Introduction

Eosinophilic gastroenteritis (EGE) disorder is one of the most common conditions listed under the category of eosinophilic gastrointestinal disorders (EGIDs).¹ It is a rare gut problem in which eosinophils (a type of white blood cell) accumulate in the stomach and small intestine.²

It is estimated that in 2011, the frequency of EGE in the United States of America (USA) was 28 in 100,000. According to current population-based studies, the overall prevalence of EGE in the United States now ranges between 5.1 and 8.4 per 100,000 people, showing a remarkable decline.²

To more clearly demonstrate the prevalence, Licari et al. showed that 1.9% of patients with gastrointestinal symptoms who were referred to clinics for non-EoE EGIDs had this condition. This is higher than the prevalence for inflammatory bowel disease (IBD), suggesting that despite the decline in prevalence, EGE is becoming more and more significant in clinical practice.²

Diagnosing EGE can be difficult because its signs can mimic common stomach issues, such as Coeliac disease, inflammatory bowel disease (IBD), or inflammatory bowel syndrome (IBS) symptoms. A biopsy is usually needed for confirmation of disease, yet, there are no set rules for the diagnosis of EGE. Treatment of EGE also faces similar hurdles: steroids can calm flare-ups quickly, but long-term use brings side effects, and relapse is also a risk.

The goal of the article is to assess the most effective treatments, which is essential to directing medical professionals and enhancing patient outcomes.

Pathophysiology and clinical presentation

Role of eosinophils in gastrointestinal inflammation

Eosinophils are a type of immune cell that are normally present in the gut wall (as well as in other areas of the body) in small amounts. Eosinophils help with gut defence against foreign organisms. With EGE, eosinophils multiply excessively and accumulate in the gut wall. This leads to damage and swelling within the gut wall, as they release toxic proteins and chemicals. These substances damage the gut lining, trigger inflammation, and also hinder nutrient absorption.³

Symptoms

• Nausea
• Vomiting
• Abdominal Pain
• Bloating
• Diarrhoea
• Ascites
• Oedema
• Fatigue
• Difficulties in eating
• Weight loss
• Poor growth in infants and children
• Anaemia

Subtypes

EGE is classified by how deeply it affects the gut lining, and so is classified as mucosal, muscular, and serosal. Subserosal disease was also identified in patients with hypereosinophilia in ascites (more than 500 eosinophils per µL). Patients with subserosal or muscular disease were not diagnosed with mucosal disease, but rather with muscular or subserosal disease if they had mucosal eosinophil infiltration. Extensive disease was defined as involving two or more intestinal segments.⁴

Current treatment approaches

Dietary therapy

Elemental diets

Elemental diets, which are made up of formulations based on amino acids and are free of whole proteins, are useful in lowering inflammation and antigen exposure. In cases of eosinophilic gastrointestinal diseases, they have demonstrated high rates of both clinical and histological remission.

Elimination diets

Elimination diets remove potential food triggers. Elimination diets are either an empirical diet or a targeted diet. The "6-FED" empirical diet excludes the six most common food allergens: milk, soy, eggs, wheat, peanuts/tree nuts, and shellfish/fish. The number of foods that must be removed and then reintroduced can be significantly decreased if 6-FED is successful.⁵

Targeted elimination diets are based on allergy testing. 

Evidence on efficacy

Research indicates that a considerable percentage of individuals with EGE experience histologic remission and notable clinical improvement as a result of dietary therapy. For example, elemental or elimination diets were effective for 75% of patients, according to Lucendo et al. (2011). More controlled trials are necessary, nevertheless, as the majority of the evidence comes from retrospective studies or tiny case series.⁶

Limitations

Dietary therapy has drawbacks despite its advantages. Due to societal constraints, high cost, and poor palatability, compliance is low. Particularly in youngsters, nutritional imbalances can happen and need to be monitored by a dietician.

Corticosteroids

Systemic steroids 

Systemic glucocorticoids remain the fastest way to cure eosinophilic gastroenteritis . Prednisone is commonly used to treat sudden symptoms. About one-fifth of patients need a steroid-saving plan or low doses. Doctors try to use steroids at the lowest dose for the shortest time, as long-term use can cause problematic side effects.⁷

Topical steroids 

Modified-release Budesonide or enteric-coated Budesonide is often given for steroid-dependent or relapsing EGE, including children with this condition. It acts locally to reduce swelling and affects the whole body less. Doctors have seen good results in studies however, these were mostly case reports and small studies. They suggest budesonide is a safer choice for ongoing treatment.⁸

Short-term vs long-term efficacy

Prednisone and budesonide, when used for a brief period of time, frequently provides immediate relief. However, symptoms frequently return after stopping these steroids. Some people may need budesonide or other drugs that lessen steroid use. They might also require repeat treatments. Currently, there are few studies to guide how long to use these drugs for lasting control.

