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BACKGROUND: In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation from the full document.METHODS: ICAR-Allergic Rhinitis 2023 employed established evidence-based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work.RESULTS: ICAR-Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost.CONCLUSION: The ICAR-Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment.

Background Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder of the esophagus marked by eosinophilic infiltration. Cumulative evidence indicates that the risk of EoE involves the complex interplay of both genetic and environmental factors. Because only a few genetic loci have been identified in EoE, the genetic underpinning of EoE remains largely elusive. Objective We sought to identify genetic loci associated with EoE. Methods Four EoE cohorts were genotyped using the Illumina single nucleotide polymorphism array platform, totaling 1,930 cases and 13,634 controls of European ancestry. Genotype imputation was performed with the Michigan Imputation Server using the Trans-Omics for Precision Medicine reference panel including whole-genome sequencing data from more than 100,000 individuals. Meta-analysis was conducted to identify potential novel genetic loci associated with EoE. Results Our study identified 11 new genome-wide significant loci, of which 6 are common variant loci, including 5q31.1 (rs2106984, P = 4.16 × 10−8; odds ratio [OR], 1.26, RAD50), 15q22.2 (rs2279293, P = 1.23 × 10−10; OR, 0.69, RORA), and 15q23 (rs56062135, P = 2.91 × 10−11; OR, 1.29, SMAD3), which have been previously associated with allergic conditions. Interestingly, a low-frequency synonymous mutation within the MATN2 gene was identified as the most significant single nucleotide polymorphism at the 8q22.1 locus. We also identified 5 sex-specific loci in the EoE cases, including an inflammatory bowel disease–associated locus at 9p24.1 (rs62541556, P = 4.4 × 10−8; OR, 1.11, JAK2). Conclusions Our findings demonstrate shared genetic underpinnings between EoE and other immune-mediated diseases and provide novel candidate genes for therapeutic target identification and prioritization.

The Core Outcome Set for Therapeutic Studies in Eosinophilic Esophagitis (COREOS) collaborators are a group of more than 70 gastroenterologists, pathologists, allergists, researchers, dietitians, psychologists, and methodologists who convened in a series of in-person and virtual meetings between 2018 and 2020 with the aim of developing a core outcome set (COS) for use in therapeutic studies of pharmacologic and dietary therapies for the treatment of eosinophilic esophagitis (EoE). Given heterogeneity in reported outcomes and uncertainties regarding the most appropriate end points for use in both randomized controlled trials (RCTs) and observational studies involving EoE patients, the EoE experts launched the COREOS exercise in 2018 to standardize outcome definitions using methods established by the Core Outcome Measures in Effectiveness Trials (COMET) initiative.1,2 The COS was developed using a multiphase approach, which is summarized in Figure 1. In the first phase, systematic reviews of the literature and patient engagement surveys were conducted to identify candidate outcomes that have been previously measured and are important to patients with EoE. Next, this information was used to build a framework of different outcome domains, and working groups for each domain were assembled to review the literature for relevant end points.3–6 The relative importance of these domains was categorized in a Delphi survey as core, important, and research agenda domains, and discussed in a moderated in-person meeting on May 17, 2019 at Digestive Disease Week (San Diego, CA). In phase 3, a comprehensive list of outcome measures within each of the core domains was evaluated by the COREOS collaborators in a 2-round Delphi survey and, finally, outcomes were ratified in a virtual meeting on December 8, 2020. In this meeting summary, we highlight the major points of discussion that occurred during the development of the EoE COS.

Objective Food protein-induced enterocolitis syndrome (FPIES) is a condition with heterogeneous features (ie, age at presentation, severity, food triggers, comorbidities) and is not as rare as initially believed. In the last few years, the first population-based epidemiologic study, few prospective birth cohort evaluating FPIES prevalence, and several larger (>100 patients) studies have been published, making epidemiologic estimation more reliable. In this review, we report on the available data on the epidemiology of FPIES. Data Sources PubMed review using the following words: FPIES, epidemiology, and prevalence. Study Selections The review focused on the population-based epidemiologic study, few prospective birth cohort evaluating FPIES prevalence, and several larger (>100 patients) studies. Results We identified 8 population or cohort studies. Conclusion FPIES is not rare in both children and adults and may affect as many as 900,000 people in the United States alone. Most children and adult with FPIES seem to react to 1 to 2 foods; however, they may need further diet restriction owing to high level of comorbidity with immunoglobulin E–mediated food allergies and eosinophilic esophagitis. Globally, cow's milk, rice/oat, and seafood seem to be the most common triggers.

