Single food allergy and reasons for multiple exclusions: a prospective study.To the Editor,Food allergies (FA) present an increasing global challenge, influenced by factors such as genetic predisposition, ethnicity, age, and cultural dietary practices. Consequently, making predictions about future allergic reactions remains challenging and uncertain (1). For instance, in Brazil, it is estimated that approximately 6% of children under the age of three and 3.5% of adults suffer from FA, some studies even report a prevalence over 10% (1,2).Patients diagnosed with IgE-mediated FA must adhere to strict dietary restrictions to avoid potential life-threatening anaphylactic reactions. Such restrictions are crucial but come with significant consequences as increased nutritional risks, higher costs for special meal preparations and medical care with potential social and psychological impacts on both the individual and their family (3-6). The impact of FA on quality of life is frequently surrounded by persistent fear of adverse reactions after consuming certain foods (3).To better manage FA, it is important to understand the reasons behind the exclusion of additional foods beyond the primary allergen. This study aims to explore whether patients with confirmed IgE-mediated FA tend to exclude other foods and to identify possible reasons for such exclusions.This is a cross-sectional analysis conducted at a tertiary referral outpatient setting in Brazil with patients from 2011 to 2022. Were considered as truly FA patients with: recurrent clinical history consistent with IgE-mediated reactions or anaphylaxis, associated with positive specific IgE or a positive oral challenge test with IgE-mediated reactions. Patients with anaphylaxis due to non-food allergens, mixed or non-IgE-mediated food allergies, or comorbidities requiring restrictive diets unrelated to IgE-mediated reactions were excluded.Out of 305 patients followed,180 met the inclusion criteria. Data on the epidemiology and allergens excluded were extracted from institutional electronic medical records, with supplementary data obtained through telephone interviews when necessary for questionnaire completion. The primary diagnosticated allergen was categorized as F1, while additional excluded foods were classified as F2. Descriptive statistical analyses were taken via SAS 9.4 software. Qualitative variables were reported as frequencies and percentages, and quantitative variables as means and standard deviations. The study was approved by the local Ethics Commitee (Comitê de ética do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - CAAE number: 77471224.7.0000.0068) and  all persons involved had provided their informed consent to be a part in the study.Most of the patients, predominantly male, were diagnosed with allergies before six months of age. The most common F1 was milk (77.78%), followed by egg (17.22%). Anaphylaxis was reported in 70.56% of the patients, with a complete F1 epidemiological profile seen in Table 1 and 2.Of the patients, 55% excluded at least one F2, with an average of 1.57 exclusions per patient, ranging from 1 to 12, and 14 detected F2s. The primary reasons for excluding additional foods were an isolated positive specific IgE test (32.24%), and symptoms attributed to foods without diagnostic confirmation (21.86%), as detailed in Table 3. This can be considered a  pioneer study in Latin America, as it examines FA within the dietary diversity of this population, and addresses the existence of other food exclusions.As supported by international literature (4), there was a high number of secondary exclusions in patients with IgE-mediated allergies. However, new foods are becoming significant on this list, such as fruits, abundant on the local diet.Milk and eggs are prevalent in Brazilian dietary guidelines, both as whole foods and in preparations since the start of complementary feeding (1,2), which explains why milk was the most described F1, followed by eggs, a widely consumed protein. Peanuts, a food strongly associated with FA in the Northern hemisphere, was less common among the studied population, as they are less used in daily local diet (1,2).Among children with secondary exclusions, the most frequent was eggs. In this context, excluding such a common food from the daily diet increases the risk of impacting nutritional development and quality of life, especially for children in growth and neuropsychomotor development stages. This highlights the importance of understanding the reasons for food exclusions in order to mitigate the risks, as well as the consequences, associated with their removal from the diet (1,3,5,6).Surprisingly, the primary cause of excluding a second food was not a second IgE-mediated allergy but rather the presence of laboratory tests without symptoms or symptoms without laboratory confirmation/criteria for IgE-mediated FA, emphasizing the importance of accurate diagnosis, avoiding misdiagnosis through indiscriminate requests for unproven diagnostic tests or specific IgEs, which can by itself lead to the development of an IgE-mediated FA upon reinsertion, as demonstrated studies involving patients with atopic dermatitis (1,9)Although fatal anaphylaxis is rare, around 30% of individuals with IgE-mediated FA seek emergency treatment for allergy-related reactions (4). This ongoing fear can prevent patients and their families from trying new foods (neophobia) and may result in a cycle of unnecessary food exclusions, which could further exacerbate nutritional deficiencies and contribute to the development of additional allergies. In fact  the combination of fear and indiscriminate specific IgE testing can pose a risk of misdiagnosis, highlighting the importance of knowledge of diagnostic and screening criteria to reduce the findings of sensitization in asymptomatic patients or those without compatible IgE-mediated reactions and unnecessary exclusions.Based on the profile of secondary exclusions, it is increasingly important for the medical community to be aware that there are no reasons to alter the age and pattern of complementary feeding introduction, with no restriction of potentially allergenic foods, preventing unnecessary food exclusions, increasing the risk of selective eating, and neophobia (1,2,3,6,8). In this study’s case, patients who started excluding foods based only on sensitization, might become truly allergic to those foods upon re-insertion, increasing the risk of FA in a potentially preventable manner.Only about 20% of patients were truly F2 allergic, also suggesting the possibility of associations among some allergies, more than just antigenic similarity, but also syndromic other phenotypes as multiple FA. This needs to be explored in future research, like the association between milk and eggs or eggs and nuts allergies. It is important to understand IgE-mediated symptoms and to recognize when to value symptoms arising from non-immunological situations, such as food contamination, viral urticaria, worsening of atopic dermatitis lesions, among others, due to the risk of incorrect diagnosis and unnecessary food exclusions (2,9).The study has also several limitations: it was conducted at a single center and relied mostly on secondary data, which may introduce bias and limit the generalizability of the findings. The sample was limited by convenience, and not all excluded foods were diagnostically tested via oral food challenges (gold standard).This study demonstrates that patients with IgE-mediated FA frequently exclude additional foods usually based on non-confirmatory tests and fear of reactions. Such practices can lead to unnecessary nutritional, social, and economic consequences. A comprehensive approach to FA management, incorporating accurate diagnostic methods and careful consideration of clinical history and test results, is crucial for improving patient outcomes and quality of life.Kind Regards,Paula Mendonça P.S Gomes-MD1, Isadora C.M. Francescantonio-MD1, Beni Morgenstern-MD,PHD1, Mayra B. Dorna-MD,PHD1, Antonio C. Pastorino-MD,PHD1, Ana Paula M Castro-MD,PHD1Affiliations: 1- Allergy and Immunology Department - Instituto da Criança- University of São Paulo, São Paulo, SP, BrazilConflict of interest: the authors have no conflict of interest to declareWord Count: 1173Keywords : Food-Allergies, IgE Mediated, motivation