Treatment Guidelines h1 >
The following is a summary of currently accepted therapies in eosinophilic esophagitis, which as noted above has been the best studied of these diseases. These treatments have been reviewed in the process of developing consensus statements on the diagnosis and management of eosinophilic esophagitis (EoE). In the case of eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC), the relative rarity of these diseases has prevented the development of treatment guidelines at this time. One of the driving forces for the creation of CEGIR is to increase the number of patients studied to allow for the development of evidence-based treatment protocols.
The following is an invited article from Girish Hiremath, MD, MPH, at Vanderbilt University.
Treatment Approaches for Eosinophilic Esophagitis
Eosinophilic esophagitis (EoE) is an allergen-mediated disease affecting all ages, worldwide.1 Histologically, it is characterized by an eosinophil-predominant inflammation (defined as peak eosinophil count (PEC) of ≥ 15 eosinophils per high-power field) in the esophagus.2 Affected individuals develop esophageal symptoms depending on their age at the onset of EoE. For instance, children commonly present with vomiting, feeding difficulties, and abdominal pain. Given its chronic and progressive course, EoE typically continues into adulthood.3–5 A delay in diagnosis or uncontrolled eosinophilic inflammation in the esophageal epithelium can be associated with suboptimal quality of life and lead to fibrostenotic complications, such as esophageal narrowing or stricture, resulting in esophageal food impaction (EFI).6,7 Therefore, resolution of clinical symptoms and histologic remission (defined as an improvement in eosinophilic inflammation (PEC < 15 eosinophils per high-power field and mucosal healing) are among the primary goals of treating EoE. Over the past three decades, our understanding of EoE has substantially improved. Once considered a rare and case-reportable disease,8 EoE has emerged as a well-characterized, clinicopathologic condition and one of the more heavily researched upper gastrointestinal diseases. Emerging evidence suggests that the type 2 helper T (Th2)–cell driven inflammation involving the T cells, eosinophils, mast cells, and the cytokines, such as interleukin (IL)-4, IL-5, thymic stromal lympopoeitin (TSLP), and IL-13, are fundamentally involved in the immunopathogenesis of EoE.9,10 In addition, the genome-wide association studies have identified multiple genes, such as thymic stromal lymphopoietin (TSLP) and STAT6, that have a role in Th2 cell differentiation and development, as well as genes that have a vital role in epithelial cell function and esophageal epithelial barrier integrity.11 More recently, the inhibitory surface receptors expressed on eosinophils, mast cells, and basophils, known as Siglecs (sialic acid-binding immunoglobulin-like lectins), have been identified. These are considered as potential therapeutic targets, especially given their specific expression on allergic inflammatory cells.12 The growth of our knowledge base has led to the evolution of diagnostic and management guidelines from an expert opinion or consensus statement to an evidence-based approach.13–17 It has also spurred a host of treatments and has raised the possibility of personalizing EoE therapies.
The currently accepted EoE therapies are categorized as diet, drugs, and dilation (3 D’s). The first line of treatment in a patient with uncomplicated EoE can be either a dietary or a drug-based approach. The goal of these approaches are to induce and maintain remission of EoE to minimize the risk of potential fibrostenotic complications. Choosing which approach to pursue is typically based on the shared decision-making between the patient, their caregivers (or parents in pediatric patients), and their healthcare providers.18 Endoscopic interventions, such as esophageal dilation, are generally considered for patients with complicated EoE.19
The rationale for dietary intervention is to control the eosinophilic inflammation in the esophagus by eliminating food-allergen(s) presumed to be causing EoE and avoiding medications and their related side effects.20 The three typical diets are the elemental diet, allergy test-directed elimination, and empiric elimination.
An elemental diet is an allergen-free diet. It involves consuming amino acid-based formulas as the sole source of nutrition. Although an elemental diet is about 91% effective in controlling eosinophilic inflammation in EoE, it has significant limitations. Some limitations include the formula's high cost, poor palatability, the long dietary reintroduction period, and frequent endoscopy (EGD) with biopsies to identify the food allergen.21–23
An allergy test-directed elimination diet is based on eliminating food and aeroallergen, identified by either a serum IgE, skin prick, or atopy patch test. Although these tests are designed to identify antigens for immediate food hypersensitivity and other atopic conditions, such as asthma, atopic rhinitis, and eczema, they have shown very limited accuracy in identifying specific triggers for EoE in an individual. Dairy, egg, wheat, and soy are among the most common antigens identified through allergy tests in children, and most adults appear to be sensitized to peanuts, eggs, and soy.24–26 A meta-analysis of 33 studies (including 1,317 individuals with EoE) reported a 45.5% success rate for an allergy test-based elimination diet, making this the least effective dietary elimination strategy and one that may be gradually falling out of favor in clinical practice.27
An empiric elimination diet is the most well-studied and the most favored dietary elimination approach. It involves the elimination of foods, including dairy, egg, wheat, soy, nuts, and seafood, identified through epidemiologic studies, and are commonly associated with EoE. There are several ways to implement the empiric elimination diet.28,29 It can be either one-food elimination (1FED, usually dairy with up to 68% cumulative efficacy), two-food elimination (2FED, usually dairy and wheat with 43% cumulative efficacy), four-food elimination (4FED, usually dairy, wheat, egg, soy with up to 71% cumulative efficacy), and six-food elimination (6FED, usually dairy, egg, wheat, soy, nuts, and seafood with incremental effectiveness of up to 78%).27 Furthermore, one can employ an empiric elimination diet as a step-up (1FED, 2FED, 4FED, and 6FED) or a step-down approach (6FED, 4FED, 2FED, and 1FED) in clinical practice.30 Once again, choosing which approach to pursue is typically based on the shared decision-making between the patient, their caregivers (or parents of pediatric patients), and their healthcare providers. CEGIR conducted a multi-site, randomized, prospective trial comparing 1FED (milk elimination) vs. 6FED (milk, wheat, fish, soy, nuts and egg).31 Interestingly, this study showed similar responses between 1FED and 6FED, both achieving ~40% remission rates. These findings provide a strong rationale for first starting with milk elimination therapy.
