Eosinophilic Esophagitis

Complex MONDO:0005361 Pathograph 6 Show in embeddings browser Allergic Disease Chronic Inflammatory Disease Gastrointestinal Disease

Eosinophilic esophagitis (EoE) is a chronic, food- and aeroallergen-driven, type 2-mediated inflammatory disease of the esophagus that develops in genetically predisposed individuals with an impaired esophageal epithelial barrier. Converging genetic and functional data place the esophageal epithelium at the center of pathogenesis: epithelial-intrinsic susceptibility (e.g., loss of the protease inhibitor SPINK7 and risk variants in the esophagus-specific protease calpain 14) and environmental exposures (food allergens, detergents) drive release of epithelial alarmins (TSLP, IL-33), which activate ILC2 and Th2 cells, recruit eosinophils via eotaxin-3 (CCL26), and produce esophageal eosinophilia, tissue damage, and progressive subepithelial fibrosis. Clinically it presents with dysphagia and food impaction in adults and feeding difficulties, vomiting, and failure to thrive in children, and is diagnosed histologically by a peak count of at least 15 eosinophils per high-power field.

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6
Pathophys.
1
Histopath.
5
Phenotypes
1
Hypotheses
3
Gaps
6
Pathograph
5
Medical Actions
3
Datasets
1
Trials
12
References
1
Deep Research
1
Hyp. Reports
◈

Mechanistic Hypotheses

1
Barrier-Antigen Type 2 Specificity Model
barrier_antigen_type2_specificity_model EMERGING
Evidence balance 3 support
Esophageal epithelial barrier dysfunction increases exposure to food and aeroallergen antigens and triggers epithelial alarmin release. TSLP and IL-33 then polarize local ILC2/Th2 inflammation, IL-5/IL-13 responses, and CCL26-mediated eosinophil recruitment. The broad barrier-to-type-2 axis is well supported, but the patient-specific selection of food antigens remains an open mechanistic subproblem rather than a settled causal edge.
Pathograph links
Esophageal Epithelial Barrier Dysfunction -> Epithelial Alarmin Release Loss of barrier integrity and unleashed epithelial protease activity drives production of proinflammatory and proallergic alarmin cytokines, including thymic stromal lymphopoietin.
Environmental Detergent Exposure -> Esophageal Epithelial Barrier Dysfunction Detergent exposure decreases esophageal barrier integrity and promotes epithelial hyperplasia, providing an environmental route to barrier disruption.
Environmental Detergent Exposure -> Epithelial Alarmin Release Detergent exposure stimulates IL-33 production by esophageal epithelium, feeding the alarmin-driven type 2 response.
Epithelial Alarmin Release -> Type 2 Immune Activation Epithelial alarmins TSLP and IL-33 activate ILC2 and Th2 cells, polarizing the local immune response toward type 2 inflammation.
Type 2 Immune Activation -> Eosinophil Recruitment to Esophagus Type 2 cytokines (notably IL-5 and IL-13) drive eosinophil maturation and induce epithelial eotaxin-3 (CCL26) expression that recruits eosinophils to the esophageal mucosa.
Eosinophil Recruitment to Esophagus -> Esophageal Fibrosis and Remodeling Persistent eosinophil-driven inflammation and the type 2 cytokine milieu promote subepithelial fibrosis and esophageal remodeling.
Deep research
OpenScientist citations 35 citations 2026-06-04T01:08:19.144453
Show evidence (3 references)
PMID:19596009 SUPPORT Other
"Eosinophilic esophagitis is a recently recognized but expanding disorder characterized by antigen-driven eosinophil accumulation in the esophagus."
Establishes antigen-driven eosinophil accumulation as a central EoE mechanism.
PMID:19596009 SUPPORT Other
"The pathogenesis of eosinophilic esophagitis involves environmental and genetic factors, particularly food antigens and expression level of the eosinophil chemoattractant eotaxin-3, respectively."
Links food antigens and eotaxin-3/CCL26 biology within the mechanistic model.
PMID:29980278 SUPPORT Human Clinical
"Furthermore, genetic and functional data establish a primary role for impaired epithelial barrier function in disease susceptibility and pathoetiology."
Supports the epithelial barrier component of the model.
?

Discussions and Knowledge Gaps

3
Why do individual EoE patients react to different specific food antigens despite sharing a common esophageal epithelial barrier defect and type 2 inflammatory program?
KNOWLEDGE GAP OPEN gap_eoe_food_antigen_specificity
Attached to
pathophysiology#Esophageal Epithelial Barrier Dysfunction pathophysiology#Type 2 Immune Activation mechanistic_hypotheses#barrier_antigen_type2_specificity_model
A shared barrier defect and type 2 axis do not explain patient-specific antigen selectivity. The connecting mechanism likely involves pre-existing local IgE sensitization and Th2 memory to particular foods, but there is no clean mechanistic consensus, and it cannot currently be modeled as a single causal edge from barrier disruption to a defined antigen response.
Show evidence (1 reference)
PMID:30364207 SUPPORT Human Clinical
"However, several unmet needs are to be solved urgently, as finding a non-invasive disease-monitoring methods and biomarkers for routine practice, the development or new therapies, novel food allergy testing to detect triggering foods, drug, and doses required for initial therapy and safety..."
Review identifies better food allergy testing to detect triggering foods as an unmet need, supporting the antigen-specificity gap.
Is environmental detergent exposure a genuine upstream human causal trigger of EoE, or only a mechanistically plausible model-system association?
KNOWLEDGE GAP OPEN gap_eoe_detergent_human_causality
Attached to
pathophysiology#Environmental Detergent Exposure
Detergent (SDS) exposure impairs the esophageal barrier and induces IL-33 and eosinophilia in cell-culture and mouse models, but direct human causal evidence is lacking. Whether this represents a true initiating exposure in patients or an experimentally tractable proxy remains unresolved.
Which eosinophil-dependent versus eosinophil-independent effector mechanisms drive dysphagia and fibrostenotic symptoms in EoE?
KNOWLEDGE GAP OPEN gap_eoe_eosinophil_symptom_causality
Attached to
pathophysiology#Eosinophil Recruitment to Esophagus pathophysiology#Esophageal Fibrosis and Remodeling mechanistic_hypotheses#barrier_antigen_type2_specificity_model
Eosinophil recruitment is a defining histologic and diagnostic axis, but eosinophil depletion alone has not consistently translated into symptom improvement. The symptom-producing tissue effectors may include epithelial remodeling, mast cells, neuromuscular dysfunction, and fibrosis in addition to eosinophils.
Show evidence (1 reference)
PMID:29372536 SUPPORT Other
"Mepolizumab and reslizumab, two anti-IL-5 antibodies, were studied in children and adults with EoE and resulted in reduction of esophageal tissue and blood eosinophils, but no significant reduction in symptoms."
Review of biologic therapy trials supports a gap between eosinophil reduction and symptom improvement.
⚙

Pathophysiology

6
Esophageal Epithelial Barrier Dysfunction
Impaired esophageal epithelial barrier function is a primary and initiating abnormality in EoE. The main disease susceptibility loci encode epithelium-produced gene products, and profound loss of the serine protease inhibitor SPINK7 unleashes proteolytic activity that disrupts barrier integrity and triggers proinflammatory and proallergic cytokine release.
Barrier-Antigen Type 2 Specificity Model
Esophageal epithelial cell CL:0002252 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Esophageal epithelial cell, annotated with epithelial cell of esophagus (CL:0002252). CL:0002252 is a cell type from the Cell Ontology.
SPINK7 hgnc:24643 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves SPINK7 (hgnc:24643). hgnc:24643 is a gene from the HUGO Gene Nomenclature Committee. CAPN14 hgnc:16664 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves CAPN14 (hgnc:16664). hgnc:16664 is a gene from the HUGO Gene Nomenclature Committee. DSG1 hgnc:3048 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves DSG1 (hgnc:3048). hgnc:3048 is a gene from the HUGO Gene Nomenclature Committee.
Downstream
Epithelial Alarmin Release Loss of barrier integrity and unleashed epithelial protease activity drives production of proinflammatory and proallergic alarmin cytokines, including thymic stromal lymphopoietin. Barrier-Antigen Type 2 Specificity Model
Show evidence (2 references)
PMID:29980278 SUPPORT Human Clinical
"Furthermore, genetic and functional data establish a primary role for impaired epithelial barrier function in disease susceptibility and pathoetiology."
Establishes impaired epithelial barrier function as a primary driver of EoE susceptibility and pathogenesis.
PMID:29980278 SUPPORT Human Clinical
"Profound lost expression of SPINK7 occurs in patients with EoE and is sufficient for unleashing increased proteolytic activity (including urokinase plasminogen activator), impaired barrier function, and production of large quantities of proinflammatory and proallergic cytokines, including thymic..."
SPINK7 loss is sufficient to impair barrier function and drive proallergic cytokine production, linking barrier dysfunction to downstream inflammation.
Environmental Detergent Exposure
Detergents such as sodium dodecyl sulfate (SDS), common in household products like dish soap and toothpaste, are proposed environmental triggers that decrease esophageal barrier integrity and stimulate IL-33 production. This node is supported by in vitro and mouse-model evidence and is best modeled as a mechanistically plausible environmental trigger rather than a confirmed human causal edge.
Barrier-Antigen Type 2 Specificity Model
Esophageal epithelial cell CL:0002252 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Esophageal epithelial cell, annotated with epithelial cell of esophagus (CL:0002252). CL:0002252 is a cell type from the Cell Ontology.
IL33 hgnc:16028 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves IL33 (hgnc:16028). hgnc:16028 is a gene from the HUGO Gene Nomenclature Committee.
Downstream
Esophageal Epithelial Barrier Dysfunction Detergent exposure decreases esophageal barrier integrity and promotes epithelial hyperplasia, providing an environmental route to barrier disruption. Barrier-Antigen Type 2 Specificity Model
Epithelial Alarmin Release Detergent exposure stimulates IL-33 production by esophageal epithelium, feeding the alarmin-driven type 2 response. Barrier-Antigen Type 2 Specificity Model
Show evidence (2 references)
PMID:35899466 SUPPORT In Vitro
"Exposure to SDS decreases esophageal barrier integrity, stimulates IL-33 production, and promotes epithelial hyperplasia and tissue eosinophilia."
Cell-culture and organoid experiments show SDS detergent exposure impairs the esophageal barrier and induces IL-33 and eosinophilia.
PMID:35899466 SUPPORT Model Organism
"Detergents may be a key environmental trigger in EoE pathogenesis."
Mouse-model data support detergent exposure as a candidate upstream environmental trigger of EoE.
Epithelial Alarmin Release
Barrier-disrupted esophageal epithelium releases alarmin cytokines, most notably thymic stromal lymphopoietin (TSLP) and IL-33, which initiate and amplify the downstream type 2 immune response. TSLP is encoded at a major EoE susceptibility locus and is produced by the esophageal epithelium.
Barrier-Antigen Type 2 Specificity Model
Esophageal epithelial cell CL:0002252 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Esophageal epithelial cell, annotated with epithelial cell of esophagus (CL:0002252). CL:0002252 is a cell type from the Cell Ontology.
TSLP hgnc:30743 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves TSLP (hgnc:30743). hgnc:30743 is a gene from the HUGO Gene Nomenclature Committee. IL33 hgnc:16028 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves IL33 (hgnc:16028). hgnc:16028 is a gene from the HUGO Gene Nomenclature Committee.
Positive regulation of inflammatory response GO:0050729 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased Positive regulation of inflammatory response (GO:0050729). GO:0050729 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Type 2 Immune Activation Epithelial alarmins TSLP and IL-33 activate ILC2 and Th2 cells, polarizing the local immune response toward type 2 inflammation. Barrier-Antigen Type 2 Specificity Model
Show evidence (1 reference)
PMID:29980278 SUPPORT Human Clinical
"In particular, the main EoE disease susceptibility loci at 2p23 and 5p22 encode for gene products that are produced by the esophageal epithelium: the intracellular protease calpain 14 and thymic stromal lymphopoietin, respectively."
TSLP is encoded at a major EoE susceptibility locus and produced by esophageal epithelium, supporting its role as an epithelial-derived driver.
Type 2 Immune Activation
Epithelial alarmins drive activation of group 2 innate lymphoid cells (ILC2) and T-helper 2 cells, generating a type 2 cytokine milieu (IL-4, IL-5, IL-13) that promotes IgE class switching, eosinophil maturation, and eotaxin-driven recruitment. Barrier dysfunction and T-helper 2 inflammation are considered the pathogenetically important factors in EoE.
Barrier-Antigen Type 2 Specificity Model
Group 2 innate lymphoid cell CL:0001069 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Group 2 innate lymphoid cell (CL:0001069). CL:0001069 is a cell type from the Cell Ontology. T-helper 2 cell CL:0000546 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves T-helper 2 cell (CL:0000546). CL:0000546 is a cell type from the Cell Ontology.
IL13 hgnc:5973 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves IL13 (hgnc:5973). hgnc:5973 is a gene from the HUGO Gene Nomenclature Committee. IL5 hgnc:6016 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves IL5 (hgnc:6016). hgnc:6016 is a gene from the HUGO Gene Nomenclature Committee.
Type 2 immune response GO:0042092 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased Type 2 immune response (GO:0042092). GO:0042092 is a biological process from the Gene Ontology. ↑ INCREASED Interleukin-13 production GO:0032616 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased Interleukin-13 production (GO:0032616). GO:0032616 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Eosinophil Recruitment to Esophagus Type 2 cytokines (notably IL-5 and IL-13) drive eosinophil maturation and induce epithelial eotaxin-3 (CCL26) expression that recruits eosinophils to the esophageal mucosa. Barrier-Antigen Type 2 Specificity Model
Show evidence (3 references)
PMID:30364207 SUPPORT Human Clinical
"Barrier dysfunction and T-helper 2 inflammation is considered to be pathogenetically important factors."
Identifies T-helper 2 inflammation, alongside barrier dysfunction, as a core pathogenetic factor in EoE.
PMID:19596009 SUPPORT Other
"Analyses of gene expression signatures and animal models have indicated the importance of adaptive T-cell immunity that involves interleukin-5 and interleukin-13-induced esophageal epithelial cell responses."
Supports IL-5/IL-13-associated adaptive immune activation and epithelial response in EoE.
PMID:39941170 SUPPORT Other
"Key mechanisms include a type 2 helper T-cell (Th2)-driven immune response, epithelial barrier dysfunction, and genetic variants such as CAPN14 and TSLP."
2025 review reaffirms the Th2-driven response, epithelial barrier dysfunction, and CAPN14/TSLP genetic susceptibility as the core mechanistic axis.
Eosinophil Recruitment to Esophagus
Type 2 cytokines induce epithelial expression of eotaxin-3 (CCL26), the dominant chemokine recruiting eosinophils into the esophageal mucosa. The resulting esophageal eosinophilia (diagnostic threshold of at least 15 eosinophils per high-power field) and degranulation cause tissue damage.
Barrier-Antigen Type 2 Specificity Model
Eosinophil CL:0000771 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Eosinophil (CL:0000771). CL:0000771 is a cell type from the Cell Ontology.
CCL26 hgnc:10625 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves CCL26 (hgnc:10625). hgnc:10625 is a gene from the HUGO Gene Nomenclature Committee.
Eosinophil chemotaxis GO:0048245 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased Eosinophil chemotaxis (GO:0048245). GO:0048245 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Esophageal Fibrosis and Remodeling Persistent eosinophil-driven inflammation and the type 2 cytokine milieu promote subepithelial fibrosis and esophageal remodeling. Barrier-Antigen Type 2 Specificity Model
Show evidence (2 references)
PMID:30364207 SUPPORT Human Clinical
"The diagnostic criteria for EoE has evolved but mainly requires symptoms of esophageal dysfunction with histologic evidence of a peak value of at least 15 eosinophils per high-power field."
Defines the histologic hallmark of esophageal eosinophilia (>=15 eos/hpf) central to this node.
PMID:19596009 SUPPORT Other
"The pathogenesis of eosinophilic esophagitis involves environmental and genetic factors, particularly food antigens and expression level of the eosinophil chemoattractant eotaxin-3, respectively."
Supports food-antigen-linked eotaxin-3/CCL26 activity as part of eosinophil recruitment biology.
Esophageal Fibrosis and Remodeling
Chronic type 2 inflammation drives subepithelial fibrosis, lamina propria remodeling, and stricture formation. This fibrostenotic remodeling underlies the dysphagia and food impaction that characterize long-standing, inadequately treated disease.
Extracellular matrix organization GO:0030198 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased Extracellular matrix organization (GO:0030198). GO:0030198 is a biological process from the Gene Ontology. ↑ INCREASED Fibroblast activation GO:0072537 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased Fibroblast activation (GO:0072537). GO:0072537 is a biological process from the Gene Ontology. ↑ INCREASED Epithelial-to-mesenchymal transition GO:0001837 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased Epithelial-to-mesenchymal transition, annotated with epithelial to mesenchymal transition (GO:0001837). GO:0001837 is a biological process from the Gene Ontology. ↑ INCREASED
Show evidence (4 references)
PMID:30364207 SUPPORT Human Clinical
"Endoscopic dilation is used for patients with severe dysphagia/food impaction with inadequate response to anti-inflammatory treatment."
The need for mechanical dilation in refractory disease reflects fibrostenotic remodeling and stricture, the clinical endpoint of this node.
PMID:26857345 SUPPORT Human Clinical
"We developed a histology scoring system for esophageal biopsies that evaluates eight features: eosinophil density, basal zone hyperplasia, eosinophil abscesses, eosinophil surface layering, dilated intercellular spaces (DIS), surface epithelial alteration, dyskeratotic epithelial cells, and..."
Direct human biopsy evidence includes lamina propria fibrosis and epithelial remodeling among EoE histologic features.
PMID:38256003 SUPPORT Other
"promoting tissue remodeling characterized by epithelial-mesenchymal transition (EMT) and collagen deposition"
Review of EoE fibrous remodeling defines epithelial-to-mesenchymal transition and collagen deposition as the tissue-remodeling mechanism underlying this node.
+ 1 more reference
✶

