Cincinnati Center for Eosinophilic Disorders

Eosinophilic disorders are part of the broad category of inflammatory disorders and are not formally considered autoimmune. There is currently no substantial data to support an autoimmune cause for eosinophilic disorders, but research on this topic is actively ongoing.

Environmental allergens, such as aeroallergens, may indeed be a factor in eosinophilic disorders. In our experimental mouse models, intranasal administration of allergens can induce eosinophilic esophagitis (EoE). Additionally, some of our prior investigations have shown that indoor insect allergens can induce EoE in mice (Rayapudi et al. J Leukoc Biol. 2010).Thus, the oral/gastrointestinal exposure of an individual to food allergens may not be the only route/allergens to consider.

Asthma is an allergic disease of the airways associated with eosinophilic lung inflammation, and it is generally believed that eosinophils are causing part of the lung problems and symptoms in this disease.

Eosinophilic esophagitis (EoE) does have seasonal variation in some patients, typically with worse symptoms in the spring and summer.

Environmental allergens, such as aeroallergens, may indeed be a factor in eosinophilic disorders. In our experimental mouse models, intranasal administration of allergens can induce eosinophilic esophagitis (EoE). Additionally, some of our prior investigations have shown that indoor insect allergens can induce EoE in mice (Rayapudi et al. J Leukoc Biol. 2010). Thus, the oral/gastrointestinal exposure of an individual to food allergens may not be the only route/allergens to consider.

The long-term consequences of eosinophilic gastrointestinal disorders (EGID) are currently being studied. However, most patients with EGID do not have a life-threatening disease and can live a long life.

Eosinophil-associated gastrointestinal disorder (EGID) can present acutely in association with a viral-appearing illness. While the start of symptoms may be sudden, it is likely that the intestinal inflammation was present well before the onset of symptoms. The new insult (i.e. the viral illness) may promote the severity of the symptoms because of the underlying problem. However, it is important to note that EGID is a chronic disorder and usually presents gradually rather than acutely; it also does not go away quickly. However, it does respond rather rapidly to effective treatment. In your child, the effective treatment appears to be an alteration in the diet. A true remission is only determined by repeat endoscopy and biopsy. Because of the unusual acute presentation in your child, an experienced physician should carefully scrutinize the biopsy slides; one must be sure that the problem is truly EGID and not another process.

Our recent research is indicating that there is a 3-10% chance of having another child with eosinophilic esophagitis (EoE) if you already have one child with this condition. There is a short video clip posted on our Facebook page Marc E. Rothenberg, MD, PhD about this topic. 

The eosinophils are sometimes elevated in the blood of individuals with eosinophilic gastrointestinal disorders (EGIDs) (in less than half of patients), and the blood eosinophil levels generally correlate with the severity of tissue disease. Thus, the eosinophil levels in the blood often return to normal.

The current research shows that eosinophilic gastrointestinal disorders (EGIDs) [i.e. eosinophilic esophagitis (EoE), eosinophilic gastritis (EG), eosinophilic colitis (EC), and eosinophilic gastroenteritis (EGE)] are associated with food allergies. However, EGIDs and food allergies are not the same. EGIDs are defined by the presence of eosinophils in the gastrointestinal tract as measured by endoscopy. It is common for people with EGIDs to have single or multiple food allergies. However, those with single or multiple food allergies do not always develop EGIDs.

This is one of the more frustrating situations encountered by families and physicians. About 25% of those with confirmed eosinophilic esophagitis (EoE) diagnosis do not test positive to foods. This does not necessarily mean that there is not an issue with a food(s). Allergy testing is not perfect. We have found that many of the children who tested negative to food(s) still respond when certain foods were removed from their diet. Figuring this out often takes patience. Medication therapy is one of the first approaches in cases like this; however, dietary changes can still be used. As always, you need to consult with your medical team to work through this. Treatment for eosinophilic disorders is not a "one glove fits all" approach.

A variety of foods can be associated with eosinophilic gastrointestinal disorders (EGIDs). Unlike classic anaphylaxis, there appears to be a broader range of foods identified as culprits. This area is under active research investigation. 

The common theme with these diseases is the presence of eosinophils; however, specific knowledge of eosinophilic disorders beyond the esophagus is limited. One reason for this lack of knowledge for eosinophilic gastritis (EG) or eosinophilic colitis (EC) is that these diseases are not seen as much as eosinophilic esophagitis (EoE) and also that there is not a standardized diagnostic criteria set for EG or EC. With the support of patients, families, organizations and others, research will continue. It is our hope that with further research more will be known about the specifics of the molecular events and mechanisms involved in each of these disorders, which will open up new possibilities for development of diagnostic criteria and therapeutic agents.

