Development of a low allergenic product for patients with milk allergy and assessment of its specific IgE reactivity.

BACKGROUND: Milk oral immunotherapy is the riskiest and most unpredictable form of oral immunotherapy. We aimed to produce a low allergenic product than conventional once baked-cake/muffin, to develop indirect in-house ELISA to check the tolerance status with milk products and evaluate IgE reactivity of patients' sera via western blotting (WB) and indirect in-house ELISA. METHOD: A low allergenic product named biscotti-twice baked-cake was developed, and the total protein concentration was determined. The protein content was studied by SDS-PAGE and proteomics. Milk-specific IgE (sIgE) binding assays were performed by WB and indirect in-house ELISA by using patients' sera. RESULTS: Casein band intensity was observed to be lower in the biscotti-twice baked-cake than in the once baked-cake (p = .014). Proteomics analysis and αS1-casein measurement showed that the lowest intensity of casein was found in biscotti. The low binding capacity of milk sIgE to biscotti compared with once baked-cake was shown by WB (p = .0012) and by indirect in-house ELISA (p = .0001). In the ROC analysis, the area under the curve (AUC) of the in-house ELISA IgE was comparable with Uni-CAP milk and casein sIgE. The AUC of the in-house ELISA IgE for cake (0.96) and biscotti (1) was slightly better than Uni-CAP milk sIgE (0.94; 0.97) and casein sIgE (0.96; 0.97), respectively. CONCLUSION: The low allergenicity of the newly developed low allergenic product "biscotti-twice baked-cake" has been demonstrated by in vitro experiments. Biscotti could be a safe treatment option than once baked-cake/muffin in patients who are reactive to once baked-milk products.

Efficacy and safety of baked milk oral immunotherapy in children with severe milk allergy: A randomized, double-blind, placebo-controlled phase 2 trial.

BACKGROUND: Cow's milk allergy is the most common food allergy in young children and has no current treatment. Oral immunotherapy studies to date have shown efficacy but high rates of adverse reactions. OBJECTIVE: We sought to evaluate the safety and efficacy of baked milk oral immunotherapy (BMOIT) in children allergic to baked milk. METHODS: Participants (3-18 years) were randomized to receive BMOIT or placebo for 12 months. Efficacy was assessed by double-blind placebo-controlled food challenge after 12 months of treatment. Safety, quality of life, and mechanistic parameters were also evaluated. RESULTS: Eleven of 15 (73%) BMOIT participants reached the primary end point, tolerating 4044 mg of baked milk protein after 12 months of oral immunotherapy, compared with 0 of 15 (0%) on placebo. The median maximum tolerated dose and median change from baseline was significantly higher in the BMOIT group than in the placebo group (median maximum tolerated dose, 4044 mg vs 144 mg; P = .001; median change in maximum tolerated dose of 3900 mg vs 0 mg, P = .0001). Dose-related reactions were common, but more than 95% in both groups were mild. There was no significant change in cow's milk- or beta lactoglobulin-IgE from baseline for either group. Cow's milk-sIgG4 did significantly increase and casein IgE decreased in the BMOIT group. For proxy-reported food allergy quality of life, there was a significant difference in the emotional impact domain only, with more improving while on placebo compared with BMOIT. Most children and adolescents in the BMOIT group directly reported improvement in at least 1 domain. CONCLUSIONS: BMOIT was well tolerated and induced a substantial level of desensitization after 12 months of treatment.

Bos d 11 in baked milk poses a risk for adverse reactions in milk-allergic patients.

