Eosinophilic Esophagitis
Disease Details
Family Health Simplified
- Description
- Eosinophilic esophagitis is a chronic immune system disease that causes inflammation or swelling of the esophagus due to an overabundance of eosinophils, a type of white blood cell.
- Type
- Eosinophilic esophagitis is a chronic, allergic/immune condition. There is some evidence suggesting that genetic factors may contribute to the development of the disease, indicating a potential familial pattern. However, the exact mode of genetic transmission is not entirely clear and is likely to be complex, involving multiple genetic and environmental factors.
- Signs And Symptoms
- 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.Predominant symptoms in school-aged children and adolescents include difficulty swallowing, food impaction, and choking/gagging with meals- particularly when eating foods with coarse textures. Other symptoms in this age group can include abdominal/chest pain, vomiting, and regurgitation. The predominant symptom in adults is difficulty swallowing; however, intractable heartburn and food avoidance may also be present. Due to the long-standing inflammation and possible resultant scarring that may have gone unrecognized, adults presenting with EoE tend to have more episodes of esophageal food impaction as well as other esophageal abnormalities such as Schatzki ring, esophageal webs, and in some cases, achalasia.Although many of these symptoms overlap with the symptoms of GERD, the majority of patients with EoE exhibit a poor response to acid-suppression therapy. Many people with EoE have other autoimmune and allergic diseases such as asthma and celiac disease. Mast cell disorders such as Mast Cell Activation Syndrome or Mastocytosis are also frequently associated with it.
- 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. It is possible that 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.
- Onset
- Eosinophilic esophagitis (EoE) can onset at any age, but it is commonly diagnosed in childhood or early adulthood. The age of onset varies widely among individuals.
- Prevalence
- The prevalence of eosinophilic esophagitis (EoE) is estimated to be approximately 1 in 2,000 individuals, though this can vary by region. It is more commonly diagnosed in males than females and is seen across all age groups, with an increasing recognition and diagnosis in both children and adults.
- 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 the majority of 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.
- Intractability
- Eosinophilic esophagitis (EoE) is not necessarily intractable, but it can be chronic and challenging to manage. Treatment typically involves dietary modifications, proton pump inhibitors, and topical corticosteroids to reduce eosinophil levels and alleviate symptoms. With appropriate treatment, many patients can achieve symptom relief and improved quality of life. However, ongoing management and monitoring are often required to control the condition and prevent recurrence.
- Disease Severity
- Disease severity for eosinophilic esophagitis (EoE) can vary from mild to severe. Symptoms may include difficulty swallowing, food impaction, and heartburn. Severity often correlates with the degree of esophageal inflammation and fibrosis found during endoscopy and biopsy.
- Healthcare Professionals
- Disease Ontology ID - DOID:13922
- Pathophysiology
- The pathophysiology of eosinophilic esophagitis is incompletely understood, but it is thought to involve some type of an 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. These helper T-cells the release pro-inflammatory cytokines including IL-13, IL-4 and IL-5. These inflammatory cytokines, coupled with the T-cell response cause inflammation in the esophagus as well as stimulate basal cell hyperplasia and dilated intracellular spaces of the esophageal cells, characteristic histologic changes of the disease. The IL-5 released by the helper T-cells and eotaxin-3 act as chemotaxins, attracting granulocytes to the esophagus, including basophils, mast cells and eosinophils, with the eosinophilic infiltration giving the disease its characteristic histological changes.Eosinophils are inflammatory cells that release a variety of chemical signals which inflame the surrounding esophageal tissue. This results in the signs and symptoms of pain, visible redness on endoscopy, and a natural history that may include stricturing. Eosinophils are normally present in other parts of a healthy gastrointestinal tract, these white blood cells are not normally found in the esophagus of a healthy individual. The reason for the migration of eosinophils to the tissue of the esophagus is not fully understood but is being studied extensively. It is thought the migration of eosinophils to the esophagus may be due to genetic, environmental, and host immune system factors.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 thought to be an allergic reaction against ingested food, based on the important role eosinophils play in allergic reactions. The eosinophils are recruited into the tissue in response to local production of eotaxin-3 by IL-13 stimulated esophageal epithelial cells.
- Carrier Status
- Eosinophilic esophagitis (EoE) is not typically associated with a carrier status. It is a chronic immune/antigen-mediated disease that involves eosinophils (a type of white blood cell) accumulating in the esophagus, leading to inflammation and damage. EoE is generally considered to be influenced by genetic and environmental factors rather than a single gene mutation with carriers.
