Chris A. Liacouras

Eosinophilic Esophagitis: A 10-Year Experience in 381 Children

BACKGROUND & AIMS Eosinophilic esophagitis (EoE) is a disorder characterized by a severe, isolated eosinophilic infiltration of the esophagus unresponsive to aggressive acid blockade but responsive to the removal of dietary antigens. We present information relating to our 10-year experience in children diagnosed with EoE. METHODS We conducted a retrospective study between January 1, 1994, and January 1, 2004, to evaluate all patients diagnosed with EoE. Clinical symptoms, demographic data, endoscopic findings, and the results of various treatment regimens were collected and evaluated. RESULTS A total of 381 patients (66% male, age 9.1 +/- 3.1 years) were diagnosed with EoE: 312 presented with symptoms of gastroesophageal reflux; 69 presented with dysphagia. Endoscopically, 68% of patients had a visually abnormal esophagus; 32% had a normal-appearing esophagus despite a severe histologic esophageal eosinophilia. The average number of esophageal eosinophils (per 400 x high power field) proximally and distally were 23.3 +/- 10.5 and 38.7 +/- 13.3, respectively. Corticosteroids significantly improved clinical symptoms and esophageal histology; however, upon their withdrawal, the symptoms and esophageal eosinophilia recurred. Dietary restriction or complete dietary elimination using an amino acid-based formula significantly improved both the clinical symptoms and esophageal histology in 75 and 172 patients, respectively. CONCLUSIONS Medications such as corticosteroids are effective; however, upon withdrawal, EoE recurs. The removal of dietary antigens significantly improved clinical symptoms and esophageal histology in 98% of patients.

ACG clinical guideline: Evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE).

Esophageal eosinophilia and eosinophilic esophagitis (EoE) are increasingly recognized and prevalent conditions, which now represent common clinical problems encountered by gastroenterologists, pathologists, and allergists. The study of EoE has become a dynamic field with an evolving understanding of the pathogenesis, diagnosis, and treatment. Although there are limited data supporting management decisions, clinical parameters are needed to guide the care of patients with eosinophilic–esophageal disorders. In this evidence-based review, recommendations developed by adult and pediatric gastroenterologists are provided for the evaluation and management of these patients. New terminology is emphasized, particularly the concepts of esophageal eosinophilia and proton-pump inhibitor-responsive esophageal eosinophilia (PPI-REE) as entities distinct from EoE.

Elemental Diet Is an Effective Treatment for Eosinophilic Esophagitis in Children and Adolescents

OBJECTIVE:Eosinophilic esophagitis (EoE), a disorder characterized by eosinophilic infiltration of the esophageal mucosa, has been defined in large part through published case reports and series leading to ambiguity in both diagnostic and treatment options. Corticosteroids, cromolyn, and elemental diet have all been reported as successful treatments for EoE. In this study, we sought to accurately define a population of patients with EoE and then assess their response to elemental diet.METHODS:A series of patients with chronic symptoms of gastroesophageal reflux disease and an isolated esophageal eosinophilia on esophagogastroduodenoscopy (EGD) were identified. Therapy with a proton pump inhibitor was instituted for 3 months, followed by repeat EGD when symptoms persisted. A 24-h pH probe study was performed, and those with significantly abnormal studies were excluded. The remaining patients were diagnosed with EoE and placed on an elemental diet for 1 month, followed by a repeat EGD.RESULTS:Of 346 patients with chronic gastroesophageal reflux disease symptoms and eosinophils on esophageal biopsy, 51 (14.7%) were ultimately diagnosed with EoE. There was significant improvement in vomiting, abdominal pain, and dysphagia after the elemental diet. The median number of esophageal eosinophils per high-powered field (HPF) decreased from 33.7 before the diet to 1.0 after the diet (p <0.01). The average time to clinical improvement was 8.5 days.CONCLUSIONS:Elemental diet resulted in striking improvement in both symptoms and histologic evidence of disease in children and adolescents with EoE, as identified by strict diagnostic criteria.

Primary eosinophilic esophagitis in children : Successful treatment with oral corticosteroids

BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSIONS 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.

