updated 2/13/2006 7:20:31 PM ET 2006-02-14T00:20:31

Genes prove it: A rare but devastating esophageal illness that's on the rise isn't hard-to-treat acid reflux as once suspected but a completely different disease — one linked to allergies.

  1. Don't miss these Health stories
    1. Splash News
      More women opting for preventive mastectomy - but should they be?

      Rates of women who are opting for preventive mastectomies, such as Angeline Jolie, have increased by an estimated 50 percent in recent years, experts say. But many doctors are puzzled because the operation doesn't carry a 100 percent guarantee, it's major surgery -- and women have other options, from a once-a-day pill to careful monitoring.

    2. Larry Page's damaged vocal cords: Treatment comes with trade-offs
    3. Report questioning salt guidelines riles heart experts
    4. CDC: 2012 was deadliest year for West Nile in US
    5. What stresses moms most? Themselves, survey says

Known by the tongue-twisting name eosinophilic esophagitis, the worst cases of this mysterious disease can force children onto liquid diets and feeding tubes, and leave adults with an esophagus so narrowed that food gets trapped in it.

With no proven treatments, doctors try creative experiments, including a new attempt to coat patients' inflamed throats with a paste made from a popular asthma medicine and the sugar substitute Splenda.

Now scientists have discovered a gene that seems to be the disease's main trigger, opening a new direction in the therapy hunt — and promising easier diagnosis for patients who can spend years dealing with vomiting, heartburn and stomach pain before doctors figure out what's wrong.

"They're suffering a lot," says Dr. Marc Rothenberg of Cincinnati Children's Hospital, who led the gene research and directs the nation's leading center for eosinophilic esophagitis, or EE. The gene discovery, he adds, "should give all these people hope."

First diagnosed in 1977, many doctors initially considered EE to be especially severe cases of the heartburn-causing acid reflux disease; some still do. Symptoms do mimic reflux. But heartburn medicines don't relieve EE.

Instead, EE occurs when the immune system goes into overdrive: Eosinophils are white blood cells that help the body fight off parasites, among other things. But sometimes too many eosinophils are produced, constantly, in the gastrointestinal tract, causing inflammation that over time damages the delicate tissue. When this eosinophil frenzy targets the esophagus, it's called EE.

It mostly strikes people prone to allergic diseases, such as asthma or food allergies, where eosinophils play some role, too.

Like allergies, EE seems to be on the rise, says Rothenberg. Last summer, he published an analysis estimating that one in 10,000 children — or 22,000 American youngsters — may have some degree of EE. Although still rare, that's a startling number. The rise is at least partly due to more doctors examining small children endoscopically, sending a tube down the throat to test for eosinophils.

The new research, published in this month's Journal of Clinical Investigation, raises the possibility of gene testing instead.

Rothenberg compared healthy people, reflux sufferers and EE patients. The EE patients harbored a unique genetic signature, more than 500 genes that operated differently in them. One gene, called eotaxin-3, was up to 100 times more active.

Eotaxin-3 attracts eosinophils circulating in the body. When Rothenberg's team bred mice without an eotaxin cell receptor, the animals were protected from EE. It's the best evidence yet that eosinophils are the culprit, says Dr. Marshall Plaut of the National Institutes of Health, which, along with the patient group Campaign Urging Research for Eosinophilic Disease, helped fund the work.

The challenge is to develop drugs to block eotaxin's bad action.

For now, patients' options:

  • Testing for food allergies, and eliminating any that seem to cause a reaction. Very severe patients who react to many foods may be fed only a special liquid formula, sometimes through a feeding tube. That's a controversial therapy because it is so difficult and socially isolating, especially for children.
  • Many patients don't have identifiable food allergies. "We don't know what to stay away from," laments Linda Roth of Liberty Township, Ohio, whose son John was diagnosed almost two years ago, at age 6.

Those patients try steroid drugs to ease the inflammation. Most common is to swallow the normally inhaled asthma medicine Flovent, so that it temporarily coats inflamed tissue.

Seeking a coating that would stick better, Dr. Ranjan Dohil and colleagues at the University of California, San Diego, made a paste with the longer-lasting asthma medicine Pulmicort and the artificial sweetener Splenda — to coat the drug's bitter taste. More than 20 patients have swallowed a dose a day so far, with good results, says Dohil, a pediatric gastroenterologist who is preparing to formally study the mixture.

  • In Cincinnati, Rothenberg has begun a clinical trial of an experimental intravenous drug that attacks an eosinophil-activating substance called interleukin-5.

First, patients must know they have EE. Specialists urge testing children with serious reflux symptoms who aren't helped by standard therapies — and teenagers or adults who have trouble swallowing, as years of inflammatory damage may have narrowed the esophagus.

© 2013 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

Discuss:

Discussion comments

,

Most active discussions

  1. votes comments
  2. votes comments
  3. votes comments
  4. votes comments