses of results. Seven-hundred and five methylation sites (505 genes) were significantly cross-sectionally associated with mid-childhood atopic sensitization, 1411 (905 genes) for environmental and 45 (36 genes) for food allergen sensitization (FDR<0.05). We observed differential methylation across multiple genes for all three phenotypes, including genes implicated previously in innate immunity (DICER1), eosinophilic esophagitis and sinusitis (SIGLEC8), the atopic march (AP5B1) and asthma (EPX, IL4, IL5RA, PRG2, SIGLEC8, CLU). In addition, most of the associated methylation marks for all three phenotypes occur in putative transcription factor binding motifs. Pathway analysis identified multiple methylation sites associated with atopic sensitization and environmental allergen sensitization located in/near genes involved in asthma, mTOR signaling, and inositol phosphate metabolism. We identified multiple differentially methylated regions associated with atopic sensitization (8 regions) and environmental allergen sensitization (26 regions). A number of nominally significant methylation sites in the cord blood analysis were epigenome-wide significant in the mid-childhood analysis, and we observed significant methylation - time interactions among a subset of sites examined. Our findings provide insights into epigenetic regulatory pathways as markers of childhood allergic sensitization.

Sevoflurane anaesthesia for nasal surgery in a patient with multiple chemical sensitivity. / Anestesia con sevoflurano para cirugía de senos paranasales en un paciente con sensibilidad química múltiple.

Multiple chemical sensitivity syndrome is a group of complex disorders that include psychiatric disorders, chronic fatigue and/or respiratory problems. This syndrome could be triggered by specific allergens and toxins that cause neurophysiological sensitization and the appearance of the clinical symptomatology. Anaesthesia for these patients always poses a challenge for the anaesthetist, because they need to find and use drugs that do not trigger or aggravate the symptoms of the disease. Therefore, sevoflurane in these circumstances might be "the ideal anaesthetic". Performing general anaesthesia with sevoflurane as the sole anaesthetic agent, together with a series of environmental measures formed the basis for successful anaesthesia and surgery in our patient with a multiple chemical sensitivity syndrome.

Debates in allergy medicine: Specific immunotherapy in children with atopic dermatitis, the "con" view.

Atopic dermatitis (AD) is a common chronic skin condition in children that has a proven association with other atopic conditions and allergies. These associations, like the general pathophysiology of AD, are complex and not fully understood. While there is evidence for the efficacy of specific immunotherapy (SIT) in pediatric asthma and allergic rhinitis (AR), there is a lack of strong data to support its use in AD. IgE has been shown to be elevated in many patients with AD, but it is an unreliable biomarker due to variability and great fluctuation over time, poor positive predictive value for clinically relevant allergy, and poor correlation with disease state. In spite of this, almost all studies of SIT use either positive skin prick testing (SPT) or serum specific IgE levels to guide therapy. Allergen avoidance, with some exceptions, is generally not effective at controlling AD in children. The few studies that have investigated the efficacy of SIT in children with AD have produced conflicting results, and a lack of reproducibility with a standard treatment protocol. Limited studies have shown clinical improvement in mild to moderate AD cases, but no effect on more severe patients. Uncontrolled studies are difficult to interpret, due to the natural history of remission or "outgrowing" of AD over time in many patients without specific interventions. Drawbacks to SIT include the length of treatment, poor compliance, cost, and potential side effect profile. The potential for misdirection of time and energy away from skin directed therapy could negatively impact on AD outcomes.