Treatment of eosinophilic esophagitis in children

Opinion statement Eosinophilic esophagitis (EE) is an increasingly recognized disease of the esophagus with distinct clinicopathologic features. Adult and pediatric patients experience upper intestinal symptoms including food impaction, vomiting, abdominal pain, or dysphagia. Histopathologic analysis of the distal and proximal esophageal mucosa demonstrates dense eosinophilic infiltration despite proton pump inhibition. Few studies document the long-term outcomes of EE but current evidence suggests that EE is a chronic condition that can sometimes lead to esophageal strictures. Although the incidence of this complication is not yet known, it has sparked significant interest in defining safe, effective treatments. Once a diagnosis of EE is made, patients should seek the consultation of the allergist in an effort to identify possible food sensitivities. This is particularly important because the etiologic agent(s) that drive the eosinophilia are likely different for each patient. If the allergic evaluation identifies a specific food, this food should be strictly avoided as a first-line treatment. If a food is not identified, an elemental formula should be used to induce a remission. If an elemental diet cannot be used, topical steroids are effective in inducing a remission. The side effects associated with long-term steroid administration limit their use as a maintenance medication. Given the lack of prognostic data, the use of systemic corticosteroids should be reserved for severe cases when dietary elimination or topical steroids are ineffective. Most importantly, patients should remain under the care of a physician so that long-term outcomes can be identified. To date, diet restriction has been identified as the only effective maintenance treatment, but montelukast and topical cromolyn may also offer benefit. Anti-interleukin-5 antibody represents an emerging form of targeted therapy.     

Frequency of eosinophilic esophagitis in patients with esophageal symptoms: a single‐center Turkish experience

Eosinophilic esophagitis (EoE) is a chronic, immune/antigen‐mediated esophageal disease characterized with symptoms related to esophageal dysfunction and eosinophil‐predominant inflammation. There has been a dramatic increase in the diagnosis of this disease in recent years. The primary objective of this study was to determine the frequency of EoE in adult patients who were evaluated by gastroenterologists in our clinic with esophageal symptoms. Between November 2010 and May 2011, 311 adult patients who were evaluated in our clinic with esophageal symptoms were enrolled prospectively. All patients underwent endoscopy and had biopsies taken. Gastroesophageal reflux disease was excluded by either proton pump inhibitory treatment or 24‐hour ambulatory pH monitorization. The diagnosis was confirmed by one independent pathologist. Frequency of EoE in patients with esophageal symptoms was 2.6% (n = 8; four men and four women). Mean age at diagnosis was 40.2 ± 8 years. Heartburn was the predominant symptom in patients (75% of the patients), and 87.5% (n = 7) of patients had more than one symptom at diagnosis. Nearly 38% of the patients (n = 3) had a history of allergic disease. Endoscopic findings were as follows: transient/fixed esophageal rings (25%), white exudates (25%), and normal appearance (50%). Median number of circulating eosinophils was 208 (93–659)/mm³. Median number of intraepithelial eosinophils in proximal‐middle 1/3 part and distal 1/3 part of esophagus were 0 (0–50)/hpf and 37 (16–50)/hpf, respectively. In conclusion, EoE is not rare in Turkey, and it should be considered in the differential diagnosis of patients with esophageal symptoms.     

The role of allergy evaluation in children with eosinophilic esophagitis

Background

To our knowledge, in Asia, data on utility of allergy tests in management of eosinophilic esophagitis are lacking. The objective of our study was to determine the role of allergy evaluation in management of Saudi children with eosinophilic esophagitis.

Methods

Children diagnosed as having eosinophilic esophagitis during the period from 2009 to 2012 were referred to an allergist for allergy evaluation. The allergy evaluation consisted of total IgE level, radio-allergosorbent assay, and skin prick test. Depending on the results of the allergy tests, a restricted or elemental diet was established. Swallowed fluticasone inhaler was prescribed to patients who rejected or failed to respond to the diet. Clinical, endoscopic, and histological evaluation was performed in 8 weeks to assess response.

