Eosinophilic Esophagitis: History
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Subjects: Nutrition & Dietetics
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Veronica Pardi

Eosinophilic esophagitis (EoE) is a unique form of non-immunoglobulin E-mediated food allergy, restricted to the esophagus, characterized by esophageal eosinophil-predominant inflammation and dysfunction. The diagnosis requires an esophago-gastroduodenoscopy with esophageal biopsies demonstrating active eosinophilic inflammation with 15 or more eosinophils/high-power field, following the exclusion of alternative causes of eosinophilia. Food allergens trigger the disease, withdairy/milk, wheat/gluten, egg, soy/legumes, and seafood the most common. Therapeutic strategies comprise dietary restrictions, proton pump inhibitors, topical corticosteroids, biologic agents, and esophageal dilation when strictures are present. However, avoidance of trigger foods remains the only option targeting the cause, and not the effect, of the disease. Because EoE relapses when treatment is withdrawn, dietary therapy offers a long-term, drug-free alternative to patients who wish to remain off drugs and still be in remission. There are currently multiple dietary management strategies to choose from, each having its specific efficacy, advantages, and disadvantages that both clinicians and patients should acknowledge. In addition, dietary regimens should be tailored around each individual patient to increase the chance of tolerability and long-term adherence. In general, liquid elemental diets devoid of antigens and elimination diets restricting causative foods are valuable options. Designing diets on the basis of food allergy skin tests results is not reliable and should be avoided.

  • eosinophilic esophagitis
  • dietary management
  • six-food elimination diet
  • elemental diet
  • target elimination diet

1. Introduction

Eosinophilic esophagitis (EoE) is a unique form of non-immunoglobulin E (IgE)-mediated food allergy, restricted to the esophagus, characterized by esophageal eosinophil-predominant inflammation and dysfunction [1][2][3]. It currently represents the most common eosinophilic gastrointestinal disorder as well as the most common cause of dysphagia and food impaction among children and young adults [4]. EoE was considered rare prior to the past three decades, but incidence rates up to 20 per 100,000 inhabitants annually have recently been reported [5]. However, EoE prevalence estimates vary with location. A significant increase in prevalence has recently been described in Europe and North America, where EoE now affects more than 1 in every 1000 people, including both children and adults [3][5]. In contrast, lower prevalence estimates have been reported in Japan and China, where EoE is diagnosed in 20 of every 100,000 esophago-gastroduodenoscopies (EGDS) [6]. Socially, EoE has a significant and negative impact on health-related quality of life (HRQoL), for both patients and caregivers [7]. Additionally, costs attributable to the disease are estimated to be of the same order of magnitude as hospital-related costs for inflammatory bowel diseases [7].
The pathogenesis of EoE lies within a complex network of disease contributors. Genetic susceptibility and environmental factors trigger cytokine pathways that drive chronic inflammation and progressive esophageal fibrosis [8][9]. Key genes that predispose patients to the development of the disease are involved in allergic inflammation and mucosal barrier integrity [10][11]. Esophageal inflammation is typically triggered by mucosal exposure to food antigens, but most patients are also sensitive to aeroallergens [12], which have been shown to induce seasonal exacerbations of esophageal eosinophilia [12][13]. Consistently, EoE is associated to other allergic conditions, including allergic rhinitis, asthma, eczema, and is believed to be a late manifestation of the atopic march [14].
The natural history of EoE is believed to be a progression [8], and clinical presentation varies with age and disease duration. Adults commonly present with dysphagia and bolus impaction, whereas children usually have reflux-like and non-specific upper gastrointestinal symptoms [3]. Esophageal chronic inflammation causes strictures, thickening, luminal narrowing, furrowing, transient and fixed rings formation [15], and is associated with esophageal dysmotility [16][17][18][19]. Of note, up to one fourth of patients lack endoscopic alterations [20].
The diagnosis requires an EGDS with esophageal biopsies demonstrating active eosinophilic inflammation with 15 or more eosinophils/high-power field (eos/hpf), following the exclusion of alternative causes of eosinophilia [1][2][21].
Therapeutic strategies comprise dietary regimens, proton pump inhibitors (PPIs), topical corticosteroids, biologic agents acting on molecular pathways of the inflammatory cascade, and esophageal dilation when strictures are present [3][21][22][23].
EoE virtually requires a lifelong therapy as it invariably relapses when treatment is withdrawn [3]. Avoidance of trigger food(s) offers a unique long-term, drug-free alternative for the management of the disease. Various dietary regimens are now available for patients with EoE who wish to remain asymptomatic without being on a pharmacological treatment. However, the choice depends on numerous patient-centered variables, as well as the healthcare setting [24].