Anaphylaxis is a rapidly evolving, acute, life-threatening reaction that occurs rapidly on contact with a trigger. Anaphylaxis is classically defined as an allergen-driven process that induces specific IgE and the activation of mast cells and basophils through the cross-linking of IgE receptors. However, it is clear that non-IgE-mediated pathways can induce symptoms indistinguishable from those of classic anaphylaxis, and their activation could explain the severity of IgE-mediated anaphylaxis. Indeed, mast cells and basophils can be activated by antibodies against IgE or their receptors, by molecules such as anaphylatoxins, or through G-coupled receptors. Some other allergens can induce antibodies of class IgG that can activate neutrophils to produce a molecule similar to histamine to induce anaphylaxis. Finally, some inflammatory mediators such as bradykinin or prostaglandin can also modulate mast cell and basophil activation as well as directly cause vasodilation and bronchoconstriction, resulting in anaphylaxis-like reactions.

Food protein-induced enterocolitis syndrome is still a mysterious disease, pathogenically poorly characterized, although the first FPIES case has been described in 1967. Mainly, food protein-induced enterocolitis syndrome diagnosis is based on clinical history. The oral food challenge remains the gold standard to confirm the diagnosis, especially in particular situations. Although there are no diagnostic laboratory or imaging tests which are specific for diagnosis, they could, however, sometimes be helpful to rule out clinical conditions which are similar to food protein-induced enterocolitis syndrome reactions. The purpose of this review is to define the clinical features of FPIES and to summarize the current available tools for the diagnosis of FPIES. This review is intended to be a practical guide for the clinician facing a patient with food protein-induced enterocolitis syndrome avoiding delayed diagnosis with unnecessary laboratory tests and detrimental treatments. Moreover, it highlights the unmet needs in diagnosis that require urgent attention from the scientific community to improve the management of patients with FPIES.

Purpose: Eosinophilic esophagitis (EoE) is a chronic immune-mediated esophageal disease. Most EoE patients have atopic comorbidities and they test positive when allergy tests are performed. Our aim is to critically assess the relation of allergens detected by allergy tests with clinically confirmed triggers of EoE. Methods: A systemic review and meta-analysis will be conducted, which will involve searching electronic databases using predetermined search terms, in order to identify relevant studies. Studies will be independently screened against predefined eligibility criteria and subgroup analysis will be used for the outcomes. Results and conclusion: The findings of this review are going to help clinicians and allied health professionals in treatment decisions.

Food allergies, defined as an immune response to food proteins, affect as many as 8% of young children and 2% of adults in western countries, and their prevalence appears to be rising like all allergic diseases. In addition to well-recognized urticaria and anaphylaxis triggered by IgE antibody– mediated immune responses, there is an increasing recognition of cell-mediated disorders, such as eosinophilic esophagitis and food protein–induced enterocolitis. Non-IgE-Mediated gastrointestinal food allergies are a heterogeneous group of food allergies in which there is an immune reaction against food but the primary pathogenesis is not a production of IgE and activation of mast cells and basophils. : Those diseases tend to affect mainly the gastrointestinal tract and can present as acute (FPIES) or chronic reaction, such as Eosinophilic Esophagitis (EoE), Food Protein-Induced Allergic Proctocolitis (FPIAP). The role of food allergy in Non-EoE gastrointestinal Eosinophilic disorders (Non- EoE EGID) is poorly understood. : In some diseases like EoE, T cell seems to play a major role in initiating the immunological reaction against food, however, in FPIES and FPIAP, the mechanism of sensitization is not clear. : Diagnosis requires food challenges and/or endoscopies in most of the patients, as there are no validated biomarkers that can be used for monitoring or diagnosis of Non-IgE mediated food allergies. : The treatment of Non-IgE food allergy is dependent on diet (FPIES, and EoE) and/or use of drugs (i.e. steroids, PPI) in EoE and Non-EoE EGID. : Non-IgE mediated food allergies are being being investigated.