BACKGROUND: Patients are commonly challenged with foods containing baked milk, for example muffins, yet little is known about the specific allergen content of muffins used in milk challenges or of the effect that baking has on allergenicity. OBJECTIVE: Our objective was to compare the levels of major milk allergens in uncooked and baked muffins using monoclonal immunoassays and IgE antibody binding before and after baking. METHODS: Uncooked and baked muffins were prepared using recipes from Mount Sinai and Imperial College. Allergen levels were compared by ELISA for Bos d 5 (ß-lactoglobulin) and Bos d 11 (ß-casein). IgE reactivity was assessed using sera from milk-sensitized donors in direct binding and inhibition ELISA. RESULTS: Bos d 5 was reduced from 680 µg/g in uncooked muffin mix to 0.17 µg/g in baked muffins, representing a >99% decrease after baking. Conversely, Bos d 11 levels in baked muffin remained high and only decreased by 30% from a mean of 4249 µg/g in uncooked muffin mix to 2961 µg/g when baked (~181 mg Bos d 11 per muffin). Baked muffins retained ~70% of the IgE binding to uncooked muffin mix. Baked muffin extract inhibited IgE binding to uncooked muffin mix by up to 80%, demonstrating retention of in vitro IgE reactivity. CONCLUSIONS AND CLINICAL RELEVANCE: High levels of Bos d 11 in baked muffins pose a risk for adverse reactions, especially in patients who have high anti-casein IgE antibodies.

Evaluation of some predictive parameters for baked-milk tolerance in children with cow's milk allergy.

BACKGROUND: Inclusion of baked-milk products to the diet appears to markedly accelerate tolerance to unheated milk compared to a strict avoidance diet. OBJECTIVE: : The present study aims to investigate the predictors of baked-milk tolerance in children with Immunoglobulin E (IgE)-mediated cow's milk (CM) allergy. METHODS: The study included 80 patients diagnosed with IgE-mediated CM allergy upon oral food challenge (OFC) testing at our clinic. Patients who developed and did not develop reactions during OFC with baked milk were compared considering clinical and laboratory parameters. RESULTS: Eighty patients with CM allergy comprised 48 male and 32 female infants with an average age of 7.25 ± 2.45 (3-13) months. We found that 62.5% of them showed tolerance to baked milk in the OFC test performed with cakes containing 2.6-g milk protein. When the patients who tolerated and could not tolerate baked-milk products were compared for test results, we detected a statistically significant intergroup difference regarding diameter of wheal in skin prick test (SPT) performed with muffin slurry, levels of specific Immunoglobulin E (sIgE) in CM, sheep's milk (SM), goat's milk (GM), casein, and the amount of unheated milk consumed until a reaction developed in the OFC test performed with unheated milk (P < 0.05). CONCLUSION: We defined novel decision points based on CM, SM, GM, casein sIgE levels, wheal diameter in SPT with muffin slurry, and the amount of milk ingested during OFC performed with unheated milk that may be useful in predicting outcomes of baked-milk ingestion.

A new Luminex-based peptide assay to identify reactivity to baked, fermented, and whole milk.

BACKGROUND: The majority of children with cow's milk allergy (CMA) tolerate baked milk. However, reactivity to fermented milk products such as yogurt/cheese has not been previously evaluated. We sought to determine whether children with CMA could tolerate yogurt/cheese and whether a patient's IgE and IgG4-binding pattern to milk protein epitopes could distinguish clinical reactivity. METHODS: Four groups of reactivity were identified by Oral food challenge: baked milk reactive, fermented milk reactive, whole milk reactive, and outgrown. sIgE and sIgG4 binding to milk protein epitopes were assessed with a novel Luminex-based peptide assay (LPA). Using machine learning techniques, a model was developed to predict different degrees of CMA. RESULTS: The baked milk reactive patients demonstrated the highest degree of IgE epitope binding, which was followed sequentially by fermented milk reactive, whole milk reactive, and outgrown. Data were randomly divided into two groups with 75% of the data utilized for model development (n = 68) and 25% for testing (n = 21). All 68 children used for training were correctly classified with models using IgE and IgG4 epitopes. The average cross-validation accuracy was much higher for models using IgE plus IgG4 epitopes by LPA (84.8%), twice the performance of the serum component proteins assayed by UniCAP (41.9%). The performance of the model on "unseen data" was tested using the 21 withheld patients, and the accuracy of IgE was 86% (AUC = 0.89) while of IgE+IgG4 model was 81% (AUC = 0.94). CONCLUSION: Using a novel high-throughput LPA, we were able to distinguish the diversity of IgE/IgG4 binding to epitopes in the varying CMA phenotypes. LPA is a promising tool to predict correctly different degrees of CMA.

Evaluation of a Standardized Bakery Product (SUTMEK) as a Potential Tool for Baked-Milk Tolerance and Immunotherapy Research Studies.