2. Tailoring the Diet to the Patient and Available Resources

Before initiating an elimination diet, a shared agreement between the clinician and the patient and/or patient’s family is necessary to identify which approach is clinically most appropriate and practically most viable. Multiple variables influence the appropriateness of a dietary regimen, including the patient’s preferences and characteristics, and availability of facilities for adequate follow-up.
First and foremost, patients should be given thorough information regarding the advantages and disadvantages of diets, so to choose judiciously. From the physician’s perspective, individual characteristics of candidates should be accurately considered before proposing an elimination diet. Although growth failure and feeding difficulties are not a contraindication for a dietary elimination therapy [25], a comprehensive assessment of pre-treatment diet, nutritional status, and possible feeding difficulties is necessary to establish whether a diet is feasible [24].
Up to 67% of patients with EoE have IgE-mediated food allergies, and 2% have celiac disease [26]. Such patients should be discouraged from undertaking elimination diets requiring additional restrictions that would hamper adherence and compromise HRQoL [27]. Similarly, patients who have more than four foods triggering the disease are not best candidates for dietary measures, as large restrictions would be necessary [28][29].
Patients and family members should be aware of the increase in weekly shopping costs and acknowledge the logistical complexity associated with the supply of foods only available at specialty stores [30]. Additionally, eating habits, ability to cook, necessity to eat out of the house, and reliance on pre-prepared foods should be considered prior to opting for a dietary treatment [31].
Candidates to dietary therapy should also be ready to undergo multiple endoscopies for the assessment of efficacy [2][21]. Finally, aspects related to the healthcare center where the follow-up is performed should be taken into consideration. The facility must guarantee EGDSs for re-assessment after food eliminationscheduled 6–12 weeks apart and be able to offer endoscopic procedures within a shorter time frame in case of recurrence upon food reintroduction [27].

3. Conclusions

Avoidance of trigger foods remains the only non-medical option to prevent esophageal chronic inflammation in patients with EoE. Dietary interventions target the cause of the disease and have comparable efficacy to pharmacological treatments, which can only act once inflammation has already occurred. EoE is a chronic condition that requires long-term treatment to prevent recurrence [3]. Accordingly, discussion of long-term management and long-term endurance on the diet needs to be addressed early when proposing alimentary restrictions to patients [24]. The dietary regimen must be tailored around patients’ preferences and characteristics. Additionally, the availability of resources for punctual follow-ups should be ensured. Multiple EGDSs are needed during a dietary treatment to establish the efficacy of a diet, reintroduce foods, and monitor the long-term efficacy of the diet and food tolerance [31]. Therefore, the best candidates for dietary restrictions are strongly motivated patients who wish to remain off drugs and still achieve remission [27]. Patients should acknowledge the drawbacks of avoidance strategies, including a significant impact on HRQoL and an increase of weekly shopping costs compared to unrestricted diets [30]. Especially for pediatric patients, the inclusion of a nutritionist for assessment of diet feasibility and nutritional follow-up is recommended [32]. Additionally, an allergist should be included in the diagnostic-therapeutic work-up of patients with present, past, or possible history of an IgE-mediated food allergy, as prolonged avoidance of specific foods during restriction periods may cause anaphylaxis upon reintroduction in those who are predisposed [33][34].
There are currently several dietary management strategies to choose from, each having its specific efficacy, advantages, and disadvantages. EDs represent the most effective treatment for EoE, having 90.8% efficacy at all ages [35]. However, burdensomeness and high costs make EDs only suitable for short-term treatments for selected patients. Elimination diets with multiple possible approaches (top-down, step-up, OFED) are adequate and effective long-term maintenance strategies, especially for those who have one or two trigger foods, in whom only few restrictions would be sufficient for disease control [36]. SPTs, APTs, and food-specific IgE results should not guide dietary restrictions in patients with EoE because they lack reproducibility and predictive value [2][21][35]. Interestingly, the possibility to evaluate esophageal sensitization through esophageal prick tests has recently been described [37]. The local injection of allergens into the esophageal mucosa detected abnormal responses to food allergens (complete luminal obstruction, blanching of the mucosa, erythematous wheals) in patients with EoE, correlating, although still imperfectly, with culprit foods. Further studies are needed to assess whether allergy testing may still have a place in the dietary management of EoE.

This entry is adapted from the peer-reviewed paper 10.3390/nu13051630

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