Esophageal Eosinophilic Infiltration Research Articles

Animal models of eosinophilic esophagitis, review and perspectives.

Eosinophilic oesophagitis (EoE) is an allergen/immune-mediated chronic esophageal disease characterized by esophageal mucosal eosinophilic infiltration and esophageal dysfunction. Although the disease was originally attributed to a delayed allergic reaction to allergens and a Th2-type immune response, the exact pathogenesis is complex, and the efficacy of existing treatments is unsatisfactory. Therefore, the study of the pathophysiological process of EOE has received increasing attention. Animal models have been used extensively to study the molecular mechanism of EOE pathogenesis and also provide a preclinical platform for human clinical intervention studies of novel therapeutic agents. To maximize the use of existing animal models of EOE, it is important to understand the advantages or limitations of each modeling approach. This paper systematically describes the selection of experimental animals, types of allergens, and methods of sensitization and excitation during the preparation of animal models of EoE. It also discusses the utility and shortcomings of each model with the aim of providing the latest perspectives on EoE models and leading to better choices of animal models.

Эозинофильный эзофагит: что мы знаем и что мы можем?

Eosinophilic esophagitis is a chronic immune-mediated disease of the esophagus. It is characterized by severe eosinophilic inflammation of the esophageal mucosa and the develop-ment of submucosal fibrosis. Clinically, it is manifested by swallowing disorders. The pathogen-esis is based on genetically determined disorder of immune response and barrier function of the esophageal mucosa. The diagnosis of esophageal eosinophilic infiltration is established by clinical manifestations and morphology, after excluding diseases that cause esophageal eosinophilia. The criterion for diagnosis is intraepithelial eosinophilic infiltration with 15 or more eosinophils per field of view at magnification ×400 (or ≥60 eosinophils per 1 mm2). Secondary tests, such as measuring serum total immunoglobulin E levels, assessing peripheral blood eosinophilia, and skin allergy tests, are of lesser importance. The primary treatment for this condition is proton pump inhibitors. If the effect is insufficient, topical steroids and dietary restrictions may also be prescribed. Treatment effectiveness is evaluated 6–12 weeks after initiation by analyzing symp-toms and performing esophagogastroduodenoscopy with biopsy. Endoscopic dilatation is rec-ommended as a treatment option for patients experiencing severe dysphagia caused by esopha-geal narrowing. Biologic agents may also be considered as a possible treatment option. KEYWORDS: eosinophilic esophagitis, esophageal dysfunction, intraepithelial eosinophilic infiltration, proton pump inhibitors, topical steroids, diet, endoscopic dilatation, biologic agents. FOR CITATION: Belan E.B., Tibir'kova E.V. Eosinophilic esophagitis: current knowledge and management options? Russian Medical Inquiry. 2024;8(3):150–154 (in Russ.). DOI: 10.32364/2587-6821-2024-8-3-5.

Mast cells disrupt the function of the esophageal epithelial barrier

Mast cells (MCs) accumulate in the epithelium of patients with eosinophilic esophagitis (EoE), an inflammatory disorder characterized by extensive esophageal eosinophilic infiltration. Esophageal barrier dysfunction plays an important role in the pathophysiology of EoE. We hypothesized that MCs contribute to the observed impaired esophageal epithelial barrier. Herein, we demonstrate that coculture of differentiated esophageal epithelial cells with immunoglobulin E-activated MCs significanly decreased epithelial resistance by 30% and increased permeability by 22% compared with non-activated MCs. These changes were associated with decreased messenger RNA expression of barrier proteins filaggrin, desmoglein-1 and involucrin, and antiprotease serine peptidase inhibitor kazal type 7. Using targeted proteomics, we detected various cytokines in coculture supernatants, most notably granulocyte-macrophage colony-stimulating factor and oncostatin M (OSM). OSM expression was increased by 12-fold in active EoE and associated with MC marker genes. Furthermore, OSM receptor-expressing esophageal epithelial cells were found in the esophageal tissue of patients with EoE, suggesting that the epithelial cells may respond to OSM. Stimulation of esophageal epithelial cells with OSM resulted in a dose-dependent decrease in barrier function and expression of filaggrin and desmoglein-1 and an increase in protease calpain-14. Taken together, these data suggest a role for MCs in decreasing esophageal epithelial barrier function in EoE, which may in part be mediated by OSM.

