PPI-responsive Esophageal Eosinophilia Research Articles

Letter: response of eosinophilic oesophagitis to proton pump inhibitor therapy—the importance of biopsies at index endoscopy

LINKED CONTENTThis article is linked to Frazzoni et al paper. To view this article, visit https://doi.org/10.1111/apt.16371

Eosinophilic Esophagitis in Children: Clinical Findings and Diagnostic Approach.

Eosinophilic esophagitis (EoE) is an emerging chronic immune and antigen-mediated clinicopathologic disease. During the last 2 decades, the incidence of this condition in children has increased significantly, thanks to practitioners for creating the awareness and higher use of diagnostic endoscopy. We have analysed paediatric literature on EoE focusing on the epidemiology, pathophysiology, clinical findings and diagnostic approach.EoE is pathogenically related to a Th2 inflammation characterized by a mixed IgE and non-IgE-mediated reaction to food and/or environmental agents. This leads to esophageal dysfunction and remodeling accompanied by subepithelial fibrosis. EoE can be presented with several range of gastrointestinal symptoms, including regurgitation, vomiting, feeding difficulties or feeding refusal in infants and toddlers, as well as heartburn, dysphagia and food bolus impaction in older children and adults. The diagnostic suspicion is based on the presence of chronic symptoms of esophgeal dysfunction and esophageal eosinophilia characterised histologically by a significant eosinophilic infiltration of the oesophageal mucosa (>15 eosinophils per high powered field). In this review, we will provide an update on clinical presentation and diagnostic approach to EoE in children. We emphasized on the relevant aspects of the new clinical condition termed “PPI responsive esophageal eosinophilia”, as entities distinct from EoE and the role of PPI trial in the diagnostic workup, therefore we proposed a new diagnostic algorithm.

DOZ047.120: The role of proton-pump inhibitors in eosinophilic esophagitis: focus on esophageal atresia children

Abstract Introduction Since recently, after detection of eosinophilic predominant inflammation of esophagus a trial with proton-pump inhibitors (PPIs) was needed to individuate children with PPI-responsive esophageal eosinophilia (PPI-REE), only those non-responders received eosinophilic esophagitis (EoE) diagnosis. In 2018 updated international consensus suggested removing the PPI trial as a diagnostic criterion and consider PPIs as a treatment together with diets and topical steroids. The role of PPIs is evaluated in children with esophageal atresia (EA) and EoE versus EoE from general population. Method A retrospective chart review of both children with EA and EoE followed-up from at January 2005 has been performed. According to ESPGHAN guidelines published in 2014 patients showing eosinophilic inflammation received high-dose PPI trial to identified PPI-REE. Those non-responders were labeled as EoE and underwent to dietary and/or topical steroid treatment. Demographics and disease characteristics of EA patients with EoE were analyzed and compared with those with EoE from general population. Results Overall, 370 EA and 118 EoE patients were analyzed. Of them 15 EA-EoE patients were detected. Consequently, in our cohorts, 4.0% of EA patients developed EoE. Male-to-female prevalence ratio was of 2.55 with no difference in gender prevalence between groups. At diagnosis EoE-EA children were significantly younger compared to EoE group (mean: 5.1 vs 10.8 years; P < 0.0001). Peak EOS/HPF at diagnosis did not differ between groups (50.1 ± 26 vs 59.8 ± 29 EOS/HPF). No difference was observed in allergy prevalence between groups (53.8 vs 68.0%). PPI-REE was significantly more prevalent in EA-EoE group that in EoE group (66.6% vs 19.4%; P = 0.0004). Conclusion Similar gender distribution and high prevalence of allergy suggest that common genetic susceptibility factors for EoE exist. However, high prevalence of PPI-REE coupled early EoE onset might also suggest that other factors (e.g. esophageal motility disorders) might play a physiopathological role in EoE development in EA children. Our study suggests that a stepwise approach with PPIs as a first-line treatment for EoE management in EA children should still be considered.

