The Journal of Allergy and Clinical Immunology published a new Northwestern Medicine study in collaboration with The Consortium of Eosinophilic Gastrointestinal Researchers. 

This is the first prospective study showing that food allergens can provoke immune system responses in the stomach and small intestine, leading to pain, nausea, vomiting, early satiety, weight loss, and diarrhoea.

Further, the study examines the therapeutic potential of an elimination diet (ELE). This dietary approach removes common food allergens like cow’s milk, wheat, eggs, soy, nuts and seafood from a person's diet. It demonstrates the effectiveness of ELE in treating Eosinophilic Gastrointestinal Disorders (EGIDs), but it also highlights the need for careful execution of this diet and further research to optimise its duration and components. 

This introduction sets the stage for the in-depth exploration of these findings and their implications.

Background: 

Eosinophilic gastrointestinal disorders (EGIDs) are rare, chronic conditions, including eosinophilic oesophagitis (EoE), eosinophilic gastritis (EoG), eosinophilic gastroenteritis (EoGE), and eosinophilic colitis (EoC). 

These conditions occur when eosinophils, a type of white blood cell, infiltrate the gastric and/or intestinal tissue. Symptoms, including abdominal pain, nausea, vomiting, early satiety, weight loss, and diarrhoea, usually relate to the specific layer of the bowel affected. 

Non-esophageal disorders like EoG, EoGE, and EoC are increasing. Their prevalence is estimated at 22 to 28 per 100,000 individuals in the US. 

Despite the last decade of evidence of elimination and elemental diets in managing EoE, their use in treating EoG/EoGE remains less studied. Current EoG/EoGE treatments mainly involve systemically active immunosuppressive agents such as corticosteroids, which effectively reduce inflammation but can have adverse long-term effects. 

Given the significant health burden these chronic conditions pose and the lack of safe, effective treatment data, further research on the pathogenesis of EoG/EoGE in this area is crucial.

Objective: 

This study aimed to assess the effectiveness of an elemental formula (ELE) or food allergen-free diet in managing gastrointestinal eosinophilia in adult EoG/EoGE patients. Additional goals included evaluating improvements in endoscopic features, peripheral eosinophilia, molecular signature, symptoms, and quality-of-life (QOL) scores.

Design: 

This prospective, single-centre study took place from August 2017 to June 2019 and initially involved 21 consenting participants. After the screening, 19 participants with histologically active EoG and/or EoGE confirmed via biopsy were eligible to continue. The study was part of the Consortium of Eosinophilic Disease Researchers (CEGIR) Pilot Program under the Rare Diseases Clinical Research Network. The National Institute of Allergy and Infectious Diseases oversaw it.

Methods: 

Adults aged 18 to 65 with active EoG/EoGE (over 30 eosinophils per high-power field in the stomach and/or duodenum) and recent gastrointestinal symptoms were enrolled. In a single-arm clinical trial, these participants underwent six weeks of treatment with a diet of solely drinking elemental formula.

The primary endpoint was to determine the percentage of participants who achieved complete histologic remission, defined as having fewer than 30 eosinophils per high-power field in both the stomach and duodenum.

In addition to this, the study also explored several other important outcomes. These included improvements in symptoms, results from endoscopy, levels of eosinophils in the blood, quality of life, Physician Global Assessment scores, and changes in the gastric transcriptome and microbiome relevant to EoG.

Results: 

Fifteen adults (47% male, average age 37.7 years, average symptom duration 8.8 years) completed the trial. 

Researchers observed histologic remission endoscopic and symptomatic improvement in all fifteen participants who completed the trial after six weeks of dietary therapy. 

After completing the therapy phase, the participants agreed to a food reintroduction protocol. Researchers reintroduced one food item to the participants’ diets every 3 to 5 days. If participants didn’t experience a symptom recurrence, researchers added more foods sequentially. If symptoms returned with a particular food or after adding an entire category of foods, the researchers performed an endoscopy with a biopsy to monitor the potential return of tissue eosinophilia.

