Evolving strategies: Enhancements in managing eosinophilic esophagitis in pediatric patients

Eosinophilic esophagitis is a newly recognized disease first described about 50 years ago.The definition,diagnosis,and management have evolved with new published consensus guidelines and newly approved treatment available to pediatricians,enabling a better understanding of this disease and more targeted treatment for patients.We describe the definition,presentation,and diagnosis of eosinophilic esophagitis including management,challenges,and future directions in children.The definition,diagnosis,and management of eosinophilic esophagitis have evolved over the last 50 years.Consensus guidelines and newly approved biologic treatment have enabled pediatricians to better understand this disease and allow for more targeted treatment for patients.We describe the definition,presentation,diagnosis,management,and treatment in addition to the challenges and future directions of eosinophilic esophagitis management in children.

Diagnostic role of fractional exhaled nitric oxide in pediatric eosinophilic esophagitis, relationship with gastric and duodenal eosinophils

BACKGROUND Eosinophilic esophagitis(EoE)is an eosinophilic-predominant inflammation of the esophagus diagnosed by upper endoscopy and biopsies.A non-invasive and cost-effective alternative for management of EoE is being researched.Previous studies assessing utility of fractional exhaled nitric oxide(FeNO)in EoE were low powered.None investigated the contribution of eosinophilic inflammation of the stomach and duodenum to FeNO.AIM To assess the utility of FeNO as a non-invasive biomarker of esophageal eosinophilic inflammation for monitoring disease activity.METHODS Patients aged 6-21 years undergoing scheduled upper endoscopy with biopsy for suspected EoE were recruited in our observational study.Patients on steroids and with persistent asthma requiring daily controller medication were excluded.FeNO measurements were obtained in duplicate using a chemiluminescence nitric oxide analyzer(NIOX MINO,Aerocrine,Inc.;Stockholm,Sweden)prior to endoscopy.Based on the esophageal peak eosinophil count(PEC)/high power field on biopsy,patients were classified as EoE(PEC≥15)or control(PEC≤14).Mean FeNO levels were correlated with presence or absence of EoE,eosinophil counts on esophageal biopsy,and abnormal downstream eosinophilia in the stomach(PEC≥10)and duodenum(PEC≥20).Wilcoxon rank-sum test,Spearman correlation,and logistic regression were used for analysis.P value<0.05 was considered significant.RESULTS We recruited a total of 134 patients,of which 45 were diagnosed with EoE by histopathology.The median interquartile range FeNO level was 17 parts per billion(11-37,range:7-81)in the EoE group and 12 parts per billion(8-19,range:5-71)in the control group.After adjusting for atopic diseases,EoE patients had significantly higher FeNO levels as compared to patients without EoE(Z=3.33,P<0.001).A weak yet statistically significant positive association was found between the number of esophageal eosinophils and FeNO levels(r=0.30,P<0.005).On subgroup analysis within the EoE cohort,higher FeNO levels were noted in patients with abnormal gastric(n=23,18 vs 15)and duodenal eosinophilia(n=28,21 vs 14);however,the difference was not statistically significant.CONCLUSION After ruling out atopy as possible confounder,we found significantly higher FeNO levels in the EoE cohort than in the control group.

Adult eosinophilic esophagitis and advances in its treatment

Eosinophilic esophagitis(EoE)is a chronic eosinophil inflammation that seems to be T helper type 2 antigen-driven.The disease is one of several eosinophilic gastrointestinal disorders in which there appears to be inflammation of the gastrointestinal tract without any apparent underlying causes.Differential diagnosis needs to be made with gastroesophageal reflux,which is characterized by chronic inflammation due to gastric refluxate from disorders related to motility.EoE,however,is considered a chronic allergic inflammatory disorder related to destructive tissue remodeling.There seems to be a higher prevalence of EoE in Western countries.It is typically found in atopic male individuals.Physiopathological risk factors include atopy,environmental factors,esophageal epithelial barrier dysfunctions,etc.EoE can cause several symptoms that include retrosternal burning sensation,dysphagia,food impaction,chronic reflux symptoms,nausea,and vomiting.Early diagnosis,which requires a biopsy to assess for esophageal inflammation,is essential for proper treatment.The aim of our brief overview is to summarize the current literature regarding the characteristics,diagnosis,complications,mechanisms of pathology,clinical features,influence of comorbidities,and treatment in patients with EoE.