Mucosal color changes on narrow-band imaging in esophageal eosinophilic infiltration.

This study aimed to examine the range of beige colored mucosa (BCM) in patients with esophageal eosinophilic infiltration (EEI) using narrow-band imaging (NBI).In this retrospective study, EEI was confirmed histologically in 12 consecutive patients from January 2014 to December 2017. The BCM tone on NBI without magnifying endoscopy was evaluated, and red, green, and blue (RGB) values of BCM and normal mucosa were measured. BCM was macroscopically classified into 2 groups (bright and dark) using cluster analysis. Histopathological analysis was performed in 1 patient who underwent biopsy for both normal mucosa and BCM.All 12 patients presented with BCM. Endoscopy revealed fixed rings, longitudinal furrows, mucosal edema, and exudate in 3, 12, 10, and 8 patients, respectively. Strictures were absent. Five patients had findings suggestive of gastroesophageal reflux disease. In the cluster analysis, 5 and 7 patients had bright and dark BCM, respectively. Consistent results were noted when we categorized patients according to their macroscopic characteristics. RGB values of the BCM and normal mucosa were measured—normal mucosa: R: 99.8 ± 16.5, G: 121.7 ± 23.1, and B: 93.4 ± 19.2; BCM: R: 152.0 ± 31.3, G: 123.9 ± 35.0, and B: 97.5 ± 29.5. BCM had significantly higher R values than normal mucosa (P = .0001). All parameters were significantly lower in the dark BCM group than in the bright BCM group (P < .001). Histopathological analysis revealed expansion of the epithelial intercellular space, eosinophilic infiltration, and basal cell hyperplasia at the BCM sites.BCM was observed in all cases of EEI. RGB values differed between bright and dark BCM. Assessing BCM tone using NBI is a potentially novel diagnostic method for EEI.

Immunogenetic, Molecular and Microbiotic Determinants of Eosinophilic Esophagitis and Clinical Practice-A New Perspective of an Old Disease.

Eosinophilic oesophagitis (EoE) is a chronic, allergic disease associated with a T-lymphocyte response inducing esophageal eosinophilic infiltration in the esophagus. Inflammation and tissue fibrosis are responsible for the main clinical symptoms such as food impaction and dysphagia. The etiopathogenesis is multifactorial in which genetic and environmental factors coexist. The most common trigger is a non-IgE-mediated food allergy to milk, wheat, egg, soybean, nuts, fish, and seafood. The second factor we focus on is the contribution of genetic variation to the risk of EoE, describing the expression profile of selected genes associated with eosinophilic oesophagitis. We raise the topic of treatment, aiming to eliminate inflammation through an elimination diet and/or use of pharmacologic therapy with the use of proton pump inhibitors or steroids and endoscopic procedures to dilate the esophagus. We demonstrate that early diagnosis and effective treatment prevent the development of food impaction and decreased quality of life. The increasing presence of EoE requires bigger awareness among medical specialists concerning clinical features, the course of EoE, diagnostic tools, and management strategies.

S3269 Common Presentations and Outcome of Eosinophilic Esophagitis in United States: Nationwide Inpatient Cohort Study

