An algorithm for the diagnosis and management of IgE‐mediated food allergy, 2024 update

The European Academy of Allergy and Clinical Immunology (EAACI) recently launched their updated Clinical Guidelines for the Diagnosis and Management of IgE-mediated Food Allergy, which provide evidence-based recommendations for the practicing clinician seeing children and/or adults with suspected IgE-mediated food allergy.1 This medical algorithm aims to summarize the practical approach to individual patients considering both diagnosis (Figure 1) and management (Figure 2), following EAACI recommendations. The first and most valuable step to reaching an accurate diagnosis is a well-conducted detailed allergy-focused clinical history, including dietary history. Key questions are listed in the Clinical Guidelines.1 It is important to ascertain, for each main allergenic food (e.g., cow's milk, egg, wheat, soya, fish, shellfish, peanut, tree nuts, sesame, legumes, fruits, and vegetables), whether these foods are consumed and whether there have been any possible allergic reactions. For foods that the patient is consuming regularly (i.e. weekly), in age-appropriate portion sizes, allergy testing should not be conducted. For foods to which the patient has or may have reacted to and to which there is epidemiological evidence for possible food allergy risk and there is opportunity for intervention (e.g., infant with early onset severe eczema who has reacted to egg and has not yet introduced peanut in the diet), IgE sensitisation should be investigated using skin prick test (SPT) to allergen extracts or the fresh food (especially important for fruits, vegetables, legumes and uncommon foods) or specific IgE (sIgE) to allergen extract. In the equivocal cases, for instance in the absence of a history of exposure and low test results, an OFC is deemed necessary. The systematic review supporting the new EAACI guidelines includes multiple meta-analyses of diagnostic accuracy of multiple allergy tests to many foods, including SPT, sIgE to allergen extracts, sIgE to allergen components and the basophil activation test (BAT).2 For instance, it included meta-analyses of diagnostic accuracy of optimal cutoffs, as reported by the study authors; commonly used cutoffs; cutoffs for maximal sensitivity; cutoffs for maximal sensitivity, and also meta-analyses comparing the diagnostic accuracy of various tests for a given food allergy, by age group and geographical location. These data provide the clinician with many tools they can consult and consider adopting if relevant to the clinical context of their practice. A clear history of IgE-mediated symptoms minutes after exposure to a specific food, together with evidence of significant IgE sensitisation to that food, confirms the diagnosis of IgE-mediated food allergy. Conversely, the absence of such a history and lack of IgE sensitisation excludes the diagnosis. However, if the history is unclear, levels of sensitisation are low or the history is not supported by the allergy tests in any other way, more tests need to be performed. Additional tests include IgE to individual allergens that are known to have high specificity (so-called “informative components”), for instance Ara h 2 from peanut, Cor a 14 from hazelnut and Ana o 3 from cashew; and the BAT (meta-analyses were performed for BAT to peanut and sesame and the results were supportive of its use, if available). If IgE to the informative component is significant and/or BAT is positive to the allergen, food allergy is confirmed. If not, an oral food challenge is required to confirm or exclude food allergy diagnosis. Once the diagnosis of IgE-mediated food allergy is confirmed, reassessment of sensitisation status periodically should be undertaken to assess for possible resolution of food allergy. This is more likely in young children, allergic to foods such as cow's milk, egg, wheat and soya, with low level sensitisation at diagnosis. Once food allergy is confirmed, dietary advice needs to be provided, including avoidance of the culprit food or food form and continued consumption of tolerated foods (that often individuals or families unnecessarily avoid after an index allergic reaction). Clinical practice has evolved from strict avoidance to active management of food allergy; thus, when certain forms of the food are tolerated (e.g., baked milk, egg or soya in children allergic to nonbaked forms of these foods or cooked fruits and vegetables in patients with pollen-food syndrome), its consumption is encouraged to broaden the diet. Individualized dietary advice is important, ideally supported by a specialised dietitian, to ensure optimal nutrition and growth (in children). A written treatment plan for eventual allergic reactions resulting from accidental exposure to the allergen is essential. In most cases, this includes oral nonsedative antihistamine (such as cetirizine or loratadine). In some scenarios, adrenaline auto-injectors (AAI) need to be prescribed (see table in Figure 2), ideally two devices per patient.3 In patients with asthma or recurrent wheeze, a salbutamol inhaler should also be part of the treatment pack. Patients and families need to be trained on the recognition of allergic reactions and the use of AAI, which should be reinforced at every follow up visit. Some patients and families may need support to cope with anxiety and changes to their lifestyle imposed by food allergies and allergen avoidance, and an appropriate referral to trained health care professionals, such as clinical psychologists, is desirable. Finally, for selected patients, immunomodulatory treatments may be indicated. Recent evidence has emerged supporting the licensing of omalizumab for IgE-mediated food allergy by the FDA, from 1 year of age.4 This is particularly suitable for patients with multiple food allergies as the treatment targets IgE irrespective of allergen specificity and, therefore, is allergen-agnostic. For children and adolescents with peanut allergy, peanut immunotherapy delivered by oral, sublingual or epicutaneous routes has been recommended, if available.5 For egg and cow's milk allergies, only oral immunotherapy has collected enough evidence to warrant recommendation, for teenagers and children, generally older than 4 years age, when the chances of natural resolution are lower. Recent studies suggest that young children have greater response rates to allergen-specific immunotherapy and may present with additional opportunities for a truly disease-modifying treatment. Of note, Palforzia has recently been approved for use from 1 year of age. There was insufficient evidence to support the use of allergen-specific immunotherapy for treatment of food allergy in adults.6 The absence of good quality evidence for multi-food OIT and allergen immunotherapy to foods other than peanut, cow's milk or egg precluded the elaboration of active recommendations for these interventions. In conclusion, an accurate diagnosis of food allergy is extremely important to avoid unnecessary dietary restrictions and identify the culprit food so that appropriate management can be implemented. This ensures dietary adequacy, prevention and appropriate treatment of accidental allergic reactions and a holistic approach to patients and families to allow them to live life fully, minimising restrictions to their lifestyle and their wellbeing. We would like to thank all expert group members for their valuable contribution to the EAACI Guidelines on Diagnosis and Management of IgE-mediated Food Allergy, and Jeanette Kobler and colleagues from the EAACI headquarters team, for logistical and administrative support. A.F. Santos reports grants from Medical Research Council (MR/M008517/1; MC/PC/18052; MR/T032081/1), Food Allergy Research and Education (FARE), the Immune Tolerance Network/National Institute of Allergy and Infectious Diseases (NIAID, NIH), Asthma UK (AUK-BC-2015-01), BBSRC, Rosetrees Trust and the NIHR through the Biomedical Research Centre (BRC) award to Guy's and St Thomas' NHS Foundation Trust, during the conduct of the study; personal fees from Thermo Scientific, Nutricia, Infomed, Novartis, Allergy Therapeutics, Buhlmann, as well as research support from Buhlmann and Thermo Fisher Scientific through a collaboration agreement with King's College London.

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