Eosinophilic oesophagitis is a chronic inflammatory condition that requires ongoing management to control symptoms and prevent long-term damage to the oesophagus, though it cannot be cured.

Understanding Treatment Goals and Approaches

When someone is diagnosed with eosinophilic oesophagitis, the primary goals of treatment focus on reducing inflammation in the oesophagus, relieving symptoms such as difficulty swallowing and food getting stuck, and preventing complications like scarring and narrowing of the oesophagus. Unlike some conditions that can be cured completely, eosinophilic oesophagitis is a lifelong disease that requires continuous management. Most people with this condition will need some form of treatment throughout their lives to keep symptoms under control and maintain a good quality of life.^[1][2]

Treatment decisions depend on several factors, including the severity of symptoms, the degree of inflammation found on biopsy, the patient’s age, and individual preferences. A key concept in managing this disease is achieving and maintaining remission, which means reducing the number of white blood cells called eosinophils in the oesophagus to below 15 per high-power field on microscopic examination. However, symptom relief does not always correspond perfectly with what is seen on biopsy results, which is why doctors consider both how a patient feels and what the tissue samples show.^[10][13]

Medical societies and expert groups have developed clinical guidelines that recommend three main approaches to treating eosinophilic oesophagitis: dietary changes, medications, and in some cases, endoscopic procedures to widen the oesophagus. The choice between diet or medication as the first line of treatment is typically made through shared decision-making between the patient, their family members or caregivers, and their healthcare team. Each approach has its own benefits and challenges, and what works best can vary from person to person.^[11][12]

Standard Treatment Options

Dietary Elimination Strategies

Dietary changes have emerged as an effective way to manage eosinophilic oesophagitis because the condition is driven by an immune response to certain foods. The principle behind dietary treatment is simple: remove the foods that trigger inflammation, and the oesophagus can heal. However, identifying which specific foods cause problems for each individual patient can be challenging, since food triggers are not the same for everyone.^[3][6]

The most comprehensive dietary approach is the elemental diet, which consists entirely of amino acid-based formulas that do not contain whole proteins that could trigger an allergic reaction. This approach resolves inflammation in more than 90% of children and shows somewhat less benefit in adults. However, the elemental diet is extremely difficult to maintain because of taste, cost, nutritional concerns, and practical barriers. Some patients, particularly infants, may even require a feeding tube placed through the abdominal wall into the stomach. Additionally, when children rely solely on formula, they miss opportunities to develop proper oral motor skills and may experience social isolation when they cannot participate in shared meals with family and friends.^[12][13]

A more practical approach is the six-food elimination diet, which involves removing the six most common food triggers: dairy products, eggs, wheat, soy, fish and shellfish, and peanuts and tree nuts. This diet resolves inflammation in approximately two-thirds of patients. Recent research has shown that less restrictive elimination diets can also be effective. For example, a four-food elimination diet or even a two-food elimination diet can be considered as initial approaches, reducing the need for repeated endoscopy procedures, shortening the time to diagnosis of specific triggers, and avoiding unnecessary food restrictions.^[2][12][13]

Another dietary strategy involves allergy testing-directed food elimination, where patients undergo allergy testing (either skin prick tests or blood tests) to identify specific food allergies, and then avoid only those foods. This approach resolves inflammation in about one-half of patients. While this success rate is lower than the six-food elimination diet, it is simpler to implement and may be preferred by some patients because it requires avoiding fewer foods based on individual test results.^[12][15]

Regardless of which dietary approach is chosen, patients need to work closely with a registered dietitian who has experience with eosinophilic oesophagitis to ensure they maintain proper nutrition while avoiding trigger foods. After a period of eliminating foods (typically eight to twelve weeks), patients undergo a follow-up endoscopy with biopsies to check whether the inflammation has improved. If inflammation has resolved, foods are gradually reintroduced one at a time, with repeat endoscopies to determine which specific foods trigger the disease in that individual patient.^[12][13]

Pharmacologic Treatment with Medications

Proton pump inhibitors (PPIs) are a class of medications originally developed to reduce stomach acid production for conditions like gastroesophageal reflux disease. However, research has shown that these drugs also have anti-inflammatory effects in the oesophagus that are independent of their acid-blocking properties. PPIs are often used as a first-line medication for eosinophilic oesophagitis because they are widely available, have a well-established safety profile, and are familiar to most doctors. Studies show that PPIs resolve inflammation in approximately one-third of patients, which is more than double the response seen with placebo. Common examples include omeprazole, lansoprazole, and esomeprazole. Most patients need to continue taking PPIs long-term to maintain remission.^[11][13][15]

Topical corticosteroids are the most effective medication option for eosinophilic oesophagitis, resolving inflammation in approximately two-thirds of patients, which is more than four times the placebo response. These are steroid medications that work by suppressing the immune response and reducing inflammation. However, unlike oral steroids that are swallowed and absorbed throughout the body, topical steroids are designed to coat the lining of the oesophagus and work locally where they are needed.^[11][13][15]