Pursuing a dietary elimination approach to identify triggering food allergen(s) can be expensive and time consuming and may require multiple endoscopies with biopsies to confirm treatment response or relapse of EoE. It may also be associated with growth issues and nutritional deficiencies, particularly in children.32 Furthermore, it can have unintended ramifications for the patients' and their caregivers' social and emotional well-being.33
The proton-pump inhibitors (PPIs) and topical corticosteroids (TCS) are currently the mainstays of the management of EoE. More recently, there has been immense interest in developing therapeutics targeting the specific molecules in the immunopathogenesis pathways to induce clinical improvement and histologic remission of EoE.
Many consider PPIs as first-line therapy since this medication has been used for a long time for non-EoE indications. Additionally, PPIs well-studied in EoE and are readily available and relatively easy to administer. It can be administered as a tablet, and for those who have difficulty swallowing a tablet, it can be administered as an oral solution, orodispersible tablets, or as granules mixed with applesauce. Once administered, the PPIs can induce gastric acid suppression, leading to a restoration of esophageal barrier function, inhibition of eosinophilic migration to the esophagus, inhibition of ATP12A, activation of the aryl hydrocarbon receptor, and reduction of STAT6 mediated eotaxin-3 (an eosinophil chemoattractant) expression.34,35 It is now appreciated that the primary mechanism of PPI therapy in EoE is not related to acid suppression but rather the anti-inflammatory effect of this class of medicines. The histologic response rate for PPI therapy in children ranges between 23-83%, and in adolescents and adults, it ranges between 40-60%. The clinical response rate in children ranges between 23-82% and 48-72% in adults.36 The current recommendation is 1-2 mg/kg/day, divided twice daily, with a maximum of 40 mg twice daily of esomeprazole and omeprazole and 30 mg twice daily of lansoprazole in children with EoE. For adults with EoE, it is 20-40 mg, once or twice daily. EGD with biopsies is recommended between 8-12 weeks to assess the treatment response.37
The American Gastroenterological Association Joint Task Force EoE management guidelines recommend PPI therapy for patients with symptomatic esophageal eosinophilia, but this is a conditional recommendation with very little quality evidence. The available evidence is limited by the lack of placebo-controlled studies and heterogeneity in study design (patient selection and type, dose, and duration of PPIs). There are limited data on the efficacy of PPIs as a maintenance therapy for EoE.14 Between 13-60% of patients with EoE lose clinical response to PPIs over a 6-month to 2.9-year follow-up period. However, most experts agree that stepping down the PPI dose to the lowest dose possible that maintains remission is recommended. The United States Food and Drug Administration (FDA) has expressly cautioned people who use PPI standard doses on the risk of Clostridioides difficile infection, bone fractures, and hypomagnesemia. In addition, there is conflicting evidence for and against the association between the standard dose PPI use and the risk of pneumonia, other enteric infections, chronic kidney disease, dementia, cardiovascular events, and all-cause mortality.38 However, one must be careful in interpreting these studies in the context of residual confounders and study designs.
The TCS can not only alleviate the eosinophilic inflammation in the esophageal epithelium, but also lower epithelial cell apoptosis, decrease esophageal molecular remodeling, reduce the dilated intercellular spaces, and downregulate mast cell activity.39 The two most used TCS in clinical practice are budesonide40–44 and fluticasone propionate.45–47
Budesonide is commonly administered as a slurry (oral viscous Budesonide (OVB)) mixed with various ‘vehicles’, including sucralose, Neocate Nutra (a semi-solid, amino acid-based hypoallergenic formula), honey, and apple sauce.48 Mixing with a vehicle of the patient’s choice allows for optimal consistency, adequate contact time with the esophageal mucosa, and palatability that can promote compliance to the medication.49 Budesonide is also approved as an orodispersible tablet for induction and maintenance of remission of EoE by the European Medicine Agency.44,50,51
Fluticasone propionate can be swallowed from a metered-dose inhaler (MDI), a diskus (a device containing medication as blister packs), or an oral viscous suspension. The most frequent method to administer Fluticasone is by MDI. The patient directly sprays medication into their mouth (without a spacer) and then swallows the aerosolized medication. They then rinse their mouth and spit it out to avoid any oral side effects. A video demonstration of this technique is available here. Although some retrospective studies have suggested that treatment with OVB leads to better endoscopic and histologic outcomes than fluticasone propionate,52,53 prospective randomized clinical trials have shown that both OVB and fluticasone MDI produced a comparable significant improvement in dysphagia and endoscopic features and a decrease in esophageal eosinophilia.54 Other TCS, although less commonly used, are ciclesonide55–57, mometasone,58 and beclomethasone.59,60 Possible adverse effects of TCS preparations include local candida overgrowth, adrenal axis suppression, and concerns for suppression of height velocity.61,62
Other medications, although very uncommonly used in clinical practice, include systemic steroids (prednisone)47 and mast cell stabilizers (cromolyn sodium)63.
