Eosinophilic esophagitis: Pathophysiology,diagnosis, and management

Eosinophilic esophagitis (EoE) is a multifactorial esophageal inflammation, with a genetic predisposition, which combines a deficient esophageal mucosal barrier, an abnormal immune reaction to environmental allergens mediated by Th2 interleukins, immediate esophageal lesions and dysmotility, with secondary remodeling and fibrosis. Symptoms include reflux, abdominal pain, and food impaction, with a variation according to age. Fibroscopy shows major and minor endoscopic and histologic criteria, with a mucosal count ≥ 15 eosinophils/high power field (Eo/hpf). A new entity has been defined, where gastroesophageal reflux disease (GERD) and EoE share responsibility: the PPIs-sensitive form of EoE (PPI-REE). Children with fibroscopy showing ≥ 15 Eo/hpf need a second endoscopy following 8 weeks of PPI treatment. EoE has a strong association with other atopic disorders. Allergy testing (specific IgE blood test and skin prick tests [SPTs]) identifies patients at risk of anaphylaxis (14.8% of cases). The dietary therapy is based on a 4- to 12-week elimination test followed by endoscopy to check the disappearance of eosinophilic infiltration. The “dietary approaches are the amino acid-based formula, the allergy testing-based targeted diet, and the six-food elimination diet (empirical elimination of milk, wheat, soy, eggs, peanut/nuts, and fish/seafood). A recent first-line trial elimination of milk has been suggested, with wheat as a second elimination, if necessary. Dietary therapy allows remission and catch-up growth in 65% of cases. Swallowed topical steroids (budesonide in viscous gel or fluticasone propionate for nebulization) are an alternative, for which efficacy varies according to clinical and/or histological criteria and with relapses occurring at dosage tapering. Their use may be restricted by side effects, such as oral and/or esophageal candidiasis. The impact on long-term bone health and growth is unknown. Maintenance therapy is not standardized and is team-dependent, combining or not elimination diets and long-term steroids. The long-term risk of EoE is esophageal stenosis (25%) and endoscopic dilation may be repeated. Biotherapies have shown isolated histological improvement without significant clinical efficacy.     

Intra- and interobserver agreement of histopathological findings in pediatric patients with eosinophilic esophagitis

ObjectiveTo assess intra- and interobserver agreement among non-expert pathologists in identifying features of the eosinophilic esophagitis histologic scoring system (EoEHSS) in pediatric patients.Patients and methodsThe authors used 50 slides from patients (aged 1-15 years; 72% male) with EoE. EoEHSS evaluates eosinophilic inflammation and other features including epithelial basal zone hyperplasia, eosinophilic abscesses, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis. Grade and stage of abnormalities are scored using a 4-point scale (0 normal; 3 maximum change). Four pathologists determined EoEHSS findings on two occasions. Intra- and interobserver agreement was assessed using Kappa (κ) statistics and intra-class correlation coefficients.ResultsIntra- and interobserver agreement for the identification of eosinophil counts ≥ 15/high power field (HPF) was excellent, however varied when assessing additional features of the EoEHSS. For the more experienced pathologist, agreement for most EoEHSS items and the composite scores was substantial to excellent. For the less experienced pathologists, intraobserver agreement ranged from absent to substantial for individual features and ranged from moderate to substantial for the composite scores.ConclusionMost items of the EoEHSS had substantial to excellent reliability when assessed by a pathologist experienced in the diagnosis of EoE but presented lower repeatability among less experienced pathologists. These findings suggest that specific training of pathologists is required for the identification of EoEHSS characteristics beyond eosinophil count, as these features are considered useful in the evaluation of response to treatment and correlation with clinical manifestations and endoscopic findings.     

Non stenotic food impaction due to eosinophilic esophagitis: a potential surgical emergency.

