Eosinophilic esophagitis: pathogenesis, genetics, and therapy

Eosinophilic esophagitis (EE) is a recently recognized disorder characterized by the accumulation of eosinophils in the esophagus. Symptoms of EE frequently mimic those of gastroesophageal reflux disease, but the 2 diseases are quite distinct in terms of the histopathology and response to therapy. We demonstrate that EE involves the interplay of numerous genes, especially the eosinophil chemoattractant eotaxin-3, allowing molecular distinction from other forms of esophagitis and consideration of targeted therapeutic intervention.     

Pediatric and adult eosinophilic esophagitis: similarities and differences

Early in the 1990s, several case series described adults suffering from dysphagia and children with refractory reflux symptoms, both accompanied by an eosinophil-predominant infiltration, thereby conclusively distinguishing it from gastroesophageal reflux disease. Eosinophilic esophagitis (EoE) was recognized as its own entity in the adult and in the pediatric literature. In the last decade, evidence has accumulated that EoE represents a T-helper (Th)2-type inflammatory disease. Remodeling of the esophagus is a hallmark of EoE, leading to esophageal dysfunction and bolus impaction. Familial occurrence and disease association with single-nucleotide polymorphisms underscore the influence of genetics in this disease. Eosinophilic esophagitis may affect individuals at any age, although the clinical presentation is highly age dependent. There is a significant allergic bias in the EoE population, with the majority of patients having concurrent allergic rhinitis, asthma, eczema, and/or a history of atopy. One noteworthy difference is that in children, EoE seems to be primarily a food antigen-driven disease, whereas in adults, mainly aeroallergen sensitization has been observed. Treatment modalities for EoE include the 3Ds: drugs, diet, and dilation. The crucial question of whether adult and pediatric EoE are different phenotypes of one single entity or whether we are confronted with two different diseases is still open. Here, we review similarities and differences between EoE in adults and children.     

Eosinophilic esophagitis in adults and children: evidence for a food allergy component in many patients

PURPOSE OF REVIEW: Eosinophilic esophagitis is a recently recognized disorder receiving increasing attention. Patients present with symptoms of gastroesophageal reflux and are not responsive to standard or aggressive reflux medications. This article reviews all literature published in English from December 2005 to November 2006 from PubMed on the topic of eosinophilic esophagitis. RECENT FINDINGS: Three articles have confirmed that food allergies are causative in more than 90% of patients. Three different diet strategies were used: elemental, elimination diet based on the prick-skin test, and the atopy patch test or removal of the six most common foods. The elemental diet had the highest success rate (> 95%), whereas the testing-based elimination diet (> 75%) and six-food elimination diet (> 70%) had lower success rates. There are no organized dietary trials in adults. SUMMARY: Recent literature on pediatric patients with eosinophilic esophagitis confirms that nearly all patients respond to an elemental diet with resolution of symptoms and normalization of biopsies. Although diets based on testing or removal of the most common allergens showed success, they were less successful than a complete elimination diet. Unfortunately, there are very limited studies in adults that address this issue.     

Eosinophile Ösophagitis

Eosinophilic esophagitis is a chronic, clinically and histologically defined, inflammatory condition of the esophagus. The histological hallmark of eosinophilic esophagitis is a relevant, often patchy infiltration of the esophageal mucosa with eosinophils. In a consensus report a threshold value of approximately 120 eosinophils per mm² was arbitrarily fixed as a diagnostic criterion. Noteworthy for the quantification of the eosinophilic infiltration are several technical facts, for instance size and covering extent of the biopsy specimen of the high-power field (hpf) and quality of embedding of biopsy specimens have to be considered. In order to establish the histological diagnosis several additional abnormalities must be included in the assessment and gastrointestinal reflux disease is the main differential diagnosis of eosinophilic esophagitis. Finally it is emphasized that for an affirmative diagnosis of eosinophilic esophagitis, in addition to the histological findings the clinical facts must be included.     

