LAUSR

Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease of the esophagus that is triggered by specific foods. EoE presents across the lifespan, with symptoms of failure to thrive, poor weight gain, feeding intolerance, food refusal, vomiting, dysphagia and food impaction [1,2]. Any patient may present with symptoms of EoE, regardless of preexisting risk factors. All patients with symptoms of esophageal dysfunction suggestive of EoE should receive screening via esophagogastroduodenoscopy (EGD) with esophageal biopsies [3,4]. However, many patients with EoE develop symptoms slowly over time, and the frequency of compensatory eating behaviors is high in this population [5–7]. Therefore, it is important to consider which patient populations may be at increased risk for the development of EoE and ask targeted screening questions in order to pinpoint esophageal symptoms. Here we review epidemiologic and clinical features that may increase suspicion for EoE. A family or personal history of the preexisting allergic disease should increase the suspicion for EoE, as it has been reproducibly demonstrated in multiple cohorts that individuals with EoE have a high prevalence of allergic comorbidity [8,9]. As atopic disorders are prevalent, screening for EoE is an important consideration for general pediatricians in addition to allergists. A recent meta-analysis by González-Cervera et al. examined 21 observational case-control studies of 53,542 individual EoE patients, demonstrating that EoE patients have higher rates of allergic comorbidity than the background population [10]. The odds of a personal history of atopy in EoE patients was increased, including reported rates of eczema (odds ratio [OR] 2.85, 95% confidence interval [CI] 1.87–4.34), allergic rhinitis (AR; OR 5.09, 95% CI 2.91–8.90), and asthma (OR 3.01, 95% CI 1.96–4.62). Using a large pediatric virtual birth cohort, we have measured these risk relationships in individuals revealed that history of AD (hazard ratio [HR] 3.2, 95% confidence interval [CI] 2.2–4.6), IgE-mediated food allergy (IgE-FA; HR 9.1, 95% CI 6.5–12.6), and asthma (HR 1.9, 95% CI 1.3–2.7) are independently and cumulatively associated with subsequent EoE diagnosis (Table 1) [11]. The relationship between IgE-FA and EoE is particularly strong – children with IgE-FA develop EoE at 9 times the rate of children without IgE-FA [12]. IgE-FA and EoE have been reported to co-occur at rates between 9.8% and 44% in EoE cohorts, up to as high as 68% [10,13]. Specifically, IgE-FA to milk, egg or shellfish has been associated with the development of EoE [13]. Barbosa et al. studied esophageal eosinophilia in a pediatric cohort with persistent milk IgEFA and found that 38% had esophageal eosinophilia on biopsy with 23.5% of the patients exhibiting symptoms [14]. In a cohort of adult patients with IgE-FA undergoing screening prior to oral immunotherapy (OIT), Wright et al. found 14% of the patients had >15 eosinophils per high-power field (eos/ hpf) [15]. These studies illustrate a growing recognition of the unique risk association between IgE-FA and EoE. An additional concern is the risk for EoE development in IgEFA patients on oral immunotherapy for food allergy. The risk of developing EoE has been quantitated in recent reviews as between 2.7%-5.3%, however, this is likely an underestimate. Gastrointestinal side effects like abdominal pain and vomiting are common in OIT, with approximately 30% of the patients reporting these symptoms which can be presenting symptoms of EoE. However, biopsies to assess for EoE were performed in a minority of studies [16,17]. This suggests that the rate of EoE is increased in OIT patients and if symptoms are persistent they should be screened with biopsy to assess for EoE. Multiple reports have shown EoE to be associatedwith several non-allergic disorders including gastrointestinal, autoimmune disorders, and connective tissue diseases (Table 2) [18–20]. The association of EoE with celiac disease has been reported but is somewhat uncertain. We have recently seen an association between EoE and celiac disease in our pediatric referral population, with 3–5.6% of the celiac disease patients with concurrent esophageal eosinophilia on biopsy [9,21,22]. While some investigators have seen similar associations, some studies have not observed this association [23,24]. Esophageal eosinophilia has been also noted to precede or coexist with the development of inflammatory bowel disease, and the incidence of IBD in patients diagnosed with EoE in our cohort of pediatric patients is increased [9,25,26]. However, the precise clinical or mechanistic relationship of tissue eosinophilia to IBD has not been established. It is debated whether the increased association of someGI disorders with EoE results from potential bias associated with increased endoscopic screening or points to commonly dysregulated immune mechanisms.