What Is Eosinophilic Esophagitis

Overview

Eosinophilic esophagitis (EoO) is a chronic immune- or allergy-mediated disease of the oesophagus (the muscular tube that carries food from the mouth to the stomach). EoO affects both adults and children, with adult males being affected more than adult females in a ratio of (3:1). 

Currently, the prevalence rate exceeds the incidence rate, and EoO, is becoming more recognised in North America, Europe and Australia. The main clinical feature of EoO is dysphagia (difficulty in swallowing), while the main histopathological feature of EoO is eosinophilia where a high number of eosinophils is present in the oesophagus. Eosinophils are white blood cells released by the body in the presence of an infection, allergic reaction, etc. 

They in turn release substances into the surrounding tissues, triggering the inflammatory cascade. EoO can progress over time to fibrotic remodelling, leading to oesophageal narrowing and oesophageal strictures. In the early stages, disease progression can be slowed down by either drug therapy (PPIs, topical steroids, monoclonal antibodies) or dietary therapy. However, in more severe stages, endoscopic dilation may be required to resolve the strictures.^1,2,3

Causes of eosinophilic esophagitis

The main cause of EoO is an allergic reaction triggered by allergens. These are mainly food allergens but can sometimes be environmental allergens. In the case of EoO caused by food allergies, it is very hard to establish the specific type of food that acted as the trigger. 

This is because the allergic reactions are delayed and can develop over days rather than within minutes, as it happens with the classical Immunoglobulin E (IgE)-mediated food allergy. Another reason is the failure of standard allergy testing (such as skin testing, blood allergy testing, and patch testing) to reliably identify food triggers.

The most common food triggers are dairy products, eggs, wheat, and soy.

If the cause is environmental allergens, EoO symptoms may become worse during pollen seasons. Environmental allergens include but are not limited to pollen, dust mites, animals, and moulds.^1,4                                                             

Signs and symptoms of eosinophilic esophagitis  

• Dysphagia which is difficulty in swallowing food (especially dry food in teenagers and adults)
• Slower growth and poor weight gain. This usually occurs in toddlers refusing to eat
• Abdominal pain, vomiting, and loss of appetite. Usually experienced by older children
• oesophageal food bolus impaction when the food gets firmly stuck with no chance of it passing down to the stomach or being vomited up. This occurs due to the ongoing inflammation in the oesophagus, which if not treated, leads to oesophageal narrowing to a point where the food can get stuck. It should be treated as a medical emergency
• Chest pain or Heartburn^1,2,4,5                                                               

Management and treatment for eosinophilic esophagitis

The main aim of treatment is to improve both the clinical and histological symptoms of EoO and avoid progression into severe stages with complications like strictures and perforations.²

EoO is a complex disease where patients need to be cooperative with their gastroenterologist and allergist/immunologist throughout the treatment period.

To listen to their advice on:

• how to manage EoO and related problems like allergic rhinitis, asthma, atopic, and dermatitis
• which foods should be eliminated and which diet to follow
• and when is the time to do check-up endoscopies¹

Currently, there are three main treatment options for EoO such as, drug therapy, dietary therapy, and endoscopic dilation. The choice of therapy should be discussed with each patient individually and his/ her family. There might be other factors to take into consideration, such as age, severity of the disease, patient lifestyle, patients’ preferences, patients’ adherence and ability to understand food labels³ which are described below:

Drug therapy

Proton pump inhibitors (PPIs)

PPIs reduce the acid production of stomach acid and are usually used to treat acid reflux conditions (for example in GERD). Currently, are used as the first-line treatment of EoO. PPIs inhibit the recruitment of eosinophils from the blood into the oesophageal tissue, reducing oesophageal inflammation. Significant improvement in dysphagia can be seen in a few days. PPIs can also be used as adjunctive therapy for those requiring oesophageal dilation.

Moreover, PPIs can help restore the oesophageal mucosal barrier function, hence limiting the entry of aeroallergens into the oesophageal mucosa.²

The healthcare professional should decide upon the dose of PPI (once a day or a lower dose twice a day). 

After 4 weeks of treatment, symptomatic/clinical response evaluation should be carried out. Those who responded should stay on the same dose for another 4 weeks, followed by follow-up and a decrease in the dose. Those who did not respond will have their dose of PPI doubled for 4 weeks and then in case of no improvement, switch to an alternative therapy such as oral corticosteroids and food elimination diets.²

Topical corticosteroids

Topical corticosteroids have become the second-line medications for the treatment of EoO. Examples include fluticasone metered dose inhaler 880 microgram and oral viscous budesonide. Fluticasone inhaler is puffed into the mouth twice a day for 6-8 weeks, while oral viscous budesonide is taken at 1mg twice daily for 6-8 weeks. 

This decreases dysphagia and oesophageal eosinophilia in the proximal oesophagus. Topical corticosteroids are more effective in histologic rather than symptomatic improvement. This is due to their minimal systemic absorption. If topical corticosteroids fail, either prolonged/higher doses of topical steroids would be suggested, or alternative therapies would be advised.²

Systemic corticosteroids

Swallowing small doses of corticosteroids allows them to adhere to the oesophageal lining and hence reduce inflammation.¹ Steroids reduce the synthesis of certain signalling proteins and induce eosinophilic apoptosis. 

