Preparation of Blinded Food Matrixes for Clinical Oral Challenges.

Food challenges

Food allergy can often cause a significant burden on patients, families, and healthcare systems. The complexity of food allergy management requires a multidisciplinary approach involving different types of healthcare providers, including allergists, dieticians, psychologists, nurses, family practitioners and, of particular relevance for this article, pediatric primary caretakers. Pediatricians may be the first-line healthcare providers for food allergy: strategies for management and guideline adherence have been highlighted. This review article summarizes the up-to-date recommendations on the role of pediatricians in the diagnosis, management, and prevention of IgE-mediated food allergy. Early introduction of allergenic foods like peanut is known to be of importance to reduce the development of peanut allergy in infants, and pediatricians are essential for educating and supporting parents in this decision. In scenarios of limited allergist availability, as is often the case among rural, Medicaid and minority populations, pediatricians can assist in the evaluation and management of food allergy, and provide action plans, education and counselling for patients and families. Pediatric primary caretakers play a key role in the diagnosis, management, and prevention of IgE-mediated food allergy. As more diagnostic tools and therapies in food allergy become available, the need for a multidisciplinary team is paramount to optimize patient care.

Although controlled oral food challenges are considered to be the gold-standard in the diagnosis of food related symptoms, especially if performed in a double-blind, placebo-controlled food challenges (DBPCFC) manner, there are still many unanswered questions and newer aspects, which may explain some pitfalls encountered during oral food challenges. For stopping an oral food challenge and declaring a challenge as positive or negative, symptoms should be objective and/or repetitive. The time interval between administering the food and observing the clinical reaction is an ambivalent factor. Possible reasons for false negative assessments include inadvertent drug use during oral challenges, and the fact that a short-term specific oral tolerance induction (SOTI) may be induced as increasing amounts of the offended food are administered during a titrated oral food challenge. Possible reasons for false positive assessments are the difficulty to maintain an appropriate strict diet throughout the oral challenge procedure, and that the elimination diet implemented before the oral food challenge in children with atopic eczema and suspected food related symptoms may itself be responsible for immediate type clinical symptoms, which had not been reported by the parents before. Finally augmentation factors are among the most plausible explanations for the inadequate reproducibility of an oral food challenge. Although a 100% standardization of the challenge procedure does not seem realistic, efforts should be made to improve the methodology used so far. On the contrary, the possible relation of DBPCFC and SOTI may offer potential advantages for future therapeutic approaches of food allergy.

Background Food allergy is defined as an adverse immune response that occurs after contact with or ingestion of a specific food. Since the clinical history can be confusing, diagnosis is challenging and may result in an overestimation of incidence, as already documented in other countries. A careful diagnosis of food allergies reflects significantly lower numbers than current estimates. Objective To establish the incidence of food allergies in the first year of life in children born in the city of Uberlândia/MG. Methods Between the years 2019 and 2022, the following steps were conducted based on the follow-up of newborns from two maternity hospitals in Uberlândia, located in the central region of Brazil: (1) an interview at the maternity ward; (2) a follow-up telephone interview after 12 months; (3) an online consultation for the investigation of suspected food allergy; and (4) the clinical evaluation and performance of allergic tests and oral food challenges for diagnostic confirmation. Results Out of the 3373 recruited newborns at the maternity ward, 2099 participated in the telephone interview after 12 months, and 144 with suspected food allergies underwent diagnostic confirmation. Seventeen skin prick tests and thirteen oral food challenges were performed on sixteen infants for eleven different foods. Only five participants confirmed food allergies to eggs (4), cow's milk (1), and peanuts (1). The incidence of IgE-mediated food allergies in the first year of life was 0.23%, while the incidence per food was 0.19% for eggs and 0.05% for both milk and peanuts. Conclusion The study demonstrates a reduced incidence of food allergy compared to previous studies and emphasizes the importance of confirming the diagnosis through oral food challenges. This practice reduces the number of unnecessary food exclusions, improving the quality of life for patients and their families, preventing potential growth and developmental impairments in infants, and reducing public spending on the treatment of food allergies. Keywords: infants; food allergy; oral food challenge.

