Eosinophilic Esophagitis

The human body has an intricate immune system; charged with the daily task of keeping the body — and all its parts — functioning in perfect order. The “leaders” of the immune system are the white blood cells. White blood cells are made up of five subsets, each structured to lead the way in fighting and destroying all that is foreign and dangerous in the body.

Sometimes, one or more of those five subsets can go a little haywire and cause imbalance in the body. Sometimes, the lymphocytes that fight viruses or the neutrophils that fight bacteria are destroyed by any number of sources, and the body’s defenses become weakened. Sometimes, the opposite occurs, and, for example, the eosinophils — which are charged with both combating infection by parasites in the body as well as mounting allergic and inflammatory responses to invasions the body dislikes — become too plentiful and complicate the proper functioning of the body.

Eosinophilic esophagitis (EE) is one such occurrence. EE is an allergic inflammatory condition of the esophagus.¹ The esophagus becomes so overwhelmed with the white blood cell that chest pain, heartburn, dysphagia and sometimes a complete blockage of the esophagus can occur (see sidebar for a full list of symptoms).

Patients of all ages are afflicted with EE, and the symptoms that develop closely resemble that of acid reflux disease or gastroesophageal reflux disease, food allergies, and inflammatory bowel disease.

A March 200 press release from the Cincinnati Center for Eosinophilic Disorders (CCED) at Cincinnati Children’s Hospital Medical Center notes that the rate of EE has risen so dramatically in recent years that it may be more prevalent than other inflammatory gastrointestinal disorders — including Crohn’s disease.²

The press release also says that EE is one the rise everywhere, and that experts have found EE affects one in 2,000 children in the Cincinnati region, and in many countries such as England, Japan, Spain, Australia, Switzerland, and Italy, more cases of EE are consistently being reported.

Diagnosis of EE is obtained during an upper GI endoscopy, during which biopsies are taken of the esophagus.¹ At the time of endoscopy, ridges or furrows may be seen in the esophagus wall. Sometimes, multiple rings may occur in the esophagus, leading to the term “multi-ring esophagus.” A high number of eosinophils are seen on microscopic examination of the biopsy specimens.

Skin testing and other allergy testing are performed to help identify which foods may be contributing to EE.

According to M. Brian Fennerty, MD, professor of medicine and section chief of gastroenterology at Oregon Health Sciences University in Portland in an online article, an allergic history or asthma is not an uncommon accompanying historical feature.³

Fennerty goes on to explain that characteristically, “endoscopy reveals evidence of a long narrowing beneath a proximal stenosis or stricture of the esophagus, a corrugated or ringed appearance, or a generalized narrow appearance of the esophagus,” adding that frank esophagitis is not part of the macroscopic endoscopic picture of EE.

Following dilation of the esophagus, the investigator may see “fracturing” of the mucosa that can be “alarmingly long and deep,” Fennerty points out. Severe chest pain following dilation is not unusual.

Fennerty further points out that while all of these endoscopic features are suggestive of a diagnosis of EE, they are not diagnostic. The diagnosis is made by the finding of increased eosinophils in the mucosa on an endoscopic biopsy specimen. However, the degree of eosinophilic infiltration diagnostic of EE has not yet been determined. It also has been observed to be quite variable, he adds.

Treatment strategies for EE include diet changes and removing any foods found to exacerbate the condition. Other strategies include proton pump inhibitors to decrease acidity in the stomach that may reflux into the esophagus, inhaled steroid puffers taken orally and swallowed, anti-histamines, H2-receptor blockers such as cimetidine, leukotriene modifiers such as montelukast, and in investigational reports, the anti-IL5 monoclonal antibody mepolizumab.¹

According to Fennerty, the currently recommended treatment for EE is based on the hypothesis of the allergic response. However, he adds, “it is important to note that none of these therapies has ever been demonstrated as effective in improving outcomes in patients with eosinophilic esophagitis in randomized, controlled clinical trials, and thus, the recommendation for this treatment approach is based on theory and observation, not fact.” He does note that periods of spontaneous remission are not uncommon for this disorder.

Of further interest, recent studies have begun to break through the mystery surrounding EE. According to a study published in the February issue of the Journal of Clinical Investigation, Marc E. Rothenberg, MD, PhD, director of the CCED at Cincinnati Children’s, and fellow researchers have now isolated a gene they are hopeful will lead to a treatment for EE. They found that the gene that most correlates with EE is eotaxin-3, which has already been identified as a powerful eosinophil-activating protein. This data, combined with analysis of the eotaxin-3 gene sequence in patients, strongly places the disease onus on eotaxin-3.² The finding will guide researchers in the development of drugs that block the protein.

1. Wikipedia. Eosinophilic esophagitis. http://en.wikipedia.org/wiki/Eosinophilic_esophagitis

2. Reyes, Amy. 2006 Pediatric Health News Releases. Gene Discovery Linked To Mysterious Chronic Food Allergy. Study offers first molecular insight into eosinophilic esophagitis. February 3, 2006. www.medscape.com/viewarticle/495405

3. Fennerty, M. Brian. Professor of Medicine, Section Chief of Gastroenterology, OregonHealthSciencesUniversity. October 16, 2004. www.medscape.com/viewarticle/495405

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