Eosinophilic colitis (EC) is also part of the broader category of eosinophilic conditions called eosinophilic gastrointestinal disorders (EGIDs), along with eosinophilic esophagitis (EoE) and eosinophilic gastritis (EG). Treatments do vary depending on the location of the disorder. Sometimes diets / elemental formulas will be used as well as systemic medications such as steroids. We do know through experience that medications used for EoE, such as Flovent and Pulmicort, do not help in the treatment of EC. An accurate diagnosis is important in understanding which treatment to take.

We have examined the amount and location of eosinophils in the colon in a limited set of healthy normal patients (Debrosse et al. Pediatr Dev Pathol. 2006) and found that the average number of eosinophils in the ascending and transverse colon were not significantly different. The peak eosinophil count was 50 eosinophils/high-powered field in the ascending colon and 42 eosinophils/high-powered field in the transverse colon. However, an exact cut-off of eosinophil levels for a diagnosis for eosinophilic colitis (EC) is not yet agreed upon.

 We have examined the amount and location of eosinophils in the colon in a limited set of patients (Debrosse et al. Pediatr Dev Pathol. 2006). The peak counts were obtained from samples containing biopsies from both the cecum and ascending colon (50 eosinophils/high-powered field) and from samples containing biopsies from both the transverse and descending colon (42 eosinophils/high-powered field). The peak count for samples containing biopsies from the ileum only was 28 eosinophils/high-powered field. Still, there is not consensus for an exact cut-off number for any of those sites; all biopsy findings must be correlated with clinical findings.

 It is not common for patients with eosinophilic colitis (EC) to have a positive antinuclear antibody (ANA) test result but points to the fact that eosinophilic colitis (EC) may be more related to autoimmunity in many patients whereas eosinophilic gastrointestinal disorders (EGIDs) are classically related to food allergy. More specifically, EC does not typically respond to dietary changes (food allergy-based treatment) but more frequently requires immunosuppressive therapy (autoimmunity-based treatment). Marc E. Rothenberg, MD, PhD authored a review of EGIDs several years ago that you may find helpful. 

The term “eosinophilic gastroenteritis” (EGE) is used to describe when someone has a confirmed eosinophilic disorder in more then one region of the gastrointestinal tract (esophagus, stomach, colon). Therefore, having both eosinophilic esophagitis (EoE) and eosinophilic gastritis (EG) would be EGE. Here at out center, a portion of our patients do have EGE with both EoE and EG. Are EoE and EG related? We are working to find this out. The common theme with these diseases is the presence of eosinophils; however, specific knowledge of eosinophilic disorders beyond the esophagus is limited. One reason for this lack of knowledge for EG or eosinophilic colitis (EC) is that these diseases are not seen as much as EoE and also that there is not a standardized diagnostic criteria set for EG or EC.

The diagnostic criteria for eosinophilic gastritis (EG) are not well defined, and the exact cause of EG is not known. To address these problems, we are examining genetic differences between the stomach tissue of patients with EG and without EG. By discovering genes with altered structure or expression, we can identify molecular pathways that are dysregulated in the stomach of EG patients, which will allow further understanding of the cause of EG. The pathways identified may also serve as targets for treatment of EG. One of the molecules that was highly increased in the stomach of EG patients was a cell adhesion molecule, cadherin-like 26 (CDH26). Cadherins can be thought of as intracellular Velcro, with each cadherin protein acting like a hook that snags cadherin on other cells, thus attaching cells to each other. CDH26 was also increased in the esophagus of patients with eosinophilic esophagitis (EoE), so it may have a common function in different types of eosinophilic gastrointestinal disorders (EGIDs). We have produced recombinant CDH26, and now have sufficient quantities of the protein to begin characterizing its biological function. We are hoping that this and related molecules will open up new diagnostic and treatment possibilities for EG and other EGIDs.

The Rothenberg Research Laboratory, a collaborator of the Cincinnati Center for Eosinophilic Disorders, takes a multi-faceted research approach to understanding eosinophils and their involvement in a wide spectrum of eosinophilic disorders, including hypereosinophilic syndrome (HES). When Marc E. Rothenberg, MD, PhD, was a PhD student, he was the first to publish that interleukin 5 (IL-5) was involved in HES. Subsequently, he confirmed this finding in pre-clinical models. More recently, he and his collaborators demonstrated that anti-IL-5 (humanized antibody against IL-5, also called "mepolizumab") is helpful for patients with HES, as reported in his landmark article in the New England Journal of Medicine in 2008.