Histopathology

1
EoE histologic remodeling score features
EoE biopsies are assessed beyond peak eosinophil counts using a composite pattern that includes eosinophil density, basal zone hyperplasia, eosinophil abscesses, surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis.
Show evidence (1 reference)
PMID:26857345 SUPPORT Human Clinical
"We developed a histology scoring system for esophageal biopsies that evaluates eight features: eosinophil density, basal zone hyperplasia, eosinophil abscesses, eosinophil surface layering, dilated intercellular spaces (DIS), surface epithelial alteration, dyskeratotic epithelial cells, and..."
Validated EoE histology score supports the composite epithelial and fibrotic remodeling pattern.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Eosinophilic Esophagitis Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

5
Digestive 3
Dysphagia HP:0002015 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Dysphagia (HP:0002015). HP:0002015 is a phenotype from the Human Phenotype Ontology.
Difficulty swallowing, particularly for solids, is the dominant presenting symptom in adolescents and adults.
Show evidence (1 reference)
PMID:30364207 SUPPORT Human Clinical
"Eosinophilic esophagitis (EoE) was first described in the 1990s, showing an increasing incidence and prevalence since then, being the leading cause of food impaction and the major cause of dysphagia."
EoE is identified as a major cause of dysphagia.
Esophageal stricture HP:0002043 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Esophageal stricture (HP:0002043). HP:0002043 is a phenotype from the Human Phenotype Ontology.
Fibrostenotic remodeling produces fixed esophageal narrowing in long-standing disease.
Show evidence (1 reference)
PMID:30364207 SUPPORT Human Clinical
"Endoscopic dilation is used for patients with severe dysphagia/food impaction with inadequate response to anti-inflammatory treatment."
The clinical use of endoscopic dilation reflects fixed strictures from fibrostenotic remodeling.
Feeding difficulties HP:0011968 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Feeding difficulties (HP:0011968). HP:0011968 is a phenotype from the Human Phenotype Ontology.
In infants and young children, EoE more often presents with feeding difficulties, vomiting, and failure to thrive than with classic dysphagia.
Show evidence (1 reference)
PMID:30364207 SUPPORT Human Clinical
"There are different patterns of clinical presentation varying with age and can be masked by adaptation habits."
Age-dependent presentation underlies the feeding-related symptoms seen in younger children.
Other 2
Esophageal food impaction HP:0031984 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Esophageal food impaction (HP:0031984). HP:0031984 is a phenotype from the Human Phenotype Ontology.
Acute bolus impaction is a common emergency presentation and the leading structural consequence of fibrostenotic disease.
Show evidence (1 reference)
PMID:30364207 SUPPORT Human Clinical
"being the leading cause of food impaction and the major cause of dysphagia."
EoE is the leading cause of food impaction.
Esophageal eosinophilia Eosinophilic infiltration of the esophagus HP:0410151 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Esophageal eosinophilia (>=15 eosinophils per high-power field), annotated with Eosinophilic infiltration of the esophagus (HP:0410151). HP:0410151 is a phenotype from the Human Phenotype Ontology.
Histologic peak count of at least 15 eosinophils per high-power field on esophageal biopsy is the diagnostic hallmark.
Show evidence (1 reference)
PMID:30364207 SUPPORT Human Clinical
"mainly requires symptoms of esophageal dysfunction with histologic evidence of a peak value of at least 15 eosinophils per high-power field."
Esophageal eosinophilia at >=15 eos/hpf is the defining histologic feature of EoE.
💊

Medical Actions

5
Proton Pump Inhibitor Therapy
Action: proton pump inhibitor agent therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is proton pump inhibitor agent therapy, annotated with Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. Ontology label: Pharmacotherapy NCIT:C15986
Agent: omeprazole CHEBI:7772 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses omeprazole (CHEBI:7772). CHEBI:7772 is a therapeutic agent from Chemical Entities of Biological Interest.
Proton pump inhibitors (e.g., omeprazole) are a first-line pharmacologic option that induces histologic and symptomatic remission in a substantial subset of patients with EoE.
Show evidence (1 reference)
PMID:30364207 SUPPORT Human Clinical
"Treatment of EoE can be started either by drugs (PPIs and topical corticosteroids) or elimination diets."
PPIs are an established first-line drug treatment for EoE.
Swallowed Topical Corticosteroid Therapy
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: budesonide CHEBI:3207 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses budesonide (CHEBI:3207). CHEBI:3207 is a therapeutic agent from Chemical Entities of Biological Interest.
Swallowed topical corticosteroids (e.g., budesonide or fluticasone formulations) deliver anti-inflammatory therapy to the esophageal mucosa and are a first-line option to induce histologic remission.
Show evidence (1 reference)
PMID:30364207 SUPPORT Human Clinical
"Treatment of EoE can be started either by drugs (PPIs and topical corticosteroids) or elimination diets."
Topical corticosteroids are an established first-line anti-inflammatory drug treatment for EoE.
Dietary Elimination Therapy
Action: dietary interventionNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is dietary intervention (NCIT:C15447). NCIT:C15447 is a clinical intervention from the NCI Thesaurus. Ontology label: Dietary Intervention NCIT:C15447
Empiric food-elimination diets (including step-up multistage and six-food elimination approaches) remove triggering antigens and can induce histologic remission, identifying causative foods through reintroduction.
Show evidence (1 reference)
PMID:30364207 SUPPORT Human Clinical
"The multistage step-up elimination diet management approach of EoE is promising."
Step-up elimination diet is an established non-pharmacologic management strategy for EoE.
Dupilumab
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: dupilumab NCIT:C162455 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses dupilumab (NCIT:C162455). NCIT:C162455 is a therapeutic agent from the NCI Thesaurus.
Dupilumab is a monoclonal antibody targeting the IL-4 receptor alpha subunit, blocking IL-4 and IL-13 signaling at the core of the type 2 inflammatory axis; it is approved for EoE.
Show evidence (3 references)
PMID:36546624 SUPPORT Human Clinical
"Among patients with eosinophilic esophagitis, subcutaneous dupilumab administered weekly improved histologic outcomes and alleviated symptoms of the disease."
The pivotal phase 3 LIBERTY EoE TREET trial (NCT03633617) demonstrated that IL-4Rα blockade with dupilumab achieves histologic remission and symptom improvement in EoE, the efficacy basis for its FDA approval (May 2022).
PMID:38135920 SUPPORT Other
"the approval (in the United States) of dupilumab for EoE"
Independent review confirms US regulatory approval of dupilumab for EoE, the first disease-specific biologic.
PMID:39941170 SUPPORT Other
"Emerging therapies targeting cytokines such as interleukin (IL)-4, IL-5, and IL-13"
Situates dupilumab within the broader class of type 2 cytokine-directed biologics (IL-4/IL-5/IL-13) under development for EoE.
Endoscopic Esophageal Dilation
Action: esophageal dilationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is esophageal dilation (NCIT:C70908). NCIT:C70908 is a clinical intervention from the NCI Thesaurus. Ontology label: Esophageal Dilation NCIT:C70908
Endoscopic dilation mechanically relieves fibrostenotic strictures and is reserved for patients with severe dysphagia or food impaction not adequately controlled by anti-inflammatory therapy.
Show evidence (1 reference)
PMID:30364207 SUPPORT Human Clinical
"Endoscopic dilation is used for patients with severe dysphagia/food impaction with inadequate response to anti-inflammatory treatment."
Defines the indication for endoscopic dilation in refractory fibrostenotic EoE.
🔬

Diagnosis

1
Esophagogastroduodenoscopy with esophageal biopsy
Upper endoscopy with esophageal biopsy establishes the diagnosis and is also used, alongside clinical and histologic assessment, to monitor treatment response and follow patients on maintenance therapy.
esophagogastroduodenoscopy NCIT:C78144 NCI Thesaurus (NCIT)
Results: Endoscopic and histologic findings used to establish diagnosis and assess treatment response.
Show evidence (1 reference)
PMID:39745304 SUPPORT Other
"Monitoring with clinical, endoscopic, and histologic assessments is recommended to assess for treatment response and follow patients over time with maintenance therapy."
The ACG clinical guideline recommends combined clinical, endoscopic, and histologic monitoring to assess treatment response and follow patients on maintenance therapy.
📊

Prevalence

1
Global
EoE has shown an increasing incidence and prevalence since its description in the 1990s and is the leading cause of food impaction and a major cause of dysphagia. It affects both children and adults, with a male predominance, and is frequently associated with atopic disease and IgE-mediated food allergies.
Show evidence (1 reference)
PMID:30364207 SUPPORT Human Clinical
"Eosinophilic esophagitis (EoE) was first described in the 1990s, showing an increasing incidence and prevalence since then, being the leading cause of food impaction and the major cause of dysphagia."
Review establishes EoE epidemiology as an increasingly prevalent disorder and the leading cause of food impaction.
📊

Related Datasets

3
RNAseq analyses of Esophageal biopsies from proton pump inhibitor (PPI)-responsive and PPI-unresponsive Pediatric patients with Eosinophilic Esophagitis. geo:GSE303169
Clinical trials have identified two distinct eosinophilic esophagitis (EoE) treatment phenotypes, proton pump inhibitor (PPI)-responsive (PPI-R) and PPI-unresponsive (PPI-UR). Herein, we performed clinical, endoscopic, and histologic evaluation of esophageal biopsies from pediatric PPI-R and PPI-UR EoE individuals prior to PPI therapy (diagnosis) and following PPI trial. RNAseq analyses of esophageal biopsy samples revealed common immune and inflammatory transcriptional signatures in both PPI-R EoE and PPI-UR EoE at diagnosis and distinct signatures enriched for processes related to neuropeptide signaling and cell cycle and division.
human BULK RNA SEQ n=25
PMID:41059573
Identified by GEO DataSets index search for Eosinophilic Esophagitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values.
MicroRNAs in plasma-derived extracellular vesicles as non-invasive biomarkers for eosinophilic esophagitis geo:GSE275710
Background: The lack of non-invasive biomarkers imposes the dependence on endoscopy with biopsies for the diagnosis and monitoring of eosinophilic esophagitis (EoE), a prevalent chronic inflammation of the esophagus mediated by a type 2 immune response. We aimed to identify potential non-invasive biomarkers using microRNAs (miRNAs) in plasma-derived extracellular vesicles (pEVs). Methods: This is a prospective single-center observational study including a discovery cohort of EoE patients (n=26) with active disease (EoE.Basal) and after anti-inflammatory treatment (EoE.Post.tx), and control subjects (n=16).
human BULK RNA SEQ n=70
PMID:39859353
Identified by GEO DataSets index search for Eosinophilic Esophagitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values.
Differing Epithelial and Immunologic Activation Patterns Following Food Reintroduction Reveal Differential Transcriptional Profiles in Active Eosinophilic Esophagitis geo:GSE278888
During food trigger reintroductions, eosinophilia can recur in a patchy manner both endoscopically and histologically. We postulated that areas containing low eosinophils represented the early stage of EoE recurrence, while areas with >15 eos/HPF represented established active EoE. We identified ten patients with prior pan-esophageal EoE who experienced patchy eosinophilia during trigger food reintroduction. The progression of recurrent EoE is illustrated by the transcriptional changes occurring from baseline remission through recurrent low and high eosinophil tissues in those with paired time points.
human BULK RNA SEQ n=28
PMID:39490770
Identified by GEO DataSets index search for Eosinophilic Esophagitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values.
🔬

Clinical Trials

1
NCT03633617 PHASE_III COMPLETED
LIBERTY EoE TREET, the pivotal three-part phase 3 randomized, placebo-controlled trial of the anti-IL-4-receptor-alpha monoclonal antibody dupilumab in adults and adolescents with EoE, assessing histologic and clinical response at 24 and 52 weeks. It provided the efficacy basis for FDA approval of dupilumab for EoE.
Target Phenotypes: Dysphagia HP:0002015 Human Phenotype Ontology (HP) Relation: this clinical trial targets this phenotype This clinical trial targets Dysphagia (HP:0002015). HP:0002015 is a phenotype from the Human Phenotype Ontology. Esophageal eosinophilia HP:0410151 Human Phenotype Ontology (HP) Relation: this clinical trial targets this phenotype This clinical trial targets Esophageal eosinophilia, annotated with Eosinophilic infiltration of the esophagus (HP:0410151). HP:0410151 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
clinicaltrials:NCT03633617 SUPPORT Human Clinical
"To demonstrate the efficacy of dupilumab treatment compared with placebo in adult and adolescent patients with EoE after 24 weeks of treatment as assessed by histological and clinical measures."
The registered phase 3 objective confirms this trial tested dupilumab against placebo on histologic and clinical endpoints, underpinning EoE approval.
{ }

