A nationwide survey of non-IgE-mediated gastrointestinal food allergies in neonates and infants

Hiroko Suzuki; Naho Morisaki; Saori Nagashima; Tamotsu Matsunaga; Shoko Matsushita; Akira Iino; Yuichiro Tanaka; Hisashi Nishimori; Shun Munakata; Manabu Kemmochi; Yoshitaka Murakami; Miori Sato; Kenji Toyokuni; Kiwako Yamamoto-Hanada; Hideaki Morita; Tatsuki Fukuie; Yoshiyuki Yamada; Yoshikazu Ohtsuka; Katsuhiro Arai; Yukihiro Ohya; Hirohisa Saito; Kenji Matsumoto; Ichiro Nomura

doi:10.1016/j.alit.2023.10.003

A nationwide survey of non-IgE-mediated gastrointestinal food allergies in neonates and infants

Allergol Int. 2024 Apr;73(2):264-274. doi: 10.1016/j.alit.2023.10.003. Epub 2023 Oct 31.

Authors

Hiroko Suzuki¹, Naho Morisaki², Saori Nagashima³, Tamotsu Matsunaga⁴, Shoko Matsushita⁵, Akira Iino⁵, Yuichiro Tanaka⁶, Hisashi Nishimori⁷, Shun Munakata⁸, Manabu Kemmochi⁹, Yoshitaka Murakami¹⁰, Miori Sato¹¹, Kenji Toyokuni¹¹, Kiwako Yamamoto-Hanada¹¹, Hideaki Morita¹², Tatsuki Fukuie¹¹, Yoshiyuki Yamada¹³, Yoshikazu Ohtsuka¹⁴, Katsuhiro Arai¹⁵, Yukihiro Ohya¹¹, Hirohisa Saito¹², Kenji Matsumoto¹², Ichiro Nomura¹⁶

Affiliations

¹ National Research Institute for Child Health and Development, Division of Eosinophilic Gastrointestinal Disorders, Tokyo, Japan; Todachuo General Hospital, Department of Pediatrics, Saitama, Japan.
² National Center for Child Health and Development, Department of Social Medicine, Tokyo, Japan.
³ National Research Institute for Child Health and Development, Division of Eosinophilic Gastrointestinal Disorders, Tokyo, Japan.
⁴ Todachuo General Hospital, Department of Pediatrics, Saitama, Japan.
⁵ Tokyo Metropolitan Children's Medical Center, Department of Allergy, Tokyo, Japan.
⁶ National Center for Child Health and Development, Department of General Pediatrics and Interdisciplinary Medicine, Tokyo, Japan.
⁷ Mie Prefectural General Medical Center, Department of Pediatrics, Mie, Japan.
⁸ Nagano Children's Hospital, Department of Neonatology, Nagano, Japan.
⁹ Kitasato University Hospital, Department of Pediatrics, Kanagawa, Japan.
¹⁰ Ehime Prefectural Imabari Hospital, Department of Pediatrics, Ehime, Japan.
¹¹ National Center for Child Health and Development, Allergy Center, Tokyo, Japan.
¹² National Research Institute for Child Health and Development, Department of Allergy and Clinical Immunology, Tokyo, Japan.
¹³ Tokai University School of Medicine, Department of Pediatrics, Kanagawa, Japan.
¹⁴ Juntendo University School of Medicine, Department of Pediatrics and Adolescent Medicine, Tokyo, Japan.
¹⁵ National Center for Child Health and Development, Allergy Center, Tokyo, Japan; National Center for Child Health and Development, Division of Gastroenterology, Tokyo, Japan.
¹⁶ National Research Institute for Child Health and Development, Division of Eosinophilic Gastrointestinal Disorders, Tokyo, Japan; National Center for Child Health and Development, Allergy Center, Tokyo, Japan. Electronic address: nomura-i@ncchd.go.jp.

PMID: 37914545
DOI: 10.1016/j.alit.2023.10.003

Abstract

Background: Non-IgE-mediated gastrointestinal food allergies (non-IgE-GIFAs) seem to be increasing rapidly worldwide. However, nationwide studies have been limited to food-protein-induced enterocolitis (FPIES) and food-protein-induced allergic proctocolitis (FPIAP), with little attention to other non-IgE-GIFA subgroups. The aim of this study was to elucidate the clinical features of all patients with non-IgE-GIFAs, not just certain subgroups.

Methods: We conducted a nationwide cross-sectional survey of non-IgE-GIFAs in Japan from April 2015 through March 2016. A questionnaire was sent to hospitals and clinics throughout Japan. The questionnaire asked about the number of physician-diagnosed non-IgE-GIFA patients, the status of fulfillment of the diagnostic criteria, tentative classification into 4 clusters based on the initial symptoms, the day of onset after birth, complications, and the suspected offending food(s).

Results: The response rate to that questionnaire was 67.6% from hospitals and 47.4% from clinics. Analyses were conducted about "diagnosis-probable" patient cohort (n = 402) and the "diagnosis-confirmed" patients (n = 80). In half of the reported non-IgE-GIFA patients, onset occurred in the neonatal period. The patients were evenly distributed among 4 non-IgE-GIFA clusters. In Cluster 1, with symptoms of vomiting and bloody stool, the onset showed a median of 7 days after birth, which was the earliest among the clusters. Cow's milk was the most common causative food.

Conclusions: In half of the patients, the onset of non-IgE-GIFAs was in the neonatal period. This highlights the importance of studying the pathogenesis in the fetal and neonatal periods.

Keywords: Eosinophilic gastrointestinal disorder (EGID); Food-protein-induced allergic proctocolitis (FPIAP); Food-protein-induced enterocolitis (FPIES); Food-protein-induced enteropathy (FPE); Non-IgE-mediated gastrointestinal food allergy (non-IgE-GIFA, non-IgE-GIFAs).

MeSH terms

Allergens
Animals
Cattle
Cross-Sectional Studies
Enterocolitis* / diagnosis
Enterocolitis* / epidemiology
Female
Food
Food Hypersensitivity* / complications
Food Hypersensitivity* / diagnosis
Food Hypersensitivity* / epidemiology
Humans
Infant
Infant, Newborn
Proctocolitis* / complications
Proctocolitis* / diagnosis
Proctocolitis* / epidemiology

Substances

Allergens