Narcolepsy Potentially Identified as a Symptom of Immediate Food Allergic Reactions in Pediatrics

Birgit Kalb, MD

Recently published in The Journal of Allergy and Clinical Immunology: In Practice, findings from a study showed that narcolepsy-like sleepiness is a frequently occurring clinical manifestation of immediate-type allergic reactions on food ingestion among children.¹ These findings provide evidence toward a significant contribution in highlighting more about this neurological allergic symptom and its clinical picture for patients with the condition.

Among 848 food-allergic children, 12.5% (n = 105) of participants showed narcolepsy-like sleepiness based on an immediate-type allergic reaction to at least 1 positive oral food challenge (OFC). This was observed in 87 patients once (10.3%), 15 twice (1.8%), 3 children 3 times (0.3%), and 1 child 4 times (0.1%). In 113 patients challenged openly, 9 (8.0%) developed narcolepsy-like sleepiness. Notably, among 735 children who were double-blind placebo-controlled challenged, 97 (13.2%) were affected by narcolepsy-like sleepiness compared with none in the placebo.

“In the case of multiple food allergies and/or in the context of persistent food allergies, participants were orally challenged at least once and some as many as 14 times during the study period. As expected, we observed that the proportion of children with narcolepsy-like sleepiness increased with the number of OFCs performed,” lead author Birgit Kalb, MD, professor in the department of pediatric respiratory medicine, immunology, and critical care medicine at Charité - University Medicine Berlin in Germany, and colleagues wrote.¹ “However, children with multiple positive food challenges were affected by narcolepsy-like sleepiness in a similar way to subjects who had only 1 positive OFC. Because of the lower numbers of children with more than 2 positive OFCs, we grouped them also with children with 3 to 4 and 5 to 14 food challenges.”

Researchers investigated the frequency of narcolepsy-like sleepiness during oral food challenges and characterized the symptom by comorbidities, eliciting allergens, and severity of reactions. In the study, children with immediate-type allergic reactions who underwent an oral food challenge were recruited between 2009 and 2020 from the ongoing Eczema and Food Allergy registry at the Charité University hospital. Authors defined narcolepsy-like sleepiness as a somnolent condition during which patients could barely be woken up again, occurring in 2 hours of food intake and which was not because of treatment adverse effects. The researchers used logistic generalized estimating equations to investigate the effect of age, severity of reactions, and eliciting allergens on the occurrence of narcolepsy-like sleepiness.

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“Moreover, in children with narcolepsy-like sleepiness, moderate to severe reactions were found more often than mild reactions. This was mainly because of an involvement of multiple organ systems rather than because of a disproportionate involvement of the respiratory or cardiovascular system, because symptoms of the various involved organ systems were quite equally distributed, with no significantly preponderant involvement of specific organ systems. Reactions on multiple organ systems however are an expression of a systemic inflammatory process, leading to a higher cytokine response, which may also affect the central nervous system, and causing narcolepsy-like sleepiness,” Kalb et al noted.¹

Researchers observed that children with atopic eczema had a significantly higher incidence (P = .006) of narcolepsy-like sleepiness. Also, the most frequently challenged allergen leading to immediate-type allergic reactions in the study cohort was hen’s egg allergy with 629 OFCs (42.2%), followed by peanut allergy with 270 OFCs (18.1%), cow’s milk allergy with 232 OFCs (15.6%), and hazelnut with 130 OFCs (8.7%).

The most allergic reactions reported were mild (grade 2A; 53%) or moderate (grade 2B; 17.6%) according to severity grading using Niggemann and Beyer.2 Among children with narcolepsy-like imperative sleepiness, moderate to severe reactions of grade 2B to 3B occurred more often than milder reactions of grade 1 to 2A (P = .026; OR, 1.521; 95% CI,1.051-2.202).

All told, the study was limited by the fact that narcolepsy-like sleepiness was diagnosed according to its clinical picture. Authors also noted that they did not perform measurement of brainwaves via electroencephalogram to assess the brain activity before and during the reaction. In addition, researchers noted that there was no measuring of cytokine release before and during challenges as well as no recording of the duration of sleep among patients.

“Regarding adequate management strategies to treat narcolepsy-like sleepiness occurring during OFCs, we would recommend a close monitoring of vital signs, especially blood pressure, because somnolence could also be the expression of cardiovascular involvement, which should be treated immediately with adrenaline and volume substitution. Furthermore, in the case of anaphylaxis because of accidental allergen exposure outside the clinic, we would recommend a resolute anaphylaxis treatment, because a drop in blood pressure could also be the reason, which is not possible to evaluate without monitoring. In general, further research is needed to develop tailored management strategies,” Kalb et al noted.¹

REFERENCES
1. Kalb B, Jentsch J, Yürek S, et al. Narcolepsy-Like Sleepiness: A Symptom of Immediate-Type Reactions in Food-Allergic Children. J Allergy Clin Immunol Pract. 2023;11(4):1147-1153. doi:10.1016/j.jaip.2022.11.038
2. Niggemann B, Beyer K. Time for a new grading system for allergic reactions?. Allergy. 2016;71(2):135-136. doi:10.1111/all.12765