Significance of feeding dysfunction in eosinophilic esophagitis

Feeding dysfunction is a frequent presenting symptom of eosinophilic esophagitis(EoE). Here we present 3 children of various ages whose manifestations of EoE associated feeding dysfunction led to significant and life altering impact on their growth and development. Early identification of presenting symptoms of EoE will allow for prompt diagnosis and initiation of appropriate treatments. Recognition of salient features of dysfunction and treatment by feeding therapists and nutritionists led to symptom resolution and growth.

Recent discoveries and emerging therapeutics in eosinophilic esophagitis

Eosinophilic esophagitis(Eo E) is an allergy-mediated disease culminating in severe eosinophilic inflammation and dysfunction of the esophagus. This chronic disorder of the esophagus causes significant morbidity, poor quality of life, and complications involving fibrosis and esophageal remodeling. Overlapping features between EoE and gastroesophageal reflux disease(GERD) pose great challenges to differentiating the two conditions, although the two disorders are not mutually exclusive. Recent findings suggest that the confounding condition proton pump inhibitor- responsive esophageal eosinophilia(PPI-REE) is likely a subset of EoE. Since PPIs have therapeutic properties that can benefit EoE, PPIs should be considered as a therapeutic option for Eo E rather than a diagnostic screen to differentiate GERD, PPIREE, and EoE. Other current treatments include dietary therapy, corticosteroids, and dilation. Immunomodulators and biologic agents might have therapeutic value, and larger trials are needed to assess efficacy and safety. Understanding the pathophysiology of EoE is critical to the development of novel therapeutics.

Food impaction in older age:Think about an eosinophilic esophagitis

Eosinophilic esophagitis is an inflammatory condition of esophagus.It is generally seen in childhood and young population.Men are more commonly affected than women.However,it is not common in an advanced age.Eosinophilic esophagitis decreases the ability of the esophagus to stretch and accommodation against foods.Therefore,the major symptom in adults with eosinophilic esophagitis is difficulty in swallowing solid food(dysphagia).Specifically,the food gets stuck in the esophagus after it is swallowed.Less common symptoms include heartburn and chest pain.Because of this,it may be incorrectly diagnosed as a gastroesophageal reflux disease.Here,we reported a case presented with food impaction at advanced age.As a conclusion,eosinophilic esophagitis is a rare entity that must be remembered in advance aged patients presenting with food impaction.

Esophageal squamous papillomas with focal dermal hypoplasia and eosinophilic esophagitis

Focal dermal hypoplasia(FDH) is a rare disorder of the mesodermal and ectodermal tissues. Here we present an eight-year-old female known to have FDH who presents with poor weight gain and dysphagia. She was diagnosed with multiple esophageal papillomas and eosinophilic esophagitis. She was successfully treated with argon plasma coagulation and ingested fluticasone propionate, which has not been described previously in a child.

Development and validation of a registry-based definition of eosinophilic esophagitis in Denmark

