Primary Eosinophilic Esophagitis Research Articles

Management of Eosinophilic Esophagitis During Oral Immunotherapy

Food allergies are antigen-driven diseases that can lead to IgE-mediated reactions of immediate hypersensitivity (eg,anaphylaxis triggered by a single food) or non-IgE reactions of delayed hypersensitivity such as eosinophilic esophagitis (eg,inability to eat multiple foods manifesting as abdominal pain, choking, dysphagia, vomiting, reflux, food impaction). Although both types of disease have their own unique set of challenges in diagnosis and management, it is a particularly vexing problem when a patient is afflicted by both conditions. This situation can happen when individuals with IgE-mediated food allergy undergo desensitization using currently available forms of oral immunotherapy. In this Grand Rounds Review, we review diagnostic approaches to oral immunotherapy-associated eosinophilic esophagitis, potential relationships between primary and secondary eosinophilic esophagitis, potential management approaches, areas of uncertainty, and upcoming research. Optimally supporting patients in their journey with food allergy requires shared decision making regarding alternative management strategiesand the stimulation of robust research.

3092 A Clinically Confounding Presentation of Dysphagia With Multiple Valid Etiologies

INTRODUCTION: Dysphagia may result from a variety of different disease processes, including inflammation, infection, motility disorders, mechanical causes, or even functional. The etiology is less clear when a patient presents with multiple individual causes of dysphagia, each alone which may account for their symptoms. Our case report describes the coexistence of dysphagia due to several factors in a single patient, and a puzzling presentation warranting further evaluation to ultimately alleviate the underlying complaint. CASE DESCRIPTION/METHODS: We present a case of a 62-year-old female with a past medical history of hypertension that presented to her PCP with 6 months of weakness and limited oral intake. She endorsed issues swallowing and sensation of food stuck in her throat. Dysphagia to solids progressed to include liquids, and with nausea, vomiting, and 40 lbs unintended weight loss. The patient was admitted and failed bedside swallow study. Upper GI series and CT thorax showed hiatal and paraesophageal hernias. EGD revealed GE junction angulation from hernias, as well as esophagitis and gastritis. Manometry demonstrated weak swallows and sparse motility representative of a motility disorder. A gastric tube was placed for continued poor oral intake. She did not tolerate tube feeds, and gastric emptying study showed decreased emptying with marked GERD. EGD biopsies resulted and were consistent with eosinophilic esophagitis and H. pylori. She was prescribed triple therapy and started on PPI. She then had good symptom improvement and was discharged. At 6 week follow-up, the patient was able to tolerate oral intake and plans were initiated for gastric tube removal. DISCUSSION: Our patient exhibited numerous clinical findings that could account for her symptoms: esophageal herniations, eosinophilic esophagitis, H. pylori, an intrinsic motility disorder, and GERD. Though dysphagia has various etiologies, it is exceedingly rare for a single patient to display multiple simultaneous findings that might each individually explain their symptoms. Our case is unique in that the patient demonstrated sources from many different levels, yet given resolution with medication, likely originated from the primary eosinophilic esophagitis. Further investigation revealed the complexities of her case, and culminated in the eventual diagnosis, treatment, and symptomatic improvement. Our case also emphasizes the importance of thorough evaluation, as initial findings may be more complex than first realized.