Dupilumab has been approved to treat atopic dermatitis, asthma, and nasal polyps and is in active clinical trials for the treatment of eosinophilic esophagitis (EoE). Given its shared immunopathology, we hypothesized that EoE symptoms and inflammation would improve when dupilumab therapy was used for other allergic indications.To measure the clinical and histologic response in EoE to dupilumab when treating other atopic diseases.We completed a retrospective chart review of all patients at Children's Hospital of Philadelphia and Rady Children Hospital who were prescribed dupilumab for atopic dermatitis, asthma, or nasal polyps and had a concomitant clinical diagnosis of EoE. Demographic information along with histology, symptom scores, medications, and diet information were collected. Response to dupilumab was evaluated.A total of 45 patients were identified. Of which, 11 patients were prescribed dupilumab for asthma, 27 for atopic dermatitis, 3 for nasal polyps, and 4 for compassionate use for EoE. There was no follow-up data for 8 patients. Follow-up histology was available for 26 patients: 22 of 26 had less than 6 eosinophils per high power field after the initiation of dupilumab with significant improvement (pre: 52.9 + 35.1 to post: 4.5 + 10.9 eosinophils/high power field, P.005). A total of 28 patients had improvement of symptoms, with 24 patients reporting complete resolution of symptoms after dupilumab initiation. Reductions in EoE treatment medications (swallowed steroids, proton pump inhibitors) or expansion of diet occurred in 29 patients treated with dupilumab.Dupilumab therapy initiated for atopic disease effectively induces symptomatic and histologic remission of esophageal disease and reduces the need for EoE-directed therapy in patients with concomitant EoE.

Eosinophilic esophagitis (EoE) is a chronic clinical-pathologic disease characterized by eosinophilic infiltration of the esophageal epithelium with esophageal dysfunction symptoms.EoE can occur at any age and has different clinical manifestations depending on the age onset.To date, esophago-gastroduodenal endoscopy (EGD) with biopsy is the gold-standard for EoE diagnosis.According to the recent consensus guidelines, proton pump inhibitors, corticosteroids and elimination diets could be a first-line therapy option. The aim of the treatment is clinical and histological remission for preventing long-lasting untreatable fibrosis.A multidisciplinary approach (allergist, gastroenterology, dietitian, and pathologist) is recommended for managing patients affected by EoE, given the complexity of its treatment.This review will provide a practical guide to assist pediatricians treating children with EoE.Moreover, it highlights the unmet needs in diagnosis and treatment that require urgent attention from the scientific community in the aim of improving the management of patients with EoE.

Background\ud \ud Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as “may contain traces of” is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin.\ud \ud \ud \ud Methods\ud \ud MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results.\ud \ud \ud \ud Results\ud \ud In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and sesame seeds.\ud \ud \ud \ud Conclusion\ud \ud Based on the literature studied for this review, it can be stated that cross-contamination of the 14 major food allergens below 0.5 mg/100 g is likely not to endanger most food allergic patients when a standard portion of food is consumed. We propose to use the statement “this product contains the named allergens in the list of ingredients, it may contain traces of other contaminations (to be named, e.g. nut) at concentrations less than 0.5 mg per 100 g of this product” for a voluntary declaration on processed food packages. This level of avoidance of cross-contaminations can be achieved technically for most processed foods, and the statement would be a clear and helpful message to the consumers. However, it is clearly acknowledged that a voluntary declaration is only a first step to a legally binding solution. For this, further research on threshold levels is encouraged.