Eosinophilic Esophagitis (EoE) - Successful Treatment With PPI Therapy in a Single-Center - Education and Engagement Are Key

Introduction: Recently, the international EoE consensus eliminated the cumbersome terminology of PPI-responsive esophageal eosinophilia. This supports our practice over the last 7 years of using PPI’s as first line therapy for EoE patients because of convenience, cost, and ease of administration. Here we present our single-center experience in treating EoE. Keys to success involve intense education on appropriate drug dosing, the mechanism of PPIs being anti-eosinophilic, and the key role of strict adherence to a proper PPI trial. Methods: From 2011 to 2017, patients at our institution with confirmed EoE were enrolled sequentially into a database. EoE diagnosis required the combination of clinical symptoms, endoscopic features, and histologic confirmation. In a retrospective manner, data was analyzed as outlined in Figure 1.379 Figure 1 No Caption available.Results: 77 patients (mean age 37, range 17-71, 69% male) with confirmed EoE were treated at our center. A PPI trial was completed on 71/77 (92%) patients with 50/71 (70%) patients having response. Complete response was seen in 44/50 (88%) and partial response in 6/50 (12%). Of those with a complete response, 27/32 (84%) were able to be reduced to once daily PPI maintenance therapy, but 5/32 (16%) relapsed. Of 33 patients with fibrostenotic EoE, an average of 2.3 dilatations were needed to reach a final average esophageal diameter of 17mm. Symptom relief was achieved in 85%; no perforations occurred. Ten patients (13%) were treated with topical steroids. Overall, 7/10 (70%) were steroid responsive. Selective diet elimination based on food allergy testing was successful in 7/8 (88%). Six-food elimination diet as primary therapy in one patient received a complete response. Conclusion: Our 70% response to PPI therapy in our EoE population over 7 years is on the high end of the reported range of 33-80%. The reason for our success in this unselected population may be due to intense education and engagement fostered in our patients. Our patients understand the drug mechanism of action/dosing, are very compliant with the PPI trial, and often rewarded by not needing topical steroids or diet restriction. In addition, the 85% with complete response were decreased to once daily PPIs, thereby lessening concern over potential side effects of long term high dose PPIs. Conclusion In our practice, PPIs have a 70% response rate in unselected EoE patients. Our excellent success may be related to intense education and engagement with our patients.

Implementation of guidelines in eosinophilic esophagitis at an academic pediatric practice.

Guidelines for eosinophilic esophagitis (EoE) require high-dose PPI (HD-PPI) trial to evaluate for PPI-responsive esophageal eosinophilia (PPI-REE) prior to EoE diagnosis and dedicated therapy. This involves a second esophagogastroduodenoscopy (EGD) to assess for PPI-REE. This study is to evaluate adherence to current guidelines in evaluation of PPI-REE and EoE. Retrospective review of new patients treated with HD-PPI after an index EGD showing>15 eos/hpf in esophageal biopsies. One hundred and eighty patients had an index EGD with esophageal eosinophilia of>15 eos/hpf. Of these, 97/180 (53.8%) received HD-PPI; remaining 83/180 were prescribed other interventions without a HD-PPI trial. Of the 180 patients, 143 (79.4%) patients returned for follow-up and of whom 96/143 (67.1%) underwent repeat EGD. Adherence to guidelines improves with time. Patients are vested in care.

Sa1142 - Absolute Peripheral Eosinophil Count Independently Distinguishes Eosinophilic Esophagitis from PPI-Responsive Esophageal Eosinophilia

Sa1142 - Absolute Peripheral Eosinophil Count Independently Distinguishes Eosinophilic Esophagitis from PPI-Responsive Esophageal Eosinophilia

Evaluation of symptomatic esophagogastric junction outflow obstruction.

Esophagogastric junction outflow obstruction (EGJOO) may be due to anatomical abnormalities, but it is unclear how to evaluate them after high-resolution manometry. We aimed to determine (i) clinical and high-resolution manometry parameters differentiating anatomical EGJOO from functional EGJOO, (ii) investigations chosen and yield for anatomical EGJOO, and (iii) clinical outcomes of functional EGJOO. Medical records of consecutive patients with symptomatic EGJOO from February 2012 to December 2015 were reviewed. EGJOO was defined as anatomical if investigations identified a macroscopic or microscopic pathology accounting for EGJOO. Forty of 292 (13.7%) had EGJOO, of which 6/40 (15%) had anatomical EGJOO (two PPI-responsive esophageal eosinophilia, two infiltrating cancers, and two external compressions). Anatomical EGJOO was more likely to present with dysphagia (100% vs 29.4%, P=0.001) and less likely with regurgitation (0% vs 41.2%, P=0.05). Anatomical EGJOO had higher frequencies of premature contraction (50% vs 5.9%, P=0.003) and lower mean values of distal latency (5.6 +/- 1.3 vs 6.7 +/- 1.2, P=0.004). Computed tomography scans revealed 50% (3/6) of etiologies of anatomical EGJOO. Approximately, 73.5% (25/34) of patients with functional EGJOO had spontaneous resolution of their symptoms. One underwent pneumatic dilatation with symptom resolution while remaining eight with persistent symptoms were attributed to gastroesophageal reflux disease. Anatomical causes are present in 15% of EGJOO. Evaluation is warranted especially in patients presenting with dysphagia. Esophageal biopsies, barium swallows, computed tomography scans, and endoscopic ultrasound are complementary in EGJOO evaluation. In patients with non-obstructive symptoms and no anatomical etiologies, monitoring for spontaneous resolution is an option.

