Researcher Uncovers Allergy-Reflux Link

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Researcher Uncovers Allergy/Reflux Link

A new Children's Hospital Medical Center of Cincinnati discovery may have

significant implications for children with a eosinophilic esophagitis, a

fast-growing new disease whose symptoms mimic gastroesophageal reflux, and for

adults with reflux who are not being helped by currently available medications.

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.