Non-IgE Mediated Hypersensitivity to Food Products or Food Intolerance—Problems of Appropriate Diagnostics

The diagnosis of food intolerance is tricky due to the different etiologies of adverse reactions. There is also a lack of clear rules for interpreting alternative tests used to diagnose these problems. The analyses of IgG4 concentration in serum or cytotoxic tests became the basis of elimination diets. However, it can result in nutritional deficiencies and loss of tolerance to eliminated foods. Our study aimed to assess the necessity of food elimination in four cases with food intolerance symptoms based on alternative diagnostic tests. Four patients without food allergies, who manifested diverse clinical symptoms after food, were presented due to the following factors: clinical history, diagnostic tests, elimination diet, and filaggrin gene (FLG) mutation. It was found that higher IgG4 levels against foods and higher cytotoxic test values are not clinically relevant in each of the studied individuals. They should not be decisive for the elimination of food products. The study of FLG-SNVs revealed the association of some clinical symptoms in patients with hypersensitivity to several food allergens and reported genetic variants in the FLG gene.

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Immunogenetic, Molecular and Microbiotic Determinants of Eosinophilic Esophagitis and Clinical Practice—A New Perspective of an Old Disease

International Journal of Molecular Sciences ◽

10.3390/ijms221910830 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10830

Author(s):

Alina Kanikowska ◽

Szymon Hryhorowicz ◽

Anna Maria Rychter ◽

Marcin A. Kucharski ◽

Agnieszka Zawada ◽

...

Keyword(s):

Clinical Symptoms ◽

Management Strategies ◽

Elimination Diet ◽

Diagnostic Tools ◽

Pharmacologic Therapy ◽

Food Impaction ◽

Eosinophilic Oesophagitis ◽

Ige Mediated ◽

Genetic And Environmental Factors ◽

New Perspective

Eosinophilic oesophagitis (EoE) is a chronic, allergic disease associated with a T-lymphocyte response inducing esophageal eosinophilic infiltration in the esophagus. Inflammation and tissue fibrosis are responsible for the main clinical symptoms such as food impaction and dysphagia. The etiopathogenesis is multifactorial in which genetic and environmental factors coexist. The most common trigger is a non-IgE-mediated food allergy to milk, wheat, egg, soybean, nuts, fish, and seafood. The second factor we focus on is the contribution of genetic variation to the risk of EoE, describing the expression profile of selected genes associated with eosinophilic oesophagitis. We raise the topic of treatment, aiming to eliminate inflammation through an elimination diet and/or use of pharmacologic therapy with the use of proton pump inhibitors or steroids and endoscopic procedures to dilate the esophagus. We demonstrate that early diagnosis and effective treatment prevent the development of food impaction and decreased quality of life. The increasing presence of EoE requires bigger awareness among medical specialists concerning clinical features, the course of EoE, diagnostic tools, and management strategies.

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Using oral food challenges to provide clarity and confidence when diagnosing food allergies

Journal of Food Allergy ◽

10.2500/jfa.2021.3.210002 ◽

2021 ◽

Vol 3 (1) ◽

pp. 3-7 ◽

Cited By ~ 1

Author(s):

Justin Greiwe

Keyword(s):

Food Allergy ◽

Immunoglobulin E ◽

Food Challenge ◽

Clinical History ◽

The United States ◽

Oral Immunotherapy ◽

Food Allergies ◽

Ige Mediated ◽

Challenge Education ◽

Food Challenges

A verified food allergy can be an impactful life event that leads to increased anxiety and measurable effects on quality of life. Allergists play a key role in framing this discussion and can help alleviate underlying fears by promoting confidence and clarifying safety concerns. Correctly diagnosing a patient with an immunoglobulin E (IgE) mediated food allergy remains a nuanced process fraught with the potential for error and confusion. This is especially true in situations in which the clinical history is not classic, and allergists rely too heavily on food allergy testing to provide a confirmatory diagnosis. A comprehensive medical history is critical in the diagnosis of food allergy and should be used to determine subsequent testing and interpretation of the results. Oral food challenge (OFC) is a critical procedure to identify patients with an IgE-mediated food allergy when the history and testing are not specific enough to confirm the diagnosis and can be a powerful teaching tool regardless of outcome. Although the safety and feasibility of performing OFC in a busy allergy office have always been a concern, in the hands of an experienced and trained provider, OFC is a safe and reliable procedure for patients of any age. With food allergy rates increasing and analysis of recent data that suggests that allergists across the United States are not providing this resource consistently to their patients, more emphasis needs to be placed on food challenge education and hands-on experience. The demand for OFCs will only continue to increase, especially with the growing popularity of oral immunotherapy programs; therefore, it is essential that allergists become familiar with the merits and limitations of current testing modalities and open their doors to using OFCs in the office.

