This chapter presents an overview of eosinophilic esophagitis (EoE) for the Primary Care Practitioner (PCP). The focus is on helping PCPs keep it in their differential diagnosis by discussing the spectrum of clinical presentations, how to screen for EoE in at-risk populations and subsequently manage the patient with this condition. The authors review epidemiology, risk factors and associated conditions, pathology, clinical presentation, diagnosis, and management options.
Eosinophilic Esophagitis , Primary Health Care , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/therapy , Eosinophilic Esophagitis/epidemiology , Humans , Risk Factors , Diagnosis, Differential , Proton Pump Inhibitors/therapeutic use
Immunotherapy is a treatment approach based on the principle of incremental allergen exposure to achieve desensitization. Recently, oral immunotherapy has been introduced as a treatment of IgE-mediated food allergy. Some patients receiving oral immunotherapy for food allergy may develop eosinophilic esophagitis. Here, we summarize the literature examining this association, its treatment, and outcomes and discuss possible explanations for this clinical phenomenon. We further identify potential associations with aeroallergen sensitivity and other forms of immunotherapy including subcutaneous immunotherapy and sublingual immunotherapy. Finally, we discuss management of immunotherapy-induced eosinophilic esophagitis. Epicutaneous immunotherapy is highlighted as an area of therapeutic investigation.
Eosinophilic Esophagitis , Food Hypersensitivity , Sublingual Immunotherapy , Humans , Eosinophilic Esophagitis/etiology , Eosinophilic Esophagitis/therapy , Desensitization, Immunologic/adverse effects , Food Hypersensitivity/drug therapy , Allergens/therapeutic use
Eosinophilic esophagitis (EoE) is a chronic and progressive immune-mediated esophageal disorder. Given its increasing incidence, it is now a leading cause of dysphagia and food impaction in the United States. Eosinophilic esophagitis is most common in adult White men and has a high concurrence rate with other atopic conditions like allergic rhinitis, bronchial asthma, and eczema. The initial presentation includes symptoms of esophageal dysfunction, classically solid-food dysphagia. Without treatment, inflammation can progress to fibrosis with the formation of strictures, leading to complications such as food impaction. It is a clinicopathologic disease requiring compatible clinical symptoms and histologic evidence of eosinophil-predominant inflammation of the esophageal epithelium with more than 15 eosinophils per high-power field. The mainstay of management includes the 3 d's (diet, drugs, dilation): dietary modifications to eliminate trigger food groups; medications including proton pump inhibitors, swallowed topical glucocorticoids, and dupilumab; and esophageal dilation to manage strictures. Various elimination diets have been found to be effective, including 1-food, 2-food, 4-food, and 6-food elimination diets. Dupilumab, a humanized monoclonal antibody that regulates interleukin 4 and 13 signaling pathways, has shown promising results in clinical trials and was approved by the Food and Drug Administration in 2022 for use in EoE. Symptom alleviation, although important, is not the sole end point of treatment in EoE as persistent inflammation, even in the absence of symptoms, can lead to esophageal fibrosis and stricture formation over time. The chronic nature and high recurrence rates of EoE warrant maintenance therapy in patients with EoE after initial remission is achieved.
Deglutition Disorders , Eosinophilic Esophagitis , Gastroenterologists , Male , Adult , Humans , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/therapy , Deglutition Disorders/etiology , Deglutition Disorders/therapy , Constriction, Pathologic/complications , Constriction, Pathologic/drug therapy , Inflammation/drug therapy , Fibrosis , Primary Health Care , Proton Pump Inhibitors/therapeutic use
Most of the major clinical signs and consequences of eosinophilic esophagitis seem to be related to tissue remodeling. Important data on remodeling activity in patients with eosinophilic esophagitis are provided by a range of current and new biologic markers and diagnostics. To completely clarify the possible advantages and restrictions of therapeutic approaches, clinical studies should take into consideration the existence and reversibility of esophageal remodeling. The degree of mucosal or submucosal disease activity may not be reflected by epithelial eosinophilic inflammation, which is used to define one criterion of disease activity".
Enteritis , Eosinophilia , Eosinophilic Esophagitis , Gastritis , Humans , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/therapy , Fibrosis
The diagnosis of eosinophilic esophagitis (EoE) is based on clinical symptoms of esophageal dysfunction and eosinophil predominant esophageal inflammation. Clinical symptoms in children with EoE vary based on age and may be nonspecific. EoE has a male predominance with the majority having comorbid atopic disorders. At present, treatment options include medications (proton pump inhibition, swallowed topical steroids), dietary therapy or biologic therapy (dupilumab, approved for those ≥12 years of age). Outside of EoE in the context of oral immunotherapy, EoE is typically chronic requiring lifelong therapy. Long-term complications including feeding difficulties, malnutrition, and fibrostenotic disease.