Eosinophilic esophagitis in Japan: Focus on response to acid suppressive therapy.

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition characterized by esophageal dysfunction and dense eosinophilic infiltration of esophageal epithelium. According to clinical consensus and guidelines published in 2011, esophageal eosinophilia was classified into two entities based on response to proton pump inhibitor (PPI) administration: EoE and PPI-responsive esophageal eosinophilia (PPI-REE). We have performed a series of investigations to determine whether EoE is actually different from PPI-REE. Consistent with Western reports, more than half of our examined patients with symptomatic esophageal eosinophilia suggestive of EoE achieved histological remission with single PPI therapy. Furthermore, our comparisons of clinical, endoscopic, and histopathological findings between patients with EoE and those with PPI-REE revealed nearly no differences between them. We also compared gene expression profiles in mucosal biopsy specimens between those groups and found that microarray findings obtained from PPI-REE patients substantially overlapped with those from EoE patients, suggesting that both represent the same condition or are variations of a single disease. In addition, we have noted that more than half of EoE patients who show resistance to a PPI therapy respond to vonoprazan, a novel potassium-competitive acid blocker that has been shown to provide more potent and sustained suppression of gastric acid secretion than PPIs. Our results indicate that PPI-REE may constitute a subtype of EoE. Based on novel evidence including results obtained in our studies, the most recently updated guidelines have included responders to PPI therapy within the spectrum of EoE, abandoning the term PPI-REE.

Clinical Applications of the Eosinophilic Esophagitis Diagnostic Panel.

Eosinophilic esophagitis (EoE) is a recently recognized upper gastrointestinal allergic disorder characterized by esophageal dysfunction (e.g., dysphagia) and esophageal eosinophilia of ≥15 eosinophils/high-power field in patients who have persistent esophagitis even on proton pump inhibitor (PPI) therapy. The histologic method is the gold standard of EoE diagnosis. However, EoE clinical symptoms do not always correlate with histology, and the histologic method has sensitivity and specificity issues due to the patchiness of EoE and the subjective nature of the method. The “EoE transcriptome” was initially discovered in 2006, which led to the invention of the EoE diagnostic panel (EDP). In addition to providing a definitive EoE diagnosis with high accuracy, the EDP has been useful in elucidating several key elements about the disease including the efficacy of specific drugs such as swallowed glucocorticoids and anti-IL-13 humanized antibody therapy, the relationship between EoE and PPI-responsive esophageal eosinophilia, and predicting the disease course and responsiveness to therapy. The EDP’s long-term potential arises from its plasticity to incorporate new genes and uncover novel disease pathogenesis. We expect that the EDP will be increasingly helpful for personalized medicine approaches and improved diagnostics and disease monitoring.

Eosinophilic Esophagitis and Esophageal Granular Cell Tumor: An Unexpected Association.

