Food Allergy Frontier Program Seeks Answers to Puzzling and Ever-Prevalent EoE

Food Allergy Frontier Program Seeks Answers to Puzzling and Ever-Prevalent EoE

Born just 13 months apart, 16-year-old brothers Dean and Cole Harris have shared a lot over the years, from the same group of friends to similar hobbies. But the Harris boys, as they’re often known by their peers, have something else in common, for better or worse: eosinophilic esophagitis (EoE), a rare allergic inflammatory disease of the esophagus, or the muscular tube that carries food from the throat to the stomach.

EoE has a strong genetic component, and thus it’s not uncommon that when one sibling has the disease, another could have the same condition. For Dean and Cole, dealing with the same digestive disorder has had its blessings. The brothers grew up fiercely supportive of each other, enduring its myriad challenges together.

“In so many ways, they needed each other,” said the boys’ mom, Suzanne Harris.

In EoE, certain food allergens trigger a congregation of cells in the esophagus, particularly large amounts of white blood cells called eosinophils. This results in a host of adverse reactions, such as vomiting, abdominal pain, heartburn sensations, and failure to thrive. Unlike classic food allergies, simply eliminating the suspect allergen from one’s diet is difficult. Those with EoE can be sensitive to a number of foods, and clinicians currently cannot predict which foods trigger a reaction.

Thanks to great progress in clinical and lab research, researchers have a clearer picture of EoE pathogenesis than they did 30 years ago, when the condition was virtually unknown. But Jonathan Spergel, MD, PhD, chief of the Division of Allergy at Children’s Hospital of Philadelphia, believes that our understanding of EoE, a puzzling and increasingly prevalent disease, is far from complete.

Clinicians still lack a noninvasive method to monitor the disease and to identify trigger foods for each patient. There are currently no approved medications to treat EoE, though doctors have had success approaching EoE with a managed diet and a topical steroid to control its symptoms. Furthermore, one big question remains: Why do some children — including Dean and Cole — end up outgrowing the disease, which was previously considered a lifelong, incurable condition? With new fuel as a designated 2018 Frontier Program at CHOP, Dr. Spergel believes his team can continue to discover more about EoE and improve the quality of life for children and adolescents like Dean and Cole around the world.

Growing Up With EoE: Dean and Cole’s Story

As infants, both Dean and Cole had problems taking in the food and nutrients they needed to thrive: As Suzanne tried to nurse baby Dean, he began to hemorrhage, leading doctors to suspect he had a milk protein allergy. Meanwhile, to Suzanne, it seemed like Cole was born vomiting, and at 3–weeks-old, he had undergone two surgeries. Doctors guessed he might have the same milk protein allergy as Dean or pyloric stenosis, a thickening of a stomach muscle that can affect how food travels to the intestine. Though Cole tolerated tube-feeding of an amino acid based formula, when he was 4-weeks-old, his heart stopped, leading Suzanne to perform life-saving CPR. She realized Cole had more than just a milk protein allergy.

Over the next few years, the boys spent years in and out of hospitals and emergency rooms, seeing allergists, pulmonologists, gastroenterologists, and other specialists for a host of problems, including compromised immune systems and growth problems due to their difficult breathing and vomiting episodes.

“Nobody knew what was wrong with them,” Suzanne said.

Finally, after a series of tests at Cincinnati Children’s Aerodigestive and Esophageal Center, doctors suggested that the Harris boys might have EoE.

“I felt as though the enemy had a name,” Suzanne said.

After finding out everything she could about EoE and taking the initiative to attend a research conference hosted by the American Partnership for Eosinophilic Disorders in Cherry Hill, NJ, Suzanne learned that CHOP was one of the only hospitals in the world with a division specifically dedicated to EoE treatment. Within 24 hours, the Harris family had packed up and moved to Ocean City, NJ, to be closer to CHOP’s Center for Pediatric Eosinophilic Disorders.

Treatment at CHOP and a Surprise Discovery

Dean and Cole began a series of food trials at CHOP under the guidance of Dr. Spergel’s team. Since clinicians can only guess what food groups trigger a reaction in patients, they often impose dietary restrictions on patients followed by an endoscopy and a biopsy to try to pinpoint allergens.

The boys loved allergy testing days for two reasons: It gave them the opportunity to taste something new along with the hope that they might learn what triggered their inability to maintain a normal diet. But after testing a variety of foods, clinicians were perplexed. In the first and second grade, Dean and Cole had to stop eating altogether in order to wipe their dietary slates clean, subsisting on a medical amino acid formula while they re-introduced food after food.

