Eosinophilic esophagitis

Immune mediated chronic disease with symptoms of esophageal dysfunction, eosinophilic infiltration of the esophagus that persists after a proton pump inhibitor trial, and excludes secondary causes of eosinophilia.

It is characterized by type 2 helper T inflammation involving T cells, eosinophils, mast cells, and the cytokines Interleukin 4, Interleukin 5, Interleukin 13, and thymic stromal lymphopoeitin: these cells and mediators are targets for anti-inflammatory drugs.

A chronic progressive, type two inflammatory disease that has substantial impairment of quality of life.

The incidence of EE is approximately 7.7/100,000 per year in adults, and affects an estimated 34.4/100,000 people in Europe and North America.
Its prevalence has increased rapidly and currently affects approximately one in 3000 persons.

Its incidence is increasing perhaps related to increased awareness of the diagnosis, increased biopsy sampling of the esophagus, and the generalized increase in atopic diseases.

EE is strongly associated with type two allergic inflammatory processes with more than 90% of patients having other atopic conditions, such as seasonal allergies, atopic dermatitis, or eosinophilic asthma.

Its etiology is related to both genetic and environmental factors: frequency of eosinophilic esophagitis of  one sibling is diagnosed with disease is 41% in monozygotic twins, 24% in dizygotic twins, and 2.4% and other siblings.

Associated with a dysregulated immune response to ingested food products including milk, egg, and wheat.
Its clinical presentation varies significantly with age at presentation.
Infants and young children are more likely to present with non-specific symptoms: signs of failure to thrive, feeding difficulties, and vomiting.
Adolescents and adults typically have symptoms associated with esophageal fibrosis, with more than 40% presenting with dysphasia and 30% present with food impaction.
Adults commonly experience, dysphasia and heartburn.
The most common symptom in adults is dysphagia with solid food intake, often leading to food impaction.
EE can cause esophageal structures and is the most common cause of esophageal food impaction, which may present with choking, chest and neck or throat, pain, dysphasia or odynophagia.
Approximately 50% of patients with EE present emergently with an esophageal food impaction requiring endoscopic removal.
With patients who have a long period of untreated inflammation there is a higher association of esophageal fibrosis, dysphasia, and food impaction.
If auntreated esophageal fibrosis and remodeling can lead to structures, food impaction and other medical complications.
In patients with symptoms of EE for more than 21 years at the time of diagnosis, patients have a higher incidence of strictures,  and esophageal food impactions at 52% and 57%, respectively.
In patients with symptom duration of less than two years at the time of diagnosis the proportions of strictures and esophageal food fractions are 19 and 24%, respectively.
It is estimated that for each year of untreated EE symptoms, the risk of stricture increases by 9%.
EE is defined by symptoms of esophageal dysfunction, such as vomiting, dysphasia, or feeding difficulties, in a patient with biopsies of the esophagus that demonstrate at least 15 eosinophils per high power field in the absence of other conditions associated with esophageal  eosinophilia,  such as GERD, achalasia, vasculitis, hypereosinophilic Syndrome, Crohn’s Disease, Ehlers-Danlos syndrome, graft versus host disease, infections, and drug hypersensitivity.

This threshold is 100% sensitive and 96% specific for diagnosis.

Also known as allergic esophagitis.

Directly related to food antigens.

Exposure to certain food types-wheat, dairy, eggs, soy, peanuts, tree nuts, fish, or shellfish, in susceptible individuals is associated with infiltration of the esophageal epithelium by eosinophils,  T cells, and mast cells.

Contributing to inflammation and stimulating fibroblast in the lamina propria to deposit collagen includes thymic stromal lymphopoietin, IL – 33, IL – 4, IL – 5, and IL – 13, resulting in esophageal fibrosis.

Leading cause of emergency department visits for food impaction in the US.

Increasing incidence and prevalence may be due to increased recognition as well as an increase in atopic diseases.

The second most common cause of chronic esophagitis, the first being gastroesophageal reflux disease.

A leading cause of esophageal morbidity among children and adults.

The diagnosis of pediatric EoE is increasing at an alarming rate and affects approximately four of every 10,000 children in the US.

A leading cause of dysphagia.

The onset can be insidious, and diagnosis is often delayed with the potential for the development of irreversible sequelae.

Effects infants, children, and adults.

A worldwide process with highest degree of disease in North America, Western Europe, and Australia.

Prevalence in the US estimated from 40-90 cases per 100,000 persons.

The prevalence ranges from 12-22% among patients undergoing upper endoscopy for evaluation of dysphasia.

Etiology incompletely understood, but suggests activation of Th2 immune cells.

Patients frequently have a history of atopic disease or food allergies.

It is more common among 1st-degree relatives of patients with EE.
Genome studies suggested 31 different genes that are associated with EE.
Endoscopic features include: linear furrows and mucosal rings, extensive infiltration of eosinophils and epithelial hyperplasia.

Allergen-free formulas are utilized to treat the condition.

Dietary antigens can be triggers of disease and it is suspected environmental factors play a larger etiologic roll and than genetics.

Symptoms are swallowing difficulty, food impaction, and heartburn.

Characterized by symptoms and signs of esophageal dysmotility from underlying chronic inflammation of the esophagus.

Characterized by eosinophilic infiltration into the esophagus that persists after a proton pump inhibitor trial.

Chronic inflammation leads to remodeling of the esophagus including fibrosis, rings, linear furrows, and stricture formation.

Children tend to present with vomiting, abdominal pain, and or a failure to thrive, while adults often have dysphagia, food impaction, and heartburn.