Esophageal granular cell tumors (GCTs) are rare. Eosinophilic esophagitis (EoE) is an immune-mediated disease characterized by esophageal eosinophilia despite proton pump inhibitor (PPI) therapy. Given that GCTs occur at sites of scarring and inflammation, we sought to determine the prevalence of EoE in patients with esophageal GCTs. Our center's pathology database was searched for GCT specimens from 1995 to 2014. Slides were blindly rereviewed. GCTs were scored for atypical cytological features. Presence and number of eosinophils in the tumor and the surrounding esophageal epithelium and any EoE features were recorded. Medical records were reviewed. From >30,000 esophageal cases, 23 esophageal GCTs were identified, with 18 available for review (16 adult, 2 pediatric). Median patient age was 38.7 years. Four adults had esophageal intraepithelial eosinophilia (peak 38 to 68 eosinophils/high power field [HPF]); 2 confirmed to have EoE, 1 with PPI-responsive esophageal eosinophilia, and 1 had not received PPI therapy. Both pediatric cases had confirmed EoE (peak 24 and 34 eosinophils/HPF). In total, 12/18 GCTs had intratumoral eosinophilia (peak 1 to 16 eosinophils/HPF). All 6 cases with esophageal eosinophilia had intratumoral eosinophilia. Two GCTs displayed atypical cytologic features. Esophageal eosinophilia was present in 25% of adult and 100% of pediatric GCTs, the majority confirmed to have EoE. Overall, 67% of cases had intratumoral eosinophilia and 2 had atypical features. On the basis of these findings, we propose evaluating surrounding tissue for eosinophilia when esophageal GCT is diagnosed, and adding GCT as a potential complication of untreated EoE. Research for an immunologic link between EoE and esophageal GCTs is needed.

Diagnosis and treatment of eosinophilic esophagitis in clinical practice

Eosinophilic esophagitis (EoE) is a chronic and abnormal Th2 type immunological response characterized by intense eosinophilic inflammation localized within the esophagus. This leads to esophageal dysfunction and remodeling accompanied by subepithelial fibrosis. Recently, EoE has been recognized as one of the major causes of dysphagia or food impaction in adults. The prevalence of EoE has been increasing over the past several decades, particularly in Western countries. EoE should be differentiated from secondary esophageal eosinophilia (EE) in gastroesophageal reflux disease (GERD) and eosinophilic gastroenteritis, involving the entire gastrointestinal tract. EoE is an uncommon condition in Asia compared with Western countries. With the growing interest and awareness of this condition during the past decade, reports of this disease are increasingly emerging in Asian countries including Japan. Typical EoE does not respond to proton pump inhibitor (PPI) therapy according to the current Western diagnostic guidelines. However, some cases of EE exhibit symptomatic relief and histological improvement in response to PPI [i.e., PPI-responsive esophageal eosinophilia (PPI-REE)]. The understanding of the clinical manifestations and unique endoscopic images of EoE, differences and similarities between GERD, PPI-REE, and EoE will all serve as the differential diagnosis. Further knowledge of the indications and efficacy of PPI therapy and topical steroid therapy will also aid in the management of these diseases. In this article, we will review the current diagnosis and treatment of EoE in clinical practice.

Eosinophilic Oesophagitis: Current Understanding and Future Directions

Eosinophilic oesophagitis (EoE) is an emerging disorder that manifests clinically with characteristic symptoms of oesophageal dysfunction and histologically by tissue eosinophilia. This chronic immune-mediated oesophageal disease represents a response primarily to food antigens. The incidence of EoE is escalating in both adults and children. This rise stems not only from heightened recognition but also an increased frequency of allergic/atopic diseases and defective immune tolerance. In adults, EoE presents as intermittent solid-food dysphagia or food impaction, heartburn, and chest pain, typically presenting in young men with known allergies. Presentation differs in children, who experience upper gastrointestinal complaints: abdominal pain, vomiting, feeding difficulties, and/or failure to thrive. Endoscopic features include circular rings, linear furrows, white exudative plaques, strictures, and mucosal fragility. The pathologic hallmark of EoE is mucosal eosinophilia (>15 eosinophils per high-power field) isolated to the oesophagus. Such tissue eosinophilia must be distinguished from gastro-oesophageal acid reflux that responds to optimal proton pump inhibitor (PPI) treatment and from PPI-responsive oesophageal eosinophilia (PPI-ROE). Innovative modalities such as high resolution digitally-enhanced endoscopy and functional luminal impedance planimetry are emerging to better detect EoE and monitor its response to treatment. Current therapeutic strategies involve elimination and elemental diets to avoid food allergens, topical corticosteroids to counter the inflammatory response, and endoscopic dilation of fibrostenotic complications. Other treatments have employed immunosuppressants, antagonists to the leukotriene and T helper Type 2 inflammatory pathways, and biologics that target interleukins, tumour necrosis factor, or immunoglobulin E with variable success. This review highlights the current understanding of the epidemiology, pathogenesis, presentation, treatment, and natural history of EoE, and scrutinises current controversies and future directions for investigation.