There is no known direct link between eosinophilic disorders and depression. However, there can be higher rates of anxiety and depression in children with chronic illness in general.

Nasal eosinophils are not directly related to eosinophilic esophagitis (EoE); however, EoE is associated with allergic disorders, including upper respiratory allergies such as allergic rhinitis and nasal polyps. Both allergic rhinitis and nasal polyps are associated with nasal eosinophilia.

Helminth therapy can certainly modulate immunity; however, it may be expected to exacerbate eosinophilic esophagitis (EoE)-like diseases. As eosinophils normally increase in response to parasites, this would likely not be an effective therapy for eosinophilic gastrointestinal disorders (EGIDs).

One of the possible side effects of oral immunotherapy (OIT) is the development of an eosinophilic gastrointestinal disorder (EGID), such as eosinophilic esophagitis (EoE). This highlights the intimate connections between allergic responses that cause anaphylaxis and those involved in EGIDs. When anaphylaxis is blocked with OIT, the immune system can continue to be allergic but manifest this continued allergy via a different response (e.g. an EGID). Indeed, patients with EGID generally have IgE against specific foods but do not have concurrent anaphylaxis, further highlighting the connection. Research concerning both disorders provides novel insight on each that may not have become apparent from researching these disorders individually, emphasizing why we strongly advocate for broad research inquiry rather than a strictly focused approach and why we aim to encourage food allergy research organizations/foundations to support EGID research. To more specifically answer your question, we do not have a formal recommendation about this but wish to point out that MOST patients on OIT have not been reported to develop EGID.

Marc E. Rothenberg, MD, PhD, was the first to show a role for chemokines in eosinophilic esophagitis (EoE; see his original publication) and is actively pursuing this for the treatment of eosinophilic gastrointestinal disorders (EGIDs). Additional suggestions and/or leads about broad-spectrum chemokine inhibitors would be welcome.

Splenda is used because it is thought to be inert, tasty and generally a safe mixture for individuals with food allergies or eosinophilic disorders. Additionally, mixing the liquid medication with Splenda provides the viscosity, or thickness, needed for the solution to coat the esophagus. A thinner solution may "rush" past the esophagus on its descent through the gastrointestinal tract.

It is unknown whether thrush would be worsened by the use of honey; however, there could be a concern regarding the use of honey simply as an added food agent.

Inhaled Flovent has been used for long-term treatment of asthma in children. It is generally considered safe, although it can have effects on the rate of stature growth. The long-term effects of swallowing topical steroids for eosinophilic esophagitis (EoE) is not known, but it is generally thought to be even safer than taking the medicine for asthma as the swallowed form is generally not absorbed and the amount absorbed is degraded by the liver.

Ketotifen is not currently available in the U.S.A.

We wish we had that answer, that we could accurately predict what the cure will be, how long it will take to find, and how much money it would take to do so. Unfortunately, the name of the process, "research", is very fitting in that we search over and over again ("re"). Research is the process of learning, discovery, and testing. We make headway with our hypotheses, learning from all research done, even (or perhaps "especially") that which overturns our theories on what may be happening. Every day we hope that one of our "Ah-ha!" moments will become the cure for eosinophilic gastrointestinal disorders (EGIDs).  We can say with confidence that our research is already greatly influencing the way people think and treat EGIDs around the world.

It is important to know whether the increased eosinophils were found only in the esophagus, in the stomach, in the duodenum or in all of them. If the esophagus is affected, it is also essential to know whether it was the lower part only, the upper part only or both. This information will help in the decision making (Is it eosinophilic esophagitis (EoE)? Is it gastroesophageal reflux disease (GERD)? Is it eosinophilic gastroenteritis (EGE)?

More than 15 eosinophils per high power field (in the microscope) in esophageal biopsies are suggestive of primary eosinophilic esophagitis (EoE) while less than that are typically associated with gastroesophageal reflux disease (GERD).

A good percentage of patients with eosinophilic disorders of the gastrointestinal tract have food allergies. This area needs to be thoroughly evaluated by a doctor who is specialized in allergy and immunology.

Many disorders are associated with increased numbers in eosinophils in the gut. A complete history and physical exam plus associated tests should narrow the diagnosis.