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Diagnosis of EGIDs

Endoscopy with biopsy is the ONLY way to confirm the diagnosis of EGID.

During an endoscopy, the gastroenterologist looks at the GI tract through an endoscope and takes multiple small samples (biopsies) which the pathologist reviews. A high number of eosinophils (counted per high power field) suggest the diagnosis of EGID. The pathologist will also look for the location of the eosinophils, changes in the tissue layers, and degranulation (spilling of the contents of the eosinophils). Eosinophils may be normally found in small numbers in all areas of the GI tract except the esophagus. The biopsy findings are evaluated along with the patient’s symptoms to determine if an EGID is present.

Once the diagnosis of EGID is confirmed, food allergy testing may be recommended to guide treatment. Tests for food allergies include skin prick testing, patch testing and Radioallergosorbent test (RAST).

Diagnosis of EGID may be made when the following are present:

  • Abnormal gastrointestinal symptoms as defined above
  • Eosinophilic infiltration in 1 or more areas of the GI tract. In healthy people small numbers of eosinophils may be present in many areas of the GI tract. Small numbers of eosinophils may be found in the esophagus with reflux. Higher numbers are seen with eosinophilic esophagitis
  • Absence of another identified cause of eosinophilia (such as a parasite infection)
  • No eosinophilic involvement of other organs

What other tests may be performed?

Laboratory

  • Complete blood count with differential – eosinophil counts are often mildly elevated, but may be normal. Anemia (low blood count) may be present
  • Serum IgE, allergy testing
  • Stool for infection, blood, fat, protein

Endoscopy and Biopsy

The diagnosis of EGID must be confirmed with tissue biopsies done at the time of endoscopy. Typically, the endoscopy and biopsies are performed after treatment for possible gastroesophageal reflux disease (GERD) with proton pump inhibitors or H2 blockers to minimize confusion between the two diseases. Depending on the symptoms, biopsies may be obtained by an upper endoscopy, a lower endoscopy or both. Biopsy is the only way to diagnose eosinophil associated gastrointestinal disorders.

Upper endoscopy (click on sketch to enlarge)  Lower endoscopy: colonoscopy (click on sketch to enlarge)

The gastroenterologist will look at the GI tract and take multiple small samples (biopsies) which are sent to the pathology laboratory for further examination. Multiple biopsies will be taken from each area of the GI tract, including areas that may appear normal. The pathologist will look at the samples under the microscope and describe any abnormalities. A high number of eosinophils (counted per high power field) suggests the diagnosis of EGID. The pathologist will also look for the location of the eosinophils, changes in the tissue layers (basal layer hyperplasia), and degranulation (spilling of the contents of the eosinophils). Eosinophils may be normally found in small numbers in all areas of the GI tract except the esophagus.

For more detailed information on colonoscopy and upper endoscopy, visit:

Why is it so difficult to obtain a diagnosis?

EGID is a relatively uncommon disorder that doctors may not be familiar with. The diagnosis of EGID is often delayed, sometimes for years, because there are no ‘classic symptoms’ or findings of EGID. Blood eosinophil levels may or may not be elevated. There is no typical endoscopic appearance. Histopathologic criteria have not yet been widely accepted. Although doctors may have minor disagreements concerning specific criteria, the diagnosis can be confirmed with biopsies in the majority of cases. In rare situations, it may be difficult to distinguish eosinophilic esophagitis from gastroesophageal reflux disease (GERD), or other secondary forms of EGID. Working closely with your health care team is the best way to ensure a proper and timely diagnosis.
 

How is EoE Diagnosed?

