Eosinophilic Esophagitis


The esophagus physiologically lacks eosinophils, and when present, the condition is considered to be pathologic. Eosinophilic esophagitis was once thought to be a component of gastroesophageal reflux disease (GERD). However, it is now known to be a separate entity as we understand more about the esophagus being an active immunogenic organ. Eosinophils can be found in the esophagus in response to various stimuli or antigen. Eosinophilic esophagitis (EoE) is a chronic immune or antigen-mediated process. Clinically, it presents with various esophageal dysfunction, and pathologically, there is mucosal inflammation predominantly with eosinophils, which is confined to the esophagus only. Diseases which can cause eosinophilia should be ruled out before diagnosing a patient with EoE.[1]


The exact etiology of EoE is unknown; however, it is thought to be a result of the interactions of environmental, genetic, and host immune factors. A food allergy may trigger EoE, but food anaphylaxis is a rare phenomenon among these patients. There is a strong correlation between atopy and EoE, with patients commonly reporting a history of chronic seasonal allergy, asthma, atopic dermatitis, or other allergic/immunologic conditions.[2]


EoE is common in both pediatric and adult populations. Epidemiologic studies have reported EoE cases in many countries on all continents except Africa. Based on many population studies, the reported incidence of EoE is between 0.1/10,000 to 1.2/10,000 worldwide. In the pediatric population, EoE is more common among boys. In the adult population, Caucasian and non-Hispanic white men are more likely to have EoE than women of respective races, 76% compared to 48%. EoE can occur in all age groups; however, it is most common in men during their 20s and 30s, and the mean age of diagnosis is 34.[2]


EoE occurs as a result of an immunogenic reaction to various antigens which are commonly found in food and air. There is a strong genetic component involved in the pathogenesis of EoE and a high concordance reported for EoE among family members. The pioneer study that described the genetic basis for EoE was a study of genome-wide microarray expression profile analysis. This study reported that the gene responsible for EoE was TSLP (thymic stromal lymphopoietin) which is located in the 5q22 region of male X chromosome. TSLP stimulates Th2 cells and induces eotaxin-3. The stimulated Th2 cells activate various proinflammatory cytokines such as IL5, IL13, and IL15, which recruit eosinophils. Eotaxin-3 is overexpressed in the esophageal mucosa in EoE patients. Overall, this immunogenic process starts as an allergic response to various environmental antigens, food, or aeroallergens and leads to the inflammation of esophageal mucosa. [3]

The other important cytokine involved in the pathogenesis is TGF-B (transforming growth factor-beta), which is released by eosinophils and mast cells recruited after immune activation. TGF-B is responsible for remodeling of esophageal mucosa and smooth muscle dysfunction. The remodeling of inflamed mucosa can occur with repeated exposure to the antigens, leading to remodeling and fibrosis which clinically manifests as various esophageal dysfunction that includes dysphagia, epigastric pain, dyspepsia, chest pain, and food impaction. It has been reported that a single exposure to airway antigen challenge and cutaneous antigen exposure may lead to recruitment of eosinophils in the esophagus leading to EoE. [3]


For patients suspect for EoE, esophageal biopsies usually should be taken from the proximal, mid, and distal esophagus. During the endoscopy, biopsies also should be taken from the antrum and duodenum to rule out other possible causes of eosinophilia.

Histopathology is an important aspect of making a diagnosis of EoE. The histopathology reveals extensive eosinophils infiltrated esophageal mucosa, in addition to mast cells, basophils, basal cell hyperplasia, elongated papillae, superficial layering of eosinophils, extracellular eosinophilic granules, and fibrosis of sub-epithelium.[3]

History and Physical

History is very important when considering a diagnosis of EoE as there are many overlapping symptoms of EoE that coincide with gastroesophageal reflux (GERD). The most common manifestation in adults is dysphagia to solid food. An emergency department visit due to food impaction has been the most common presenting symptom in patients with EoE. Other symptoms such as chest pain or heartburn are common as well. Pediatric patients can present with nausea, vomiting, food intolerance, abdominal pain, and weight loss. A history of various atopic conditions such as asthma, atopic dermatitis, seasonal allergy, food allergy, allergic rhinitis, and eczema may be present as well. [2]

A physical exam is less useful than the history in making the diagnosis of EoE. The most common finding is tenderness to palpation of the abdomen without signs of peritonitis.


Clinicians should arrive at the diagnosis of EoE only after positive findings on clinical, endoscopic, and histopathologic examinations. Patients who present with food impaction, dysphagia, and history of atopy should undergo an upper endoscopy evaluation with esophageal biopsy to diagnose EoE.[1]

Upper endoscopy with esophageal biopsy also should be done on patients with a presumed diagnosis of GERD who are resistant to optimal proton pump inhibitor (PPI) dose (20 to 40 mg orally twice daily) and duration (8 to 12 weeks). Esophageal biopsies normally should be taken from the proximal, mid, and distal esophagus. During the endoscopy, biopsies also should be taken from the antrum and duodenum to rule out other possible causes of eosinophilia.[1][4]