Source YAML

click to show 
name: Eosinophilic Esophagitis
creation_date: '2026-06-03T00:00:00Z'
category: Complex
parents:
- Allergic Disease
- Chronic Inflammatory Disease
- Gastrointestinal Disease
description: >-
  Eosinophilic esophagitis (EoE) is a chronic, food- and aeroallergen-driven,
  type 2-mediated inflammatory disease of the esophagus that develops in
  genetically predisposed individuals with an impaired esophageal epithelial
  barrier. Converging genetic and functional data place the esophageal
  epithelium at the center of pathogenesis: epithelial-intrinsic susceptibility
  (e.g., loss of the protease inhibitor SPINK7 and risk variants in the
  esophagus-specific protease calpain 14) and environmental exposures
  (food allergens, detergents) drive release of epithelial alarmins
  (TSLP, IL-33), which activate ILC2 and Th2 cells, recruit eosinophils via
  eotaxin-3 (CCL26), and produce esophageal eosinophilia, tissue damage, and
  progressive subepithelial fibrosis. Clinically it presents with dysphagia
  and food impaction in adults and feeding difficulties, vomiting, and failure
  to thrive in children, and is diagnosed histologically by a peak count of at
  least 15 eosinophils per high-power field.
synonyms:
- EoE
- allergic esophagitis
prevalence:
- population: Global
  notes: >-
    EoE has shown an increasing incidence and prevalence since its description
    in the 1990s and is the leading cause of food impaction and a major cause of
    dysphagia. It affects both children and adults, with a male predominance,
    and is frequently associated with atopic disease and IgE-mediated food
    allergies.
  evidence:
  - reference: PMID:30364207
    reference_title: "Eosinophilic Esophagitis: Review and Update."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Eosinophilic esophagitis (EoE) was first described in the 1990s, showing an increasing incidence and prevalence since then, being the leading cause of food impaction and the major cause of dysphagia."
    explanation: Review establishes EoE epidemiology as an increasingly prevalent disorder and the leading cause of food impaction.
mechanistic_hypotheses:
- hypothesis_group_id: barrier_antigen_type2_specificity_model
  hypothesis_label: Barrier-Antigen Type 2 Specificity Model
  status: EMERGING
  description: >-
    Esophageal epithelial barrier dysfunction increases exposure to food and
    aeroallergen antigens and triggers epithelial alarmin release. TSLP and
    IL-33 then polarize local ILC2/Th2 inflammation, IL-5/IL-13 responses, and
    CCL26-mediated eosinophil recruitment. The broad barrier-to-type-2 axis is
    well supported, but the patient-specific selection of food antigens remains
    an open mechanistic subproblem rather than a settled causal edge.
  evidence:
  - reference: PMID:19596009
    reference_title: "Biology and treatment of eosinophilic esophagitis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Eosinophilic esophagitis is a recently recognized but expanding disorder characterized by antigen-driven eosinophil accumulation in the esophagus."
    explanation: Establishes antigen-driven eosinophil accumulation as a central EoE mechanism.
  - reference: PMID:19596009
    reference_title: "Biology and treatment of eosinophilic esophagitis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The pathogenesis of eosinophilic esophagitis involves environmental and genetic factors, particularly food antigens and expression level of the eosinophil chemoattractant eotaxin-3, respectively."
    explanation: Links food antigens and eotaxin-3/CCL26 biology within the mechanistic model.
  - reference: PMID:29980278
    reference_title: "Epithelial origin of eosinophilic esophagitis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Furthermore, genetic and functional data establish a primary role for impaired epithelial barrier function in disease susceptibility and pathoetiology."
    explanation: Supports the epithelial barrier component of the model.
pathophysiology:
- name: Esophageal Epithelial Barrier Dysfunction
  conforms_to: "epithelial_barrier_dysfunction#Epithelial Barrier Insult and Junctional Disruption"
  description: >-
    Impaired esophageal epithelial barrier function is a primary and initiating
    abnormality in EoE. The main disease susceptibility loci encode
    epithelium-produced gene products, and profound loss of the serine protease
    inhibitor SPINK7 unleashes proteolytic activity that disrupts barrier
    integrity and triggers proinflammatory and proallergic cytokine release.
  genes:
  - preferred_term: SPINK7
    term:
      id: hgnc:24643
      label: SPINK7
  - preferred_term: CAPN14
    term:
      id: hgnc:16664
      label: CAPN14
  - preferred_term: DSG1
    term:
      id: hgnc:3048
      label: DSG1
  cell_types:
  - preferred_term: Esophageal epithelial cell
    term:
      id: CL:0002252
      label: epithelial cell of esophagus
  downstream:
  - target: Epithelial Alarmin Release
    description: >-
      Loss of barrier integrity and unleashed epithelial protease activity
      drives production of proinflammatory and proallergic alarmin cytokines,
      including thymic stromal lymphopoietin.
    hypothesis_groups:
    - barrier_antigen_type2_specificity_model
  evidence:
  - reference: PMID:29980278
    reference_title: "Epithelial origin of eosinophilic esophagitis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Furthermore, genetic and functional data establish a primary role for impaired epithelial barrier function in disease susceptibility and pathoetiology."
    explanation: Establishes impaired epithelial barrier function as a primary driver of EoE susceptibility and pathogenesis.
  - reference: PMID:29980278
    reference_title: "Epithelial origin of eosinophilic esophagitis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Profound lost expression of SPINK7 occurs in patients with EoE and is sufficient for unleashing increased proteolytic activity (including urokinase plasminogen activator), impaired barrier function, and production of large quantities of proinflammatory and proallergic cytokines, including thymic stromal lymphopoietin."
    explanation: SPINK7 loss is sufficient to impair barrier function and drive proallergic cytokine production, linking barrier dysfunction to downstream inflammation.
- name: Environmental Detergent Exposure
  description: >-
    Detergents such as sodium dodecyl sulfate (SDS), common in household products
    like dish soap and toothpaste, are proposed environmental triggers that
    decrease esophageal barrier integrity and stimulate IL-33 production. This
    node is supported by in vitro and mouse-model evidence and is best modeled
    as a mechanistically plausible environmental trigger rather than a confirmed
    human causal edge.
  genes:
  - preferred_term: IL33
    term:
      id: hgnc:16028
      label: IL33
  cell_types:
  - preferred_term: Esophageal epithelial cell
    term:
      id: CL:0002252
      label: epithelial cell of esophagus
  downstream:
  - target: Esophageal Epithelial Barrier Dysfunction
    description: >-
      Detergent exposure decreases esophageal barrier integrity and promotes
      epithelial hyperplasia, providing an environmental route to barrier
      disruption.
    hypothesis_groups:
    - barrier_antigen_type2_specificity_model
  - target: Epithelial Alarmin Release
    description: >-
      Detergent exposure stimulates IL-33 production by esophageal epithelium,
      feeding the alarmin-driven type 2 response.
    hypothesis_groups:
    - barrier_antigen_type2_specificity_model
  evidence:
  - reference: PMID:35899466
    reference_title: "Detergent exposure induces epithelial barrier dysfunction and eosinophilic inflammation in the esophagus."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "Exposure to SDS decreases esophageal barrier integrity, stimulates IL-33 production, and promotes epithelial hyperplasia and tissue eosinophilia."
    explanation: Cell-culture and organoid experiments show SDS detergent exposure impairs the esophageal barrier and induces IL-33 and eosinophilia.
  - reference: PMID:35899466
    reference_title: "Detergent exposure induces epithelial barrier dysfunction and eosinophilic inflammation in the esophagus."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Detergents may be a key environmental trigger in EoE pathogenesis."
    explanation: Mouse-model data support detergent exposure as a candidate upstream environmental trigger of EoE.
- name: Epithelial Alarmin Release
  description: >-
    Barrier-disrupted esophageal epithelium releases alarmin cytokines, most
    notably thymic stromal lymphopoietin (TSLP) and IL-33, which initiate and
    amplify the downstream type 2 immune response. TSLP is encoded at a major
    EoE susceptibility locus and is produced by the esophageal epithelium.
  genes:
  - preferred_term: TSLP
    term:
      id: hgnc:30743
      label: TSLP
  - preferred_term: IL33
    term:
      id: hgnc:16028
      label: IL33
  biological_processes:
  - preferred_term: Positive regulation of inflammatory response
    term:
      id: GO:0050729
      label: positive regulation of inflammatory response
    modifier: INCREASED
  cell_types:
  - preferred_term: Esophageal epithelial cell
    term:
      id: CL:0002252
      label: epithelial cell of esophagus
  downstream:
  - target: Type 2 Immune Activation
    description: >-
      Epithelial alarmins TSLP and IL-33 activate ILC2 and Th2 cells, polarizing
      the local immune response toward type 2 inflammation.
    hypothesis_groups:
    - barrier_antigen_type2_specificity_model
  evidence:
  - reference: PMID:29980278
    reference_title: "Epithelial origin of eosinophilic esophagitis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In particular, the main EoE disease susceptibility loci at 2p23 and 5p22 encode for gene products that are produced by the esophageal epithelium: the intracellular protease calpain 14 and thymic stromal lymphopoietin, respectively."
    explanation: TSLP is encoded at a major EoE susceptibility locus and produced by esophageal epithelium, supporting its role as an epithelial-derived driver.
- name: Type 2 Immune Activation
  description: >-
    Epithelial alarmins drive activation of group 2 innate lymphoid cells (ILC2)
    and T-helper 2 cells, generating a type 2 cytokine milieu (IL-4, IL-5,
    IL-13) that promotes IgE class switching, eosinophil maturation, and
    eotaxin-driven recruitment. Barrier dysfunction and T-helper 2 inflammation
    are considered the pathogenetically important factors in EoE.
  genes:
  - preferred_term: IL13
    term:
      id: hgnc:5973
      label: IL13
  - preferred_term: IL5
    term:
      id: hgnc:6016
      label: IL5
  biological_processes:
  - preferred_term: Type 2 immune response
    term:
      id: GO:0042092
      label: type 2 immune response
    modifier: INCREASED
  - preferred_term: Interleukin-13 production
    term:
      id: GO:0032616
      label: interleukin-13 production
    modifier: INCREASED
  cell_types:
  - preferred_term: Group 2 innate lymphoid cell
    term:
      id: CL:0001069
      label: group 2 innate lymphoid cell
  - preferred_term: T-helper 2 cell
    term:
      id: CL:0000546
      label: T-helper 2 cell
  downstream:
  - target: Eosinophil Recruitment to Esophagus
    description: >-
      Type 2 cytokines (notably IL-5 and IL-13) drive eosinophil maturation and
      induce epithelial eotaxin-3 (CCL26) expression that recruits eosinophils
      to the esophageal mucosa.
    hypothesis_groups:
    - barrier_antigen_type2_specificity_model
  evidence:
  - reference: PMID:30364207
    reference_title: "Eosinophilic Esophagitis: Review and Update."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Barrier dysfunction and T-helper 2 inflammation is considered to be pathogenetically important factors."
    explanation: Identifies T-helper 2 inflammation, alongside barrier dysfunction, as a core pathogenetic factor in EoE.
  - reference: PMID:19596009
    reference_title: "Biology and treatment of eosinophilic esophagitis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Analyses of gene expression signatures and animal models have indicated the importance of adaptive T-cell immunity that involves interleukin-5 and interleukin-13-induced esophageal epithelial cell responses."
    explanation: Supports IL-5/IL-13-associated adaptive immune activation and epithelial response in EoE.
  - reference: PMID:39941170
    reference_title: "The Dynamic Evolution of Eosinophilic Esophagitis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Key mechanisms include a type 2 helper T-cell (Th2)-driven immune response, epithelial barrier dysfunction, and genetic variants such as CAPN14 and TSLP."
    explanation: 2025 review reaffirms the Th2-driven response, epithelial barrier dysfunction, and CAPN14/TSLP genetic susceptibility as the core mechanistic axis.
- name: Eosinophil Recruitment to Esophagus
  description: >-
    Type 2 cytokines induce epithelial expression of eotaxin-3 (CCL26), the
    dominant chemokine recruiting eosinophils into the esophageal mucosa. The
    resulting esophageal eosinophilia (diagnostic threshold of at least 15
    eosinophils per high-power field) and degranulation cause tissue damage.
  genes:
  - preferred_term: CCL26
    term:
      id: hgnc:10625
      label: CCL26
  biological_processes:
  - preferred_term: Eosinophil chemotaxis
    term:
      id: GO:0048245
      label: eosinophil chemotaxis
    modifier: INCREASED
  cell_types:
  - preferred_term: Eosinophil
    term:
      id: CL:0000771
      label: eosinophil
  downstream:
  - target: Esophageal Fibrosis and Remodeling
    description: >-
      Persistent eosinophil-driven inflammation and the type 2 cytokine milieu
      promote subepithelial fibrosis and esophageal remodeling.
    hypothesis_groups:
    - barrier_antigen_type2_specificity_model
  evidence:
  - reference: PMID:30364207
    reference_title: "Eosinophilic Esophagitis: Review and Update."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The diagnostic criteria for EoE has evolved but mainly requires symptoms of esophageal dysfunction with histologic evidence of a peak value of at least 15 eosinophils per high-power field."
    explanation: Defines the histologic hallmark of esophageal eosinophilia (>=15 eos/hpf) central to this node.
  - reference: PMID:19596009
    reference_title: "Biology and treatment of eosinophilic esophagitis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The pathogenesis of eosinophilic esophagitis involves environmental and genetic factors, particularly food antigens and expression level of the eosinophil chemoattractant eotaxin-3, respectively."
    explanation: Supports food-antigen-linked eotaxin-3/CCL26 activity as part of eosinophil recruitment biology.
- name: Esophageal Fibrosis and Remodeling
  description: >-
    Chronic type 2 inflammation drives subepithelial fibrosis, lamina propria
    remodeling, and stricture formation. This fibrostenotic remodeling underlies
    the dysphagia and food impaction that characterize long-standing,
    inadequately treated disease.
  biological_processes:
  - preferred_term: Extracellular matrix organization
    term:
      id: GO:0030198
      label: extracellular matrix organization
    modifier: INCREASED
  - preferred_term: Fibroblast activation
    term:
      id: GO:0072537
      label: fibroblast activation
    modifier: INCREASED
  - preferred_term: Epithelial-to-mesenchymal transition
    term:
      id: GO:0001837
      label: epithelial to mesenchymal transition
    modifier: INCREASED
  evidence:
  - reference: PMID:30364207
    reference_title: "Eosinophilic Esophagitis: Review and Update."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Endoscopic dilation is used for patients with severe dysphagia/food impaction with inadequate response to anti-inflammatory treatment."
    explanation: The need for mechanical dilation in refractory disease reflects fibrostenotic remodeling and stricture, the clinical endpoint of this node.
  - reference: PMID:26857345
    reference_title: "Newly developed and validated eosinophilic esophagitis histology scoring system and evidence that it outperforms peak eosinophil count for disease diagnosis and monitoring."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We developed a histology scoring system for esophageal biopsies that evaluates eight features: eosinophil density, basal zone hyperplasia, eosinophil abscesses, eosinophil surface layering, dilated intercellular spaces (DIS), surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis."
    explanation: Direct human biopsy evidence includes lamina propria fibrosis and epithelial remodeling among EoE histologic features.
  - reference: PMID:38256003
    reference_title: "Fibrous Remodeling in Eosinophilic Esophagitis: Clinical Facts and Pathophysiological Uncertainties."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "promoting tissue remodeling characterized by epithelial-mesenchymal transition (EMT) and collagen deposition"
    explanation: Review of EoE fibrous remodeling defines epithelial-to-mesenchymal transition and collagen deposition as the tissue-remodeling mechanism underlying this node.
  - reference: PMID:38256003
    reference_title: "Fibrous Remodeling in Eosinophilic Esophagitis: Clinical Facts and Pathophysiological Uncertainties."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "transforming growth factor beta (TGF)-beta have been involved in fibrotic phenomena in EoE"
    explanation: Implicates TGF-beta signaling in the fibrotic remodeling driving esophageal stricture, while noting the dependence is not fully established.
histopathology:
- name: EoE histologic remodeling score features
  description: >-
    EoE biopsies are assessed beyond peak eosinophil counts using a composite
    pattern that includes eosinophil density, basal zone hyperplasia,
    eosinophil abscesses, surface layering, dilated intercellular spaces,
    surface epithelial alteration, dyskeratotic epithelial cells, and lamina
    propria fibrosis.
  evidence:
  - reference: PMID:26857345
    reference_title: "Newly developed and validated eosinophilic esophagitis histology scoring system and evidence that it outperforms peak eosinophil count for disease diagnosis and monitoring."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We developed a histology scoring system for esophageal biopsies that evaluates eight features: eosinophil density, basal zone hyperplasia, eosinophil abscesses, eosinophil surface layering, dilated intercellular spaces (DIS), surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis."
    explanation: Validated EoE histology score supports the composite epithelial and fibrotic remodeling pattern.
phenotypes:
- name: Dysphagia
  category: Gastrointestinal
  diagnostic: true
  notes: Difficulty swallowing, particularly for solids, is the dominant presenting symptom in adolescents and adults.
  phenotype_term:
    preferred_term: Dysphagia
    term:
      id: HP:0002015
      label: Dysphagia
  evidence:
  - reference: PMID:30364207
    reference_title: "Eosinophilic Esophagitis: Review and Update."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Eosinophilic esophagitis (EoE) was first described in the 1990s, showing an increasing incidence and prevalence since then, being the leading cause of food impaction and the major cause of dysphagia."
    explanation: EoE is identified as a major cause of dysphagia.
- name: Esophageal food impaction
  category: Gastrointestinal
  notes: Acute bolus impaction is a common emergency presentation and the leading structural consequence of fibrostenotic disease.
  phenotype_term:
    preferred_term: Esophageal food impaction
    term:
      id: HP:0031984
      label: Esophageal food impaction
  evidence:
  - reference: PMID:30364207
    reference_title: "Eosinophilic Esophagitis: Review and Update."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "being the leading cause of food impaction and the major cause of dysphagia."
    explanation: EoE is the leading cause of food impaction.
- name: Esophageal eosinophilia
  category: Histopathological
  diagnostic: true
  notes: Histologic peak count of at least 15 eosinophils per high-power field on esophageal biopsy is the diagnostic hallmark.
  phenotype_term:
    preferred_term: Esophageal eosinophilia (>=15 eosinophils per high-power field)
    term:
      id: HP:0410151
      label: Eosinophilic infiltration of the esophagus
  evidence:
  - reference: PMID:30364207
    reference_title: "Eosinophilic Esophagitis: Review and Update."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "mainly requires symptoms of esophageal dysfunction with histologic evidence of a peak value of at least 15 eosinophils per high-power field."
    explanation: Esophageal eosinophilia at >=15 eos/hpf is the defining histologic feature of EoE.
- name: Esophageal stricture
  category: Gastrointestinal
  notes: Fibrostenotic remodeling produces fixed esophageal narrowing in long-standing disease.
  phenotype_term:
    preferred_term: Esophageal stricture
    term:
      id: HP:0002043
      label: Esophageal stricture
  evidence:
  - reference: PMID:30364207
    reference_title: "Eosinophilic Esophagitis: Review and Update."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Endoscopic dilation is used for patients with severe dysphagia/food impaction with inadequate response to anti-inflammatory treatment."
    explanation: The clinical use of endoscopic dilation reflects fixed strictures from fibrostenotic remodeling.
- name: Feeding difficulties
  category: Gastrointestinal
  notes: In infants and young children, EoE more often presents with feeding difficulties, vomiting, and failure to thrive than with classic dysphagia.
  phenotype_term:
    preferred_term: Feeding difficulties
    term:
      id: HP:0011968
      label: Feeding difficulties
  evidence:
  - reference: PMID:30364207
    reference_title: "Eosinophilic Esophagitis: Review and Update."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "There are different patterns of clinical presentation varying with age and can be masked by adaptation habits."
    explanation: Age-dependent presentation underlies the feeding-related symptoms seen in younger children.
diagnosis:
- name: Esophagogastroduodenoscopy with esophageal biopsy
  description: >-
    Upper endoscopy with esophageal biopsy establishes the diagnosis and is
    also used, alongside clinical and histologic assessment, to monitor
    treatment response and follow patients on maintenance therapy.
  diagnosis_term:
    preferred_term: esophagogastroduodenoscopy
    term:
      id: NCIT:C78144
      label: Esophagogastroduodenoscopy
  results: Endoscopic and histologic findings used to establish diagnosis and assess treatment response.
  evidence:
  - reference: PMID:39745304
    reference_title: "ACG Clinical Guideline: Diagnosis and Management of Eosinophilic Esophagitis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Monitoring with clinical, endoscopic, and histologic assessments is recommended to assess for treatment response and follow patients over time with maintenance therapy."
    explanation: The ACG clinical guideline recommends combined clinical, endoscopic, and histologic monitoring to assess treatment response and follow patients on maintenance therapy.

