The age-specific microbiome of children with milk, egg, and peanut allergy.

BACKGROUND: Immune regulation by gut microbiota is affected by dysbiosis and may precede food allergy onset. Prior studies lacked comparisons stratified by age and clinical phenotype. OBJECTIVE: To assess the microbiome of children with food allergy (<3 years, 3-18 years) compared with similar aged children without food allergy. METHODS: A real-world prospective cross-sectional study performed from 2014 to 2019 recruited children highly likely to have milk, egg, or peanut allergy defined by history and serum IgE or confirmed by food challenge. 16S ribosomal RNA sequencing identified stool microbial DNA. Alpha and beta diversity was compared between groups with food allergy and healthy controls stratified by age. Differential abundance for non a priori taxa was accepted at absolute fold-change greater than 2 and q value less than 0.05. RESULTS: A total of 70 patients were included (56 with food allergy and 14 healthy controls). Groups were not significantly different in age, gender at birth, race, mode of delivery, breastfeeding duration, or antibiotic exposure. Younger children with food allergy had similar alpha diversity compared with controls. Beta diversity was significantly different by age (P = .001). There was differential abundance of several a priori (P < .05) taxa (including Clostridia) only in younger children. Both a priori (including Coprococcus and Clostridia) and non a priori (q < 0.05) Acidobacteria_Gp15, Aestuariispira, Tindallia, and Desulfitispora were significant in older children with food allergy, especially with peanut allergy. CONCLUSION: Dysbiosis associates with food allergy, most prominent in older children with peanut allergy. Younger children with and without food allergy have fewer differences in gut microbiota. This correlates with clinical observations of persistence of peanut allergy and improved efficacy and safety of oral immunotherapy in younger children. Age younger than 3 years should be considered when initiating therapeutic interventions.

Comparison of allergen immunotherapy practice patterns in inhalant allergies in the United States of America and Europe: Similarities and differences 2023.

IgE-mediated atopic diseases such as allergic rhinitis and rhinoconjunctivitis are common chronic diseases in the western world. Allergen immunotherapy (AIT) plays a fundamental role in the treatment of allergic patients by modulating the underlying immune mechanisms. Though this treatment is integrated in practice-patterns globally, many differences are found in the application of AIT on the national or international level due to heterogeneous methods, and clinical recommendations are given in different parts of the world. This review from authors in Europe and the United States highlights differences and similarities in important aspects of AIT application in the 2 global regions. First, the regulatory situation differs regarding marketing authorization and licensing. Secondly, differences are elaborated in manufacturing practices, marketing distribution and formulations of AIT products. Thirdly, clinical administration patterns in the current guidelines show similarities in indications and contraindications of AIT, but also are divergent in some practical aspects. Informing the readership on similarities, as well as differences of standards in AIT in the United States and Europe, the authors highlight the unmet need of thorough harmonization of standards of AIT, as it is the only disease modifying treatment option available for patients with allergic rhinitis and rhinoconjunctivitis.

The Need for Required Stock Epinephrine in All Schools: A Work Group Report of the AAAAI Adverse Reactions to Foods Committee.

Epinephrine is the first line of treatment for anaphylaxis that can occur outside a medical setting in community environments such as schools. Patients with diagnosed IgE-mediated food allergy at risk of anaphylaxis are prescribed self-injectable epinephrine and given an individualized anaphylaxis action plan. As students, such patients/families provide their school with completed medication forms, a copy of their anaphylaxis plan, and additional student-specific epinephrine. However, students approved to self-carry prescribed self-injectable epinephrine may forget to do so or have other reasons for lacking prescribed epinephrine such as familial inability to fill the prescription due to cost or other access barriers. Undiagnosed students lacking prescribed epinephrine may also experience anaphylaxis at school. The presence of non-student-specific school stock epinephrine allows school nurses and other staff the ability to treat anaphylaxis onsite while awaiting Emergency Medical Services. Notably, not all states legally mandate K-12 schools to stock epinephrine. In states with laws only voluntarily allowing schools to stock epinephrine, it provides the ability to opt-out. Herein, we present a comprehensive review of barriers to school stock epinephrine, related improvement strategies, and workgroup recommendations supporting the need for mandated stock epinephrine in all schools in every state. Proposed solutions include ensuring legal immunity from liability for prescribers; advocacy for legislation to stabilize cost of self-injectable epinephrine; educational initiatives to schools promoting merits and safety of epinephrine and related anaphylaxis training; and partnerships between patient advocacy groups, medical and nursing organizations, public health departments and other health professionals to promote laws and district policies addressing need for stock epinephrine and school nurses to train and supervise school staff.

Dose Adjustment After Gaps in Administration of Subcutaneous Immunotherapy From a Past Survey: Work Group Report of the AAAAI Allergen Standardization and Allergy Diagnostics Committee.

