Pediatric Multi-Food Allergy Phenotypes May Guide Screening in Primary Care

Recent findings suggesting the identification of distinct phenotypes and comorbidities in pediatric multi-food allergy may necessitate expanded allergy screening protocols within primary care settings, will be presented at the 2026 American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting.¹

“Multi-food allergy is heterogenous in its presentation among US children—but analyses reveals distinct multi-FA phenotypes that may warrant targeted screening and interventional approaches,” wrote investigators, led by Christopher Warren, PhD, assistant research professor of Preventive Medicine and director of Population Health Research at Center for Food Allergy and Asthma Research at Northwestern University Feinberg School of Medicine, in the Journal of Allergy and Clinical Immunology (JACI).²

Drawing from a National Institute of Allergy and Infectious Diseases (NIAID) supported longitudinal cohort of 1382 children under 12-years-old, investigators found 75.5% of participants suffered from multiple current food allergies. Among those with only a single allergy, nearly half (49.2%) were allergic to peanuts. The study utilized latent class analytic methods and electronic health record (EHR) extraction to determine multi-food allergy risk can be predicted by factors such as race, ethnicity, age, socioeconomic status, comorbid atopy, and total IgE levels.^1,2,4

The data revealed significant variance in comorbid FA rates based on the specific allergen. Clinicians should note an exceptionally high probability of comorbidity (>0.9) between specific tree nut pairs, specifically cashew-pistachio and walnut-pecan. Conversely, the lowest rates of comorbidity (<0.2) were observed between seafood and milk or egg allergies.

The researchers identified three primary clinical clusters of multi-food allergy:

• Cluster 1 (55%): Characterized by a dual peanut and tree nut allergy.
• Cluster 2 (30%): Characterized by a combined peanut, egg, and milk allergy.
• Cluster 3 (15%): A broadly multi-food allergic class with allergies to many common foods.

The study comes at a time of renaissance for the allergy community, with multiple regulatory developments of note in the last half decade, including the FDA approval of the first agent indicated for multiple food allergies in omalizumab (Xolair) in February 2024. This approval was based on data from the phase 3 OutMATCH trial, which headlined AAAAI 2024 as a late-breaking presentation.

In that trial, which recruited 471 patients aged 1 to 55 years who are allergic to peanuts and at least 2 other food allergens, concluded a statistically significant higher proportion of patients (68%) treated with omalizumab for 16 to 20 weeks tolerated at least 600 mg of peanut protein without moderate to severe allergic symptoms, compared to 5% of those treated with placebo (P <.0001).

Results also suggested a statistically significant higher proportion of patients treated with omalizumab tolerated at least 1000 mg of protein from milk (66% vs. 11%; P <.0001), egg (67% vs. 0%; P <.0001) or cashew (42% vs. 3%; P <.0001) without moderate to severe allergic symptoms compared to placebo.

"The stress of living with food allergies can weigh heavily on people and their families, particularly when navigating events like children's birthday parties, school lunches, and holiday dinners with friends and family," said Kenneth Mendez, president and CEO of the Asthma and Allergy Foundation of America (AAFA) in a press release around the February 2024 approval. "Given the growing prevalence of food allergies, this news offers hope to the many children and adults who may benefit from a new way to help manage their food allergies."³

For the primary care physician, these findings underscore the importance of recognizing pediatric food allergies rarely exist in isolation. Understanding these specific clusters and high-probability pairings can help guide more targeted referral and screening strategies for young patients displaying initial signs of atopy.

References:

1. Multi-Food Allergy Comorbidities Warrant Screening. Aaaai.org. Published February 10, 2026. Accessed February 28, 2026. https://www.aaaai.org/about/news/news/2026/multi
2. Understanding the distribution and determinants of allergy to multiple foods within a large, multi-site observational cohort of pediatric food allergy patients. Warren, Christopher et al. Journal of Allergy and Clinical Immunology, Volume 157, Issue 2, AB286
3. FDA approves Xolair® (omalizumab) as first and only medicine for children and adults with one or more food allergies. Novartis United States of America. Published February 16, 2024. Accessed February 28, 2026. https://www.novartis.com/us-en/news/media-releases/fda-approves-xolair-omalizumab-first-and-only-medicine-children-and-adults-one-or-more-food-allergies
4. ClinicalTrials.gov. clinicaltrials.gov. Published September 20, 2025. Accessed February 28, 2026. https://clinicaltrials.gov/study/NCT03881696?term=NCT03881696&rank=1