treatments:
- name: Proton Pump Inhibitor Therapy
  description: >-
    Proton pump inhibitors (e.g., omeprazole) are a first-line pharmacologic
    option that induces histologic and symptomatic remission in a substantial
    subset of patients with EoE.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: proton pump inhibitor agent therapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: omeprazole
      term:
        id: CHEBI:7772
        label: omeprazole
  evidence:
  - reference: PMID:30364207
    reference_title: "Eosinophilic Esophagitis: Review and Update."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Treatment of EoE can be started either by drugs (PPIs and topical corticosteroids) or elimination diets."
    explanation: PPIs are an established first-line drug treatment for EoE.
- name: Swallowed Topical Corticosteroid Therapy
  description: >-
    Swallowed topical corticosteroids (e.g., budesonide or fluticasone
    formulations) deliver anti-inflammatory therapy to the esophageal mucosa and
    are a first-line option to induce histologic remission.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: budesonide
      term:
        id: CHEBI:3207
        label: budesonide
  evidence:
  - reference: PMID:30364207
    reference_title: "Eosinophilic Esophagitis: Review and Update."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Treatment of EoE can be started either by drugs (PPIs and topical corticosteroids) or elimination diets."
    explanation: Topical corticosteroids are an established first-line anti-inflammatory drug treatment for EoE.
- name: Dietary Elimination Therapy
  description: >-
    Empiric food-elimination diets (including step-up multistage and six-food
    elimination approaches) remove triggering antigens and can induce histologic
    remission, identifying causative foods through reintroduction.
  therapeutic_modality: BEHAVIORAL
  treatment_term:
    preferred_term: dietary intervention
    term:
      id: NCIT:C15447
      label: Dietary Intervention
  evidence:
  - reference: PMID:30364207
    reference_title: "Eosinophilic Esophagitis: Review and Update."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The multistage step-up elimination diet management approach of EoE is promising."
    explanation: Step-up elimination diet is an established non-pharmacologic management strategy for EoE.
- name: Dupilumab
  description: >-
    Dupilumab is a monoclonal antibody targeting the IL-4 receptor alpha subunit,
    blocking IL-4 and IL-13 signaling at the core of the type 2 inflammatory
    axis; it is approved for EoE.
  therapeutic_modality: MONOCLONAL_ANTIBODY
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: dupilumab
      term:
        id: NCIT:C162455
        label: Dupilumab
  evidence:
  - reference: PMID:36546624
    reference_title: "Dupilumab in Adults and Adolescents with Eosinophilic Esophagitis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Among patients with eosinophilic esophagitis, subcutaneous dupilumab administered weekly improved histologic outcomes and alleviated symptoms of the disease."
    explanation: The pivotal phase 3 LIBERTY EoE TREET trial (NCT03633617) demonstrated that IL-4Rα blockade with dupilumab achieves histologic remission and symptom improvement in EoE, the efficacy basis for its FDA approval (May 2022).
  - reference: PMID:38135920
    reference_title: "Review article: Emerging insights into the epidemiology, pathophysiology, diagnostic and therapeutic aspects of eosinophilic oesophagitis and other eosinophilic gastrointestinal diseases."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "the approval (in the United States) of dupilumab for EoE"
    explanation: Independent review confirms US regulatory approval of dupilumab for EoE, the first disease-specific biologic.
  - reference: PMID:39941170
    reference_title: "The Dynamic Evolution of Eosinophilic Esophagitis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Emerging therapies targeting cytokines such as interleukin (IL)-4, IL-5, and IL-13"
    explanation: Situates dupilumab within the broader class of type 2 cytokine-directed biologics (IL-4/IL-5/IL-13) under development for EoE.
- name: Endoscopic Esophageal Dilation
  description: >-
    Endoscopic dilation mechanically relieves fibrostenotic strictures and is
    reserved for patients with severe dysphagia or food impaction not adequately
    controlled by anti-inflammatory therapy.
  therapeutic_modality: DEVICE
  treatment_term:
    preferred_term: esophageal dilation
    term:
      id: NCIT:C70908
      label: Esophageal Dilation
  evidence:
  - reference: PMID:30364207
    reference_title: "Eosinophilic Esophagitis: Review and Update."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Endoscopic dilation is used for patients with severe dysphagia/food impaction with inadequate response to anti-inflammatory treatment."
    explanation: Defines the indication for endoscopic dilation in refractory fibrostenotic EoE.
discussions:
- discussion_id: gap_eoe_food_antigen_specificity
  prompt: >-
    Why do individual EoE patients react to different specific food antigens
    despite sharing a common esophageal epithelial barrier defect and type 2
    inflammatory program?
  kind: KNOWLEDGE_GAP
  status: OPEN
  attaches_to:
  - pathophysiology#Esophageal Epithelial Barrier Dysfunction
  - pathophysiology#Type 2 Immune Activation
  - mechanistic_hypotheses#barrier_antigen_type2_specificity_model
  rationale: >-
    A shared barrier defect and type 2 axis do not explain patient-specific
    antigen selectivity. The connecting mechanism likely involves pre-existing
    local IgE sensitization and Th2 memory to particular foods, but there is no
    clean mechanistic consensus, and it cannot currently be modeled as a single
    causal edge from barrier disruption to a defined antigen response.
  evidence:
  - reference: PMID:30364207
    reference_title: "Eosinophilic Esophagitis: Review and Update."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "However, several unmet needs are to be solved urgently, as finding a non-invasive disease-monitoring methods and biomarkers for routine practice, the development or new therapies, novel food allergy testing to detect triggering foods, drug, and doses required for initial therapy and safety issues with long-term maintenance therapy, amongst others."
    explanation: Review identifies better food allergy testing to detect triggering foods as an unmet need, supporting the antigen-specificity gap.
- discussion_id: gap_eoe_detergent_human_causality
  prompt: >-
    Is environmental detergent exposure a genuine upstream human causal trigger
    of EoE, or only a mechanistically plausible model-system association?
  kind: KNOWLEDGE_GAP
  status: OPEN
  attaches_to:
  - pathophysiology#Environmental Detergent Exposure
  rationale: >-
    Detergent (SDS) exposure impairs the esophageal barrier and induces IL-33
    and eosinophilia in cell-culture and mouse models, but direct human causal
    evidence is lacking. Whether this represents a true initiating exposure in
    patients or an experimentally tractable proxy remains unresolved.
- discussion_id: gap_eoe_eosinophil_symptom_causality
  prompt: >-
    Which eosinophil-dependent versus eosinophil-independent effector mechanisms
    drive dysphagia and fibrostenotic symptoms in EoE?
  kind: KNOWLEDGE_GAP
  status: OPEN
  attaches_to:
  - pathophysiology#Eosinophil Recruitment to Esophagus
  - pathophysiology#Esophageal Fibrosis and Remodeling
  - mechanistic_hypotheses#barrier_antigen_type2_specificity_model
  rationale: >-
    Eosinophil recruitment is a defining histologic and diagnostic axis, but
    eosinophil depletion alone has not consistently translated into symptom
    improvement. The symptom-producing tissue effectors may include epithelial
    remodeling, mast cells, neuromuscular dysfunction, and fibrosis in addition
    to eosinophils.
  evidence:
  - reference: PMID:29372536
    reference_title: "Biological Therapies for Eosinophilic Esophagitis: Where Do We Stand?"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Mepolizumab and reslizumab, two anti-IL-5 antibodies, were studied in children and adults with EoE and resulted in reduction of esophageal tissue and blood eosinophils, but no significant reduction in symptoms."
    explanation: Review of biologic therapy trials supports a gap between eosinophil reduction and symptom improvement.
clinical_trials:
- name: NCT03633617
  phase: PHASE_III
  status: COMPLETED
  description: >-
    LIBERTY EoE TREET, the pivotal three-part phase 3 randomized, placebo-controlled
    trial of the anti-IL-4-receptor-alpha monoclonal antibody dupilumab in adults and
    adolescents with EoE, assessing histologic and clinical response at 24 and 52
    weeks. It provided the efficacy basis for FDA approval of dupilumab for EoE.
  target_phenotypes:
  - preferred_term: Dysphagia
    term:
      id: HP:0002015
      label: Dysphagia
  - preferred_term: Esophageal eosinophilia
    term:
      id: HP:0410151
      label: Eosinophilic infiltration of the esophagus
  evidence:
  - reference: clinicaltrials:NCT03633617
    reference_title: "A Phase 3, Randomized, 3-Part Study to Investigate the Efficacy and Safety of Dupilumab in Adult and Adolescent Patients With Eosinophilic Esophagitis (EoE)"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "To demonstrate the efficacy of dupilumab treatment compared with placebo in adult and adolescent patients with EoE after 24 weeks of treatment as assessed by histological and clinical measures."
    explanation: The registered phase 3 objective confirms this trial tested dupilumab against placebo on histologic and clinical endpoints, underpinning EoE approval.
disease_term:
  preferred_term: eosinophilic esophagitis
  term:
    id: MONDO:0005361
    label: eosinophilic esophagitis
references:
- reference: PMID:19596009
  title: Biology and treatment of eosinophilic esophagitis.
  findings: []
- reference: PMID:26857345
  title: Newly developed and validated eosinophilic esophagitis histology scoring system and evidence that it outperforms peak eosinophil count for disease diagnosis and monitoring.
  findings: []
- reference: PMID:29372536
  title: 'Biological Therapies for Eosinophilic Esophagitis: Where Do We Stand?'
  findings: []
- reference: PMID:29980278
  title: Epithelial origin of eosinophilic esophagitis.
  findings: []
- reference: PMID:35899466
  title: Detergent exposure induces epithelial barrier dysfunction and eosinophilic inflammation in the esophagus.
  findings: []
- reference: PMID:40521400
  title: 'Eosinophilic Esophagitis Pathogenesis: All Clear?'
  findings: []
- reference: PMID:30364207
  title: 'Eosinophilic Esophagitis: Review and Update.'
  findings: []
- reference: PMID:36546624
  title: Dupilumab in Adults and Adolescents with Eosinophilic Esophagitis.
  findings: []
- reference: PMID:38256003
  title: 'Fibrous Remodeling in Eosinophilic Esophagitis: Clinical Facts and Pathophysiological Uncertainties.'
  findings: []
- reference: PMID:39941170
  title: The Dynamic Evolution of Eosinophilic Esophagitis.
  findings: []
- reference: PMID:38135920
  title: 'Review article: Emerging insights into the epidemiology, pathophysiology, diagnostic and therapeutic aspects of eosinophilic oesophagitis and other eosinophilic gastrointestinal diseases.'
  findings: []
- reference: clinicaltrials:NCT03633617
  title: 'A Phase 3, Randomized, 3-Part Study to Investigate the Efficacy and Safety of Dupilumab in Adult and Adolescent Patients With Eosinophilic Esophagitis (EoE).'
  findings: []
datasets:
- accession: geo:GSE303169
  title: RNAseq analyses of Esophageal biopsies from proton pump inhibitor (PPI)-responsive and PPI-unresponsive Pediatric patients with Eosinophilic Esophagitis.
  description: Clinical trials have identified two distinct eosinophilic esophagitis (EoE) treatment phenotypes, proton pump inhibitor (PPI)-responsive (PPI-R) and PPI-unresponsive (PPI-UR). Herein, we performed clinical, endoscopic, and histologic evaluation of esophageal biopsies from pediatric PPI-R and PPI-UR EoE individuals prior to PPI therapy (diagnosis) and following PPI trial. RNAseq analyses of esophageal biopsy samples revealed common immune and inflammatory transcriptional signatures in both PPI-R EoE and PPI-UR EoE at diagnosis and distinct signatures enriched for processes related to neuropeptide signaling and cell cycle and division.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_count: 25
  publication: PMID:41059573
  notes: Identified by GEO DataSets index search for Eosinophilic Esophagitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE275710
  title: MicroRNAs in plasma-derived extracellular vesicles as non-invasive biomarkers for eosinophilic esophagitis
  description: 'Background: The lack of non-invasive biomarkers imposes the dependence on endoscopy with biopsies for the diagnosis and monitoring of eosinophilic esophagitis (EoE), a prevalent chronic inflammation of the esophagus mediated by a type 2 immune response. We aimed to identify potential non-invasive biomarkers using microRNAs (miRNAs) in plasma-derived extracellular vesicles (pEVs). Methods: This is a prospective single-center observational study including a discovery cohort of EoE patients (n=26) with active disease (EoE.Basal) and after anti-inflammatory treatment (EoE.Post.tx), and control subjects (n=16).'
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_count: 70
  publication: PMID:39859353
  notes: Identified by GEO DataSets index search for Eosinophilic Esophagitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE278888
  title: Differing Epithelial and Immunologic Activation Patterns Following Food Reintroduction Reveal Differential Transcriptional Profiles in Active Eosinophilic Esophagitis
  description: During food trigger reintroductions, eosinophilia can recur in a patchy manner both endoscopically and histologically. We postulated that areas containing low eosinophils represented the early stage of EoE recurrence, while areas with >15 eos/HPF represented established active EoE. We identified ten patients with prior pan-esophageal EoE who experienced patchy eosinophilia during trigger food reintroduction. The progression of recurrent EoE is illustrated by the transcriptional changes occurring from baseline remission through recurrent low and high eosinophil tissues in those with paired time points.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_count: 28
  publication: PMID:39490770
  notes: Identified by GEO DataSets index search for Eosinophilic Esophagitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values.
📚

References & Deep Research

References

12
PMID:19596009
Biology and treatment of eosinophilic esophagitis.
No top-level findings curated for this source.
PMID:26857345
Newly developed and validated eosinophilic esophagitis histology scoring system and evidence that it outperforms peak eosinophil count for disease diagnosis and monitoring.
No top-level findings curated for this source.
PMID:29372536
Biological Therapies for Eosinophilic Esophagitis: Where Do We Stand?
No top-level findings curated for this source.
PMID:29980278
Epithelial origin of eosinophilic esophagitis.
No top-level findings curated for this source.
PMID:35899466
Detergent exposure induces epithelial barrier dysfunction and eosinophilic inflammation in the esophagus.
No top-level findings curated for this source.
PMID:40521400
Eosinophilic Esophagitis Pathogenesis: All Clear?
No top-level findings curated for this source.
PMID:30364207
Eosinophilic Esophagitis: Review and Update.
No top-level findings curated for this source.
PMID:36546624
Dupilumab in Adults and Adolescents with Eosinophilic Esophagitis.
No top-level findings curated for this source.
PMID:38256003
Fibrous Remodeling in Eosinophilic Esophagitis: Clinical Facts and Pathophysiological Uncertainties.
No top-level findings curated for this source.
PMID:39941170
The Dynamic Evolution of Eosinophilic Esophagitis.
No top-level findings curated for this source.
PMID:38135920
Review article: Emerging insights into the epidemiology, pathophysiology, diagnostic and therapeutic aspects of eosinophilic oesophagitis and other eosinophilic gastrointestinal diseases.
No top-level findings curated for this source.
clinicaltrials:NCT03633617
A Phase 3, Randomized, 3-Part Study to Investigate the Efficacy and Safety of Dupilumab in Adult and Adolescent Patients With Eosinophilic Esophagitis (EoE).
No top-level findings curated for this source.