Pathogenesis of esophageal rings in eosinophilic esophagitis

Eosinophilic esophagitis and eosinophilic gastroenteritis is being recognized more frequently among the adult patients. The disease is characterized by massive infiltration of the wall of gastrointestinal tract by sheets of eosinophils. The clinical features depend upon the site of involvement. They include dyspepsia, dysphagia, nausea, vomiting, chest pain, diarrhea and protein-losing enteropathy. Eosinophilic esophagitis may present as chest pain, dysphagia or dyspepsia. The characteristic endoscopic feature of eosinophilic esophagitis is the formation of fine concentric mucosal rings (corrugated esophagus). Regarding the pathogenesis of these mucosal rings our hypothesis is that mast cells in the esophageal wall in response to allergens release histamine, eosinophilic chemotactic factor and platelet activating factor, etc. which activate eosinophils to release toxic cationic proteins. Activation of acetyl choline by histamine may cause contraction of the muscle fibers in the muscularis mucosae resulting in the formation of esophageal rings. This hypothesis can be tested by demonstrating the contraction of muscle layers of muscularis mucosae with the use of high frequency endoscopic ultrasonic probe introduced via the biopsy channel of an endoscope.     

Anti-IL-5 (mepolizumab) therapy for eosinophilic esophagitis

BACKGROUND: Eosinophilic esophagitis (EE) is characterized by high numbers of eosinophils in the esophagus and epithelial hyperplasia, and is being increasingly recognized. IL-5 promotes eosinophil trafficking to the esophagus, and positively regulates eosinophil growth, activation, survival, and tissue recruitment. OBJECTIVE: We hypothesized that the humanized monoclonal IgG(1) antibody against human IL-5 (mepolizumab) may be useful in the control of EE. METHODS: An open-label phase I/II safety and efficacy study of anti-IL-5 in 4 adult patients with EE and longstanding dysphagia and esophageal strictures was conducted. Patients received 3 infusions of anti-IL-5 (750 mg intravenously monthly) without change in their current therapy. The levels of plasma IL-5, peripheral blood eosinophils, and CCR3+ cells in blood, quality of life measurements, and histological analysis of esophageal biopsies were determined before and 1 month after treatment. RESULTS: Peripheral blood eosinophilia and percent of CCR3+ cells decreased by 6.4-fold and 7.9-fold (P < .05), respectively, after anti-IL-5 treatment. Notably, mean and maximal esophageal eosinophilia decreased from 46 to 6 and from 153 to 28 eosinophils/high-power field (x400; average, 8.9-fold, P < .001, and 6-fold, P < .05), respectively. Patients reported a better clinical outcome and improved quality of life (P = .03). Therapy was generally well tolerated, and responsiveness to anti-IL-5 therapy did not correlate with plasma IL-5 levels. CONCLUSION: Anti-IL-5 therapy is associated with marked decreases in peripheral blood and esophageal eosinophilia (including the number of CCR3+ blood cells) in patients with EE and improved clinical outcomes. CLINICAL IMPLICATIONS: Anti-IL-5 is a promising therapeutic intervention for EE.     

Dichotomy of food and inhalant allergen sensitization in eosinophilic esophagitis

BACKGROUND: Eosinophilic esophagitis (EE) is an emerging condition where patients commonly present with symptoms of gastroesophageal reflux disease and fail to respond adequately to anti-reflux therapy. Food allergy is currently recognized as the main immunological cause of EE; recent evidence suggests an etiological role for inhalant allergens. The presence of EE appears to be associated with other atopic illnesses. OBJECTIVES: To report the sensitization profile of both food and inhalant allergens in our EE patient cohort in relation to age, and to profile the prevalence of other allergic conditions in patients with EE. METHOD: The study prospectively analyzed allergen sensitization profiles using skin prick tests to common food allergens and inhalant allergens in 45 children with EE. Patch testing to common food allergens was performed on 33 patients in the same cohort. Comorbidity of atopic eczema, asthma, allergic rhinitis and anaphylaxis were obtained from patient history. RESULTS: Younger patients with EE showed more IgE and patch sensitization to foods while older patients showed greater IgE sensitization to inhalant allergens. The prevalence of atopic eczema, allergic rhinitis and asthma was significantly increased in our EE cohort compared with the general Australian population. A total of 24% of our cohort of patients with EE had a history of anaphylaxis. CONCLUSION: In children with EE, the sensitization to inhalant allergens increases with age, particularly after 4 years. Also, specific enquiry about severe food reactions in patients presenting with EE is strongly recommended as it appears this patient group has a high incidence of anaphylaxis.     

