Recent Advances in the Treatment of Eosinophilic Esophagitis

Shauna Schroeder; Dan Atkins; Glenn T Furuta

Disclosures

Expert Rev Clin Immunol. 2010;6(6):929-937. 

In This Article

Dietary Management

Elemental Diet/Elimination Diet

Rationale Since eosinophils are associated with allergic reactions, early hypotheses proposed food allergens as the instigating factor in EoE. Since then, a number of clinical studies support a role for food allergies in the pathogenesis of EoE.[60] The first evidence that protein allergens may induce EoE came from Kelly et al., who treated children with an elemental diet or amino acid-based formula.[60] All children experienced symptom resolution and improved histology. No murine models have yet been developed that are based on protein hypersensitivity leading to esophageal eosinophilia, and thus this hypothesis has escaped further study. The role of allergy evaluation in the adult population has also been elucidated. In a recent paper, allergy evaluation had a high yield in adult EoE as 81% of referred patients had one or more allergens identified and 50% had one or more skin tests positive to foods. Therefore, allergy evaluation should be considered in adult patients with EoE.[61]

Studies of Elemental Diet The elimination of food allergens can be achieved by different approaches and has been primarily used in children. For instance, the removal of all food allergens, an elemental diet, which is the most extreme approach, can lead to resolution of symptoms and histological changes in EoE.[35] A directed elimination based on the results of allergy testing with SPTs and atopy patch testing (APT) in combination with the clinical history is effective in children.[62,63] Another approach that avoids any form of allergy testing is the empiric elimination of the eight most common food allergen groups (milk, soy, egg, wheat, shellfish, fish, tree nuts and peanuts).[64]

The elemental diet requires the replacement of all solid food with a nutritionally complete elemental formula. Kelly et al. studied ten children (aged 8 months to 12.5 years of age) who had persistent reflux symptoms but who had not responded to GERD treatments, including six who had prior Nissen fundoplications.[60] All ten patients had fewer symptoms on an amino acid-based formula, with eight patients reaching complete histological resolution. Symptoms returned when food was reintroduced into the diet, with milk causing symptoms in seven patients, soy in four patients, wheat and peanut in two patients, and egg in one patient. In larger studies involving over 160 patients at The Children's Hospital in Philadelphia (PA, USA), more than 98% of the patients demonstrated resolution of symptoms and normalization of biopsies when treated with an amino acid-based diet.[65,66] The most frequently encountered barriers to success with an elemental diet are linked to compliance; this approach often requires the use of a nasogastric tube for formula administration.[67]

Studies of Directed Elimination Diet Allergy testing has been used as a method to identify allergenic culprit foods in children with EoE. Two methods used to test for IgE-mediated food allergies include serum food allergen-specific IgE immunoassays and SPT. IgE-mediated reactions are characterized by classical symptoms of allergic disease resulting from the effects of mediators released and generated by crosslinking of IgE on the surface of mast cells. Classic IgE-mediated reactions are not typically thought to be the sole etiology of EoE. Because tests that accurately identify foods responsible for delayed allergic reactions are not available and because the exact immunologic mechanisms for EoE have not been elucidated, some studies and practitioners report the successful use of these forms of testing to identify the food allergens that are clinically relevant for a specific patient with EoE. In EoE, the positive predictive value (PPV) of SPT for milk, egg, beef and peanut was greater than 75%, but the PPV of SPT for oat, rice, potato, peanut, chicken and barley ranged from 33 to 43%.[62] Many patients with EoE do not present with the clinical picture of IgE-mediated reactions, thus leading to the use of APT to look for foods causing non-IgE-mediated reactions. APT is thought to provide evidence for a T-cell-mediated reaction. APT is performed by placing the food in its native state in contact with the skin under an aluminum Finn Chamber for 48 h on the patient's back. The chamber is removed and the reaction is examined for induration and papules 24 h later. One center's experience with APT in children with EoE showed that the PPV for APT was 94% for beef, 83% for milk, 60–70% for most foods and 48% for oats.[26] The negative predictive value was more consistent and generally was in the mid-80% to mid-90% range for all foods except for milk, which was 59%. These findings suggest that if a food is negative on skin testing and APT, it is probably not responsible for the EoE.

Studies of Empiric Elimination Diet In an effort to avoid allergy testing completely, Kagalwalla et al. removed the eight most common food allergen groups (milk, soy, egg, wheat, shellfish, fish, tree nut and peanut) from the diets of 35 pediatric patients.[64] Approximately 74% of the 35 patients who received the eight-food group elimination diet demonstrated improvement. The children treated with this elimination diet showed clinicopathologic improvement (80.2 ± 44 eosinophils per HPF before elimination vs 13.6 ± 23.8 after elimination). The study also compared the results of the empiric food elimination diet to the results obtained in 25 patients treated with an elemental diet consisting of an amino acid-based formula with no other added foods. The comparison revealed that, although both diets significantly improved the clinicopathologic features of the disease, the elemental diet was more effective in regard to the number of patients who responded (22 out of 25) and regarding the residual number of eosinophils per HPF (13.6 in the eight-food group; 3.7 in the amino acid formula group).[64]

Summary Dietary therapy is effective in resolving symptoms and improving the histopathology associated with EoE. When deciding on the use of a specific dietary therapy, the patient's and parent's goals and quality of life need to be assessed and considered. Nutritional evaluation by registered dieticians is strongly encouraged to ensure that proper calories, vitamins and micronutrients are provided. Typical vitamin and micronutrient deficiencies occur from avoidance of specific foods. For example, milk avoidance places patients at increased risk for vitamin D, calcium, phosphorus and vitamin B12 deficiencies. Wheat products are typically enriched and fortified with iron, niacin, riboflavin, thiamine, folate and fiber.

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