Key points

Introduction

Eosinophilic esophagitis (EoE) is an immune-mediated chronic inflammatory disorder of the esophagus that is triggered by food antigens in most patients. Dietary therapy has been established as an effective first-line therapy in children with EoE. However, support for the effectiveness of dietary therapy in adults is only now beginning to emerge in the literature. The highest response rates of up to 96% are achieved with dietary treatment, and thus, dietary approach is superior to the other available therapies to treat EoE. The natural history of EoE is progression to remodeling and subepithelial fibrosis. Dietary treatment has been shown to reverse subepithelial fibrosis and is likely to alter the natural history of EoE.

The goals of dietary treatment in EoE include: (1) symptom resolution; (2) maintenance of sustained histologic remission and thus prevention of disease-related complications, including fibrosis and strictures; and (3) prevention of iatrogenic treatment-related adverse reactions, such as nutritional deficiencies.

Because food antigens trigger eosinophilic inflammation, the dietary approach of identification and exclusion of causative food antigens to induce and maintain both clinical and histologic remission addresses the root cause of the disease. The current recommendations for treatment of EoE with diet are based on several retrospective and observational studies in children as well as prospective studies in adults. The available dietary approaches include: (1) elemental diet with an amino acid–based complete liquid formulation, (2) empirical or nondirected elimination diet with elimination of several common food antigens from the diet, and (3) directed elimination diet based on the results of allergy testing. The type of dietary treatment selected should be tailored to the needs of the individual patient. The treatment selection in children depends on the age of the patient, the presence of comorbid malnutrition, and feeding aversion. In adults and older children, the diet selection depends on the comfort and acceptance of the specific elimination diet. Outcomes of the different dietary approaches are summarized in Table 1 .

Introduction

Eosinophilic esophagitis (EoE) is an immune-mediated chronic inflammatory disorder of the esophagus that is triggered by food antigens in most patients. Dietary therapy has been established as an effective first-line therapy in children with EoE. However, support for the effectiveness of dietary therapy in adults is only now beginning to emerge in the literature. The highest response rates of up to 96% are achieved with dietary treatment, and thus, dietary approach is superior to the other available therapies to treat EoE. The natural history of EoE is progression to remodeling and subepithelial fibrosis. Dietary treatment has been shown to reverse subepithelial fibrosis and is likely to alter the natural history of EoE.

The goals of dietary treatment in EoE include: (1) symptom resolution; (2) maintenance of sustained histologic remission and thus prevention of disease-related complications, including fibrosis and strictures; and (3) prevention of iatrogenic treatment-related adverse reactions, such as nutritional deficiencies.

Because food antigens trigger eosinophilic inflammation, the dietary approach of identification and exclusion of causative food antigens to induce and maintain both clinical and histologic remission addresses the root cause of the disease. The current recommendations for treatment of EoE with diet are based on several retrospective and observational studies in children as well as prospective studies in adults. The available dietary approaches include: (1) elemental diet with an amino acid–based complete liquid formulation, (2) empirical or nondirected elimination diet with elimination of several common food antigens from the diet, and (3) directed elimination diet based on the results of allergy testing. The type of dietary treatment selected should be tailored to the needs of the individual patient. The treatment selection in children depends on the age of the patient, the presence of comorbid malnutrition, and feeding aversion. In adults and older children, the diet selection depends on the comfort and acceptance of the specific elimination diet. Outcomes of the different dietary approaches are summarized in Table 1 .

Elemental diet

Several pediatric studies have reported that ingestion of a crystalline amino acid–based elemental formula in lieu of a regular diet induced clinical and histologic remission in 88% to 96% of children. Subsequent controlled reintroduction of individual specific foods resulted in recurrence of gastrointestinal symptoms, thereby establishing a clear link between food allergy and esophageal injury. The likelihood of achieving mucosal healing with lower residual eosinophil counts is higher with this modality than other dietary therapy or pharmacologic treatment with corticosteroids. A recent study in a small group of adults treated with elemental diet reported histologic improvement in 70% (eosinophil count <10 per high power field) with an average decrease in the eosinophil count from 54 to 10 after the elemental diet. Similar to the pediatric experience, 50% of adults had eosinophil counts less than 5 per high power field. Patients did not show symptomatic improvement; however, that may be because of limitations in the dysphagia assessment tool used in this study. The decreased efficacy in this study compared with that of pediatrics could be attributed to adherence issues on the diet in the adult population.

