Eosinophilic esophagitis

EoE often presents with difficulty swallowing, food impaction, stomach pains, regurgitation or vomiting, and decreased appetite. Although the typical onset of EoE is in childhood, the disease can be found in all age groups, and symptoms vary depending on the age of presentation. In addition, young children with EoE may present with feeding difficulties and poor weight gain. It is more common in males and affects both adults and children. Many people with EoE have other autoimmune and allergic diseases such as asthma Mast cell disorders such as mast cell activation syndrome or mastocytosis are also frequently associated with it. == Pathophysiology ==

The pathophysiology of eosinophilic esophagitis is incompletely understood. Still, it is thought to involve some type of antigen exposure (coupled with a pre-existing genetic susceptibility), which causes a hyperactive immune response from immune cells in the esophagus. The antigenic exposure is thought to stimulate the esophageal epithelial cells to release the inflammatory cytokines IL-33 and thymic stromal lymphopoietin, which attract and activate Th2 helper T-cells. At a tissue level, EoE is characterized by a dense infiltrate with white blood cells of the eosinophil type into the epithelial lining of the esophagus. This is considered an allergic reaction against ingested food, based on eosinophils' important role in allergic reactions. The eosinophils are recruited into the tissue in response to the local production of eotaxin-3 by IL-13-stimulated esophageal epithelial cells. == Diagnosis ==

image of esophagus in a case of eosinophilic esophagitis. Concentric rings are termed trachealization of the esophagus. of the esophagus on the left side shows multiple rings associated with eosinophilic esophagitis. The diagnosis of EoE is typically made based on the combination of symptoms and findings from diagnostic testing. Radiologically, the term "ringed esophagus" has been used for the appearance of eosinophilic esophagitis on barium swallow studies to contrast with the appearance of transient transverse folds sometimes seen with esophageal reflux (termed "feline esophagus"). Endoscopy Endoscopically, ridges, furrows, or rings may be seen in the esophageal wall. Sometimes, multiple rings may occur in the esophagus, leading to the term "corrugated esophagus" or "feline esophagus" due to the similarity of the rings to the cat esophagus. The presence of white exudates in the esophagus also suggests the diagnosis. On biopsy taken at the time of endoscopy, numerous eosinophils can be seen in the superficial epithelium. A minimum of 15 eosinophils per high-power field are required to make the diagnosis. Eosinophilic inflammation is not limited to the esophagus alone and does extend through the whole gastrointestinal tract. Profoundly degranulated eosinophils may also be present, as may micro-abscesses and an expansion of the basal layer. Esophageal mucosal biopsy ), and edema seen as white clearings. Endoscopic mucosal biopsy remains the gold standard diagnostic test for EoE and is required to confirm the diagnosis. Atopy patch testing has been used in some cases for the potential identification of delayed, non-IgE (cell-mediated) reactions. Diagnostic criteria The diagnosis of eosinophilic esophagitis requires all of the following: • Symptoms related to esophageal dysfunction. • Eosinophil-predominant inflammation on esophageal biopsy, characteristically consisting of a peak value of ≥15 eosinophils per high power field (HPF). • Exclusion of other causes that may be responsible for symptoms and esophageal eosinophilia. == Treatment ==