Deep Research

1
Falcon ▸
1. Disease Information
Edison Scientific Literature 49 citations 2026-07-05T19:06:04.205005

1. Disease Information

Overview

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammatory disease of the esophagus characterized clinically by symptoms of esophageal dysfunction and histologically by eosinophil-predominant inflammation of the esophageal squamous epithelium (farah2025thedynamicevolution pages 2-4, gautam2026eosinophilicesophagitismechanisms pages 1-2). EoE is now recognized as a leading cause of dysphagia and food impaction in both children and adults, with its incidence and prevalence rising significantly over the past three decades (gautam2026eosinophilicesophagitismechanisms pages 1-2). The condition is classified as a type 2 inflammatory disease driven primarily by food allergen-mediated immune responses (farah2025thedynamicevolution pages 4-5, khokhar2022eosinophilicesophagitisimmune pages 1-2).

Key Identifiers

  • MONDO ID: MONDO_0005361 (OpenTargets Search: eosinophilic esophagitis)
  • ICD-10: K20.0
  • ICD-11: DA22.0
  • MeSH: D057765
  • OMIM: 610247 (Eosinophilic Esophagitis)
  • Orphanet: ORPHA:73247

Common Synonyms

  • EoE
  • Allergic esophagitis
  • Eosinophilic oesophagitis
  • Primary eosinophilic esophagitis

Data Source

The information in this report is derived from aggregated disease-level resources including systematic reviews, meta-analyses, clinical guidelines (ACG 2025, ESPGHAN 2024), genome-wide association studies, clinical trials, and the OpenTargets database.

2. Etiology

Disease Causal Factors

EoE results from a complex interplay of genetic predisposition, environmental exposures, epithelial barrier dysfunction, and abnormal type 2 immune responses (gautam2026eosinophilicesophagitismechanisms pages 1-2). The disease is fundamentally a food allergen-driven condition, confirmed by the universal response to elemental formula diets that eliminate all intact food proteins (low2024reviewarticleemerging pages 4-6). Key causal factors include:

  • Genetic susceptibility: GWAS have identified multiple susceptibility loci including 5q22 (TSLP/WDR36), 2p23 (CAPN14), 11q13 (LRRC32/C11orf30), and 12q13 (STAT6), with recent expansions to 24 loci and 90 candidate genes (khokhar2022eosinophilicesophagitisimmune pages 1-2, low2024reviewarticleemerging pages 4-6, trimarchi2026multitraitanalysisof pages 10-11).
  • Environmental triggers: Dietary allergens (milk, wheat, eggs, soy), aeroallergens, Westernized diet, poor water quality, and high particulate air pollution (farah2025thedynamicevolution pages 2-4, farah2025thedynamicevolution pages 4-5).
  • Epithelial barrier dysfunction: Loss of structural proteins (E-cadherin, claudins, desmoglein-1, filaggrin) and reduced SPINK7 protease inhibitor levels facilitate allergen penetration (farah2025thedynamicevolution pages 4-5, bertin2026theimmunearchitecture pages 4-6).

Risk Factors

Genetic Risk Factors: - Polymorphisms at TSLP (5q22) enhancing Th2 polarization (farah2025thedynamicevolution pages 2-4, gautam2026eosinophilicesophagitismechanisms pages 1-2) - CAPN14 variants (2p23) disrupting epithelial barrier function (khokhar2022eosinophilicesophagitisimmune pages 1-2, gautam2026eosinophilicesophagitismechanisms pages 1-2) - STAT6 variants (12q13) affecting IL-4/IL-13 signaling (sato2023geneticandmolecular pages 3-4) - Filaggrin (FLG) loss-of-function variants increasing allergen penetration susceptibility (farah2025thedynamicevolution pages 4-5) - DSG1 and DSP variants linked to familial EoE through desmosomal disruption (gautam2026eosinophilicesophagitismechanisms pages 1-2) - Individuals with risk variants at both TSLP and IL4 loci show 3.7-fold increased odds of developing EoE (gautam2026eosinophilicesophagitismechanisms pages 1-2) - African ancestry-specific loci at 1p22.3, 9p13.3, and 12q24.23 (sato2023geneticandmolecular pages 3-4) - Male-specific association at SCARB2 (12q24.31) (trimarchi2026multitraitanalysisof pages 10-11)

Environmental Risk Factors: - Westernized diets with processed foods and preservatives (farah2025thedynamicevolution pages 2-4) - Poor water quality and high particulate air pollution (farah2025thedynamicevolution pages 2-4) - Gut microbiome disruptions from maternal antibiotic use during pregnancy (farah2025thedynamicevolution pages 2-4) - Acid suppression in infancy (farah2025thedynamicevolution pages 2-4) - Seasonal symptom variations related to aeroallergen exposure (farah2025thedynamicevolution pages 4-5) - Male sex (3:1 male-to-female ratio) (farah2025thedynamicevolution pages 2-4, bertin2026theimmunearchitecture pages 2-4) - White/Caucasian ethnicity (bertin2026theimmunearchitecture pages 2-4) - History of atopic diseases (asthma, allergic rhinitis, eczema, food allergies) (farah2025thedynamicevolution pages 2-4)

Gene-Environment Interactions

The disease is multifactorial with only 2.4% concordance in non-twin siblings, despite familial clustering, suggesting substantial environmental influences on disease expression (low2024reviewarticleemerging pages 4-6). The rising incidence is outpacing endoscopy and biopsy rates, suggesting environmental factors are major contributors to EoE pathogenesis beyond diagnostic awareness alone (low2024reviewarticleemerging pages 4-6). EoE associates with both Mendelian genetic conditions (PHTS, hyper-IgE syndromes, SAM syndrome) and connective tissue disorders with increased TGF-β signaling (sato2023geneticandmolecular pages 3-4).

3. Phenotypes

Clinical Symptoms

Adults and Adolescents: - Dysphagia (especially to solids): Cardinal symptom; HP:0002015 (farah2025thedynamicevolution pages 2-4, bertin2026theimmunearchitecture pages 2-4) - Food impaction (food bolus requiring emergency endoscopy in 33–54% of adult patients): HP:0030217 (bertin2026theimmunearchitecture pages 2-4) - Heartburn/chest pain: HP:0040279 (savarino2024eosinophilicesophagitisin pages 3-6) - Nausea: HP:0002018 (savarino2024eosinophilicesophagitisin pages 3-6)

Children: - Feeding difficulties/food avoidance: HP:0011968 (pasta2025endoscopicmanagementof pages 2-4, pasta2025endoscopicmanagementof pages 1-2) - Vomiting: HP:0002013 (pasta2025endoscopicmanagementof pages 2-4, bertin2026theimmunearchitecture pages 2-4) - Regurgitation: HP:0002020 (bertin2026theimmunearchitecture pages 2-4) - Failure to thrive: HP:0001508 (savarino2024eosinophilicesophagitisin pages 3-6, pasta2025endoscopicmanagementof pages 1-2) - Abdominal pain: HP:0002027 (savarino2024eosinophilicesophagitisin pages 3-6)

Histological Features

  • Eosinophilic esophageal infiltration (≥15 eos/HPF diagnostic threshold): HP:0410018 (farah2025thedynamicevolution pages 2-4)
  • Basal zone hyperplasia: HP:0011024 (khokhar2022eosinophilicesophagitisimmune pages 1-2, musburger2025currentandemerging pages 3-4)
  • Dilated intercellular spaces (DIS): (khokhar2022eosinophilicesophagitisimmune pages 1-2, khokhar2022eosinophilicesophagitisimmune pages 3-5)
  • Lamina propria fibrosis: HP:0025578 (farah2025thedynamicevolution pages 5-7)
  • Eosinophilic microabscesses: (musburger2025currentandemerging pages 3-4)

Endoscopic Features (EREFS Score)

  • Linear furrows (48%): Most predictive of active inflammation (farah2025thedynamicevolution pages 5-7, musburger2025currentandemerging pages 3-4)
  • White exudates/plaques (indicating eosinophil clusters): (pasta2025endoscopicmanagementof pages 2-4, farah2025thedynamicevolution pages 5-7)
  • Concentric rings/trachealization (44%): Indicates chronic remodeling (farah2025thedynamicevolution pages 5-7, musburger2025currentandemerging pages 3-4)
  • Esophageal strictures (21–40%): (musburger2025currentandemerging pages 3-4)
  • Mucosal edema with pallor/loss of vascular markings: (pasta2025endoscopicmanagementof pages 2-4)
  • Normal-appearing esophagus in 7–32% of patients: (pasta2025endoscopicmanagementof pages 2-4, pasta2025endoscopicmanagementof pages 1-2)
  • Crepe paper effect (59%): (musburger2025currentandemerging pages 3-4)

Symptom Characteristics

  • Age of onset: Variable—can present in infancy through adulthood; diagnosis peaks in early adulthood (bertin2026theimmunearchitecture pages 2-4)
  • Symptom progression: Progressive; untreated disease carries ~9% annual increase in stricture risk (pasta2025endoscopicmanagementof pages 2-4, pasta2025endoscopicmanagementof pages 1-2)
  • Severity: Variable from mild dysphagia to severe fibrostenotic disease requiring emergency intervention (pasta2025endoscopicmanagementof pages 2-4)

Quality of Life Impact

EoE significantly impacts quality of life, with the greatest negative effects on dysphagia-related anxiety, social activities involving food, and maintaining friendships (savarino2024eosinophilicesophagitisin pages 3-6). Diagnostic delays averaging 3 years are common, attributed to delayed referral, postponed endoscopy, and inadequate biopsy evaluation (savarino2024eosinophilicesophagitisin pages 3-6).

4. Genetic/Molecular Information

GWAS Susceptibility Loci

The following table summarizes the major genetic susceptibility loci identified for EoE through genome-wide association studies:

Chromosomal Locus Gene(s) Function/Role Evidence Source
5q22 TSLP, WDR36 TSLP encodes thymic stromal lymphopoietin, an epithelial alarmin that promotes allergic/Th2 polarization, activates dendritic cells and ILC2s, and is strongly implicated in EoE initiation; WDR36 is co-localized at the susceptibility locus and repeatedly recovered in GWAS/OpenTargets associations. This is one of the most reproducible EoE loci. Established locus in GWAS and reviews (khokhar2022eosinophilicesophagitisimmune pages 1-2, low2024reviewarticleemerging pages 4-6, sato2023geneticandmolecular pages 3-4, gautam2026eosinophilicesophagitismechanisms pages 1-2, OpenTargets Search: eosinophilic esophagitis)
2p23 CAPN14 Encodes calpain-14, an esophagus-enriched protease induced by IL-13; contributes to epithelial barrier dysfunction, desmosomal destabilization, and EoE-specific epithelial remodeling. One of the most disease-specific EoE loci. Established locus in GWAS and mechanistic studies (khokhar2022eosinophilicesophagitisimmune pages 1-2, low2024reviewarticleemerging pages 4-6, sato2023geneticandmolecular pages 3-4, gautam2026eosinophilicesophagitismechanisms pages 1-2, OpenTargets Search: eosinophilic esophagitis)
11q13 LRRC32, C11orf30/EMSY Associated with epithelial and immune regulation; repeatedly identified across EoE genetic studies and also linked to broader atopic susceptibility. Often cited as a reproducible shared atopy/EoE locus. Established locus in GWAS/meta-analysis (khokhar2022eosinophilicesophagitisimmune pages 1-2, low2024reviewarticleemerging pages 4-6, gautam2026eosinophilicesophagitismechanisms pages 1-2)
12q13 STAT6 Central transcription factor downstream of IL-4/IL-13 signaling; regulates Th2 effector programs and eosinophilic inflammation. Variants may also influence treatment-related phenotypes such as PPI response. Established locus and functional relevance in EoE (khokhar2022eosinophilicesophagitisimmune pages 1-2, sato2023geneticandmolecular pages 3-4)
16p13 CLEC16A, DEXI Reproducible susceptibility region identified in more recent genetic studies/meta-analyses; likely contributes to immune regulation and shared atopic disease architecture rather than being EoE-exclusive. Reproducible susceptibility locus in recent reviews/meta-analysis (low2024reviewarticleemerging pages 4-6, trimarchi2026multitraitanalysisof pages 14-15)
15q23 SMAD3 Encodes a key mediator of TGF-β signaling, linking genetic susceptibility to remodeling/fibrostenotic biology and tissue fibrosis in EoE. Additional genome-wide significant locus from newer GWAS/meta-analysis (low2024reviewarticleemerging pages 4-6, sato2023geneticandmolecular pages 3-4)
Additional validated/implicated loci DSG1, DSP, FLG and other barrier genes Not always the lead GWAS locus in summary tables, but repeatedly implicated as susceptibility or familial-risk genes affecting epithelial integrity, allergen penetration, and barrier failure. Barrier-gene evidence from human genetics and mechanistic reviews (gautam2026eosinophilicesophagitismechanisms pages 1-2, farah2025thedynamicevolution pages 4-5)
Recent GWAS expansion 8 risk loci with 11 independent variants in EoE GWAS Newer analyses expanded the map beyond the classic loci, identifying additional signals including loci near GATA3 and IL4R, reinforcing overlap with type 2 immunity and atopic disease genetics. Expanded GWAS findings (trimarchi2026multitraitanalysisof pages 14-15, trimarchi2026multitraitanalysisof pages 10-11)
Recent MTAG expansion 24 loci; ~90 candidate genes Multi-trait analysis with related atopic diseases substantially expanded susceptibility architecture to 24 loci with 90 candidate genes, showing shared genetic basis with asthma, allergic rhinitis, and atopic dermatitis, and supporting polygenic risk modeling. MTAG expansion/preprint summary (trimarchi2026multitraitanalysisof pages 14-15, trimarchi2026multitraitanalysisof pages 10-11)

Table: This table summarizes the main established and newly expanded genetic susceptibility loci for eosinophilic esophagitis, emphasizing how classic barrier and type 2 immunity genes have been extended by recent GWAS/MTAG analyses to a broader polygenic architecture.