An example is oral methylprednisolone, which produces marked clinical and histological improvement in paediatric EoO patients. Nevertheless, because of the associated systemic side effects, this option is reserved upon the failure of others.²

Leukotriene inhibitors (Monoclonal antibodies)

One of the effective monoclonal antibodies is Dupixent (dupilumab). It is an interleukin-4 receptor antagonist which helps reduce oesophageal eosinophilia and oesophageal inflammation and hence improves the patient’s ability to swallow. It is the only medical therapy approved by the Food and Drug Administration (FDA) in 2020 for the treatment of EoO. It is an injectable solution administered weekly and can be used in patients 12 years of age or older weighing at least 40 kilograms.^1,2

Dietary therapy

It is one of the very effective management techniques in EoO which involves identifying and eliminating the major food allergens from the diet. It is usually used when Drug therapy has failed, or it can be used as an initial therapy in case the trigger allergen is known. It is advisable to do this with the help of a dietician who has experience in dealing with EoO. There are different approaches to diet modifications, the four most common ones are:

Amino acid base formula

This is suitable for children with multiple EoO food triggers and who did not respond to other forms of treatment. A strict elimination diet where all the sources of allergens are removed from the diet. In this case, the patient receives amino acid formula alone or with one to two simple foods for a minimum of 6 weeks.^1,2

Six food group elimination diet (SFGED)

This includes the removal of the six most common food allergens milk, egg, wheat, soy, peanuts/nuts and seafood.²

Targeted elimination diet

This involves identifying the specific trigger allergen by skin/prick test or blood test. This should be done under the supervision of a dietitian and an allergist. This method can be time-consuming and sometimes inaccurate.²

Exclusion/Inclusion diet

Can be done in two ways, one is by the exclusion of the suspected foods (usually dairy, wheat, egg, and soy) from the diet and then gradually adding them back to the diet one at a time with follow-up endoscopies. The second way is excluding food one by one until inflammation starts to resolve.¹

Endoscopic treatment

Endoscopic treatment is indicated for those patients with a symptomatic oesophagal stricture/ narrowed oesophagus i.e., oesophagal diameter <10mm. It is performed with either hydrostatic balloon dilation⁶ or wire-guided biugie dilation⁷. To relieve dysphagia, the oesophageal diameter should reach 15-18mm in diameter, which might need multiple sessions to do this. This method improves dysphagia and quality of life but doesn’t reduce eosinophilia. 

Also, it has certain drawbacks, such as mucosal tears causing post-dilation chest pain for several days. Nevertheless, it should be offered to those patients with complicated EoO. Like the therapeutic approach used in inflammatory bowel disease, endoscopic treatment should not be used alone because it does not affect oesophageal inflammation. It can be combined with topical corticosteroids to achieve even quicker clinical, endoscopic, and histological remission. ^2,3

Diagnosis

Diagnosis of EoO can be tricky and not straightforward, involving three different specialists, allergists, gastroenterologists, and pathologists to decide. Nevertheless, the golden standard is to perform an upper endoscopy where a flexible tube with a camera and a light source on its tip, is passed down the oesophagus to see how the oesophageal tissue looks like from the inside.¹ During this, small pieces of oesophageal tissue (biopsies) are taken to be examined under the microscope.

Certain criteria help with the diagnosis, these include:

• Presence of symptoms of oesophageal dysfunction such as dysphagia and food impaction
• The presence of characteristic endoscopic features such as oedema, rings, exudates, furrows, and strictures
• Confirmed oesophageal eosinophilia, defined as >15 eosinophils per high power field
• Absence of other conditions related to oesophageal eosinophilia such as GERD

It is important to identify the symptoms of eosinophilic esophagitis clinically, endoscopically, and pathologically, to make the proper diagnosis. Therefore, all these criteria should be satisfied before proceeding with the diagnosis of EoO. One condition called symptomatic oesophagal eosinophilia is indistinguishable from EoO, and hence is treated as EoO, given that all other causes are excluded.^1,2,3

Most of the patients with EoO, present with symptoms of one or more allergic disorders such as asthma, atopic dermatitis, allergic rhinitis, and food allergy. Therefore, allergists are probably the first specialists approached by patients. In this case, the allergist should suspect EoO, and direct the patient to a gastroenterologist to confirm the diagnosis. 

If the patient went first to the gastroenterologist and was diagnosed with EoO, he/she might still be referred to an allergist who can do an allergy test to identify the specific allergen involved and provide information on how to properly treat the allergic aspect of EoO. Moreover, the allergist can help you plan your therapy diet and reintroduce certain foods to your diet.¹

Risk factors

• Male Gender: Numerous studies have shown that the frequency of EoO is higher in males than in females
• People with atopy: These people have a genetic tendency to develop allergic diseases such as allergic rhinitis, asthma, and atopic dermatitis. This is usually associated with intensified immune responses to common allergens, especially inhaled allergens and food allergens^1,3
• Family history of EoO⁴

Complications

• Strictures: these can occur when the disease is left untreated. Around 10% of patients suffer from strictures
• Food bolus obstruction: a very distressing condition that requires immediate medical attention
• Oesophageal perforation and mucosal tear: this can occur during the endoscopic examination or the oesophageal dilation procedure⁸

FAQs

How can I prevent eosinophilic esophagitis?

You cannot prevent it if it runs in your family, but you can minimise the risk factors, such as identifying the allergy triggers and avoiding them.

How common is eosinophilic esophagitis?

It affects about 1 in 2000 people and is more common in white adult males.

When should I see a doctor?

In case of unexplained weight loss or increased or persistent vomiting. In case of food bolus obstruction, you need to go to the emergency.

Summary

To summarize, living with EoO is not easy and brings lots of disruptions in the patient’s daily life. Although there is no specific cure for EoO, there are lots of options on how to manage and treat it. These include drug therapy (PPIs, topical steroids, monoclonal antibodies) or diet modification and, in severe cases, endoscopic dilation. The most important is for the patient to work closely with their gastroenterologist and/or allergist who can guide them on how to manage this disease.