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Immunoglobulin E (IgE)-Mediated Food Allergy in Children: Epidemiology, Pathogenesis, Diagnosis, Prevention, and Management

Medicina ◽

10.3390/medicina56030111 ◽

2020 ◽

Vol 56 (3) ◽

pp. 111 ◽

Cited By ~ 1

Author(s):

Simona Barni ◽

Giulia Liccioli ◽

Lucrezia Sarti ◽

Mattia Giovannini ◽

Elio Novembre ◽

...

Keyword(s):

Food Allergy ◽

Immunoglobulin E ◽

Public Health Problem ◽

Elimination Diet ◽

Food Allergies ◽

Major Public Health Problem ◽

Double Blind ◽

Detailed Medical History ◽

Ige Mediated

A food allergy is an immunoglobulin E (IgE)-mediated hypersensitive reaction to food, which consists in the appearance of allergic symptoms; it can vary from common urticaria to even fatal anaphylaxis. The prevalence of food allergies has been increasing in the past twenty years and it represents a major public health problem in industrialized countries. The mechanism that leads to food allergies is the lack of immunologic and clinical tolerance to food allergens. The diagnosis of IgE-mediated food allergies is based on the combined use of a detailed medical history, in-vivo, and in-vitro research of specific IgE, the elimination diet, and the double-blind placebo-controlled food challenge. The only currently available treatment for allergies is the strict elimination diet. This type of attitude, which we could define as “passive”, does not overcome the risk of accidental reactions due to involuntary intake of the culprit food. For food allergy management, an “active” approach is urgently needed, such as specific allergen immunotherapy, which is currently under development and only used for research purposes. This article aims to give an updated review of IgE-mediated food allergies in pediatric populations in terms of epidemiology, pathogenesis, prevention, diagnosis, and management.

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Non-IgE-Mediated Gastrointestinal Food Protein-Induced Allergic Disorders. Clinical Perspectives and Analytical Approaches

Foods ◽

10.3390/foods10112662 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2662

Author(s):

Elisa Zubeldia-Varela ◽

Tomás Clive Barker-Tejeda ◽

Frank Blanco-Pérez ◽

Sonsoles Infante ◽

José M. Zubeldia ◽

...

Keyword(s):

Treatment Options ◽

Clinical History ◽

Food Allergies ◽

Clinical Aspects ◽

Food Protein ◽

Ige Mediated ◽

Gastrointestinal Food Allergy ◽

Allergic Proctocolitis ◽

Analytical Approaches ◽

Allergic Disorders

Non-IgE-mediated gastrointestinal food allergy (non-IgE-GI-FA) is the name given to a series of pathologies whose main entities are food protein-induced allergic proctocolitis (FPIAP), food protein-induced enteropathy (FPE), and food protein-induced enterocolitis syndrome (FPIES). These are more uncommon than IgE-mediated food allergies, their mechanisms remain largely unknown, and their diagnosis is mainly done by clinical history, due to the lack of specific biomarkers. In this review, we present the latest advances found in the literature about clinical aspects, the current diagnosis, and treatment options of non-IgE-GI-FAs. We discuss the use of animal models, the analysis of gut microbiota, omics techniques, and fecal proteins with a focus on understanding the pathophysiological mechanisms of these pathologies and obtaining possible diagnostic and/or prognostic biomarkers. Finally, we discuss the unmet needs that researchers should tackle to advance in the knowledge of these barely explored pathologies.