The epithelium is integral to the protection of many different biological systems and for the maintenance of biochemical homeostasis. Emerging evidence suggests that particular children have epithelial vulnerabilities leading to dysregulated barrier function and integrity, that resultantly contributes to disease pathogenesis. These epithelial vulnerabilities likely developin uteroor in early life due to various genetic, epigenetic and environmental factors. Although various epithelia are uniquely structured with specific function, prevalent allergic-type epithelial diseases in children potentially have common or parallel disease processes. These include inflammation and immune response dysregulation stemming from atypical epithelial barrier function and integrity. Two diseases where aetiology and pathogenesis are potentially linked to epithelial vulnerabilities include Paediatric Asthma and Eosinophilic Oesophagitis (EoE). For example, rhinovirus C (RV-C) is a known risk factor for paediatric asthma development and is known to disrupt respiratory epithelial barrier function causing acute inflammation. In addition, EoE, a prevalent atopic condition of the oesophageal epithelium, is characterised by similar innate immune and epithelial responses to viral injury. This review examines the current literature and identifies the gaps in the field defining viral-induced effects on a vulnerable respiratory epithelium and resulting chronic inflammation, drawing from knowledge generated in acute wheezing illness, paediatric asthma and EoE. Besides highlighting the importance of epithelial structure and barrier function in allergic disease pathogenesis regardless of specific epithelial sub-types, this review focuses on the importance of examining other parallel allergic-type disease processes that may uncover commonalities driving disease pathogenesis. This in turn may be beneficial in the development of common therapeutics for current clinical management and disease prevention in the future.

Eosinophilic esophagitis (EoE) is an immune-mediated esophageal disorder, linked with sensitization to food and airborne allergens. Dietary manipulations are proposed for the management of EoE inflammation and are often successful, confirming the etiological role of food allergens. Three different dietary approaches are widely used: the elemental, the empirical, and the allergy-test-driven approach. We performed a systematic review to assess the evidence on the association of allergens, detected by allergy tests, with clinically confirmed triggers of EoE. We systematically searched PubMed, Scopus, Embase, and the Cochrane Library, through 1 June 2021. We sought studies examining the correlation of skin-prick tests (SPT), atopy patch tests (APT), specific IgE, and serum-specific IgG4, with confirmed triggers of EoE. Data on the use of prick–prick tests were also extracted. Evidence was independently screened by two authors against predefined eligibility criteria. Risk of bias was assessed with the ROBINS-I tool. Of 52 potentially eligible studies, 16 studies fulfilling quality criteria were included. These studies used one to three different allergy tests detecting food sensitization. The positive predictive value was generally low to moderate but higher when a combination of tests was used than single-test evaluations. None of the selected studies used serum-specific IgG4. Although an extreme methodological variability was noticed in the studies, allergy-based elimination diets were estimated to be efficient in 66.7% of the cases. The efficacy of targeted elimination diets, guided by SPT, sIgE, and/or APT allergy tests, does not appear superior to empirical ones. In the future, tests using esophageal prick testing or ex vivo food antigen stimulation may prove more efficient to guide elimination diets.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food allergic disorder that has gained a major interest the past decade. FPIES prevalence, which still needs to be accurately determine in different populations, appears to be higher than previously thought (ie up to 0.7% in infants in the 1st year of life). FPIES to seafood in adults is also increasingly reported; limited data suggest that adult FPIES is most commonly triggered by shellfish, tends to affect females more than men, is characterized by a significant delay in diagnosis and a prolonged course. The first international consensus guidelines on diagnosis and management of FPIES have been published in 2017, proposing new diagnostic criteria as well as new criteria for a positive oral food challenge. However, there is a need to develop new biomarkers to improve the diagnosis and management of FPIES patients, and this requires a better understanding of the pathophysiology. Recently, the role of T cells has been questioned and a major role of innate immune cells has been suggested in acute FPIES. Regarding the treatment of acute FPIES reaction, ondansetron has emerged as an adjunct to intravenous rehydration in moderate-severe reactions and as a first-line treatment in mild reactions. Important information regarding the nutritional management of FPIES patients that might be complex has also been provided in the international guidelines. In this review, we discuss recent advances regarding all those different aspects.

