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Allergic Oesophagitis – Causes, Symptoms, Treatment

Allergic Oesophagitis/Eosinophilic Esophagitis (EoE) is a chronic, allergic inflammatory disease of the esophagus (the tube connecting the mouth to the stomach). It occurs when a type of white blood cell, the eosinophil, accumulates in the esophagus. The elevated number of eosinophils cause injury and inflammation to the esophagus.

Eosinophilic esophagitis (EoE, also spelled eosinophilic oesophagitis), also known as allergic oesophagitis, is an allergic inflammatory condition of the esophagus that involves eosinophils, a type of white blood cell. Eosinophils migrate to the esophagus in large numbers, then precipitate an allergic reaction when a trigger food is eaten. Symptoms are swallowing difficulty, food impaction, vomiting, and heartburn.^[rx]

Eosinophilic esophagitis was first described in children but also occurs in adults. The condition is not well understood, but food allergy may play a significant role.^[rx] The treatment may consist of removal of known or suspected triggers and medication to suppress the immune response. In severe cases, it may be necessary to enlarge the esophagus with an endoscopy procedure.

Synonyms of Eosinophilic Esophagitis

allergic esophagitis
EoE

Subdivisions of Eosinophilic Esophagitis

atopic and non-atopic
endotype 1, 2 and 3 defined by esophageal transcript expression

Pathophysiology

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. [rx]

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 the 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 the recruitment of eosinophils in the esophagus leading to EoE. [rx]

Causes of Allergic Oesophagitis

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.[rx]

Reaction of the esophagus – The lining of your esophagus reacts to allergens, such as food or pollen.
Multiplication of eosinophils – The eosinophils multiply in your esophagus and produce a protein that causes inflammation.
Damage to the esophagus – Inflammation can lead to scarring, narrowing and formation of excessive fibrous tissue in the lining of your esophagus.
Dysphagia and impaction – You may have difficulty swallowing (dysphagia) or have food become stuck when you swallow (impaction).
Additional symptoms – You may have other symptoms, such as chest pain or stomach pain.

Symptoms of Allergic Oesophagitis

EoE often presents with difficulty swallowing, food impaction, stomach pains, regurgitation or vomiting, and decreased appetite. In addition, young children with EoE may present with feeding difficulties and poor weight gain. It is more common in males, and affects both adults and children.^[rx]

Many people with EoE have other autoimmune and allergic diseases such as asthma^[rx] and celiac disease.^[rx] Mast cell disorders such as Mast Cell Activation Syndrome or Mastocytosis are also frequently associated with it.

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Signs and symptoms include

Adults

Difficulty swallowing (dysphagia)
Food getting stuck in the esophagus after swallowing (impaction)
Chest pain that is often centrally located and does not respond to antacids
Backflow of undigested food (regurgitation)

Children

Difficulty feeding, in infants
Difficulty eating, in children
Vomiting
Abdominal pain
Difficulty swallowing (dysphagia)
Food getting stuck in the esophagus after swallowing (impaction)
No response to GERD medication
Failure to thrive (poor growth, malnutrition and weight loss)

Diagnosis of Allergic Oesophagitis

Histopathology

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.[rx]

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. [rx]

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.

Evaluation

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.[rx]

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.[rx][rx]

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.[rx]

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.[rx]

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.

Prior to the development of the EE Diagnostic Panel, EoE could only be diagnosed if gastroesophageal reflux did not respond to a six-week trial of twice-a-day high-dose proton-pump inhibitors (PPIs) or if a negative ambulatory pH study ruled out gastroesophageal reflux disease (GERD).^[rx]^[rx]

Endoscopically, ridges, furrows, or rings may be seen in the esophageal wall. Sometimes, multiple rings may occur in the esophagus, leading to the term “corrugated esophagus” or “feline esophagus” due to the similarity of the rings to the cat esophagus. The presence of white exudates in the esophagus is also suggestive of the diagnosis.^[rx] On biopsy taken at the time of endoscopy, numerous eosinophils can be seen in the superficial epithelium. A minimum of 15 eosinophils per high-power field are required to make the diagnosis. Eosinophilic inflammation is not limited to the esophagus alone, and does extend through the whole gastrointestinal tract. Profoundly degranulated eosinophils may also be present, as may microabscesses and an expansion of the basal layer.^[rx]^[rx]

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Tests to diagnose eosinophilic esophagitis include:

Upper endoscopy – Your doctor will use a long narrow tube (endoscope) containing a light and tiny camera and insert it through your mouth down the esophagus. The doctor will inspect the lining of your esophagus for inflammation and swelling, horizontal rings, vertical furrows, narrowing (strictures), and white spots. Some people with eosinophilic esophagitis will have an esophagus that looks normal.
Biopsy – During an endoscopy, your doctor will perform a biopsy of your esophagus. A biopsy involves taking a small bit of tissue. Your doctor will likely take multiple samples from your esophagus and then examine the tissue under a microscope for eosinophils.
Blood tests – If doctors suspect eosinophilic esophagitis, you may undergo some additional tests to confirm the diagnosis and to begin to look for the sources of your allergic reaction (allergens). You may be given blood tests to look for higher than normal eosinophil counts or total immunoglobulin E levels, suggesting an allergy.
Esophageal sponge – This test is performed in the doctor’s office and involves swallowing a capsule attached to a string. The capsule will dissolve in your stomach and release a sponge that the doctor will pull out your mouth with the string. As the sponge is pulled out, it will sample the esophageal tissues and allow the doctor to determine the degree of inflammation in your esophagus without having to undergo endoscopy.