AIM:To develop and validate a case definition of eosinophilic esophagitis(EoE) in the linked Danish health registries.METHODS:For case definition development,we queried the Danish medical registries from 2006-2007 to identify candidate cases of EoE in Northern Denmark.All International Classification of Diseases-10(ICD-10) and prescription codes were obtained,and archived pathology slides were obtained and re-reviewed to determine case status.We used an iterative process to select inclusion/exclusion codes,refine the case definition,and optimize sensitivity and specificity.We then re-queried the registries from 2008-2009 to yield a validation set.The case definition algorithm was applied,and sensitivity and specificity were calculated.RESULTS:Of the 51 and 49 candidate cases identified in both the development and validation sets,21 and 24 had EoE,respectively.Characteristics of EoE cases in the development set [mean age 35 years;76% male;86% dysphagia;103 eosinophils per high-power field(eos/hpf)] were similar to those in the validation set(mean age 42 years;83% male;67% dysphagia;77 eos/hpf).Re-review of archived slides confirmed that the pathology coding for esophageal eosinophilia was correct in greater than 90% of cases.Two registrybased case algorithms based on pathology,ICD-10,and pharmacy codes were successfully generated in the development set,one that was sensitive(90%) and one that was specific(97%).When these algorithms were applied to the validation set,they remained sensitive(88%) and specific(96%).CONCLUSION:Two registry-based definitions,one highly sensitive and one highly specific,were developed and validated for the linked Danish national health databases,making future population-based studies feasible.

Current hurdles in the management of eosinophilic oesophagitis:The next steps

Eosinophilic oesophagitis (EoE) is a chronic,antigen mediated disease of the disease of the oesophagus that may present in both adults and children.It is characterised by intermittent dysphagia,food bolus obstruction and weight loss.The pathogenesis is incompletely understood but is thought to culminate in poor compliance,or reduced distensibility.The condition is being reported and studied in the literature with increasing incidence,although equally it is highly likely that the diagnosis is being missed altogether with alarming frequency.Diagnosis of the condition requires at least one oesophageal biopsy with an eosinophil count greater than 15 per high power field.Endoscopic features include trachealisation,furrows,white exudate,narrowing and in the most severe cases stricture formation although none are pathognomonic of the condition.Therapy is often not required,but in the acute setting may take the form of dietary therapy or topical steroids.Long term maintenance therapy is usually only required in the most severe cases and the most effective treatment is the subject of ongoing research.There are a number of hurdles to be overcome in the management of patients with EoE.These include;improving our understanding of the aetiologyof the condition,investigating the individual causes,assessing the true disease severity and planning the best long term maintenance therapy.Distinguishing EoE from EoE gastro-oesophageal reflux disease is also a hurdle because the two conditions,both being common,can co-exist.In order to overcome these hurdles,a multifaceted approach is required.The management of food bolus obstruction requires a management algorithm that is accepted and endorsed by a number of specialties.National and international disease registers should be established in order to facilitate future research but more importantly to address areas where further education or increased diagnostic capabilities may be required.Assessment of disease severity should become a key goal,and the development of specific biomarkers for EoE should also be a priority.Finally,randomised controlled trials of new agents are required to assess the best treatment in both the acute and long term setting.

Influence of gender and race on presentation of eosinophilic esophagitis in children

Background: Eosinophilic esophagitis (EoE) is thought to be more common in males and Caucasians, yet little data exists regarding the presentation of EoE among children. Methods: A retrospective study of children undergoing esophagogastroduodenoscopy (EGD) was done to determine gender and racial differences in the prevalence and presenting symptoms of EoE. Data collected included gender, race, indication for EGD, and presence of EoE. Results: No gender or racial differences were found for indication for EGD. EoE was identified in 4.1% of children, more commonly in males than females (6% vs. 2.5%,

Histological remission of eosinophilic esophagitis under asthma therapy with IL-5 receptor monoclonal antibody:A case report

BACKGROUND Benralizumab is a monoclonal antibody targeting the IL-5 receptor used in the treatment of asthma.The use of benralizumab in other conditions is only emerging and could represent a therapeutic option for other eosinophil-associated diseases.Here,we report the case of a patient suffering from eosinophilic esophagitis and asthma who achieved histological remission of eosinophilic esophagitis(EoE)under benralizumab treatment for his asthma.CASE SUMMARY Our patient was a 56-year-old white male with a history of eosinophilic esophagitis and severe asthma.After years of usual treatments,including topical steroids,biological treatment with mepolizumab,and standard asthma treatment,only poor control of both conditions was obtained.A control gastroscopy after the initiation of benralizumab showed complete histological remission of his EoE.CONCLUSION Our case shows the effects of therapy with a novel agent not yet approved for this condition but for other diseases,with histological resolution of EoE after treatment.Complete clinical remission was not observed,which exemplifies the complex nature of EoE,its associated psychosomatic burden,and the chronification of the disease.Nevertheless,monoclonal antibodies targeting the Th2 response and,in our case,an IL5 receptor antagonist,achieved complete histological remission,which was not the case with an antibody against IL-5,which was also initiated to treat asthma.