Clinical Analysis of Primary Eosinophilic Esophagitis

Background/AimsEosinophilic esophagitis (EoE) is a chronic inflammatory disorder of the esophagus. Similar to asthma, EoE can induce irreversible structural changes in the esophagus as a result of chronic and persistent eosinophilic inflammation. The aim of this study was to analyse changes in symptoms, eosinophil counts and endoscopic findings after treatment.MethodsNine patients with EoE (6 men and 3 women; mean age, 36.44 years) were diagnosed with EoE based on typical symptoms, endoscopic abnormalities and infiltration of the esophageal epithelium with ≥ 15 eosinophils/high-power field. The average endoscopic follow-up period was 10 months, ranging from 1 to 25 months. Symptoms and endoscopic and pathological findings at initial observation and follow-up were evaluated.ResultsSeven of the 9 patients had dysphagia symptoms, which improved in 4 of 6 patients who were treated with proton pump inhibitor. Two patients were unresponsive to proton pump inhibitor and another 2 patients were treated with corticosteroid, which led to symptomatic relief. In 8 patients, esophageal eosinophilia was improved histologically at follow-up after treatment. Six of the 9 patients had typical endoscopic findings of EoE at initial examination. Despite treatment, these findings remained in 5 of the 6 patients at follow-up endoscopy.ConclusionsAfter treatment, the symptoms and eosinophil counts were temporarily improved, but the endoscopic findings of EoE were generally not improved. This indicates that deformity of esophageal structure due to eosinophilic inflammation might be irreversible despite proper management.

Emerging clinical evidence in the treatment of eosinophilic esophagitis

Primary eosinophilic esophagitis (EoE) is no longer rare. The treatment is currently ad hoc with no licensed medications available. Symptom improvements occur with diet, drugs or esophageal dilatation and these have been applied to patients depending on their age, severity of illness and their need for continuing symptom relief. Problems in treating EoE include difficulties in assessing disease severity and lack of a prognostic markers of disease progression. This article describes the current status of diet and topical steroid therapy. The evidence from randomized trials of biologic agents such as infliximab, mepolizumab, reslizumab and omalizumab show disappointing symptom benefit, despite changes to the immunobiology of the esophageal epithelium. Concerns regarding perforation during dilatation are discussed, and the use of EndoFLIP® to measure esophageal compliance is presented. CRTH-2 antagonists and montelukast are discussed. EoE will continue to require scientific and clinical research until an eff...

High Density Eosinophilic Infiltration in Gastro-Esophageal Reflux Disease is Rare and Probably Not Related to Primary Eosinophilic Esophagitis; A Cohort Study From the LOTUS trial

High Density Eosinophilic Infiltration in Gastro-Esophageal Reflux Disease is Rare and Probably Not Related to Primary Eosinophilic Esophagitis; A Cohort Study From the LOTUS trial

Index of Suspicion

Index of Suspicion

Potential of Blood Eosinophils, Eosinophil-Derived Neurotoxin, and Eotaxin-3 as Biomarkers of Eosinophilic Esophagitis

Eosinophilic esophagitis (EE) is an increasingly recognized disorder characterized by eosinophilic inflammation of the esophageal mucosa, and typically requires serial invasive endoscopic biopsy examinations to document the characteristic histologic features of the disorder. The aim of this study was to identify noninvasive biomarkers that correlated with disease activity and response to treatment as measured by esophageal eosinophilia. A prospective, cross-sectional analysis was performed on 47 pediatric patients undergoing endoscopic evaluation of possible EE. Blood samples were collected for measurement of peripheral blood absolute eosinophil count (AEC) and levels of eosinophil-derived neurotoxin (EDN), eotaxin-1, -2, and -3, and interleukin-5. Stool samples were collected for measurement of EDN. Biomarker levels were correlated with esophageal eosinophil density, and differences in biomarker levels based on disease activity and treatment were determined. AEC, plasma EDN levels, and eotaxin-3 levels significantly correlated with esophageal eosinophil density (AEC: r = 0.56, P < .0001; EDN: r = 0.54, P < .0001; eotaxin-3: r = 0.32, P = .04), and were increased in patients with active EE vs controls (AEC: 440 vs 140 eosinophils/muL, P < .05; EDN: 50.3 vs 31.1 ng/mL, P = .01; eotaxin-3: 37.7 vs 11.5 pg/mL, P = .01). Cut-off values were established to maximize the sensitivity, specificity, and predictive values of these biomarkers alone and in combination. Eotaxin-1, eotaxin-2, interleukin-5, and fecal EDN levels did not correlate with esophageal eosinophil density, and were not increased in active EE vs controls or those with inactive EE. These data show that blood levels of AEC, EDN, and eotaxin-3 may have value as noninvasive biomarkers for monitoring EE.