IL-4 receptor alpha signaling alters oral food challenge and immunotherapy outcomes in mice

Diagnosis and Management of Food Allergy

Gastroesophageal reflux disease (GERD) and food allergy are frequent disorders of childhood. The purpose of this study was to determine the frequency of food allergy in children with refractory GERD. A total of 151 children resistant to pharmacologic GERD treatment underwent skin prick test, specific immunoglobulin E, eosinophil count, atopy patch test (APT), and oral food challenge, and were then divided into three groups according to the results of oral milk challenge and allergy work-up: group A1, positive oral milk challenge and positive IgE-mediated allergy test; group A2, positive milk challenge and negative IgE-mediated allergy test; and group B, negative oral milk challenge and negative allergy tests. There were 35, 30 and 86 patients in group A1, group A2 and group B, respectively. A total of 28 of 35 patients in group A1 had cow's milk allergy and the other seven patients had egg allergy. APT positivity was more common in group A2. Endoscopic esophagitis was observed in six group A1 patients and in four group A2 patients. Bloody stools, atopic dermatitis and recurrent wheezing episodes were significantly more common in group A1 than in group A2 and group B (P < 0.001, for both). Cow's milk allergy was observed frequently in children resistant to pharmacologic GERD treatment. Combined skin prick and specific IgE tests, APT and oral food challenge is essential for avoidance of unnecessary elimination diet.

Barriers and Solutions to Optimal Food Allergy Prevention, Diagnostic, and Management Strategies.

Rate of food introduction after a negative oral food challenge in the pediatric population

RationaleFood allergy is documented to result in considerable morbidity, negative impact on quality of life, and substantial medical care costs. Although anecdotal data suggest widely varying practices in the diagnosis and management of food allergies, the diversity and relative frequency of these practices have not been documented.MethodsA questionnaire was developed evaluating allergists’ management approaches of individuals with peanut allergy (PA) in Germany (DE), France (FR), and the United Kingdom (UK).ResultsHere, we report the survey results from a total of 109 allergists from DE, FR and the UK. They reported to confirm PA at initial diagnosis using skin prick test (≥60%), while allergists from DE and FR reported using allergen-specific IgE testing more (>86%) compared to the UK (<50%). At initial diagnosis, oral food challenge was used less in DE (13%) and FR (14%) and very rarely in the UK (3%) to confirm diagnosis. Recognition of acute reactions, use of adrenaline auto-injectors and allergen avoidance were reported to be discussed with the patient/caregiver at the initial office visit by most allergists (>75%). Half of the responders reported assessing the patient’s quality of life. 63% allergists reported retesting for PA resolution at a later date, with 45% allergists indicated to recommend ingestion of a normal serving of peanut regularly upon resolution. Lack of effective PA treatment was reported to be a ‘very significant’ barrier for optimal PA treatment, with allergists being less than ‘moderately familiar’ with data from clinical trials testing new treatments options for PA. Lastly, allergists stated that the severity of patient’s PA ranked as the most important factor in their decision to recommend oral immunotherapy for PA treatment.ConclusionsThis survey provides essential insights into the practice of allergists and highlights some areas that would inform strategies for education and improving PA healthcare.

Atopic dermatitis (AD) is commonly associated with food allergy. Oral food challenge is the gold standard in the diagnosis of food allergy, but still has some troubles. The aim of this study was to evaluate whether a single test among skin prick test (SPT), measurement of specific immunoglobulin E (IgE), and atopy patch test (APT) or a combination of them could make food challenges unnecessary in patients with AD. Twenty patients affected by AD, under 6 years of age, were evaluated. Every child was investigated for cow's milk and hen's egg allergy using SPT, measurement of serum IgE (sIgE), APT, diagnostic elimination diet for 4 weeks, and open food challenges for milk and egg. The diagnosis of food allergy was established according to the results of the food challenge. We compared the results of all the tests with those of the open food challenge and calculated for each test the following parameters: sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Eight of 40 open food challenges were assessed as positive. None of the diagnostic tools showed a sufficient accuracy to be able to replace the food challenge. However, SPT, APT, and the measurement of sIgE as single parameters showed an NPV of 90%, and the combination of SPT and APT showed an NPV of 92%. Food challenge remains the gold standard for food allergy diagnosis in young children with AD, but the combination of SPT and APT is useful when both tests are negative, because this result provides a guidance in excluding an allergy to the investigated food and could make the food challenge superfluous in this case.