Gastro-oesophageal reflux disease and eosinophilic oesophagitis: What is the relationship?

Eosinophilic oesophagitis(EoE) and gastro-oesophageal reflux disease(GORD) are the most common causes of chronic oesophagitis and dysphagia associated with oesophageal mucosal eosinophilia. Distinguishing between the two is imperative but challenging due to overlapping clinical and histological features. A diagnosis of EoE requires clinical, histological and endoscopic correlation whereas a diagnosis of GORD is mainly clinical without the need for other investigations. Both entities may exhibit oesophageal eosinophilia at a similar level making a histological distinction between them difficult. Although the term proton-pump inhibitor responsive oesophageal eosinophilia has recently been retracted from the guidelines, a relationship between Eo E and GORD still exists. This relationship is complex as they may coexist, either interacting bidirectionally or are unrelated. This review aims to outline the differences and potential relationship between the two conditions, with specific focus on histology, immunology, pathogenesis and treatment.

Confounding factors affect the pathophysiology of eosinophilic esophagitis

Eosinophilic esophagitis is a newly diagnosed esophageal disease in adult and children. The clinical and pathological characteristics of this disease have been established and were recently summarized in the expert clinical guideline published in 2011. In spite of the wide knowledge accumulated on this disease, there are many areas where scientific data are missing, especially in regard to the disease's pathophysiology. Recent publications have suggested that other confounding factors modify the disease and may affect its clinicalphenotypic presentation. Those factors may include place of living, air pollution, race, genetic factors and other. In the present report we discussed and review those confounding factors, the new developments, and what direction we should go to further advance our knowledge of this disease.

Endoscopic findings in patients with Schatzki rings:Evidence for an association with eosinophilic esophagitis

AIM:To investigate endoscopic findings in patients with Schatzki rings(SRs) with a focus on evidence for eosinophilic esophagitis(EoE).METHODS:We consecutively approached all adult patients scheduled for elective outpatient upper endoscopy for a variety of indications at the German Diagnostic Clinic,Wiesbaden,Germany between July 2007 and July 2010.All patients with endoscopically diagnosed SRs,defined as thin,symmetrical,mucosal structures located at the esophagogastric junction,were prospectively registered.Additional endoscopic findings,clinical information and histopathological findings with a focus on esophageal eosinophilia(≥ 20 eosinophils/high power field) were recorded.The criteria for active EoE were defined as:(1) eosinophilic tissue infiltration ≥ 20 eosinophils/hpf;(2) symptoms of esophageal dysfunction;and(3) exclusion of other causes of esophageal eosinophilia.Gastroesophageal reflux disease was excluded by proton pump inhibitor treatment prior to endoscopy.The presence of ≥ 20 eosinophils/hpf in esophageal biopsies in patients that did not fulfil the criteria of EoE was defined as esophageal hypereosinophilia.RESULTS:A SR was diagnosed in 171(3.3%;128 males,43 females,mean age 66 ± 12.9 years) of the 5163 patients that underwent upper gastrointestinalendoscopy.Twenty of the 116 patients(17%) from whom esophageal biopsies were obtained showed histological hypereosinophilia(≥ 20 eosinophils/hpf).Nine of these patients(8 males,1 female,mean age 49 ± 10 years) did not fulfill all diagnostic criteria of EoE,whereas in 11(9%) patients with ≥ 20 eosinophils/hpf,a definite diagnosis of EoE was made.Three of the 11 patients(27%) with definite EoE had no suspicious endoscopic features of EoE.In contrast,in the 25 patients in whom EoE was suspected by endoscopic features,EoE was only confirmed in 7(28%) patients.Patients with EoE were younger(mean age 41.5 ± 6.5 vs 50.5 ± 11.5 years,P = 0.012),were more likely to have a history of allergies(73% vs 29%,P = 0.007) and complained more often of dysphagia(91% vs 34%,P = 0.004) and food impaction(36% vs 6%,P = 0.007) than patients without EoE.Endoscopically,additional webs were found significantly more often in patients with EoE than in patients without EoE(36% vs 11%,P = 0.04).Furthermore,the SR had a tendency to be narrower in patients with EoE than in those without EoE(36% vs 18%,P = 0.22).The percentage of males(73% vs 72%,P = 1.0) and frequency of heartburn(27% vs 27%,P = 1.0) were not significantly different in both groups.The 9 patients with esophageal hypereosinophilia that did not fulfil the diagnostic criteria of EoE were younger(mean age 49 ± 10 years vs 58 ± 6 years,P = 0.0008) and were more likely to have a history of allergies(78% vs 24%,P = 0.003) than patients with < 20 eosinophils/hpf.Predictors of EoE were younger age,presence of dysphagia or food impaction and a history of allergies.CONCLUSION:A significant proportion of patients with SRs also have EoE,which may not always be suspected according to other endoscopic features.

