Paradigm Shift in the Management of Milk and Egg Allergy: Baked Milk and Egg Diet

We compared education regarding BE/BM introduction and preferences regarding future education between countries and found significant differences in the rate and form information was received. This underscores the need for increased post-oral food challenge education and highlights country-specific education differences.

Denaturation of β-lactoglobulin (BLG) was studied in relation to its antigenicity at two heat treatments in several native protein mixtures; allergenicity was determined by enzyme-linked immunosorbent assay based on BLG capacity to bind with immunoglobulin G (IgG) antibodies. The influence of other proteins on BLG denaturation correlated with altered antigenicity. Treatment at 72 °C/15 s enhanced antigenicity in a BLG+α-lactalbumin (ALA) mixture, possibly due to exposed epitopes in the unfolded structure. Treatment at 100 °C/30 s mostly resulted in BLG-led protein aggregation through thiol/disulphide interactions and decreased antigenicity by fragmentation and masking of epitopes, the extent of which was mixture-dependent. The presence of IgG resulted in diminished antigenicity in BLG + ALA + IgG at 100 °C/30 s in comparison with BLG + ALA. ALA governed whey protein denaturation over BLG in BLG + ALA + IgG + bovine serum albumin (BSA), possibly catalysed by BSA at 100 °C/30 s, resulting in a higher retention of antigenicity than in other mixtures.

Background Consumption of baked egg by raw egg allergic children is associated with immune changes suggesting development of tolerance. However, causation has not been tested using a double blind randomized controlled trial (RCT). We aimed to compare clinical and immunological outcomes after baked egg (BE) consumption in young BE tolerant egg allergic children.

Methods In a double blind RCT, BE tolerant egg allergic children consumed 10 g BE (1.3 g protein) 2 to 3 times per week for 6 months (n = 21 intervention group) or similar egg free baked goods (n = 22 control group) while maintaining an otherwise egg free diet. The final assessment was a raw egg oral food challenge (OFC) 1 month after ceasing the intervention product. Egg specific IgE and IgG4 were assessed at baseline and 7 months.

Results After the intervention there was no difference in raw egg tolerance between groups, (23.5% (4/17) intervention group and 33.3% (6/18) control group). This was independent of age and amount of BE consumed (aOR 0.50 CI 0.11–2.40 p = 0.39). Both groups demonstrated decreased egg specific serum IgE titres and decreased whole egg specific IgE/IgG4 ratios.

Discussion We conducted this trial because inclusion of baked egg protein in the diet of egg allergic children appears to move children towards a more tolerant immune profile. Strengths of our study include design of the blinded intervention, the consistent dosing protocol and the regular monitoring of symptoms and intake. However, the study was limited by small sample size resulting in insufficient power to show statistically significant results.

Conclusion Our study suggests that short term, regular consumption of BE by BE tolerant 1 to 5 year old children with IgE mediated raw egg allergy may not induce, accelerate or slow development of tolerance to raw egg in this selected population. Trials with larger sample sizes are required to further test this hypothesis.

Trial Registration The trial was registered on 7^th February 2012 with the Australian New Zealand Clinical Trials Registry (ACTRN 12612000173897).

Bovine milk proteins, apart from provision of essential amino acids, impact on the human immune system. Heat treatments applied in processing of bovine milk directly influence milk protein structure and changes in associated epitopes, altering the immunogenic and antigenic potential of milk proteins, and thus modulating the human immune system in different ways. The severity of some processing technologies impact on important minor proteins that may exert immunomodulatory properties, in such a way as to prevent occurrence of allergies. In this review, heat-induced modifications of milk protein structure, associated changes in epitopes, alteration of immunomodulatory properties of milk and their effects on immunogenic and antigenic potential of milk proteins are discussed. Thermal processing in the dairy industry could be further optimised in a way to preserve and utilise the favourable immunomodulatory properties of milk, in addition to ensuring food safety, eventually making the final dairy product both hygienic and hypoallergenic.

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.

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.

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 (2.8 g of cow's milk protein). To exclude cow's milk (CM) tolerance, the patients were subsequently challenged with unheated CM.

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).

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.

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).

We sought to test whether patients who are BM reactive can progress in BM oral immunotherapy (OIT) and become desensitized to UM as well.

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.

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.

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.