Key Molecular Targets (OpenTargets)

OpenTargets (MONDO_0005361) identifies the following validated disease-target associations for EoE (OpenTargets Search: eosinophilic esophagitis): - TSLP (thymic stromal lymphopoietin; ENSG00000145777): Association score 0.44 - WDR36 (WD repeat domain 36; ENSG00000134987): Association score 0.41 - NR3C1 (glucocorticoid receptor; ENSG00000113580): Association score 0.41 - IL13 (interleukin 13; ENSG00000169194): Association score 0.39 - CAPN14 (calpain 14; ENSG00000214711): Association score 0.38 - IL4R (interleukin 4 receptor; ENSG00000077238): Association score 0.37 - IL5 (interleukin 5; ENSG00000113525): Association score 0.33

EoE Transcriptome and Molecular Profiling

The EoE transcriptome, established through gene expression profiling of esophageal biopsies, reveals characteristic dysregulation of epithelial differentiation genes (DSG1, FLG, CAPN14), type 2 effector molecules (CCL26/eotaxin-3, POSTN, SPINK7), and remodeling mediators (TGFB1, COL1A1) (dsilva2026insightsintothe pages 1-2). Expression profiling has identified an EoE Diagnostic Panel that enables molecular-level diagnosis and monitoring (dsilva2026insightsintothe pages 1-2).

Single-Cell RNA Sequencing Findings: Single-cell RNA sequencing of ~14,000 esophageal cells has identified 8 distinct cell clusters and revealed increased clonality of pathogenic GPR15+ Th2 cells enriched in dairy-triggered EoE (uchida2022modelsandtools pages 2-3). Single-cell analyses have uncovered remarkable cellular heterogeneity including distinct cellular subsets, epithelial cell states associated with barrier dysfunction and proliferation, activated fibroblasts, and spatial organization of inflammatory microenvironments (dsilva2026insightsintothe pages 1-2).

Epigenetic Changes: Epigenetic studies have uncovered changes in DNA methylation and chromatin structure affecting gene expression in EoE pathology, including aberrant CDX2 expression linked to methyl-CpG binding proteins, suggesting epigenetic contributions to esophageal epithelial remodeling and metaplasia-like processes. Suppressed zinc-related pathways (MT1X, MT1F, MT2A) indicate barrier dysfunction through zinc transporter dysregulation.

Genetic Inheritance

EoE exhibits complex, polygenic inheritance with increased familial clustering. Only 2.4% concordance in non-twin siblings suggests that while genetic susceptibility is important, environmental factors substantially modulate disease expression (low2024reviewarticleemerging pages 4-6). GWAS identified 31 genetic risk loci, with most variants being non-coding (36.7% intergenic, 42.4% intronic), suggesting involvement of regulatory elements (khokhar2022eosinophilicesophagitisimmune pages 1-2). Sex-specific genetic variants have been identified, and recent MTAG analyses demonstrate a polygenic risk score with OR of 11.57 in the top versus bottom decile (trimarchi2026multitraitanalysisof pages 10-11).

5. Environmental Information

Environmental Factors

  • Westernized diets with processed foods and preservatives (farah2025thedynamicevolution pages 2-4)
  • Poor water quality and high particulate air pollution (farah2025thedynamicevolution pages 2-4)
  • Early-life acid suppression therapy (farah2025thedynamicevolution pages 2-4)
  • Maternal antibiotic use during pregnancy disrupting gut microbiome (farah2025thedynamicevolution pages 2-4)
  • Seasonal aeroallergen exposure influencing symptom flares (farah2025thedynamicevolution pages 4-5)

Lifestyle Factors

  • Dietary allergen exposure, particularly milk, wheat, eggs, soy, tree nuts, and seafood (farah2025thedynamicevolution pages 4-5, musburger2025currentandemerging pages 3-4)
  • Western dietary patterns associated with increased disease prevalence (farah2025thedynamicevolution pages 2-4)

6. Mechanism / Pathophysiology

Molecular Pathways

Type 2 Inflammatory Cascade: The central pathogenic mechanism involves a type 2 (Th2)-driven immune response. Upon allergen exposure, esophageal epithelial cells release alarmins—TSLP, IL-33, and IL-25—which activate dendritic cells and group 2 innate lymphoid cells (ILC2s) (farah2025thedynamicevolution pages 4-5, bertin2026theimmunearchitecture pages 4-6). This triggers production of IL-4, IL-5, and IL-13, the key effector cytokines: - IL-13 plays the central pathobiological role, driving eotaxin-3 (CCL26) expression, impairing epithelial barrier function by suppressing barrier proteins (filaggrin, claudins, DSG1), and upregulating CAPN14, which destabilizes desmosomal junctions (bertin2026theimmunearchitecture pages 7-9, farah2025thedynamicevolution pages 4-5). - IL-5 promotes eosinophil proliferation, survival, maturation, bone marrow release, and trafficking to the esophagus (farah2025thedynamicevolution pages 4-5, ariasgonzalez2024fibrousremodelingin pages 1-2). - IL-4 promotes Th2 differentiation, inhibits apoptosis, and drives B cell class switching to IgE and IgG4 (ariasgonzalez2024fibrousremodelingin pages 1-2, imam2026theroleof pages 5-5).

GO terms: GO:0006955 (immune response), GO:0045087 (innate immune response), GO:0002286 (T-helper 2 type immune response), GO:0006954 (inflammatory response).

Epithelial Barrier Dysfunction: Barrier dysfunction is central to EoE pathogenesis. Loss of structural proteins (E-cadherin, claudins, desmoglein-1, SPINK7) weakens tight junctions and facilitates allergen penetration (farah2025thedynamicevolution pages 4-5, bertin2026theimmunearchitecture pages 4-6). IL-13-driven upregulation of calpain-14 destabilizes desmosomal junctions, while SPINK7 loss amplifies protease activity and TSLP production, creating barrier-to-alarmin feedback loops (bertin2026theimmunearchitecture pages 4-6).

GO terms: GO:0045104 (intermediate filament cytoskeleton organization), GO:0016337 (single organismal cell-cell adhesion).

ILC2-Areg-EGFR Signaling: ILC2s serve as a critical bridge between epithelial alarmin signals and adaptive Th2 responses, producing amphiregulin (Areg) that binds EGFR on basal cells, triggering ERK1/2 and AKT signaling and causing pathological epithelial hyperproliferation and thickening (bertin2026theimmunearchitecture pages 7-9).

Tissue Remodeling and Fibrosis

Chronic inflammation causes progressive tissue remodeling including fibrosis, angiogenesis, and smooth muscle hypertrophy. TGF-β1 upregulation mediates fibroblast activation and extracellular matrix deposition, causing esophageal stiffening and stricture formation. Periostin (POSTN), upregulated by IL-13, enhances fibrosis and eosinophil recruitment (farah2025thedynamicevolution pages 4-5, ariasgonzalez2024fibrousremodelingin pages 1-2). Epithelial-mesenchymal transition (EMT) and collagen deposition contribute to esophageal strictures proportional to a patient's age and untreated disease duration (ariasgonzalez2024fibrousremodelingin pages 1-2).

GO terms: GO:0030198 (extracellular matrix organization), GO:0001525 (angiogenesis).

Eosinophil Effector Functions

Eosinophil degranulation releases major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil-derived neurotoxin (EDN), causing epithelial damage and oxidative stress (bertin2026theimmunearchitecture pages 7-9). Eosinophils also produce TGF-β and ATRA, promoting Treg differentiation as a regulatory counter-circuit (bertin2026theimmunearchitecture pages 7-9).

Cell Types Involved

  • Eosinophils: CL:0000771
  • Th2 cells: CL:0000546
  • ILC2s (group 2 innate lymphoid cells): CL:0001069
  • Mast cells: CL:0000097
  • Basophils: CL:0000767
  • Dendritic cells: CL:0000451
  • Esophageal epithelial cells: CL:0002252
  • Fibroblasts: CL:0000057
  • B cells/plasma cells: CL:0000236/CL:0000786

7. Anatomical Structures Affected

Primary Organ

  • Esophagus (UBERON:0001043): The primary and often sole organ affected, with inflammation spanning the esophageal squamous epithelium and potentially deeper layers (farah2025thedynamicevolution pages 2-4, ariasgonzalez2024fibrousremodelingin pages 1-2).

Tissue and Cellular Level

  • Esophageal squamous epithelium (UBERON:0006920): Eosinophilic infiltration, basal zone hyperplasia, dilated intercellular spaces (khokhar2022eosinophilicesophagitisimmune pages 1-2, khokhar2022eosinophilicesophagitisimmune pages 3-5)
  • Lamina propria (UBERON:0000030): Fibrosis and inflammatory cell infiltration (farah2025thedynamicevolution pages 5-7)
  • Subepithelial connective tissue: Collagen deposition and fibrosis (ariasgonzalez2024fibrousremodelingin pages 1-2)
  • Smooth muscle layers: Hypertrophy in chronic disease (farah2025thedynamicevolution pages 4-5)

Localization

  • Disease affects the entire esophagus but biopsies should be obtained from both proximal and distal regions to account for patchy distribution of inflammation (farah2025thedynamicevolution pages 2-4).

8. Temporal Development

Onset

  • Typical age of onset: Can occur at any age from infancy to late adulthood; incidence rises during adolescence and peaks in early adulthood (bertin2026theimmunearchitecture pages 2-4)
  • Onset pattern: Chronic and insidious, often with diagnostic delays averaging 3 years (savarino2024eosinophilicesophagitisin pages 3-6)

Progression

  • Disease course: Chronic, progressive if untreated, with a ~9% annual increase in esophageal stricture risk (pasta2025endoscopicmanagementof pages 2-4, pasta2025endoscopicmanagementof pages 1-2)
  • Stages: Inflammatory (early) → fibrostenotic (advanced), with adults displaying more subepithelial fibrosis and esophageal narrowing than children (musburger2025currentandemerging pages 3-4)
  • Duration: Chronic lifelong disease requiring maintenance therapy (farah2025thedynamicevolution pages 10-12)
  • Remission patterns: Treatment-induced remission is achievable but disease recurs upon treatment cessation in most patients (farah2025thedynamicevolution pages 10-12)

9. Inheritance and Population

Epidemiology

  • Global incidence: 5.3 per 100,000 person-years (farah2025thedynamicevolution pages 2-4, bertin2026theimmunearchitecture pages 2-4, low2024reviewarticleemerging pages 1-3)
  • Global prevalence: 40.0 per 100,000 persons, representing an 800% increase from 1976–2001 to 2017–2022 (bertin2026theimmunearchitecture pages 2-4)
  • Prevalence in Western countries: Exceeds 1 in 1,000 individuals (bertin2026theimmunearchitecture pages 2-4)
  • European incidence: 3.64 per 100,000 person-years (nationwide) to 7.16 (regional/center-based studies), with significant increases over the last 30 years
  • Danish incidence: Increased from 3.9 to 11.7 per 100,000 person-years between 2011 and 2018
  • US prevalence estimates: Range from 1 per 1,000 to >150 per 100,000 (pasta2025endoscopicmanagementof pages 1-2)
  • Italy prevalence: Estimated at 41 per 100,000 (savarino2024eosinophilicesophagitisin pages 3-6)

Population Demographics

  • Sex ratio: Approximately 3:1 male-to-female predominance (farah2025thedynamicevolution pages 2-4, bertin2026theimmunearchitecture pages 2-4); male prevalence 53.8 per 100,000 versus female 20.1 per 100,000 (savarino2024eosinophilicesophagitisin pages 3-6)
  • Ethnicity: Predominantly affects white/Caucasian individuals; African ancestry-specific risk loci identified (sato2023geneticandmolecular pages 3-4, bertin2026theimmunearchitecture pages 2-4)
  • Age distribution: Higher incidence in adults than children; children have approximately one-quarter the incidence of adults aged 40–64 years (bertin2026theimmunearchitecture pages 2-4)
  • Comorbidities: Most frequently associated with rhinitis, asthma, food allergy, and gastroesophageal reflux disease (farah2025thedynamicevolution pages 2-4)

Genetic Inheritance

  • Pattern: Complex polygenic/multifactorial (khokhar2022eosinophilicesophagitisimmune pages 1-2, sato2023geneticandmolecular pages 3-4)
  • Concordance: Only 2.4% in non-twin siblings (low2024reviewarticleemerging pages 4-6)
  • Familial clustering: Present, with increased risk in second-degree relatives (khokhar2022eosinophilicesophagitisimmune pages 1-2)
  • Mendelian associations: PHTS, hyper-IgE syndromes, SAM syndrome (sato2023geneticandmolecular pages 3-4)

10. Diagnostics

Clinical Diagnostic Criteria

Diagnosis requires: (1) symptoms of esophageal dysfunction, (2) eosinophil-predominant inflammation with ≥15 eosinophils per high-power field on esophageal biopsy, and (3) exclusion of other causes of esophageal eosinophilia (farah2025thedynamicevolution pages 2-4, musburger2025currentandemerging pages 3-4). At least six biopsies from multiple esophageal sites are recommended to account for patchy inflammation (farah2025thedynamicevolution pages 2-4).

Endoscopic Assessment

The EoE Endoscopic Reference Score (EREFS) standardizes endoscopic evaluation across five domains: Edema, Rings, Exudates, Furrows, and Strictures (farah2025thedynamicevolution pages 5-7). Functional lumen imaging probe (FLIP) panometry and high-resolution manometry (HRM) provide additional assessment of fibrostenotic features.

Histological Assessment

The EoE Histological Scoring System evaluates inflammatory activity including eosinophilic infiltration density, basal zone hyperplasia, dilated intercellular spaces, eosinophilic microabscesses, papillary elongation, and lamina propria fibrosis (farah2025thedynamicevolution pages 5-7, musburger2025currentandemerging pages 3-4).

Biomarkers

  • Peak eosinophil count (PEC): Gold standard histologic measure (farah2025thedynamicevolution pages 2-4)
  • Serum biomarkers: No single serum biomarker has sufficient sensitivity; 49 serum proteins tested without reliable diagnostic capacity (savarino2024eosinophilicesophagitisin pages 3-6)
  • TSLP and periostin: Show promise as potential biomarkers but require further validation (farah2025thedynamicevolution pages 5-7)
  • Extracellular matrix proteins (CTX-III, PRO-C3, PRO-C6): Potential surrogate biomarkers for fibrosis assessment
  • TSLP-responsive memory CD4+ T cells: TSLP-induced STAT5 phosphorylation in circulating CD4+ T cells correlates with esophageal eosinophil counts, providing a basis for a blood-based diagnostic test
  • Eosinophil-derived mediators (ECP, EDN, EPO, MBP): Investigated as non-invasive biomarkers

Emerging Diagnostic Tools

  • Esophageal string test and Cytosponge for non-invasive monitoring
  • Transnasal endoscopy for non-sedated assessment
  • EndoFlip for assessing esophageal distensibility

Differential Diagnosis

Conditions to exclude: GERD, proton pump inhibitor-responsive esophageal eosinophilia (now integrated into EoE), eosinophilic gastroenteritis, Crohn's disease involving the esophagus, pill esophagitis, infection, hypereosinophilic syndrome, and achalasia.

11. Outcome/Prognosis

Disease Course

EoE is a chronic, progressive disease that, if left untreated, leads to esophageal remodeling with fibrosis and stricture formation. The risk of strictures increases by approximately 9% annually without treatment (pasta2025endoscopicmanagementof pages 2-4, pasta2025endoscopicmanagementof pages 1-2). Esophageal stricture formation is proportional to a patient's age and untreated disease duration (ariasgonzalez2024fibrousremodelingin pages 1-2).

Morbidity

  • Food bolus impaction precipitates emergency endoscopy in 33–54% of adult patients (bertin2026theimmunearchitecture pages 2-4)
  • 25% of patients have a history of esophageal dilations; 30% report EoE-related emergency room visits in the preceding year (savarino2024eosinophilicesophagitisin pages 3-6)
  • Approximately 58% of patients undergoing dilation require repeated procedures within the first year (farah2025thedynamicevolution pages 12-13)

Mortality

EoE is not typically associated with significant mortality. Epidemiological evidence suggests that EoE patients do not develop esophageal malignancy, and EoE-associated epithelial remodeling may actually limit esophageal carcinogenesis.

Quality of Life

Quality of life impacts include dysphagia-related anxiety, impaired social activities involving food, and difficulty maintaining friendships (EoE Impact Questionnaire scores 1.6–2.2 on 1–5 scale) (savarino2024eosinophilicesophagitisin pages 3-6). Heartburn was the most commonly reported symptom (69%) among surveyed patients.

