Educational resources received by families after successful baked egg/baked milk oral food challenge: An international survey

Food challenges

Background This study assessed the utility of a prick-by-prick test with pasteurised cow's milk in predicting a pasteurised cow's milk allergy (CMA) diagnosis. Methods This was a retrospective study of 86 paediatric patients who had undergone open pasteurised cow's milk oral food challenges (OFCs). We evaluated the diagnostic performance of a prick-by-prick test with pasteurised cow's milk in predicting a positive OFC result. We calculated the threshold values representing high test specificity and predictive probability in children aged ≤24 and >24 months. Results A prick-by-prick test with pasteurised cow's milk was a good classifier of a positive cow's milk OFC outcome. The mean prick − by − prick test wheal diameter ≥ 3 mm yielded 100% sensitivity in both groups of children. Thresholds representing high test specificity and 95% predicted probability were 7 and 11 mm in children ≤ 24 months and 11 and 17 mm in children > 24 months of age, respectively. Conclusion A prick-by-prick test with pasteurised cow's milk is valuable in paediatric practice when diagnostic thresholds are implemented.

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

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.

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.

To the Editor,\nA lip dose or labial food challenge (LFC) is a simple, easy to perform method of diagnosis that could potentially be a convenient alternative to conducting an oral food challenge in children (1). Rance and Dutau (1) published a paper on LFC in 1997 demonstrating their clinical utility, according to the technique described by Moneret-Vautrin et al. (2). This involved a drop of the allergen being placed on the lower lip and left for 10 seconds to two minutes, with the mouth slightly opened. However, in the study by Rance et al. (1), children with positive LFC did not continue to have an oral food challenge (OFC). A subsequent study by Cantani et al.(3) concluded that the LFC should not replace the OFC, but be used at the first step in a food challenge, particularly where there is a risk of anaphylaxis (4). LFCs are not currently included in international food challenge guidelines (5) (7). Here we present data from lip dose reactions in the Food Allergy and Intolerance (FAIR) study from the Isle of Wight in the United Kingdom (UK), with the aim of demonstrating the predictive value of LFCs for diagnosis of food allergy, compared to OFCs

To evaluate the frequency of office-based oral food challenge (OFC) failures to previously tolerated foods eliminated from diets to treat atopic dermatitis (AD) based on positive skin prick test (SPT) results and/or specific immunoglobulin E (sIgE) testing.A total of 442 patients were included who had undergone OFCs to peanut, wheat, soy, milk, and egg (the top 5 allergens in the United States) at the allergy clinics of Riley Hospital for Children at Indiana University Health from 2008 to 2014.By retrospective chart review, subjects were classified into 3 groups according to the reason for food avoidance, as follows: food allergy (defined as typical signs of an allergic reaction within 2 hours of ingestion, with supporting SPT or sIgE results), sensitization without introduction (food item never introduced because of positive SPT and/or sIgE results found during evaluation for AD or other food allergies), and avoidance based on positive SPT and/or sIgE test results found during AD workup (all had previously tolerated the food without reaction within 2 hours). OFCs were offered if the subject had sIgE levels predicting passing the OFC on the basis of 95% positive predictive values and no reaction to the food in the last 12 months. Plain and extensively heated milk OFCs were grouped together, as were those for egg. Extensively heated food challenges were offered regardless of sIgE levels. Total IgE levels were not reported.Indications for OFCs were a history of food allergy (320 of 442, 72.4%) and sensitization (77 of 442, 17.4%) and AD (45 of 442, 10.2%). There were no significant differences among these 3 groups at OFC in age, sex, race, asthma, allergic rhinitis, or percentage of positive SPT results to the food. The overall OFC failure rate was 20.1%, including 21.9% of the food allergy group, 16.9% of the sensitization group, and 13.3% of the AD group, which was not statistically significant comparing groups (P = .30). There was no significant difference with regard to OFC pass and fail rates among the 5 foods challenged or the length of time of food avoidance (range: 3–120 months, P = .97). Wheat was significantly more likely to be avoided because of AD (P < .001), and milk was likely to be avoided because of food allergy (P = .002).In this study, 13.3% of children with AD who had removed a previously tolerated food from their diet because of a positive SPT and/or sIgE test result failed an OFC to that food in as quickly as after 3 months of avoidance. This demonstrates the potentially rapid loss of tolerance that can occur with food elimination for AD therapy and bolsters evidence that SPT and/or sIgE test results in patients with AD who do not have a history of immediate reaction to the foods tested are often clinically irrelevant.Data on the role of food triggers in AD have been conflicting, but overall there is lack of high-quality evidence. Aggressive skin care regimens should be pursued over elimination diets, which carry the risk of loss of tolerance to a food previously consumed without immediate reaction.