Overlap of reflux and eosinophilic esophagitis in two patients requiring different therapies:A review of the literature

Eosinophilic esophagitis (EE) and gastroesophageal reflux disease (GERD) have overlapping clinical, manometric, endoscopic and histopathologic features. The diagnosis of EE is nowadays based upon the presence of 15 or more eosinophils per high power field (eo/HPF) in esophageal biopsies. We report the cases of two young males suffering from dysphagia and recurrent food impaction with reflux esophagitis and more than 20 eo/HPF in upper-mid esophagus biopsies, both of which became asymptomatic on proton pump inhibitor (PPI) therapy. The first patient also achieved a histologic response, while EE remained in the other patient after effective PPI treatment, as shown by 24-h esophageal pH monitoring. Topical steroid therapy combined with PPI led to complete remission in this latter patient. GERD and EE may be undistinguishable, even by histology, so diagnosis of EE should only be established after a careful correlation of clinical, endoscopic and pathologic data obtained under vigorous acid suppression. These diagnostic difficulties are maximal when both diseases overlap. Limited data are available about this topic, and the interaction between EE and GERD is a matter of debate. In this setting, upper-mid esophagus step biopsies and esophageal pH monitoring of patients on PPI therapy are pivotal to evaluate the role of each disease. A PPI trial is mandatory in patients with a histopathologic diagnosis of EE; in those unresponsive to PPI treatment, EE should be suggested. However, a clinical response to PPI may not rule out quiescent EE, as shown in this report.

Circumferential mucosal dissection and esophageal perforation in a patient with eosinophilic esophagitis

A young man with a previous history of episodes of mild solid food dysphagia was admitted with a total dysphagia. The esophagogastroduodenoscopy (EGDS) showed an extensive disruption of mucosal layer with a cul-de-sac in the lower part of the esophagus. Soon after the procedure, the patient suffered from an acute chest pain and subsequent CT scan demonstrated an intramural circumferential dissection of thoracic esophagus, and a mediastinal emphysema. An emergency right thoracotomy was performed, followed by a total esophagectomy with esophagogastroplasty and jejunostomy. The histopathology confirmed that mucosal and submucosal layers were circumferentially detached from muscular wall and showed an eosinophilic infiltration of the whole organ with necrosis and erosions of mucosal, submucosal and muscular layers. The diagnosis was esophageal perforation in eosinophilic esophagitis.

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 2010were 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 tears3.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.

