Scientists at Mayo Clinic have invented a quick new way to diagnose a puzzling digestive condition that has rocketed from a virtually "unheard of" disease to one that, in less than a decade, has become increasingly common.
Incidence of eosinophilic oesophagitis, also called EoE, or allergic oesophagitis, has been on the rise since its initial identification in the late 1980s. Now, estimates suggest that more than 300,000 Americans currently suffer from this chronic condition – more males than females, and about a fifth of them children.
Eosinophilic oesophagitis is an inflammatory condition in which the walls of the oesophagus become filled with eosinophils – white blood cells that originate in the bone marrow. Generally caused by an allergic reaction, the condition can cause swallowing and other problems leading to painful, impacted food constricture in the oesophagus.
"For the vast majority of cases, the diagnosis will now be faster, easier and hopefully more reliable. Moreover, this new strategy can be conducted without specialised equipment," said James J. Lee, PhD, the Mayo Clinic biologist who led the team that developed the new diagnostic test and who, with his wife, Nancy A. Lee, PhD, has been pioneering eosinophil research at Mayo Clinic for 16 years.
The method, a scoring system of tissue samples, grew out of talks between doctors and researchers at Mayo Clinic and The Children’s Hospital in Denver, according to Dr Lee, who is senior author of a study describing this new test that appears in the 1 July issue of Clinical Gastroenterology and Hepatology.
Dr Lee notes, "Together with our Mayo Clinic clinical colleagues (Drs Lucinda Harris, Tisha Lunsford and Shabana Pasha), a Mayo Clinic pathologist (Dr Giovanni DePetris), as well as Dr Glenn Furuta from The Children’s Hospital in Denver, this collective group created the needed synergy to propel basic research activities to the forefront of patient care."
Until now, a stumbling block in treating EoE has been the ambiguous character of the disease in some settings, often preventing a clear diagnosis. Clinical evaluations of patients, including assessments of symptoms and changes in the oesophagus, are critical for the diagnosis of this disease. Thus, symptoms such as trouble swallowing, impacted food and heartburn are indicators of EoE, as are specific structural abnormalities of the oesophagus. Unfortunately, many of these observations are also present in other common conditions, such as gastro-oesophageal reflux disease (GORD). Moreover, mistaking the allergic condition for GORD can extend patient discomfort and decrease quality of life as EoE disease severity increases.
The telltale clue physicians use to identify EoE patients is a soaring increase in the number of eosinophils, rare white blood cells related to allergic reactions, in tissue samples from the oesophagus; in healthy subjects these cells are completely absent. However, despite this hallmark feature, tissue eosinophils are also found in GORD patients and in some cases these cells (and/or their activities) are difficult to identify. These difficulties often necessitate gastroenterologists and pathologists to subject patients (particularly children) to multiple endoscopic examinations and the repeated recovery of many biopsies.
The Mayo Clinic/Children’s Hospital team developed a way around the problem by developing an antibody that uniquely identifies a protein (eosinophil peroxidase, EPX) released by activated eosinophils in the oesophagus of patients. Using this newly created tool, the team developed a staining method that could be used on available tissue samples, as well as a unique scoring system with which to evaluate each patient. The seed of the idea arose when Lee’s team was invited to accompany Mayo Clinic gastroenterologists on rounds and talk about their findings on EoE patients. During the visit, the scientists were surprised to find the clinicians didn’t create a "work-around", a way to get around the difficulties of counting the inscrutable eosinophils or assessing their level of activation. "We were surprised that some of the technologies and diagnostics we created to evaluate our mouse models of human disease were not routinely done in the hospital," Lee said.
"Work-arounds in mouse model labs are common because our goal is the creation and evaluation of ever-better models of diseased patients," explained Dr Lee. He also notes, "Unlike clinical colleagues, we don’t have the luxury of asking our patients how they are doing. Therefore, we have to be far more clever in our evaluations of symptoms and disease-associated changes."
This multicentre study incorporated using the EPX antibody to test archived tissue specimens for 60 patients – adults from Mayo Clinic and paediatric patients from The Children’s Hospital in Denver. By comparing these results with diagnoses using currently available guidelines, researchers were able to create and then verify the validity of this new strategy. In particular, the data from this study demonstrated the test’s unique ability to identify patients that have evaded diagnosis by traditional methods.
Dr Lee believes that this study represents an important first step that may soon provide Mayo Clinic physicians with a new weapon that they didn’t have previously in the arsenal for the care of their patients. "Our strategy still has to go through a validation process before it can be adopted universally, but I’m hopeful it will become a standard of care," said Dr Lee.
(Source: Mayo Clinic: Clinical Gastroenterology and Hepatology: July 2009)