Anaphylaxis Management in Paediatric Patients Undergoing Milk Oral Immunotherapy

Following anaphylaxis, previous guidelines mandate the transfer of the affected individual to the emergency department (ED) for further assessment. The Canadian Paediatric Society (CPS) suggests a minimum period of observation in the ED of 4–6 h following onset of allergic symptoms to evaluate the need for additional interventions and manage potential biphasic reactions. Translating Emergency Knowledge for Kids (TREKK) has similar recommendations depending on the severity of the reaction and patient-specific risk factors, ranging from a 2-h observation to an overnight stay if deemed necessary [1, 2]. More recent US guidelines call against routine transfer to ED of all anaphylaxis cases following epinephrine use, advising case-by-case evaluation based on patient factors and relation circumstances [3, 4]. This paper aims to examine the differences in anaphylaxis management and associated characteristics among two groups: those who presented to the ED after an anaphylactic episode and those who did not in a cohort of children who have challenge-confirmed diagnoses of milk allergy and are currently undergoing oral immunotherapy to cow's milk (OIT).

In this retrospective cohort study, we analysed data from the year 2014 to 2023 inclusively. Participants selected were paediatric patients undergoing milk OIT at three children's hospitals across Canada: the Montreal Children's Hospital (Montreal), the British Columbia Children's Hospital (Vancouver) and the Hospital for Sick Children (Toronto). Only adverse reactions meeting the definition of anaphylaxis according to the National Institute of Allergy and Infectious Disease classification were included in the analysis [5]. The Muraro et al. [6] grading system was used to categorise the severity of anaphylactic reactions. Participants were grouped into two categories based on their response post-reaction: those who visited the ED and those who managed the reaction entirely at home. Descriptive statistics were used to present demographic, clinical management characteristics and levels of biomarkers. All statistical data were analysed using R 4.2.3 binary for macOs 10.3 (R Foundation for Statistical Computing, Vienna, Austria). Categorical data were presented as percentages, and continuous data as a median (interquartile range [IQR]). Fisher's test was used to compare categorical variables and Mann–Whitney test was used to compare continuous variables. This study was approved by participating centres ethics committees.

The study included 27 paediatric patients undergoing cow's milk OIT. The median age of patients at the start of OIT was 12.0 years (9.5–14.0) and 51.9% were males. Out of the 27 patients included in the study, 92.6% had asthma. A total of 60 anaphylactic reactions were reported from 2014 to 2023. Notably, 63.3% resulted in a visit to the ED. The updosing phase was identified as a particularly vulnerable period, with most anaphylactic reactions (68.3%) occurring during this stage. Over 71.7% of anaphylactic reactions were of moderate severity and 8.3% were classified as severe (Table 1).

Over 22 reactions were managed at home whereas 38 reactions were managed in the ED. Antihistamines were the most common treatment in home management (63.6%) and ED management (31.6%). Among all 60 reactions, respiratory manifestations were the most prevalent in 83.3% of reactions, followed by dermatologic (71.7%) and gastrointestinal (45.0%). No significant differences were found in the degree of severity of reaction between reactions managed at home and reactions managed in the ED.

All patients received at least one IM epinephrine dose for their reaction. Within reactions managed at home, 95.5% required only one dose of IM epinephrine versus 78.9% in reactions managed in the ED. In the pre-hospital setting, 68.4% of reactions managed in the ED received a single-dose epinephrine prior to this. In contrast, pre-hospital epinephrine was significantly higher (p = 0.01) in reactions managed at home (100.0%).

This retrospective cohort study assessed the management of anaphylaxis in paediatric patients undergoing cow's milk OIT. The role of intramuscular epinephrine in managing anaphylaxis is well recognised and is considered the gold standard first-line treatment [7]. The administration of epinephrine in the pre-hospital setting was significantly higher among patients managed at home compared to those transferred to the ED. This suggests that early epinephrine use intervention at home can potentially successfully treat reactions without the need for further treatment in a hospital setting, especially if prompt administration is sufficient to control symptoms. This raises questions about some of the current recommendations for mandatory transfer to the ED following epinephrine administration. This study has some limitations including potential selection bias given that patients were undergoing OIT and likely have higher health literacy and access to care. Additionally, perception of reaction severity and hence the decision on the use of epinephrine may vary between patients who manage reactions at home and physicians in-hospital. However, it is noteworthy that all reactions assessed met the definition of anaphylaxis according to the standardised questionnaire used in this study and hence merit the use of epinephrine regardless of severity. Furthermore, our study does not have data regarding the exact timing of the first epinephrine. Finally, it is important to recognise that anaphylaxis often self-resolves, with or without intervention. Consequently, the decision of self-treated patients to not attend the ED may reflect behavioural tendencies rather than evidence of treatment efficacy.

With the shift in guidelines in some regions retiring the advice to transfer all patients to the ED post-epinephrine administration [5], our study provides timely evidence that supports the safety and efficacy of at-home management of certain anaphylactic reactions. This could lead to a re-evaluation of current protocols and the development of a more nuanced, patient-centred approach to anaphylaxis management.

R.K. and D.B. wrote the article. S.G. helped with data analysis. J.U., E.G., E.S.C., I.B., L.B., D.K., B.M., C.M. and D.L. helped with data collection and review of the article. M.B.-S. was the principal investigator of this study and helped with data collection, analysis, manuscript writing and review.

The authors declare no conflicts of interest.