Enteritis , Eosinophilia , Eosinophilic Esophagitis , Gastritis , Child , Male , Humans , Female , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/therapy , Glucocorticoids/therapeutic use , Enteritis/drug therapy
Adult patients with eosinophilic esophagitis (EoE) typically present with a history of dysphagia for solids, sometimes with additional reflux-like pain and a history of prior food impactions. In contrast to these alarming symptoms, the general appearance and physical examination of adult patients with EoE is in line with apparently healthy individuals. Therefore, the diagnosis is based on a history of solid-food dysphagia and eosinophilic tissue infiltration. Importantly, the increasing prevalence of EoE variants, that is, typical EoE symptoms in the absence of a relevant eosinophilia, and several studies with eosinophil-targeting drugs, call the pathogenic role of eosinophils into question.
Deglutition Disorders , Enteritis , Eosinophilia , Eosinophilic Esophagitis , Gastritis , Adult , Humans , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/epidemiology , Eosinophilic Esophagitis/therapy , Deglutition Disorders/diagnosis , Deglutition Disorders/etiology , Deglutition Disorders/pathology , Eosinophils , Inflammation/pathology
Edema, rings, exudates, furrows, and strictures (EREFS) represent the major endoscopic features of eosinophilic esophagitis (EoE). The Endoscopic Reference System (EREFS) grading system is easy to learn and apply during daily clinical practice in the diagnosis and follow-up of EoE patients. When endoscopy is performed by an EoE-experienced physician, the EREFS criteria will identify the majority of EoE patients. The EREFS score from the area of greatest involvement of the esophagus should be reported. The EREFS grading system was formally validated as an endoscopy score and several randomized placebo-controlled trials have shown responsiveness of the EREFS score to therapeutic interventions.
Eosinophilic Esophagitis , Humans , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/therapy , Esophagoscopy , Severity of Illness Index
Microscopic examination of esophageal biopsies is essential to diagnose eosinophilic esophagitis (EoE). Eosinophil inflammation is the basis for the diagnosis, but additional abnormalities may contribute to persistent symptoms and epithelial barrier dysfunction. Both peak eosinophil count and assessments of additional features should be included in pre-therapy and post-therapy pathology reports. Pathologic abnormalities identified in esophageal biopsies of EoE are reversible in contrast to esophageal strictures.
Enteritis , Eosinophilia , Eosinophilic Esophagitis , Gastritis , Humans , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/therapy , Eosinophils , Biopsy
Eosinophilic esophagitis (EoE) is a chronic immune-mediated food allergy-driven disease characterized by eosinophilic inflammation of the esophagus leading to symptoms of esophageal dysfunction. Prior studies have supported the key role of food allergen exposure as the main driver behind the etiopathogenesis showing that removal of food antigens can result in disease remission in both children and adults. These landmark studies serve as the basis for the rising interest and evolution of dietary therapy in EoE. This article will focus on the rationale for dietary therapy in EoE and provide helpful tools for the implementation of dietary therapy in practice.
Eosinophilic Esophagitis , Food Hypersensitivity , Adult , Child , Humans , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/therapy , Diet , Food Hypersensitivity/therapy , Food Hypersensitivity/diagnosis , Food , Allergens
Feeding is a complex skill requiring coordination of multiple body systems. Multiple factors are considered in feeding dysfunction in pediatric patients with eosinophilic gastrointestinal disorders, including overall development, nutritional status, mealtime behaviors, and medical comorbidities. Symptoms of feeding dysfunction vary by age, with maladaptive learned feeding behaviors spanning all age ranges. Knowledge of the normal acquisition of feeding skills is critical to interpret the impact of the disease and plan appropriate intervention. Assessment and treatment from a feeding and swallowing disorders specialist can dramatically impact successful outcomes in nutrition, growth, mealtime dynamics and ultimatly quality of life for children and their caregivers in home and social settings.
Deglutition Disorders , Enteritis , Eosinophilia , Eosinophilic Esophagitis , Gastritis , Child , Humans , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/therapy , Quality of Life , Deglutition Disorders/diagnosis , Deglutition Disorders/etiology , Deglutition Disorders/therapy
Mast cells play a central role in the pathogenesis of eosinophilic gastrointestinal disorders (EGIDs), including eosinophilic esophagitis. Their interactions with immune and structural cells, involvement in tissue remodeling, and contribution to symptoms make them attractive targets for therapeutic intervention. More is being discovered regarding the intricate interplay of mast cells and eosinophils. Recent studies demonstrating that depletion of eosinophils is insufficient to improve symptoms of EGIDs have raised the question of whether other cells may play a role in symptomatology and pathogenesis of EGIDs.
Enteritis , Eosinophilia , Eosinophilic Esophagitis , Gastritis , Humans , Mast Cells , Enteritis/therapy , Enteritis/diagnosis , Gastritis/diagnosis , Gastritis/therapy , Eosinophilic Esophagitis/therapy , Eosinophilic Esophagitis/diagnosis
Eosinophilic gastrointestinal disorders (EGIDs) are becoming more common causing significant suffering and reduced quality of life. These conditions can affect different parts of the digestive system, either individually or in combination. Recognition of their link to allergic disorders or other gastrointestinal (GI) diseases has raised questions about their shared underlying mechanisms, which has had implications for diagnosis and management. The authors critically examine the current understanding of the connection between EGIDs and allergic conditions (ie, atopic dermatitis, allergic rhinitis, asthma, and food allergy) and GI diseases (ie, inflammatory bowel disease, celiac disease, gastroesophageal reflux disease, and motility disorders).