BACKGROUND AND OBJECTIVES: About 65-80% of children with IgE-mediated cow's milk allergy (CMA) can tolerate extensively heated milk. We have invested in the mass fabrication of a test product containing milk protein baked at 180°C for 30 min (SUTMEK-milk) and a milk-free placebo (SUTMEK-placebo) to carry out a standardised double-blind placebo-controlled food challenge (DBPCFC) test in patients with CMA. METHODS: We studied children with IgE-mediated CMA between 13 and 48 months of age. Specific IgEs (spIgE) to milk proteins were quantified. A DBPCFC with our bakery products was performed, and factors determining reactivity to extensively heated milk were evaluated. We also tested the applicability of SUTMEK products in baked-milk oral immunotherapy in a pilot assessment. RESULTS: We studied 15 children (8 girls, 7 boys) with a median age of 26 months (range: 13-48 months). Nine (60%) patients tolerated a challenge with extensively heated milk, while 6 (40%) were found reactive (anaphylaxis: 2, wheezing: 2, urticaria: 2). spIgE to milk, α-lactalbumin, and casein, and the wheal diameter on skin prick testing were higher in the reactive group than the tolerant groups (p = 0.001, p = 0.001, p = 0.002, and p = 0.048, respectively). Receiver-operating characteristic curve analyses yielded the following cut-off values for spIgEs that would predict a reactivity to extensively heated milk; milk: 25 kU/L (area under curve, AUC: 0.981), casein: 32 kU/L (AUC: 0.983), and α-lactalbumin: 17 kU/L (AUC: 0.981). Nine patients have tolerated well a continued daily consumption of SUTMEK-milk or -placebo for 6 months at the desired doses. CONCLUSIONS: Our bakery products were successfully used in DBPCFC studies and qualified as an acceptable tool for use in the research of interventional tolerance induction. Although spIgE appears useful in determining children at high risk of reacting to extensively heated milk, the predictive cut-off values are still far from being perfect.

The effect of baked milk on accelerating unheated cow's milk tolerance: A control randomized clinical trial.

BACKGROUND: Assessing the effect of adding baked milk products to the diet of patients with cow's milk allergy on accelerating the formation of tolerance. METHOD: A randomized clinical trial was carried out with 84 patients (6 months-3 years old) diagnosed with allergy to cow's milk who tolerated baked milk in form of muffin in oral food challenge (OFC). The subjects were divided randomly into case and control groups matched for age and sex. Patients in the case group were asked to consume baked milk in the form of muffin for 6 months and then to consume baked cheese in the form of pizza for another 6 months. The control group were instructed to strictly avoid any milk products for 1 year. Skin prick test (SPT) and serum-specific immunoglobulin E (sIgE) levels (ImmunoCAP) of milk, casein, and beta-lactoglobulin were measured before and after the study. In addition, those in the case group who had satisfactorily tolerated baked products during the study as well as all the subjects in the control group underwent an OFC to evaluate unheated milk tolerance at the end of the study. RESULTS: It was shown that by the end of the 1-year study period, 88.1% (37/42) of the patients in the case group and 66.7% (28/42) of those in control group had developed tolerance to unheated milk (P-value: 0.018). The results of milk-specific SPT and sIgE levels showed a significant decrease in the case group. Initial sIgE levels could not predict unheated milk tolerance in case and control groups. CONCLUSION: Introducing baked milk products into the diet of patients with milk allergy can accelerate the tolerance of unheated milk in these patients. sIgE levels of milk, casein, and beta-lactoglobulin did not predict the tolerance of unheated milk.

Contribution of Molecular Allergen Analysis in Diagnosis of Milk Allergy.