AIM: Eosinophilic esophagitis (EoE) is an emergent condition in which a mucosal infiltrate of > 20 eosinophils per high power microscopic field is accompanied by motor disturbances that may cause food impaction in the absence of esophageal stricture. We report a series of such cases to point out the potential involvement of pediatric surgeons in diagnosis and treatment. Furthermore, data on the motor function of the esophagus investigated manometrically is included. MATERIAL AND METHODS: Thirteen patients with EoE were referred to our emergency room for acute food bolus impaction. Their median age at diagnosis was 12 years (range 7.6-14.4). History of allergy, endoscopy with biopsy and esophageal function (24-h combined ambulatory manometry with simultaneous pH-metry) were investigated. RESULTS: In 7 patients emergency endoscopic extraction of the impacted bolus was necessary. Allergic tests were positive in eight patients. The pH probe showed gastroesophageal reflux in two cases. Upon endoscopy, typical features of EoE (esophageal trachealization and whitish papular exudates) were found. Ambulatory 24-h manometry revealed abnormal motility of the distal esophagus with strikingly high amplitudes (> 150 mmHg) and long duration (> 7 sec) of the waves, particularly during the night. Six patients responded rapidly to steroids and/or antiallergic treatment. The remaining patients had a good outcome with dietary treatment alone. CONCLUSIONS: EoE is an emergent condition that may involve the pediatric surgeon in both the diagnosis and treatment. Typical endoscopic findings and biopsy are required for proper diagnosis. Ambulatory manometry reveals a marked propulsive dysfunction that explains impaction. This dysfunction is reversible, since the symptoms usually disappear with steroids or antiallergic treatment.     

Gastrointestinal manifestations of food allergies

The rates of eosinophilic gastrointestinal disorders appear to be increasing. The most common of these is eosinophilic esophagitis (EoE) which is a clinicopathologic condition consisting of characteristic symptoms and endoscopic features accompanied by a pan-esophageal, acid resistant epithelial eosinophilia of greater than equal to 15 per high power field. Typical symptoms include dysphagia and abdominal pain. Typical endoscopic features include pallor, plaques, furrows, concentric rings. Complications include food impactions and strictures. EoE resolution with food elimination diets provides evidence that EoE is a food-antigen driven process. In vitro and microarray studies have identified specific immunologic factors underlying EoE pathogenesis. Other gastrointestinal manifestations of food intolerances/allergy include food protein induced enterocolitis syndrome.     

Management of eosinophilic esophagitis in children according to atopic status: A retrospective cohort in northeast of France

IntroductionMost children with eosinophilic esophagitis (EoE) are atopic, but the impact of atopy on the remission and development of EoE is still unclear. The aim of our study was to determine the impact of atopy on remission of EoE and to describe allergy tests and the choice of treatment for a cohort of EoE children in France.MethodsAll children diagnosed with EoE between January 2013 and June 2018 in the five pediatric centers in the northeast of France were included. Children were divided into two groups according to personal atopic disorders. Histological remission was defined on the basis of an eosinophilic count below 15 eosinophils per high-power field.ResultsAmong the 49 children included, 38 (78%) were atopic. Allergy tests were performed for 45 children (92%). Rates of sensitization were similar in both groups: 64% had food sensitization and 64% had aeroallergen sensitization. The most commonly attempted first-line therapy was with proton pump inhibitors (63%), followed by swallowed topical steroids (STS) (18%). First-line therapy was not associated with atopic status (P = 0.88). Atopic children had a nonsignificant tendency for a higher remission rate after STS (55% vs. 0%, P = 0.24) and a higher global remission rate (54% vs. 33%, P = 0.18) compared with non-atopic children.ConclusionAllergy testing is relevant in the majority of children with EoE whether or not they have atopic disorders. Atopy seems to be associated with better response to STS. Further studies are needed to determine whether atopic status determines histological response.     

Eosinophilic esophagitis

PURPOSE OF REVIEW: Previously perceived as an anomaly, eosinophilic esophagitis is now frequently diagnosed by both pediatric and adult specialists including gastroenterologists, allergists, pathologists, and otolaryngologists. Research efforts initially focused on characterization of the clinical, endoscopic, and histologic features of this disorder. In the last 3 years, the research focus has evolved into understanding its immunologic and demographic features as well as the development of efficacious therapies. RECENT FINDINGS: Population-based demographic studies have documented the unique epidemiologic parameters of eosinophilic esophagitis, some of its natural history, and its increasing frequency. Basic research efforts have identified cytokines relevant toward development of eosinophilic esophagitis, including interleukin-5 and interleukin-13. Clinical efforts have established the efficacy of dietary and medical treatments. Some treatments result in symptomatic improvement with ongoing inflammation, so a debate is ensuing over the long-term effect of asymptomatic esophageal inflammation. SUMMARY: Understanding of eosinophilic esophagitis has evolved to a point at which patients can be appropriately diagnosed and initially treated; however, a paucity of long-term outcome data prevents the creation of uniform recommendations for the clinical care of patients with eosinophilic esophagitis.     