Results

Eighteen children with eosinophilic esophagitis were included (13 males; mean age 5 years, range 1–11). Sensitization to foods was demonstrated in 14 patients: 4 with a positive test for a single food (28.5 %), 1 for 2 food allergens (7 %), and 9 for ≥3 food allergens (64.5 %). The most common food allergens were milk, soybean, wheat, egg, and nuts. Three young children out of the total 14 patients responded to elemental formula. Four of the 10 older children on the allergy testing guided-dietary restriction achieved partial remission and the remaining 6 did not respond. All 10 patients responded to a swallowed fluticasone inhaler.

Conclusion

Although food sensitizations in Saudi children with eosinophilic esophagitis are common, the allergy tests had limited predictive value for the response to dietary elimination.     

Emerging management concepts for eosinophilic esophagitis in children

Eosinophilic esophagitis (EoE) is a newly recognized condition that appears to be increasing in incidence for as yet unknown reasons. It can occur at any age and presents both to gastroenterologists and allergists. Clinical manifestations range from gastrointestinal symptoms (vomiting, feeding difficulties, dysphagia or food bolus impaction) to co-existing atopic conditions (asthma, allergic rhinitis or eczema). The diagnosis requires demonstration of at least 15 eosinophils per high power field on esophageal histology, usually in the context of resistance to proton pump inhibitor treatment or a normal 24-h esophageal pH monitoring study. The differential diagnosis between EoE and gastroesophageal reflux disease (GERD) can be problematic as there is significant clinical overlap between both conditions. Although difficult-to-manage esophageal strictures are well recognized in patients with long-standing EoE, little is known about risk factors for the development of this complication. There is a paucity of data on both the natural history and optimal long-term management of EoE. Current treatment options include food allergen elimination diets, use of topical aerosolized corticosteroids, or a combination of the two. Pediatric case studies have been provided to illustrate the complexity of decision points that often arise in the management of these patients. This paper aims to discuss the various strategies currently available to clinicians in the management of EoE and highlights gaps in the current evidence base that urgently require further research.     

Esophageal dilations in eosinophilic esophagitis: A single center experience

AIM: To diagnose the clinical and histologic features that may be associated with or predictive of the need for dilation and dilation related complications; examine the safety of dilation in patients with eosinophilic esophagitis (EoE).METHODS: The medical records of all patients diagnosed with EoE between January 2002 and July 2010 were retrospectively reviewed. Esophageal biopsies were reexamined by an experienced pathologist to confirm the diagnosis (≥ 15 eos/hpf per current guidelines). Patients were divided into 2 groups: patients who did not receive dilation therapy and those who did. Demographics, clinical history, the use of pharmacologic therapy, endoscopic and pathology findings, and the number of biopsies and dilations carried out, if any, and their locations were recorded for each patient. The dilation group was further examined based on the interval between diagnosis and dilation, and whether or not a complication occurred.RESULTS: Sixty-one patients were identified with EoE and 22 (36%) of them underwent esophageal dilations for stricture/narrowing. The peak eos/hpf was significantly higher in patients who received a dilation (P = 0.04). Four (18% of pts.) minor complications occurred: deep mucosal tear 1, and small mucosal tears 3. There were no cases of esophageal perforations. Higher peak eos/hpf counts were not associated with increased risk of complications.CONCLUSION: Esophageal dilation appears to be a safe procedure in EoE patients, carrying a low complication rate. No correlation was found between the peak of eosinophil count and complication rate. Complications can occur independently of the histologic features. The long-term outcome of EoE treatment, with or without dilation, needs to be determined.     

The differential diagnosis of eosinophilic esophagitis

Eosinophilic esophagitis is a morphologic finding that may result from a wide spectrum of clinical conditions. The distinctive histological features accompanying eosinophilic esophagitis may facilitate the diagnosis of the underlying disease entity. Unfortunately, there are no pathognomonic histologic characteristics associated with eosinophilic esophagitis. Clinical signs and symptoms, immunological markers, endoscopic findings, and response to therapy may help establish or confirm the diagnosis of a clinical condition that results in eosinophilic esophagitis. The following discussion outlines the causes of eosinophilia in an esophageal biopsy sample.     