PURPOSE OF REVIEW: We sought to describe the available evidence supporting the utilization of the molecular allergen analysis (MAA) for diagnosis and management of cow milk protein allergy (CMPA). RECENT FINDINGS: Cow milk proteins are among the most common food allergens in IgE- and non-IgE-mediated food allergic disorders in children. Most individuals with CMPA are sensitized to both caseins and whey proteins. Caseins are more resistant to high temperatures compared to whey proteins. MAA is not superior to the conventional diagnostic tests based on the whole allergen extracts for diagnosis of CMPA. However, MAA can be useful in diagnosing tolerance to extensively heated milk proteins in baked foods. Children with CMPA and high levels of casein IgE are less likely to tolerate baked milk compared to children with low levels of casein IgE. Specific IgE-binding patterns to casein and betalactoglobulin peptides may predict the natural course of CMPA and differentiate subjects who are more likely to develop CMPA at a younger age versus those with a more persistent CMPA. Specific IgE-binding patterns to casein and beta-lactoglobulin peptides may also predict response to milk OITand identify patientsmost likely to benefit fromOIT.

Baked milk tolerant patient: Is there any special feature?

BACKGROUND: Determining whether patients with cow's milk allergy (CMA) can tolerate foods produced with baked milk could provide a better quality of life, a better prognosis, and an option for desensitization. OBJECTIVES: The aim of this study was to identify which patients over four years of age with persistent CMA could tolerate baked milk, to compare the clinical and laboratory characteristics of reactive and non-reactive groups and to describe their clinical evolution. MATERIALS AND METHODS: A cross-sectional study was conducted (January/13 to November/14) that included all the patients followed at a food allergy center who met the inclusion criteria. The patients underwent an oral food challenge (OFC) with a muffin (2.8g of cow's milk protein). To exclude cow's milk (CM) tolerance, the patients were subsequently challenged with unheated CM. RESULTS: Thirty patients met all the inclusion criteria. Fourteen patients (46.7%) were considered non-reactive to baked milk and reactive to unheated CM. When the groups that were reactive and non-reactive to baked milk were compared, no statistically significant differences in clinical features were found. The prick test for α-lactalbumin (p=0.01) and casein (p=0.004) and the serum specific IgE for casein (p=0.05) presented statistical differences. After one year, none of the patients who were reactive to baked milk were ingesting CM, while 28% of the tolerant patients were consuming fresh CM (p=0.037). CONCLUSIONS: Baked milk can be tolerated by patients with CMA, especially those with lower levels of casein and α-lactalbumin. This option can improve quality of life and accelerate tolerance.

Tolerance to baked and fermented cow's milk in children with IgE-mediated and non-IgE-mediated cow's milk allergy in patients under two years of age.

BACKGROUND: IgE-mediated cow's milk allergy (CMA) has been shown consistent in milder heated-milk tolerant and severe heated-milk reactant groups in patients older than two years. Little is known whether fermentation of milk gives rise to similar clinical phenotypes. We aimed to determine the influence of extensively heated and fermented cow's milk on the IgE-mediated and non-IgE-mediated CMA in children younger than two years. METHODS: Subjects followed with the diagnosis of IgE-mediated and non-IgE-mediated CMA for at least six months underwent unheated milk challenge. IgE-mediated and non-IgE-mediated groups were categorised as unheated milk-reactive and tolerant, separately. Unheated milk-reactive groups were further challenged sequentially with fermented milk (yoghurt) and baked milk, 15 days apart. Allergy evaluation with skin tests, prick-to-prick tests and atopy patch tests were performed. RESULTS: Fifty-seven children (median age: 14 months; range: 7-24 months) underwent unheated milk challenge. Eleven of 27 children with IgE-mediated CMA and 14 of 30 children with non-IgE-mediated CMA tolerated unheated milk. Among subjects who reacted to unheated milk; 15 of 16 subjects (93%) with IgE-mediated CMA also reacted to yoghurt, whereas 11 of 16 subjects (68%) with non-IgE-mediated CMA tolerated fermented milk. Thirteen subjects (81%) of the unheated milk-reactive IgE-mediated group tolerated to heated milk. None of 16 subjects of unheated milk-reactive non-IgE-mediated group reacted to baked milk. CONCLUSION: The majority of children under the age of two years with both IgE-mediated and non-IgE-mediated CMA tolerated baked-milk products. Yoghurt was tolerated in two thirds of unheated milk reactive patients suffering from non-IgE-mediated CMA.

Baked Egg and Milk Exposure as Immunotherapy in Food Allergy.

