Q & A with Experts

A. Dr. Jonathan Spergel, Children’s Hospital of Philadelphia responds:

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 Specific IgE blood testing (also called RAST. CAP-RAST or Immuno-cap testing). Prick skin and specific IgE blood 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.   Patch testing was used in EoE for many years; however, recent studies have shown that it typically misses milk and empiric elimination works as well as directed food removal based on allergy testing (combination of skin and patch testing).  Empiric elimination has less visits and has replaced testing directed diets.

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 and most recent studies just indicate that is just a marker of what you are eating more than a true food allergy.

A: Jesus R. Guajardo, M.D., M.H.P.E., University of Missouri at Columbia, responds:
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 EoE after mold has been introduced to their lungs. This process is not proven in humans, but we think that people develop EoE as a combination of genetic and environmental factors; someone might be more prone to develop EoE 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.

A: Jesus R. Guajardo, M.D., M.H.P.E., University of Missouri at Columbia, responds:
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.

A: Jesus R. Guajardo, M.D., M.H.P.E., University of Missouri at Columbia, responds:
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.

A: By Jonathan E. Markowitz, M.D., M.S.C.E., University of South Carolina School of Medicine, Greenville responds: Symptoms and biopsy findings can be discordant for several reasons.One possibility is that the disease is still present but the biopsies did not detect it.This can occur because EoE can be patchy within the esophagus and the area that was sampled (which represents a very small portion of the entire esophagus) may have had normal findings, but an adjacent area could have shown active inflammation if it had been sampled.

Sometimes, ongoing exposure to a food that a patient is allergic to can cause symptoms even if they are on swallowed steroids that reduce the number of eosinophils in the esophageal specimens.In those cases, a patient may need a combination of dietary restriction and steroids.

An alternative possibility is that the symptoms are coming from a different cause.One likely possibility is ongoing acid reflux, which can occur along with EoE in many patients.This possibility could be addressed in several ways, including some specific testing (pH study or MII study) or by adjusting medical therapy.Occasionally the motility of the esophagus can be affected in patients with EoE, meaning that the muscles of the esophagus do not function as well as they should in moving food from the top to the bottom.These symptoms may lag behind improvement in biopsy specimens but would be expected to improve with time if the disease remains in remission.

Additionally, some patients with a history of swallowing problems continue to experience those symptoms without a clear explanation after the disease seems to be in remission.This may sometimes relate to being overly sensitive to what used to be a normal sensation, but after having had problems for so long, that normal sensation is now interpreted as being abnormal. Some children are particularly susceptible to this type of problem, and may benefit from working with a psychologist or counselor to help reduce the sensitivities after the other possibilities have been eliminated as concerns.

In any of these cases, it is important to remain in contact with the treating specialist and work through the possibilities together to achieve the ultimate goal of improving both symptoms and the biopsy findings.

A: Dr. Philip E. Putnam, Cincinnati Children’s Hospital and Medical Center, responds:
There have been no formal studies to answer this question, so no one knows what amount and frequency of ingestion of a food that is known to cause esophagitis but not a severe immediate reaction might be permitted. My common sense approach has been to recommend strictly avoiding all known offending foods, because we don’t know if it’s safe.

More importantly, as a practical matter, it is hard to argue with a child whose non-adult/immature logic is, “Well, if I could eat it yesterday and it didn’t bother me, why can’t I eat it today?” If the answer is set, predictable, and consistently applied (i.e., “No, you can’t even try it once”), then the argument is avoided. We have seen many families wherein the parent loses control over the situation with one food, and then more foods as the child continues to test the limit again and again. Eventually, the esophagitis comes back and it is impossible to determine which food or foods might have been responsible, so there are few options other than to start over.

