Biopsies may overlook esophagus disease—Study reveals limitations in detecting allergic disorder
These are microscope images of tissue from the esophagus of a patient with a disease named eosinophilic esophagitis, or EoE. The bar graphs around each image depict the number of white blood cells called eosinophils along the perimeter of each tissue sample. The cells eat away at the lining of the esophagus to cause the disorder. A University of Utah study suggests that the current method of diagnosing EoE by taking tissue samples with an endoscope may lead to under- or misdiagnosis of the disease. Credit: Hedieh Saffari, University of Utah, for the Journal of Allergy and Clinical Immunology.
University of Utah engineers mapped white blood cells called eonsinophils and showed an existing diagnostic method may overlook an elusive digestive disorder that causes swelling in the esophagus and painful swallowing.
By pinpointing the location and density of eosinophils, which regulate allergy mechanisms in the immune system, these researchers suggest the disease eosinophilic esophagitis, or EoE, may be under- or misdiagnosed in patients using the current method, which is to take tissue samples (biopsies) with an endoscope.
These findings are published as the cover article in the September 2012 issue of the Journal of Allergy and Clinical Immunology. Despite the limitations of current detection methods for EoE, the study authors say biopsies remain the current standard of care, but the engineers are working toward new diagnostic methods that could be available in five years.
In EoE, eosinophils typically found in the bloodstream invade the esophagus and start chewing away at its lining. Often triggered by food allergies, EoE symptoms overlap with other disorders such as acid reflux.
"The gold standard for understanding this disease is detecting the location and presence of eosinophils in the esophagus. Unfortunately, eosinophils are not uniformly distributed within the esophagus, which can lead to underdiagnosis," says study co-author Leonard Pease, assistant professor of chemical engineering at the University of Utah. He is also an adjunct professor of gastroenterology and pharmaceutics.
The University of Utah team showed that even a patient with known EoE would require more than 31 random tissue samples, or biopsies, from an area in the esophagus with low eosinophil density to reliably diagnose EoE. Currently, if a patient is suspected of having EoE, five to 12 biopsies are collected along the esophagus using an endoscope. If more than 15 eosinophils turn up in any one of these samples, a diagnosis of EoE is made.
"This is the first quantitative assessment of how eosinophils are distributed in the esophagus," says co-author Gerald Gleich, professor of dermatology at the University of Utah and specialist in eosinophil-related diseases. "Until now, someone would go in and snip around, but they wouldn't have this map to quantify the degree of infiltration of this disease in relationship to the actual anatomy. These findings impact how many biopsies a doctor should perform."
Since eonsinophils are scattered within the esophagus, EoE can go undetected until severe symptoms surface, ranging from painful swallowing to chest pains that mimic a heart attack.
"This is not the ideal way to diagnose EoE," says Pease. "If the distribution of eosinophils was 100 percent uniform, it wouldn't matter where you sample, but in fact it's patchy. Our mapping shows if you sample in one region, no diagnosis would be made, but if you took another region about an inch away, the same patient would appear to be severely diseased."
To generate a map of eosinophil distribution in the esophagus, lead author Hedieh Saffari examined each of 17 tissue sections taken at intervals every one-eighth to one-fifth of an inch along the esophagus of a known adult EoE patient. A typical adult esophagus is 10 inches long.
"For every cross section, I used microscopy to count the number of eosinophil cells along the entire perimeter of the tissue surface in each high-power field of view image," said Saffari, a chemical engineering graduate student. "There were somewhere between 40 and 120 of these images per cross section so it took a lot of time, but it was worth it to extract the information we were looking for. No one has done this type of mapping before."
Saffari's diligence paid off. With her painstakingly collected data, she and Pease used a statistical simulation technique to determine whether randomly sampling tissue would result in a positive diagnosis of EoE based on eonsinophil density.
"Our analysis shows that with current diagnostic conventions, you are only going to catch the patients with medium-to-high eonsinophil densities, which means we may be misdiagnosing patients as much as one out of every five times," says Pease. "Given this data, clearly endoscopy is not sufficient for a disease this patchy."
Gleich says their findings will inform future revisions of EoE diagnosis guidelines, but biopsies are "currently the standard of care and will not change in the near future."
Building on this study, Pease and Saffari are investigating technologies for labeling and detecting proteins shed by eosinophils in the esophagus, which would help detect EoE at an earlier stage. They have also filed a patent to use radiolabeled antibodies to map eosinophils throughout the entire esophagus, a new technique that would be evaluated with a clinical trial. "We're optimistic that such a diagnostic tool could be available in the next five years," Pease says.
Saffari adds this is part of the team's long-term goal to develop new strategies to enhance EoE diagnosis and understand what causes the disease.