Baked milk and egg have the potential to act as a form of oral immunotherapy (OIT). Clinical studies have shown that a majority of milk- and egg-allergic children can tolerate these allergens modified in baked form, and immunologic changes reported in subjects ingesting baked milk and egg mirror those seen in food allergy OIT trials. In addition, several studies have indicated that resolution of milk and egg allergies occur sooner in populations regularly ingesting baked milk and egg. Oral food challenges remain the best method for determining tolerability of baked milk and egg since baseline characteristics and diagnostic testing have not been reliable predictors. In this review, we explore the tolerability of baked milk and egg and their potential as OIT treatment for milk and egg allergy.

Matrix effect on baked milk tolerance in children with IgE cow milk allergy.

BACKGROUND: Children with IgE-mediated cow's milk allergy (IgE-CMA) often tolerate baked milk within a wheat matrix. In our study we evaluated the impact of wheat matrix and of little standardised cooking procedures on tolerance of baked milk. We also tested tolerance versus parmigiano reggiano (PR) and whey-based partially hydrolysed formula (pHF). METHODS: Forty-eight children with IgE-CMA were enrolled. They underwent prick-by-prick (PbP) and open oral food challenge (OFC) with baked cow's milk (CM), both within a wheat matrix (an Italian cake named ciambellone) and without (in a liquid form), with PR and with pHF. After a passed OFC, children continued to eat the food tolerated. In particular, after passed OFC with ciambellone, children were allowed to eat any food containing CM within a wheat matrix, with the only condition that it was baked at 180°C for at least 30min. Three months after, parents were asked to answer a survey. RESULTS: 81% of children tolerated ciambellone, 56% liquid baked CM, 78% PR and 82% pHF. Negative predictive value of PbP performed with tested foods was 100%. No IgE-mediated adverse reactions were detected at follow-up carried out by the survey. CONCLUSIONS: Wheat matrix effect on tolerance of baked milk was relevant in slightly less than half of cases. If our results are confirmed by larger studies, a negative PbP will allow patients to eat processed CM without undergoing OFC. Moreover, in order to guarantee tolerance towards baked milk, strict standardised cooking procedures do not seem to be necessary.

Efficacy of baked milk oral immunotherapy in baked milk-reactive allergic patients.

BACKGROUND: Patients with IgE-mediated cow's milk allergy who are nonreactive to baked milk (BM) can be desensitized with BM to promote tolerance to unheated milk (UM). OBJECTIVE: We sought to test whether patients who are BM reactive can progress in BM oral immunotherapy (OIT) and become desensitized to UM as well. METHODS: Fifteen patients (>4 years) who previously failed to complete our milk OIT program were enrolled into the BM OIT protocol. A dose of BM (180 °C for 30 minutes) which was less than the eliciting dose was increased 50% monthly while under medical supervision until the primary outcome dose of 1.3 g/d BM protein was achieved. Basophil reactivity and milk protein-specific IgE binding were analyzed at the first round of BM OIT therapy (T0) and at 12 months of BM treatment. RESULTS: In terms of the primary outcome, only 3 (21%) of 14 patients tolerated the 1.3 g/d BM dose. Although some patients initially progressed in BM OIT, 8 of 11 failed because of IgE-mediated reactions. Three did not complete the program because of non-IgE-mediated factors. An increase in challenge threshold to UM was noted in patients continuing until 12 months (P = .003), including those among whom reactions precluded continuation in the program. Patients (n = 3) who successfully reached maintenance had decreased milk-specific IgE reactivity. Furthermore, the mean difference at T0 between induced HM and UM percentages of CD203c expression was significantly lower in patients who successfully completed BM OIT than in those who did not (-11% vs 4.4%, P = .0002), which is consistent with their decreased clinical reactivity to BM. CONCLUSIONS: Although use of hypoallergenic BM in OIT is a promising therapy, care must be taken before its administration in BM-reactive patients because of the risk for anaphylaxis and only limited increase in challenge threshold attained.

Effect of heat treatment on milk and egg proteins allergenicity.