By this time, EoE was taking a bigger toll on their school, social lives, and general well-being. Dean wore braces on his legs due to poor bone health. The boys worried about attending social events due to their diets. And Suzanne was trying her best to make family meals fun despite the not-so-fun taste and feel of medical formula.

Finally, Dr. Spergel suggested that Dean might like to participate in the SMILEE study, a trial designed by Dr. Spergel in partnership with the pharmaceutical company, DBV Technologies, to investigate the effectiveness of a skin patch with novel epicutaneous immunotherapy (EPIT) for treating EoE. The patch is intended to desensitize allergic reactions to dairy by keeping an allergen — in this case milk — on the skin for repeated and prolonged periods. Dean’s decision to participate in the study led to a surprise discovery for Dr. Spergel and a game-changer for Suzanne and the boys.

The study had required that Dean stop taking his medication and begin to consume dairy, which had always made him very sick. For the first time in 13 years, Dean ate a slice of cheese pizza. A few weeks into the study, Suzanne received a call from CHOP. The nurse couldn’t explain it, but Dean’s biopsy had come back clear. Two biopsies later, it was more or less confirmed: Dean had outgrown his EoE. Suzanne remembers her son’s first reaction to the news.

“I picked up Dean from school that day, and I told him, you’re cured. And the first thing he says to me is, what about Cole?”

Hoping that Cole might have also outgrown his EoE, that August, Cole stopped his medication and began to consume foods that he previously could not tolerate. After a scope about three months later, Suzanne received another surprise call from CHOP. Cole’s biopsy, too, showed up completely normal. Almost miraculously, the boys could tolerate foods that had made them very sick for most of their childhood.

“It changed our lives,” Suzanne said. “Dean was the kid with braces on his leg, but when he graduated eighth grade, he was on the wrestling team, the cross-country team, and he was the class president who gave the commencement address. That was not his fate. So, my wish is that clinicians learn more about that differentiating factor in children who get well — knowing those differences has to bring hope to people.”

Dean and Cole are two of Dr. Spergel’s small subset of pediatric patients who were discovered to have outgrown their EoE. As described in one of his papers published in the Journal of Allergy and Clinical Immunology this past year, the discovery forms a key building block in our understanding of the disease. Contrary to existing knowledge, EoE was not a lifelong condition, and with more research, clinicians could very well develop effective treatments.

Accelerating EoE Research: Past and Future Findings

Frontier Program funding and support will accelerate the Food Allergy Center’s search for a cure and effective ways to monitor the disease. These advances hold the potential to improve the difficult experiences that patients like Dean and Cole endured growing up with EoE. On top of continuing work with DBV Technologies on the SMILEE trial (with results to be published in the near future), food allergy researchers at CHOP are developing a novel blood test that will help clinicians establish better treatment regimens for EoE.

“One of the major difficulties of EoE research is that we have no way to monitor the disease without doing endoscopies and invasive biopsies,” Dr. Spergel said. “So one of the goals of the Frontier program is to develop a noninvasive biomarker to follow the disease without putting patients under anesthesia.”

Dr. Spergel’s team has already laid much of the groundwork for this research pipeline this past year. In research published in the Annals of Allergy, Asthma and Immunology, a team led by Antonella Cianferoni, MD, PhD, attending physician in the Allergy Section at CHOP, described their development of an assay for T-cells to examine how the cells function in the peripheral blood of patients with EoE; the researchers had discovered that in patients with EoE, T-cells have specific activation to milk allergens.

“With patients with EoE, we’ve seen T-cells get activated, so the idea is to try to take that to the next step, not just for milk but for other foods like wheat and dairy, and seeing if we can develop a clinically useful test to measure what foods are causing disease,” Dr. Spergel said.

In the last decade, EoE has become increasingly recognized in clinical settings. And as awareness grows, clinicians have the opportunity to learn more about the underlying genetics and pathogenesis of the disease. For this reason, Suzanne believes it’s important to stay close to CHOP and continue returning to see Dr. Spergel — for both her boys’ health, and that of other children who could benefit from what clinicians learn from Dean and Cole’s experiences.

“My boys are getting scoped in November (2018) because they’re among the first [patients] to be well,” Suzanne said. “So are they well forever? We don’t know. Some patients who outgrew the disease might not continue following up. But we want to stay plugged in. And my boys are so excited.”