Eosinophilic Esophagitis

TITLE: Eosinophilic Esophagitis
SOURCE: Grand Rounds Presentation, UTMB, Dept. of Otolaryngology
DATE: January 31, 2011
RESIDENT PHYSICIAN: Andrew Co= ughlin M.D
FACULTY PHYSICIAN: Patricia Maeso MD
DISCUSSANT: Harold Pine, MD SERIES EDITOR: Francis B. Quinn, Jr., MD
ARCHIVIST: Melinda Stoner Qui= nn, MSICS

&q= uot;This material was prepared by resident physicians in partial fulfillment of educational requirements established for the Postgraduate Training Program = of the UTMB Department of Otolaryngology/Head and Neck Surgery and was not intended for clinical use in its present form. It was prepared for the purp= ose of stimulating group discussion in a conference setting. No warranties, eit= her express or implied, are made with respect to its accuracy, completeness, or timeliness. The material does not necessarily reflect the current or past opinions of members of the UTMB faculty and should not be used for purposes= of diagnosis or treatment without consulting appropriate literature sources and informed professional opinion."

Introduction

As an otolaryngologist we have a plethora of patients = come through the office each day with complaints of dysphagia. Many times we cha= lk the diagnosis up to the reflux gods and place patients on proton pump inhibitors. Rightfully so, reflux has been associated with many other disea= se processes such as rhinitis, rhinosinusitis, otitis media, laryngitis, lymph= oid hypertrophy, and even asthma. Although reflux is at least a contributor to = head and neck disease, it is a requirement of the profession to keep an open mind and always be thinking, “What else could this be?”, rather than falling into the trap of cookbook medicine. In this article a relatively new entity, eosinophilic esophagitis (EoE), will be presented as a disease proc= ess to look out for, especially in our population of patients who are resistant to standard therapies for dysphagia.

History

EoE was first described in 1978 based off of biopsies = from the esophagus, but reflux was thought to be the driving force behind the di= sease (1). This notion was supported by several studies in the 1980’s. Wint= er et al. correlated intraepithelial eosinophils (>1eos/hpf) with pH, manometry, endoscopy and histologic findings all suggestive of reflux disea= se (2). Lee et al. presented a case series of 11 patients, showing 91% with &g= t;5 eos/hpf had reflux esophagitis (3).

In the early 1990’s, however, work was being don= e that would revolutionize the thinking behind esophageal eosinophilia. In 1993, Attwood et al., performed a retrospective review of 12 patients who had all undergone esophagram, PH monitoring, esophageal manometry, and endoscopy wi= th biopsy. They characterized patients as having either high grade (≥20 eos/hpf) and low grade (<20eso/hpf) eosinophilia. On average the patient= s in this study had 56 eos/hpf. Ninety-two percent of patients had high grade eosinophilia but none of these patients had reflux based on pH studies. Interestingly, 58% of patients have allergies, asthma, or other atopic dise= ase. The authors then compared this group with 90 controls that had pH proven GE= RD, and only 48% had intraepithelial eosinophilia with an average of only 3.3 eos/hpf (4). This study clearly paved the way for other studies to refute G= ERD as the sole cause for eosinophilia.

In 1995 Kelly et al. suggested a different cause of the disease. They evaluated a cohort of 75 pediatric patients with finding of reflux who were resistant to therapy and found that 31% had persistent eosinophilia on biopsy. Of the 75 patients evaluated, 12 agreed to proceed = with a prospective trial of an elemental diet for 6 weeks. Upon treatment with t= he elemental diet, 80% showed complete resolution of symptoms and 60% showed complete resolution of eosinophilia on repeat biopsy. Average eosinophilia dropped from 41 to 0.5 eos/hpf over the study period, and again, 70% of patients also had atopic dermatitis or asthma as a co-morbidity. Ten of the twelve patients had foods reintroduced and within a median of 1 hour, sympt= oms returned with the most common foods causing problems being cow’s milk, soy, wheat, peanut, and egg (5). Their conclusion, then, was that EoE may be due to more of a food allergy than reflux and that elemental diets are very effective in treating symptoms in patients resistant to medical therapy for= dysphagia.

