Frequently Asked Questions

Answered by doctors on our medical board 

Adult Issues 

Question 1:  Please discuss the current trends in adult EE specifically with relation to esophageal dilatations.  There seem to be more issues with esophageal narrowing in adults.  Controversy remains, even among those adult GIs who are more experienced with EE about using dilatations. 

This is an excellent question and the issue is indeed controversial.  There have been two reports that have indicated that some adult patients with EE do have esophageal narrowing and dilatation did relieve symptoms.  These observations were not controlled and any benefit of esophageal dilatation remains unclear.  Subsequently, another study reported an esophageal perforation with endoscopy without any dilatation.  These authors recommended dilatation only be considered in patients with eosinophilic esophagitis (EE) who failed to respond to medical therapy and have clear-cut esophageal rings that appear to be blocking the passage of food.  Currently, EE can only be diagnosed at endoscopy and biopsy so while there may be a slightly higher risk of perforation in this setting, it is probably relatively rare.  On the other hand, esophageal dilatation needs to be approached very cautiously based on the uncertainty.  I do not recommend routine esophageal dilatation unless there is clear-cut obstruction of the esophageal lumen despite medical treatment.

Question 2:  What damage, or effects (if any) have you seen in adults with EE who have had symptoms for a long period of time but were undiagnosed and untreated?

 Many patients with EE probably go unrecognized even now.  I have not seen any long term problems from a delay in diagnosis.  One study from Switzerland followed patients for an average of seven years with eosinophilic esophagitis.  There were 30 adult patients in the study.  While difficulty swallowing continued in 29 of these patients, and esophageal eosinophilic infiltration persisted in all of the symptomatic cases, the inflammation with eosinophils did not extend elsewhere and there was no other significant health impact of the disease.  In particular, there was no evidence of any obvious malignancy associated with eosinophilic esophagitis.  There was also no evidence of patients evolving to the hypereosinophilic syndrome.  A diagnosis of eosinophilic esophagitis seems to be increasingly made as the syndrome is now recognized, which suggests patients in the past were probably often misclassified.  So the good news is not making a diagnosis or receiving any treatment for a long period of time doesn’t seem at all likely to cause any serious problems for the patient, aside from food impacting or difficulty swallowing continuing.  Making doctors more aware of this disease is likely to lead to earlier diagnosis for most patients.

 Nicholas J. Talley, M.D., Ph.D., Mayo Clinic

General Questions about eosinophil related gastrointestinal disorders

 Question 3: I've noticed that most doctors seem to distinguish between EE and EG, as if the two disorders were very different.  Other than a different part of the GI tract affected, are the disease processes different?

 Answer: This is an excellent, clinically-relevant question. As the reader may know, the esophageal epithelium is free of eosinophils in the healthy state. On the other hand, eosinophils can be present in the stomach, small intestine, and large intestine (especially cecum) in the absence of disease. EE stands for Eosinophilic Esophagitis and is defined as severe eosinophilia of the esophageal epithelium (defined, at our center, as presence of >15 eosinophils per high power field). The definition of EG, on the other hand, is somewhat fluid. It may connote eosinophilic gastritis with/without esophagitis, and/or enteritis.

The symptomatology of the two conditions, EE and EG, can be similar. Both appear to be allergic reactions of the delayed hypersensitivity type, and patients with either entity may have positive skin tests to food antigens. The diagnosis, and differentiation, is based upon histological examination of mucosal biopsies, and diligent recording of the intensity of the eosinophilic inflammation. I do encounter more of EE than EG. In my experience, patients with EG are more likely to respond to leukotriene antagonists, like montelukast, and cromoglycate (a mast cell stabilizer), than patients with EE. It remains to be seen if EE and EG are two entirely separate entities or part of a spectrum of eosinophilic disorders of the gastrointestinal tract.

 Dr. Sandeep Gupta 

Question 4:  What is patch testing for foods?  Can patch testing help determine which foods are causing my son's EE?