Pease, Gleich and Saffari conducted the study with gastroenterologists Kathryn Peterson and John Fang and pathologist Carolin Teman at the University of Utah. This study was funded by the University of Utah, the Utah Governor's Office of Economic Development and the National Science Foundation.
Journal reference: Journal of Allergy and Clinical Immunology
Provided by University of Utah
- Mast cell tryptase test may aid in diagnosis of eosinophilic esophagitis May 04, 2010 | not rated yet | 0
- Genetic marker for painful food allergy points to improved diagnosis, treatment Mar 09, 2012 | not rated yet | 0
- Food elimination diet identifies causes of difficulty swallowing and swelling of the throat Jun 20, 2012 | not rated yet | 0
- Elimination diet can treat eosinophilic esophagitis in adults Jun 08, 2012 | not rated yet | 0
- Food allergy-related disorder linked to master allergy gene Mar 07, 2010 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Change in momentum when a body is thrown up and falls back down.
6 hours ago Say, a body of mass 'm' is thrown at a certain angle with the vertical with certain initial velocity 'u'. The initial momentum of this object is mu....
change in speed and wavelength of light while travelling from one med
7 hours ago what is the mechanism by which light changes its speed and wavelength while travelling from one medium to other. I know it is c/n or lamda/n and know...
Calculus of Variation - Classical Mechanics
9 hours ago I'm reading Classical Mechanics (Taylor), and the 6th chapter is a basic introduction to calculus of variations. I'm super confused :confused: ...
Frictional Force Equation Doesn't Make Sense
10 hours ago Frictional Force is mathematically defined as: Ff = μ*m*g*cos(θ) , where μ is the coefficient of friction, m is the mass of the object, g is...
Calculating Steam Pressure in Closed Container
15 hours ago I am trying to calculate the volume of liquid water i need to place in a sealed container in order to obtain 10 psi of steam pressure in that closed...
Learning curve of Electromagnetism?
20 hours ago I'm taking a first year physics course and have been having a little trouble with the basics of newtons laws and forces and whatnot, though nothing...
- More from Physics Forums - Classical Physics
More news stories
Raising hopes for cell-based therapies, UC San Francisco researchers have created the first functioning human thymus tissue from embryonic stem cells in the laboratory. The researchers showed that, in mice, ...
Immunology May 16, 2013 | 4.8 / 5 (5) | 0 |
Researchers from CNRS, Université Toulouse III - Paul Sabatier and IRD have elucidated new molecular mechanisms involved in resistance to visceral leishmaniasis, a serious parasitic infection. They have shown that dectin-1 ...
Immunology May 16, 2013 | not rated yet | 0
Women's immune systems age more slowly than men's, suggests research in BioMed Central's open access journal Immunity & Ageing. The slower decline in a woman's immune system may contribute to women living longer than men. ...
Immunology May 14, 2013 | not rated yet | 0
Newly described type of immune cell and T cells share similar path to maturity, according to new study
(Medical Xpress)—Labs around the world, and a core group at Penn, have been studying recently described populations of immune cells called innate lymphoid cells (ILCs). Some researchers liken them to foot soldiers that ...
Immunology May 14, 2013 | 5 / 5 (3) | 0 |
(Medical Xpress)—Cytokines are molecules produced by immune cells that induce the migration of other cells to sites of infection or injury, promote the production of anti-microbial agents, and signal the production of inflammatory ...
Immunology May 13, 2013 | 5 / 5 (1) | 0 |
The hunt for an HIV vaccine has gobbled up $8 billion in the past decade, and the failure of the most recent efficacy trial has delivered yet another setback to 26 years of efforts.
1 hour ago | not rated yet | 0
Regular consumption of coffee is associated with a reduced risk of primary sclerosing cholangitis (PSC), an autoimmune liver disease, Mayo Clinic research shows. The findings were being presented at the Digestive Disease ...
9 hours ago | not rated yet | 0 |
Patients with treatment-resistant major depression saw dramatic improvement in their illness after treatment with ketamine, an anesthetic, according to the largest ketamine clinical trial to-date led by researchers from the ...
9 hours ago | 4.7 / 5 (3) | 0 |
Research presented at Digestive Disease Week (DDW) explores new methods for managing digestive health through diet and lifestyle.
9 hours ago | not rated yet | 1
An increasing number of U.S. children are experiencing gastrointestinal issues that require interventions to resolve, according to research presented at Digestive Disease Week (DDW).
23 hours ago | not rated yet | 0 |
The use of a smartphone application significantly improves patients' preparation for a colonoscopy, according to new research presented today at Digestive Disease Week (DDW). The preparation process, which begins days in ...
8 hours ago | not rated yet | 0