Other studies began to look at the possibility of alle= rgy playing a role in the disease process. One patient was reported to have relapsing disease visualized on endoscopy when pollen counts were high, with resolution of symptoms and endoscopic findings in the winter months were reported (6). Ruchelli et al found that 56% of patients failing anti-reflux therapy had wheezing, atopic disease, or rhinitis. Of 16 patients in the failure group, 8 completely resolved with corticosteroids and 4 improved wi= th elemental diet (7). Had this been due to reflux patients would have theoretically worsened with corticosteroid therapy given the side effects of the medicati= on.

By 2003 the elemental diet = had really caught on as a valid treatment in patients with esophageal eosinophi= lia that were resistant to medical therapy. Markowitz et al. looked at 51 child= ren and treated then with 4 weeks of an elemental diet. Ninety-six percent show= ed symptomatic improvement in vomiting, abdominal pain, and dysphagia. The mean time to improvement was only 8.5 days and a drop of 33.7 to 1.0 eos/hpf was observed in those treated (8). In contrast to earlier studies with small numbers this study showed that in a large population earlier trends could be repeated on a larger scale. Therefore in 2007 the first consensus statement= for EoE was published with diagnostic criteria for the disease. Diagnostic crit= eria can be found in Table 1 below.

Presence of= Symptoms

Adults

Dysphagia=

Heartburn=

Retroster= nal chest pain

Odynophag= ia

Regurgita= tion

Food Impa= ction

Children

Heartburn=

Dysphagia=

Nausea/Vo= miting

Abdominal= pain

Regurgita= tion

Failure t= o Thrive

Histologic = Findings

1. Patients must have biopsies after 6–8 weeks= of twice daily acid suppression with proton pump inhibitors or have a docume= nted negative pH study.

2. Normal gastric and duodenal biopsies

3. Esophageal biopsies ≥15 eos/HPF

Table 1. Showing diagnostic = criteria for EoE determined in the 2007 consensus statement (9).

Epidemiology and Characteristics of Disease

At this point in the evolution of defining the disease= we had ruled out reflux as the primary culprit, assumed allergy as the new tar= get for disease development, and set diagnostic criteria, but there was still a= lot more to learn about the disease.

EoE seems to be relegated to the westernized world. Pr= evalence studies have been performed to look at just how many of us are affected. A random population survey was performed on 3000 adults, and 1563 were invite= d to have an endoscopy performed based on survey findings suggestive of upper gastrointestinal disease. Of the 1563 patients, 100 had endoscopies perform= ed with biopsy. Eosinophilia was present in 5% of patients but only 1% met histologic criteria for EoE (10). One study showed that prevalence is actua= lly on the rise and that it mirrors atopic or allergic disease increases over t= he same time period. In 1995 the prevalence was only 0.5/100,000, but in 2004, just 10 years later the prevalence was nearly 8.9/100,000 (11). Part of the= se increases can be attributed to better awareness of the disease as an entity, but there is a clear increase over the 10 year period.

Males represent approximately 60-80% of cases and this= is thought to be in part to the cytokine IL-13 being present on the X chromoso= me (11). Since males have only one copy they are more susceptible to mutations. The age at presentation is bimodal with adults presenting within the 4^=
th to 6^th decade and children presenting between 5 and 10 years of = age. It is still unclear whether childhood disease progresses into adulthood giv= en the lack of longitudinal studies. Genetics plays an important role with 7% = of patients having a parent with EoE or a stricture and 5% having a sibling wi= th EoE.

Children with EoE tend to present with more systemic symptoms such as nausea and vomiting, abdominal pain, and failure to thrive (1). More children are affected by foods than adults by comparison (70% vs = 30% respectively). Those with IgE mediated forms tend to be less responsive to = long term corticosteroid therapy and strictures are rarely present in children supporting the idea that this is a chronic disease. Again it is common for children with EoE to have parents with longstanding dysphagia or documented eosinophilia/strictures on endoscopy.