 Answer:  Patch testing or atopy patch testing is another way to test for food allergies.  To better understand patch testing, the differences between “regular” allergy testing and patch testing should be explored.  The standard or regular tests for food allergy are scratch test or prick skin test and RAST blood testing (also called CAP-RAST testing).  Prick skin testing examines IgE-mediated reactions.  IgE-mediated reactions occur within seconds to hours after ingestion of the food causing hives or anaphylaxis.  Patch testing examines for non-IgE mediated reactions.  These reactions are often delayed, occurring hours to days after ingestion of the food.  Many patients with non-IgE mediated reactions have difficulty in identifying the food causing the reactions.  Patch testing was first done in 1890’s for reactions to perfumes, dyes and metals.  Patch testing for foods have been done since 1990's in Europe and in the US since 2000.

 Another major difference between prick skin tests and patch testing is the standardization of reagents.  The materials for prick skin testing are commercially available and standardized.  For prick skin testing, we use purified extracts and prick or scratch with a needle or specialized tool.  After scratching, the results are read for redness and swelling (wheal and flare) in 10-15 minutes.  In contrast, the reagents for patch testing are not standardized.   In patch testing, fresh foods are prepared into a porridge-like consistency and placed on aluminum chambers on the patient’s back for 48 hours.  The patches are then removed and read 24 hours later for redness and swelling. The preparation of the fresh food is not standardized and probably accounts for the variability in the testing results from one physician to another.  However, the time frame for reading, placement and scoring of the patch is standardized.

 Most patients can identify the foods that are positive on prick skin testing as the immediate time frame from ingestion to reaction, thus helping the family and physician decide which foods to test for. This is not the case for patch testing.   Since there is a delayed reaction to foods and difficulty identifying foods, we typically screen for the most commons foods in the patient’s diet including milk, soy, egg, grains and meats.

 The adverse effect from either prick skin testing or patch testing is minimal.  You can get local itching and swelling at the site of skin testing, which typically resolves within 1 hour.   The most common reaction from patch testing is minor skin irritation by the tape, which resolves with 24 hours.  Occasionally, patients have a strong positive patch test reaction that take about 4-7 days to resolve.

 Other testing including IgG, Immune-complexes to foods have not been well studied in food allergy.

 We have examined the usefulness of patch testing and prick skin testing in our 300 patients with EE.  We have used the combination of skin testing and patch testing to help identify the foods that may be contributing to EE.  We have found that in 99% of all EE patients foods play an essential role as symptoms resolve and biopsies normalize after removal of food in the diet.  Skin testing detects only the foods that cause immediate symptoms.  In our patients, 1/3 of the patients are negative to all foods on prick skin testing.  When these patients have patch testing, we are able to detect some foods in almost all patients. Patch testing is able to find foods in about 75% of the patients. Interestingly, the foods that are positive on prick skin test are different than the foods that are positive on patch testing.  We have eight patients that we were not able to detect any positive foods.

 We instruct our patients to avoid all the foods that are positive on skin test or patch testing. Patients reported improvement in symptoms and normalization in biopsies about 75% of the time, including the patients that were started directly on elemental diet for nutritional reasons.  The reasons for missing foods in 25% include not testing for the appropriate foods, poor testing techniques or non-compliance with diet. It is also important to note that testing can have false positives or false negatives, by either skin testing or patch testing and biopsies remain the gold standard.

 Dr. Jonathan Spergel, Children’s Hospital of Philadelphia

 Question 5: Will allergy shots for environmental allergies be recommended as part of treatment of eosinophilic disorders?

 Answer: Immunotherapy (IT), is helpful in treating allergic rhinitis and asthma. For eosinophilic disorders we need to look at the specific disorder for each patient and assess individually. Some cases of EE, for example, are allergic in nature and some are not; those patients that test positive to allergens via SPT, RAST or patch testing may improve their general wellness by participating in IT.  The treatment may not help those with eosinophilic gastroenteritis, and each case should be reviewed individually. There are some disorders that might get worse with IT, such as allergic bronchopulmonary aspergillosis (ABPA), but in general, if someone has allergies, immunotherapy may help.  Immunotherapy for eosinophilic disorders has not been proven, but might help the ones that have an allergic component. EGE, if not allergic, may not improve with IT, but I would not expect it to get worse.

Question 6: Does medication to treat environmental allergies have any positive effect on treatment of EGID?

 Answer: Again, this depends on the disease, but most likely yes.  If a patient with EE is allergic to molds for example (aspergillus), medication might help prevent and treat a reaction, and help with their EE if their disease is allergic in nature.  Those patients that have IgE allergies and respond with positive results via SPT and RAST testing to environmental allergens may be helped.  Those patients with T cell responses that are indicated by patch testing might not be helped.