Treatment of eosinophilic esophagitis with specific food elimination diet directed by a combination of skin prick and patch tests.

BACKGROUND Eosinophilic esophagitis (EE) is a recently described disorder identified in patients with symptoms suggestive of gastroesophageal reflux disease (GERD) but unresponsive to conventional reflux therapies. Therapies have included corticosteroids, elemental diet, and diet restriction. We report our experience with skin prick and atopy patch testing and food elimination diets in patients diagnosed as having EE. OBJECTIVE To identify food antigens that cause EE and the characteristics of patients who respond to food elimination vs those who are unresponsive. METHODS Patients diagnosed as having EE had restricted diets based on skin prick and atopy patch testing results. Additional biopsies were performed after 4 to 8 weeks of restricted diet. Demographics, atopic tendencies, and food antigens were identified retrospectively in our food allergy database. RESULTS A total of 146 patients diagnosed as having EE were evaluated with skin prick and atopy patch testing. Thirty-nine patients had unequivocal demonstration of food causing EE, with normalization of biopsy results on elimination and reoccurrence on reintroduction. An additional 73 patients, for a total 112 (77%) of 146 patients, had resolution of their EE as demonstrated by biopsy results. Fifteen (10%) of 146 patients were nonresponders manifested by no significant reduction in esophageal eosinophils despite restricted diet based on skin prick and atopy patch testing. Egg, milk, and soy were identified most frequently with skin prick testing, whereas corn, soy, and wheat were identified most frequently with atopy patch testing. CONCLUSION In more than 75% of patients with EE, both symptoms and esophageal inflammation can be significantly improved with dietary elimination of foods. Skin prick and atopy patch testing can help identify foods in most patients.

14 years of eosinophilic esophagitis: clinical features and prognosis.

Objective: To determine the natural history of treated and untreated eosinophilic esophagitis (EE) and examine the presenting symptoms of EE. Patients and Methods: Retrospective and prospective chart review of all patients diagnosed with EE at The Childrens Hospital of Philadelphia. EE was defined as greater than 20 eosinophils per high power field after treatment with reflux medications. Results: We identified 620 patients in our database in the last 14 years and 330 patients with greater than 1 year of follow-up for analysis. The number of new EE patients has increased on an annual basis. Of the patients presenting with EE, 68% were younger than 6 years old. Reflux symptoms and feeding issues/failure to thrive were the most common presenting symptoms for EE. Eleven patients had resolution of all of their food allergies and 33 patients had resolutions of some of their food allergies. No patients have progression of EE into other gastrointestinal disorders. Conclusions: EE is a chronic disease with less than 10% of the population developing tolerance to their food allergies. EE does not progress into other gastrointestinal diseases.

Common variants at 5q22 associate with pediatric eosinophilic esophagitis

Eosinophilic esophagitis (EoE) is an allergic disorder characterized by the accumulation of eosinophils in the esophagus. We report association of EoE with variants at chromosome 5q22 encompassing TSLP and WDR36 (rs3806932, combined P = 3.19 × 10−9). TSLP is overexpressed in esophageal biopsies from individuals with EoE compared with unaffected individuals, whereas WDR36 expression is unaltered between the two groups. These data implicate the 5q22 locus in the pathogenesis of EoE and identify TSLP as the most likely candidate gene in the region.

Identification of causative foods in children with eosinophilic esophagitis treated with an elimination diet.

