Food Refusal During Oral Food Challenge: Warning Sign Or Red Herring?

Food challenges

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.

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

AAAAI Work Group Report: Trends in Oral Food Challenge Practices Among Allergists in the United States

Oral Food Challenge Implementation: The First Mixed-Methods Study Exploring Barriers and Solutions

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

Oral food challenges (OFCs) are used to confirm or reject a diagnosis of food allergy. However, younger children may encounter difficulties in consuming all offered doses during an OFC in the absence of symptoms, resulting in inconclusive outcomes. Our aim is to assess the eliciting dose for objective symptoms among various age groups and determine the necessity of consuming the final dose step during an uneventful OFC to avoid false negative outcomes. OFCs for common food allergens performed between 2012 and 2019 were analyzed retrospectively. The primary outcome was the association of age with stop dose for OFCs with inconclusive outcome. Secondary outcome measures were the association of age with eliciting dose and the potential number of false negative outcomes. A total of 1327 OFCs were performed in 707 patients. Of these, 514 (38.7%) were positive, 589 (44.4%) negative, and 224 (16.9%) inconclusive. In OFCs with inconclusive outcome, age appeared to be a significant predictor of the stop dose only for almond (p = .005). Objective symptoms occurred after the last dose step in 2%-13% of all OFCs with positive outcome. In our cohort, potential false negative outcomes may have been drawn in 27.6% of uneventful OFCs. Two third of children under 6 years of age successfully consumed all the provided doses during OFCs with a negative outcome. The eliciting dose for objective symptoms was not associated with age, and in a substantial number of OFCs with positive outcome, symptoms occurred after eating the final dose. These findings suggest that in case of an uneventful OFC, the outcome should be drawn only after a cumulative dose of 4.4 g has been consumed to avoid the risk of a potential false negative outcome.

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.

Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food hypersensitivity usually due to cow’s milk or soy. Among the solid foods, rice is one of the most causative foods worldwide, but it varies depending on the geographic area. In the Mediterranean countries, fish is one of the most important triggers of FPIES. There is not a specific biological marker for the disease that allows us to confirm the diagnosis or to predict when tolerance to the offending food has been achieved, so all patients with a FPIES diagnosis undergo an oral food challenge (OFC) at least once. The OFC is a risky procedure and many patients develop severe symptoms. Objective: We sought to evaluate the safety of a new OFC protocol in children with fish-FPIES. Methods: A retrospective study was performed over a 22-year period (1996–2018). We compared two methodologies used in the OFC: Method 1 that consisted in giving several doses during the same day versus Method 2 that consisted in giving a unique dose per day on 2 or three non-consecutive days. Results: A total of 75 positive OFC with fish done in 40 children were included. Forty-three (57.3%) OFC were performed following Method 1 and 32 (42.7%) with Method 2.The severity of the symptoms of the OFC done with Method 1 was mostly moderate (41.9%) followed by severe (39.5%) and mild (18.6%). The adverse reactions with Method 2 were mostly mild (68.8%) and only 18.8 and 12.5% presented moderate or severe symptoms, respectively. Conclusions: OFC performed in children with fish-FPIES are risky and many patients develop moderate or severe symptoms after this procedure. We propose a new protocol that has demonstrated to improve safety.

Better management of cow's milk allergy using a very low dose food challenge test: A retrospective study

Food Protein–Induced Enterocolitis Syndrome Food Challenges: Experience from a Large Referral Center

Better management of wheat allergy using a very low-dose food challenge: A retrospective study

Inappropriate dietary eliminations may impair quality of life, affect children's growth and unnecessarily impact on healthcare costs. Previous retrospective studies reported that around 25% of children continue a food-avoidance diet despite a negative oral food challenge (OFC). A definite pattern has not been found yet for patients not reintroducing the food. This study aimed to examine the role of child's nutritional attitudes and maternal anxiety in reintroducing food after a negative OFC. A prospective study was conducted involving 81 mothers of children with IgE-mediated food allergy. They completed a survey on nutritional behaviour and attitudes and the State-Trait Anxiety Inventory on the day of OFC and 6months later. In total, 11.1% of children never or rarely ate the food after a negative OFC. Consumption of the reintroduced food is positively correlated to child's interest in tasting new foods before and after OFC and to changes in child's nutritional habits after OFC. It is negatively correlated to monotony of the diet after OFC. No correlations were found with other participants' characteristics or maternal anxiety. State anxiety significantly decreased after the OFC. A correlation was found between trait and state anxiety and the degree of change in nutritional habits after OFC. Evaluating child's approach towards food before the OFC is a promising approach to identify patients at risk of food reintroduction failure. Furthermore, it underlined the importance of reassessing food consumption in all patients after a negative OFC and supporting patients in the reintroduction of food.

The effect of age, sex, race/ethnicity, health insurance, and food specific serum immunoglobulin E on outcomes of oral food challenges

Oral food challenges (OFCs) are necessary to diagnose food allergies; however, these tests can cause anaphylaxis. Higher specific immunoglobulin E (sIgE) levels to causative food have been associated with a positive OFC. To date, no data have been found to indicate the factors associated with severe symptoms or anaphylaxis among challenge-positive patients. This study aimed to clarify the association of sIgE with causative foods and anaphylaxis during OFC among the whole study population and challenge-positive patients. This cross-sectional study collected symptom and severity data between June 2012 and December 2016 during an open OFC to diagnose food allergy or confirm tolerance acquisition. We analyzed the risk factors for anaphylaxis during OFC. A total of 2272 cases were analyzed (median age: 3.5years; egg: 1166 cases; milk: 589 cases; wheat: 388 cases; and peanut: 129 cases). Among 979 challenge-positive patients, anaphylactic reactions were observed in 334 cases. A statistically significant association was observed between anaphylaxis during OFC and higher sIgE levels to causative foods (odds ratio: 2.71, 95% confidence interval: 1.94-3.78, for the third compared to the first tertile, P-value for trend <.001). Only gastrointestinal, respiratory, cardiovascular, and neurological symptoms were also statistically significantly associated with higher sIgE levels to causative foods. The risk of all symptoms, except skin symptoms, during OFCs increased with increasing sIgE levels, and this consequently increased anaphylaxis during OFCs. The mechanism of how sIgE affects the prevalence of gastrointestinal, respiratory, cardiovascular, and neurological symptoms or anaphylaxis is unknown; thus, further study is required.