Question 7: Do environmental allergies play a bigger role in EGID than originally thought? 

 Answer: They might, in some cases, it depends on the specific patient and the type of allergies.  Most likely, yes, environmental factors can play a role in eosinophilic disorders.  Allergic reactions do not occur exclusively in the GI tract; various systems are processes are linked.  What you breathe in might make you more prone to react.  Dr Marc Rothenberg of Cincinnati Children’s has shown in his research that mice develop EE after mold has been introduced to their lungs.  This process is not proven in humans, but we think that people develop EE as a combination of genetic and environmental factors; someone might be more prone to develop EE genetically, but the disorder only develops when a specific set of conditions in their outside environment trigger the response.  Limiting exposure to known environmental allergens is recommended to help reduce reactions.

Question 8: Are food trials recommended during the seasonal allergy season that affects the patient?

 Answer: If a patient is sick or having symptoms, it is not recommended to trial foods. The level of reactions of an allergic patient during the allergy season is increased, leaving a patient at risk for more severe reactions and false positives to a food during a trial, and thus it is preferable not to test during this time.

Question 9:  I've read that many people with eosinophilic esophagitis have a soybean allergy.  Is soy lecithin okay to ingest?  I've found it in several things including ice cream, chocolate candy bars, chewing gum and vitamins, to name a few examples.

 Answer: The great majority of food allergies are to food proteins.  Lecithin is a phospholipid (a type of fat) and I would not expect an allergic reaction to it. Some patients, however, could react to a product containing soy lecithin due to cross contamination of other soy protein during the manufacturing process.

 Jesus R. Guajardo, M.D., M.H.P.E.
Allergy and Pulmonary Division
University of Missouri at Columbia

Pathology Q & A with Dr. Margaret Collins, Cincinnati Children’s Medical Center

Question 10: Some doctors count the number of eosinophils when they biopsy and other docs don’t count.  What’s the significance of the cell counts?

Answer: 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 (EE), who are very unlikely to find relief from symptoms using anti-GERD medications, and who generally require other sorts of interventions.  The exact number that can be used to identify EE is not universally accepted, but most laboratories use at least 15 eosinophils in a high power field, and many require 20-25 eosinophils in a high power field to identify EE.  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 EE biopsies also have other changes that help to identify EE, 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 have just completed a project at Cincinnati Children’s Hospital Medical Center (CCHMC), which will be published soon, 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.  

Question 11: What does it mean when there’s degranulation of eosinophils?  Is it significant? 

 Answer:  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.

Question 12: Can you explain basal cell  hyperplasia?

 Answer:  This term refers specifically to a thickening of the lining, or epithelim, of the esophagus.  That epithelium is unique to the esophagus, is not found elsewhere in the GI tract, and is very similar to skin.  The basal cells form a layer deep in the lining that is generally thin.  The basal cells in that layer are responsible for maintaining the lining of the esophagus, by forming new cells that migrate upward into the rest of the epithelium.  There is normally some cell turnover, and shedding of older cells into the lumen of the esophagus, and the cells in the basal layer divide to ensure that the integrity of the lining is maintained and the lining does not become too thin.  If the lining is turning over more rapidly, the basal layer cells will divide rapidly, and that layer will become thicker.  The medical word to indicate a greater number of cells than is normally present is hyperplasia.  Basal cell or layer hyperplasia can be quite impressive in EE, and is often most impressive when the number of intraepithelial eosinophils is very increased.  Basal layer hyperplasia is a common finding in EE, and indicates that the epithelium is reacting to an irritant, probably inflammation.

 Normal Esophageal epithelium

This picture shows normal esophageal eptihelium.  The arrow points to the top of the basal layer, and the bar spans the depth of the basal layer.  Normally, this layer is no more than 3 cells thick.

Basal layer hyperplasia, below.  There is significant basal layer hyperplasia in this biopsy.  The arrow points to the top of the basal layer, and the bar spans the depth of the basal layer.  The epithelium is thicker than normal, mostly due to impressive expansion of the basal layer.  The basal layer in this biopsy consists of significantly more than 3 cell layers.

Updated 2-16-2006, Wendy Book wendy@apfed.org