With a greater understanding of the molecular mechanisms underlying EoE, limitations and side effects of existing therapeutic approaches, and advances in biotechnological methods, there is burgeoning interest in developing biologic therapies for EoE.
The first biologics tested for EoE were the antibodies against circulating IL-5, including mepolizumab and reslizumab.64,65 The IL-5 is a cytokine that regulates eosinophils' development, differentiation, and survival, including eosinophil trafficking to the esophagus in EoE.66 In clinical trials, both mepolizumab and reslizumab significantly reduced esophageal eosinophil levels compared to a placebo. However, the clinical outcomes (physician global assessment scores) were not significantly better than the placebo.65,67 Likewise, benralizumab, a monoclonal antibody targeting IL-5Rα-chain with cytotoxic effects on eosinophils, resulted in histologic remission, but the clinical response was heterogeneous (MESSINA trial).
In an open-label, pilot study, omalizumab, an anti-IgE antibody commonly used in IgE-mediated asthma and food allergies, showed early promise by inducing clinical and histologic remission in 33% of the 15 patients enrolled.68 However, a follow-up randomized control trial in 30 patients showed that omalizumab did not offer a significant clinical benefit or histologic improvement compared with a placebo.69 Likewise, infliximab, a chimeric IgG1 monoclonal antibody, and a potent tumor necrosis factor-α inhibitor with demonstrated efficacy in treating inflammatory bowel disease, including Crohn disease, has been used in adult patients with severe, corticosteroid-dependent EoE. However, in a prospective T1 translational study, infliximab in a standard induction dosage schedule did not induce histologic resolution nor improve the clinical symptoms. In addition, like omalizumab, it evoked heterogeneous reactions ranging from non-response to a mild flare-up.70 There have been reports of the use of Vedolizumab, an anti-α4β7 integrin agent that inhibits leukocyte trafficking and mediates Th2 cytokine effects by binding with high affinity to eosinophils and CD4 T cells in patients. This was used in patients with Crohn disease and concomitant EoE with limited success.71–73
In an initial study, AK002 (or lirentelimab), a siglec 8 inhibitor, led to histologic remission in 93% of patients with EoE compared to 11% in the placebo group and improved dysphagia in the EoE group compared to the placebo group.74 Subsequently, in a phase 2/3, 24-week, randomized, placebo-controlled study of lirentelimab in patients with EoE, although a significant improvement in the histologic resolution was noted compared to the placebo group, the difference in the absolute mean change in the dysphagia symptom questionnaire score in the EoE group compared to the placebo group did not achieve statistical significance (KRYPTOS study). Finally, in a clinical trial, QAX576, a fully humanized anti-IL-13 monoclonal antibody, improved the esophageal intraepithelial eosinophilia, eotaxin-3, and periostin expression but did not significantly improve clinical symptoms compared to the placebo.75
Currently, the biologics targeting IL-4 and IL-13, key and upstream Th2 cytokines central to EoE pathogenesis, are being extensively studied. In 2022, Dupilumab, a fully humanized monoclonal antibody that blocks IL-4 and IL-13 signaling, became the first FDA-approved medication for EoE, or any EGID. In the three-part, randomized, double-blind, placebo-controlled trials, Dupilumab administered subcutaneously at a weekly dose of 300 mg resulted in histologic remission and improvement in symptoms of EoE in adolescents (≥ 12 years and ≥ 40 kgs) and adults. The histologic improvement in every two-week dosing regimen was qualitatively like the weekly dosing regimen. However, the differences between the every two-week regimen and the placebo did not achieve statistical significance. Notably, impedance planimetry was studied as an exploratory endpoint, and Dupilumab therapy significantly improved esophageal distensibility by 18% compared with placebo. Injection site reaction (most common), upper respiratory infections, arthralgia, and conjunctivitis were some of the adverse events reported (PMID: 36546624). Although having an FDA-approved drug for EoE is a significant milestone, several important questions remain about the placement of Dupilumab in the treatment algorithm for EoE. For instance, can Dupilumab be used as first-line therapy for EoE instead of tried and tested approaches, such as PPI and TCS, and should the use of Dupilumab be limited to difficult-to-treat EoE cases?
There are several promising therapeutic options in the pipeline. Cendakimab (or CC-93538, previously RPC4046), a humanized monoclonal antibody blocking IL-13 and its binding to IL-13Ra1 and IL-13Ra2, has been shown to reduce esophageal eosinophilia, improve endoscopic features, and reduce clinical dysphagia in patients with EoE, particularly in patients with steroid-refractory EoE. A phase 2/3, multicenter, multinational, randomized, double-blind, placebo-controlled induction and long-term controlled study to evaluate the efficacy and safety of Cendakimab in adolescents and adults with EoE is currently underway (NCT04991935).