Epicutaneous Antigen Exposure Primes for Experimental Eosinophilic Esophagitis in Mice

Eosinophilic esophagitis (EE) is frequently associated with atopic disease, including dermatitis and asthma. Data are emerging that atopic skin may provide an early entry point for antigen sensitization. We aimed to test the hypothesis that epicutaneous exposure to antigen primes for subsequent respiratory antigen-induced EE. Wild-type and genetically engineered mice were subjected to epicutaneous antigen sensitization and the development of experimental EE, and immune responses were examined. We show that exposure to antigen via the epicutaneous route primes for marked eosinophilic inflammation in the esophagus triggered by a single airway antigen challenge. The development of experimental EE is associated with significant skin eosinophilia, accelerated bone marrow eosinophilopoiesis, blood eosinophilia, and large increases in serum antigen-specific immunoglobulin G1/immunoglobulin E using ovalbumin or Aspergillus fumigatus as the epicutaneous antigen. Mechanistic analysis with gene-targeted mice showed that interleukin-5 was required for esophageal eosinophilia and that interleukin-4, interleukin-13, and STAT6 contributed to a lesser extent. These findings provide the first evidence that epicutaneous exposure to allergens potently primes for EE via a Th2-dependent mechanism.

Natural history of primary eosinophilic esophagitis: a follow-up of 30 adult patients for up to 11.5 years

Background & Aims : Primary eosinophilic esophagitis is a chronic, increasingly recognized, interleukin 5-driven inflammatory disorder of the esophagus. The leading symptom in adults is uniform attacks of dysphagia, and the established histologic sign is a dense eosinophilic infiltration of the esophageal epithelium. Before this study, the natural course of eosinophilic esophagitis had not been defined and information regarding potential long-term risks was lacking. Methods : This prospective case series included 30 adult patients with eosinophilic esophagitis (22 men and 8 women; mean age, 40.6 years) whose diagnosis had been made >1 year before study debut based on typical history, consistent endoscopic abnormalities, and infiltration of the esophageal epithelium with >24 eosinophils/high-power field. After a mean of 7.2 years, patients underwent a comprehensive follow-up examination. Results : All patients survived the study period in good health and stable nutritional state. Dysphagia persisted in 29 patients, exerting a major negative effect on socioprofessional activities on 1 patient and a minor impact on 15. Attacks of dysphagia were more frequent in patients with blood eosinophilia or pronounced endoscopic alterations. The esophageal eosinophilic infiltration persisted in all symptomatic patients, but cell numbers spontaneously decreased significantly (78.7 vs. 40.3 cells/high-power field). The inflammatory process evoked fibrosis of the esophageal lamina propria but did not spread to the stomach or duodenum. No case evolved to a hypereosinophilic syndrome. Conclusions : Eosinophilic esophagitis, a primary and chronic disease restricted to the esophagus, leads to persistent dysphagia and structural esophageal alterations but does not impact the nutritional state. To date, no malignant potential has been associated with this disease.

Esophageal Eosinophilia In Children With Dysphagia

ABSTRACTObjectivesChildren 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.MethodsA 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.ResultsPatients with esophageal eosinophilia were more often male (p&lt;0.01) with a history of allergy (p&lt;0.001) and food bolus obstruction (p&lt;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.ConclusionChildren with dysphagia who have esophageal eosinophilia are unlikely to have pathologic gastroesophageal reflux.

Esophageal eosinophilia in children with dysphagia.

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. 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. 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. Children with dysphagia who have esophageal eosinophilia are unlikely to have pathologic gastroesophageal reflux.

Natural history primary eosinophilic esophagitis: A follow-up of 30 adult patients for up to 12 years

Natural history primary eosinophilic esophagitis: A follow-up of 30 adult patients for up to 12 years

Fragility of the esophageal mucosa: A pathognomonic endoscopic sign of primary eosinophilic esophagitis?

