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\begin{document}

\title{Reintroduction failure after undergoing oral immunotherapy or oral food
challenges with cooked egg}



\author[1]{Paula Cabrera-Freitag}%
\author[1]{Alberto Alvarez-Perea}%
\author[2]{Maria Jose Goikoetxea}%
\author[3]{Sonsoles Infante}%
\author[3]{Victoria Fuentes-Aparicio}%
\author[2]{Carmen D'Amelio}%
\affil[1]{Hospital General Universitario Gregorio Marañón}%
\affil[2]{Clínica Universidad de Navarra}%
\affil[3]{Hospital Materno-Infantil Gregorio Marañón}%


\vspace{-1em}



  
  \date{June 15, 2024}


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\textbf{Reintroduction failure after undergoing oral immunotherapy or
oral food challenges with cooked egg}

To the editor,

Food allergy has increased in recent decades currently affecting almost
6\% of the european pediatric population (1). Egg is the second leading
cause in food allergy (1) and in anaphylactic food reactions (2) among
preschool-aged children in Europe. Recent studies have suggested a
persistent tendency for egg allergy, estimating that less than 50\% of
these children can tolerate it by 2 years of age (3). However, up to
70\% of egg-allergic children tolerate cooked egg (4). Some studies
suggest that regular consumption of cooked egg in these children might
increase their probability of tolerating egg in any presentation in the
future (5, 6). In the past decades, complete egg avoidance was the
recommended treatment in egg allergic patients. This recommendation has
an important impact in quality of life of the patients and their
families and does not guarantee the prevention of severe reactions due
to accidental ingestion of even small amounts of the offending food (2,
7). Oral immunotherapy (OIT) for persistent egg allergy has emerged as
an alternative therapy to egg avoidance. Tolerance can be induced by the
administration of different egg products and maintained by the regular
ingestion of egg several times per week, indefinitely.

Previous retrospectives studies had shown, that around 25\% of children
with negative oral food challenges OFC) did not reintroduce the food at
home with a lower successful introduction rate for peanut (32-60\%) than
for milk (10-22\%) or egg (13-29\%) (8-10). Aversion and refusal of the
food, reactions at home after being tolerated in hospital and fear of
reactions were the most reported reasons for peanut reintroduction
failure (8-10).

As the type of food significantly influences the rate of non-adherence
to its regular consumption (9), its causes might be also different
depending on the food involved. The aim of our study was to analyze the
leading causes of lack of adherence to the regular ingestion of cooked
egg after undergoing OIT or an OFC with cooked egg.

Egg allergic patients among 2-17 years old, not following the
recommendation of maintaining the intake of three eggs per week after
undergoing OIT or OFC with cooked egg, were prospectively recruited from
the Allergy Service of Hospital General Universitario Gregorio Mara\selectlanguage{ngerman}ñón
(Madrid) and Clínica Universidad de Navarra (Pamplona) between January
2019 and May 2020. The patients or their legal representatives, in the
case of children under 12 years, fulfilled a questionnaire (supplemental
file) regarding demographic and clinical information and the causes of
lack of adherence or abandonment of regular intake of cooked egg. The
questionnaire was also published in Twitter (Twitter Inc, San Francisco,
Calif) and anonymously fulfilled. Qualitative variables were expressed
in percentages and quantitative variables were expressed as median and
interquartile range (IQR). The study was approved by the Ethics
Committee for Investigation of both participating hospitals.

Twenty patients were included in the study {[}55\% female; median age:
10.7 years (IQR: 9-16.3){]}. Fifteen (75\%) were recommended to maintain
regular intake of cooked egg after OIT and 5 (20\%) after OFC. Patient´s
diagnosis of egg allergy was performed by a median age of 14.5 months
(IQR: 11-16 months). Median time of egg avoidance before OFC or OIT with
cooked egg was 6.1 years (IQR: 3.6-9.4 years).

Four (20\%) patients referred a frequency intake of two cooked eggs
weekly, seven (35\%) referred the ingestion of one egg weekly and nine
(45\%) only consumed breaded/floured foods with egg. The causes of lack
of adherence to the regular intake of cooked egg are summarized in the
figure. Most of the patients reported poor compliance as they did not
like the taste (85\%), the texture (70\%) or the smell (65\%) of egg.
Other causes of lack of adherence were being tired of eating the food in
the same cooking presentation (55\%), the difficulty to find a variety
of recipes (50\%), reactions at home after tolerance assessment by OFC
or OIT (35\%), considering the recommended intake excessively frequent
(25\%), fear of having a reaction (20\%), forgetting (20\%) and
rejection of the appearance of the egg (10\%). One out of 20 patients
(5\%) reported lack of adherence due to interference with other
activities such as sports, other food allergies and living with egg
allergic relatives.

According to our results, the most frequent cause for which patients
decreased or stopped the regular ingestion of cooked egg is aversion of
the food (related to the organoleptic characteristics of the egg: taste,
texture, and/or smell) which is in accordance with other studies
performed with other allergens (9, 10). The second cause of poor
adherence in our study, was the lack of variety in their cooking
preparation which has not been observed in other studies with other
foods.

While in the case of peanuts, fear of having a reaction is among the
first three causes of reintroduction failure (10), this does not seem to
be an important cause in the case of egg, being the fifth cause referred
by the patients in our study. We therefore believe that it is important
to analyze the causes of lack of adherence to regular consumption of a
food after having verified its tolerance, depending on the food and the
type of presentation in which it is indicated to consume since they seem
different and therefore the possible measures on which to act.

Our study has some limitations, as the relative small sample group. Time
spam between food challenge and completion of the questionnaire is wide
and probably those children fulfilling the questionnaire closer to the
challenge, did it more correctly. Moreover, we do not have data on the
exact timing of failure. The questionnaire is not validated, thus we
cannot rule out that the content and way of asking may have influenced
the results of our study. In addition, the inclusion criteria in those
patients who fullfilled the questionnaire via Twitter could not be
verified.

In our opinion, strategies to promote regular cooked egg consumption
such as providing a variety of recipes for safe consumption with masked
egg, suggesting practical recommendations to favor the regular intake or
emphasizing in patient education regarding the importance of maintaining
the regular consumption of the food could be useful to facilitate
compliance in these patients and maintain the acquired tolerance.

\textbf{Key messages statement}

The causes of lack of adherence to regular consumption of a food after
having verified its tolerance, seem to be different depending on the
food and the type of presentation in which it is indicated to consume
and therefore the possible measures on which to act.

Our study shows that the two most frequent causes for which patients
decreased or stopped the regular ingestion of cooked egg after
undergoing OIT or OFC with cooked egg, is aversion of the food (related
to the organoleptic characteristics of the egg: taste, texture, and/or
smell) and the lack of variety in their cooking preparation.

Strategies to promote regular cooked egg consumption such as providing a
variety of recipes for safe consumption with masked egg, could be useful
to facilitate compliance in these patients and maintain the acquired
tolerance.

\textbf{References}

\begin{enumerate}
\tightlist
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  Grabenhenrich LB, Dölle S, Moneret-Vautrin A, Köhli A, Lange L,
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  Xepapadaki P, Fiocchi A, Grabenhenrich L et al. Incidence and natural
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\end{enumerate}

\textbf{Hosted file}

\verb`Figure Avoidnace of cooked egg after OIT or OFC .docx`  available at \url{https://authorea.com/users/438321/articles/539553-reintroduction-failure-after-undergoing-oral-immunotherapy-or-oral-food-challenges-with-cooked-egg}

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