Radiologically, the term “ringed esophagus” has been used for the appearance of eosinophilic esophagitis on barium swallow studies to contrast with the appearance of transient transverse folds sometimes seen with esophageal reflux (termed “feline esophagus”).^[rx]

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

Treatment of Allergic Oesophagitis

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.[rx][rx]

Dietary Treatment

Patients with a history of atopy to food generally respond well to dietary therapy. The approach to dietary therapy is to avoid specific food if present. If no specific allergenic food or agent is present, a trial of the six food elimination diet (SFED) can be pursued. The six most common allergenic food that should be avoided in EoE patients are cow’s milk, wheat, peanut/tree nut, egg, soy, and seafood/shellfish. Alternative options to SFED is an elemental diet, which is an amino acid-based diet. Patients on an elemental diet sometimes require gastrostomy tube placement for adequate caloric intake. Research has shown that the elemental diet is superior to SFED or modified SFED (avoidance of food detected by allergic skin test plus SFED). It is also recommended, although the evidence is low, that the clinical response should be measured based on esophageal symptom control and endoscopically with esophageal biopsy to ascertain that the numbers of eosinophils have decreased or not. Upper endoscopy with esophageal biopsy should be done whenever food is reintroduced or removed from the dietary regimen to assess the success of therapy.[rx]

Allergy testing is not particularly effective in predicting which foods are driving the disease process. Various approaches have been tried, where either six food groups (cow’s milk, wheat, egg, soy, nuts, and fish/seafood), four groups (animal milk, gluten-containing cereals, egg, legumes), or two groups (animal milk and gluten-containing cereals) are excluded for a period of time, usually six weeks. A “top-down” (starting with six foods, then reintroducing) approach may be very restrictive. Four- or even two-group exclusion diets may be less difficult to follow and reduce the need for many endoscopies if the response to the limited restriction is good.^[rx]

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Pharmacological Treatment

In patients diagnosed with EoE, a trial of PPI 20 mg to 40 mg orally daily or twice daily as first-line therapy is a reasonable option. For those who respond to PPI therapy with symptomatic improvement, endoscopy with esophageal biopsy should be repeated. If no eosinophils present in repeat biopsy, the diagnosis is either acid-mediated GERD with eosinophilia or non-GERD PPI-responsive EoE with an unknown mechanism. If both symptoms and eosinophils persist after treatment with PPI, the diagnosis is immune-mediated EoE. In the case of immune-mediated EoE, the American College of Gastroenterology (ACG) highly recommend using topical (swallowed not inhaled) steroids for a total of 8 weeks. Oral suspension of fluticasone 880-1760 mcg per day or budesonide 1 mg to 2 mg per day is available options in the United States. For patients who do not respond to topical steroids, systemic steroids, Prednisone 2 mg per Kg per day (maximum 60 mg per day), may be used. For patients who initially respond but symptom recurs, a longer duration of topical steroid or systemic steroid may be used in addition to elemental diet or SFED.[rx]

Proton pump inhibitor (PPI) – Your doctor will likely first prescribe an acid blocker such as a PPI. This treatment is the easiest to use, but most people’s symptoms don’t improve.
Topical steroid – If you do not respond to the PPI, your doctor will then likely prescribe a topical steroid, such as fluticasone or budesonide, which is a liquid that is swallowed to treat eosinophilic esophagitis. This type of steroid is not absorbed into the bloodstream, so you are unlikely to have the typical side effects often associated with steroids.

Endoscopic Management

For patients who present with food impaction, flexible upper endoscopy is recommended to remove impacted food. Dilation is deferred in EoE until patients are adequately treated with pharmacological or dietary therapy, and the result of a response to therapy is available. The goal of therapy for treating EoE is to improve the patient’s symptoms as well as a reduction in the eosinophils on biopsy. The initial treatment is started after failure to improve after 2 months of PPI therapy to make the diagnosis of EoE.[rx]

For patients with persistent symptoms of dysphagia even after treatment with dietary elimination and medical therapy, endoscopic dilation is performed. Esophageal strictures and rings can be safely dilated in EoE. It is recommended to use a graduated balloon catheter for gradual dilation. The patient should be informed that after dilation they might experience chest pain and in addition risk of esophageal perforation and bleeding.

Due to the strong association of EoE with allergies, it is also suggested that all patients with diagnosed EoE undergo evaluation by an allergist or immunologist.

Endoscopic dilatation

Endoscopic dilatation is sometimes required if there is a significant narrowing of the esophagus. This is effective in 84% of people who require this procedure.^[rx]