At present, the only way to definitively diagnose EoE is through endoscopy with biopsies. The endoscopy is often performed after treatment with reflux medications (acid suppressors) have failed to relieve the symptoms. During an upper endoscopy, the gastroenterologist looks at the esophagus, stomach, and duodenum (first part of the small bowel) through an endoscope (small tube inserted through the mouth) and takes multiple biopsies (small tissue samples) which a pathologist reviews under the microscope. The gastroenterologist may be able to see a problem through the endoscope, but eosinophilic esophagitis may be present even if the esophagus looks normal to the doctor. That is why the biopsy samples are important to making the diagnosis of EoE. A high number of eosinophils throughout the length of the (> 15 per high power field) suggest the diagnosis of EoE. GERD also causes eosinophils in the esophagus, but typically far fewer and only in the part of the esophagus closest to the stomach. The pathologist will also look for tissue injury, inflammation, and thickening of the esophageal layers. With EoE, the increased eosinophils are limited to the esophagus and not found in other areas of the intestinal tract. Once the diagnosis of EoE is confirmed, food allergy testing is typically recommended to guide treatment. Skin prick testing to different foods is the most common type of allergy testing.

The examples below are of endoscopic findings that may be seen in eosinophilic esophagitis*.

 

Furrows Rings White plaques

*Images courtesy of Dr. Chris Liacouras, Children’s Hospital of Philadelphia.
 

Frequently Asked Questions

Some doctors count the number of eosinophils when they biopsy and other doctors don’t count. What’s the significance of the cell counts?

Dr. Margaret Collins, Cincinnati Children’s Medical Center, answers:

The significance of the number of eosinophils in a biopsy is best known for biopsies from the esophagus. The esophagus normally has very few, if any, eosinophils in the epithelium, the part of the wall that lines the inner surface of the esophagus. Biopsies of patients who have gastroesophageal reflux disease (GERD) may contain a few eosinophils in the epithelium, but generally intraepithelial eosinophils are not numerous in those biopsies.

The number of eosinophils can be used to distinguish patients who have GERD, or at least patients who will respond to anti-GERD medications, from those who have eosinophilic esophagitis (EoE), who are very unlikely to find relief from symptoms using anti-GERD medications, and who generally require other sorts of interventions. The number that can be used in the updated consensus recommendations to identify EoE is at least 15 eosinophils in the high power field. A high power field is a very close-up view of the biopsy on a glass slide using a microscope. Pathologists should include the peak or maximum number of eosinophils in a high power field in the pathology report, and patients may contact the pathologist to obtain that information if it is not contained in the report.

Most EoE biopsies also have other changes that help to identify EoE, including marked basal layer hyperplasia. The number of eosinophils that are normally found in the remainder of the gastrointestinal (GI) tract is less agreed-upon than in the esophagus. There is some data that suggests that the normal number of eosinophils in the colon varies in different parts of the country. We do not know if the normal number varies with age. It is probably prudent for each laboratory or region of the country to develop its own norms. We completed a project at Cincinnati Children’s Hospital Medical Center (CCHMC), to identify the normal number of eosinophils in biopsies from the entire GI tract in children, and we have begun using these numbers in our daily practice to help us identify abnormal biopsies. (See publication titled "Quantity and Distribution of Eosinophils in the Gastrointestinal Tract of Children”)

What does it mean when there’s degranulation of eosinophils? Is it significant?

Dr. Margaret Collins, Cincinnati Children’s Medical Center, answers:

This is a very timely question! Until recently, I had adhered to the classic pathology teaching, that to see cytoplasmic granules outside of the eosinophil free in the tissue signified degranulation, and that meant that the eosinophil was activated, responding to some allergen or stimulus. The classic teaching is that this finding is significant. At least one paper has challenged that teaching. In the study that we just completed at CCHMC of the normal number of eosinophils in the GI tract in children, we found that eosinophils at the edges of the tissue more often had granules outside the cytoplasm than eosinophils that were more centrally located in the tissue. This finding implies that handling of the tissue, which is maximal at the edges of the tissue in the process of obtaining the biopsy, contributes to finding extracytoplasmic granules. In point of fact, we don’t see extracytoplasmic granules in all biopsies. I believe we are more likely to see them when the number of eosinophils is plentiful. More work is required to settle this issue. Currently, I concentrate more on eosinophils in the center of the biopsy to decide if extracytoplasmic granules are present, and I continue to report their presence in the biopsy.

Resources

© American Partnership for Eosinophilic Disorders 2008. Revised 4-10-2011.
Authors: Wendy Book MD, Harvey Leo MD
Images contained on this website may not be reproduced without the express written permission of the American Partnership for Eosinophilic Disorders.
Contact mail@apfed.org