BACKGROUND: Heating destroys many conformational epitopes and reduces allergenicity of some foods. IgE-epitope binding has been shown to be different among patients who outgrew their cow's milk or hen's egg allergy and those who did not. A significant proportion of milk- or egg-allergic children are tolerant to these foods in their baked forms. We sought to explore the effects of heating on milk and egg proteins and to evaluate for differences in immunolabeling among children with regard to reactivity to heated milk or egg. METHODS: Sera from participants in clinical dietary intervention trials were utilized. Milk and egg samples were variably heated and prepared (at times within a wheat matrix). Sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE), protein transfer, and Western blot were completed. RESULTS: Sera from 20 milk-allergic and 24 egg-allergic children were utilized. Gel electrophoresis showed strongly staining casein bands that persisted for up to 60 min of heating. In contrast, ß-lactoglobulin and α-lactalbumin bands became progressively weaker with increasing heating times, with no detectable ß-lactoglobulin after 15-20 min of heating. The ovalbumin band became progressively weaker, whereas ovomucoid remained stable after 25 min of heating. Immunolabeling revealed that all heated milk-reactive children possessed IgE antibodies that bound the casein fraction regardless of heating time. Presence of wheat during heating resulted in decreased IgE antibody binding to milk and egg white proteins. CONCLUSION: Heating has a different effect on whey and caseins in cow's milk and ovalbumin and ovomucoid in hen's egg white. The effect of heat on protein allergenicity is affected by the temperature and duration, along with the presence of wheat.

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines update - XVI - Nutritional management of cow's milk allergy.

Cow's milk allergy (CMA) is one of the most common presentations of food allergy in early childhood. Management of CMA involves individualized avoidance of cow's milk and other mammalian milk and foods containing these. Optimal elimination of cow's milk avoidance includes: label reading; information about safe and nutritious substitute foods; appropriate choice of infant formula or a plant-based food; establishing tolerance to baked milk and monitoring nutritional intake and growth. Substitute formulas are divided into soy formula (not hydrolyzed), milk-based extensively hydrolyzed formulas, rice based extensive, and partially hydrolyzed formulas and amino acid-based formulas. The use of other mammalian milks is not recommended for the management of cow's milk allergy due to a high level of cross-reactivity and nutritional concerns. For toddlers who are eating well, children, and adults, a suitable plant-based beverage may be a suitable alternative to a specialized formula, following careful nutritional considerations. Families need to be instructed on finding suitable nutritious foods and how to prepare suitable meals at home. Individuals with CMA also need to know how to identify and treat acute severe reactions.

The Safety and Efficacy of Baked Egg and Milk Dietary Advancement Therapy: A Systematic Review and Meta-Analysis.

BACKGROUND: Cow's milk and egg allergy affect approximately 1.9% and 0.9% of children, respectively. Dietary advancement therapies (DATs), including milk (ML) and egg (EL) ladders, and baked milk (BM-OIT) and baked egg (BE-OIT) oral immunotherapy, are potential therapeutic options for these patients. OBJECTIVE: To perform systematic review and meta-analysis of the safety and efficacy of DATs in children with IgE-mediated milk or egg allergy. METHODS: A systematic literature review was conducted, exploring 22 potential outcomes, with meta-analysis performed where ≥3 studies reported data. The GRADE approach was used to determine the certainty of evidence for each outcome, and the Johanna Briggs Institute tools were used for determining risk of bias. RESULTS: Twenty-nine studies met inclusion criteria among 9946 titles screened. Tolerance occurred in 69% of EL, 58% of ML, 49% of BE-OIT, and 29% of BM-OIT patients. All-severity allergic reactions occurred in 21% of EL, 25% of ML, 20% of BE-OIT, and 61% of BM-OIT patients, with epinephrine use in 3% of EL, 2% of ML, and 9% of BM-OIT patients. At-home reactions occurred in 19% of BE-OIT and 10% of BM-OIT patients. Discontinuation occurred in 14% of EL, 17% of ML, 17% of BE-OIT, and 20% of BM-OIT patients. The mean time to BE egg and BE-OIT tolerance was 13.25 months (4 studies) and 19.1 months (3 studies). Certainty of evidence was very low, and risk of bias high. Study heterogeneity was high, attributable to multiple factors. CONCLUSIONS: There is very low certainty of evidence supporting DAT safety and efficacy. We cannot conclude that DAT accelerates tolerance development.