Eosinophilic esophagitis (EoE) is a disorder which affects all ages, from infancy through adulthood. It typically affects atopic individuals (Table 1) and is a chronic allergic disorder, with foods ubiquitous in the diet being the most described trigger of this isolated eosinophilic inflammation of the esophagus in both adults and children. This inflammatory process leads to esophageal symptoms such as dysphagia and feeding intolerance. In this review, we provide a brief overview of the current state of EoE therapy and symptomatology and then try to make the case for early diagnosis and treatment to prevent some of the long-term consequences of esophageal inflammation.

Eosinophilic oesophagitis (EoE) is a chronic disease associated with significant morbidity that can result in permanent fibrosis and stricture formation. Given the complexity, a multidisciplinary approach is recommended to manage these patients. In the majority of children with EoE not responsive to proton-pump inhibitor (PPI), inflammation is driven by sensitivity to foods and treatment with an elimination diet can be effective. Foods most commonly identified to trigger EoE in children are milk and wheat, but egg, soy, meats and grains can also be triggers. Foods can be eliminated using a step-down or step-up approach. If the goal is to achieve quick remission, elemental diet or six food elimination diets are the most effective. A step-up approach starting from a 1-2 food elimination diet and increasing the number of foods based on a personalized dietary approach is recommended if the goal is to achieve remission using the least number of endoscopies and with increased acceptability to the patient. Children with EoE on elimination diets require frequent monitoring of growth and nutrition, as well as screening for symptoms of EoE, allergy and mindfulness regarding psychosocial impact of chronic disease on the family and child. Current research focused on tools to select patients who mostly will benefit from dietary treatment, identify relevant food allergens, obtain oesophageal tissue non-invasively and induce tolerance will greatly improve the treatment of EoE.

Background Food protein–induced enterocolitis syndrome (FPIES) is a non–IgE-mediated food allergy that is diagnosed based on clinical findings, but can be confirmed with oral food challenge (OFC). OFC is more often performed to assess the development of tolerance. Most studies describing OFCs in FPIES are limited in size. Objective We sought to describe our experience with OFCs using our FPIES protocol. Patients were given one-third of serving size with a 4-hour observation period, followed by home titration to full dose. Methods We conducted a retrospective chart review of patients who underwent OFC via the FPIES protocol from 2014 to 2017. Data regarding the history of reaction, age at the time of challenge, and reactions during challenge or with home introduction were collected. Results A total of 169 OFCs were completed under the FPIES protocol, in 119 patients to 19 different foods. Thirty challenges (18%) were positive, with 17 challenges (10%) during initial challenge and 13 (7.7%) during home dosing. Most reactions during initial challenge required intravenous fluids (IVF), but hypotension was uncommon. One hundred thirty-nine (82%) OFCs were negative with home introduction, indicating tolerance to the challenged foods. The mean age of passing a challenge to milk, soy, and grain was earlier than that of other solid foods. Conclusions: Our data suggest that our FPIES OFC protocol is safe. Early administration of IVF may prevent the development of hypotension. It is difficult to stratify the risk of severe or delayed reaction based on patient characteristics, and more data are needed to identify those appropriate for home introduction.