The natural history of disease has shown that most pat= ients with EoE have a lag of 4.3 years between symptom onset and the diagnosis of disease. It is restricted to the esophagus and is a chronic disorder. The chronicity can be either chronic persistent with no intermittent relief or chronic relapsing with spontaneous resolution of symptoms at any time durin= g the course of disease followed by recurrence. Prolonged disease leads to remode= ling of the esophagus with fibrosis and stricture formation, however unlike refl= ux disease and Barrett’s esophagus, EoE is not associated with any premalignant or malignant transformation to date. A 17 year database has al= so shown no deaths related to EoE. One study looked at quality of life issues = and showed that about 50% of people with disease just learn to deal with the symptoms however the other 50% require diet and lifestyle modifications. So= me patients will actually refuse solid foods unless they have water or other liquids to help wash the food down (12).

Several conditions have been shown to be implicated wi= th EoE in otolaryngology. Clearly allergies are implicated in anywhere from 60-80%= of patients, and rhinosinusitis is present in about 19-25% of patients. Other = diseases found to be associated have been laryngitis, subglottic stenosis, and recur= rent croup (13).

Pathophysiology

While there are still many facets to the disease proce= ss to be worked out it is clear that EoE is a multifactorial disease. Genetics, t= he immune system, and environmental or external allergens all seem to play a r= ole, but how do we know that there are multiple pathways involved. First, allerg= ic disease is present in some but not all patients with EoE, so allergy cannot= be the only cause. Second, only a minority of patients present with anaphylaxi= s. This argues that the classical IgE mediated response is not the primary pla= yer in the immune system. Third, seasonal variation disease has led to the stud= y of aeroallergens. Allergens have been shown to increase IL-5 and IL-13, both of which are cytokines from the Th-2 cell mediated hypersensitivity pathway (1= 4).

As the Th-2 cell mediated hypothesis gained ground, se= veral studies were performed to determine how the process actually unfolds. Two studies looked at epicutaneous exposure of antigens and showed that despite= a strong systemic Th-2 response, chronic cutaneous exposure of antigen, bone marrow eosinophilopoiesis, and circulating eosinophilia; EoE and lung inflammation could not be obtained. In the presence of a nasal challenge of antigen, however, a robust inflammatory reaction and episode of EoE could be produced (15, 16). Another study looked at knockout mice deficient in IL-4, IL-5, and IL-13 who were unable to amount a response to antigenic stimulati= on unless intratracheal IL-13 was administered. Upon administration both airway and esophageal eosinophilia ensued (17,18). Taking these studies into consi= deration it was proven that both external triggers as well as a strong intrinsic Th-2 response was required thus making the argument that this disease was in fact multifactorial.

As I discussed earlier, genetics plays a healthy role = in the development of the disease as well. Certainly atopic disease can be passed = on from parents to child. Also males are more affected than females potentially due the two changes for the IL-13 receptor being located on the X chromosome (14). More importantly is the presence of eotaxin-3. This substrate/gene has been found to be the signature gene for EoE. It is a powerful eosinophil activator and chemo attractant and is induced in all patients with EoE regardless of allergy, gender, or in patients with associated reflux. IL-13 actually induces eotaxin-3 in keratinocytes through the STAT-6 pathway lead= ing to epithelial proliferation and fibrosis. Mice with genes targeted against = the eotaxin-3 receptor, CCR3, are protected from the development of the disease. One single nucleotide polymorphism of the gene has been found in EoE patien= ts and is 50 times more prominent compared to normal controls (18).

The esophageal epithelium is the only GI segment devoi= d of eosinophils. Therefore any eosinophilia is pathologic. The epithelium of the esophagus is squamous but not keratinized and therefore the esophageal lini= ng is directly exposed to esophageal contents as well as their antigens. There= fore the esophageal epithelium is though to play a role in the induction of esophageal inflammation (19).