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Oral Food Challenge

Medicina ◽

10.3390/medicina55100651 ◽

2019 ◽

Vol 55 (10) ◽

pp. 651

Author(s):

Calvani ◽

Bianchi ◽

Reginelli ◽

Peresso ◽

Testa

Keyword(s):

Food Allergy ◽

Food Challenge ◽

Clinical History ◽

Specific Ige ◽

Oral Food Challenge ◽

Food Allergies ◽

Pediatric Allergy ◽

Expert Review ◽

Ige Mediated ◽

Food Specific Ige

: Oral food challenge (OFC) is the gold standard for diagnosis of IgE-mediated and non-IgE mediated food allergy. It is usually conducted to make diagnosis, to monitor for resolution of a food allergy, or to identify the threshold of responsiveness. Clinical history and lab tests have poor diagnostic accuracy and they are not sufficient to make a strict diagnosis of food allergy. Higher concentrations of food-specific IgE or larger allergy prick skin test wheal sizes correlate with an increased likelihood of a reaction upon ingestion. Several cut-off values, to make a diagnosis of some food allergies (e.g., milk, egg, peanut, etc.) without performing an OFC, have been suggested, but their use is still debated. The oral food challenge should be carried out by experienced physicians in a proper environment equipped for emergency, in order to carefully assess symptoms and signs and correctly manage any possible allergic reaction. This review does not intend to analyse comprehensively all the issues related to the diagnosis of food allergies, but to summarize some practical information on the OFC procedure, as reported in a recent issue by The Expert Review of Food Allergy Committee of Italian Society of Pediatric Allergy and Immunology (SIAIP)

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Intrinsic Atopic Dermatitis: Titration of Precipitins in the Screening of Food Allergens for Prescription of Elimination Diets and Desensitization Strategies

European Journal of Clinical Medicine ◽

10.24018/clinicmed.2021.2.6.129 ◽

2021 ◽

Vol 2 (6) ◽

pp. 1-9

Author(s):

Celso E. Olivier ◽

Daiana G. Pinto ◽

Ana P. M. Teixeira ◽

Jhéssica L. S. Santana ◽

Raquel A. P. G. Santos ◽

...

Keyword(s):

Atopic Dermatitis ◽

Food Allergy ◽

Food Allergen ◽

Elimination Diet ◽

Food Allergies ◽

P Value ◽

Food Allergens ◽

Diagnosis And Management ◽

Ige Mediated ◽

Positive Correlation Coefficient

Background: The diagnosis of non-IgE mediated food allergies may be a complex puzzle when there is no start point to establish an elimination diet to allow a clear clinical field to initiate diagnostic Oral Food Challenges tests. Objective: To evaluate the opportunity of the tube titration of precipitins to select food allergens to proceed with elimination diets to assist the diagnosis and management of adult patients with Food Allergy manifested as Intrinsic Atopic Dermatitis (IAD). Methods: The tube titration of specific precipitins against anamnesis-chosen food allergens were performed in 64 IAD patients and their titers were associated with an Improvement Verbal Scale Rate (IVSR) of the patient’s perception of the benefits of the Precipitins-based Elimination Diet (PED) performed with these specific food allergens, as well correlated with their positive or negative perception of the impairment of symptoms after the reintroduction of the Symptom-Related Food Allergen (SRFA). Results: In most cases, the PED contributed to a significant clinical improvement that allowed the patients to evaluate the individual effect of the reintroduction of each food allergen on their diets. There was a significant positive correlation coefficient between the titers of the food-specific titration of precipitins and the percentage of positive SRFA (Pearson r = 0.91; p-value = 0.0004). Conclusion: The semiquantitative titration of specific precipitins against food allergens is a promising triage test to select food allergens to proceed with elimination diets to support the diagnosis and management of non-IgE mediated Food Allergy in patients with Intrinsic Atopic Dermatitis.

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Fifteen-minute consultation: The EATERS method for the diagnosis of food allergies

Archives of Disease in Childhood - Education and Practice ◽

10.1136/archdischild-2018-316397 ◽

2019 ◽

Vol 104 (6) ◽

pp. 286-291 ◽

Cited By ~ 2

Author(s):

Mich Erlewyn-Lajeunesse ◽

Thomas Weir ◽

Lindsay Brown ◽

Helen Howells ◽

Jennie Rowley ◽

...