Etrsimod, an oral sphingosine 1-phosphate receptor modulating targeting multiple S1P receptors (S1P1, S1P4, and S1P5) with demonstrated effectiveness in improving clinical and endoscopic disease in moderate to severe ulcerative colitis, is currently being tested for safety and efficacy in EoE in phase 2, randomized, double-blind, placebo-controlled study (NCT04682639).
The levels of IL-15 and its receptor IL-15R alpha are increased six and ten-fold, respectively, in esophageal tissues in patients with EoE. Furthermore, IL-15 regulates immune responses, particularly at gastrointestinal mucosal interfaces. The safety, tolerability, pharmacokinetics, and pharmacodynamics of intravenous treatment of CALY-002, an anti-IL-15 antibody, in a cohort of healthy subjects and subjects with celiac disease and EoE is currently underway (NCT04593251).
Finally, Tezepelumab, an anti-TSLP monoclonal antibody that has shown promise in patients with uncontrolled asthma, has been granted Orphan Drug Designation in the US for EoE. A phase 3 trial to investigate the efficacy and safety of Tezepelumab in EoE is currently underway (NCT05583227).
Conceivably, one or more of these additional promising therapeutic options (see Table below) may soon become available for clinical use (in addition to the dupilumab). However, several factors, including the cost, accessibility, effectiveness, safety, and the duration of clinical and histologic response over time, will influence the use of biologics in clinical practice.
Table: Biologics currently being investigated for EoE
|Active/Study Drug||Mechanism of Action||Ages (Years)||Clinical Trail*|
Monoclonal antibody against IL-4 receptor alpha 1 (blocks IL-4 and IL-13 signaling)
Monoclonal antibody against IL-4 receptor alpha 1 (blocks IL-4 and IL-13 signaling)
Tezepelumab (CROSSING study)
|Monoclonal antibody against TSLP#||≥ 12 (and ≥ 40 kilograms)||Phase 3||NCT05583227|
|>Alpha-1 proteinase inhibitor||18-70||
Phase 2 (open label)
|EP-104IAR||18-75||Phase 1b (open label)||NCT05608681|
*Per ClinicalTrials.gov accessed on 01.13.2023; #TSLP: Thymic stromal lymphopoietin
Currently, repeated EGD with biopsies is required for diagnosing and monitoring EoE. EGD also has a crucial therapeutic role in the management of esophageal strictures, EFIs, and related complications, including esophageal perforation and bleeding.
Esophageal strictures are graded as mild (> 9 mm in diameter) and moderate to severe (< 9 mm). A goal esophageal caliber of at least 16 mm in adolescents and adults is reported to relieve dysphagia and possibly decrease the likelihood of EFIs.76 Although esophageal dilations are performed to manage esophageal strictures related to EoE, this alone may not treat the underlying eosinophilic inflammation that led to the stricture formation. Additional, concomitant treatment will be required to control the inflammation, increase the esophageal caliber, and potentially decrease the need for future dilations.77
The techniques and approaches for endoscopic dilation have evolved over the years. However, existing techniques and approaches are considered safer and result in better-tolerated procedures. Balloon dilators are commonly used through the scope, followed by Savary dilators and Maloney dilators.19,78 There is limited guidance regarding what type of dilator is best, and it largely depends on the endoscopist’s training, experience, preference, and comfort level.
EFI is relatively common in adolescents and adults with EoE. It can be the presenting symptom of EoE in up to 55% of patients, and a quarter of patients have recurrent food impactions.79,80 An urgent or emergent flexible EGD to remove the lodged food is usually necessary, depending on whether there is complete or near a complete esophageal obstruction. En bloc, piecemeal, cap-assisted, and push techniques are different methods for managing EFIs.81 The push technique has been used in adults with a low risk of complications but has not been well described in children.82,83 Various tools have been described for removing the impacted food, including forceps (rat tooth, alligator, and biopsy forceps), snare, retrieval net, tripod grasper, basket, and suction. More than one tool and technique may be required in complex cases. For example, an overtube in older children can limit mucosal trauma if multiple passes are needed.84 Regardless of the tool(s) and/or technique(s) used to remove the impacted food, it is strongly recommended that multiple biopsies (away from the site of impaction) be obtained after removal, given the strong association between esophageal food impaction and EoE and the requirement for histologic confirmation of the diagnosis.85 Mucosal friability related to active inflammation and esophageal remodeling may place individuals with EFI at an increased risk of perforation and bleeding during the removal of the impacted food bolus or dilation of esophageal strictures.86 Typically, these complications are managed conservatively. Rarely, metal esophageal stents, endoscopic clips, and surgical interventions may be indicated. No deaths have been reported related to either esophageal perforation or therapy.87
Leveraging complex data and Precision medicine
With a robust understanding of the genetic underpinnings and molecular mechanisms of EoE, the treatment and prevention strategies can perhaps be tailored for each EoE patient using artificial intelligence or machine learning.88 For instance, how the pharmacogenetic variants influence PPI response (e.g., CYP2C19*17) and PPI pharmacodynamics (e.g., STAT6 rs324011 is associated with a 6.1-fold increased risk of failure to achieve a complete remission with PPI therapy) has already been reported.89,90 There have been attempts at identifying molecular endotypes of patients with EoE.91 Phenotypic classifications (fibrostenotic phenotype) have also shown promise in predicting response to PPI both in the induction and maintenance phases.92 In addition, esophageal microRNAs in the esophageal biopsies appear to discriminate between PPI responders and non-responders at baseline.93 Response to diet therapy may be predicted by baseline levels of milk-specific IgG4.94
EoE is an increasingly prevalent, chronic, and progressive disease affecting all ages worldwide. Dietary elimination of food allergens, drugs including biologics, and esophageal dilation are the prevailing treatment options. However, new therapeutic targets are being discovered and this is promoting development of novel therapies for EoE. It is conceivable that soon we will transition from a 'one fits all' approach to a 'precision medicine' approach wherein the phenotype and the endotype of a patient with EoE would guide the patient's treatment.