Although universal guidelines regarding optimal duration of dietary therapy and period of reintroduction have not been established, based on available data, we propose the following approach. After 4 to 6 weeks of exclusive elemental diet and evidence of histologic remission on repeat endoscopy with biopsy, food reintroduction is initiated, beginning with the least allergenic foods from vegetable or fruit groups; single foods may be introduced every 5 to 7 days from within these less allergenic food groups. Once all foods in a given food group are successfully introduced, endoscopy is performed to show remission before moving to the next food group. If this strategy is successful, single food reintroductions from the most allergic food group, which includes foods such as cow’s milk, soy, wheat, egg, chicken, and corn, may be undertaken. The reintroductions are outlined by Markowitz and colleagues, as shown in Table 2 . In this process, if symptoms are elicited with an ingested food, then the symptom-inducing food is excluded from the diet, and the next food in that group is introduced once the symptoms have resolved. Some may wish to hold off on additional food reintroductions after that food has been removed from the diet for 4 to 6 weeks to ensure an adequate amount of time to wash out any potential histologic changes caused by the latest food reintroduction.

Although treatment with elemental formula has been shown to be highly effective in treatment of EoE, several disadvantages are worth noting, the most important one being compliance/adherence to the therapy secondary to the poor taste in both children and adults. Many children require either nasogastric or gastrostomy tubes to deliver adequate nutrients because of the palatability of the formula. Limiting a child to an exclusive elemental diet may also restrict the child’s participation in social activities, because many childhood activities involve food, which can lead to impaired quality of life. Although most adults are able to drink the formula without the use of feeding tubes, quality of life is also severely affected because of the inability to participate in social eating and engagement in activities involving food intake. The elemental formulas are also expensive, and this can place significant financial and social burden on the families. There may also be additional costs related to tubes, pumps, bags, and other supplies, particularly in children who require a feeding tube to administer the formulation.

Empirical elimination diets

The major advantage of the empirical or nondirected elimination diet is that allergy testing is not required to determine the foods to be eliminated. One of the most recognized empirical elimination diets is the 6-food elimination diet (SFED), in which patients exclude cow’s milk protein, wheat, egg, soy, peanut/tree nuts, and fish/shellfish from the diet. In 74% of children, this approach has shown significant clinical and histologic improvement. Two additional pediatric studies have recently validated the results of SFED, with histologic response ranging from 50% to 81%. Subsequent food reintroduction in the SFED responders identified milk (74%) as the single most common food responsible for triggering eosinophilic esophageal inflammation, followed by wheat (26%), egg (17%), and soy (10%). Other investigators have validated milk, wheat, egg, and soy as the 4 foods most likely to trigger inflammation in children with EoE.

Empirical dietary elimination has also been shown to have comparable effectiveness in adults. A prospective study excluding the same 6 foods as the study in children reported histologic remission in 70% of the patients studied after completing the diet for 6 weeks. These results mirror the pediatric experience. In patients who responded to the diet, serial food reintroduction was undertaken and resulted in symptom recurrence within 5 days of adding the trigger food. After exposure to the trigger food, esophageal eosinophil counts also returned to pretreatment values, and endoscopic features of EoE recurred on follow-up endoscopy. Common food allergens identified in this adult study were wheat (60%), milk (50%), soy (10%), nuts (10%), and egg (5%). A second adult study from Spain reported similar results, with remission in 73% of adults with EoE after empirical elimination of wheat, rice, corn, legumes, peanuts, soy, egg, milk, fish, and shellfish. More than 6 foods were excluded in this study. Food reintroduction in the Spanish study identified the common triggers as milk (61%), wheat (28%), eggs (26%), and legumes (23%). These investigators also found that continued elimination of these food triggers was effective in maintaining remission. Thus, in both adults and children, the 4 foods most likely to trigger esophageal inflammation include milk, wheat, egg, and soy.

In a small retrospective series of children, single food elimination with milk induced clinical and histologic improvement in only 65% of patients. Validation of this approach in a prospective study of children and adults is warranted.

The primary advantage of an elimination diet over exclusive elemental diet is that it allows intake of a variety of table foods, including meats, grains, fruits, vegetables, and legumes compared with a single nutrient source taken orally or via a feeding tube. The major limitation of empirical elimination diet is the difficulty with adherence to elimination of multiple food groups, even if for a limited time. Other concerns are that because of the lack of symptom/histology correlation, multiple endoscopies are required during the food reintroduction phase to help identify food triggers until noninvasive testing becomes available.