JACI: Aceves et al - Why Some Kids Have a Hard Time Swallowing

When Seema Aceves, MD, PhD was an Allergy/Immunology fellow here at UC San Diego, she noticed an increasing number of pediatric patients who were allergic and had a hard time swallowing. Often displaying symptoms similar to gastroesophageal reflux disease, these young patients complained of abdominal pain, heartburn, chest pain, and poor appetite. But unlike many children with acid reflux, these children did not get better with acid blocking medications.

First diagnosed in the early 1980’s, it turns out that these children actually have a chronic disease called ‘eosinophilic esophagitis’ (EE), an antigen driven allergic disease of increasing prevalence which causes dysphagia (trouble swallowing) as well as esophageal dysmotility (abnormal contraction of the esophagus). While there are successful therapies for EE, such as topical steroids that coat the esophagus, there is no known cure for this chronic disease. Hence, the need for in-depth research to understand the mechanisms and inflammatory mediators that contribute to esophageal smooth muscle dysfunction.

“It is a rare opportunity to step into a new disease like EE,” Dr. Aceves remarks. “We hope to help understand the disease mechanisms in EE so that we can find new ways to help these patients feel better.”

As a physician-scientist, Dr. Aceves had the right background in both basic science and clinical research in order to begin her translational studies in EE. In 2004, Dr. Aceves, Dr. Ranjan Dohil (Pediatric Gastroenterology), and Dr. John Bastian (Allergy, Immunology) formed the first multidisciplinary pediatric EE clinic on the West Coast. Today, Dr. Seema Aceves is the Director of the RCSHD-UCSD Eosinophilic Esophagitis (EE) Clinic, and Assistant Professor of Pediatrics and Medicine in the Allergy , Immunology division at UC San Diego. Her translational studies have been done in collaboration with Dr. David Broide, Professor of Medicine.

Recently published in the Journal of Allergy and Clinical Immunology (JACI), Aceves is the first author on a research paper entitled, Mast cells infiltrate the esophageal smooth muscle in patients with eosinophilic esophagitis, express TGF-b1, and increase esophageal smooth muscle contraction. She and her colleagues were the first to document an increased number of mast cells in the smooth muscle (muscularis mucosa) of the esophagus of patients with EE as compared with patients without EE and, further demonstrated that TGFb1 could affect esophageal smooth muscle function.

It is widely known that mast cell products such as histamine can increase the airway contraction. What is noteworthy of this research is that Aceves et al. demonstrated for the first time that esophageal mast cells produce the pro-fibrotic factor transforming growth factor-beta-1 (TGFb1) and that TGFb1 increases esophageal smooth muscle contraction in vitro.

“TGFb1 may be an explanation for why EE patients have problems with swallowing,” shares Aceves. “In addition, therapies that block TGFb1 and/or decrease smooth muscle mast cells in the esophagus may be useful for improving esophageal motility and decreasing dysphagia.”

According to an editorial review on the research paper by Aceves et al published in JACI by Dr. Marc Rothenberg, a world renowned expert in eosinophilic disorders, ‘TGF-b1 and mast cells represent a unique and exciting pharmacologic target with the potential to modulate varied features of EE through a single major pathway.’

The prevalence of children with EE is currently reported at 4/10000, which is as common as Crohn’s disease. Children with EE often have another allergic disease such as asthma, food allergies/anaphylaxis, allergic rhinitis, and eczema, which can complicate their EE. In order to diagnose EE, patients must undergo an esophageal biopsy.

When asked why she does what she does, Dr. Aceves responds enthusiastically.

“We’re passionate about conducting research and sharing our findings so that we can not only help our pediatric EE patients here in San Diego, but also EE patients everywhere.”

Written by: Shivani Singh, Sr. Web Writer, Department of Pediatrics, UC San Diego, s1singh@ucsd.edu

Scientific Contact:

Seema S. Aceves, MD, PhD, Assistant Professor, Pediatrics and Medicine, Division of Allergy, Immunology; Director of the Pediatric EE Clinic, UC San Diego/Rady Children’s Hospital, San Diego.

To contact the San Diego Pediatric EE Clinic, call: 858-966-5961