Getting in Step: Scientists Suggest Eosinophilic Esophagitis Part of Allergic March

New research findings by physician-scientists at Children’s Hospital of Philadelphia suggest that eosinophilic esophagitis (EoE) can be added as another “step” on the allergic march.

The allergic march, also known as atopic march, classically describes a progression of allergic diseases as they develop from infancy to adolescence, beginning with atopic dermatitis (eczema) early in life, and followed by anaphylactic food allergy, asthma, and allergic rhinitis (hay fever). Scientists suggest that for highly allergic individuals, early march members predispose to late march members, as a result of common genetic and inflammatory pathways. In a study published June 25 in The Journal of Allergy and Clinical Immunology: In Practice, CHOP researchers provide first evidence that EoE is a late manifestation of the allergic march, a finding that supports more active screening of allergic children for EoE symptoms.

During an allergic reaction to specific foods and pollens associated with EoE, high quantities of eosinophils, a type of white blood cell, congregate in the esophagus. This muscular tube that carries food from the throat to the stomach gets swollen, and children with EoE can experience belly pain, trouble swallowing, uncontrollable reflux, and failure to thrive as a result. CHOP’s Center for Pediatric Eosinophilic Disorders treats about 1,500 patients with EoE from all over the world.

“We are realizing that the age of EoE onset may be earlier than previously appreciated,” said the study’s lead author David Hill, MD, PhD, a fellow in the Division of Allergy and Immunology at CHOP. “Our paper suggests that the age of onset is between 2 to 3 years.”

In a systematic and rigorous, retrospective longitudinal birth cohort study, Dr. Hill and colleagues used electronic medical records to look at the acquisition of allergic diseases in a group of 130,435 children seen in the CHOP primary care network from birth into adolescence.

They found that presence of early allergic march members correlated with development of late allergic march members. When they compared allergic and non-allergic children, the study results showed that children with atopic dermatitis, anaphylactic food allergy, asthma, or allergic rhinitis were more likely to develop EoE than non-allergic children. The more allergic comorbidities a child had, the higher the risk of developing EoE.

“If a patient had any three allergic conditions other than EoE, they developed EoE nine times more often than a patient who didn’t have an allergy,” Dr. Hill pointed out. “The risk increases with the more allergic conditions that a child has.”

The study’s head-to-head comparison of population-level disease incidence rates showed that allergic rhinitis and EoE are closely associated with each other. In addition, the risk relationship between these conditions was bi-directional: The presence of allergic rhinitis was associated with an increased rate of subsequent EoE diagnosis, and the presence of EoE was associated with an increased rate of subsequent allergic rhinitis diagnosis. Scientists want to know more about this pathophysiologic relationship, Dr. Hill said, adding that previous studies have shown EoE symptoms flare during periods of high pollen.

No medication is currently available to cure EoE, so physicians approach treatment in two ways. First is avoidance of the food that causes the allergic reaction; for example, about 70 percent of patients have milk-induced EoE. Second is prescription of topical steroids to coat the esophagus. These options do not address the underlying disease; they only control the symptoms, which often go undiagnosed and become a substantial patient burden on a day-to-day basis. Now that scientists recognize EoE as a member of the allergic march, this could lead to better diagnosis and new studies to figure out how to avert the onset of EoE.

“A future research area would be to determine if early intervention might slow the atopic march and possibly prevent the development of later manifestations such as EoE,” Dr. Hill said.

Newly named a Frontier Program at CHOP, the Division of Allergy’s Food Allergy program led by Jonathan Spergel, MD, PhD, chief of the Allergy Section, is poised to advance EoE research as it significantly grows the clinical program, develops new diagnostic assays, and tests novel therapies with the ultimate goal of curing some types of childhood food allergy. The Frontier Programs initiative provides funding and support to the CHOP programs that best combine translational research and clinical care.

Read more on Cornerstone about Dr. Hill’s previous research on the idea that food allergies and respiratory allergies tend to occur together.