Primary eosinophilic esophagitis

Eosinophilic esophagitis is an uncommon pathology that generally affects children with a history of allergies and intrinsic asthma. We present a clinical case of eosinophilic esophagitis in a 16-year-old boy with upper dysphagia for solids since childhood. The analytical study showed only a repeat serum eosinophilia. Barium transit disclosed a reduction in caliber of the whole esophagus. Functional esophageal tests with pH monitoring and manometry were normal. Endoscopy showed a small-diameter esophagus and fibrosis with a very friable mucosa. The histological study of the esophageal biopsies revealed a full thickness major eosinophil infiltration of the esophagus. These findings suggest a differential diagnosis with a great variety of pathologies that can cause similar lesions in the esophagus, especially between primary eosinophilic esophagitis and eosinophilic esophagitis secondary to gastro-esophageal reflux disease (GERD). We implemented medical treatment with oral corticoids and total suppression of allergens from the diet, and the patient was asymptomatic.     

Treatment outcomes for eosinophilic esophagitis in children with esophageal atresia

Eosinophilic esophagitis (EoE) has been reported to be more prevalent in patients with esophageal atresia/tracheoesophageal fistula (EA‐TEF). To date, there is limited data on the management of EoE in this group of patients. The aim of this study is to evaluate the treatment outcomes of EoE in children with EA‐TEF. A retrospective chart review was performed on all EA‐TEF children who were diagnosed with and treated for EoE between January 2000 and September 2013 at the Sydney Children's Hospital. Data collected included details of the patient's treatment, post‐treatment endoscopy, symptoms and nutrition. Twenty patients were included in the study. Median age at diagnosis was 26 months (8–103 months), and median time from diagnosis to last follow‐up was 23 months (2–132 months). Patients were treated with budesonide slurry, swallowed fluticasone, elimination diet alone or in combination. All patients were on proton pump inhibitors at time of diagnosis of EoE which was continued. Six out of seven patients who had furrowing/exudate in endoscopy at diagnosis had complete resolution at a median follow‐up period of 26 months (P = 0.031). Median peak intraepithelial eosinophil count reduced significantly from 30/high‐powered field (HPF) (19–80/HPF) to 8/HPF (0–85/HPF) (median time for improvement = 24 months) (P = 0.015). There was a significant reduction in symptoms of dysphagia and reflux post‐treatment (P < 0.001). Prevalence of strictures significantly decreased (P = 0.016), as did need for dilatations (P = 0.004). In four out of six patients with gastrostomies at baseline, the feeding improved on treatment of EoE and the gastrostomy could be closed. There was also a nonsignificant trend towards improvement in weight and height ‘z scores’ of the patients. Treatment of EoE in children with EA‐TEF was found to significantly reduce intraepithelial eosinophil count, symptoms, strictures and need for dilatations.     

High-resolution EUS in children with eosinophilic "allergic" esophagitis

BACKGROUND: The pathophysiology of dysphagia associated with eosinophilic esophagitis is unknown. This study investigated possible anatomic alterations in children with eosinophilic esophagitis in comparison with healthy children by using high-resolution EUS to precisely measure individual tissue layers of the esophagus. METHODS: Children with eosinophilic esophagitis (n = 11) and control children (n = 8) without esophagitis were prospectively evaluated by high-resolution EUS with a 20-MHz catheter US probe during an endoscopic examination. Real-time measurements of the distal esophagus were obtained including the thickness of the total wall, combined mucosa and submucosa, muscularis propria, and circular muscle. RESULTS: Statistically significant differences were found between patients with eosinophilic esophagitis and control patients for mean values for thickness of the total wall (respectively, 2.8 vs. 2.1 mm; p = 0.004), combined mucosa and submucosa (respectively, 1.6 vs. 1.1 mm; p = 0.001), and muscularis propria (respectively, 1.2 vs. 1.0 mm; p = 0.043). Mean values for circular muscle did not differ between patient groups. CONCLUSION: High-resolution EUS reveals significant expansion of the esophageal wall and individual tissue layers including the combined mucosa and submucosa, and muscularis propria in children with eosinophilic esophagitis compared with healthy control patients.     

嗜酸细胞性食管炎研究进展

嗜酸细胞性食管炎(EoE)是一种以嗜酸性粒细胞浸润为主要特征的慢性食管炎症.主要临床表现为吞咽梗阻、食物嵌顿及反流样症状等.诊断主要依据其典型临床表现及食管病理,并且排除可能导致该类临床表现的其他食管及食管外疾病.其治疗方法亦多种多样,包括抑酸、饮食调节、糖皮质激素、食管扩张等,以激素治疗为主.     