Introduction: Eosinophilic esophagitis (EoE) is a newly described disorder characterized by esophageal dysfunction and eosinophilic infiltration of the esophagus, once considered a rare entity, is becoming a commonly encountered gastroenterological condition. In addition to increased clinical recognition of EoE, rising EoE related hospitalization in the United States has been reported. We aimed to identify the most common presentations, medical and surgical outcomes Methods: A retrospective analysis utilizing the de-identified data from the National Inpatient Sample (NIS) was used to analyze patients hospitalized with Eosinophilic esophagitis as a primary admission diagnosis from 2004 through 2014. Hospital encounters for EoE were identified using the International Classification of Diseases (ICD-9) diagnostic codes; '53013'. The NIS is a component of the Healthcare Cost and Utilization Project, a national health care database developed through a partnership among federal and state governments and health care institutions sponsored by the Agency for Healthcare Research and Quality. We extracted the most common presentations, in-hospital diagnostic procedures, medical and surgical outcomes. Results: A total of 625,380 patients with a principal diagnosis of Eosinophilic Esophagitis were obtained through data analysis (2004 through 2014). The majority of the patients were between 35 and 79 years old, the most common presentations were: 49.6% presented with gastroesophageal reflux disease symptoms, 8.3% presented with dysphagia, 5.6% with atypical chest pain, 5.1% with vomiting, 4.1% with weight loss &failure to thrive, 3.7% with abdominal pain, and 1% with acute food impaction. Interesting associations with the EoE were asthma (4.7%), Food allergy (2.7%), and Atopic dermatitis (0.8%). 44.9% of the patients had Upper Endoscopy and Biopsy upon the same admission. The most common EGD findings were: Esophageal plaques or Candida (8.2%), Esophageal strictures (5%), Esophageal Furrows (4.7%), Steroid Use Induced infection (4.6%), Esophageal Ulceration (4 %), and esophageal rings (0.7%). Conclusion: In summary, national databases such as the NIS are handy tools to address questions surrounding low-frequency events like the EoE and outcomes that would otherwise escape study on a nationally representative level. However, caution must be used when interpreting results, as they are subject to several limitations.Table 1.: We Analyzed from the NIS data the most common presentations, in-hospital diagnostic procedures, medical and surgical outcomes between the years 2004 through 2014.

Simultaneous Examination of Eosinophil Infiltration in Esophageal Mucosa and Muscle in Patients with Achalasia: Direct Biopsy of the Esophageal Muscle at Per-oral Endoscopic Myotomy.

BackgroundThe relationship between eosinophilic esophagitis (EoE) and achalasia is not completely understood. There have been reports of eosinophilic infiltration of all esophageal layers in patients with achalasia. However, a routine endoscopic biopsy of the muscular layer is usually not feasible. We evaluate the safety and efficacy of muscle layer biopsy during per-oral endoscopic myotomy (POEM) as well as the prevalence of eosinophilic infiltration of the esophageal mucosa and muscular layer in patients with achalasia.Patients and MethodsAll enrolled patients had diagnosed achalasia and had simultaneous biopsies of the muscular layer at the middle esophagus and distal esophageal sphincter as well as the mucosal layer of the proximal and distal esophagus during POEM. All POEM procedures took place from August 2018 to December 2018 or September 2019 to November 2019. Various demographic, disease-related, and procedure-related data were collected from chart review. Eosinophilic infiltration in the biopsy specimen was examined.Key ResultsTwenty consecutive patients (65% female, age range: 21–84) with a pre-procedure Eckardt score of >6 were enrolled during the study period, with the duration of their achalasia ranging from 1 to 32 years. Eighteen patients had clinical symptomatic improvement after POEM, as defined by an Eckardt score <3. Endoscopic examination did not reveal any signs of eosinophilic esophagitis. Pathologic examination of biopsies revealed eosinophilic infiltration in three of 20 patients (15%) in the distal esophageal mucosa (all <15 eosinophils/HPF) and none in the proximal esophageal mucosa. There was no eosinophilic infiltration in the distal esophageal sphincter and the middle esophageal muscle. No complication was noted due to muscle biopsy.Conclusions and InferencesSubmucosal tunneling during POEM provides a safe access for direct esophageal muscle biopsy. This is the first report of the simultaneous biopsy of the esophageal mucosa and muscle in patients with achalasia. Contrary to all previously published studies, the association of esophageal eosinophilic infiltration and achalasia was not observed in this small sample study. Based on our findings, immune or autoimmune reaction rather than direct eosinophilic infiltration in the muscle is more likely the cause of achalasia.

MiR-4668 as a Novel Potential Biomarker for Eosinophilic Esophagitis.