Background: As there is limited data on the sustainability of desensitization of multifood-oral immunotherapy (multifood-OIT), we conducted a multisite multifood-OIT study to compare the efficacy of successful desensitization with sustained dosing vs discontinued dosing after multifood-OIT. Methods: We enrolled 70 participants, aged 5–22 years with multiple food allergies confirmed by double-blind placebo-controlled food challenges (DBPCFCs). In the open-label phase of the study, all participants received omalizumab (weeks 1–16) and multi-OIT (2–5 allergens; weeks 8–30) and eligible participants (on maintenance dose of each allergen by weeks 28–29) were randomized 1:1:1 to 1 g, 300 mg, or 0 mg arms (blinded, weeks 30–36) and then tested by food challenge at week 36. Success was defined as passing 2 g food challenge to at least 2 foods in week 36. Findings: Most participants were able to reach a dose of 2 g or higher of each of 2, 3, 4, and 5 food allergens (as applicable to the participant's food allergens in OIT) in week 36 food challenges. Using an intent-to-treat analysis, we did not find evidence that a 300 mg dose was effectively different than a 1 g dose in maintaining desensitization, and both together were more effective than OIT discontinuation (0 mg dose) (85% vs 55%, P = 0.03). Fifty-five percent of the intent-to-treat participants and 69% of per protocol participants randomized to the 0 mg arm showed no objective reactivity after 6 weeks of discontinuation. Cross-desensitization was found between cashew/pistachio and walnut/pecan when only one of the foods was part of OIT. No statistically significant safety differences were found between the three arms. Interpretation: These results suggest that sustained desensitization after omalizumab-facilitated multi-OIT best occurs through continued maintenance OIT dosing of either 300 mg or 1 g of each food allergen as opposed to discontinuation of multi-OIT. Funding: Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Jeff and MacKenzie Bezos, NIAID AADCRC U19AI104209. Trial Registration Number: ClinicalTrials.gov number, NCT02626611. Keywords: Food allergy, Oral immunotherapy, Omalizumab, Sustained unresponsiveness, Food allergen

INTRODUCTION: Diagnostic and therapeutic strategies in eosinophilic esophagitis (EoE) are evolving. New knowledge regarding the pathophysiology of EoE has been the foundation for updated diagnostic recommendations and new therapeutic trials. AREAS COVERED: We performed structured literature searches in Medline and PubMed, Cochrane meta-analyses, and abstracts of international congresses to review therapeutic approaches for EoE in July 2018. Additional articles were obtained by perusing the references of articles identified in the original PubMed search. Articles were excluded if they did not focus on the mechanism of disease, diagnosis, or treatment of humans with eosinophilic esophagitis. EXPERT COMMENTARY: Recent advances in the understanding of mechanisms underlying the pathology of eosinophilic esophagitis (EoE) have resulted in significant change in the diagnostic algorithm for EoE, and are identifying promising potential targets for personalized medicine. There is clinical need for improved targeted therapy for EoE, and better understanding the underlying pathophysiology of EoE will help to determine therapeutic targets. In this review, we highlight key mechanisms in the pathophysiology of EoE and how they are being utilized to change therapy in EoE.

Adverse food reactions include immune-mediated food allergies and non-immune-mediated intolerances. However, this distinction and the involvement of different pathogenetic mechanisms are often confused. Furthermore, there is a discrepancy between the perceived vs. actual prevalence of immune-mediated food allergies and non-immune reactions to food that are extremely common. The risk of an inappropriate approach to their correct identification can lead to inappropriate diets with severe nutritional deficiencies. This narrative review provides an outline of the pathophysiologic and clinical features of immune and non-immune adverse reactions to food—along with general diagnostic and therapeutic strategies. Special emphasis is placed on specific nutritional concerns for each of these conditions from the combined point of view of gastroenterology and immunology, in an attempt to offer a useful tool to practicing physicians in discriminating these diverging disease entities and planning their correct management. We conclude that a correct diagnostic approach and dietary control of both immune- and non-immune-mediated food-induced diseases might minimize the nutritional gaps in these patients, thus helping to improve their quality of life and reduce the economic costs of their management.

BACKGROUND: End points used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments. OBJECTIVE: We sought to develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE. METHODS: Candidate outcomes were generated from systematic literature reviews and patient engagement interviews and surveys. Consensus was established using an iterative Delphi process, with items voted on using a 9-point Likert scale and with feedback from other participants to allow score refinement. Consensus meetings were held to ratify the outcome domains of importance and the core outcome measures. Stakeholders were recruited internationally and included adult and pediatric gastroenterologists, allergists, dieticians, pathologists, psychologists, researchers, and methodologists. RESULTS: The COS consists of 4 outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life. A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a 2-round Delphi process, and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, Eosinophilic Esophagitis Histology Scoring System, Eosinophilic Esophagitis Endoscopic Reference Score, and patient-reported measures of dysphagia and quality of life. CONCLUSIONS: This interdisciplinary collaboration involving global stakeholders has produced a COS that can be applied to adult and pediatric studies of pharmacologic and diet therapies for EoE and will facilitate meaningful treatment comparisons and improve the quality of data synthesis. ispartof: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY vol:149 issue:2 pages:659-670 ispartof: location:United States status: published