BackgroundThe diagnosis of food allergy is based on a history of immediate allergic reaction following food ingestion, and skin prick test (SPT) demonstrating sensitization with commercial extracts (CE) or fresh food (FF). For most food allergens, the SPT with FF is considered more accurate and predictive. Regarding cow’s milk, the results are inconclusive. This retrospective study aimed to evaluate the accuracy of SPT with fresh milk compared to CE (cow’s milk and casein) for evaluation of cow’s milk allergy (CMA).MethodsThis study summarized the medical records of children, diagnosed with CMA. The data include demographics, skin tests and oral food challenge results, as well as atopic comorbidities.ResultsRecords of 698 patients with the diagnosis of CMA were reviewed, 388 fulfilled the inclusion criteria. Overall, 134 patients (34.54%) had an additional atopic disease. The SPT wheal size with fresh milk was significantly larger than with CE (cow's milk and casein) at first evaluation or before oral food challenge (OFC). Combination of SPT results (CE and FF) gave the maximal odds ratio for reaction during OFC and SPT with fresh milk alone gave the minimal OR (34.18 and 4.74, respectively).ConclusionsSPT with CE for CMA evaluation is more reliable than SPT performed with fresh milk. In patients suspected of having IgE-mediated CMA, before deciding on performing OFC, it is advised to perform SPT with at least two different extracts, and always include casein. Fresh milk can serve as a backup if commercial extracts are not available. In cases that the SPT with fresh milk is 3 mm or less, there is 93.3% chance that the OFC will pass without reaction.Trial registration This study protocol was reviewed and approved by the Ethics Committee of Meir Medical Center, IRB Number 0083-18 MMC.

Food allergy is increasing in prevalence, posing significant challenges for individuals and their families and adversely affecting their quality of life. Misdiagnosis can lead to unnecessary dietary and social limitations and increased food allergy risk, whereas failure to diagnose may result in life-threatening anaphylaxis. Therefore, a precise diagnosis is of the utmost importance; however, barriers exist at every stage of the diagnostic process. Diagnosis of food allergy relies on clinical history, IgE sensitization tests, and oral food challenge. Component testing and identification of optimal cutoffs have improved diagnostic accuracy. Nevertheless, many patients still require an oral food challenge, and better tests are needed to reduce this need. Novel ways of detecting biomarkers, such as the basophil activation test and peptide-specific IgE level, are transitioning into clinical practice. Future approaches may include the use of alternative biologic samples, novel laboratory technologies, and analytic tools (including artificial intelligence) to integrate test results and clinical information. Conscientious use of existing tests, access to tests with superior diagnostic accuracy, and combination of tests, can lead to improved precision of diagnosis of food allergy and timely introduction of tolerated foods into the diet. This review summarizes recent advances in novel approaches to food allergy diagnosis that can enhance clinical decision making both now and in the future.

Oral food challenge (OFC) is the gold-standard to diagnose food allergy; however, it is a labour and resource-intensive procedure with the risk of causing an acute allergic reaction, which is potentially severe. Therefore, OFC are reserved for cases where the clinical history and the results of skin prick test and/or specific IgE do not confirm or exclude the diagnosis of food allergy. This is a significant proportion of patients seen in Allergy clinics and results in a high demand for OFC. The basophil activation test (BAT) has emerged as a new diagnostic test for food allergy. With high diagnostic accuracy, it can be particularly helpful in the cases where skin prick test and specific IgE are equivocal and may allow reducing the need for OFC. BAT has high specificity, which confers a high degree of certainty in confirming the diagnosis of food allergy and allows deferring the performance of OFC in patients with a positive BAT. The diagnostic utility of BAT is allergen-specific and needs to be validated for different allergens and in specific patient populations. Standardisation of the laboratory methodology and of the data analyses would help to enable a wider clinical application of BAT.

BackgroundIt is of major importance to diagnose food allergy accurately. Current guidelines support the use of oral food challenges to do so. The double‐blind placebo‐controlled food challenge (DBPCFC) has been regarded as the ‘gold standard’ for decades. However, DBPCFCs are costly, and time‐ and resource‐intensive procedures. Structural implementation of less demanding open food challenges will only find support if research demonstrates that their outcome is comparable to DBPCFC, yet this has been proven difficult to investigate.MethodsWe performed a literature review to investigate the diagnostic accuracy of oral food challenges and interviewed 19 parents of children with proven or suspected food allergy about the design of a trial to study this.ResultsAn overview of the dilemma of diagnosing food allergy using oral food challenges, and the methodological issues and parents’ opinions to study this. No comparative studies have been performed using the latest guidelines on oral food challenges.ConclusionsThere is an urgent need to investigate the diagnostic accuracy of different oral food challenge protocols. We present the rationale and design of the ALDORADO trial (ALlergy Diagnosed by Open oR DOuble‐blind food challenge) that has been set up to investigate whether the outcome of the open food challenge is comparable to DBPCFC.