Cytokines involved in the Th-2 response are mainly IL-= 5 and IL-13. IL-5 is the most specific cytokine for the eosinophil. It is involve= d in the growth, differentiation, activation, survival and maturation of the cell and has been show to be overexpressed in esophageal biopsies of patients wi= th EoE. Interestingly, studies have also shown that mice deficient in IL-5 do = not produce an esophageal response to antigens, thus proving that IL-5 is criti= cal in the development of the disease. IL-13 is a more no-specific cytokine tha= t is more involved with the systemic aspect of atopic disease. Overexpression of IL-13 leads to eosinophilia, mucous hyper production, and airway hyper responsiveness, and has been implicated in the development of asthma, atopic dermatitis, and allergic rhinitis. Again, studies looking at patients treat= ed with intratracheal IL-13 show inflammation of both the lungs and esophagus (19).

Once all the above players have been assembled it is u= p to the mast cells and eosinophils to produce their effects locally. Mast cells represent the IgE mediated pathway of disease with preformed antibodies and eosinophils represent the non-IgE cell mediated response, both of which are implicated in the disease process. Both cells release lipid mediators that induce smooth muscle contraction, vascular permeability, and mucous secreti= on, but they also release leukotrienes and TGF-β which lead to the recruitment= of inflammatory cells and tissue fibrosis. Below is a schematic describing the pathogenesis of the disease process in Figure 1 (19).

Figure 1. This figure shows the pathogenesis of EoE. First allergens are engu= lfed by antigen presenting cells (APC’s) near the esophageal lumen or skin. The APC then presents the antigen to a T cell which then goes on to induce = both IgE mediated and Th-2 cell mediated pathways. B cells that have been activa= ted produce preformed antibodies that attach to mast cells through the IgE medi= ated pathway. T cells that have been activated produce cytokines that attract eosinophils to the esophageal lumen through the non-IgE mediated pathway. W= hen an antigen is encountered both eosinophils and mast cells degranulate, increasing inflammation and vascular permeability, thus increasing the infl= ux of other inflammatory cells. Once the inflammatory reaction is present eotaxin-3 and TGF-β produce epithelial hyperplasia and fibrosis and the reaction continues until an intervention is made. Mishra A. Mechanism of eosinophilic esophagitis. Immunol Allergy Clin North Am 2009; 29(1): 29-40

Making the Diagnosis

At this point we have talked a lot about the disease process, but have neglected the disease findings. For patients that come to= the office complaining of dysphagia, the differential diagnosis can be vast. Allergy and reflux are often diagnoses that come to mind first, but it is entirely possible for the problem to be infectious. Candida, CMV, HSV, parasites, and bacteria may all cause similar complaints. Autoimmune disease such as celiac, inflammatory bowel disease, scleroderma, and autoimmune enteropathy are also possibilities. Therefore it is important to keep an op= en mind especially for patients complaining of residual disease despite adequa= te therapy.

Pointed historical questions are important since patie= nts with EoE have very specific complaints. If you suspect EoE you should eluci= date if there is any food avoidance, if they eat very slowly, if they chew excessively, if they have to drink water after each bite of food, or if they have other gastrointestinal complaints to suggest another etiology. Although physical exam is important in all patients it is likely going to be very be= nign in the patient who has EoE or other esophageal disorders. The esophagus is buried deep in the neck and chest and therefore we rely on endoscopy to actually appreciate any pathology.

In the consensus statement on EoE from 2007, many reco= mmendations were made regarding the ancillary tests used to evaluate patients with EoE = (9). Below these tests will be discussed individually.