The treatment may consist of removal of known or suspected triggers, medication to suppress the immune response, but it may be necessary to dilate the esophagus.

Treatment has 2 important goals: to control symptoms and to control inflammation.

There os no excepted first line therapy, and no therapy is 100% effective.
Diet modifications may lead to remission by eliminating causative triggers.
Removal of foods, including: dairy, wheat, eggs, soy, peanuts, and tree nuts, fish, and shellfish.
Rarely an elemental liquid diet is used to is composed of amino acids, sugars, fats, vitamins, and minerals.
PPIs or effective in 30 to 50% of patients with EE.

EE has only two medications, budesonide, a swallowed topical glucocorticoid and dupilumab that have been approved.

BecauseEE  is a non-IgE mediated allergic disease, attempts to eliminate allergens may result in disease remission in some patients.

Dietary therapy includes: an elemental diet of drinking of formula without any intact proteins, empirical food elimination, and allergy test directed food elimination.

An elemental diet consists of a liquid form of nutrition with amino acids, fats, sugars, vitamins, nutrients that are readily assimilated and absorbed.

An elemental diet is associated with a 93.6% histologic remission rate compared with 13.3% for a historical placebo.

An elemental diet is costly, inconvenient, associated with an undesirable taste, and it can be difficult to insure  sufficient formula to maintain weight.

 This dietary elimination diet is associated with the histological response in EE of 67.9% of patients compared with 13.3% in historical placebo comparison group.

Dairy, wheat, and eggs are the most commonly implicated food groups.

 PPIs in EE may have anti-inflammatory effects independent of gastric acid suppression with antioxidant properties, inhibition of immune cell function, and reduction of epithelial cell inflammatory cytokines expression.

PPI therapy is associated with a 40% histological and 60% clinical response in EE.

PPIs are a reasonable first line therapy.

Swallowed corticosteroids are the mainstay of treatment for EE.

Fluticasone swallowed twice daily from a multidose inhaler or oral viscous budesonide are efficacious.

Topical corticosteroid treatment has  a response rate with histological remission  in up to 65% of patients.

Dupilumab binds to the interleukin 4 receptor alpha subunit shared by interleukin 4 and interleukin 13 receptors and inhibits the signaling signaling of two key drivers of eosinophilic esophagitis.

Approximately 60% of patients have histological remission after 24 weeks of treatment.

Young children may present with feeding difficulties and poor weight gain.

More common in males.

Many patients with have other autoimmune and allergic disease, including asthma and celiac disease.

Histologically, characterized by a dense infiltrate with white blood cells of the eosinophil type into the epithelial lining of the esophagus.

Thought to be an allergic reaction against ingested food, based on the important role eosinophils play in allergic reactions.

Eosinophils inflame the surrounding esophageal tissue.

Visible redness on endoscopy, and

Natural history that may include stricturing.

Endoscopic image of esophagus includes concentric rings termed trachealization of the esophagus.

The barium swallow of the esophagus shows multiple rings associated with eosinophilic esophagitis.

Endoscopically, ridges, furrows, or rings may be seen.

The diagnosis made on the combination of symptoms and findings on diagnostic testing.

The diagnosis is established by clinical symptoms and esophageal eosinophils with 15 or more eosinophils per high-powered field.
Diagnosis requires endoscopy with biopsy.
Endoscopic findings include furrows trachealization, , exudates,edema, and stricture.
It is recommended that a minimum of six biopsies be obtained for diagnostic purposes, as approximately 10-25% of patients with EE have a normal appearance on endoscopy.
Circulating levels of Eosinophil granule proteins including major basic protein are elevated in eosinophilic disorders and cause side of toxic activities.

The disease affects the esophagus and then a regular, patchy pattern and at least five or more biopsies should be obtained for diagnosis.

Does not respond to a 6 week trial of proton-pump inhibitors (PPIs.

White exudates in esophagus is also suggestive of the diagnosis.

On biopsy numerous eosinophils seen in the superficial epithelium, with a minimum of 15 eosinophils per high-power field are required to make the diagnosis.

Eosinophilic inflammation extends through the whole gastrointestinal tract.

Eosinophils release  cationic toxic granular proteins including eosinophil major basic protein-1 into the affected esophagus and this deposition may be a better indicator of disease activity than eosinophili counts.
Electron microscopy shows that more than 80% of eosinophils have disrupted membranes.
The initial approach is often allergy evaluation in an attempt to identify the allergens in the diet or environment that may be triggering the condition.

Treatments include an elimination diet, proton pump inhibitors, topical steroids, dilation.

Treatment is with swallowed liquid corticosteroids and other anti-inflammatories.

Patients with severe symptoms may require oral corticosteroids.

Mechanical dilatation may be considered in cases that have progressed to esophageal stricture or severe stenosis.

Endoscopic dilatation is an option for treating esophageal strictures, rings, and narrow caliber esophagus from eosinophilic esophagitis.

Esophageal dilatation is associated with clinical improvement in 95% of patients with EE and a median duration of improvement of 12 months.

After treatment follow up endoscopy is typically recommended to document histologic remission.
Remission must be maintained, because actively  esophageal Inflammation  is associated with fibrostenosis and stricture.
A mesh sponge capsule analysis has a sensitivity of 75% in specificity of 86% for determining skin determining disease activity, anddefined by Eosinophilic count on biopsy.
An esophageal string test uses a capsule within absorptive string, has a similar sensitivity and specificity for determining disease activity.
Because of the likelihood of recurrent symptoms maintenance topical steroids are considered.
Among patients with eosinophilic esophagitis subcutaneous dupilumab improves histological outcomes and alleviated symptoms of the disease.

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