BACKGROUND Eosinophilic esophagitis (EoE) is a chronic inflammatory disease with isolated eosinophils in the esophagus predominantly triggered by foods. The optimal testing to identify inciting foods remains unclear. OBJECTIVES We sought to determine the effectiveness of allergy testing-directed diets in patients with EoE. METHODS A retrospective analysis of all children with EoE seen at the Childrens Hospital of Philadelphia between 2000 and 2011 identified 941 patients with EoE. Skin prick tests (SPTs) and atopy patch tests (APTs) were conducted, and predictive values were calculated. IgE-mediated food reactions were also identified. A food was considered to cause EoE if its elimination led to resolution of esophageal eosinophilia or reintroduction led to reoccurrence of EoE. The effectiveness of the various elimination diets was compared with targeted food antigen elimination. RESULTS Definitive foods causing EoE were identified, with milk, egg, wheat, and soy as the most common foods in 319 patients. IgE-mediated reactions (urticaria and anaphylaxis) were seen in 15%. The negative predictive value for the combination of SPTs and APTs averaged 92%, with the exception of milk at 44%, and the positive predictive value averaged 44%. An empiric 6-food elimination diet or removal of positive foods on allergy testing (SPTs/APTs) both had a histologic success rate of 53%. Removal of foods identified on SPTs/APTs plus empiric elimination of milk leads to resolution in 77% of patients. CONCLUSION An elimination diet based on SPT/APT results leads to resolution of esophageal eosinophilia in a similar proportion of patients as empiric removal of foods but required that fewer foods be removed. These observations suggest that both methods are acceptable options.

Severity of Esophageal Eosinophilia Predicts Response to Conventional Gastroesophageal Reflux Therapy

ABSTRACT Pediatric patients who present with symptoms of gastroesophageal reflux and severe eosinophilic esophagitis may be unresponsive to aggressive anti-reflux medical therapy. In order to determine whether the degree of eosinophilia predicts anti-reflux treatment response and possibly distinguishes different etiologies, we reviewed the initial biopsies of patients with esophageal eosinophilia and compared the number of eosinophils with the response to anti-reflux treatment. Over a 1-year period, 102 patients with a biopsy demonstrating at least 1 intraepithelial eosinophil were identified among patients undergoing initial endoscopy for symptoms of reflux. All patients were treated with H2 blockers and prokinetic agents. Treatment response was classified into three categories: improvement, relapse, and failure. There were significant differences between the group who improved (mean eosinophil count [MEC] 1.1 ± 0.3 SEM) and those who failed (24.5 ± 6.1 SEM, P < 0.0025) or relapsed 6.4 ± 2.4 SEM, P < 0.05). A threshold MEC value of ≥7 provided a sensitivity of 61.3%, a specificity of 95.7%, and a predictive value for treatment failure of 86.1. A MEC value of <7 provided an 85% predictive value of successful therapy. From these data we made the following conclusions: (1) The number of eosinophils has a predictive value of treatment response with ≥7 per high power field offering a valuable clinical threshold for predicting outcome of conventional therapy. (2) The variable response to conventional reflux treatment may reflect different etiologies. (3) Alternate medical treatment modalities may be appropriate in the presence of severe eosinophilia, before considering surgical intervention.

Advances in Clinical Management of Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is a chronic immune/antigen-mediated clinicopathologic condition that has become an increasingly important cause of upper gastrointestinal morbidity in adults and children over the past 2 decades. It is diagnosed based on symptoms of esophageal dysfunction, the presence of at least 15 eosinophils/high-power field in esophageal biopsy specimens, and exclusion of competing causes of esophageal eosinophilia, including proton pump inhibitor-responsive esophageal eosinophilia. We review what we have recently learned about the clinical aspects of EoE, discussing the clinical, endoscopic, and histological features of EoE in adults and children. We explain the current diagnostic criteria and challenges to diagnosis, including the role of gastroesophageal reflux disease and proton pump inhibitor-responsive esophageal eosinophilia. It is also important to consider the epidemiology of EoE (with a current incidence of 1 new case per 10,000 per year and prevalence of 0.5 to 1 case per 1000 per year) and disease progression. We review the main treatment approaches and new treatment options; EoE can be treated with topical corticosteroids, such as fluticasone and budesonide, or dietary strategies, such as amino acid-based formulas, allergy test-directed elimination diets, and nondirected empiric elimination diets. Endoscopic dilation has also become an important tool for treatment of fibrostenotic complications of EoE. There are a number of unresolved issues in EoE, including phenotypes, optimal treatment end points, the role of maintenance therapy, and treatment of refractory EoE. The care of patients with EoE and the study of the disease span many disciplines; EoE is ideally managed by a multidisciplinary team of gastroenterologists, allergists, pathologists, and dieticians.