Endoscopic findings of EoE include corrugated mucosa, longitudinal mucosal furrows, fixed esophageal rings or trachealization, whitish mucosal plaque or exudate, stricture, superficial mucosa tear upon passing endoscope, diffusely narrow lumen, and mucosal friability giving the appearance of crepe paper. Clinicians also should note that some patients may have normal esophagus in upper endoscopy.[4]

The pathological diagnosis of EoE is made when eosinophils are present greater than or equal to 15 per high power field (HPF). Other histological findings suggestive of EoE include basal cell hyperplasia, elongation of papillae, superficial layering of eosinophils, extracellular eosinophilic granules, and fibrosis of sub-epithelium.[1]

There is no diagnostic laboratory test available for EoE, but a mildly elevated serum IgE level is present in patients with EoE. Another common nonspecific finding would be a barium swallow study. Findings can show different types of strictures or a ringed esophagus that could be caused by EoE.

An allergist and immunologist should evaluate patients with a history of atopy or food allergy and a diagnosis of EoE.

Differential Diagnosis

  • Achalasia
  • Celiac disease
  • Crohn’s disease
  • Connective tissue disease
  • Drug hypersensitivity
  • GERD
  • Graft-versus-host disease
  • Hypereosinophilic disease
  • Pemphigus vegetans
  • Vasculitis

Pearls and Other Issues

The challenge in diagnosing EoE is the differential of GERD as there is much overlap between the two diseases. GERD also can have eosinophils in the esophagus on pathology. The major difference between the diseases is the response to a PPI. Due to this difference, endoscopy with biopsy should be done at least two months after a trial of PPI therapy.[5][6][7][8][5]

Other disease conditions that can have esophageal eosinophilia should be excluded before diagnosing a patient with EoE. Some of the diseases that have esophageal eosinophilia are gastroesophageal (GI) reflux disease, eosinophilic GI disease, PPI-responsive esophageal eosinophilia, Celiac disease, Crohn disease, infection, Achalasia, drug hypersensitivity, vasculitis, connective tissues disorders, and the use of a PPI.

Enhancing Healthcare Team Outcomes

The diagnosis of EoE is not always easy and the condition is best managed by an interprofessional team that includes a gastroenterologist, primary care provider, pathologist, nurse practitioner and an internist. A biopsy is needed to confirm the diagnosis.

The goal of EoE treatment is to control the symptoms by decreasing the number of eosinophils in the esophagus and, subsequently, reducing the esophageal inflammation. Management consists of dietary, pharmacological, and endoscopic treatment.[5][4]

Patients who remain compliant with dietary and medication instructions do have a good outcome but for those who fail to make any adjustments in their lifestyle or diet continue to have symptoms.[9][10]

Article Details

Article Author

Jordan Roussel

Article Editor:

Sudha Pandit


8/14/2020 9:22:54 PM



Clinical Applications of the Eosinophilic Esophagitis Diagnostic Panel., Wen T,Rothenberg ME,, Frontiers in medicine, 2017     [PubMed PMID: 28770203]


Epidemiology and Natural History of Eosinophilic Esophagitis., Dellon ES,Hirano I,, Gastroenterology, 2017 Jul 31     [PubMed PMID: 28774845]


Pathophysiology of Eosinophilic Esophagitis., O'Shea KM,Aceves SS,Dellon ES,Gupta SK,Spergel JM,Furuta GT,Rothenberg ME,, Gastroenterology, 2017 Jul 27     [PubMed PMID: 28757265]


Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults., Lucendo AJ,Molina-Infante J,Arias Á,von Arnim U,Bredenoord AJ,Bussmann C,Amil Dias J,Bove M,González-Cervera J,Larsson H,Miehlke S,Papadopoulou A,Rodríguez-Sánchez J,Ravelli A,Ronkainen J,Santander C,Schoepfer AM,Storr MA,Terreehorst I,Straumann A,Attwood SE,, United European gastroenterology journal, 2017 Apr     [PubMed PMID: 28507746]


Diagnostic approaches and treatment of eosinophilic esophagitis. A review article., Akhondi H,, Annals of medicine and surgery (2012), 2017 Aug     [PubMed PMID: 28721213]


Peiris CD,Tarbox JA, Eosinophilic Esophagitis. JAMA. 2019 Apr 9;     [PubMed PMID: 30964530]


Mehr S,Brown-Whitehorn T,     [PubMed PMID: 30935977]


McGowan EC,Platts-Mills TAE,Wilson JM, Food Allergy, Eosinophilic Esophagitis and the Enigma of IgG4. Annals of allergy, asthma     [PubMed PMID: 30928417]


Sawada A,Hashimoto A,Uemura R,Otani K,Tanaka F,Nagami Y,Yamagami H,Tanigawa T,Watanabe T,Fujiwara Y, Association between endoscopic findings of eosinophilic esophagitis and responsiveness to proton pump inhibitors. Endoscopy international open. 2019 Apr;     [PubMed PMID: 30931374]


Safroneeva E,Schoepfer AM, Symptom-based patient-reported outcomes in adults with eosinophilic esophagitis: value for treatment monitoring and randomized controlled trial design. Current opinion in allergy and clinical immunology. 2019 Apr;     [PubMed PMID: 30649010]