IntroductionEosinophilic esophagitis (EoE) is a clinico-pathological diagnosis characterized by esophageal dysfunction and eosinophilic infiltration of the esophagus. Demonstration of esophageal eosinophilia (more than 15 eosinophils/hpf) in biopsy specimen obtained by esophagogastroduodenoscopy (EGD) continues to be the gold standard for diagnosis and monitoring of response to therapy. There is a growing necessity for non-invasive biomarkers that can accurately diagnose this condition and assess response to therapy. While microRNAs (miRNA) are being investigated in allergic diseases, including EoE, not many studies have explored the role of salivary miRNAs in EoE. MiR-4668-5p is a particularly interesting candidate, as it is predicted to regulate TGF-beta signaling and has not previously been identified as a target in any allergy disease. We sought to further investigate the role of miR-4668 as a biomarker to characterize and monitor response to treatment with swallowed topical glucocorticoids.MethodsAfter IRB approval, twenty-two adult patients with EoE were randomly enrolled to provide a saliva sample before and after 2 months of swallowed fluticasone therapy. Differences of miRNA expression before and after treatment were analyzed by paired T-test. A significance cutoff of <0.05 was used for all analyses.ResultsExpression of miR-4668 was higher in EoE vs. non-EoE subjects. The level of miR-4668 decreased in all subjects except one, with a mean fold change 0.49 ± 0.25. There was an association between miRNA expression and number of positive aeroallergens. The miR-4668 high group had a higher number of positive aeroallergen tests, while the miR-4668 low group had a greater number of subjects with drug allergies.ConclusionsIn this study, we identified that salivary miRNAs may serve as biomarkers to characterize EoE and response to topical corticosteroids. We specifically identified miR-4668 as a novel potential biomarker, which was not previously discovered as a target in EoE or any other allergic disease.

Oesophageal eosinophilia accompanies food allergy to hen egg white protein in young pigs.

Esophagitis with eosinophilia, inflammation, and fibrosis represent a chronic condition in humans with food allergies. In this investigation, we asked whether esophagitis with an eosinophilic component is observed in young pigs rendered allergic to hen egg white protein (HEWP). Food allergy was induced in young pigs using two protocols. In one protocol, sensitized pigs were challenged by gavage with a single dose of HEWP. Clinical signs were monitored for 24hours, and then, gastrointestinal (GI) tissues were collected for histological examination. The phenotype of circulating, ovalbumin (OVA)-specific T cells also was examined in HEWP challenged animals. In the second protocol, sensitized animals were fed HEWP for 28days. Animals were then examined by endoscopy and gastrointestinal tissues collected for histological examination. In pigs challenged by gavage with HEWP, clinical signs were noted in 5/6 pigs including diarrhoea, emesis, and skin rash. Clinical signs were not seen in any control group. Histological analysis revealed significant levels of oesophageal eosinophilic infiltration (P<.05) in 4/6 of these animals, with two also displaying eosinophilic infiltration in the stomach. Eosinophils were not increased in ileum or colon samples. Increased numbers of circulating, OVA-specific CD4+ T cells also were observed in pigs that received HEWP by gavage. In the group of animals fed HEWP, endoscopy revealed clinical signs of esophagitis including oedema, granularity, white spots, and furrowing, while histology revealed oedema, immune cell infiltration, and basal zone hyperplasia. Food allergy in the pig can be associated with esophagitis based on histological and endoscopic findings, including eosinophilic infiltration. The young pig may, therefore, be a useful large animal model for the study of eosinophilic esophagitis in humans.

P217 SAFETY OF ESOPHAGEAL DILATION IN PATIENTS WITH EOSINOPHILIC ESOPHAGITIS IN A SINGLE CENTER COHORT

Abstract Aim This study is aimed to assess the safety of esophageal dilation (ED) in a large cohort of eosinophilic esophagitis (EoE) cases in a single center. Background &amp; Method EoE, the leading cause of food impaction, is a chronic immune-mediated disorder characterized by esophageal dysfunction and mucosal eosinophilic infiltration (≥ 15 eos/hpf). ED is considered a second-line therapy for EoE after failure of medication, due to concern of perforation. We performed a retrospective review of EoE patients who received ED at University of Iowa Hospitals and Clinics from 2006 to 2018. ED types, complications, and symptomatic improvement were extracted via chart review. Descriptive statistic with univariate analysis was performed. Results Of 1050 EoE patients, 160 received 295 EDs, ranging from 1-12 dilations per patient, with 67 patients requiring &gt;1 dilations. Procedures were generally well-tolerated, without major bleeds or perforations. The overall complication rate was 6.1%, mostly post-procedural chest pain (4.8%). Three patients had sedation-related complications: one aspiration pneumonia and two ICU admissions for respiratory distress. Symptomatic improvement was documented in 87% of dilations on follow up. Conclusion EoE prevalence is increasing with rates of 1 cases per 1000 individuals, with up to one-third requiring ED for symptomatic relief. Previous reports suggested an increased procedure-related risk, mainly esophageal perforation. However, recent systematic reviews have shown low perforation rate of &lt;0.3%, approximating that of other benign conditions. Our findings are consistent with current data, suggesting that ED should be considered a safe treatment for EoE along with dietary and pharmacological interventions.