The allergen immunotherapy practice parameters third update recommendations on dose adjustment after a gap in administration during the build-up are based solely on expert opinion, and no recommendations for gaps during maintenance are given. In a previous survey among American Academy of Allergy, Asthma & Immunology (AAAAI) members on subcutaneous allergen immunotherapy, this was addressed, but details were never published. Members of the Immunotherapy, Allergen Standardization, and Allergy Diagnostics Committee of the AAAAI convened a workgroup to address this issue and reanalyze results on the particular survey section. Build-up: many practitioners start dose-adjusting if a patient comes in 14.1/14 days (mean/median) after the last dose and restart immunotherapy after an interruption of 85/90 days. Dosing frequency during maintenance is generally every 3 (12%) to 4 weeks (73%). Maintenance: allergists start dose-adjusting if a patient comes in 5.1/5 weeks (mean/median) after the last dose and completely restart after an interruption of 16/12 weeks (some replied in days [90.4/90 days] or months [4.43/4 months]). Subgroups: physicians with ≥11 years in practice in nonacademic centers or rural/suburban settings tolerate longer gaps before restarting subcutaneous immunotherapy (SCIT). There is no uniform dose-adjustment protocol after gaps in SCIT administration. Prospective studies shall have to help find the best trade-off between safety (dose reduction) without giving in on efficacy (too much dose reduction).

Nonallergic Rhinitis, Allergic Rhinitis, and Immunotherapy: Advances in the Last Decade.

Chronic rhinitis encompassing both allergic and nonallergic rhinitis affects a significant portion of the population worldwide, having a great impact on patient quality of life, and associated comorbid conditions, with an important societal economic burden. Allergists are often the first to evaluate and treat allergic and nonallergic rhinitis, addressing the individual triggers of the disease as well as the patient-specific responses to these triggers. This review focuses on the advances that have been made in the diagnosis, management, and treatment of nonallergic and allergic rhinitis over the past 10 years, including specific allergen immunotherapy, care pathways, and digital health.

How primary care providers can help prevent food allergies.

PURPOSE OF REVIEW: IgE-mediated food allergy rates have increased in recent decades, yet treatment options remain limited. Prevention strategies are thus essential. We will review recent research and consensus guidelines for food allergy prevention. RECENT FINDINGS: Research has continued to support that early introduction of allergens via the gastrointestinal tract induces tolerance and prevents development of food allergy. In contrast, allergen sensitization may occur via transcutaneous allergen exposure. This is supported by research that shows a decreased risk of food allergy with aggressive treatment of atopic dermatitis. More recent research suggests that transcutaneous sensitization could also be facilitated by frequent emollient use in the absence of atopic dermatitis but definitive research is lacking. Murine models have shown a likely role of dysbiosis, or disruption of the body's normal healthy microbiome, in development of food allergy, yet human studies have yet to show a conclusive benefit of probiotics in the prevention of food allergy. SUMMARY: Important approaches for food allergy prevention are: introduction of peanut and cooked egg at 4-6 months, early introduction of other allergenic foods, and early diagnosis and treatment of atopic dermatitis (because of a predisposition to food sensitization through the damaged skin barrier). More research is needed to clarify the role, if any, of emollient use and probiotics.

Allergic reactions to coronavirus disease 2019 vaccines and addressing vaccine hesitancy: Northwell Health experience.

BACKGROUND: Allergic and nonallergic adverse reactions have been reported with global coronavirus disease 2019 (COVID-19) vaccination. It was previously hypothesized that polyethylene glycol (PEG) may be responsible for anaphylactic reactions to messenger RNA (mRNA) COVID-19 vaccines. OBJECTIVE: To report the workflow established at our institution, types, and frequency of adverse reactions to mRNA COVID-19 vaccines in patients presenting for allergy evaluation. METHODS: A COVID-19 vaccine adverse reaction registry was established. We used PEG prick skin testing, followed by PEG challenges in selected cases, to ensure PEG tolerance and encourage completion of COVID-19 vaccination series. RESULTS: A total of 113 patients were included. Most vaccine reactions (86.7%) occurred in women. Anaphylaxis occurred only in women, all of which had a history of allergic disease and two-thirds had asthma. Anaphylaxis rate was 40.6 cases per million. None of the anaphylactic cases developed hypotension, required intubation, or required hospital admission. Systemic allergic symptoms, not fulfilling anaphylaxis criteria, were significantly more common in Pfizer-BioNTech than Moderna-vaccinated patients (P = .02). We observed a higher incidence of dermatologic nonurticarial reactions in men (P = .004). Among first-dose reactors, 86.7% received and tolerated the second dose. We observed a high rate of false-positive intradermal skin test results and frequent subjective symptoms with oral PEG challenge. CONCLUSION: Intradermal PEG testing has limited utility in evaluating anaphylaxis to mRNA vaccines. Most severe postvaccination allergic symptoms are not caused by hypersensitivity to PEG. Most people with reaction to the initial mRNA vaccine can be safely revaccinated. Patients with anaphylaxis to COVID-19 vaccines benefit from physician-observed vaccination.

Allergen Immunotherapy Extract Shortages and Their Effects on Clinical Care: A Work Group Report of the AAAAI Immunotherapy, Allergen Standardization, and Allergy Diagnostics Committee.

