Not so fast, my friend: are dietary advancement therapies with extensively heated milk and egg safe or effective?

Published online June 18, 2024

Dietary advancement therapies (DAT) using extensively heated egg and milk products are popular ways to manage milk and egg allergy, especially because a high percentage of children are tolerant to these forms at baseline. Many endorse their safety and effectiveness in promoting tolerance, but are such conclusions valid?

In The Journal of Allergy and Clinical Immunology: In Practice, Anagnostou et al. undertook a systematic review of studies of children 18 years old and younger, which assessed the use of baked milk or egg, milk or egg ladders and baked milk or egg oral immunotherapy (OIT). Baked milk or egg was defined as ingesting extensively heated cow’s milk or hen’s egg, generally in a wheat or other grain matrix. Baked OIT was defined as the use of titrated quantities of baked milk or egg to a target maintenance dose of a full serving of the product (without changing the form). A ladder was defined as a titrated incorporation of sequentially less extensively heated milk- or egg-containing products over multiple steps, progressing from a small piece through the entire product, then advancing to the next slightly less extensively heated product form until an unheated milk or lightly cooked (or uncooked) egg form is reached. The authors explored 22 potential outcomes related to safety or efficacy in producing desensitization or tolerance and how rapidly this occurred. Meta-analysis was performed where >3 studies reported data for each outcome. The GRADE approach was used to determine the certainty of evidence for each outcome.

From among 9946 titles screened, 29 DAT studies meet the inclusion criteria. Meta-analysis showed tolerance occurred in 69% of egg ladder, 58% of milk ladder, 49% of baked egg OIT and 29% of baked milk OIT patients. Allergic reactions occurred in 21% of egg ladder, 25% of milk ladder, 20% of baked egg OIT and 61% of baked milk OIT patients. At-home reactions occurred in 19% of baked egg OIT and 10% of baked milk OIT patients. Discontinuation occurred in 14% of egg ladder, 17% of milk ladder, 17% of baked egg OIT and 20% of baked milk OIT patients. Mean time to baked egg and baked egg OIT tolerance was 13.25 months (4 studies) and 19.1 months (3 studies) but were not assessed for the other outcomes. The authors conclude DATs are relatively safe and effective. This relativity conclusion is because DAT studies are largely single-arm observational studies, with high heterogeneity and high risk of bias mainly resulting from selection bias (=enrichment of already baked-tolerant subjects) and incomplete reporting of outcomes. Most studies also lacked appropriate control groups. Overall, the meta-analyzed estimates had very low certainty of evidence, and it could not be differentiated if baseline baked tolerance or the DAT itself leveraged the estimate of safety or efficacy. Therefore, concluding DAT is safe and effective is premature, and requires more rigorous study. There may be more risk and less efficacy than has been reported to date.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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