Clinical,endoscopic, and histologic features of eosinophilic inflammation of the gastrointestinal tract in pediatric liver transplant patients

Immunosuppression during the post‐transplantation period has led to dramatic outcome improvements in PLTR patients. There have been reports describing the development of food allergies and an increased predilection for development of EGI in PLTR. We aimed to identify the clinical, endoscopic and histologic features of EGI in PLTR patients. In this retrospective case series we analyzed medical record of all PLTR who underwent EGD and/or colonoscopy at our institution from 2000 to 2006. From 2000 to 2006, 32 PLTR patients underwent endoscopic evaluation. Seventeen (53%) of 32 patients were diagnosed with EGI. Endoscopic abnormalities were seen in the esophagus, stomach, and small intestine in 11 (65%), 11 (65%), and four (24%) patients, respectively. Eosinophilic inflammation was seen in the esophagus, stomach, and small intestine in 13 (76%), 10 (59%), and five (29%) patients, respectively. Nine of 17 patients underwent colonoscopy and endoscopic abnormalities were seen in four (44%) patients. Five patients (56%) had eosinophilic inflammation. In conclusion, we have characterized the clinical, endoscopic, and histologic features of EGI. Histologic and endoscopic examination reveals that, when present, EGI is often found at multiple segments along the gastrointestinal tract.     

Eosinophilic esophagitis—Where are we today?

ObjectiveThe objective of this review is to provide an overview of the practical diagnostic and therapeutic approaches to eosinophilic esophagitis and to increase the visibility of the disease among pediatricians.SourcesA search of the MEDLINE, Embase, and CINAHL databases and recent consensus statements and guidelines were performed.Summary of the findingsThe definition of eosinophilic esophagitis is based on symptoms and histology. It is important to rule out other diseases associated with esophageal eosinophil-predominant inflammation. It is not yet clear whether the increased prevalence is due to a real increase in incidence or a result of increased awareness of the disease. Various options for management have been used in pediatric patients, including proton pump inhibitors, dietary restriction therapies, swallowed topical steroids, and endoscopic dilations. More recently, proton pump inhibitor-responsive esophageal eosinophilia and eosinophilic esophagitis have been contemplated on the same spectrum, and proton pump inhibitors should be considered the initial step in the treatment of these patients.ConclusionsEosinophilic esophagitis is a relatively new disease with a remarkable progression of its incidence and prevalence in the past two to three decades, and diagnostic criteria that are constantly evolving. It is important to better understand the pathogenesis of the disease, the predisposing factors, the natural history, and the categorization of varying phenotypes to develop diagnostic and therapeutic strategies that meet the clinical needs of patients.     

Association of Schatzki ring with eosinophilic esophagitis in children

OBJECTIVE: To describe the clinicopathologic characteristics of children with Schatzki ring and to determine if Schatzki ring is associated with eosinophilic esophagitis. METHODS: The authors report 18 adolescents with radiographically diagnosed Schatzki ring (SR). Their clinical and histologic characteristics were reviewed in a blinded fashion. RESULTS: The mean age of the patients was 15.8 +/- 0.8 years and mean duration of symptoms was 2.6 +/- 0.4 years. By histologic criteria, two groups of patients were defined. Eight had clinical and histologic criteria of eosinophilic esophagitis (EE) and 10 of peptic esophagitis. There were no differences in the symptoms or radiographic findings in the two groups. The SR was not identified by endoscopy in any EE patient and was identified in 70% of peptic esophagitis patients. Grossly apparent mucosal features associated with EE were significantly more common in those with EE. Those with peptic esophagitis had a significantly higher acid exposure than did those with EE (12.6 +/- 2.9 v 2.0 +/- 1.1%; P < 0.01) by esophageal pH probe. Patients with peptic esophagitis responded to proton pump inhibitors and/or dilatation, whereas those with EE did not have good response and required specific therapy for EE. CONCLUSIONS: EE may play a role in the pathogenesis of some patients with SR.     