- Navarro P, Arias Á, Arias-González L, et al. Systematic review with meta-analysis: the growing incidence and prevalence of eosinophilic oesophagitis in children and adults in population-based studies. Aliment Pharmacol Ther 2019;49.
- Furuta GT, Katzka DA. Eosinophilic Esophagitis Definition and Differential Diagnosis. N Engl J Med 2016;373:1640-1648.
- Hiremath G, Rogers E, Kennedy E, et al. Relationship between eating behavior in school aged children with eosinophilic esophagitis and their caregiver’s quality of life: It’s complicated! J Pediatr Gastroenterol Nutr 2018;67.
- Hiremath G, Rogers E, Kennedy E, et al. A Comparative Analysis of Eating Behavior of School-Aged Children with Eosinophilic Esophagitis and Their Caregivers’ Quality of Life: Perspectives of Caregivers. Dysphagia 2019;34.
- Straumann A, Aceves SS, Blanchard C, et al. Pediatric and adult eosinophilic esophagitis: Similarities and differences. Allergy: European Journal of Allergy and Clinical Immunology 2012;67:477-490.
- Dellon ES, Kim HP, Sperry SLW, et al. A phenotypic analysis shows that eosinophilic esophagitis is a progressive fibrostenotic disease. Gastrointest Endosc 2014;79.
- Schoepfer AM, Safroneeva E, Bussmann C, et al. Delay in diagnosis of eosinophilic esophagitis increases risk for stricture formation in a time-dependent manner. Gastroenterology 2013;145:1230-1236.e2.
- Kelly KJ, Lazenby AJ, Rowe PC, et al. Eosinophilic esophagitis attributed to gastroesophageal reflux: Improvement with an amino acid-based formula. Gastroenterology 1995;109.
- Blanchard C, Wang N, Rothenberg ME. Eosinophilic esophagitis: Pathogenesis, genetics, and therapy. Journal of Allergy and Clinical Immunology 2006;118.
- Ryu S, Lee KH, Tizaoui K, et al. Pathogenesis of eosinophilic esophagitis: A comprehensive review of the genetic and molecular aspects. Int J Mol Sci 2020;21.
- Sleiman PMA, Wang ML, Cianferoni A, et al. GWAS identifies four novel eosinophilic esophagitis loci. Nat Commun 2014;5.
- T. K, N. K, J.C. P, et al. Siglec-8 as a drugable target to treat eosinophil and mast cell-associated conditions. Pharmacol Ther 2012;135.
- Lucendo AJ, Molina-Infante J, Arias Á, et al. Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults. United European Gastroenterol J 2017;5:335-358.
- Hirano I, Chan ES, Rank MA, et al. AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters Clinical Guidelines for the Management of Eosinophilic Esophagitis. Gastroenterology 2020;158.
- Liacouras CA, Furuta GT, Hirano I, et al. Eosinophilic esophagitis: Updated consensus recommendations for children and adults. Journal of Allergy and Clinical Immunology 2011;128:3-20.e6.
- Dellon ES, Liacouras CA, Molina-Infante J, et al. Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the AGREE Conference. In: Gastroenterology. Vol 155. , 2018:1022-1033.e10.
- Furuta GT, Liacouras CA, Collins MH, et al. Eosinophilic Esophagitis in Children and Adults: A Systematic Review and Consensus Recommendations for Diagnosis and Treatment. Sponsored by the American Gastroenterological Association (AGA) Institute and North American Society of Pediatric Gastroenterol. Gastroenterology 2007;133:1342-1363.
- Sauer BG, West A, McGowan EC. Multidisciplinary Eosinophilic Esophagitis Care: A Model for Comprehensive Patient-Centered Care Through Shared Decision Making Between Gastroenterology, Allergy, and Nutrition. Clinical Gastroenterology and Hepatology 2021;19.
- Lucendo AJ, Arias Á, Molina-Infante J, et al. The role of endoscopy in eosinophilic esophagitis: from diagnosis to therapy. Expert Rev Gastroenterol Hepatol 2017;11.
- Visaggi P, Mariani L, Pardi V, et al. Dietary management of eosinophilic esophagitis: Tailoring the approach. Nutrients 2021;13.
- Peterson KA, Byrne KR, Vinson LA, et al. Elemental diet induces histologic response in adult eosinophilic esophagitis. American Journal of Gastroenterology 2013;108.
- Markowitz JE, Spergel JM, Ruchelli E, et al. Elemental diet is an effective treatment for eosinophilic esophagitis in children and adolescents. American Journal of Gastroenterology 2003;98.
- Kliewer KL, Cassin AM, Venter C. Dietary Therapy for Eosinophilic Esophagitis: Elimination and Reintroduction. Clin Rev Allergy Immunol 2018;55.