Clinicopathological characteristics of esophageal squamous papillomas in Japanese patients--with comparison of findings from Western countries

To clarify the characteristics of esophageal squamous papillomas (ESPs) in the Japanese population, we investigated 38 ESPs of 35 Japanese patients from a file with 17,387 upper gastrointestinal endoscopies in our university hospital. ESPs accounted for 0.20% of the total number of endoscopies and comprised 21 females and 14 males with an average age of 59.2 years. More than half of the ESPs (52.6%) were located in the middle esophagus. The ratio of human papilloma virus (HPV) positive ESPs was 10.5% and all were located in the middle esophagus of female patients only. HPV-positive ESP cases were younger (46.8 years) than HPV-negative cases (60.8 years). Based on comparison with the reports from western countries, we attribute the low prevalence in the lower esophagus to the relatively fewer occurrences of severe reflux esophagitis (RE) due to chronic gastritis with low gastric acid secretion among Japanese patients.     

Eosinophilic esophagitis in children: frequency, clinical manifestations, endoscopic findings, and seasonal distribution

PurposeEosinophilic esophagitis (EoE) is a chronic disease characterized by eosinophilic infiltration of the esophageal mucosa, which is associated with clinical and endoscopic manifestations. The objective of our study was to determine the frequency of EoE and to outline the clinical manifestations of EoE in Polish children.Material/methodsTen large regional pediatric gastroenterology centers participated in the study. A database of endoscopy reports from January 2004 till December 2009 was reviewed. A total of 35,631 esophagogastroduodenal endoscopy studies in children, aged from 4 months to 18 years, were performed. Data pertaining to the children's age, gender, indications for endoscopy, clinical findings and histopathology diagnosis were made.ResultsIn 84 children (20 girls and 64 boys), aged between 4 months and 18 years, EoE was diagnosed. This constituted one case per 424 endoscopic studies. In children with changes in the esophageal mucosa the frequency of EoE was higher and reached one case per 73 children. The most frequent symptoms of EoE differed between the younger (1–6 years old) and older children (aged 13–18 years old). Feeding aversion, vomiting and/or regurgitation were most frequently observed in the younger children, while in older children: abdominal pain, dysphagia and chest pain. Granular mucosa, longitudinal furrows, and mucosal rings belong to the findings most often observed in endoscopic studies. EoE was more frequently diagnosed in the spring (45.2%) and summer (28.5%).ConclusionsEoE was diagnosed in every age, with frequency of 1/424 gastrointestinal endoscopies, more frequently in boys than in girls.     

Eosinophilic esophagitis: an "emerging disease"

Eosinophilic esophagitis is a recently identified disease. The histological examination of esophageal biopsies is essential for its diagnosis, which is made with steadily increasing frequency. Eosinophilic esophagitis is an anatomoclinical entity, involving both children and adults, characterized by a dense and isolated infiltration of the esophageal mucosa by eosinophils, revealed by clinical symptoms of upper digestive tract origin and resistant to anti-acid treatment with IPP at high doses. Eosinophilic esophagitis is currently interpreted as an allergic disease, even though its pathogenesis remains unclear. The disease has a chronic course with persistent or relapsing symptoms, present with symptoms similar to those of gastro-esophageal reflux or with dysphagia. Endoscopic examination shows the presence of characteristic, but not pathognomonic, lesions (stenoses, strictures, circular rings, reduction of calibre, white specks, granularity of the mucosa). The histological diagnosis requires multiple biopsies taken all along the esophagus. The main sign is the presence of a dense eosinophilic infiltrate of the mucosa: a peak density of more than 15 eosinophils in at least one x400 field is the minimal criteria required for diagnosis. Associated lesions correspond to tissue damage and repair secondary to eosinophil activation (basal hyperplasia, microabscesses, fibrosis of the lamina propria). The treatment is based on dietary measures (allergen exclusion) and on the use of anti-inflammatory drugs, mainly corticoids. In conclusion, eosinophilic esophagitis is an emerging disease, important to identify, since it requires a specific treatment, different from that of reflux esophagitis.     

Eosinophilic esophagitis: an allergist's approach.

OBJECTIVE: To enhance the recognition of eosinophilic esophagitis by reviewing the presentation, diagnosis, and pathogenesis and then summarizing the epidemiology and treatment options. DATA SOURCES: MEDLINE was searched for articles using the keywords esophagitis and either allergy or eosinophil. Additional sources include searches limited to therapy, including corticosteroids and leukotrienes, and those limited to review articles, including chemokines and cytokines, from January 1990 to April 2006. All searches were limited to the English language. STUDY SELECTION: The authors selected relevant and current sources for inclusion in this review. RESULTS: Eosinophilic esophagitis is a diagnosis made by identifying 20 to 24 eosinophils per high-power field on examination of esophageal biopsy specimens. In recent years, a marked increase in incidence worldwide may have occurred. Although the pathogenesis is still unclear, therapy involves the use of corticosteroids and appropriate dietary elimination. CONCLUSION: Patients with atopy, especially males, who present with dysphagia, reflux symptoms, vomiting, abdominal pain, or failure to thrive should be considered for endoscopy to establish the diagnosis of eosinophilic esophagitis.     