2860 Safety of Esophageal Dilation in Patients With Eosinophilic Esophagitis in a Single Center Cohort

INTRODUCTION: Eosinophilic esophagitis (EoE), a chronic immune-mediated disorder, is a leading cause of food impaction due to fibrotic formation of rings, narrowing, and strictures. Historically, esophageal dilation (ED) was reserved as second-line therapy for EoE after failure of medical management, due to concern of complications, mainly perforation. Now, ED is recognized as an effective treatment for symptomatic relief. The aim of this study is to assess the safety of ED in a large cohort of EoE cases in a single center. METHODS: A retrospective review of patients with biopsy confirmed EoE at University of Iowa Hospitals and Clinics between the years 2006 – 2018 was conducted. All subjects met diagnostic criteria for EoE; presence of esophageal dysfunction and mucosal eosinophilic infiltration (≥15 eos/hpf). Histologic and clinical features, ED characteristics and related complications, and self-reported symptomatic improvement were extracted via chart review. Descriptive statistic with univariate analysis was performed. RESULTS: A total of 160 patients were dilated 295 times, ranging from 1-12 dilations per patient, with an average of 1.91 dilations per patient. 67 patients (41.88%) required &gt;1 dilation. Procedures were generally tolerated well, with no major bleeds or perforations. The overall complication rate was 6.1%, primarily due to post-procedural chest pain (4.8%). Three patients had sedation related complications: one aspiration pneumonia and two ICU admissions for respiratory distress. Clinical improvement was documented in 87% of dilations on follow up. Table 1 and Figure 1 and 2. CONCLUSION: The prevalence of EoE is increasing with rates of 0.5 – 1 cases per 1000 individuals, with 25-35% of these patients requiring ED for symptomatic management. In the early 2000s, many reports suggested an increased procedure-related risk, including esophageal perforation. Recent systematic review and meta-analysis have shown otherwise. Present published rate of perforation in dilation in EoE occurs in &lt; 0.3% of procedures, which approximates that of dilation for other benign esophageal indications. Our study is consistent with current data. Taking the above safety data of ED into account along with the rising incidence of EoE, lends evidence to the acceptance of ED as a safe and effective treatment. ED should therefore be considered a safe procedure in EoE patients for symptomatic management in addition to dietary and pharmacological interventions.

Is There a Role for pH Impedance Monitoring in Identifying Eosinophilic Esophagitis in Children with Esophageal Atresia?

To evaluate clinical, endoscopic, and pH-impedance measures in a cohort of children with esophageal atresia and concomitant eosinophilic esophagitis (EoE) and compared it with disease-matched controls, to identify predictive factors for the development of EoE and esophageal stricture. We reviewed 63 patients with esophageal atresia assessed for refractory upper gastrointestinal symptoms between January 2015 and September 2017 at 2 tertiary referral centers. All patients underwent upper gastrointestinal endoscopy and pH-impedance monitoring. Based on esophageal histology, patients were classified as (1) esophageal atresia without evidence of esophagitis; (2) esophageal atresia with evidence of esophagitis (including esophageal eosinophilia not meeting the criteria for EoE); (3) esophageal atresia with concomitant EoE. Age and sex matched patients with gastroesophageal reflux disease were used as disease controls. The presence of atopy and peripheral eosinophilia at baseline were significantly associated with EoE (P<.05). Although there was a tendency toward an increased number of strictures in patients with esophageal atresia-EoE, this did not reach statistical significance (P=.06). Higher esophageal acid exposure time and lower baseline impedance values were significantly associated with eosinophilic infiltration (P<.05 and P<.01, respectively). Using logistic regression analysis, the presence of mucosal eosinophilia was the most predictive factor for stricture formation (P<.05). A history of atopy and the presence of peripheral eosinophilia in patients with esophageal atresia are predictive factors for the development of EoE, which in turn is a predictive factor for stricture occurrence. Higher esophageal acid exposure time and lower baseline impedance are associated with esophageal eosinophilic infiltration, suggesting their value in selecting which patients with esophageal atresia should undergo endoscopic examination.