Originally, doctors adapted asthma inhalers containing steroid medications such as fluticasone or budesonide for use in eosinophilic oesophagitis. Patients would spray the medication into their mouths and then swallow it rather than inhaling it into the lungs. While this off-label use proved effective, the formulations were not optimal for coating the oesophagus. More recently, pharmaceutical companies have developed medications specifically designed for this condition, including effervescent orodispersible tablets and viscous formulations (thick liquids or slurries) that better coat the oesophageal mucosa. These newer formulations provide increased effectiveness at reduced doses compared to the repurposed asthma inhalers.^[12][13]

Studies of topical steroids for eosinophilic oesophagitis have generally shown good safety profiles, with adverse effects similar to placebo in most trials. However, some patients may develop localized fungal infections in the mouth or oesophagus (oral or oesophageal candidiasis) or, rarely, viral infections. There have been isolated reports of adrenal suppression, which is a concern with any steroid medication. Patients are typically advised not to eat or drink for at least 30 minutes after taking topical steroids to allow the medication to stay in contact with the oesophagus rather than being washed away.^[13][15]

Oral systemic corticosteroids (steroid pills such as prednisone) demonstrate the same benefit as topical steroids in resolving inflammation, but they cause significant adverse effects in approximately 40% of patients. Because of this unfavorable risk-benefit profile, oral steroids are generally reserved for patients who have serious swallowing problems or significant weight loss and need rapid improvement, or for those who have not responded to other treatments.^[15]

Monoclonal antibodies represent a newer class of targeted biologic therapies that can reduce inflammation and help with swallowing in patients with eosinophilic oesophagitis. These medications work by blocking specific immune system proteins that drive the inflammatory process. Currently, they are approved for use in adults and adolescents aged 12 years and older. While still relatively new compared to dietary and standard medication approaches, biologics offer another option for patients, particularly those who have not achieved adequate disease control with other treatments.^[6][16]

Duration of Therapy

Because eosinophilic oesophagitis is a chronic condition, most treatments need to be continued indefinitely to maintain remission. When medications are stopped, inflammation typically returns, and symptoms can recur. Similarly, if patients reintroduce trigger foods after successfully eliminating them, the disease will usually flare up again. This means that whether someone chooses dietary management or medication, they are making a long-term commitment to ongoing treatment. The good news is that with proper management, most people can achieve good symptom control and prevent complications.^[2][10]

Endoscopic Dilation for Narrowing

When chronic inflammation leads to scarring and narrowing of the oesophagus (called strictures), swallowing becomes difficult and food may get stuck. In these cases, an endoscopic dilation procedure may be necessary. During this procedure, a gastroenterologist passes an endoscope (a flexible tube with a camera) down the oesophagus and uses special instruments to gently stretch and widen the narrowed areas. This provides significant symptom improvement in approximately 87% of patients.^[8][15]

Endoscopic dilation is generally safe, with complication rates similar to dilation performed for other types of benign oesophageal narrowing. Major complications are rare, with perforation (a tear through the oesophagus wall) occurring in approximately 0.4% of procedures and significant bleeding in about 0.1% of cases. It is important to understand that dilation addresses the mechanical problem of narrowing but does not treat the underlying inflammation. Therefore, patients who undergo dilation still need dietary or medication therapy to control the disease and prevent future narrowing.^[15]

Treatments Not Currently Recommended

Several other therapies have been proposed and studied for eosinophilic oesophagitis but have not shown clear evidence of benefit. These include medications that block specific immune system chemicals (such as anti-interleukin-5, anti-interleukin-13, anti-interleukin-4 receptor-alpha, and anti-immunoglobulin E), anti-tumor necrosis factor therapies like infliximab, and medications like montelukast and cromolyn sodium. While research continues in these areas, current guidelines do not recommend these treatments as standard options.^[15]

Treatment in Clinical Trials

Research into new treatments for eosinophilic oesophagitis is rapidly expanding as scientists gain a better understanding of the immune system processes that drive the disease. Over the past three decades, this condition has evolved from being rarely recognized to becoming one of the most heavily researched upper gastrointestinal diseases. Clinical trials are testing innovative therapies that target specific molecular pathways involved in the inflammatory process.^[10][12]

Understanding Disease Mechanisms

The immune system dysfunction in eosinophilic oesophagitis involves a complex interaction between genetic susceptibility and exposure to food or environmental allergens. Research has identified that the condition is driven by type 2 helper T-cell (Th2) inflammation, which involves multiple immune cells including T cells, eosinophils, and mast cells, as well as inflammatory signaling molecules called cytokines. Important cytokines in this disease include interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-13 (IL-13), and thymic stromal lymphopoietin (TSLP).^[4][12]

Scientists have also discovered that certain genes play a role in eosinophilic oesophagitis. Genome-wide association studies have identified multiple genes involved in Th2 cell development and function, such as TSLP and STAT6, as well as genes important for the function and barrier integrity of the cells that line the oesophagus (epithelial cells). Understanding these genetic and molecular mechanisms has opened new avenues for developing targeted therapies.^[4][12]

