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Clinical bottom lines
Dietary introduction of cooked hen’s egg can reduce the risk of egg allergy in infants. (Grade B)
The degree to which egg has been processed for early introduction seems to affect clinical outcomes with raw egg powders causing more complications due to increased allergenicity. (Grade C)
Pre-testing with either SPT or specific serum markers (e.g., sIgE) in high-risk infants can inform the clinician whether clinical supervision of early egg introduction may be useful. (Grade C)
A 4-year-old infant comes into allergy clinic with her parents who say that after eating eggs and egg-containing foods she develops a ‘nettle sting’ rash around the mouth. This usually happens within an hour of eating. After an oral food challenge, an egg allergy is diagnosed. At a follow-up appointment, the parents ask you whether this could have somehow have been prevented. You look into whether early dietary introduction of egg would have played a role.
Structured clinical question
In children (population), does early introduction of egg (intervention) compared with later introduction (comparison) prevent the development of egg allergy (outcome)?
All searches were all performed on 17 February 2021.
Cochrane Library searched: ‘egg allergy prevention’ and ‘early introduction’; 26 results, none relevant. National Institute for Health and Care Excellence evidence searched: ‘egg allergy prevention’; 204 results, none relevant.
PubMed searched (“infant*“[Title/Abstract] OR “child*“[Title/Abstract] OR “paediatric”[Title/Abstract]) AND “introduction”[Title/Abstract] AND (“egg”[Title/Abstract] OR “hen’s egg”[Title/Abstract]) AND (“egg allergy”[Title/Abstract]) with 80 results, 6 studies included.
See table 1.
Egg allergy, an adverse immunological reaction to egg proteins, is one of the most common food allergies in infants and young children.1 With the incidence rates of over 2% in the UK, it has the highest prevalence rate of 8.9% (95% CI 7.8% to 10.0%) in the first year of life.2 3 Egg allergy can cause life-threatening anaphylactic reactions that significantly impair the quality of life4 and adversely affect morbidity; therefore, the development of effective prevention strategies is key. Early allergen introduction has been associated with reduced food allergy rates with a recent systematic review and meta-analysis by Al-Saud and Sigurdardóttir confirming findings.5–7
The search generated six randomised clinical trials (table 1) with the majority looking into egg allergy and egg sensitisation rates as primary and secondary outcomes. Allergic sensitisation is biochemical evidence of IgE response to an allergen but does not correlate in every case with clinical allergy as evidenced by studies showing significantly higher rates of allergen sensitisation in comparison with true allergy rates.8–10
The high heterogeneity from the study participants (healthy infants,11 12 infants with hereditary risk13 14 or infants with eczema15 16) to varied age ranges at introduction and follow-up times as well as a variation of egg vehicles used (raw egg powders12–15 to cooked egg11 16), length of treatment and outcome measures complicates analysis.
Perkin et al and Natsume et al all showed significantly reduced rates of egg allergy with early introduction (p=0.05).11 16 Tan et al and Palmer et al showed reduced egg allergy rates that were not statistically significant.13 14 Two studies, Bellach et al and Palmer et al, had to be terminated early due to safety concerns, however, this is thought to be due to the raw egg powder vehicle used and not due to early introduction itself.12 15 Conversely, Natsume et al used heated egg powder with no allergic reactions and showed a protective effect of early egg introduction between the ages of 6 and 9 months with a significant reduction in the prevalence of egg allergy at 12 months.16 The change in safety data can be explained by higher allergenicity of raw egg powder in comparison with cooked as children outgrow cooked-egg allergy two times faster than raw-egg allergy.17
In addition to rates of clinical allergy, several studies measured the rates of egg sensitisation prior to entering the trials, addressing the question of which infants are sensitised (but are not allergic) to egg but can develop tolerance via regular ingestion, and those who will react on ingestion and become allergic. Four studies (Bellach et al, Natsume et al, Palmer et al and Tan et al) measured the level of egg sensitisation prior to ingestion, either as a primary or secondary outcome measure.12–14 16 Two of the studies showed an increase in egg sensitisation with early egg introduction with Natsume et al showing statistically significant levels (p=0.001).16 Although Palmer et al and Tan et al showed a general decrease in egg sensitisation in the early introduction groups, Tan et al showed statistically significantly higher levels of IgE to egg protein prior to ingestion already present in the serum of infants in the early introduction group (p=0.001).13 14 These mixed results warrant further investigation to understand the significance of egg sensitisation, especially in high-risk children with atopic conditions or hereditary risk as Palmer et al showed that many infants with eczema are already sensitised to egg by the age of 4 months.15 The current tests for egg sensitisation are not sensitive and specific enough to predict which pre-ingestion sensitised infants will react or be able to induce tolerance with early introduction without confirmatory oral challenges. Therefore, the judicious use of pre-testing in certain high-risk demographic groups may be useful to identify the sensitised patients who might develop clinical reactions with early introduction18 meaning high-risk infants require specialist input before early egg introduction, but not the general low-risk population.
In conclusion, with the mixed evidence available, an early introduction of egg seems to have a positive effect on egg allergy rates. Future studies will need to consider the egg vehicle used, egg dosage, the length of egg consumption as well as participant comorbidities and demographics (age range, follow-up period and ethnicity among others). There is some evidence that pre-testing for sensitisation may offer useful clinical information; therefore, further research should consider them in their outcome measures. For real-life applicability of results, there needs to be an approach in which egg would be prepared to simulate true-to-life circumstances.
Patient consent for publication
Contributors VK and SL together decided to pursue this specific topic idea. VK was responsible for the researching, writing and editing. SL contributed her expertise to the write-up and was involved in the editing process.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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