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??Objective To approach the diagnosis and treatment of eosinphilic gastroenteritis in children. Methods In 12 cases of children with eosinophilic gastroenteritis in Nanjing Children's Hospital Affiliated to Nanjing Medical University from May 2009 to Nov.2011??the clinical manifestations??laboratory data??endoscopic and pathological findings and treatment were collected and analyzed. Results In the 12 patients??mucosal type was present in 8 cases??muscle-type in 1 case??and serous type in 3 cases. Most of the pediatric eosinophilic gastroenteritis had no specific clinical manifestations. From direct endoscopic vision??edema and erosion were the main performance of gastrointestinal mucosa. Histopathologic examination revealed that there was dense infiltration in gastrointestinal mucosa lamina propria by eosinophils. The effects of dietetic and antianaphylactic treatments were good. Conclusion The clinical manifestations of pediatric eosinophilic gastroenteritis are various and nonspecific. The dietetic and antianaphylactic treatments have obvious therapeutic effect . About 1 to 2 weeks of glucocorticoids therapy can rapidly alleviate the symptoms??and it continues for 3 months by reducing the dosage gradually.     

Eosinophilic esophagitis in children following cardiac transplantation: Association with post‐transplant lymphoproliferative disorder and other transplant outcomes

Although cardiac transplantation is life‐saving, morbidities from immunosuppression are significant. EoE is a complication of calcineurin inhibitors following liver transplant causing feeding intolerance, weight loss, vomiting, and dysphagia. There are limited reports of EoE following heart transplantation. We performed a retrospective single‐center review of pediatric cardiac transplant patients from 2000 to 2010. A case–control analysis of patients with and without EoE was performed evaluating heart transplantation outcomes such as rates of rejection, CAV, PTLD, and graft loss. Eighty‐six transplants were performed in 84 patients; 34 (40%) underwent diagnostic endoscopy, and 10 (12%) had EoE. Median time to diagnosis of EoE was 3.7 yr (IQR: 2.0–5.2). There were no differences in demographics or use of induction medications between patients with or without EoE. Patients with EoE had fewer episodes of treated rejection (1.0 vs. 2.5; p = 0.04). Four of 10 (40%) EoE patients had PTLD compared with only 2/24 (8%) of those without EoE (p = 0.048; OR 7.33 [95% CI: 1.1–50.2]). There were no differences in CAV or graft loss between groups. EoE should be considered as a cause of GI symptoms in children after cardiac transplantation and may be associated with fewer rejection episodes and increased rates of PTLD, thus representing a marker of over‐immunosuppression.     

Allergic eosinophilic esophagitis

Allergic eosinophilic esophagitis is an increasingly recognized disease in various parts of the world. The clinical presentation mimics other gastrointestinal diseases, especially gastroesophageal reflux disease, making endoscopic examination and histological evaluation of esophageal mucosal biopsies crucial to accurate diagnosis. The pathogenesis likely involves allergen-initiated, TH2-dependent, IL-5 mediated infiltration of eosinophilis into the esophageal mucosa. Therapies currently favored include dietary modifications and use of corticosteroids.     

Upper gastrointestinal endoscopy in children: indications and results

OBJECTIVE: To present and discuss the indications, the endoscopic and histologic findings and the complications of upper digestive endoscopies carried out in children and adolescents.METHODS: We have done 228 endoscopies in pediatric patients with ages between 3 months to 19 years (x=5.7 y) during a period of 8 months. General anesthesia was used in 80% of patients (182). Biopsies were done in 210 patients and the Helicobacter pylori was searched for in 130 patients by antral biopsies with Hematoxylin-Eosin coloration.RESULTS: The endoscopy indication was diagnostic in all patients, and in 18 cases there was some therapeutic procedure. Fifty-eight percent of examinations presented endoscopic alteration and 84% had abnormal histologic findings. The most frequent endoscopic findings were esophagitis in 50 patients, gastritis in 44 and duodenitis in 29. Ten peptic ulcers were diagnosed. Between the histologic findings the most frequent ones were gastritis in 87 patients, esophagitis in 50 and atrophy of duodenal mucosa in 9. The H. pylori was positive in 25 (19.2%) patients.CONCLUSION: The upper digestive endoscopy has become an essential procedure to the pediatric gastroenterology practice, amplifying the available diagnostic means and enabling therapeutic endoscopy in the presence of upper digestive lesions. In the present report, 58% of the studied population presented some endoscopic lesion.     