Adverse effects and relapse issues

Use of systemic steroids should be avoided for long-term use. They can cause weight gain, high blood sugar, high blood pressure, mood changes, weak bones, and more problems. Additionally, studies show the rates of disease return are about 30% or higher, and increased steroid use seems to raise the chance of the disease returning. Budesonide may be used long-term because it is relatively safer, though you still need to be monitored closely.⁷

Immunomodulators

Azathioprine, 6-mercaptopurine

Azathioprine (AZA) and 6-mercaptopurine (6-MP) are thiopurine immunosuppressant drugs. These drugs suppress the immune system’s activity. Doctors use them for eosinophilic gut issues, including eosinophilic gastroenteritis. They help reduce the need for steroids in patients who are dependent on them, which helps the disease under control for longer. Reports show AZA/6-MP helps patients stay in remission; this is true for those who are reliant on or who are taking steroids.⁷

Risks vs benefits

A key advantage of using immunosuppressant drugs is that it reduces steroid use, resulting in fewer flare-ups that require strong steroid doses to manage. It also leads to better long-term control for certain patients. 

Potential downsides include bone marrow suppression which can increase infection risk, liver damage, and rare pancreatitis. There is also a slight link to certain blood disorders seen with similar drugs. 

Patients must be counselled on these risks and have regular blood tests. Since strong studies on EGE are limited, doctors decide treatment by balancing these risks with the harm from long-term steroid use for each person.

Biologic therapies

Biologic drugs aim at specific immune parts that fuel eosinophil growth. They also target eosinophil survival or activity. These treatments offer new hope for people with eosinophilic gastroenteritis. This is especially true for those who need steroids or do not get better with standard care.

Anti–IL-5 agents

Interleukin-5 (IL-5) is essential for the production and migration of eosinophils. Drugs that target IL-5 lower eosinophil counts in blood and tissues. These drugs have been tested for stomach and gut diseases driven by eosinophils. Early findings from small groups suggest mepolizumab and reslizumab can cut down tissue eosinophils, sometimes help with symptoms, but results vary. Many reports are from small, unplanned studies. Benralizumab, a newer drug, gets rid of eosinophils. It uses the body's immune system to attack them. In studies of eosinophilic gastritis, benralizumab led to near-total eosinophil removal. However, some patients still show signs of illness or changes in their gut lining.¹⁰

Anti–IL-4/IL-13

Dupilumab stops IL-4/IL-13 signals, has shown good results, and is used for eosinophilic gut problems. Past studies and reports show symptom relief, and tissue eosinophils decreased. New trials and cases show promise that Dupilumab may be a strong choice for gut issues.¹¹

Anti-IgE

Omalizumab has been tried in individual cases of EGE with reported clinical benefit in some patients, supporting a possible IgE-mediated component in selected cases. A planned study has been registered, but strong randomised data for EGE are still missing.¹²

Other therapies

Mast cell stabilisers

Cromolyn sodium prevents toxic chemicals from being released by mast cells. It helps some EGE patients, especially with stomach pain and loose stools.

Leukotriene inhibitors

Montelukast helps control swelling caused by certain cells. It lowers inflammation from eosinophils and mast cells, eases symptoms, and lowers steroid use. However, symptoms return when use stops. 

Antihistamines and supportive therapies

Antihistamines can help with stomach pain, sickness, or loose stools, but do not often address the condition. Doctors often add other treatments, including drugs for stomach acid and food support for poor nutrient use. This is common when diet changes or steroids are also used.

Comparative effectiveness: what works best?

Although long-term use is limited by relapse and side effects, evidence from clinical trials and case series indicates that corticosteroids continue to be the most effective first-line medication for quick symptom alleviation.

Although adherence is challenging, dietary therapy is a safe substitute that can provide remission, particularly in children. 

Steroid-dependent or refractory cases are treated with immunomodulators such as azathioprine or 6-MP, while biologics (anti-IL-5, dupilumab) show promise but are currently being studied. 

The severity of the disease, the GI layer that is impacted (mucosal, muscular, or serosal), and any comorbidities should all be considered when making a personalised therapy decision. Combining medication and food is frequently necessary for long-term care in order to lower steroid exposure and relapses.

Future directions

Clinical trials are currently being conducted on biologic treatments, which could eventually provide more therapeutic alternatives than steroids. It is anticipated that precision medicine techniques, such as genetic and immunologic profiling, will more precisely direct the choice of medication. By predicting how a patient will react to nutrition, steroids, or biologics, biomarkers may enable more individualised care plans and less trial-and-error therapy.

Summary

Currently, nutrition therapy and immunomodulators are crucial for certain patients, although corticosteroids continue to be the mainstay of treatment. Though more proof is needed before normal usage, biologics offer increasing promise for long-term illness control. Individualised therapy that balances patient lifestyle characteristics, safety, and efficacy yields the best results. To improve the quality of life in eosinophilic gastroenteritis and develop uniform treatment algorithms, more thorough, long-term research is required.