Lymphocytic esophagitis: a histologic subset of chronic esophagitis

A novel histologic phenotype of chronic esophagitis, ie, lymphocytic esophagitis, is reported in 20 patients. Lymphocytic esophagitis is characterized by high numbers of intraepithelial lymphocytes (IELs) gathered mainly around peripapillary fields and by none (n = 12) to occasional (n = 8) CD15+ intraepithelial granulocytes. IELs expressed CD3, CD4 (42%), CD8 (36%), and granzyme B (0.2%), whereas T-cell intracytoplasmic antigen (TIA) 1 was not expressed. Of the 20 patients, 11 (55%) were 17 years or younger. Of 20 patients, 5 had no symptoms in the upper gastrointestinal tract. Only 4 (20%) of 20 patients had symptoms of gastroesophageal reflux disease and 6 (30%) of gastroduodenitis; 2 (10%) had celiac disease; 4 (20%) had carcinoma of the esophagus (1) or elsewhere (3); 1 (5%) each had hiatus hernia, gastric ulcer/asthma/blood hypertension, Hashimoto thyroiditis, and cirrhosis/diabetes; and 8 (40%) had Crohn disease. Hence, a novel histologic phenotype of chronic esophagitis called lymphocytic esophagitis is reported. Because phenotype is defined as the visible features resulting from the interaction between the genetic makeup and the environment, it is suggested that those factors might have a decisive role in the development of lymphocytic esophagitis.     

Eosinophilic esophagitis in adults--no clinical relevance of wheat and rye sensitizations

BACKGROUND: Eosinophilic esophagitis (EE) is often associated with concomitant atopic diseases. In children with EE in whom food allergens have been identified as causative factors, elemental and elimination diets result in an improvement or resolution of symptoms. Most adult EE patients are sensitized to aeroallergens, which cross-react with plant-derived food allergens, most commonly to grass pollen and cereals. AIMS OF THE STUDY: To investigate the clinical relevance of the sensitization to wheat and rye, and the efficacy of an allergen-specific elimination diet in adult EE patients. METHODS: Six patients (five men, one women) with permanently active EE sensitized to grass pollen and the cereals wheat and rye underwent a double-blind placebo-controlled food challenge and were kept on an elimination diet avoiding wheat and rye for 6 weeks. RESULTS: The challenge tests with wheat and rye did not provoke any EE symptoms in all patients. The elimination diet failed in reducing disease activity. Although one patient noticed an improvement of symptoms, endoscopic and histopathologic findings remained unchanged. CONCLUSIONS: In adult EE patients, sensitization to wheat and rye does not seem causative for EE. Elimination diet is not a reliable and efficient therapeutic measure in EE patients sensitized to wheat and rye. Low specific immunoglobulin-E levels to wheat and rye may be a consequence of the underlying grass pollen allergy.     

Eosinophilic esophagitis in adults: distinguishing features from gastroesophageal reflux disease: a study of 41 patients.

Eosinophilic esophagitis in adults is a recently described entity occurring in young males with dysphagia, in whom esophageal biopsies show eosinophilic infiltration. This study defines the clinical and histological features of patients with eosinophilic esophagitis, distinguishing it from gastroesophageal reflux disease. Esophageal biopsies from patients with dysphagia or esophagitis were reviewed blindly, and assessed for: epithelial eosinophil counts, presence of eosinophilic microabscesses, edema, basal zone hyperplasia, lamina propria papillae elongation, eosinophils and fibrosis. Clinical and endoscopic findings were obtained. Eosinophilic esophagitis was diagnosed with epithelial eosinophils > or = 15 in > or = 2 high-power fields (hpfs) or > or = 25 in any hpf. Analysis was performed with Mann-Whitney, chi2 and ANOVA tests. Of 157 cases, 41 had eosinophilic esophagitis. Male gender (81%) and age < or = 45 (54%) were commoner in patients with eosinophilic esophagitis (P = 0.001, 0.010, respectively). Dysphagia was more common in eosinophilic esophagitis patients (63%, P < 0.001); heartburn was more common in noneosinophilic esophagitis patients (53%, P < 0.001). Endoscopic rings were more common in eosinophilic esophagitis patients (27%, P = 0.023); hiatus hernia was more common in noneosinophilic esophagitis patients (11%, P = 0.022). Eosinophils were more numerous in eosinophilic esophagitis biopsies (mean 39/hpf, P < or = 0.001). Only eosinophilic esophagitis biopsies had eosinophilic microabscesses (42%, P < or = 0.001). Edema, basal zone hyperplasia, lamina propria papillae elongation and lamina propria eosinophils were commoner in eosinophilic esophagitis (P < or = 0.001-0.002), while lamina propria fibrosis was specific for eosinophilic esophagitis (39%, P < 0.001). Eosinophilic esophagitis is a disease with a predilection for young males with dysphagia and rings on endoscopy. Biopsies in eosinophilic esophagitis have high epithelial eosinophil counts, averaging nearly 40/hpf. Increased awareness of eosinophilic esophagitis is necessary, since treatment with allergen elimination or anti-inflammatory therapy may be more effective than acid suppression.     