12. Treatment

The following table provides a comprehensive summary of current and emerging treatment options for EoE:

Treatment Category Specific Agent/Approach Mechanism of Action Histologic Remission Rate (%) Regulatory Status Key Notes
Acid suppression / anti-inflammatory therapy (MAXO: proton pump inhibitor administration) Proton pump inhibitors (PPIs; e.g., omeprazole, esomeprazole) Reduce acid exposure and also exert anti-inflammatory effects, including suppression of Th2-associated inflammatory signaling beyond acid suppression 41.7% in meta-analytic data; ~45–50.5% in recent reviews/real-world summaries Used off-label but guideline-recommended first-line therapy for EoE Clinical response reported around 60.8–71%; long-term histologic response ~60% in some cohorts; often first pharmacologic option (bertin2026theimmunearchitecture pages 10-12, farah2025thedynamicevolution pages 10-12, musburger2025currentandemerging pages 6-7, low2024reviewarticleemerging pages 9-11)
Topical corticosteroid (MAXO: topical corticosteroid therapy) Budesonide oral suspension (BOS; Eohilia) Local glucocorticoid anti-inflammatory effect in esophageal mucosa via NR3C1 signaling 53.1% FDA-approved in the US for induction treatment in adolescents/adults; formulation-specific approval noted in recent reviews Maintenance remission reported up to 83.3% at lower doses; adverse effects include esophageal candidiasis (farah2025thedynamicevolution pages 10-12, musburger2025currentandemerging pages 6-7)
Topical corticosteroid (MAXO: topical corticosteroid therapy) Budesonide orodispersible tablet (BOT; Jorveza) Local glucocorticoid anti-inflammatory effect optimized for esophageal contact time Up to 93% Approved in Europe/Canada/Australia for adults in recent reviews Sustained remission ~75% at 48 weeks; among the highest efficacy topical options reported (bertin2026theimmunearchitecture pages 10-12, bertin2026theimmunearchitecture pages 12-14)
Topical corticosteroid (MAXO: topical corticosteroid therapy) Fluticasone swallowed from inhaler / esophagus-targeted preparation Local glucocorticoid anti-inflammatory effect in esophageal epithelium 64–71% Commonly used off-label; guideline-recommended topical steroid option Histologic remission superior to placebo; candidiasis reported in ~5–30% with topical steroids overall (musburger2025currentandemerging pages 6-7, low2024reviewarticleemerging pages 9-11)
Biologic therapy (MAXO: monoclonal antibody therapy) Dupilumab (anti-IL-4Rα) Blocks IL-4/IL-13 signaling through IL4Rα, targeting core type 2 inflammatory pathway 59–60% at 24 weeks; 100% in long-term open-label extension reported in review summary FDA-approved for EoE since 2022; label expanded in 2024 to younger children; also approved in Europe/Canada per reviews First disease-specific biologic for EoE; particularly useful in refractory disease and patients with atopic comorbidities; marked eosinophil reduction (~96%) reported (bertin2026theimmunearchitecture pages 10-12, bertin2026theimmunearchitecture pages 12-14, farah2025thedynamicevolution pages 12-13, musburger2025currentandemerging pages 3-4)
Dietary therapy (MAXO: dietary modification) Single-food elimination diet (often milk-first approach) Removes food antigen triggers driving esophageal type 2 inflammation 44–54% Guideline-recommended first-line non-pharmacologic therapy Less restrictive than broader elimination diets; requires serial endoscopy/biopsy to confirm remission and identify triggers (bertin2026theimmunearchitecture pages 10-12, bertin2026theimmunearchitecture pages 12-14, musburger2025currentandemerging pages 3-4)
Dietary therapy (MAXO: elimination diet) Empiric multi-food elimination diet (e.g., 2-food, 4-food, 6-food elimination) Sequential removal of common food allergens Variable within broader dietary range; higher than 1-food approaches but below elemental diet in most summaries Guideline-recommended first-line option Common targets include dairy, wheat, egg, soy/legumes, nuts, fish/shellfish; adherence burden is substantial (bertin2026theimmunearchitecture pages 12-14, musburger2025currentandemerging pages 3-4)
Dietary therapy (MAXO: elemental diet) Elemental amino-acid formula diet Complete removal of intact food antigens 90–94% Effective but limited by palatability, cost, and practicality Highest remission rates among dietary therapies; often reserved for selected or refractory cases (bertin2026theimmunearchitecture pages 10-12, bertin2026theimmunearchitecture pages 12-14)
Endoscopic/mechanical therapy (MAXO: esophageal dilation) Esophageal dilation for fibrostenotic disease Mechanically disrupts strictures and increases luminal diameter; does not treat inflammation Histologic remission: not applicable Standard adjunctive interventional approach Symptomatic relief ~85–95%; often targets 15–18 mm luminal diameter; repeat dilations common; perforation risk ~0.38%; should be combined with anti-inflammatory treatment (bertin2026theimmunearchitecture pages 12-14, farah2025thedynamicevolution pages 12-13)
Emerging biologic (MAXO: monoclonal antibody therapy) Cendakimab (anti-IL-13) Selectively blocks IL-13, aiming to reduce epithelial dysfunction, eotaxin-3 induction, and remodeling 28.6% vs 2.2% placebo in review summary Investigational / not broadly approved for EoE Mechanistically attractive because IL-13 is central to EoE biology; under active clinical development (bertin2026theimmunearchitecture pages 12-14)
Emerging biologic (MAXO: monoclonal antibody therapy) Tezepelumab (anti-TSLP) Blocks epithelial alarmin TSLP upstream of Th2 polarization and eosinophilic inflammation Not established in the cited summaries Investigational Rationale is strong given TSLP genetic and mechanistic evidence in EoE, but robust remission data were not provided in the retrieved summaries (bertin2026theimmunearchitecture pages 4-6, musburger2025currentandemerging pages 3-4)
Emerging biologic (MAXO: monoclonal antibody therapy) Benralizumab (anti-IL-5Rα) Depletes eosinophils by targeting IL-5 receptor alpha Not recommended / no consistent efficacy for routine EoE treatment in recent reviews Investigational; not approved for EoE Despite a compelling eosinophil-depleting mechanism, recent reviews summarize insufficient clinical benefit for routine use in EoE (bertin2026theimmunearchitecture pages 12-14, musburger2025currentandemerging pages 3-4)

Table: This table summarizes current and emerging treatment options for eosinophilic esophagitis, including mechanisms, remission rates, regulatory status, and practical notes. It is useful for comparing first-line therapies, procedural management, and biologic pipeline agents in one place.

Treatment Strategy

The ACG 2025 Clinical Guideline and AGA/JTF guidelines recommend proton pump inhibitors, topical steroids, empiric diet elimination, dupilumab, and esophageal dilation as treatment options (bertin2026theimmunearchitecture pages 10-12, farah2025thedynamicevolution pages 10-12, low2024reviewarticleemerging pages 9-11). Treatment selection should be individualized based on disease phenotype, severity, and patient preference (bertin2026theimmunearchitecture pages 10-12).

First-line options: PPIs or swallowed topical corticosteroids, with corticosteroids highlighted as most potent for severe cases (farah2025thedynamicevolution pages 10-12). Dietary elimination is also recommended as a first-line non-pharmacologic option (musburger2025currentandemerging pages 3-4).

Second-line/refractory disease: Dupilumab is recommended for patients failing first-line treatment, particularly those with atopic comorbidities. It is approved for patients aged ≥1 year (FDA expanded 2024) or ≥12 years (EMA) (farah2025thedynamicevolution pages 12-13, musburger2025currentandemerging pages 3-4).

Maintenance therapy: Recommended for all treatment approaches given disease recurrence upon cessation (farah2025thedynamicevolution pages 10-12, low2024reviewarticleemerging pages 9-11).

Current Clinical Trials

Active recruiting Phase 3 trials include: - NCT06596252: Once daily vs. twice daily budesonide orodispersible tablets for EoE remission induction (Dr. Falk Pharma; n=308) - NCT07112378: Dupilumab in small children (1–11 years) with EoE (Regeneron; n=20)

Active Phase 2 trials include: - NCT06705387: Dupilumab vs. topical corticosteroid effectiveness comparison in stenotic EoE (n=72) - NCT05608681: EP-104GI (novel formulation) in adults with EoE (Eupraxia Pharmaceuticals; n=117) - NCT05485155: Zemaira (alpha-1 antitrypsin) pilot study in EoE (Cincinnati Children's; n=15)

Emerging Biologics

  • Cendakimab (anti-IL-13): Achieved 28.6% histologic remission vs. 2.2% placebo (bertin2026theimmunearchitecture pages 12-14)
  • Tezepelumab (anti-TSLP): Investigational, targeting upstream alarmin pathway
  • Dectrekumab (anti-IL-13): Under investigation
  • Other agents investigated but showing insufficient efficacy include anti-IL-5 agents (mepolizumab, reslizumab, benralizumab), anti-IgE (omalizumab), and anti-Siglec-8 (lirentelimab) (bertin2026theimmunearchitecture pages 12-14)

MAXO terms: MAXO:0000874 (proton pump inhibitor administration), MAXO:0000753 (dietary modification), MAXO:0001298 (monoclonal antibody therapy), MAXO:0000004 (surgical procedure).

13. Prevention

Primary Prevention

No established primary prevention strategies exist, but modifiable risk factors include: - Avoiding unnecessary early-life acid suppression therapy (farah2025thedynamicevolution pages 2-4) - Judicious antibiotic use during pregnancy (farah2025thedynamicevolution pages 2-4) - Attention to environmental pollutant exposure (farah2025thedynamicevolution pages 2-4)

Secondary Prevention

  • Early diagnosis and treatment to prevent fibrostenotic progression
  • Monitoring of patients with atopic comorbidities who are at increased risk
  • At least six biopsies from multiple esophageal sites for diagnostic accuracy (farah2025thedynamicevolution pages 2-4)

Tertiary Prevention

  • Maintenance therapy to prevent disease relapse and progressive fibrostenosis
  • Monitoring with clinical, endoscopic, and histologic assessments (bertin2026theimmunearchitecture pages 10-12)
  • Esophageal dilation for fibrostenotic complications combined with anti-inflammatory therapy (farah2025thedynamicevolution pages 12-13)

14. Other Species / Natural Disease

Comparative Biology

No naturally occurring EoE analogue has been documented in veterinary medicine. However, eosinophilic esophagitis-like conditions can be experimentally induced in multiple species for research purposes. A novel swine biomedical research model for EoE has been developed using intraperitoneal sensitization and oral challenge with hen egg white protein, producing esophageal eosinophilia (>15 eosinophils/0.24 mm²), systemic Th2/IgE responses, local eotaxin-1 expression, and endoscopic findings including linear furrows and white exudates consistent with human EoE hallmarks.

15. Model Organisms

Mouse Models

Multiple murine models have been developed spanning five major categories (dsilva2026insightsintothe pages 2-4):

  1. Allergen-driven models: Aspergillus fumigatus intranasal exposure (first established model, 2001); OVA-alum sensitization with intragastric challenge; house dust mite exposure (jackson2025mousemodelsof pages 9-11, uchida2022modelsandtools pages 1-2)

  2. Chemical/hapten models: Oxazolone (OXA) producing robust EoE phenotypes with esophageal eosinophilia, epithelial thickening, and collagen deposition, showing ~25% overlap with human EoE genetic signatures (jackson2025mousemodelsof pages 9-11)

  3. Cytokine overexpression models: IL-13, IL-33, and IL-18 administration or transgenic overexpression; IL-33 produces EoE-like phenotype in an IL-13-dependent manner (jackson2025mousemodelsof pages 14-16, uchida2022modelsandtools pages 1-2)

  4. Spontaneous genetic models: Nik⁻/⁻ mice developing severe eosinophilia with basal cell hyperplasia, mucosal thickening, and increased collagen deposition; Tgfbr1M318R/+ variant model recapitulating EoE clinically, immunologically, histologically, and transcriptionally, correlating best with human EoEe2 endotype (jackson2025mousemodelsof pages 14-16, dsilva2026insightsintothe pages 11-13)

  5. Barrier disruption models: SDS detergent exposure inducing eosinophilia, barrier changes, and increased IL-33 expression (jackson2025mousemodelsof pages 9-11)

Phenotype Recapitulation

Key features recapitulated across models include: lamina propria eosinophilia, intraepithelial eosinophilia, subepithelial fibrosis, basal cell hyperplasia, epithelial thickening, multi-cellular inflammation, epithelial barrier dysfunction, angiogenesis, neuronal remodeling, and epithelial transcriptomic remodeling (dsilva2026insightsintothe pages 11-13). No single model fully recapitulates all aspects of human disease (dsilva2026insightsintothe pages 2-4).

Model Limitations

  • Most models use inbred strains (C57BL/6, BALB/c) differing in baseline immune polarization (dsilva2026insightsintothe pages 14-16)
  • Single-antigen models do not replicate polyvalent sensitization to multiple food antigens seen in human EoE (dsilva2026insightsintothe pages 14-16)
  • Mouse and human esophageal anatomy differ significantly (keratinized vs. non-keratinized epithelium)
  • Most models lack assessment of disease-relevant functional outcomes such as esophageal motility

Swine Model

A novel swine model using sensitization with hen egg white protein produces systemic Th2/IgE responses, local eotaxin-1 expression, esophageal eosinophilia (>15 eos/0.24 mm²), and endoscopic findings (linear furrows, white exudates) closely matching human EoE.

Summary

Eosinophilic esophagitis is a chronic, immune-mediated disease of growing global significance, with incidence and prevalence increasing dramatically over the past three decades (bertin2026theimmunearchitecture pages 2-4). The disease results from complex interactions between genetic susceptibility (24+ GWAS loci, 90 candidate genes), environmental triggers, epithelial barrier dysfunction, and type 2 inflammatory responses driven by the IL-4/IL-13/TSLP axis (khokhar2022eosinophilicesophagitisimmune pages 1-2, trimarchi2026multitraitanalysisof pages 10-11, farah2025thedynamicevolution pages 4-5). Diagnosis requires endoscopy with biopsies demonstrating ≥15 eosinophils/HPF, and management involves a growing therapeutic armamentarium including PPIs, topical corticosteroids, dietary elimination, and biologics (bertin2026theimmunearchitecture pages 10-12). The FDA approval of dupilumab in 2022 represented a landmark advance as the first disease-specific biologic, achieving 59–60% histologic remission versus 5–6% with placebo (bertin2026theimmunearchitecture pages 10-12, farah2025thedynamicevolution pages 12-13). Emerging therapies targeting IL-13, TSLP, and other pathways offer promise for more personalized, mechanism-based treatment strategies (bertin2026theimmunearchitecture pages 12-14). Critical unmet needs include development of validated non-invasive biomarkers for diagnosis and monitoring, long-term safety data for biologics, and personalized approaches to address the heterogeneous nature of this disease (savarino2024eosinophilicesophagitisin pages 3-6, gautam2026eosinophilicesophagitismechanisms pages 1-2).

References

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  2. (gautam2026eosinophilicesophagitismechanisms pages 1-2): Ravi Gautam and Melanie A. Ruffner. Eosinophilic esophagitis: mechanisms of disease and approach to treatment. Current Allergy and Asthma Reports, Mar 2026. URL: https://doi.org/10.1007/s11882-026-01253-w, doi:10.1007/s11882-026-01253-w. This article has 2 citations and is from a peer-reviewed journal.

  3. (farah2025thedynamicevolution pages 4-5): Amir Farah, Tarek Assaf, Jawad Hindy, Wisam Abboud, Mostafa Mahamid, Edoardo Vincenzo Savarino, and Amir Mari. The dynamic evolution of eosinophilic esophagitis. Diagnostics, 15:240, Jan 2025. URL: https://doi.org/10.3390/diagnostics15030240, doi:10.3390/diagnostics15030240. This article has 14 citations.

  4. (khokhar2022eosinophilicesophagitisimmune pages 1-2): Dilawar Khokhar, Sahiti Marella, Gila Idelman, Joy W. Chang, Mirna Chehade, and Simon P. Hogan. Eosinophilic esophagitis: immune mechanisms and therapeutic targets. Jul 2022. URL: https://doi.org/10.1111/cea.14196, doi:10.1111/cea.14196. This article has 56 citations and is from a domain leading peer-reviewed journal.