Objective There are no disease‐modifying therapies for the treatment of eosinophilic oesophagitis (EoE), which is driven by non‐IgE‐mediated allergic inflammation. A recent clinical trial of milk epicutaneous immunotherapy (EPIT) has shown initial promise, with 47% of treated EoE patients tolerating milk without recurrence of disease. Mechanisms of EPIT in EoE have not been studied in humans. Here, we identify transcriptional changes in the peripheral CD4+ T‐cell compartment during active EoE and following EPIT. Methods RNA isolation, sequencing and integrative data analysis were performed on peripheral CD4+ T cells isolated from 15 of 20 patients enrolled in a clinical trial of EPIT for EoE. Gene expression changes in peripheral CD4+ T cells were examined during diet therapy and following trial of milk antigen EPIT. Results We identify 244 differentially expressed genes in peripheral blood CD4+ cells of EoE patients consuming versus those eliminating milk, and 129 DEGs in CD4+ cells were isolated after EPIT versus after placebo (FDR ≤ 0.05). Gene set enrichment analysis identifies enrichment of hallmark interferon‐α and interferon‐γ response pathways in peripheral CD4+ T cells from EoE patients during active disease on a milk‐containing diet. We demonstrate overlap of this gene signature with the altered gene expression signature seen in EoE patient biopsy tissue. EPIT therapy response is associated with significant enrichment in pathways related to T‐cell receptor signalling (P = 1.16 × 10−14), antigen presentation and costimulation, and cytokine signalling (P = 1.11 × 10−16), as well as upregulation of genes associated with regulatory T‐cell function. Conclusions EoE is associated with distinct global transcriptional changes in CD4+ T cells, one feature of which is an IFN response signature. Clinically favorable response to EPIT is likely multifactorial but is associated with a distinct transcriptional profile in peripheral CD4+ cells supporting the hypothesis that EPIT alters peripheral CD4+ responses in EoE patients.

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), also known as COVID‐19, is a new strain of coronavirus that has not been previously identified in humans. SARS‐CoV‐2 is recognized as a highly contagious respiratory virus with severe morbidity and mortality, especially in vulnerable populations. Being a novel disease, everyone is susceptible, there are no vaccine and no treatment. To contain the spread of the disease, health authorities throughout the world have restricted the social interactions of individuals in various degrees. Allergists, like other physicians, are faced with the challenge of providing care for their patients, while protecting themselves and patients from getting infected, with strategies that are in continuous evolution as states work through the different stages of social distance. Allergist provides care for patients with the most common non‐communicable disease in the world: asthma, allergic rhinitis, food allergy, venom allergy, drug allergy atopic dermatitis, and urticarial syndromes. Some of these diseases are not only considered risk factors for severe reactions but also have symptoms such as cough and sneezing that are in differential diagnosis with COVID‐19. As we move forward, allergy symptoms may prevent patients from working, go to school, or access medical services that increasingly are allowing only asymptomatic individuals. In this review, we will outline how to take care safety of different allergic patients during the pandemic.

Severe asthma is an important topic in respiratory diseases, due to its high impact on morbidity and mortality as well as on health-care resources. The many challenges that still exist in the management of the most difficult-to-treat forms of the disease, and the acknowledgement of the existence of unexplored areas in the pathophysiological mechanisms and the therapeutic targets represent an opportunity to gather experts in the field with the immediate goals to summarize current understanding about the natural history of severe asthma and to identify gaps in knowledge and research opportunities, with the aim to contribute to improved medical care and health outcomes. This article is a consensus document from the “International Course on Severe Asthma” that took place in Palermo, Italy, on May 10–11, 2019. Emerging topics in severe asthma were addressed and discussed among experts, with special focus on patient’s needs and research opportunities, with the aim to highlight the unanswered questions in the diagnostic process and therapeutic approach.