Immunoglobulin G-mediated food intolerance and metabolic syndrome influence the occurrence of reflux esophagitis in Helicobacter pylori-infected patients

BACKGROUND Reflux esophagitis has an increasing prevalence and complex and diverse symptoms.Identifying its risk factors is crucial to understanding the etiology,prevention,and management of the disease.The occurrence of reflux esophagitis may be associated with food reactions,Helicobacter pylori(H.pylori)infection,and metabolic syndromes.AIM To investigate the risk factors for reflux esophagitis and analyze the effects of immunoglobulin(Ig)G-mediated food intolerance,H.pylori infection,and metabolic syndrome on reflux esophagitis.METHODS Outpatients attending the Second Medical Center of the PLA General Hospital between 2017 and 2021 were retrospectively enrolled.The patients’basic information,test results,gastroscopy results,H.pylori test results,and IgG-mediated food intolerance results were collected.Multivariate logistic regression analysis was used to analyze risk factors for reflux esophagitis.Statistical mediation analysis was used to evaluate the effects of IgG-mediated food intolerance and metabolic syndrome on H.pylori infection affecting reflux esophagitis.RESULTS A total of 7954 outpatients were included;the prevalence of reflux esophagitis,IgG-mediated food intolerance,H.pylori infection,and metabolic syndrome were 20.84%,61.77%,35.91%,and 60.15%,respectively.Multivariate analysis showed that the independent risk factors for reflux esophagitis included IgG-mediated food intolerance(OR=1.688,95%CI:1.497-1.903,P<0.00001)and metabolic syndrome(OR=1.165,95%CI:1.030-1.317,P=0.01484),and the independent protective factor for reflux esophagitis was H.pylori infection(OR=0.400,95%CI:0.351-0.456,P<0.00001).IgG-mediated food intolerance had a partially positive mediating effect on H.pylori infection as it was associated with reduced occurrence of reflux esophagitis(P=0.0200).Metabolic syndrome had a partially negative mediating effect on H.pylori infection and reduced the occurrence of reflux esophagitis(P=0.0220).CONCLUSION Patients with IgG-mediated food intolerance and metabolic syndrome were at higher risk of developing reflux esophagitis,while patients with H.pylori infection were at lower risk.IgG-mediated food intolerance reduced the risk of reflux esophagitis pathogenesis in patients with H.pylori infection;however,metabolic syndrome increased the risk of patients with H.pylori infection developing reflux esophagitis.

Analysis of the Effectiveness of Biling Weitong Granules Combined with Trimethoprim and Vonoprazan in The Treatment of Reflux Esophagitis

Objective:To analyze the effectiveness of Biling Weitong Granules(BLWTG)combined with trimethoprim and vonoprazan in treating reflux esophagitis.Methods:Sixty patients with reflux esophagitis admitted to our hospital from March 2020 to March 2023 were selected as study subjects and randomly divided into a control group and an experimental group,with 30 cases in each group.The control group received only the combination treatment of trimethoprim and vonoprazan,while the experimental group was treated with BLWTG based on the control group.The acid reflux and heartburn symptom scores,quality-of-life scores,clinical efficacy,Chinese medicine symptom incidences,and the occurrence of adverse reactions before and after treatment in the two groups were compared.Results:After treatment,the acid reflux and heartburn symptom scores of patients in the experimental group were lower than those of the treatment control group,and the quality-of-life scores were higher than those of the treatment control group(P<0.05).The total clinical efficacy of the experimental group was 96.66%,which was significantly higher than that of the control group(73.33%,P<0.05).After treatment,the incidence of Chinese medicine symptoms,such as nausea and vomiting,abdominal distension and abdominal pain,and loss of appetite of the patients in the experimental group were significantly lower than those of the control group(P<0.05).During the treatment period,there was no significant difference in the incidence of adverse reactions between the two groups,which indicated that the safety of the two treatments was comparable(P>0.05).Conclusion:BLWTG combined with trimethoprim and vonoprazan was safe and reliable in treating reflux esophagitis,effectively relieving the symptoms and improving its clinical efficacy.This treatment is worthy of popularization.