Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus that affects both children and adults. The main symptoms are swallowing difficulties and food impaction, and the diagnosis is established by the presence of more than 15 eosinophils per high power field (HPF) in the esophageal epithelium. Corrugations and linear furrows in the esophagus are common endoscopic findings, but are not always present.
Until recently, EoE was often mistaken for gastroesophageal reflux disease (GERD). Although investigators now recognize eosinophilic esophagitis as a distinct disorder, the complex relationship between EoE and GERD is not well understood.
The etiopathogenesis of EoE also remains a mystery. Most researchers believe the disease is an immunological response to environmental allergens, but its natural history, precise etiology and increasing incidence in developed countries over the past few years are not clear. And although some treatment options have been proposed, physicians have not yet determined optimal management of the disorder.
In order to shed more light on EoE, investigators from all Mayo Clinic campuses are participating in a multinational, observational study involving 20 centers in Canada, Switzerland and the United States. The aim of the study is to develop an eosinophilic esophagitis activity index for adult and pediatric patients to assess the symptoms and biological activity of the disease.
According to Shabana F. Pasha, M.D., principal investigator for the study at Mayo Clinic in Arizona, such an index is not only essential for evaluation and follow-up of patients in clinical practice, but also for use in future clinical trials. "No validated activity index currently exists for determining the efficacy of medical therapy in these patients," she explains.
During phase I of the study, which is now complete, experts at the University of Bern in Switzerland developed four items for the activity index: clinical symptoms, laboratory markers, endoscopic findings and histopathologic findings. The second phase of the study, slated to last one year, is under way.
"The purpose of phase II is to finalize the activity index," Dr. Pasha says. "The goal is to enroll 100 children and 100 adults in the study. All patients have known EoE or a high suspicion of the disease."
Each participant completes a dysphagia questionnaire, and the physician completes a questionnaire with clinical symptoms, laboratory markers and endoscopic findings. A histopathology questionnaire is completed by the pathologist. Each patient then receives a global assessment score to grade the severity of the disease.
Phase III, scheduled to begin in 2013 and end two years later, will validate the activity index and assess for test-retest reliability. Two hundred adults and 200 children will be enrolled in phase III.
Dr. Pasha, who directs the small bowel disorders clinic and is the vice-chair of research in the Division of Gastroenterology and Hepatology in Arizona, says that the clinic typically sees two or three people with EoE a month, most of them men in their 20s and 30s.
"EoE was previously described in children, but we now recognize that it also commonly affects adults, especially young men and people with asthma, atopic disorders and allergies," she says.
The most studied treatment for EoE is topical corticosteroids — either swallowed fluticasone or an oral suspension of budesonide. Because food allergies have been implicated in children with the disease, allergy testing and an elemental or elimination diet are part of pediatric care.
Although symptoms in children and adults generally improve with treatment, recurrence is common when therapy is discontinued. The hope is that information from the current study will help guide response to therapy and future management of the disorder.
"The assessment of eosinophilic esophagitis activity and response to medical management is presently more subjective than objective," Dr. Pasha says. "It is essential to develop a validated activity index with standardized items to allow a fair comparison of the results of EoE trials, and this is the goal of the current study."
Members of the esophageal clinic are co-investigators in Arizona. Other study investigators include Yvonne Romero, M.D., at Mayo Clinic in Rochester, Minn., Sami R. Achem, M.D., at Mayo Clinic in Jacksonville, Fla., and Michael D. Crowell, Ph.D. at Mayo Clinic in Arizona.