Food reintroduction reversed improvements achieved on ELE, giving researchers insight into the influence of food on EoG/ EoGE pathogenesis.

Conclusion: 

An amino acid–based elemental diet effectively improves histologic, symptomatic, endoscopic, and molecular disease activity. These data and disease relapse after food reintroduction suggest a dominant role for food allergens in EoG/ EoGE pathogenesis.

The study data validate the effectiveness of dietary therapy for individuals with non-EoE Eosinophilic Gastrointestinal Disorders (EGIDs), offering a viable alternative to corticosteroids and showing improvements in patient-reported outcomes (PROs). This effective approach can be personalised by further investigating the optimal duration and type of dietary therapy for non-EoE EGIDs.

We are excited to share our results from the ELEMENT study in hopes it will provide new insights into the pathophysiology of these rare disorders as well as provide an alternative treatment options for patients suffering from these conditions.  

Nirmala Gonsalves, MD, Division of Gastroenterology and Hepatology,

Department of Medicine Northwestern University, Feinberg School of Medicine, Chicago, Ill

Concerns 

When discussing elemental formula therapy, it is important to consider various concerns carefully.

Dietary support

In this study, all participants adhered to drinking the formula diet exclusively, with no reliance on non-oral (tube) feeding. They had unrestricted access to their care providers throughout the trial and received close monitoring from a registered dietitian and gastroenterologist specialising in EGID.

Therefore, a trained team should oversee the ELE therapy providing adequate dietary support, which is unrealistic for some patients.

Long-Term Compliance

The level of support from a clinical professional impacted how much effort participants felt they were putting in while on a diet. As the study continued, participants reported feeling less effort was required, indicating that the early stages of transitioning to the diet were crucial.

However, it's important to note that ELE is not intended for extended periods of restriction and can be challenging to maintain when eliminating multiple food groups.

While the adherence to ELE in this study was high, likely due to the severe disease conditions of the patients, compliance may be less strict in cases of milder EoG/EoGE.

Chronic Kidney Disease

It is important to approach this method cautiously in patients with chronic kidney disease taking multiple diuretics. Hyponatremia is risky if they do not follow the recommended formula and fluid intake guidelines.

Cost

The cost of implementing the formula diet is also of concern, as formula insurance coverage is only universal in some US states. Costs in other countries may also mean access to this treatment may vary.

It is also important to note that if problematic foods are identified on reintroduction patient's ability to maintain long-term dietary restrictions can be affected by the additional financial burden of specialist dietary foods.

Amanda Cordell, CEO and Founder of EOS Network

Minimally Invasive Tools or Biomarkers

The data confirm that individuals with EoG/EoGE typically have multiple food triggers driving their disease process, unlike individuals with EoE alone, who can commonly have fewer food triggers.

These findings along with our previously reported delayed or missed diagnosis highlight the urgent need for developing minimally invasive tools or biomarkers to supplant endoscopy for diagnosis and disease activity assessment.

Amanda Cordell, CEO and Founder of EOS Network

EOS Networks thoughts for discussion

This study offers important information about EGIDS, its pathogenesis and treatment options. But it also raises questions for those living with the condition.

In this study, the participants had experienced an average of 8.8 years of symptoms with suboptimal treatments.

Due to the past lack of diagnosis consensus, some people control their EGIDS by following specific diets for many years, often without an official diagnosis. Once they have found that certain foods trigger their EGIDS, they might wonder: do they need to stop their diet to confirm their diagnosis? And if they do, for how long?

It's also worth noting that even after cutting out the six main food allergens (dairy, wheat, soy, eggs, nuts and fish), some people still don't feel well. This could mean other foods are causing issues, or food isn't the only trigger. Some people may need medication to control their symptoms, even with diet changes.

For the patients' community, this study is an important but not last step in providing a sustainable long-term therapy approach or cure. 

As an advocacy group, we are grateful to work with organisations like CEGIR to pursue greater insights into EGIDs.

Read the publication 

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