Introduction to Eosinophilic Esophagitis (EoE)
Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease triggered by allergens. It is characterized by an infiltration of eosinophils (a type of white blood cell) into the esophagus, leading to esophageal dysfunction. The prevalence of EoE is increasing, affecting approximately one in 1,000 people. Food and environmental factors are recognized as important triggers of the disease. The connection between EoE and diet was identified early in the history of this disorder, as attested by the marked clinical-histological improvement of children with EoE through elemental diets consisting of amino acids (allergen-free) and subsequent relapse after food reintroduction. EoE is often seen in individuals with other allergic conditions like allergic rhinitis (hay fever) and asthma. Symptoms of EoE can include dysphagia (difficulty swallowing), food impaction, chest pain, and heartburn.
Understanding the 2-Food Elimination Diet (2-FED)
The two-food elimination diet (2FED) is a dietary intervention used in the management of eosinophilic esophagitis (EoE). It involves eliminating two of the most common food allergens - cow's milk (dairy) and wheat - from the diet to reduce inflammation of the esophagus. The rationale behind this diet is that by removing these common allergens, esophageal inflammation will decrease, and symptoms will improve. This approach is in line with current guidelines that encourage empirical diets with a reduced number of eliminated food categories and a step-up approach to maximize clinical results and adherence.
Historical Context
EoE is thought to be a food allergen-mediated disease of the esophagus as most patients respond well to elimination and elemental diets.
Purpose of the 2-FED
The primary goal of the 2-FED is to identify food triggers responsible for inflammation in the esophagus. It serves both a diagnostic and therapeutic role.
How the 2-FED Works
The 2-FED involves the elimination of cow’s milk and wheat from the diet for a trial period, typically 8 to 12 weeks. After this period, an esophagogastroduodenoscopy (EGD) and esophageal biopsy are performed to assess the results of the diet. If the diet is successful in reducing inflammation, foods are reintroduced one by one every 2-4 weeks, with esophageal histologic sampling during the reintroduction phase to identify specific triggers.
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General Dietary Practices during the 2-FED
During the 2-FED, individuals must avoid all foods containing cow's milk and wheat. In Australia and New Zealand, food manufacturers must declare the presence of any cow’s (and other animal) milk (dairy), wheat and other gluten containing grains however small the amount. It is important to carefully read food labels to identify hidden sources of these allergens. Otherwise, all plain meat, fish, chicken, egg, legumes, non-wheat grains, fruits, nuts, seeds and vegetables can be included.
Foods to Avoid
- Cow's Milk (Dairy): This includes milk, cheese, yogurt, butter, ice cream, and any products containing milk-derived ingredients. Note: Other animal milks such as goat, sheep, camel, buffalo products are too similar to cow’s milk (dairy) products, so they should not be used as substitutes. Some soy cheeses may also contain cow’s milk protein.
- Wheat: This includes bread, pasta, cereals, and baked goods made with wheat flour. It also includes products containing wheat-derived ingredients. Brands made from hops or barley should also be avoided.
Food Alternatives
- Dairy Alternatives: Soy, rice, oat, nut, pea protein-based drinks can be used as alternatives. Choose one with 120-160 mg calcium per 100 ml. A calcium supplement may need to be taken if inadequate volumes of milk replacement or specialised formula are taken.
- Wheat Alternatives: The biggest challenge when avoiding wheat is finding alternative breads, cereals and pasta.
Important Considerations
- Existing Food Allergies: If you have existing food allergies, it is important to continue to avoid those foods whilst following this diet for EoE.
- Label Reading: People with food allergy should check foods labels each time products are purchased. Food manufacturers must declare the presence of any cow’s (and other animal) milk (dairy), wheat and other gluten containing grains. These statements are voluntary and used by manufacturers to indicate that the product may be contaminated with food allergen ingredients through processing and packaging.
- Not Exhaustive Food Lists: The food lists included in this document are not exhaustive.
Step-Up Approach and the 2-4-6 Study
According to guidelines, a step-up approach, starting with the elimination of a reduced number of food categories, usually two in 2-FED, and progressing to 4-FED or 6-FED, the latter in highly motivated patients, is currently the preferred approach to food elimination since it is cost-effective and improves compliance. A minimum duration of 6 weeks, usually 8 to 12, for each step of food elimination is usually warranted. After confirming clinical and histological remission through endoscopy, the patient should then reintroduce one food at a time for at least 8-12 weeks and be rescoped after reintroduction to identify the food trigger.
The 2-4-6 study, a multinational prospective study in 130 patients with EoE, including 25 children, evaluated the effect of a step-up strategy, which consisted of a 2-FED for 6 weeks, gradually followed by a 4-FED and a 6-FED in case of no response. In responders, at any step, previously eliminated food groups were reintroduced to identify the trigger through endoscopy. The 2-FED strategy achieved histopathology remission in 43% of patients independently of age. Of note, 43% of patients in the study were allowed to receive PPI during 2-FED. Milk was the most frequent trigger (52%), along with gluten-containing cereals (16%); both were present in 28% of cases. The remission rates with 4-FED and 6-FED were 60% and 79%, respectively, and, consistent with previous data, most patients (91.6%) had only one or two food triggers. Compared to a 6-FED diet, the 2-FED in this multistep approach allowed early recognition of two-thirds of patients responding to any empiric diet, whereas the 4-FED identified all patients responding to one or two triggers. Altogether, this multistep approach identified the majority of patients responding to a simplified empiric diet early and shortened the diagnostic process by 30% and the number of endoscopies by 20%.