Adult-onset IgE-mediated cow's milk allergy-a rare phenotype.

Cow's milk allergy has been studied extensively in infants and young children and has public health importance around the globe. We describe the clinical and demographic characteristics of 3 cases of a rare presentation of adult-onset IgE-mediated cows' milk allergy.

Are There Hidden Dangers Associated With Milk and Egg Dietary Advancement Therapy?

Dietary advancement therapies (DATs) constitute a continuum spanning extensively heated item ingestion, progressive milk or egg ladders, and oral immunotherapy (OIT). These represent an evolution in food allergy management from strict avoidance to an active therapy that may modulate the immune system to develop tolerance to particular forms of the allergen. Many egg or milk individuals are tolerant to baked egg or milk at baseline, and regular consumption (at home ingestion) of baked milk or egg is a safe process with potential quality of life and immunologic benefit. Milk and egg ladders, developed for non-IgE mediated allergy, are increasingly being adapted to IgE-mediated allergy as a potentially safe at-home option for gradual dietary advancement. However, data are limited regarding how safe and effective these approaches are or what patient is best suited for which DAT. It is also unclear whether extensively heated allergen consumption and ladders are susceptible to the same patient-specific factors that affect day-to-day tolerance and safety in OIT. Several recent events involving near-fatal or fatal reactions to milk or egg products (all among patients with asthma) have highlighted that DATs are not risk-free, and that physician guidance in these therapies is essential. Such guidance may include obtaining informed consent before starting any DAT and instituting the same safe dosing rules for OIT across any form of DAT. This rostrum discusses practical concerns about the safety of DAT, and considerations regarding how clinicians can maximize patient protection while defining the safety and efficacy of real-world implementation of these concepts.

Baked Milk and Baked Egg Survey: A Work Group Report of the AAAAI Adverse Reactions to Foods Committee.

Most milk- and egg-allergic children can tolerate milk and egg in baked forms. Some allergists have extended the use of baked milk (BM) and baked egg (BE) to advocating for the stepwise introduction of small amounts of BM and BE to children who are reactive to larger amounts of BM and BE. Little is known about the practice of introducing BM and BE and existing barriers to this approach. The purpose of this study was to gather a current assessment of the implementation of BM and BE oral food challenges and diets for milk- and egg-allergic children. We conducted an electronic survey of North American Academy of Allergy, Asthma & Immunology members offering BM and BE introduction in 2021. The response rate was 10.1% of distributed surveys (72 of 711). Surveyed allergists had a similar approach to both BM and BE introduction. Demographic features of time in practice and region of practice were significantly associated with the odds of introducing BM and BE. A wide variety of tests and clinical features guided decisions. Some allergists determined BM and BE to be appropriate for home introduction and offered this for BM and BE more often than other foods. The use of BM and BE as a food for oral immunotherapy was endorsed by almost half of respondents. Less time in practice was the most significant factor associated with offering this approach. Published recipes were used and written information was widely provided to patients by most allergists. The wide practice variabilities reveal a need for more structured guidance about oral food challenges, in-office versus home procedures, and patient education.

Milk ladder as a therapeutic option for cow's milk allergy: Proposal for a step-by-step plan for cow's milk introduction in cow's milk allergy.

In regard to cow's milk allergy, the current option of avoiding can be expanded by (re-)introducing milk using a milk ladder. So-called "food ladders" are internationally well known and utilized for both non-IgE-mediated and IgE-mediated cow's milk allergy. Stepping up the stairs from highly processed baked goods with milk via cooked milk products to pasteurized fresh milk reflects the status of acquired tolerance of each level. The allergenicity of milk depends on processing and amount. By implementing the milk ladder, it can enhance the clinical process of tolerance development, lead to meeting nutrient requirements quickly, and involve parents actively in the therapeutical process. The milk ladder, for the first time being published and adapted for Germany, describes a structured framework that might be adapted individually regarding the time period on a certain level or other variations such as preparation/amount of milk products. From a safety perspective, healthcare professionals should pay great attention to patient selection and education prior to implementing the milk ladder. Detailed advice as well as recipes and a graphical presentation can be found in the supplemental material.