Background: Primary eosinophilic esophagitis, a chronic inflammatory disorder of the esophagus, evokes recurrent dysphagia. Endoscopy is often unremarkable, and no consensus exists regarding management of resultant dysphagia. The response of a series of patients with primary eosinophilic esophagitis to dilation is reported together with a description of a possibly pathognomonic sign: fragile esophageal mucosa, for which the term “crêpe-paper” mucosa is introduced. Methods: Five men underwent endoscopy because of dysphagia confirmed (clinically, endoscopically, and histologically) to be caused by primary eosinophilic esophagitis and were treated by bouginage. Observations: All patients had extremely fragile, inelastic, and delicate mucosa, which tore easily even with minor trauma. After the procedure, patients remained asymptomatic for 3 to 24 months. Conclusions: Primary eosinophilic esophagitis is characterized by fragile esophageal mucosa that readily tears in response to minor trauma during otherwise uneventful diagnostic endoscopy. This “crêpe-paper” sign may alert endoscopists to the presence of the disease when other mucosal alterations are lacking. Dilation is effective for patients with symptoms with minimal morbidity, despite development of disquieting lesions in response to the procedure.

Primary Eosinophilic Esophagitis in Children: SuccessfulTreatment With Oral Corticosteroids

Liacouras CA, Wenner WJ, Brown K, Ruchelli EJ Pediatr Gastroenterol Nutr.261998380To describe a group of children with gastroesophageal reflux disease (GERD) and persistent esophageal eosinophilia despite traditional antireflux therapy.From a total of 1809 children evaluated prospectively over a 2.5-year period for symptoms of GERD, 20 were identified with persistent symptoms and esophageal eosinophilia despite aggressive therapy with omeprazole and cisapride.The 20 children were treated with 1.5 mg/kg/d of oral methylprednisolone for 4 weeks. All patients underwent an extensive evaluation before treatment, including questionnaires about symptoms, blood counts, serum chemistries, immunoglobulin E (IgE) level, pH probe, and endoscopy. After treatment the questionnaires and endoscopy with biopsies of the esophagus, stomach, and duodenum were repeated.Histologic findings in pretreatment esophageal biopsies in the 20 children diagnosed with primary eosinophilic esophagitis revealed significantly greater eosinophilia (34.2 ± 9.6 eosinophils per high power field [HPF]) compared with biopsies from children with GERD who responded to medical therapy (2.26 ± 1.16 eosinophils per HPF, P < .001). After corticosteroid therapy, 19 of 20 children with primary eosinophilic esophagitis had dramatic clinical and histological improvement (1.5 ± 0.9 eosinophils per HPF). After 12 months of follow-up, 10 patients had remained asymptomatic and 9 redeveloped symptoms. In those with a recurrence of symptoms, treatment with an elemental diet lead to an improvement in 7, while 2 remained symptomatic and required further corticosteroid therapy.Children with GERD who were unresponsive to aggressive medical treatment and who displayed significant esophageal eosinophilia had both clinical and histologic improvement after oral corticosteroid therapy.This is a very useful study from a large pediatric gastroenterology clinic. It points out that the presence of significant eosinophilia in the esophagus may be a very different entity than standard GERD. Although the major conclusion that corticosteroids are helpful in this population is justified, from an allergist's viewpoint I would rather look for a dietary cause before embarking on a course of steroids. Their approach, however, of looking for food allergy only in those whose symptoms recurred after steroid therapy is also reasonable, especially because they found that a relatively short course of corticosteroid therapy was effective. In any event, we should not lose sight of the fact that the presence of significant eosinophilia is commonly associated with allergy, no matter where the eosinophils are located.

Primary Eosinophilic Esophagitis in Children: SuccessfulTreatment With Oral Corticosteroids