- Spergel JM, Beausoleil JL, Mascarenhas M, et al. The use of skin prick tests and patch tests to identify causative foods in eosinophilic esophagitis. Journal of Allergy and Clinical Immunology 2002;109.
- Molina-Infante J, Martin-Noguerol E, Alvarado-Arenas M, et al. Selective elimination diet based on skin testing has suboptimal efficacy for adult eosinophilic esophagitis. Journal of Allergy and Clinical Immunology 2012;130.
- Spergel JM, Andrews T, Brown-Whitehorn TF, et al. Treatment of eosinophilic esophagitis with specific food elimination diet directed by a combination of skin prick and patch tests. Annals of Allergy, Asthma and Immunology 2005;95.
- Arias Á, González-Cervera J, Tenias JM, et al. Efficacy of dietary interventions for inducing histologic remission in patients with eosinophilic esophagitis: A systematic review and meta-analysis. Gastroenterology 2014;146.
- Lucendo AJ, Arias Á, González-Cervera J, et al. Empiric 6-food elimination diet induced and maintained prolonged remission in patients with adult eosinophilic esophagitis: A prospective study on the food cause of the disease. Journal of Allergy and Clinical Immunology 2013;131.
- Kagalwalla AF, Shah A, Li BUK, et al. Identification of specific foods responsible for inflammation in children with eosinophilic esophagitis successfully treated with empiric elimination diet. J Pediatr Gastroenterol Nutr 2011;53.
- Molina-Infante J, Arias Á, Alcedo J, et al. Step-up empiric elimination diet for pediatric and adult eosinophilic esophagitis: The 2-4-6 study. Journal of Allergy and Clinical Immunology 2018;141.
- Kliewer K, Gonsalves N, Dellon ES, et al. 535 EFFICACY OF ONE-FOOD VERSUS SIX-FOOD ELIMINATION DIET FOR TREATMENT OF EOSINOPHILIC ESOPHAGITIS IN ADULTS: RESULTS FROM THE MULTICENTER RANDOMIZED CONTROLLED SOFEED TRIAL. Gastroenterology 2021;160.
- Bashaw H, Schwartz S, Kagalwalla AF, et al. Tutorial: Nutrition Therapy in Eosinophilic Esophagitis—Outcomes and Deficiencies. Journal of Parenteral and Enteral Nutrition 2020;44.
- Hiremath G, Kodroff E, Strobel MJ, et al. Individuals affected by eosinophilic gastrointestinal disorders have complex unmet needs and frequently experience unique barriers to care. Clin Res Hepatol Gastroenterol 2018;42:483-493.
- Cheng E, Zhang X, Huo X, et al. Omeprazole blocks eotaxin-3 expression by oesophageal squamous cells from patients with eosinophilic oesophagitis and GORD. Gut 2013;62.
- Zhang X, Cheng E, Huo X, et al. Omeprazole Blocks STAT6 Binding to the Eotaxin-3 Promoter in Eosinophilic Esophagitis Cells. PLoS One 2012;7.
- Lucendo AJ, Arias Á, Molina-Infante J. Efficacy of Proton Pump Inhibitor Drugs for Inducing Clinical and Histologic Remission in Patients With Symptomatic Esophageal Eosinophilia: A Systematic Review and Meta-Analysis. Clinical Gastroenterology and Hepatology 2016;14:13-22.e1.
- Tamarit-Sebastian S, Ferrer-Soler FM, Lucendo AJ. Current options and investigational drugs for the treatment of eosinophilic esophagitis. Expert Opin Investig Drugs 2022;31.
- Franciosi JP, Mougey EB, Dellon ES, et al. Proton Pump Inhibitor Therapy for Eosinophilic Esophagitis: History, Mechanisms, Efficacy, and Future Directions. J Asthma Allergy 2022;15.
- Nennstiel S, Schlag C. Treatment of eosinophlic esophagitis with swallowed topical corticosteroids. World J Gastroenterol 2020;26.
- Chen X, Li X. Budesonide Oral Suspension Improves Outcomes in Patients With Eosinophilic Esophagitis. Clinical Gastroenterology and Hepatology 2022;20.
- Straumann A, Conus S, Degen L, et al. Budesonide is effective in adolescent and adult patients with active eosinophilic esophagitis. Gastroenterology 2010;139.
- Hirano I, Collins MH, Katzka DA, et al. Budesonide Oral Suspension Improves Outcomes in Patients With Eosinophilic Esophagitis: Results from a Phase 3 Trial. Clinical Gastroenterology and Hepatology 2022;20.
- Dohil R, Newbury R, Fox L, et al. Oral viscous budesonide is effective in children with eosinophilic esophagitis in a randomized, placebo-controlled trial. Gastroenterology 2010;139.
- Lucendo AJ, Miehlke S, Schlag C, et al. Efficacy of Budesonide Orodispersible Tablets as Induction Therapy for Eosinophilic Esophagitis in a Randomized Placebo-Controlled Trial. Gastroenterology 2019;157.
- Willis A, Mani S. Efficacy of Budesonide versus Fluticasone in Children with Eosinophilic Esophagitis. Journal of Allergy and Clinical Immunology 2022;149.
- Peterson KA, Thomas KL, Hilden K, et al. Comparison of esomeprazole to aerosolized, swallowed fluticasone for eosinophilic esophagitis. Dig Dis Sci 2010;55.