Diagnosis and treatment of eosinophilic esophagitis in Japan

Patients in Japan affected by eosinophilic esophagitis (EoE), considered to be a dietary allergen related chronic esophageal disease, are slowly increasing. For diagnosis, careful assessments of atopic diathesis and symptoms, an endoscopic examination focusing on EoE characteristic findings, and histopathological examination of appropriate biopsy samples are important. When clinicopathological examination results suggest EoE, proton pump inhibitor (PPI) administration should be attempted to determine the response (PPI-responsive esophageal eosinophilia, PPI-REE). For PPI-refractory cases, oral topical glucocorticoid administration is the first therapeutic option, followed by systemic glucocorticoids as necessary. Evidence-based guidelines are currently under development in Japan for standardizing diagnosis and treatment.

PPI-Responsive Esophageal Eosinophilia: Is It Reflux Disease in Disguise?

National guidelines recommend that clinicians rule out proton-pump inhibitor (PPI)-responsive esophageal eosinophilia (PPI-REE) before diagnosing

Editorial: management of eosinophilic oesophagitis – efficacy vs. effectiveness. Authors’ reply

We thank Frazier et al. for their insightful commentary concerning our paper concerning the treatment outcome of adult patients with eosinophilic oesophagitis (EoE).1, 2 We agree with much of the analysis, although a few clarifications appear justified. The use of twice daily proton pump inhibitors (PPIs) for 8 weeks prior to the diagnosis of PPI-responsive oesophageal eosinophilia is (as eloquently summarised by Frazier et al.) an arbitrary intervention based upon the GERD treatment paradigm. Indeed, so called ‘step – down’ therapy, where the dose of PPI is reduced (and remission sustained in most patients) suggests that lower doses may be effective in treating the oesophageal eosinophilia.2 The mechanism whereby PPI's exert their therapeutic effect is of ongoing debate, and effects distinct from the ability to decrease gastric pH appear possible, including the ability to downregulate eotaxin-3 expression.3 It may however be premature to conclude that the ability of PPIs to increase gastric pH plays no part in treatment response. It is not unreasonable to propose that decreasing refluxate of acidic, and thus erosive, gastric contents will improve barrier integrity and lessen food antigen interaction with the immune system.4 Evolving research appears aimed at determining the significance of proposed impairments in barrier function in this patient group.4 Frazier et al. point out a number of potential limitations in study design including that perceived as a lack of treatment standardisation, no symptom report measures, and an intensive endoscopy protocol. It is our belief that treatment was standardised both in terms of dose and duration of medication (esomeprazole 40 mg PO BD or budesonide 1 mg PO b.d.), duration and sequence of dietary reintroduction, that endoscopic surveillance was the minimum necessary, and not dissimilar to previous studies, and that symptom report correlates poorly with disease relapse in any case.5 Furthermore, we utilised minimally invasive transnasal endoscopy without sedation in some patients.6 In the future, alternatives such as cytosponge may decrease the need for endoscopy.7 The difference between effectiveness and efficacy appears to hold particular significance when considering the steps required to institute successful dietary therapy in EoE. Previous studies had conclusively demonstrated that resolution of oesophageal eosinophilia can be achieved with dietary ‘restriction’.8, 9 What had been overlooked was the need to ‘reintroduce’ foods (requiring multiple gastroscopies) and then ‘maintain’ a diet. A clearer perspective of the difficulties likely to be encountered is thus achievable if this process is considered to entail multiple steps. The results of our study are testament to the real world difficulties of such a regimen. The authors’ declarations of personal and financial interests are unchanged from those in the original article.2

Mo1190 Comparative Analysis of the Association of Environmental Allergens in Eosinophilic Esophagitis versus PPI-Responsive Esophageal Eosinophilia

Mo1190 Comparative Analysis of the Association of Environmental Allergens in Eosinophilic Esophagitis versus PPI-Responsive Esophageal Eosinophilia

Mo1194 PPI-Responsive Esophageal Eosinophilia (PPI-Ree) Is Significantly Associated With Distal-Predominant Eosinophilia Compared to Eosinophilic Esophagitis (EoE)

Mo1194 PPI-Responsive Esophageal Eosinophilia (PPI-Ree) Is Significantly Associated With Distal-Predominant Eosinophilia Compared to Eosinophilic Esophagitis (EoE)

Oesophageal narrowing on barium oesophagram is more common in adult patients with eosinophilic oesophagitis than PPI-responsive oesophageal eosinophilia.