Esophageal eosinophilia in children with dysphagia

OBJECTIVES: Children occasionally have dysphagia in the absence of an apparent primary cause. Esophageal eosinophilia is sometimes seen in these patients at the time of upper endoscopy but its significance is not clear. Although eosinophilia is regarded by some as a histologic hallmark of childhood reflux esophagitis, it may in fact signal a primary eosinophilic esophagitis in children with dysphagia. Our aim was to evaluate esophagitis, acid reflux determined by pH probe, and esophageal eosinophilia in children with the primary complaint of dysphagia. METHODS: A retrospective study was performed in 42 children, admitted for investigation of dysphagia, in whom no primary cause could be found. Twenty-one children (mean age +/- SD, 10.1 +/- 4.0 years) had esophageal eosinophilia and 21 children (8.3 +/- 4.7 years) did not. Clinical, endoscopic, manometric and esophageal pH parameters in these two groups were compared. RESULTS: Patients with esophageal eosinophilia were more often male (p<0.01) with a history of allergy (p<0.001) and food bolus obstruction (p<0.05) requiring endoscopic removal. Their esophageal mucosa appeared wrinkled and thickened at endoscopy with basal cell proliferation, and large numbers of eosinophils in esophageal mucosal biopsies. Continuous esophageal pH records and motility studies, when obtained, were similar in both groups and were within normal values. CONCLUSION: Children with dysphagia who have esophageal eosinophilia are unlikely to have pathologic gastroesophageal reflux.     

Pediatric "PSC-IBD": a descriptive report of associated inflammatory bowel disease among pediatric patients with psc

BACKGROUND: Inflammatory bowel disease (IBD) in adults with primary sclerosing cholangitis (PSC) is characterized by pancolonic involvement, a high frequency of rectal sparing, and an increased risk of pouchitis and colorectal neoplasia. The clinical features of IBD in pediatric patients with PSC have not been well described. The aim of this study was to characterize the frequency, clinical features, and natural history of IBD in pediatric patients diagnosed with PSC. METHODS: A retrospective chart review was performed for all patients 18 years of age or younger diagnosed with PSC seen at the Mayo Clinic between 1975 and 1999. Endoscopic and histologic features and surgical and postsurgical outcomes were recorded. RESULTS: Fifty-two children with PSC were identified. Forty-three patients (84%) were also diagnosed with IBD. In 36 of 43 cases, there was a sufficient diagnostic evaluation to allow a detailed review. Thirty-two of 36 patients (89%) had ulcerative colitis and 4 of 36 patients (11%) had Crohn's disease. In 4 of 36 patients (11%), IBD was asymptomatic. Although the most frequent endoscopic presentation of IBD was universal colitis, endoscopic rectal sparing was frequently noted (27% of colonoscopic studies). Of the four patients diagnosed with Crohn disease, in none did perianal, fistulizing, or stricturing disease develop. Proctocolectomy was performed in six patients (17%); three operations were performed for dysplasia. Pouchitis complicated four of the five ileal pouch-anal anastomoses procedures. CONCLUSIONS: Among pediatric patients (1) PSC without IBD is uncommon; (2) asymptomatic IBD may be associated with PSC; (3) because the time to dysplasia may be accelerated, once the diagnosis of IBD is made in the setting of PSC, heightened endoscopic surveillance may be indicated; (4) pouchitis occurs frequently in these patients.     