Sa1136 - Efficacy of and Predictors for Proton Pump Inhibitor Response in Esophageal Eosinophilic Infiltration

Sa1136 - Efficacy of and Predictors for Proton Pump Inhibitor Response in Esophageal Eosinophilic Infiltration

Understanding fibrosis in eosinophilic esophagitis: Are we there yet?

Eosinophilic esophagitis (EoE) is an immune/antigen-mediated, progressive fibrostenotic disease characterized by symptoms of esophageal dysfunction and abnormal eosinophilic infiltration in the esophagus. Despite current treatment modalities of dietary antigen elimination or topical corticosteroids, a subset of patients do not have clinical or histologic response. Even with resolution of superficial epithelial eosinophilia, patients may still have progressive subepithelial fibrosis, which may lead to esophageal strictures over time. Histologic identification of subepithelial fibrosis requires deep esophageal biopsies, which are not routinely obtained. Herein, we review the challenges in diagnosing and treating fibrosis in EoE. We propose the novel concept of vitamin D supplementation to treat fibrosis in EoE through downregulation of profibrotic mediator, transforming growth factor-beta.

Gastrointestinal Manifestations of STAT3-Deficient Hyper-IgE Syndrome.

STAT 3 deficiency (autosomal dominant hyper immunoglobulin E syndrome (AD-HIES)) is a primary immunodeficiency disorder with multi-organ involvement caused by dominant negative signal transducer and activator of transcription gene 3 (STAT3) mutations. We sought to describe the gastrointestinal (GI) manifestations of this disease. Seventy subjects aged five to 60years with a molecular diagnosis of AD-HIES were evaluated at the National Institutes of Health (NIH). Data collection involved a GI symptom questionnaire and retrospective chart review. In our cohort of 70 subjects, we found that 60% had GI symptoms (42/70). The most common manifestations were gastroesophageal reflux disease (GERD) observed in 41%, dysphagia in 31%, and abdominal pain in 24%. The most serious complications were food impaction in 13% and colonic perforation in 6%. Diffuse esophageal wall thickening in 74%, solid stool in the right colon in 50% (12/24), and hiatal hernia in 26% were the most prevalent radiologic findings. Esophagogastroduodenoscopy (EGD) demonstrated esophageal tortuosity in 35% (8/23), esophageal ulceration in 17% (4/23), esophageal strictures requiring dilation in 9% (2/23), and gastric ulceration in 17% (4/23). Esophageal eosinophilic infiltration was an unexpected histologic finding seen in 65% (11/17). The majority of AD-HIES subjects develop GI manifestations as part of their disease. Most notable are the symptoms and radiologic findings of GI dysmotility, as well as significant eosinophilic infiltration, concerning for a secondary eosinophilic esophagitis. These findings suggest that the STAT3 pathway may be implicated in a new mechanism for the pathogenesis of several GI disorders.

Preferential Secretion of Thymic Stromal Lymphopoietin (TSLP) by Terminally Differentiated Esophageal Epithelial Cells: Relevance to Eosinophilic Esophagitis (EoE).

Eosinophilic esophagitis (EoE) is a chronic Th2 and food antigen-mediated disease characterized by esophageal eosinophilic infiltration. Thymic stromal lymphopoetin (TSLP), an epithelial derived cytokine which bridges innate and Th2-type adaptive immune responses in other allergic conditions, is overexpressed in esophageal biopsies of EoE subjects. However, the triggers of TSLP expression in the esophageal epithelium are unknown. The objective of the current study was to characterize TSLP expression in human esophageal epithelium in EoE in vivo and to determine the role of food antigens upon epithelial TSLP expression in vitro. Using immunohistochemistry (IHC), we localized TSLP in esophageal biopsies of active EoE (≥15 eos/hpf), inactive EoE (<15 eos/hpf) and non-EoE control subjects, and found that TSLP expression was restricted to the differentiated suprabasal layer of the epithelium in actively inflamed EoE biopsies. Consistent with these results in vivo, inducible TSLP protein secretion was higher in CaCl2 differentiated telomerase-immortalized esophageal epithelial cells (EPC2-hTERT) compared to undifferentiated cells of the basal phenotype, following stimulation with the TLR3 ligand poly(I:C). To determine whether food antigens could directly induce epithelial TSLP secretion, differentiated and undifferentiated primary esophageal epithelial cells from EoE and non-EoE subjects were challenged with food antigens clinically relevant to EoE: Chicken egg ovalbumin (OVA), wheat, and milk proteins beta-lactoglobulin (blg) and beta-casein. Food antigens failed to induce TSLP secretion by undifferentiated cells; in contrast, only OVA induced TSLP secretion in differentiated epithelial cells from both EoE and control cell lines, an effect abolished by budesonide and NF-κb inhibition. Together, our study shows that specific food antigens can trigger innate immune mediated esophageal TSLP secretion, suggesting that esophageal epithelial cells at the barrier surface may play a significant role in the pathogenesis of EoE by regulating TSLP expression.