Understanding eosinophilic esophagitis: the cellular and molecular mechanisms of an emerging disease

Eosinophilic esophagitis (EoE) has been increasingly recognized as a unique clinicopathological entity over the past two decades. In this short time, the mechanisms of a complex disease have begun to emerge. Patient studies suggest that EoE is an immunologic disease related to atopy. At the cellular level, eosinophils, mast cells, and B and T lymphocytes are increased in the esophageal mucosa in a patchy distribution throughout the length of the esophagus. Laboratory investigations have implicated aeroallergens, food allergens, and a unique T helper type 2 cytokine profile. EoE appears to be an antigen-driven hypersensitivity reaction characterized by a mixed IgE-dependent/delayed-type reaction and a distinct cascade of cytokines and growth factors. The causative events that lead to EoE in humans remain unknown.     

Periostin facilitates eosinophil tissue infiltration in allergic lung and esophageal responses

Periostin is an extracellular matrix protein that has been primarily studied in the context of the heart, where it has been shown to promote cardiac repair and remodeling. In this study, we focused on the role of periostin in an allergic eosinophilic inflammatory disease (eosinophilic esophagitis (EE)) known to involve extensive tissue remodeling. Periostin was indeed markedly overexpressed (35-fold) in the esophagus of EE patients, particularly in the papillae, compared with control individuals. Periostin expression was downstream from transforming growth factor-β and interleukin-13, as these cytokines were elevated in EE esophageal samples and markedly induced periostin production by primary esophageal fibroblasts (107- and 295-fold, respectively, at 10 ng ml⁻¹). A functional role for periostin in eliciting esophageal eosinophilia was demonstrated, as periostin-null mice had a specific defect in allergen-induced eosinophil recruitment to the lungs and esophagus (66 and 72% decrease, respectively). Mechanistic analyses revealed that periostin increased (5.8-fold) eosinophil adhesion to fibronectin. As such, these findings extend the involvement of periostin to esophagitis and uncover a novel role for periostin in directly regulating leukocyte (eosinophil) accumulation in T helper type 2-associated mucosal inflammation in both mice and humans.     

Major determinants and long-term outcomes of successful balloon dilatation for the pediatric patients with isolated native valvular pulmonary stenosis: a 10-year institutional experience

PURPOSE: We report herein major determinants and long-term outcomes of balloon dilatation (BD) for 27 pediatric patients with isolated native valvular pulmonary stenosis (VPS). MATERIALS AND METHODS: From May 1997 to May 2003, 27 pediatric patients with VPS (pressure gradients >or= 40 mmHg) were enrolled in this retrospective study. Single-balloon maneuver was applied in 26 patients, and double-balloon maneuver in 1. After BD, the pressure gradients were documented simultaneously by pullback maneuver by cardiac catheterization and echocardiography within 24 hours, at 1-month, 3-month, 1-year, and 4-to-10-year follow-ups. RESULTS: Before BD, the echocardiographic gradients ranged from 40 to 101 mmHg (61+/-19, 55), and from 40 to 144 mmHg (69+/-32, 60) by pressure recordings. After BD, the gradients ranged from 12 to 70 mmHg (29+/-13, 27) by pressure recording (p<0.001), and from 11 to 64 mmHg (27+/-12, 26) by echocardiography within 24 hrs (p<0.001). The ratios of the systolic pressure of the right ventricle to those of the left ventricle were 55 to 157% (89+/-28, 79%) before BD, and 30 to 79% (47 +/- 13, 42%) after BD (p<0.001). Follow-up (7.7+/-5.7, 4.5 years) echocardiographic gradients ranged from 11 to 61 mmHg (25+/-11, 24). Two patients did not have immediate success owing to infundibular spasm. Improved right ventricular compliance could be accounted for the ultimate success in these 2 patients. The ultimate successful rate was 100%. CONCLUSION: BD can achieve excellent long-term outcomes in the pediatric patients with isolated native VPS.     