  5. (OpenTargets Search: eosinophilic esophagitis): Open Targets Query (eosinophilic esophagitis, 13 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.

  6. (low2024reviewarticleemerging pages 4-6): Eric E. Low and Evan S. Dellon. Review article: emerging insights into the epidemiology, pathophysiology, diagnostic and therapeutic aspects of eosinophilic oesophagitis and other eosinophilic gastrointestinal diseases. Alimentary Pharmacology & Therapeutics, 59:322-340, Dec 2024. URL: https://doi.org/10.1111/apt.17845, doi:10.1111/apt.17845. This article has 41 citations and is from a highest quality peer-reviewed journal.

  7. (trimarchi2026multitraitanalysisof pages 10-11): Michael P. Trimarchi, Bahram Namjou-Khales, Netali Ben-Baruch Morgenstern, Mark Rochman, Xiaoting Chen, Garrett Osswald, John Besse, Molly Shook, Julie Caldwell, Michael Lape, Tetsuo Shota, Matthew T. Weirauch, Melanie Ruffner, Gregory Constantine, Lisa J. Martin, Leah C. Kottyan, Marc E. Rothenberg, and Consortium of Eosinophilic Gastrointestinal Disease Researchers. Multi-trait analysis of gwas expands eosinophilic esophagitis genetic susceptibility and polygenic risk scores. Research Square, May 2026. URL: https://doi.org/10.21203/rs.3.rs-6630283/v2, doi:10.21203/rs.3.rs-6630283/v2. This article has 2 citations.

  8. (bertin2026theimmunearchitecture pages 4-6): Luisa Bertin, Federico Caldart, Alberto Barchi, Niccolò Seregni, Andrea Pasta, Francesco Calabrese, Elisa Marabotto, Amir Mari, Amir Farah, Emma Sirinic, Andrea Sorge, Matteo Ghisa, Javier Chahuán, Vincenzo Savarino, and Edoardo Vincenzo Savarino. The immune architecture of eosinophilic esophagitis: mechanisms, therapeutic targets, and precision management. ImmunoTargets and Therapy, Volume 15:1-27, May 2026. URL: https://doi.org/10.2147/itt.s510865, doi:10.2147/itt.s510865. This article has 0 citations.

  9. (sato2023geneticandmolecular pages 3-4): Hiroki Sato, Kasumi Osonoi, Colby S. Sharlin, and Tetsuo Shoda. Genetic and molecular contributors in eosinophilic esophagitis. Current Allergy and Asthma Reports, 23:255-266, Apr 2023. URL: https://doi.org/10.1007/s11882-023-01075-0, doi:10.1007/s11882-023-01075-0. This article has 17 citations and is from a peer-reviewed journal.

  10. (bertin2026theimmunearchitecture pages 2-4): Luisa Bertin, Federico Caldart, Alberto Barchi, Niccolò Seregni, Andrea Pasta, Francesco Calabrese, Elisa Marabotto, Amir Mari, Amir Farah, Emma Sirinic, Andrea Sorge, Matteo Ghisa, Javier Chahuán, Vincenzo Savarino, and Edoardo Vincenzo Savarino. The immune architecture of eosinophilic esophagitis: mechanisms, therapeutic targets, and precision management. ImmunoTargets and Therapy, Volume 15:1-27, May 2026. URL: https://doi.org/10.2147/itt.s510865, doi:10.2147/itt.s510865. This article has 0 citations.

  11. (savarino2024eosinophilicesophagitisin pages 3-6): Edoardo Vincenzo Savarino, Giovanni Barbara, Maria Beatrice Bilò, Nicola De Bortoli, Antonio Di Sabatino, Salvatore Oliva, Roberto Penagini, Francesca Racca, Annalisa Tortora, Filippo Rumi, and Americo Cicchetti. Eosinophilic esophagitis in adults and adolescents: epidemiology, diagnostic challenges, and management strategies for a type 2 inflammatory disease. Therapeutic Advances in Gastroenterology, Jan 2024. URL: https://doi.org/10.1177/17562848241249570, doi:10.1177/17562848241249570. This article has 29 citations and is from a peer-reviewed journal.

  12. (pasta2025endoscopicmanagementof pages 2-4): Andrea Pasta, Francesco Calabrese, Manuele Furnari, Edoardo Vincenzo Savarino, Pierfrancesco Visaggi, Giorgia Bodini, Elena Formisano, Patrizia Zentilin, Edoardo Giovanni Giannini, and Elisa Marabotto. Endoscopic management of eosinophilic esophagitis: a narrative review on diagnosis and treatment. Journal of Clinical Medicine, 14:3756, May 2025. URL: https://doi.org/10.3390/jcm14113756, doi:10.3390/jcm14113756. This article has 13 citations.

  13. (pasta2025endoscopicmanagementof pages 1-2): Andrea Pasta, Francesco Calabrese, Manuele Furnari, Edoardo Vincenzo Savarino, Pierfrancesco Visaggi, Giorgia Bodini, Elena Formisano, Patrizia Zentilin, Edoardo Giovanni Giannini, and Elisa Marabotto. Endoscopic management of eosinophilic esophagitis: a narrative review on diagnosis and treatment. Journal of Clinical Medicine, 14:3756, May 2025. URL: https://doi.org/10.3390/jcm14113756, doi:10.3390/jcm14113756. This article has 13 citations.

  14. (musburger2025currentandemerging pages 3-4): Brooke G. Musburger, Maria Gonzalez Echeandia, Elias L. Suskind, David L. Suskind, Hengqi Betty Zheng, and Dominique Mark. Current and emerging therapies for eosinophilic esophagitis (eoe): a comprehensive review. Pharmaceutics, 17:753, Jun 2025. URL: https://doi.org/10.3390/pharmaceutics17060753, doi:10.3390/pharmaceutics17060753. This article has 4 citations.

  15. (khokhar2022eosinophilicesophagitisimmune pages 3-5): Dilawar Khokhar, Sahiti Marella, Gila Idelman, Joy W. Chang, Mirna Chehade, and Simon P. Hogan. Eosinophilic esophagitis: immune mechanisms and therapeutic targets. Jul 2022. URL: https://doi.org/10.1111/cea.14196, doi:10.1111/cea.14196. This article has 56 citations and is from a domain leading peer-reviewed journal.

  16. (farah2025thedynamicevolution pages 5-7): Amir Farah, Tarek Assaf, Jawad Hindy, Wisam Abboud, Mostafa Mahamid, Edoardo Vincenzo Savarino, and Amir Mari. The dynamic evolution of eosinophilic esophagitis. Diagnostics, 15:240, Jan 2025. URL: https://doi.org/10.3390/diagnostics15030240, doi:10.3390/diagnostics15030240. This article has 14 citations.

  17. (trimarchi2026multitraitanalysisof pages 14-15): Michael P. Trimarchi, Bahram Namjou-Khales, Netali Ben-Baruch Morgenstern, Mark Rochman, Xiaoting Chen, Garrett Osswald, John Besse, Molly Shook, Julie Caldwell, Michael Lape, Tetsuo Shota, Matthew T. Weirauch, Melanie Ruffner, Gregory Constantine, Lisa J. Martin, Leah C. Kottyan, Marc E. Rothenberg, and Consortium of Eosinophilic Gastrointestinal Disease Researchers. Multi-trait analysis of gwas expands eosinophilic esophagitis genetic susceptibility and polygenic risk scores. Research Square, May 2026. URL: https://doi.org/10.21203/rs.3.rs-6630283/v2, doi:10.21203/rs.3.rs-6630283/v2. This article has 2 citations.

  18. (dsilva2026insightsintothe pages 1-2): Anish Dsilva and Ariel Munitz. Insights into the pathogenesis of eosinophilic esophagitis using mouse models. Myeloid Cells, Jan 2026. URL: https://doi.org/10.70401/mc.2026.0003, doi:10.70401/mc.2026.0003. This article has 0 citations.

  19. (uchida2022modelsandtools pages 2-3): Amiko M. Uchida, Gabrielle Ro, John J. Garber, Kathryn A. Peterson, and June L. Round. Models and tools for investigating eosinophilic esophagitis at the bench. Frontiers in Immunology, Jul 2022. URL: https://doi.org/10.3389/fimmu.2022.943518, doi:10.3389/fimmu.2022.943518. This article has 6 citations and is from a peer-reviewed journal.

  20. (bertin2026theimmunearchitecture pages 7-9): Luisa Bertin, Federico Caldart, Alberto Barchi, Niccolò Seregni, Andrea Pasta, Francesco Calabrese, Elisa Marabotto, Amir Mari, Amir Farah, Emma Sirinic, Andrea Sorge, Matteo Ghisa, Javier Chahuán, Vincenzo Savarino, and Edoardo Vincenzo Savarino. The immune architecture of eosinophilic esophagitis: mechanisms, therapeutic targets, and precision management. ImmunoTargets and Therapy, Volume 15:1-27, May 2026. URL: https://doi.org/10.2147/itt.s510865, doi:10.2147/itt.s510865. This article has 0 citations.

  21. (ariasgonzalez2024fibrousremodelingin pages 1-2): Laura Arias-González, Leticia Rodríguez-Alcolado, Emilio J. Laserna-Mendieta, Pilar Navarro, Alfredo J. Lucendo, and Elena Grueso-Navarro. Fibrous remodeling in eosinophilic esophagitis: clinical facts and pathophysiological uncertainties. International Journal of Molecular Sciences, 25:927, Jan 2024. URL: https://doi.org/10.3390/ijms25020927, doi:10.3390/ijms25020927. This article has 21 citations.

  22. (imam2026theroleof pages 5-5): Manal Bel Imam, Hang Du, Özge Ardicli, Jenne Meinema, and Willem van de Veen. The role of b cells and antibodies in eosinophilic esophagitis. Inflammatory Intestinal Diseases, 11:105-122, Feb 2026. URL: https://doi.org/10.1159/000551065, doi:10.1159/000551065. This article has 0 citations.

  23. (farah2025thedynamicevolution pages 10-12): Amir Farah, Tarek Assaf, Jawad Hindy, Wisam Abboud, Mostafa Mahamid, Edoardo Vincenzo Savarino, and Amir Mari. The dynamic evolution of eosinophilic esophagitis. Diagnostics, 15:240, Jan 2025. URL: https://doi.org/10.3390/diagnostics15030240, doi:10.3390/diagnostics15030240. This article has 14 citations.

  24. (low2024reviewarticleemerging pages 1-3): Eric E. Low and Evan S. Dellon. Review article: emerging insights into the epidemiology, pathophysiology, diagnostic and therapeutic aspects of eosinophilic oesophagitis and other eosinophilic gastrointestinal diseases. Alimentary Pharmacology & Therapeutics, 59:322-340, Dec 2024. URL: https://doi.org/10.1111/apt.17845, doi:10.1111/apt.17845. This article has 41 citations and is from a highest quality peer-reviewed journal.

  25. (farah2025thedynamicevolution pages 12-13): Amir Farah, Tarek Assaf, Jawad Hindy, Wisam Abboud, Mostafa Mahamid, Edoardo Vincenzo Savarino, and Amir Mari. The dynamic evolution of eosinophilic esophagitis. Diagnostics, 15:240, Jan 2025. URL: https://doi.org/10.3390/diagnostics15030240, doi:10.3390/diagnostics15030240. This article has 14 citations.

  26. (bertin2026theimmunearchitecture pages 10-12): Luisa Bertin, Federico Caldart, Alberto Barchi, Niccolò Seregni, Andrea Pasta, Francesco Calabrese, Elisa Marabotto, Amir Mari, Amir Farah, Emma Sirinic, Andrea Sorge, Matteo Ghisa, Javier Chahuán, Vincenzo Savarino, and Edoardo Vincenzo Savarino. The immune architecture of eosinophilic esophagitis: mechanisms, therapeutic targets, and precision management. ImmunoTargets and Therapy, Volume 15:1-27, May 2026. URL: https://doi.org/10.2147/itt.s510865, doi:10.2147/itt.s510865. This article has 0 citations.

  27. (musburger2025currentandemerging pages 6-7): Brooke G. Musburger, Maria Gonzalez Echeandia, Elias L. Suskind, David L. Suskind, Hengqi Betty Zheng, and Dominique Mark. Current and emerging therapies for eosinophilic esophagitis (eoe): a comprehensive review. Pharmaceutics, 17:753, Jun 2025. URL: https://doi.org/10.3390/pharmaceutics17060753, doi:10.3390/pharmaceutics17060753. This article has 4 citations.

  28. (low2024reviewarticleemerging pages 9-11): Eric E. Low and Evan S. Dellon. Review article: emerging insights into the epidemiology, pathophysiology, diagnostic and therapeutic aspects of eosinophilic oesophagitis and other eosinophilic gastrointestinal diseases. Alimentary Pharmacology & Therapeutics, 59:322-340, Dec 2024. URL: https://doi.org/10.1111/apt.17845, doi:10.1111/apt.17845. This article has 41 citations and is from a highest quality peer-reviewed journal.

  29. (bertin2026theimmunearchitecture pages 12-14): Luisa Bertin, Federico Caldart, Alberto Barchi, Niccolò Seregni, Andrea Pasta, Francesco Calabrese, Elisa Marabotto, Amir Mari, Amir Farah, Emma Sirinic, Andrea Sorge, Matteo Ghisa, Javier Chahuán, Vincenzo Savarino, and Edoardo Vincenzo Savarino. The immune architecture of eosinophilic esophagitis: mechanisms, therapeutic targets, and precision management. ImmunoTargets and Therapy, Volume 15:1-27, May 2026. URL: https://doi.org/10.2147/itt.s510865, doi:10.2147/itt.s510865. This article has 0 citations.

  30. (dsilva2026insightsintothe pages 2-4): Anish Dsilva and Ariel Munitz. Insights into the pathogenesis of eosinophilic esophagitis using mouse models. Myeloid Cells, Jan 2026. URL: https://doi.org/10.70401/mc.2026.0003, doi:10.70401/mc.2026.0003. This article has 0 citations.

  31. (jackson2025mousemodelsof pages 9-11): Jazmyne L. Jackson, Abigail J. Staub, Annie D. Fuller, John M. Crespo, Travis H. Bordner, Courtney Worrell, No’ad Shanas, Danielle Waheed, Tatiana A. Karakasheva, Melanie A. Ruffner, Amanda B. Muir, and Kelly A. Whelan. Mouse models of eosinophilic esophagitis: molecular and translational insights. Jul 2025. URL: https://doi.org/10.1152/ajpgi.00396.2024, doi:10.1152/ajpgi.00396.2024. This article has 2 citations.

  32. (uchida2022modelsandtools pages 1-2): Amiko M. Uchida, Gabrielle Ro, John J. Garber, Kathryn A. Peterson, and June L. Round. Models and tools for investigating eosinophilic esophagitis at the bench. Frontiers in Immunology, Jul 2022. URL: https://doi.org/10.3389/fimmu.2022.943518, doi:10.3389/fimmu.2022.943518. This article has 6 citations and is from a peer-reviewed journal.

  33. (jackson2025mousemodelsof pages 14-16): Jazmyne L. Jackson, Abigail J. Staub, Annie D. Fuller, John M. Crespo, Travis H. Bordner, Courtney Worrell, No’ad Shanas, Danielle Waheed, Tatiana A. Karakasheva, Melanie A. Ruffner, Amanda B. Muir, and Kelly A. Whelan. Mouse models of eosinophilic esophagitis: molecular and translational insights. Jul 2025. URL: https://doi.org/10.1152/ajpgi.00396.2024, doi:10.1152/ajpgi.00396.2024. This article has 2 citations.

  34. (dsilva2026insightsintothe pages 11-13): Anish Dsilva and Ariel Munitz. Insights into the pathogenesis of eosinophilic esophagitis using mouse models. Myeloid Cells, Jan 2026. URL: https://doi.org/10.70401/mc.2026.0003, doi:10.70401/mc.2026.0003. This article has 0 citations.

  35. (dsilva2026insightsintothe pages 14-16): Anish Dsilva and Ariel Munitz. Insights into the pathogenesis of eosinophilic esophagitis using mouse models. Myeloid Cells, Jan 2026. URL: https://doi.org/10.70401/mc.2026.0003, doi:10.70401/mc.2026.0003. This article has 0 citations.

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