An Overview of the Diagnosis and Management of Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition characterized by symptoms of esophageal dysfunction and eosinophilic infiltration of the esophageal mucosa. The diagnosis requires esophageal biopsies demonstrating at least 15 eosinophils per high-powered field following a course of high-dose proton pump inhibitors. Management of EoE consists of the three Ds: drugs, dietary therapy, and esophageal dilation. In this review, we discuss the epidemiology, pathogenesis, diagnosis, and treatment of EoE to include the role of emerging therapies.

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.

Proton Pump Inhibitor-responsive Esophageal Eosinophilia: An Overview of Cases from One University Hospital Center

Eosinophilic esophagitis (EoE) is a chronic, immune/antigen-mediated esophageal disease, with eosinophilic infiltration limited to the esophagus. A minority of EoE patients respond well to proton pump inhibitor (PPI) therapy alone, and that condition is labelled PPI-responsive esophageal eosinophilia (PPI-REE). The prevalence of PPI-REE among EoE cases is unknown. We aimed to identify clinical manifestations of PPI-REE, and the proportion of PPI-REE among all EoE cases. We reviewed pathology of the 4,075 patients who underwent esophageal biopsy at an institution from March 2003 to July 2015. EoE was diagnosed based on esophageal symptoms and eosinophilic infiltration limited to the esophagus, with ≥15 eosinophils per high-power field. We collected endoscopic and pathologic findings, and clinical features for these patients. Thirteen (0.3%) patients were diagnosed with EoE. Clinical manifestations were dysphagia (30.8%), foreign body sensation (23.1%), regurgitation (23.1%), cough (15.4%), heartburn (15.4%), nausea (7.7%), dyspepsia (7.7%). The endoscopic findings noted were polypoid lesion (23.1%), whitish plaque or exudate (23.1%), linear furrow (7.7%), concentric ring (7.7%), nodularity (7.7%), erosion (7.7%), and normal (30.8%). Of these patients, five had a favorable course with PPI as monotherapy. The proportion of EoE among all patients undergoing endoscopic biopsy was 0.3%. Of those, PPI-REE comprised 38%. Most of the endoscopic findings were atypical or normal when compared to the typical findings in EoE. In conclusion, patients who present with symptoms related to esophageal dysfunction need esophageal biopsy, regardless of the endoscopic findings. Moreover, patients diagnosed with EoE need to be treated first with PPI alone.

Eosinophilic esophagitis: New insights in pathogenesis and therapy.

Eosinophilic esophagitis (EoE) is a clinico-pathological entity with esophageal symptoms and dense esophageal eosinophilic infiltration throughout the esophagus that may persist despite treatment with proton pump inhibitors. This eosinophilic infiltration is usually absent in the stomach, small intestine and colon, although there are a number of reports of patients with a multi-organ involvement. EoE is associated with abnormalities involving TH2-dependent immunity, with multiple environmental factors strongly contributing to disease expression. The layer of the esophagus affected by the eosinophilic infiltration causes the specific symptoms. Esophageal involvement results mostly in dysphagia for solids that can be severe enough to cause recurrent esophageal obstruction with typical endoscopic features suggesting esophageal remodeling and pathological changes of eosinophilic infiltration of the mucosa, sub-epithelial fibrosis and muscle hypertrophy. This disease is frequently associated with other allergic conditions such as allergic asthma, allergic dermatitis and eosinophilia. The treatment of patients with EoE depends on the severity of the symptoms and of the inflammatory process as well as to their response to a gradual step-up treatment. The first line of treatment consists of steroid containing local inhalers. If unresponsive they are then treated with oral steroids. Intravenous interleukin blockers seem to have a consistent positive therapeutic effect.