EoE treatment aims to control the symptoms by decreasing the number of eosinophils in the esophagus and, subsequently, reducing esophageal inflammation. Management consists of dietary, pharmacological, and endoscopic treatment. Dietary management Dietary treatment can be effective, as allergies appear to play a role in developing EOE. Allergy testing is ineffective in predicting which foods drive the disease process. If no specific allergenic food or agent is present, a trial of the six-food elimination diet (SFED) can be pursued. Alternative options to SFED include the elemental diet, which is an amino acid-based diet. The elemental diet demonstrates a high rate of response (almost 90% in children, 70% in adults), with a rapid relief of symptoms associated with histological remission. This diet involves using amino acid-based liquid formulas for 4-6 wk, followed by the histological evaluation of response. If remission is achieved, foods are slowly reintroduced. Pharmacologic treatment In patients diagnosed with EoE, a trial of proton-pump inhibitors (PPI), such as esomeprazole 20 mg to 40 mg oral daily or twice daily as a first-line therapy, is a reasonable option. In those who respond to PPI therapy with symptomatic improvement, endoscopy with esophageal biopsy should be repeated. If no eosinophils are present in the repeat biopsy, the diagnosis is either acid-mediated GERD with eosinophilia or non-GERD PPI-responsive EoE with an unknown mechanism. If both symptoms and eosinophils persist after treatment with PPI, the diagnosis is immune-mediated EoE. Medical therapy for immune-mediated EoE primarily involves using corticosteroids. Systemic (oral) corticosteroids were one of the first treatment options shown to be effective in patients with EoE. Both clinical and histologic improvement have been noted in approximately 95% of EoE patients using systemic corticosteroids. However, upon discontinuation of therapy, 90% of patients using corticosteroids experience a recurrence in symptoms. In May 2022, U.S. Food and Drug Administration approved dupilumab (Dupixent) to treat eosinophilic esophagitis (EoE) in adults and pediatric patients 12 years and older weighing at least 40 kilograms (which is about 88 pounds) making it the first US FDA approved treatment for EoE. Endoscopic dilatation Flexible upper endoscopy is recommended to remove impacted food in patients with food impaction. Dilation is deferred in EoE until patients are adequately treated with pharmacological or dietary therapy and the result of a response to therapy is available. The goals of therapy for treating EoE are to improve the patient's symptoms and reduce the number of eosinophils on biopsy. Esophageal strictures and rings can be safely dilated in EoE. A graduated balloon catheter is recommended for gradual dilation. The patient should be informed that after dilation, they might experience chest pain and, in addition, risk of esophageal perforation and bleeding. == Prognosis ==

The long-term prognosis for patients with EoE is unknown. Some patients may follow a "waxing and waning" course characterized by symptomatic episodes followed by periods of remission. There have also been reports of apparent spontaneous disease remission in some patients; however, the risk of recurrence in these patients is unknown. Long-standing, untreated disease may result in esophageal remodeling, leading to strictures, Schatzki ring and, eventually, achalasia. The risk of esophageal strictures increases the longer eosinophilic esophagitis goes untreated, with a 9% increased incidence of strictures each year. == Risk factors ==

Many environmental factors can increase the risk of developing EoE, along with genetic factors that contribute to the disorder. The prevalence of EoE seems to be trending. There are many ongoing studies to try to find out why this may be the case. Risk factors for EoE include autoimmune conditions such as, inflammatory bowel disease and rheumatoid arthritis. Those with celiac disease, another autoimmune condition, are at higher risk of developing EoE as well. Individuals living in dry or cold climates as well as those living in areas of low population density are associated with higher rates of EoE. Food allergens are a risk factor of EoE and can often be directly attributed to the disease. Often, removing these food allergens from the diet can resolve EoE symptoms. == Epidemiology ==

The prevalence of eosinophilic esophagitis has increased over time and currently ranges from 1 to 6 per 10,000 persons. Gender and ethnic variations exist in the prevalence of EoE, with most cases reported in Caucasian males. In addition to gender (male predominance) and race (mainly a disease of Caucasian individuals), established risk factors for EoE include atopy and other allergic conditions. Other recognized genetic and environmental risk factors for EoE include alterations in gut barrier function (e.g. GERD), variation in the nature and timing of oral antigen exposure, lack of early exposure to microbes, and an altered microbiome. A study comparing active EoE children to non-EoE children found an altered microbiome due to a positive correlation between a relatively high abundance of Haemophilus and disease activity seen through an increasing Eosinophilic Esophagitis Endoscopic Reference Score and Eosinophilic Esophagitis Histologic Scoring System (q value = 5e-10). Measuring the relative abundance of specific taxa in children's salivary microbiome could serve as a noninvasive marker for eosinophilic esophagitis. ==History==

The first case of eosinophilic esophagitis was reported in 1978. In the early 1990s, it became recognized as a distinct disease. == See also ==