Laboratory testing has been evaluated in its ability to identify severity or progression of disease. Peripheral eosinophilia has been found in approximately 5-50% of patients and IgE levels are elevated in up to 7= 0% of patients with eosinophilia (20). Although these numbers are impress= ive, remember that many patients with EoE have other atopic diseases and go= od reasons to have elevated eosinophil and IgE levels. Therefore it is recommended that neither test be used to diagnose or predict progression of the disease.
pH studies are required for the diagnosis of EoE unless a patient has been treated with 6 weeks of PPI therapy in order to rule out GERD. Twenty studies have reported on patients with EoE who have had pH studies performed. In 228 adults 40% were studied with pH probes and 82% were normal. Of 223 children 78% were evaluated with pH probes and 90% were= found to be normal (9). Therefore the recommendation is that pH testing is required only initially to rule out reflux disease and then only if the provider believes that reflux has developed later in the disease proce= ss.
Manometry has been reported in 10 studies of patients with EoE. The lower esopha= geal sphincter (LES) is normal in 66/77 patients however 10 have shown hypotensive LES and 1 was shown to have hypertensive LES. Peristaltic abnormalities were found in 30/77 patients but the majority show nonsp= ecific peristaltic abnormalities. Of the 14 children that have been reported = on, none have shown any abnormalities. Clearly this shows that manometry studies can show abnormalities in over half of the patients who were studies but it provides no diagnostic value and is therefore not requi= red unless patients have specific complaints.
Upper gastrointestinal series with contrast have been shown to be discordant with endoscopy findings. Many times a stricture will be seen on plain films however this is often due to intermittent contraction of the esophagus appearing like a stricture. Nonetheless contrasted studies c= an help identify strictures, small caliber esophagus, malrotation, and hi= atal hernia and are recommended as ancillary tests in pediatric patients wh= o have a negative endoscopy to help identify other sources of the problem.

Because these other tests are not recommended for routine evaluation of the dysphagia patient, and because physical exam is n= ot reliable as a diagnostic tool, we rely on endoscopic findings. Unfortunately there are no “cardinal signs” of EoE (21). Thus making the diagnosis with endoscopy alone is difficult and this is why we rely on biop= sy specimens to show us what is going on beneath the surface.

Common finding on endoscopic examination can inc= lude: crepe paper mucosa, friability, shearing, edema, white plaques, linear furrowing, small caliber esophagus, concentric mucosal rings, and stricture= s. Thirty percent of children and 9% of adults will have a visually normal endoscopy (22,23). The normal endoscopic exam will show smooth mucosa, prominent submucosal vessels, and a whitish pink color. Linear furrowing wi= ll be present in 25 to 100% of patients and loss of vascularity occurs in about 93% of patients. White exudates can be challenging to determine whether or = not they are due to microabscesses of eosinophils, or if they are candida infections. The sensitivity of white exudates is only 30-50% for EoE, howev= er the specificity is 95% (21). It is important to differentiate between GERD = and EoE. GERD may present with linear furrowing similar to that seen in EoE how= ever there will also likely be a distal component of ulceration near the gastroesophageal junction. Also, strictures in EoE tend to occur both proximally and distally whereas isolated distal strictures are more commonly seen in reflux.

As stated previously the= need for biopsy is paramount. If the distal esophagus is the only place biopsied, nearly 20% of the time you will miss the diagnosis (24). In order to achiev= e a sensitivity of 10% you must take 4 biopsies in children and 5 biopsies in adults (24,25). Therefore the recommendation is to take 4 biopsies distally (5cm above GE junction) and 4 biopsies proximally (10cm above distal site),= in order to have adequate samples. It is important to remember that biopsies of the stomach and duodenum are also required as part of the diagnostic criter= ia for EoE.

After biopsies are performed there are several histologic findings that may be seen under standard H&E staining. Basal layer thickening and increase rete papillae will be present as will the cla= ssic >15 eos/hpf. Eosinophils are often scattered superficially in the esopha= geal epithelium and microabscesses can form when there are more than 4 eosinophi= ls clustered together at the surface. These microabscesses produce the white exudate seen on endoscopy. Finally eosinophilic degranulation can occasiona= lly be seen as well.

The Role of Allergy Testing

It has been shown that allergy is involved in the pathogenesis of EoE. As any allergist worth their salt will tell you, avoid= ance is the key to any successful anti-allergy regimen. There are two types of testing commonly performed in patients with EoE: skin prick testing (IgE mediated) and atopy patch testing (non-IgE mediated). Skin prick testing is standardized and has been show to produce very consistent results. Atopy pa= tchy testing is much more variable in it preparations and methodologies but beca= use it is able to associate Th-2 type responses, it is helpful in the evaluatio= n of EoE patients.