Adult versus pediatric eosinophilic esophagitis: important differences and similarities for the clinician to understand

Eosinophilic esophagitis (EoE) is recognized as a common, allergy-associated cause of chronic esophageal symptoms affecting both children and adults. Research has begun to shed light on its epidemiology with consistent results from various geographical areas. Differences in clinical presentation, endoscopic aspects and response to treatment have all been reported for patients of different ages, and the question as to whether adult and pediatric EoE are manifestations of a single entity or in fact two distinct disorders has been posed. The most relevant differences between pediatric and adult EoE come from evolutionary changes in the consequences of the disease, including fibrous remodeling, and the ability to express symptoms. However, most studies support a common pathogenesis and similar histopathological features for adult and pediatric patients, being the same diagnostic criteria applied to them. This article comprehensively reviews the most recently published information and addresses important questions about the natural history of EoE.     

Proliferative characteristics of intestinalized mucosa in the distal esophagus and gastroesophageal junction (short-segment Barrett's esophagus): a case control study

Intestinalized epithelium in traditional long-segment Barrett's esophagus (BE) shows increased proliferative activity, which is postulated to be an early step in the metaplasia-dysplasia-carcinoma sequence. The aim of this study was to evaluate the proliferative activity of intestinalized epithelium of the distal esophagus and gastroesophageal junction (IMEGEJ). Tissue sections from 78 consecutive patients (20 with IMEGEJ, 58 without IMEGEJ) who had elective upper gastrointestinal endoscopy over a 6-month period were immunohistochemically stained with MIB-1, the Ki-67 proliferation-antigen-associated marker, for evaluation of the crypt MIB-1 proliferation index (PI), size of the proliferative zone (PZ), and the presence of surface epithelial staining. Data from the IMEGEJ and non-IMEGEJ groups, and from 15 age-matched patients with traditional long-segment BE (>3.0 cm), were compared statistically. IMEGEJ patients showed a statistically significant increase in the mean crypt PI compared with non-IMEGEJ controls (21.9+/-19.5 v 14.3+/-9.3; P=.01). In addition, IMEGEJ cases showed an increase in the mean crypt PZ (52.3+/-16.4 v 45.2+/-17.2; P=.05), and a trend toward an increase in the percentage of cases with MIB-1-positive surface epithelial cells (50% v 33%, P=.18). Patients with IMEGEJ did not differ from patients without IMEGEJ with respect to any other clinical or histological feature, including signs or symptoms of gastroesophageal reflux disease and presence or absence of esophagitis or carditis. The MIB-1 results of the patients with long-segment BE (MIB-1 PI = 22.6+/-20.5, MIB-1 PZ = 51.8+/-19.6, proportion of cases with MIB-1-positive surface cells = 66%) were similar to those with IMEGEJ. Intestinalized epithelium in the distal esophagus or gastroesophageal junction shows increased proliferative activity in comparison with patients without intestinalized epithelium. This finding supports an increased risk of carcinogenesis in patients with IMEGEJ.     

Eosinophilic esophagitis: an immune-mediated esophageal disease

Eosinophilic esophagitis (EoE) is an emerging disease defined by esophageal dysfunction, by typical endoscopic findings and by abnormal eosinophilic inflammation within the esophagus. Eosinophilic accumulation in the esophagus occurs as a result of esophageal overexpression of pro-inflammatory mediators, including T cells and mast cells, cytokines such as interleukin (IL)-13, IL-5 and IL-15, as well as chemoattractants (eotaxin and transforming growth factor-β1, fibroblast growth factor and the newly characterized gene—thymic stromal lymphopoietin, which is a key regulator of allergic sensitization initiation). The role of allergy, particularly food allergy in EoE is indisputable, as elimination diet is a proven commonly used treatment for the disease. However, unlike classical immediate IgE-mediated reaction to allergen, EoE is associated with an altered immune response, characterized by a combination of IgE-mediated and non-IgE-mediated mechanisms. In this review, we aim to discuss the many typical aspects of EoE as opposed to other entities involving the esophagus, with focusing on the aberrant immune-mediated key players contributing to the pathogenesis of this unique disease.