A: Dr. Philip E. Putnam, Cincinnati Children’s Hospital and Medical Center, responds:
No. In truth, a relatively small proportion of children who have EoE have a feeding tube. As with all diseases, there is very broad spectrum of disease severity and management possibilities under the rubric of EoE. As such, there are certainly some children who have EoE who undergo an elemental diet trial and who won’t take the amino acid-based formula orally. Those children have a feeding tube (either temporary nasogastric tube or gastrostomy tube) placed so that the formula can be delivered directly to the stomach. That avoids the child needing to taste the formula and assures that enough is administered to meet the child’s needs for growth and development. So, although it’s true for a small subset of children who have EoE, the word “most” is a gross exaggeration.

A: Dr. Philip E. Putnam, Cincinnati Children’s Hospital and Medical Center, responds:
No. There is a small subset of children who have EoE who are highly allergic and who have not been able to advance their diet without a recurrence of EoE. The nutritional quality of the foods they are permitted is too limited to meet their needs for normal growth. As such, they remain dependent on the elemental formula to meet their nutritional requirements. The fraction of children who have this form of EoE is small, but they get a lot of attention and we work hard to find ways to improve their quality of life within the confines and limitations of their condition. The good news is that the vast majority of children who have EoE can be managed in a way that ultimately permits adequate oral nutrition without the continued use of an elemental formula or a feeding tube.

A: Raquel Durban, MS, RD, LDN, Asthma and Allergy Specialists, Charlotte, NC, responds:
Transitioning from an elemental diet to a full diet can pose many challenges. For example, in the case of a child, depending on the age at the time an elemental diet was introduced, he or she may have delayed feeding skills that should be addressed.

Your child may also be referred to a speech language pathologist, who can assist with promoting age-appropriate feeding skills, aid in reintroduction of approved foods, and help to improve oral aversions.

It is not uncommon for a child and/or their caregiver to experience anxiety and fear during a diet transition and during food trials. If these feelings become a concern, consult with a therapist who can help work through these feelings.

In terms of deciding which food to trial first, your allergist and dietitian will be able to assist you in making the best choice for your particular case/needs. Selecting a food that can be prepared in a variety of ways can increase acceptability and limit the likelihood of “burn out” that can occur with having limited food choices in the diet.

Keep your child focused on the foods that he or she can eat. Create a list of “safe foods” and allow your child to choose from this list whenever possible. This can help provide a better sense of control during situations where food is present, such as at a party or a playdate.

Finally, be sure to track any symptoms that arise during a food trial, and share them with your child’s doctor.

A: Ikuo Hirano, M.D., Northwestern University Feinberg School of Medicine, responds:
The word “remodeling” probably conjures up images of home improvement projects such as a new kitchen or bathroom. In eosinophilic esophagitis (EoE), remodeling refers to alterations in the microscopic and macroscopie structure of the esophagus. Remodeling can be a protective mechanism involved in the repair of tissue following an injury, such as healing of a skin abrasion from a scraped knee.

On the other hand, the remodeling consequences of chronic eosinophil predominant inflammation in EoE have negative implications: the accumulation of fibrosis or “scar tissue” that results in esophageal strictures. In EoE, microscopic evidence of remodeling is evidenced by increased thickness of the esophageal lining and muscle layers as well as fibrosis of the inner layers of the esophagus.[1] I will address three fundamental questions: (1) Why does remodeling matter? (2) Does remodeling reverse with available therapies? (3) What is the role of esophageal dilation in treating remodeling?