A study by Penfield et al looked at allergy test= ing in a group of patients with EoE. 50% of patients testing had ≥1 food allergy, 93% of those tested had ≥1 aeroallergen, and overall 81% of patients had ≥1 allergy (26). The most common allergic foods were pea= nut, egg white, soy, cow’s milk, and tree nuts.

Complications of Disease

EoE is a chronic disease that progresses to tiss= ue remodeling and fibrosis within the esophagus. Therefore many structural cha= nges can lead to complications. Strictures for instance are present in a bout 57= % of patients on endoscopy, however they are much less common in children at onl= y 6% (6). Because strictures form narrow regions within the esophagus they predispose patients to the ever dreaded food impaction. Amazingly, food impaction occurs in nearly 60% of patients with EoE and about 50% of patien= ts with food impaction will eventually be diagnosed as having EoE (1). Food impaction is characterized by retrosternal discomfort, delayed passage of t= he bolus, and followed by hypersalivation. Meats and dry rice are often the culprits, and obstruction can persist for hours.

Secondary reflux is a common problem as chronic inflam= mation can lead to hypotension of the LES. Remedios looked at 26 patients with chr= onic EoE and found that 10/26 had reflux on pH probe testing and 8/10 showed red= uced LES pressures on manometric studies (27). Therefore it is important to cons= ider that although initially EoE patients are reflux free, they may eventually become symptomatic and require therapy.

Candida infections are a common complication of steroid therapy but can also occur spontaneously in EoE. It is important to get biopsies of the esophageal mucosa to decipher infection from eosinophil microabscess.

Finally, the most feared complication is esophageal ru= pture or Borhaave’s disease. Three cases have been reported in the literatu= re and all have involved severe/prolonged retching and vomiting during a gastrointestinal infection or impacted food bolus (1). Although this is an uncommon complication it is one to be aware of due to is dreaded consequenc= es.

Treatment<= o:p>

Because of the multifactorial process of EoE, providers have attempted several therapies for the disease process. Dietary modifications, steroids, anti-inflammatory drugs, and supportive therapies = have all been evaluated and several novel therapies are still under evaluation. =

Although there has been no randomized control tr= ial looking at the effects of an elemental diet on EoE, several case reports ha= ve been studied. Case series data have shown 92-98% response rate to elemental diets both symptomatically and histologically. Patients are usually treated= for 6 weeks with reintroduction of the least antigenic foods first (vegetables = and fruits) and going to higher protein foods last. Foods are reintroduced with about 1 new food per week and patients are re-evaluated with endoscopy and biopsy after every 5-7 new foods to look for recurrent disease (28). This process can be very psychosocially daunting and is often very difficulty to follow. Because these diets are so difficult to follow others have attempted elimination diets where the most antigenic foods are removed from the diet rather than all food altogether. Dairy, soy, egg, wheat, beef, peanut, and = corn are the usual offenders. Reports have shown that 74% of patients will respo= nd symptomatically and histologically to this diet (28).

Because this is an inflammatory condition steroi= ds were often attempted as a first line agent. Prednisone at 1mg/kg/day up to a maximum of 60mg/day has been shown to improve both symptoms and histologic findings in 95% of patients, however upon stopping therapy, 90% of patients will show recurrence (28). Because of the long term consequences of systemic steroid therapy we consider this to be used only for acute exacerbations or= for refractory cases. In contrast to systemic steroids topical steroids have be= en shown to be just as effective. In a randomized control trial of 80 patients= on prednisone versus topical fluticasone for 4 weeks with an 8 week weaning pe= riod. Ninety-eight percent showed complete symptom relief and 94% showed complete histologic response with no significant differences between the groups stud= ied. Forty-five percent of patients relapsed by the 24 week follow up just 12 we= eks after weaning off the steroids (29). Therefore it is argued that topical steroids with long term management is the first line therapy and treatment = of choice. Since this study budesonide has also shown promising results. Oral candidiasis has been found to occur in about 15% of patients treated with topical steroid therapy (29).