Esophageal dilation in eosinophilic esophagitis

Solid-food dysphagia and food impaction are the hallmark symptoms of eosinophilic esophagitis (EoE) and are a result of subepithelial fibrosis, leading to esophageal stricture formation and loss of compliance of the esophagus. This fibrosis can be mechanically disrupted by esophageal dilation, which leads to a significant improvement in dysphagia in more than 80% of patients. The esophageal mucosa is quite fragile in patients with EoE, and dilation frequently leads to deep mucosal tears. The risk of esophageal perforation with dilation in EoE is likely increased over that seen with dilation in other benign esophageal diseases, but this risk has been overestimated in the earlier literature. Dilation in EoE, when done with some precaution, can be done relatively safely and in many cases of small-caliber esophagus, it needs to be done to alleviate symptoms. However, this dilation is frequently associated with postprocedure chest pain. In this article, we discuss the mechanisms of dysphagia in EoE to better understand the indications and timing of esophageal dilation in this disease. Then, we discuss the technique, efficacy, and importantly, the safety of esophageal dilation in EoE.     

Esophageal stenosis in eosinophilic esophagitis

Eosinophilic esophagitis is a rare, recently discovered disease, characterized by esophageal symptoms, such as dysphagia and food impaction, associated with dense eosinophilia on endoscopic biopsy of the esophagus. Other entities such as gastroesophageal reflux disease are absent and there is a lack of response to proton pump inhibitor therapy. This disease mainly affects the pediatric population but is becoming more prevalent in adults. There are several theories on the etiopathogenesis of this entity, which may involve allergies and atopy. In advanced disease, complications such as esophageal stenosis can appear. Treatment is based on dietary elimination, corticosteroids and endoscopic dilatation. We report a case of eosinophilic esophagitis with esophageal stenosis.     

Radiographic abnormalities in eosinophilic esophagitis

Eosinophilic gastroenteritis is an unusual condition of unknown cause in which there is eosinophilic infiltration of the gastrointestinal tract usually accompanied by a peripheral eosinophilia. Rarely, it can also involve the esophagus. Recently, the authors have encountered 3 cases of eosinophilic infiltration of the esophagus. All patients had a strong history of allergies. Two of our patients have had upper esophageal strictures, as have 2 other previously reported cases. This appears to be the most common manifestation. One patient had polypoid lesions of the esophagus as well as of the rest of the gastrointestinal tract. Motility disturbances may also be present. Although steroid treatment may be beneficial, the esophageal strictures usually require mechanical dilatation to relieve submucosal fibrosis. This entity should be considered in any patient who has an esophageal disorder in the presence of either a strong history of allergy or peripheral eosinophilia.     

Update on dietary therapy for eosinophilic esophagitis in children and adults

Introduction: Eosinophilic esophagitis (EoE) is a chronic inflammatory esophageal disease triggered predominantly, but not excusively, by food antigens. Elimination diet thus remains the only therapy targeting the cause of the disease. Importantly, EoE is a unique form of non-IgE mediated food allergy, largely dependant upon delayed, cell-mediated hypersensitivity.

Areas covered: A comprehensive review of literature to summarize and update the most relevant advances on dietary therapy for pediatric and adult EoE patients is conducted.

Expert commentary: None of the currently available food allergy tests adequately predict food triggers for EoE, especially in adults. Elemental diet (exclusive feeding with aminoacid-based formulas) and empiric six-food elimination diet, withdrawing cow´s milk, wheat, egg, soy, nuts and fish/seafood for 6 weeks, have consistently shown the best cure rates. However, their high level of restriction and need for multiple endoscopies (top-down approach) have been a deterrent for patients and physicians. Less restrictive empiric schemes, like a four-food (animal milk, gluten-containing cereals, egg, legumes) or a two-food (animal milk and gluten-containing cereals) elimination diet have lately shown encouraging results. Therefore, a novel step-up strategy (2–4-6) may enhance patient uptake and promptly identify most responders to empiric diets with few food triggers, besides saving unnecessary dietary restrictions and endoscopic procedures.     

嗜酸细胞食管炎研究进展

由于嗜酸细胞食管炎(eosinophilic esophagitis,EE)的发病率逐年升高,因此越来越引起国内外医师的重视.近年来关于EE发病机制、病理生理表现、诊断及有效治疗方法的研究越来越多,本文就以上诸多问题的研究进展作一综述.