Other Dietary Strategies for EoE
Elemental Diets
The evidence of the complete remission of refractory cases of EoE achieved by feeding for 6 weeks with an amino acid-based or elementary formula (devoid of allergens) constitutes the etiologic demonstration of the allergic nature of EoE. According to guidelines, this strategy may be used as a rescue therapy in both adults and children, and it is particularly suitable for malnourished children in order to avoid further loss of weight. However, its poor palatability reduces adherence, hampers the acquisition of oral and motor skills in infants, and leads to the development of nutritional deficiencies. Moreover, this strategy does not allow trigger identification. Due to this consideration, elemental diets have a limited role in EoE.
Allergy Testing-Based Diets
Given that allergens trigger EoE in a significant proportion of patients, the use of allergy testing to guide elimination diets has a strong theoretical rationale. However, results of food allergy testing-based diets have been modest in adults and variable in children independently of the test used, such as skin prick tests, specific IgE or recombinant molecules, and patch tests, according to a systematic review and meta-analysis. Collectively, the response rate is around 50%. It is possible that IgE testing is not accurate in predicting food-related exacerbations since EoE is not an IgE-mediated allergy but a food-induced cell-mediated reaction. Patch tests are performed with the application of food extracts on the skin and have a strong diagnostic rationale since they detect delayed reactions to allergens that are cellular-mediated. Altogether, given the low rate of reproducibility and predictability in trigger identification and the time-consuming procedures of allergic tests in EoE, food allergy testing-based diets are currently not encouraged by most guidelines to choose the type of dietary restriction.
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Six-Food Elimination Diet (6-FED)
The 6-FED consists of the elimination of the six food groups more commonly associated with the disease, i.e., cow milk or wheat or all gluten-containing cereals, egg, soy, peanut/tree nut, fish, and sea food. This diet is highly effective, being associated with a high response rate of up to 75% in children. A major disadvantage of this dietary strategy is that it requires a relevant number of endoscopies for histological evaluation after each individual food category reintroduction in order to identify the trigger. Moreover, patients should be highly motivated to carry out this diet, which, though less restrictive than an elemental formula, is still demanding. So long-term adherence is an important issue, along with possible associated nutritional deficiencies.
One-Food Elimination Diet (1-FED)
In a 1-FED, one food, usually milk or wheat, is eliminated, based on the assumption that milk or wheat represent the most common trigger food in patients with EoE and that up to 70% of patients responding to a 2-FED have one single food trigger. As opposed to children, the elimination of cow’s milk in the 1-FED seems to be associated with a lower rate of histological remission in adults (18-25%), possibly highlighting the diverse importance of this food trigger according to age.
Key Concerns and Considerations
Initially, this diet is very restrictive making it hard to follow and may lead to long-term dietary limitations. There are no known associated health risks of the diet however due to its restrictive nature there are potential risks for nutrient deficiencies.
Professional Guidance
Professional guidance is recommended when eliminating and reintroducing food groups. Dietary therapies in eosinophilic oesophagitis should be carried out by a multidisciplinary team comprising, among others, an allergist, a gastroenterologist, a dietitian and a psychologist. The interaction between these professionals is suggested by the circle. The interaction between the allergist for adults and a paediatrician is especially important in the transition age. To adequately carry out elimination diets, ensuring correct label reading through written information is important.
Patient-Specific Considerations
The prescription of an elimination diet should be carefully pondered in patients who already have multiple dietary restrictions, such as due to IgE-mediated food allergies or celiac disease, which are present in up to 67% and 25% of patients with EoE, respectively. Dietary strategies should be adapted to patient needs, taking into consideration patient age and medical history, feeding behaviours and weight, geographical, social and economic factors, among other elements.
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Geographic and Individual Variability
It's important to recognize that allergenic sensitization patterns can vary geographically. For instance, in Spain, legumes have been shown to be a particularly frequent trigger of the disease, as opposed to the United States and Australia. Moreover, sensitization to some allergens is geographically restricted, such as non-specific lipid transfer protein, nsLTP, which are pan-allergens and are present in the peel of most fruits and vegetables and are a relevant cause of severe IgE-mediated food allergy in the Mediterranean area due to their thermal and proteolytic resistance.
Unmet Needs and Future Directions
Despite relevant progress being achieved in the dietary management of EoE, some unmet needs remain. The main areas of unsolved issues regard the number and categories of eliminated foods, the optimal duration of the elimination diet, the development of new IgE-mediated food allergies, the adoption of less invasive modalities of endoscopic evaluation, such as the Cytosponge, for both the diagnosis of EoE and food reintroduction, and diet long-term efficacy. The current lack of reliable non-invasive biomarkers for EoE is also of importance. Future studies should also define which diet treatment, among tho…