BackgroundThe aim of this study was to investigate the role of specific IgG4 antibodies to hen’s egg white and determine their utility as a marker for the outcome of oral challenge test in children sensitized to hen’s eggMethodsThe hen’s egg oral food challenge test was performed in 105 sensitized children without atopic dermatitis, and the titers of egg white-specific immunoglobulin G4 (IgG4) and immunoglobulin E (IgE) antibodies were measured. To set the cut-off values of IgG4, IgE, and the IgE/IgG4 ratio for predicting positive results in oral challenges, receiver operating characteristic curves were plotted and the area under the curves (AUC) were calculated.ResultsSixty-four of 105 oral challenges with whole eggs were assessed as positive. The AUC for IgE, IgG4, and IgE/IgG4 for the prediction of positive results were 0.609, 0.724, and 0.847, respectively. Thus, the IgE/IgG4 ratio generated significantly higher specificity, sensitivity, positive predictive value (%), and negative predictive value (%) than the individual IgE and IgG4. The negative predictive value of the IgE/IgG4 ratio was 90% at a value of 1.ConclusionsWe have demonstrated that the egg white-specific serum IgE/IgG4 ratio is important for predicting reactivity to egg during food challenges.

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

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.

Work Group report: Oral food challenge testing

While immediate-type clinical reactions to food can quite easily be identified by history or measurement of specific IgE in combination with positive oral food challenges, the evaluation of food allergy in the absence of immediate clinical reactions still presents diagnostic difficulties--particularly in children with atopic dermatitis. The objective of this study was to evaluate the diagnostic value of the atopy patch test (APT) with regard to late-phase reactions observed in double-blind, placebo-controlled food challenges with cow's milk, hen's egg, wheat, and soybean. We investigated 75 children (median age 2.1 years) with suspected food allergy by double-blind, placebo-controlled food challenges, specific IgE in serum, skin prick test, and APT. Of the subjects, 69/75 suffered from atopic dermatitis. Of 209 oral challenges, 133 were performed with allergen and 76 with placebo. We assessed 77/133 allergen and 2/76 placebo challenges as positive. In 66 of 77 (86%) positive oral challenges, specific IgE in serum to the corresponding allergen was positive; in 64/77 (83%) the skin prick test, and in 42/77 (55%) the APT was positive. While immediate-type reactions were associated with positive skin prick test and proof of specific IgE in serum, late-phase clinical reactions were associated with a positive APT (sensitivity 76%, specificity 95%). The APT seems to be a valuable additional tool in the diagnostic work-up of food allergy in children with atopic dermatitis - especially with regard to late-phase clinical reactions. The APT may help to prevent unnecessary restrictive diets which may be the consequence of misjudging late reactions by clinical assessment alone.

Benhamou AH, Zamora SA, Eigenmann PA. Pediatr Allergy Immunol. 2008;19(2):173–179 PURPOSE OF THE STUDY. To determine if specific immunoglobulin E (IgE) antibody titers to egg were predictive of the severity of reaction during a standardized food challenge. STUDY POPULATION. The study was a retrospective review of children who underwent oral food challenges to egg over a 2-year period. Median age of patients was 3.9 years (range: 16 months to 11.9 years). Children with high egg-specific IgE titers and those with a severe reaction &amp;lt;2 years earlier were not tested. METHODS. Children with immediate-type reactions were tested by open food challenge, and those with atopic dermatitis or equivocal reactions were tested by double-blind, placebo-controlled food challenge. Graded challenges were performed with pasteurized raw egg, cooked egg, or egg hidden in a chocolate testing preparation. The challenge was terminated when the patient reached a total dose of 45 g of egg or if there was unambiguous clinical reactivity and reaction severity was graded. RESULTS. Of the 51 challenges performed during the study period, 35 (69%) were positive. Thirteen (37%) of the positive challenges were considered severe. An egg radioallergosorbent (RAST) assay result of ≥17.4 kU/L was associated with 95% probability of having a positive challenge; 8.2 kU/L was associated with a 90% probability. For all challenges, egg-specific IgE titers ranged from &amp;lt;0.35 to 14.9 kU/L. The negative challenge group had a median egg-specific IgE titer of 1.17 kU/L (range: 0.35–6.41 kU/L); the mild-to-moderate group median was 2.47 kU/L (range: 0.35–14.9 kU/L); and the severe group median was 3.70 kU/L (range: 1.18–11 kU/L). The differences of median egg-specific IgE levels were statistically significant (P = .006). Children with a positive challenge who received cooked egg were found to have a higher specific IgE level versus those who received raw egg (P = .016), but there was no statistically significant difference between severity of reactions between these groups. The median dose that caused a mild-to-moderate reaction was 6 g (range: 2.5–20 g) and was the same median dose that caused severe reactions (range: 0.5–15 g). CONCLUSIONS. There is a correlation between median egg-specific IgE levels and the severity of reaction during oral food challenge to egg. These levels may be helpful in predicting a potential reaction to egg. REVIEWER COMMENTS. It is often assumed that reaction severity correlates with the food-specific IgE level, but most studies have refuted this notion. Here, a relationship was determined. However, it is difficult to assess the clinical utility of these results, because there was considerable overlap of the ranges of egg-specific IgE levels between groups. These findings may be more relevant to the controlled setting of a diagnostic food challenge rather than to the community setting in which a large or uncontrolled dose of egg might be ingested. In a real-life setting, a severe reaction may occur even with a low egg-specific IgE level, particularly if one considers patient-dependent factors such as concurrent diagnosis of asthma or personal history of a previous severe reaction.

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