Researcher Uncovers Allergy/Reflux Link

In a study published in the January issue of The Journal of Clinical Investigation, Marc E. Rothenberg, M.D., Ph.D., has established a link between reflux and allergy - not only food allergies but also environmental allergens such as pollens and molds. Dr. Rothenberg, the study's senior author, and his colleague Anil Mishra, Ph.D., have developed the first experimental system, a mouse model, for eosinophilic esophagitis - a disease whose numbers have exploded in recent years.

"We're saying that what a person breathes in can actually affect the gastrointestinal system," says Dr. Rothenberg, who directs the section of allergy and clinical immunology in Cincinnati Children's division of Pulmonary Medicine, Allergy and Clinical Immunology. "There is a direct link between exposure to allergens that go to the lung -- aeroallergens -- and development of esophageal inflammation."

Moreover, Dr. Rothenberg has discovered that this pathway is mediated by a molecule called interleukin-5. When Dr. Rothenberg's research group gave mice an allergen that induced asthma, all the mice developed esophagitis. But none of the mice deficient in IL-5 who were given the allergen developed esophagitis. "They were completely protected," says Dr. Mishra, Ph.D., a research associate in Dr. Rothenberg's lab and the study's lead author.

"Two major pharmaceutical companies have an antibody in human trials that blocks IL-5," adds Dr. Rothenberg. "These drugs are being tried for asthma, but based on our findings I'd like to see IL-5 blockers tried in patients with eosinophilic esophagitis."

Children with eosinophilic esophagitis often have abdominal pain, difficulty swallowing, vomiting, failure to thrive and weight loss. Just a few years ago, incidents of the disease were rare. Now, Dr. Rothenberg and his colleagues at Cincinnati Children's food allergy clinic treat about 60 cases each year. Physicians throughout the United States also report an explosion in the number of cases.

Adults with reflux have some similar symptoms. While many are helped by currently available medications, there is a significant subset that, like children with esophagitis, is not helped. Dr. Rothenberg believes that "a significant number of those may have an allergen-driven process; they have a different form of reflux that we're calling eosinophilic esophagitis."

Dr. Rothenberg derives the name from the fact that when patients came to Cincinnati Children's with esophagitis, biopsy showed a large infiltration of eosinophils, a type of white blood cell not normally seen in the esophagus, into the gastrointestinal tract. Eosinophils in tissue are also a hallmark feature of an allergic response.

The assocations between eosinophils and esophagitis and eosinophils and reflux have been previously reported, but Dr. Rothenberg noticed that many children in allergy clinic had gastrointestinal complaints. "When you skin test patients with eosinophilic esophagitis, 80 percent have allergies," he says, "not only food allergies but also environmental aeroallergens. This suggested that allergies may be a cause for the esophagitis."

"One of the things that struck me," adds Dr. Rothenberg, "is that we know that people who develop reflux often have asthma. There seems to be some link between the two. In fact, when those with asthma are treated for reflux they sometimes get better. Based on this clinical observation, and with the hunch that there was likely to be an association between the development of allergy and esophagitis, our research group subsequently developed the mouse model to prove it."

The results, which shed new light on a possible cause of esophagitis, suggest that therapy should be directed at controlling allergies and preventing exposure to environmental allergens.