To date there have been no clear features that aid in differentiating patients with eosinophilic oesophagitis (EoE) from PPI-responsive oesophageal eosinophilia (PPI-REE). However, barium swallow roentgenography is a more sensitive and specific measure to detect subtle fibrostenotic remodeling changes present in EoE. We aim to characterise any clinical, endoscopic, histiological or barium roentgenographic differences between EoE and PPI-REE. To characterise any clinical, endoscopic, histiological or barium roentgenographic differences between EoE and PPI-REE. We performed a retrospective cohort analysis on data collected from a tertiary referral centre population from 2010 to 2015. Data from 66 patients with EoE and 28 patients with PPI-REE were analysed. Cases were adults who met consensus guidelines for EOE, and had a barium swallow study within 6 months of the index endoscopy. Clinical, endoscopic, histiological and barium swallow findings were collected. Patients with EoE reported similar characteristics as PPI-REE patients, except EoE patients were younger (35.6 vs. 46.6 years; P = 0.011), had earlier symptom onset (29.0 vs. 38.0 years; P = 0.026), and smaller oesophageal diameters on barium swallow (19.5 mm vs. 20; P = 0.042). Patients with EoE were more likely to have distal strictures (EoE 77% vs. 25%; P = 0.02) and, importantly, a greater likelihood of small calibre oesophagus (51.5% vs. 17.9%; P = 0.002). Moreover, EoE patients had a higher probability of developing small calibre oesophagus after 20 years of symptoms (72.3% vs. 30.2%; P = 0.074) compared to PPI-REE patients. When compared with eosinophilic oesophagitis, PPI-REE patients demonstrate findings that suggest PPI-responsive oesophageal eosinophilia to be a later onset, less aggressive form of oesophageal stricturing disease than eosinophilic oesophagitis.

A prospective open clinical trial of a proton pump inhibitor, elimination diet and/or budesonide for eosinophilic oesophagitis

Elimination diets and high-dose proton pump inhibitors (PPI) are advocated as first-line treatments in patients with eosinophilic oesophagitis (EoE). To record the treatment outcome for patients with EoE prospectively managed according to a clinical algorithm. Patients with oesophageal eosinophilia commenced esomeprazole 40 mg twice daily for 8 weeks. Those in histological remission were re-classified as PPI-responsive oesophageal eosinophilia. Nonresponders were offered the 6-food elimination diet with a PPI, or topical budesonide monotherapy (1 mg orally twice daily as an aqueous gel). Once disease control was achieved remission was reassessed at 3 months (all modalities) and an additional 6 months (diet group). Of 107 patients who completed 8 weeks of PPI, 25 (23%) were PPI-responsive. 56 of 81 (69%) of patients with EoE chose the elimination diet with PPI. 29 (52%) had complete remission, 23 completed dietary reintroduction and food triggers were identified in 20 (36%). 25 chose budesonide with 23/25 (92%) responding. Remission was sustained in >85% of patients at 3 months with all treatment modalities. At 9 months, only 10/18 (55%) of patients who responded to the elimination diet with PPI remained complaint and sustained remission. Many patients previously diagnosed with EoE will respond to PPI. Initial response >50% is possible with the elimination diet plus PPI, but many will fail to undergo food reintroduction, or will cease the diet and relapse, resulting in only one in four patient sustaining remission at 9 months. Budesonide is very effective short term, but longer term study is needed.

Current Management of Eosinophilic Esophagitis 2015.

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition characterized by esophageal dysfunction and eosinophilic infiltrate (≥15/hpf) in the esophageal epithelium and the absence of other potential causes of eosinophilia. The prevalence is increasing and is the most common cause of solid food dysphagia in children and young adults. This article will review the diagnosis and management of EoE based on consensus conferences, systematic reviews, and meta-analysis and highlights seminal studies in our evolving treatment of this disease. However, all answers are not available and I will remark about the lessons learned in my clinical practice seeing EoE patients over the last 25 years. The complicated etiology of the complaint of dysphagia in EoE patients will be reviewed. The importance of utilizing endoscopy, biopsies, and barium esophagram to help define the 2 phenotypes (inflammatory, fibrostenosis) of EoE will be highlighted. The controversy about PPI-responsive esophageal eosinophilia will be discussed and contrasted with idiopathic EoE. Finally, the 3 treatment options for EoE (drugs, diet, dilation) will be reviewed in detail and a useful clinical management algorithm presented.