Biologic Therapies Under Investigation

Many clinical trials are exploring biologic medications that target specific components of the immune response in eosinophilic oesophagitis. These therapies are designed to block particular cytokines or their receptors, thereby interrupting the inflammatory cascade. Some of these biologics are already approved for other allergic conditions like asthma or atopic dermatitis and are being studied to see if they are also effective for oesophageal inflammation.^[12]

Researchers are investigating drugs that block interleukin-5, which is a key cytokine that promotes the production, activation, and survival of eosinophils. By blocking IL-5 or its receptor, these medications aim to reduce the number of eosinophils that accumulate in the oesophagus. Clinical trials are evaluating both the safety and efficacy of these anti-IL-5 therapies, typically starting with Phase I studies to assess safety in a small number of participants, followed by Phase II studies to determine the optimal dose and evaluate preliminary effectiveness, and then larger Phase III studies comparing the new treatment to standard therapy.^[12]

Other promising targets include interleukin-13 and interleukin-4 receptor-alpha. IL-13 is particularly interesting because it plays a central role in driving many of the changes seen in eosinophilic oesophagitis, including disrupting the barrier function of the oesophagus lining and promoting eosinophil recruitment. Blocking the IL-4 receptor-alpha affects both IL-4 and IL-13 signaling pathways. Clinical trials of medications targeting these pathways are ongoing in both adults and children with eosinophilic oesophagitis.^[12]

Novel Therapeutic Approaches

Scientists have recently identified a family of inhibitory receptors called Siglecs (sialic acid-binding immunoglobulin-like lectins) that are expressed on the surface of eosinophils, mast cells, and basophils. These receptors act as natural brakes on the immune system. Because Siglecs are specifically expressed on allergic inflammatory cells, they represent potential therapeutic targets. Researchers are exploring whether activating these inhibitory receptors could dampen the inflammatory response in eosinophilic oesophagitis.^[12]

Other areas of investigation include improved formulations of topical steroids that better coat the oesophagus and maintain contact with the inflamed tissue for longer periods. Researchers are also studying combination approaches that use both dietary elimination and medication together to see if this provides better disease control than either strategy alone.^[13]

Clinical Trial Phases and Participation

Clinical trials for eosinophilic oesophagitis follow a standard progression through different phases. Phase I trials primarily focus on safety, involving small numbers of participants to determine whether a new treatment causes unacceptable side effects and to find the appropriate dose range. Phase II trials enroll more patients and evaluate both safety and preliminary efficacy, looking at whether the treatment shows promise in improving symptoms and reducing inflammation. Phase III trials are large, randomized studies that compare the new treatment directly with standard therapy or placebo to definitively establish whether it is effective. Finally, Phase IV trials occur after a treatment has been approved and is in widespread use, monitoring long-term safety and effectiveness in real-world conditions.^[12]

Clinical trials for eosinophilic oesophagitis are being conducted at medical centers across the United States, Europe, and other regions worldwide. Patients interested in participating in clinical trials should discuss this option with their gastroenterologist or allergist, who can help determine eligibility based on factors such as disease severity, previous treatments, and other health conditions. Participation in clinical trials not only provides access to cutting-edge therapies but also contributes to advancing medical knowledge that will benefit future patients.^[12]

Most Common Treatment Methods

• Dietary elimination
  • Elemental diet using amino acid-based formulas resolves inflammation in over 90% of children but is difficult to maintain due to taste, cost, and practical challenges
  • Six-food elimination diet removes dairy, eggs, wheat, soy, fish/shellfish, and nuts, resolving inflammation in approximately two-thirds of patients
  • Four-food and two-food elimination diets offer less restrictive approaches that can be effective as initial therapy
  • One-food elimination diet removing only dairy products has been shown to be as effective as six-food elimination for many adults
  • Allergy testing-directed food elimination resolves inflammation in about one-half of patients
• Proton pump inhibitors
  • Medications like omeprazole, lansoprazole, and esomeprazole that reduce stomach acid and have anti-inflammatory effects
  • Resolve inflammation in approximately one-third of patients
  • Widely available with well-established safety profile
  • Usually require long-term use to maintain remission
• Topical corticosteroids
  • Most effective medication option, resolving inflammation in approximately two-thirds of patients
  • Originally adapted from asthma inhalers (fluticasone, budesonide) that are swallowed rather than inhaled
  • Newer formulations include effervescent orodispersible tablets and viscous preparations designed specifically for coating the oesophagus
  • Generally well-tolerated with local side effects such as oral thrush or oesophageal fungal infections being most common
  • Require long-term use to maintain disease control
• Monoclonal antibody therapies
  • Biologic medications that target specific immune system proteins driving inflammation
  • Can reduce inflammation and improve swallowing in patients with eosinophilic oesophagitis
  • Currently approved for adults and adolescents aged 12 years and older
  • Offer an option for patients who have not responded adequately to dietary or standard medication approaches
• Endoscopic dilation
  • Procedure to stretch and widen narrowed areas of the oesophagus caused by scarring
  • Provides symptom improvement in approximately 87% of patients with strictures
  • Low risk of serious complications (perforation in 0.4% and significant bleeding in 0.1% of procedures)
  • Addresses mechanical narrowing but does not treat underlying inflammation
  • Patients still require dietary or medication therapy to control disease after dilation