- Schaefer ET, Fitzgerald JF, Molleston JP, et al. Comparison of Oral Prednisone and Topical Fluticasone in the Treatment of Eosinophilic Esophagitis: A Randomized Trial in Children. Clinical Gastroenterology and Hepatology 2008;6.
- Lee J, Shuker M, Brown-Whitehorn T, et al. Oral viscous budesonide can be successfully delivered through a variety of vehicles to treat eosinophilic esophagitis in children. Journal of Allergy and Clinical Immunology: In Practice 2016;4.
- Główczewski A, Krogulska A. Formulations of Topical Steroids in Eosinophilic Esophagitis—Current Treatment and Emerging Possibilities. J Clin Med 2022;11.
- Miehlke S, Schlag C, Storr M, et al. Eosinophilic Esophagitis Update: New Guidelines of the European Study Group EUREOS. Laryngorhinootologie 2019;98.
- Miehlke S, Lucendo AJ, Straumann A, et al. Orodispersible budesonide tablets for the treatment of eosinophilic esophagitis: a review of the latest evidence. Therap Adv Gastroenterol 2020;13.
- Fable JM, Fernandez M, Goodine S, et al. Retrospective comparison of fluticasone propionate and oral viscous budesonide in children with Eosinophilic esophagitis. J Pediatr Gastroenterol Nutr 2018;66.
- Albert D, Heifert TA, Min SB, et al. Comparisons of Fluticasone to Budesonide in the Treatment of Eosinophilic Esophagitis. Dig Dis Sci 2016;61.
- Dellon ES, Woosley JT, Arrington A, et al. Efficacy of Budesonide vs Fluticasone for Initial Treatment of Eosinophilic Esophagitis in a Randomized Controlled Trial. Gastroenterology 2019;157:65-73.e5.
- Schroeder S, Fleischer DM, Masterson JC, et al. Successful treatment of eosinophilic esophagitis with ciclesonide. Journal of Allergy and Clinical Immunology 2012;129.
- Nistel M, Nguyen N, Atkins D, et al. Ciclesonide Impacts Clinicopathological Features of Eosinophilic Esophagitis. Journal of Allergy and Clinical Immunology: In Practice 2021;9.
- Lee JJ, Fried AJ, Hait E, et al. Topical inhaled ciclesonide for treatment of eosinophilic esophagitis. Journal of Allergy and Clinical Immunology 2012;130.
- Syverson EP, Hait E, McDonald DR, et al. Oral viscous mometasone is an effective treatment for eosinophilic esophagitis. Journal of Allergy and Clinical Immunology: In Practice 2020;8.
- Bhardwaj N, Ishmael F, Lehman E, et al. Effect of Topical Beclomethasone on Inflammatory Markers in Adults with Eosinophilic Esophagitis: A Pilot Study. Allergy and Rhinology 2017;8.
- Ghaffari G. A randomized double blind placebo controlled crossover study of the effect of swallowed beclomethasone dipropionate on inflammatory markers in adult patients with eosinophilic esophagitis:a pilot study. Annals of Allergy, Asthma and Immunology 2011;107.
- Tomizawa Y, Melek J, Komaki Y, et al. Efficacy of Pharmacologic Therapy for Eosinophilic Esophagitis A Systematic Review and Network Meta-Analysis. J Clin Gastroenterol 2018;52.
- Kumar S, Choi SS, Gupta SK. Eosinophilic esophagitis: current status and future directions. Pediatr Res 2020;88.
- Lieberman JA, Zhang J, Whitworth J, et al. A randomized, double-blinded, placebo-controlled study of the use of viscous oral cromolyn sodium for the treatment of eosinophilic esophagitis. Annals of Allergy, Asthma and Immunology 2018;120.
- Walsh GM. Reslizumab, a humanized anti-IL-5 mAb for the treatment of eosinophil-mediated infammatory conditions. Curr Opin Mol Ther 2009;11.
- Stein ML, Villanueva JM, Buckmeier BK, et al. Anti-IL-5 (mepolizumab) therapy reduces eosinophil activation ex vivo and increases IL-5 and IL-5 receptor levels. Journal of Allergy and Clinical Immunology 2008;121.
- Otani IM, Anilkumar AA, Newbury RO, et al. Anti-IL-5 therapy reduces mast cell and IL-9 cell numbers in pediatric patients with eosinophilic esophagitis. Journal of Allergy and Clinical Immunology 2013;131.
- Stein ML, Collins MH, Villanueva JM, et al. Anti-IL-5 (mepolizumab) therapy for eosinophilic esophagitis. Journal of Allergy and Clinical Immunology 2006;118.
- Loizou D, Enav B, Komlodi-Pasztor E, et al. A pilot study of omalizumab in eosinophilic esophagitis. PLoS One 2015;10.
- Clayton F, Fang JC, Gleich GJ, et al. Eosinophilic esophagitis in adults is associated with IgG4 and not mediated by IgE. Gastroenterology 2014;147.
- Straumann A, Bussmann C, Conus S, et al. Anti-TNF-α (infliximab) therapy for severe adult eosinophilic esophagitis. Journal of Allergy and Clinical Immunology 2008;122.
- McLean LP, Cross RK. Integrin antagonists as potential therapeutic options for the treatment of Crohns disease. Expert Opin Investig Drugs 2016;25.