1. Liacouras CA, 2. Wenner WJ, 3. Brown K, 4. Ruchelli E (1998) J Pediatr Gastroenterol Nutr. 26:380. [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] #### Purpose of the Study To describe a group of children with gastroesophageal reflux disease (GERD) and persistent esophageal eosinophilia despite traditional antireflux therapy. ##### Study Population From a total of 1809 children evaluated prospectively over a 2.5-year period for symptoms of GERD, 20 were identified with persistent symptoms and esophageal eosinophilia despite aggressive therapy with omeprazole and cisapride. ##### Methods The 20 children were treated with 1.5 mg/kg/d of oral methylprednisolone for 4 weeks. All patients underwent an extensive evaluation before treatment, including … [1]: {openurl}?query=rft.jtitle%253DJournal%2Bof%2Bpediatric%2Bgastroenterology%2Band%2Bnutrition%26rft.stitle%253DJ%2BPediatr%2BGastroenterol%2BNutr%26rft.aulast%253DLiacouras%26rft.auinit1%253DC.%2BA.%26rft.volume%253D26%26rft.issue%253D4%26rft.spage%253D380%26rft.epage%253D385%26rft.atitle%253DPrimary%2Beosinophilic%2Besophagitis%2Bin%2Bchildren%253A%2Bsuccessful%2Btreatment%2Bwith%2Boral%2Bcorticosteroids.%26rft_id%253Dinfo%253Adoi%252F10.1097%2525176-199804000-00004%26rft_id%253Dinfo%253Apmid%252F9552132%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1097/00005176-199804000-00004&link_type=DOI [3]: /lookup/external-ref?access_num=9552132&link_type=MED&atom=%2Fpediatrics%2F104%2FSupplement_2%2F364.3.atom [4]: /lookup/external-ref?access_num=000072804300004&link_type=ISI

Eosinophilic esophagitis: A subset of eosinophilic gastroenteritis.

Eosinophilic gastroenteritis (EG) was first described over 50 years ago. Despite its long history, it remains an ill-defined and poorly understood entity. EG can present in a number of ways, none of which are exclusive to the disorder. EG has features of allergy and immune dysregulation but does not clearly fit into the category of allergic or immune disorder. While EG has been reported to affect all locations and layers of the gastrointestinal tract, the vast majority of reported cases have demonstrated mucosal involvement of the gastric antrum and small intestine in addition to disease activity of other locations of the gastrointestinal tract. Recently, several reports have identified a disease consisting of an isolated esophageal eosinophilia. Eosinophilic esophagitis (EE), also known as primary eosinophilic esophagitis or idiopathic eosinophilic esophagitis, occurs in adults and in children and represents a subset of EG with an isolated severe esophageal eosinophilia. Patients with EE present with symptoms similar to those of gastroesophageal reflux but are unresponsive to antireflux medication. Reports have demonstrated that patients with EE respond to either dietary restriction or corticosteroids.

Primary eosinophilic esophagitis in children: successful treatment with oral corticosteroids.

The histologic appearance of esophageal eosinophils has been correlated with esophagitis and gastroesophageal reflux disease in children. Esophageal eosinophilia that persists despite traditional antireflux therapy may not represent treatment failure, but instead may portray early eosinophilic gastroenteritis or allergic esophagitis. In this study, a series of pediatric patients with severe esophageal eosinophilia who were unresponsive to aggressive antireflux therapy were examined and their clinical and histologic response to oral corticosteroid therapy assessed. Of 1809 patients evaluated prospectively over 2.5 years for symptoms of gastroesophageal reflux, 20 had persistent symptoms and esophageal eosinophilia, despite aggressive therapy with omeprazole and cisapride. These patients were treated with 1.5 mg/kg oral methylprednisolone per day, divided into twice-daily doses for 4 weeks. All patients underwent clinical, laboratory, and histologic evaluation before and after treatment. Histologic findings in examination of specimens obtained in pretreatment esophageal biopsies in children with primary eosinophilic esophagitis indicated significantly greater eosinophilia (34.2+/-9.6 eosinophils/high-power field [HPF]) compared with that in children with gastroesophageal reflux disease who responded to medical therapy (2.26+/-1.16 eosinophils/HPF; p < 0.001). After corticosteroid therapy, all but one patient with primary eosinophilic esophagitis had dramatic clinical improvement, supported by histologic examination (1.5 +/-0.9 eosinophils/HPF, p < 0.0001). Pediatric patients in a series with marked esophageal eosinophilia and chronic symptoms of gastroesophageal reflux disease unresponsive to aggressive medical antire-flux therapy had both clinical and histologic improvement after oral corticosteroid therapy.