Early-Onset Food Allergy in Infants and Toddlers Increases Atopic March Risk

Early-onset food allergy (FA) in infants and toddlers with atopic dermatitis (AD) enhances the risk of atopic march (AM) from ages 5-11 years for future moderate-severe asthma, anaphylaxis, and allergic rhinitis (AR), according to results from a new retrospective observational study.

AD is one of the most common skin disorders in young children, typically manifesting during the first 6 months of life. It has been broken up into 3 distinct, sequential phases: infantile, childhood, and adult. Disease progression also tends to follow a pattern, known as the atopic march.2

AD and other atopic disorders share a common genetic basis and pathogenesis. Several trials have provided evidence for the march, which typically consists of a progression of atopic diseases with common genetic predisposing factors and results in the development of AR and asthma.2

However, recent findings have challenged the sequential AM model, with one four cohort study in particular reporting no evidence for the progression. To that end, investigators conducted a birth cohort study to prove the connection.1

“A better understanding of the clinical risk factors for development of atopic disorders is crucial, given the potential for environmental interventions and biologic treatment to attenuate the AM in children and adults,” wrote Robert S. Zeiger, MD, PhD, director of allergy research at Kaiser Permanente Medical Center, and colleagues.1

Investigators utilized administrative data from the KPSC Research Data Warehouse, collecting information on a birth cohort of children with AD diagnosed by age 36 months. Patients were excluded if they had been diagnosed with AD between the years 2008 and 2020, if they had at least two separate dispensing records of AD medications, or if they had continuous enrollment in health plan with pharmacy benefit from birth to 11 years of age. This group was then further divided into those with and without FA, based on IgE immunoCAP testing or skin prick testing to a specific food.1

Asthma and anaphylaxis were diagnosed using ICD-9 and ICD-10 codes, while allergic rhinitis also required a positive IgE immunoCAP test (≥35 IU/ml) or a skin prick test (≥3 mm vs saline control) to an aeroallergen. The team also determined the association between maternal and child characteristics from the perinatal period until 36 months of age.1

Prevalence, number of encounters, any and frequency of rescue and controller medication dispensed, healthcare utilization including emergency department visits, and severity based on Global Initiative for Asthma (GINA)-step care were all determined yearly and throughout ages 5-11.1

A collective 10,688 children with AD onset from birth to 36 months were included in the study. This group was then stratified into those with food allergy (FA+, n = 2273) and those without food allergy (FA-, n = 8415). Baseline data to 36 months were compared between the subgroups, including demographics, birth features, and atopic disorders, respiratory infections, allergen sensitization, and blood eosinophil levels.1

The number of AD visits per child was 4.9 +/- 3.6 and the mean number of AD medication dispensing records was 5.1 +/- 4.5. By the first diagnosis, children were 7.6 +/- 6.5 months old, with roughly 57.5% being male. Notably, when compared to the FA- group, the FA+ group exhibited a substantially higher number of AD diagnoses and medications dispensed, as well as higher numbers of asthma encounters and healthcare visits, higher proportion of AR with aeroallergen sensitization, diagnosis of EoE, elevated blood eosinophil levels (≥300 cells/mm3 and ≥500 cells/mm3).1

Compared to the FA- group, FA+ children were substantially more likely to be male, of Asian/Pacific Islander ethnicity, develop AD earlier, and have a higher incidence of asthma-related physician visits by age 36 months (P <.001). Through multivariate analysis, investigators also found increased adjusted risk ratios (aRR, 99% CI) (P <.001) for moderate-severe asthma prevalence (aRR 1.42, 1.14-1.76), AR (aRR 1.34, 1.19-1.51) and anaphylaxis (aRR: 1.69, 1.33-2.15).1

Based on these data, Zeiger and colleagues indicated that early-onset FA in infants and toddlers with AD significantly enhances atopic march by increasing the risk of future moderate-severe asthma, AR, and anaphylaxis.1

“The findings from this retrospective administrative data analysis strongly support the importance of early-onset FA as an additive atopic disorder in promoting the AM in AD children,” Zeiger and colleagues wrote. “FA enhances both present and future atopic conditions including asthma, AR, anaphylaxis, EoE, allergen sensitization, and elevated levels of blood eosinophils levels.”1

References

1. Zeiger RS, Schatz M, Zhou B, et al. Impact of Food Allergy on the Atopic March Progression from Atopic Dermatitis in Early Childhood to Other Atopic Disorders at School Age. J Allergy Clin Immunol Pract. Published online May 7, 2025. doi:10.1016/j.jaip.2025.05.001

2. Spergel JM, Paller AS. Atopic dermatitis and the atopic march. J Allergy Clin Immunol. 2003;112(6 Suppl):S118-S127. doi:10.1016/j.jaci.2003.09.033