Keyword(s):

Health Care Professionals ◽

Clinical Skills ◽

Clinical History ◽

Food Allergies ◽

Test Results ◽

Allergy Test ◽

Degree Of Certainty ◽

History Of ◽

Novel Method ◽

Ige Mediated

The EATERS mnemonic is a novel method for taking an allergy focused clinical history. It provides a degree of certainty for diagnosing food allergy and can be used in both IgE and non IgE mediated reactions. EATERS will allow health care professionals to use their existing clinical skills to interpret the history of an allergic reaction, and by doing so will help to make sense of allergy test results.

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Non-IgE-Mediated Gastrointestinal Food Allergies in Children: An Update

Nutrients ◽

10.3390/nu12072086 ◽

2020 ◽

Vol 12 (7) ◽

pp. 2086 ◽

Cited By ~ 1

Author(s):

Roxane Labrosse ◽

François Graham ◽

Jean-Christoph Caubet

Keyword(s):

Immunoglobulin E ◽

Food Allergies ◽

Nutritional Deficiencies ◽

Food Protein ◽

Dietary Antigens ◽

Ige Mediated ◽

Before School ◽

Allergic Proctocolitis ◽

Conclusive Diagnosis

Non-immunoglobulin E-mediated gastrointestinal food allergic disorders (non-IgE-GI-FA) include food protein-induced enterocolitis syndrome (FPIES), food protein-induced enteropathy (FPE) and food protein-induced allergic proctocolitis (FPIAP), which present with symptoms of variable severity, affecting the gastrointestinal tract in response to specific dietary antigens. The diagnosis of non-IgE-GI-FA is made clinically, and relies on a constellation of typical symptoms that improve upon removal of the culprit food. When possible, food reintroduction should be attempted, with the documentation of symptoms relapse to establish a conclusive diagnosis. Management includes dietary avoidance, nutritional counselling, and supportive measures in the case of accidental exposure. The prognosis is generally favorable, with the majority of cases resolved before school age. Serial follow-up to establish whether the acquisition of tolerance has occurred is therefore essential in order to avoid unnecessary food restriction and potential consequent nutritional deficiencies. The purpose of this review is to delineate the distinctive clinical features of non-IgE-mediated food allergies presenting with gastrointestinal symptomatology, to summarize our current understanding of the pathogenesis driving these diseases, to discuss recent findings, and to address currents gaps in the knowledge, to guide future management opportunities.

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

Allergy and Asthma Proceedings ◽

10.2500/aap.2020.41.200061 ◽

2020 ◽

Vol 41 (5) ◽

pp. 336-340

Author(s):

Yasmin Hamzavi Abedi ◽

Cristina P. Sison ◽

Punita Ponda

Keyword(s):

Retrospective Chart Review ◽

Clinical History ◽

Specific Ige ◽

Exact Test ◽

Ara H 1 ◽

Sige Level ◽

History Of ◽

Laboratory Procedures ◽

Ige Mediated ◽

The Relationship

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.

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Allergenomics and analysis of causes of unintentional incorpo‑ ration of substances capable of causing IgE‑mediated food allergy into meat products

Theory and practice of meat processing ◽

10.21323/2414-438x-2020-5-3-4-11 ◽

2020 ◽

Vol 5 (3) ◽

pp. 4-11

Author(s):

E. V. Kryuchenko ◽

Yu. A. Kuzlyakina ◽

V. S. Zamula ◽

I. M. Chernukha

Keyword(s):

Food Allergy ◽

Risk Analysis ◽

Meat Products ◽

Food Product ◽

Food Products ◽

Legal Regulation ◽

Comprehensive Assessment ◽

Ige Mediated

The article discusses the definition and mechanism of IgE‑mediated food allergy, provides an overview of the legal regulation of the production and labeling of allergen-containing food products. In order to prevent the inadvertent appearance of allergens in products during their production, an allergenomics procedure is required — a comprehensive assessment of the allergic potential of a food product: allergenicity of product ingredients, risk analysis, and the procedure for managing allergens in the production.

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