Medical Advisory Board Member Dr. Marc Rothenberg Gets Pediatric Society Research Award

Dr. Rothenberg received the E. Mead Johnson Award for Research in Pediatrics for his research in allergic and eosinophilic disorders. The annual award is in recognition of outstanding scientific contributions to pediatric-related research.

Dr. Rothenberg discovered the first gene associated with eosinophilic esophagitis, a disease whose symptoms mimic acid reflux. The Journal of Clinical Investigation published "Eotaxin-3 and a uniquely conserved gene expression profile in eosinophilic esophagitis" in the February 2006 issue.

Dr. Rothenberg has been on APFED"s medical advisory board since its inception, guiding our organization's growth, education and research programs. He is professor of pediatrics and director of the Division of Allergy and Immunology at Cincinnati Children’s Hospital Medical Center.

Congratulations to Dr. Rothenberg!

Understanding Swallowing Difficulties in EE

Clues to the Cause of Difficulty with Swallowing in Children
Eosinophilic esophagitis (EE) is disease that was first described in children only 20 years ago, but has shown a rising incidence in both children and adults.  An inflammatory condition of the esophagus, its symptoms including vomiting, heartburn and difficulty in swallowing.
In findings published on line January 10, 2007 in the Journal of Allergy & Clinical Immunology, researchers at the University of California, San Diego (UCSD) School of Medicine and Rady Children’s Hospital and Health Center, San Diego show that the disease causes many of the same kinds of tissue changes seen in pediatric asthma.  Their research may lead to new drug targets for EE, which appears to be allergy-driven in some patients.

The esophagus is the soft tube-like portion of the digestive tract that leads from the back of the mouth to the stomach.  In patients with EE, the disease leads to scarring and narrowing of the esophagus, so that food can’t readily pass through it.

“We set out to find whether the kind of structural changes seen in other long-standing inflammatory diseases like childhood asthma also occur in EE,” said Seema Aceves, M.D., Ph.D., of UCSD’s Allergy Immunology section of the Department of Pediatrics.  Aceves is also a physician at Rady Children’s Hospital in San Diego and directs a treatment center for children with eosinophilic gastrointestinal disorders.

The research team studied biopsies of the esophagus from children with an initial diagnosis of EE who had not yet been treated, comparing them to biopsies of children with acid reflux disease as well as those of children with normal esophageal biopsies.

 “We found fibrosis, or scarring, as well as remodeling of the esophagus in pediatric EE patients which is similar to airway remodeling found in patients with asthma,” said Aceves.

Remodeling occurs in chronic inflammatory diseases such as asthma and results in alterations in structural cells and tissues not found in normal tissues.  The UCSD study showed that children with EE were found to have previously unrecognized changes to their esophagus, including an increased number of blood vessels in the sub-epithelium, the region below the surface of the interior lining of the esophagus. There were also a larger number of adhesion molecules present in these blood vessels, which cause the vessel wall to become sticky. As a result, allergy cells adhere to the sticky vessels and are then able to cross the blood barrier, resulting in inflammation in the esophagus.

These studies – performed by Aceves through an ongoing collaboration with the laboratory of David Broide, M.B. Ch.B., professor of medicine at UCSD School of Medicine and an expert in airway remodeling in asthma – identified three molecules that contribute to these changes in the esophagus, and could provide new therapeutic targets for EE.  Their data suggests that increased expression of the molecules TGF-beta 1, phospohrylated-SMAD2/3, and VCAM-1 may be involved in remodeling that leads to scarring and narrowing of the esophagus.  These molecules may serve as markers to provide physicians with a basis for predicting disease severity.

FIRST INTERNATIONAL GASTROINTESTINAL
EOSINOPHILIC RESEARCH SYMPOSIUM ON EMERGING DISEASE WORLDWIDE

North American Society for Pediatric Gastroenterology, Hepatology and Nutrition
Hosts Collaborative Landmark Meeting
Shares New Diagnostic Guidelines and Sets Stage for Research Agenda

Orlando, FL; October 17, 2006 – The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) today hosted the First International Gastrointestinal Eosinophilic Research Symposium (FIGERS) focusing on the role of eosinophils in gastrointestinal diseases.   The Symposium shared new diagnostic criteria, built interest among young investigators, developed a research agenda for cooperative multi-center studies, and offered therapeutic strategies for the thousands of children and adults who suffer from this disease.

In a first-ever worldwide collaborative effort, experts met to discuss an increasingly recognized disease “Eosinophilic Esophagitis (EE).” EE is an isolated eosinophilic inflammation of the esophagus.  It may cause abdominal pain, nausea, regurgitation and/or vomiting. If EE persists for years, it may cause a narrowing of the esophagus that leads to dysphagia or difficulty in swallowing.  In young children, many of the symptoms of EE mimic those of gastroesophageal reflux.  GERD and EE are clearly separate diseases that demand different treatment strategies and carry potentially different long-term consequences.

Held in Orlando Florida in conjunction with the NASPGHAN annual scientific meeting, FIGERS involved the participation of 16 world-renowned speakers and panelists who reviewed and discussed the first scientific guidelines on EE.  “FIGERS is unique in that it brought together multiple subspecialists including pediatric and adult gastroenterologists, allergists, pathologists and basic science researchers all working toward understanding the disease process of eosinophilic esophagitis,” stated Chris Liacouras, MD, Co-Chair of the Symposium’s Steering Committee, who is based at The Children’s Hospital of Philadelphia and the University of Pennsylvania School of Medicine.

Research indicates that the prevalence of EE is increasing with diagnosis and treatment continuing to be a challenge. According to a population based demographic study of the pediatric population with EE residing in Hamilton County, Ohio, the incidence of pediatric EE was one in 10,000 with the prevalence being four in 10,000 which may be higher than those for other well-recognized inflammatory gastrointestinal disorders such as Crohn’s disease.

To address the critical issues, the Panel at the Symposium discussed diagnostic criteria, the natural history of the disease, the pathogenesis and evolving treatment strategies. “This symposium posed an extraordinary opportunity to initiate a long lasting research agenda for this emerging disease.  Through multi-center collaborations and cross specialty fertilizations, we will be able to understand more about the pathogenesis, trace the natural history and determine the best therapeutic approaches,” explained FIGERS Co-Chair Glenn Furuta MD who is based at Children’s Hospital Boston and Harvard Medical School.

President of NASPGHAN, Philip M. Sherman, MD, FRCPC, who is on the faculty at the Hospital for Sick Children, University of  Toronto, Canada said,  “The diversity of support and interest including an R13 award through the National Institutes of Health, support from professional and advocacy groups and industry, as well as the tremendous attendance at the meeting demonstrates the need to address the issue through a multidisciplinary approach.”

APFED President and Founder Beth Mays concurred, “The FIGERS meeting provides a ray of hope for our families living with life-altering eosinophilic disorders. The new guidelines will help make the distinction between EE and reflux common knowledge among medical professionals.”

The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) represents more than 1300 pediatric gastroenterologists in the United States, Canada, and Mexico.  NASPGHAN is a world leader in advancing the science and clinical practice of pediatric gastroenterology, hepatology, and nutrition. NASPGHAN’s mission is to improve clinical care, promote research, and facilitate medical education relating to infants, children, and adolescents with digestive disorders.

FIGERS support was provided through a National Institutes of Health R13 award as well as additional support from a grateful family, the American Academy of Asthma, Allergy and Immunology, American Partnership for Eosinophilic Diseases, AstraZeneca, Genzyme, GlaxoSmithKline, Ross Products, Nutricia North America and TAP Pharmaceuticals.