Eosinophilic esophagitis (EoE) is a chronic, antigen-mediated disease characterized by localized eosinophilic inflammation of the esophagus. Symptoms vary depending on the child's age, with vomiting, nausea, and feeding difficulties resulting in failure to thrive being prominent in young children. Meal-associated cough, epigastric pain, dysphagia, and even food impaction are more prevalent in older children and adolescents (1, 2). The diagnostic criteria for EoE necessitate the presence of both clinical manifestations consistent with esophageal dysfunction and histological evidence of >15 eosinophils per high-power microscopy field (HPF) in esophageal biopsies (1). Treatment strategies include proton pump inhibitors (PPIs), topical corticosteroids (tCS), or elimination diets to achieve disease remission.

In Europe, the six most common food triggers are cow's milk (CM), hen's egg (HE), wheat, soy, (pea)nuts, and (shell)fish. Empirically, avoiding one or more of these allergens can often induce remission (3). However, recent findings suggest that in EoE triggered by cow's milk, baked milk products can in some cases be tolerated (4–6). Similar to cow's milk, we present two cases of hen's egg-triggered pediatric (Ped)EoE (while under treatment with tCS) that remained in remission after the introduction of highly heated forms of egg. Unfortunately, EoE relapse occurred after the introduction of less heated forms of hen's egg, which resulted in renewed exclusion of hen's egg from the children's diet.

PedEoE is a heterogeneous disease that necessitates a tailored therapeutic approach. Historically, PPIs were considered the first-line treatment for EoE, with administration of tCS or dietary elimination reserved for cases in which remission was not achieved. However, the current guidelines now position PPIs, tCS, and dietary elimination as equally appropriate first-line therapeutic strategies (1). Histological remission is achieved in 59%–66% of children treated with tCS, in 30%–70% of children treated with PPIs, and in 42%–57.2% of children undergoing dietary interventions (1, 2). When dietary elimination is selected as the therapeutic approach, several strategies are available, each associated with different histological remission outcomes. Remission rates have been reported as ranging from 60.2% to 74% with a six-food elimination diet (SFED), from 56.3% to 64% with a FFED, from 30% to 67% with a one-food elimination diet (OFED), and from 52.6% to 58% with a targeted elimination diet (TED) (1, 9–11). In some cases, monotherapy may prove insufficient, necessitating a combination approach involving PPIs and/or dietary elimination and/or tCS to achieve optimal disease control (1). We have recently reviewed all PedEoE cases at our institution, highlighting the treatment difficulties in daily practice (12). Dietary elimination requires complete avoidance of the causative food. Adherence to such a diet is challenging due to the presence of allergenic protein in numerous (processed) foods. Furthermore, strict elimination diets may adversely impact both nutrition and overall quality of life (QoL), especially as more foods are restricted (8).

In the context of IgE-mediated food allergy, recent articles in the literature recommend heated allergen reintroduction, while avoiding less heated allergens during the tolerance introduction process. Indeed, emerging data show that a notable proportion (69%–83%) of children with an IgE-mediated CM allergy successfully tolerate baked CM products such as cake, whereas 63%–83% of children with IgE-mediated HE allergy tolerate baked HE products (4, 13). The allergenicity of CM and HE appears to be influenced by heating temperature and duration (8). Allowing the consumption of baked CM or HE products has the potential to improve compliance and enhance overall nutrition and QoL in children with a CM or HE allergy (4). Furthermore, we have provided evidence that consumption of heated HE may accelerate HE allergy resolution and that raw HE tolerance develops gradually through progressively less heated steps (e.g., cake, hard-boiled HE, omelet, and soft-boiled HE) (8).

Similar to what has been observed in IgE-mediated CM allergy, recent articles in the literature have shown that in a limited number of children with CM-triggered PedEoE, tolerance to baked CM was observed (4–6). In 2013, a retrospective analysis by Leung et al. showed that in a subgroup of children with CM-triggered EoE, 11/15 (73%) maintained histologic remission following the introduction of baked CM products (4). In 2019, Teoh et al. reported on a cohort of CM-triggered PedEoE with 24 children on a strict CM-free diet and 7 under a liberalized diet permitting the consumption of foods with traces of CM, including baked CM products. EoE remission was observed in 16/24 in the strict avoidance group and 2/7 in the liberalized group (5). Furthermore, González-Cervera et al. conducted a prospective study involving 18 patients with CM-triggered EoE in remission, where subjects consumed a minimum of 200 ml of sterilized CM (>100°C for 20') 2×/day over an 8-week period with 12/18 subjects maintaining endoscopic remission (6).

In contrast, Bianchi et al. reported on a 15-year-old who developed EoE during oral immunotherapy for a CM allergy and was initially permitted to eat baked CM products rather than adhering to a strict CM-free diet. Despite symptom resolution, a strict CM-free diet was ultimately required to induce histological remission (14).

Similar to the observed tolerance of heated CM in EoE, our two cases of HE-triggered PedEoE under treatment with tCS strongly suggest that heated HE may be well tolerated in HE-triggered PedEoE and that strict HE avoidance may not be universally required. In the first case, the introduction of a baked HE product (cake) resulted in the maintenance of EoE remission. Remarkably, the second case also tolerated a less heated form (hard-boiled HE) suggesting that in HE-triggered PedEoE, tolerance to less heated HE may be attainable.

The lower allergenic protein content of cake compared to a hard-boiled egg probably contributes to its reduced allergenicity. In the first case, it is plausible that reducing the amount of hard-boiled egg consumed may have been sufficient to maintain remission. However, the second case indicates that higher quantities of hard-boiled hen's egg may be tolerated in certain patients with HE-triggered PedEoE, while a less heated omelet in similar amounts was not tolerated.

Both patients received tCS therapy, which may have contributed to the maintenance of their remission. In case 1, the patient experienced a relapse following the reintroduction of wheat. tCS were reduced to 0.5 mg daily 3 months prior to this reintroduction. Unfortunately, remission did not occur after wheat was again eliminated but was only reestablished after the tCS dose was increased to 1 mg. This indicates that higher doses of tCS were needed to achieve remission. It is plausible that higher doses of tCS facilitated tolerance to the heated HE (rice flour cake), and that even this cake might not have been tolerated with a lower tCS dose. However, even at higher doses, less heated forms of hen's egg were not tolerated. In addition, it is clinically challenging to determine the exact timeframe during which therapeutic adjustments may still exert an effect (especially when multiple therapies are used concurrently). However, the literature suggests that an 8–12-week interval is generally considered sufficient to detect relapse on endoscopy (1). Complete withdrawal of tCS could, in this case, have indicated true tolerance to heated HE (cake), but this has not (yet) been performed.

In our two cases, tolerance acquisition may follow a gradual process analogous to that described in IgE-mediated HE allergy (8). This indicates that, on an individual basis, searching for the extent of HE tolerance in children with HE-triggered EoE may be worthwhile, and that further research is required to assess the extent to which complete raw HE tolerance can be achieved in children with HE-triggered EoE.

We presented two cases of successful heated HE reintroduction in children diagnosed with HE-triggered PedEoE under concomitant treatment with a tCS, while less heated forms were not tolerated, drawing parallels with the observed tolerance of baked CM products in children with CM-triggered EoE. Further research is imperative to investigate the potential for raw HE tolerance induction by introducing these HE products and to understand whether this tolerance acquisition follows a gradual process.