Anti-inflammatory drugs have been evaluated and cromolyn has not been shown to be an effective agent at all. Montelukast, a leukotriene inhibitor on the other hand, has been evaluated with minimal success. Attwood et al. in 2008 looked at a small number of patients (n=3D8= ) and treated them with 100mg initially with a maintenance dose of 20-40mg daily = for up to 14 months. All but one showed symptom relief but upon stopping the medication, 6/8 had recurrence of symptoms (30). In addition to small sample size, another weakness of this study was that they did not evaluate patients with repeat endoscopy and therefore eosinophilia/histologic response could = not be evaluated.

Several novel therapies are currently under clin= ical trials. Mepolizumab is a monoclonal antibody against IL-5 and has shown some good results in early clinical studies. Anti-TNF-β has also been evalu= ated to try and decrease hyper vascularity and fibrosis. Both are awaiting furth= er clinical trial data prior to large scale therapy, but will probably be rese= rved for refractory cases due to the expense of the medication.

Supportive therapy include stricture dilatation = and food disimpaction as indicated. Stricture dilatation is looked at as a last resort when medical treatment has failed or patients develop a food impacti= on. There have been reports of esophageal tears or perforations upon instrumentation of the esophagus. In 2008 Schoepfer et al. looked at a small series of patients that were resistant to medical therapy. All patients experienced prompt relief after dilatation, with mild odynophagia post-procedure, no complications and sustained response for 6 months (31). A systematic review of all papers describing esophageal dilations was reporte= d in 2010 looking at esophageal dilations in 468 patients with 671 dilations performed. Most authors reported mucosal tears but only one perforation was descr= ibed leaving a perforation rate of 0.1% (32).

Conclusion and Future

EoE is a new disease that is becoming increasing= ly common in the westernized world. It is a diagnosis of exclusion, the pathogenesis is multifactorial, and the keys to diagnosis are history and endoscopy with biopsy. Much is still left to be learned about the disease however. The future requires that we answer questions about non-invasive markers of disease, long term management strategies, developing novel therapies, whether we treat the symptoms or the eosinophilia, and finally should we be empirically treating all patients with PPI’s. The past 10 years has brought many= new ideas to the table and the next 10 will be just as important.

DISCUSSION: = HAROLD PINE, MD

That was a nice review Dr. Cou= ghlin and certainly one of those interesting problems that we need to be aware of= in ENT. A couple of things strike me. Number one, all the great pictures you showed were clearly from flexible endoscopes with the ability = of insufflation. It’s hard= to get those nice views with the rigid endoscopes so commonly used in ENT practices. That said, more an= d more ENT surgeons are becoming proficient with the flexible TNE scope. (Transnas= al esophagoscope). I encourage t= he residents to see out opportunities to learn this technique while in trainin= g.

Number two, based on the crite= ria you showed to make the diagnosis, you have to have biopsies from the stomach and duodenum which we’re not doing. We are down there in the esophagus and certainly are capable of doing esophageal biopsies but I get the sense = that most ENT surgeons would not be doing the multiple level, multiple quadrant technique. Every once in a wh= ile during a microlaryngoscopy and bronchoscopy in children I’ll do a postcricoid biopsy, more to just look for changes of reflux versus this eosinophilia esophagitis. But= the thing I wonder about, and it would make a really nice prospective study, is= why not for any patient that does come in with a food bolus stuck in their esophagus, as part of bringing them to the operating room, sign them up to = do some biopsies to rule this out. If that statistic is right we’re going to have a pretty good hit rate and not only are we going to make them better, we can perhaps figure out why th= ey got it in the first place.

I suppose the best take home p= oint for me would be if you suspect this issue or are having kids with presumed reflux not getting better with medical management, refer to a gastroenterologist and perhaps an allergist as well. =

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