Novel diagnostics in food allergy.

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.

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.

Food challenges

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.

Can conjunctival provocation test facilitate the diagnosis of food allergy in children?

Basophil Activation Test Discriminates Between Allergy and Tolerance Among Peanut Sensitized Children

Clinically, oral food challenges have value in the diagnosis and management of food allergy. Oral food challenges are used not only for diagnostic confirmation that ingestion of a specific food elicits an adverse reaction, but also for determining individual threshold doses, tracking the progress toward desensitization during immunotherapy, determining the effect of processing on the allergenicity of a specific food, assessing the allergenicity of an ingredient derived from an allergenic source, and tracking the progress toward development of age-related tolerance to a specific food. To eliminate bias in oral challenges, the food under investigation is masked in a matrix so that it is not sensorially detectable by the patient or the clinical observer. The preparation of oral challenge foods requires care in the selection of the allergenic components, the selection of the components of the matrix, the masking of the allergenic component, and the homogeneity of the allergen in the overall matrix.

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

The basophil activation test (BAT) has proven to be a useful tool for the diagnosis of IgE-mediated food allergy and the evaluation of clinical tolerance in food allergic patients. Until now, successful oral desensitization to food allergen has been correlated with changes in cytokine production (IL-4 and INF-γ) and allergen-specific IgE and IgG4 antibodies. We report a case of a 12-year-old male affected by cow’s milk allergy. The diagnosis was based on a positive allergological work-up, included skin prick test with commercial food extracts (Alk-Abello) and fresh cow’s milk (prick-by-prick method), detection in serum of total and specific IgE (ImmunoCAP System, Phadia), basophil activation test and finally a double-blind placebo-controlled food challenge. Skin prick test, specific IgE, BAT and oral food challenge were positive and so we decided to carry on a sublingual-oral desensitization treatment with cow’s milk, performed according to standardized protocol. In order to evaluate the immunological changes occurred during the immunotherapy, we performed further laboratory tests, included the detection in serum of total and specific IgE and BAT at the end of protocol. Desensitization was successfully carried out within 12 months, reaching the maximum dose of 150 ml of cow’s milk without side effects. The patient showed a decrease of specific IgE levels without reaching normal values and an increase of specific IgG4 levels; whereas the BAT starting from a positive value of 59% became negative after 12 months of treatment. This case report shows how it is possible to monitor allergen-specific basophil responses using the flow cytometry in order to identify an acquired tolerance induced by desensitization. Although further studies are needed, it was interesting to note that the basophil activation test seems to be more sensitive and characterized by a close correlation with the clinical tolerance.

BackgroundThe literature on diagnostic tests for food allergy currently lacks clear consensus regarding the accuracy and safety of different investigative approaches. The European Academy of Allergy and Clinical Immunology is in the process of developing its Guideline for Food Allergy and Anaphylaxis, and this systematic review is one of seven inter-linked evidence syntheses that are being undertaken in order to provide a state-of-the-art synopsis of the current evidence base in relation to epidemiology, prevention, diagnosis and clinical management, and impact on quality of life, which will be used to inform the formulation of clinical recommendations. The aim of this systematic review will be to assess the diagnostic accuracy of tests aimed at supporting the clinical diagnosis of IgE-mediated food allergy.MethodsThe following databases from inception to September 30, 2012 will be searched for studies of diagnostic tests: Cochrane Library (Wiley&Sons); MEDLINE (OVID); Embase (OVID); CINAHL (Ebscohost); ISI Web of Science (Thomson Web of Knowledge); TRIP Database (web http://www.tripdatabase.com); and Clinicaltrials.gov (NIH web). These database searches will be supplemented by contacting an international panel of experts. Studies evaluating APT, SPT, specific-IgE, and component specific-IgE in participants of any age with suspected food allergy will be included. The reference standard will be DBPCFC in at least 50% of the participants. Studies will be quality assessed by using the QUADAS-2 instrument. We will report summary statistics such as sensitivity, specificity, and/or likelihood ratios. We will use the hierarchical summary ROC (HSROC) model to summarize the accuracy of each test and to compare the accuracy of two or more tests.DiscussionDecisions on which tests to use need to be guided by availability of tests, populations being cared for, risks, financial considerations and test properties. This review will examine papers from around the world, covering children and adults with suspected food allergy in varying populations and concentrated on four type of tests: APT, SPT, specific-IgEs, and component specific-IgEs.

Human basophil activation measured by CD63 expression and LTC4 release in IgE-mediated food allergy.

Utilization of basophil activation in the diagnosis and monitoring of food allergy has gained increasing recognition. An ex-vivo functional assay, basophil activation reflects clinical reactivity, thereby providing clinically relevant insights. Moreover, as a biomarker of reactivity and tolerance, basophil activation testing (BAT) may provide a useful tool for management of food allergies. Despite its utility, significant limitations of BAT have prevented widespread use. Addressing these limitations will increase the future application and adoption of BAT in food allergy. A number of clinical trials in the past few years have demonstrated the use of BAT in the diagnosis and treatment of food allergy. Specifically, BAT has been found to be a biomarker of tolerance. Basophil activation testing is an effective biomarker for diagnosis and monitoring of food allergy.

Diagnosis and Management of Food Allergy

Adverse food reactions (hypersensitivity) can be either immune mediated (food allergy) or nonimmune mediated (intolerance). Nonimmune mediated reactions (intolerance) are classified as enzymatic, pharmacologic, or undefined food intolerance; together they account for the majority of food hypersensitivity reactions. Diagnosis of food allergy is based on medical history, physical examination, and diagnostic tests; the oral food challenge is considered the “gold standard” for diagnosis. Therapy for food allergy is complete exclusion of the allergen-containing food(s). It is recommended that practitioners consider patient referral to a registered dietitian for education on elimination diets and monitoring for nutritional adequacy. Initiating early intervention in high-risk infants may decrease prevalence.

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