Dermatitis, Atopic , Enteritis , Eosinophilia , Eosinophilic Esophagitis , Gastritis , Humans , Quality of Life , Eosinophilia/diagnosis , Eosinophilia/complications , Gastritis/diagnosis , Gastritis/complications , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/epidemiology , Eosinophilic Esophagitis/therapy
Measuring health-related quality of life (HRQOL) gained relevance in research and clinical practice in patients with eosinophilic esophagitis. The physical discomfort and social and psychological consequences of this food-related disease substantially affect HRQOL. Determinant of an impaired HRQOL include symptom severity, disease duration, biological disease activity, and psychological factors. Patients prioritize symptom relief and improved HRQOL as treatment objectives. Available treatment options can address these goals; however, there is a suboptimal adherence to treatment. There is a need for enhanced patient guidance and education. The assessment of HRQOL will help to prioritize patient's needs in management.
Enteritis , Eosinophilia , Eosinophilic Esophagitis , Gastritis , Humans , Quality of Life/psychology , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/therapy , Food
Eosinophilic gastrointestinal diseases (EGIDs) including eosinophilic esophagitis (EoE) are rare diseases in which eosinophils abnormally infiltrate the gastrointestinal tract. Because these are rare diseases, there is limited information regarding race and ethnicity in EGIDs and even less is known about the impact of socioeconomic factors. There is some evidence that access to care in rural settings may be affecting epidemiologic understanding of EGIDs in the pediatric populations. Future work should try to evaluate bias in research and strive for representation in clinical trials and medicine.
Enteritis , Eosinophilia , Eosinophilic Esophagitis , Gastritis , Child , Humans , Diversity, Equity, Inclusion , Rare Diseases , Eosinophilic Esophagitis/epidemiology , Eosinophilic Esophagitis/therapy
Endoscopic evaluation with biopsies is a mainstay of the diagnosis of eosinophilic esophagitis (EoE) and non-EoE eosinophilic gastrointestinal diseases (EGIDs). Increasing knowledge has resulted in the development of 2 standardized scoring systems: the Endoscopic REFerence Score (EREFS) for EoE and the EG-REFS for eosinophilic gastritis, although the latter has not been validated. In EGIDs, diagnosis and follow-up focus on eosinophil infiltration in biopsies. In this article, we will discuss the most commonly used endoscopic scores in EoE and non-EoE EGIDs, their validity for the diagnosis and follow-up of disease activity, as well as endoscopic interventions and areas of uncertainty.
Enteritis , Eosinophilia , Eosinophilic Esophagitis , Gastritis , Humans , Endoscopy/methods , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/therapy , Enteritis/diagnosis , Enteritis/therapy , Gastritis/diagnosis
Eosinophilic gastrointestinal diseases (EGID), such as eosinophilic gastritis (EoG), eosinophilic enteritis, and eosinophilic colitis (EoC), are chronic inflammatory conditions characterized by persistent gastrointestinal symptoms and elevated levels of activated eosinophils in the gastrointestinal tract. EoG and eosinophilic duodenitis (EoD) are strongly associated with food allergen triggers and TH2 inflammation, whereas EoC shows minimal transcriptomic overlap with other EGIDs. The level of expression of certain genes associated with TH2 immune response is associated with certain histopathologic findings of EoG, EoD, and EoC. Current immune therapy for EoG depletes tissue eosinophilia with persistence of other histopathologic features of disease.
Enteritis , Eosinophilia , Eosinophilic Esophagitis , Gastritis , Humans , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/therapy , Enteritis/diagnosis , Enteritis/therapy , Gastritis/diagnosis , Gastritis/therapy , Inflammation
The clinical presentation of eosinophilic gastrointestinal diseases beyond eosinophilic esophagitis (non-EoE EGIDs) varies depending on the gastrointestinal segments affected by the eosinophilic inflammation, the extent of eosinophilic inflammation within the gastrointestinal tract and its depth through the bowel wall. Non-EoE EGIDs with mucosal involvement tend to present with diarrhea, malabsorption, and sometimes bleeding, those with muscular involvement may present with symptoms of obstruction or pseudo-obstruction, intussusception, and even perforation, whereas those with serosal involvement may present with eosinophilic ascites. Here we describe the differences in symptoms experienced by children with non-EoE EGIDs with varying degrees of eosinophilic inflammation through the bowel wall.
Enteritis , Eosinophilia , Eosinophilic Esophagitis , Gastritis , Child , Humans , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/therapy , Gastritis/diagnosis , Enteritis/diagnosis , Enteritis/therapy , Inflammation
