Elevated Atopic Comorbidity in Patients with Food Protein-Induced Enterocolitis

Abstract

Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy. Its relationship to the major atopic manifestations (atopic dermatitis [AD], IgE-mediated food allergy [IgE-FA], allergic rhinitis [AR], asthma) is not understood.

Objective: To determine the clinical characteristics, epidemiologic features, and natural history of FPIES in relation to the major atopic manifestations.

Methods: We examined our primary care birth cohort of 158,510 pediatric patients, of whom 214 patients met 2017 FPIES diagnostic criteria. We measured the influence of FPIES on developing subsequent atopic disease.

Results: Pediatric FPIES incidence was between 0.17% and 0.42% depending on birth year. As in prior reports, most patients had an acute presentation (78%), and milk, soy, oat, rice, potato, and egg were common triggers. The mean age of diagnosis was 6.8 months. Atopic comorbidity was higher in patients with FPIES compared with healthy children (AD, 20.6% vs 11.7%; IgE-FA, 23.8% vs 4.0%; asthma, 26.6% vs 18.4%; AR, 28.0% vs 16.7%; P < .001 χ²). However, longitudinal analyses indicated that prior FPIES did not influence the rate of atopy development.

Conclusions: The incidence of FPIES in our cohort was initially low, but is increasing. Food allergen distribution, presentation, and age of onset are similar to prior reports. Patients with FPIES have high rates of atopic comorbidity. However, longitudinal analysis does not support direct causation as the etiology of these associations. Rather it suggests a shared predisposition to both types of allergy, or associative bias effects. This work refines our understanding of the natural history of FPIES by elucidating associations between FPIES and atopy.

Keywords: Asthma; Atopic march; Dermatitis, atopic; Epidemiology; FPIES; Food hypersensitivity; Food protein–induced enterocolitis syndrome; IgE-mediated food allergy; Rhinitis, allergic.

Figure 1:. Study Design.

We performed a retrospective review of 158,510 patients using an EMR-based primary care birth cohort to identify patients with Food protein-induced enterocolitis syndrome (FPIES) and Non-FPIES patients with atopic diagnoses. To do so, we used a combination of ICD-9/10 codes, allergen and medication information, and manual chart review.

Figure 2:. Incidence of FPIES.

A) Incidence of FPIES by birth year. B) Incidence of FPIES by age. FPIES, Food protein-induced enterocolitis syndrome.

Figure 3:. FPIES food allergens and presentation.

A) Frequency of the most common food allergens in patients with FPIES. Frequency of FPIES allergens within categories of B) grains, C) vegetables, and D) meats. E) Percent of patients presenting with acute or chronic FPIES phenotype. F) Onset of acute FPIES to milk and soy as compared with solid foods, in relation to patient age. FPIES, Food protein-induced enterocolitis syndrome.

Figure 4:. Development of atopy in FPIES and non-FPIES cohorts, irrespective of timing of FPIES onset.

Kaplan-Meier curves and 95% confidence intervals displaying diagnosis of A) atopic dermatitis (AD), B) IgE-mediated food allergy (IgE-FA), C) asthma, D) allergic rhinitis (AR) in FPIES patients or healthy controls. Hazard ratios (HR), 2.5% to 97.5% confidence intervals (CI), and p-values from logistic regression for each comparison are shown in each panel.

Figure 5:. Interaction of FPIES and atopic dermatitis (AD) on development of IgE-mediated food allergy.

Kaplan-Meier curves and 95% confidence intervals from analysis of IgE-FA development in patients with or without FPIES (as a categorical variable) or AD.

Figure 6:. IgE food allergy triggers in FPIES patients.

A) Percent of total FPIES cohort patients with IgE-FA to one, two, three, or four or more eliciting allergens. B) Percent of total FPIES cohort patients with IgE-FA to the eliciting allergens shown.

Figure 7:. Development of atopy in patients with preceding FPIES.

Kaplan-Meier curves and 95% confidence intervals displaying diagnosis of A) atopic dermatitis (AD), B) IgE-mediated food allergy (IgE-FA), C) asthma, D) allergic rhinitis (AR) in FPIES patients or healthy controls.