Esophageal Crohn disease in children: a clinical spectrum

BACKGROUND: The incidence of esophageal Crohn disease (ECD) in adults ranges from 0.2% to 11.2% and in children is up to 43%. The aim of the study was to determine the clinical and endoscopic spectrum of ECD and its prevalence in our patient population. METHODS: Chart review of children with Crohn disease (CD). Esophageal Crohn disease was defined by accepted endoscopic and/or histologic findings. RESULTS: 210 children with CD were identified; 27 of those children had ECD. Nine children presented with specific upper GI symptoms; dysphagia, heartburn, nausea, vomiting, and odynophagia. Esophagoscopy in children with upper gastrointestinal symptoms revealed deep ulcers (n = 2), aphthous ulcers (n = l), erosions (n = l), edematous nodules, (n = l) and normal mucosa (n = 4). In asymptomatic children aphthous ulcers (n = 5), erosions (n = 3), deep ulcers (n = 3), and normal looking mucosa (n = 7) were seen. Twenty children also had gastric lesions, 3 children had duodenal lesions, and 3 children had both duodenal and gastric involvement. All 27 children had evidence of ileo-colonic or colonic disease. Acid suppressive medications were given only to children with upper GI symptoms and endoscopic esophageal lesions. The mean duration of follow-up from diagnosis of CD was 3.02 years (range 2 months-11.7 years). At last follow-up review, 7 children were receiving acid suppression and no children were receiving steroids. There were no complications related to ECD. CONCLUSION: The prevalence of endoscopic ECD is 7.6% but as many as 17.6% of our patient population had histologic evidence of ECD. The clinical and endoscopic spectrum of ECD are highly variable and poorly correlate with each other.     

Omalizumab in the treatment of eosinophilic esophagitis and food allergy

Omalizumab is currently used in severe asthma and has been tried in other allergic disorders. The authors report two patients with multiple food allergies and eosinophilic esophagitis on a very restrictive diet who have been treated with omalizumab, in order to improve food intolerance—the major distressing factor in their lives. The patients significantly improved in the reported symptoms. However, no improvement was seen regarding esophageal endoscopy and histology. Given the poor histological and endoscopy response, eosinophilic esophagitis persistence is unlikely to be IgE dependent. Omalizumab may improve the quality of life of patients with severe food allergy by improving symptoms, but it does not appear to change endoscopic and histological features of eosinophilic esophagitis in a short follow-up.     

硬化剂治疗食管静脉曲张破裂出血的远期疗效分析

目的 探讨经硬化剂治疗食管静脉曲张破裂出血后的远期疗效。方法 1996-2003年在内镜下用硬化剂(1％乙氧硬化醇)注射治疗15例食管静脉曲张破裂出血患儿,年龄3—14岁,采用静脉内和静脉旁联合注射。注射后长期临床与内镜随访,观察再出血率及曲张静脉消失率与并发症发生率。结果 15例共作了43次硬化剂注射治疗,依治疗时间先后不同,随访时间从3年4个月到7年2个月不等,平均5年6个月。10例经2次治疗,5例经3次治疗,曲张静脉基本消退,内镜随访发现曲张静脉平均消退时间为3-6个月。15例长期随访发现仅3例曲张静脉复发。再出血率明显减少,15例中仅3例发生再出血,其中2例因长期失访,直至再出血来院检查,发现1例系十二指肠溃疡,1例为静脉曲张出血,而治疗前几乎每1-2个月出血1次。此外未见一例食管穿孔、食管狭窄的并发症。结论 食管静脉曲张硬化剂疗法治疗儿童食管静脉曲张安全有效,尤其是肝外血管畸形所致的门脉高压症效果显著,是挽救患儿生命,提高患儿生命质量的有效内科治疗方法。     

Gastroduodenal endoscopic-histologic correlation in pediatric patients

The histopathologic abnormalities in endoscopic biopsies from the stomach and duodenal bulb were correlated with the visual findings of upper gastrointestinal endoscopy in 94 children (mean age, 8.4 years; 51 boys and 43 girls) with a variety of complaints. Histology was graded by observers blinded to the endoscopic findings, and both endoscopy and histology were graded using scales reflecting increasing severity with increasing grade. In all three locations studied (gastric body, antrum, and duodenal bulb), endoscopic grade was significantly higher than the histologic grade. Correlation was especially poor with mild endoscopic findings such as erythema and granularity/nodularity, which had little predictive value for histologic inflammation. Few patients had severe disease with eight of 94 having ulcer by endoscopy and seven of 94 having greater than grade 2 histologic disease in any location. We conclude that endoscopy without biopsy should not be used to diagnose gastroduodenal inflammation in pediatric patients.