Allergen immunotherapy (AIT) is the only disease-modifying therapy indicated for treatment of allergic asthma, rhinitis, conjunctivitis, and Hymenoptera hypersensitivity. Manufacturing of the extracts used in AIT involve multistep complex processes as well as regulatory oversight. Furthermore, some source materials are vulnerable to unexpected events of nature. Given these circumstances, allergen extract supply can be disrupted with a potential to adversely impact patient care. A group of members from the American Academy of Allergy, Asthma, and Immunology (AAAAI) Immunotherapy, Allergy Standardization and Allergy Diagnostic Committee formed a workgroup to assess the frequency and effects of allergen extract shortages and associated factors. This workgroup developed a survey that was distributed to a random 20% of the AAAAI membership. In addition, the group also performed a review of the scientific literature on allergen extract supply and shortage. Based on the findings of the survey study and literature review, the workgroup reports frequency and extent of shortages, potential ways to improve communication with suppliers, and need for further guidance in patient care during times of shortage.

Component resolved diagnostics in peanut sensitized children with and without a history of clinical reaction.

Background: Serum Peanut-specific-IgE (PN-sIgE) and peanut-component-resolved-diagnostics (CRD) are often ordered simultaneously in the evaluation for peanut allergy. Results often guide the plans for peanut oral challenge. However, the clinical utility of CRD at different total PN-sIgE levels is unclear. A commonly used predefined CRD Ara h2 cutoff value in the literature predicting probability of peanut challenge outcomes is 0.35kUA/L. Objective: To examine the utility of CRD in patients with and without a history of clinical reactivity to peanut (PN). Methods: This was a retrospective chart review of 196 children with PN-sIgE and CRD testing, of which, 98 patients had a clinical history of an IgE-mediated reaction when exposed to PN and 98 did not. The Fisher's exact test was used to assess the relationship between CRD and PN-sIgE at different cutoff levels, McNemar test and Gwet's approach (AC1 statistic) were used to examine agreement between CRD and PN-sIgE, and logistic regression was used to assess differences in the findings between patients with and without reaction history. Results: Ara h 1, 2, 3, or 9 (ARAH) levels ≤0.35 kUA/L were significantly associated with PN-sIgE levels <2 kUA/L rather than ≥2 kUA/L (p < 0.0001). When the ARAH threshold was increased to 1 kUA/L and 2 kUA/L, these thresholds were still significantly associated with PN-sIgE levels of <2, <5, and <14 kUA/L. These findings were not significantly different in patients with and without a history of clinical reactivity. Conclusion: ARAH values correlated with PN-sIgE. Regardless of clinical history, ARAH levels are unlikely to be below 0.35, 1, or 2 kUA/L if the PN-sIgE level is >2 kUA/L. Thus, if possible, practitioners should consider PN-sIgE rather than automatically ordering CRD with PN-sIgE every time. Laboratory procedures that allow automatically and reflexively adding CRD when the PN-sIgE level is ≤5 kUA/L can be helpful. However, further studies are needed in subjects with challenge-proven PN allergy.

Comparison of Pediatric and Adult Systemic Reactions to Subcutaneous Immunotherapy.

BACKGROUND: Subcutaneous immunotherapy (SCIT) has been used to treat allergic rhinitis for over a century, and current regimens have wide variability with an array of practice styles and dosing strategies. Although there are some statements about contraindications and cautions, no specific formal age- or weight-based dosing guidelines are utilized when administering SCIT. OBJECTIVE: The primary objective of this study was to estimate the overall incidence rate of any reaction to SCIT and to consider the severity of the reaction by grade in children and adults. METHODS: A retrospective chart review was conducted to document the number and severity of episodes of systemic reactions (SRs) in pediatric and adult subjects. Crude incidence rates were estimated as the number of SRs relative to the total injections administered. Adjusted incidence rate ratios were generated using a generalized estimating equation approach, which accounted for multiple visits within subjects. RESULTS: The incidence rate for any SR was 0.2%. The unadjusted incidence rate of any SR was significantly higher in children compared with adults (P < .001), although not significant when adjusted for asthma, gender, and phase of SCIT (P < .054). However, the incidence rate for grade 1 and 2 SRs in children was 1.89 times the incidence rate for adults, adjusting for these variables (P < .015). CONCLUSIONS: These results suggest that current SCIT practices are associated with a higher rate of SRs, specifically of grade 1 and 2 SRs, in children than adults. Further studies are necessary to evaluate if changes in dosing strategies for children, such as a lower starting dose, a decrease in target maintenance dose, or a slower build-up phase, are warranted.

Antigen-based immunotherapy for autoimmune disease: current status.

Autoimmune diseases are common chronic disorders that not only have a major impact on the quality of life but are also potentially life-threatening. Treatment modalities that are currently favored have conferred significant clinical benefits, but they may have considerable side effects. An optimal treatment strategy for autoimmune disease would specifically target disease-associated antigens and limit systemic side effects. Similar to allergen-specific immunotherapy for allergic rhinitis, antigen-specific immunotherapy for autoimmune disease aims to induce immune deviation and promote tolerance to specific antigens. In this review, we present the current status of studies and clinical trials in both human and animal hosts that use antigen-based immunotherapy for autoimmune disease.