A: Ikuo Hirano, M.D., Northwestern University Feinberg School of Medicine, responds: Remodeling is important because it is a major cause of the clinical symptoms and major complications of EoE, particularly in adults.[2] Recent studies from the Northwestern group have identified that measurement of esophageal remodeling in EoE is significantly linked with patients’ risk of food impaction. This study utilized a device, known as the functional luminal imaging probe (FLIP), applied at the time of endoscopy to measure the “stiffness” of the esophagus. The esophageal stiffness is related to the inflammation and fibrosis of EoE, as well as normal structures of the esophageal wall. In our first study, we showed that esophageal stiffness was substantially increased in EoE.[3] In a second study, we showed that patient’s past and future risk of food impaction was related to the degree of esophageal stiffness.[4]

Upper endoscopic (“EGD”) is an important test in the evaluation of patients with EoE. Endoscopically detected esophageal features of EoE include longitudinal furrows, white exudates (plaques), edema (loss of vascular markings), rings (trachealization), and strictures.[5] Endoscopic findings in patients with EoE have been shown to vary by age. Younger patients commonly have features of inflammation that include exudates, furrows and edema. In contrast, adult patients commonly have features of esophageal remodeling that include strictures, rings, narrow caliber esophagus, and crepe-paper mucosa. Strictures can be found in 30-80% of adults with EoE, with higher estimates noted in patients with longer duration of untreated disease.[6] These observations support the concept of progression of remodeling with duration of untreated disease that leads to increase risk of stricture formation.

A: Ikuo Hirano, M.D., Northwestern University Feinberg School of Medicine, responds: Numerous studies have demonstrated the benefits of swallowed steroids and elimination diet therapies in EoE. Both forms of therapy result in convincing reduction and in many cases complete healing of eosinophilic inflammation based on biopsy results. Inflammatory features on endoscopy such as furrows and exudates improve with both steroids and diet therapies. Available studies provide evidence that medical therapy can at least partially reverse existing remodeling effects in EoE. Both Dr. Aceves and Dr. Straumann have demonstrated that budesonide decreased symptom severity, esophageal eosinophilia, subepithelial fibrosis as well as TGFß1 expression in EoE.[7, 8] TGFß1 is a protein mediator that is a key player in the remodeling process in EoE.

In another study by Dr. Alexander, significant improvement in esophageal strictures, albeit modest, was demonstrated using x-ray measurements (barium esophagram).[9] On the other hand, other pediatric and adult investigators have demonstrated variable and less impressive reversal of fibrosis with diet and steroids in spite of prolonged treatment periods. Clearly, more work is needed to fully understand the role of medical and diet therapies in reversing the remodeling effects in EoE.

A: Ikuo Hirano, M.D., Northwestern University Feinberg School of Medicine, responds: There is little doubt that esophageal dilation is a highly effective means to deal with the fibrostenotic strictures of EoE. I have performed several hundred dilations for my patients with EoE. The majority of patients achieve immediate and lasting relief of dysphagia. In a survey administered to patients who had been treated with esophageal dilation, almost all voiced a high degree of satisfaction with procedure.[10] When carefully performed, the risks of complications from esophageal dilation in EoE are very low.

While esophageal dilation is effective and generally safe, it does nothing to arrest the chronic inflammatory process that leads to strictures. Medical and diet therapies remain fundamental to the appropriate management of EoE to eliminate active inflammation and thereby prevent the progression of esophageal fibrostenosis and other remodeling effects. Dilation should not be utilized for children and adults who lack the symptoms or signs of fibrostenosis. Dilation should be viewed as adjunctive therapy, targeting aspects of esophageal remodeling that are not amenable to medical and diet therapies.

We eagerly await approval of medications for both children and adults suffering from the consequences of EoE and related eosinophilic gastrointestinal disorders. While currently used “off label” therapies are helping many of our patients, not all achieve an adequate response. As discussed, the incomplete reversal of remodeling is one reason for persistent symptoms. Several pharmaceutical trials are ongoing to improve formulations of steroids developed to optimize delivery to the esophagus. Furthermore, very novel treatments are being tested that target specific pathways involved in EoE. Several of these emerging therapies offer the hope of addressing both inflammatory and remodeling consequences of EoE.[11] At the same time, researchers continue to design studies to better understand the mechanisms and improve clinical detection of remodeling in EoE. The “designers” are busy at work to “remodel the remodeling” of EoE and thereby improve the care of their patients.