- Taft TH, Mutlu EA. The Potential Role of Vedolizumab in Concomitant Eosinophilic Esophagitis and Crohn’s Disease. Clinical Gastroenterology and Hepatology 2018;16.
- Nhu QM, Chiao H, Moawad FJ, et al. The Anti-a4β7 Integrin Therapeutic Antibody for Inflammatory Bowel Disease, Vedolizumab, Ameliorates Eosinophilic Esophagitis: A Novel Clinical Observation. American Journal of Gastroenterology 2018;113.
- Hirano I, Peterson K, Murray J, et al. AK002, an Anti-Siglec-8 Antibody, Depletes Tissue Eosinophils and Improves Dysphagia Symptoms in Patients with Eosinophilic Esophagitis. Journal of Allergy and Clinical Immunology 2020;145.
- Rothenberg ME, Wen T, Greenberg A, et al. Intravenous anti-IL-13 mAb QAX576 for the treatment of eosinophilic esophagitis. Journal of Allergy and Clinical Immunology 2015;135.
- Menard-Katcher C, Furuta GT, Kramer RE. Dilation of Pediatric Eosinophilic Esophagitis: Adverse Events and Short-term Outcomes. J Pediatr Gastroenterol Nutr 2017;64.
- Feo-Ortega S, Lucendo AJ. Evidence-based treatments for eosinophilic esophagitis: insights for the clinician. Therap Adv Gastroenterol 2022;15.
- Moawad FJ, Molina-Infante J, Lucendo AJ, et al. Systematic review with meta-analysis: endoscopic dilation is highly effective and safe in children and adults with eosinophilic oesophagitis. Aliment Pharmacol Ther 2017;46.
- Hiremath GS, Hameed F, Pacheco A, et al. Esophageal Food Impaction and Eosinophilic Esophagitis: A Retrospective Study, Systematic Review, and Meta-Analysis. Dig Dis Sci 2015;60:3181-3193.
- Pasha SF, DiBaise JK, Kim HJ, et al. Patient characteristics, clinical, endoscopic, and histologic findings in adult eosinophilic esophagitis: A case series and systematic review of the medical literature. Diseases of the Esophagus 2007;20.
- Singh B, Nijhawan S, Narayan KS, et al. Endoscopic management of ingested foreign bodies and food impaction in esophagus. Journal of Digestive Endoscopy 2015;6.
- Birk M, Bauerfeind P, Deprez PH, et al. Removal of foreign bodies in the upper gastrointestinal tract in adults: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy 2016;48.
- Kramer RE, Lerner DG, Lin T, et al. Management of ingested foreign bodies in children: A clinical report of the NASPGHAN endoscopy committee. J Pediatr Gastroenterol Nutr 2015;60.
- Lightdale JR, Liu QY, Sahn B, et al. Pediatric Endoscopy and High-risk Patients: A Clinical Report From the NASPGHAN Endoscopy Committee. J Pediatr Gastroenterol Nutr 2019;68:595-606.
- Hiremath GS, Vaezi MF, Gupta SK, et al. Management of Uncomplicated Esophageal Food Impaction Varies Substantially between Pediatric and Adult Gastroenterologists Practicing in the US. Gastroenterology 2017;152:S433-S434.
- Runge TM, Eluri S, Cotton CC, et al. Causes and Outcomes of Esophageal Perforation in Eosinophilic Esophagitis. J Clin Gastroenterol 2017;51.
- Arias-González L, Rey-Iborra E, Ruiz-Ponce M, et al. Esophageal perforation in eosinophilic esophagitis: A systematic review on clinical presentation, management and outcomes. Digestive and Liver Disease 2020;52.
- Visaggi P, de Bortoli N, Barberio B, et al. Artificial intelligence in the diagnosis of upper gastrointestinal diseases. J Clin Gastroenterol 2022;56.
- Mougey EB, Williams A, Coyne AJK, et al. CYP2C19 and STAT6 Variants Influence the Outcome of Proton Pump Inhibitor Therapy in Pediatric Eosinophilic Esophagitis. J Pediatr Gastroenterol Nutr 2019.
- Molina-Infante J, Rodriguez-Sanchez J, Martinek J, et al. Long-term loss of response in proton pump inhibitor-responsive esophageal eosinophilia is uncommon and influenced by CYP2C19 genotype and rhinoconjunctivitis. American Journal of Gastroenterology 2015;110.
- Shoda T, Wen T, Aceves SS, et al. Eosinophilic esophagitis endotype classification by molecular, clinical, and histopathological analyses: a cross sectional study by the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Lancet Gastroenterol Hepatol 2018;3.
- Alexander R, Alexander JA, Akambase J, et al. Proton Pump Inhibitor Therapy in Eosinophilic Esophagitis: Predictors of Nonresponse. Dig Dis Sci 2021;66.
- Cañas JA, Tabares A, Barbero C, et al. Proton-pump Inhibitor Response Prediction Using Esophageal microRNAs in Children With Eosinophilic Esophagitis. J Pediatr Gastroenterol Nutr 2020;71.
- Dellon ES, Guo R, McGee SJ, et al. A Novel Allergen-Specific Immune Signature-Directed Approach to Dietary Elimination in Eosinophilic Esophagitis. Clin Transl Gastroenterol 2019;(12):e00099.