- Mechanism
-
Eosinophilic esophagitis (EoE) is an allergic/immune condition characterized by eosinophil accumulation in the esophagus, leading to inflammation and esophageal dysfunction.
**Mechanism:**
1. **Allergen exposure:** The condition is often triggered by exposure to certain allergens, either through ingestion (food allergens) or inhalation (environmental allergens).
2. **Immune response:** These allergens stimulate an immune response that involves various components of the immune system, particularly Th2 helper T cells, which release cytokines such as IL-4, IL-5, and IL-13.
3. **Eosinophil recruitment:** These cytokines promote the recruitment and activation of eosinophils, which are a type of white blood cell, to the esophageal tissue.
4. **Inflammation and tissue damage:** Eosinophils release cytotoxic granules and other inflammatory mediators, causing tissue damage, chronic inflammation, and remodeling of the esophageal lining, which can lead to fibrosis and strictures.
**Molecular mechanisms:**
1. **Cytokines and chemokines:** Interleukins IL-5 and IL-13 are critical for the proliferation and survival of eosinophils. Chemokines such as eotaxin-3 (CCL26) are also involved in attracting eosinophils to the esophagus.
2. **Barrier dysfunction:** Allergen exposure can lead to increased esophageal epithelial permeability, allowing more allergens to penetrate the tissue and perpetuate the immune response.
3. **Cell signaling pathways:** The signaling pathways mediated by the cytokines and chemokines activate various intracellular mechanisms in the eosinophils and esophageal epithelial cells, contributing to their activation, survival, and the production of more inflammatory mediators.
4. **Genetic predisposition:** Several genetic factors have been associated with a predisposition to EoE, including variations in the genes encoding for thymic stromal lymphopoietin (TSLP) and calpain 14 (CAPN14), which may influence the immune response and esophageal epithelial integrity.
Understanding these mechanisms provides insight into potential therapeutic targets and treatment strategies for managing eosinophilic esophagitis. - Treatment
- The goal of EoE treatment is to control the symptoms by decreasing the number of eosinophils in the esophagus and, subsequently, reducing the esophageal inflammation. Management consists of dietary, pharmacological, and endoscopic treatment.
- Compassionate Use Treatment
-
Eosinophilic esophagitis (EoE) may sometimes be treated with compassionate use, off-label, or experimental treatments when standard therapies are ineffective or unavailable. Such treatments might include:
1. **Dupilumab**: Originally approved for the treatment of asthma, atopic dermatitis, and chronic rhinosinusitis with nasal polyposis, it has shown promise in treating EoE by targeting IL-4 and IL-13 cytokines, which play a key role in the disease.
2. **Budesonide Oral Suspension**: This corticosteroid is formulated specifically to coat the esophagus and is often used off-label to manage EoE.
3. **Elemental Diet**: This involves consuming an amino acid-based formula and eliminating all other foods, which can be effective in reducing inflammation and symptoms.
4. **Biologics targeting IL-5 (e.g., Mepolizumab and Reslizumab)**: These are primarily used for treating eosinophilic asthma but are being investigated for EoE due to their potential to reduce eosinophil levels.
5. **JAK Inhibitors**: These are under investigation as they have the potential to modulate immune responses by inhibiting Janus kinase pathways involved in inflammatory processes.
Always consult healthcare professionals before starting any new treatment. - Lifestyle Recommendations
-
For eosinophilic esophagitis (EoE), lifestyle recommendations can help manage symptoms and improve quality of life. Here are some key suggestions:
1. **Dietary Modifications:**
- **Elimination Diet:** Consider eliminating common allergenic foods such as dairy, eggs, wheat, soy, nuts, and seafood. A physician or dietitian can guide this process.
- **Elemental Diet:** In severe cases, an amino acid-based formula can be used temporarily.
- **Slow Introduction:** Gradually reintroduce eliminated foods to identify specific triggers.
2. **Eating Habits:**
- **Chew Thoroughly:** Thoroughly chewing food can help prevent food impaction.
- **Small Bites:** Take small bites and eat slowly to reduce esophageal strain.
3. **Avoid Triggers:**
- Identify and avoid foods that trigger symptoms through trial and error or allergy testing.
4. **Manage Symptoms:**
- **Stay Hydrated:** Drink plenty of water, especially during meals.
- **Avoid Late Meals:** Avoid eating right before bedtime to reduce reflux.
5. **Medication Adherence:**
- Continue prescribed medications such as proton pump inhibitors (PPIs) or topical corticosteroids as directed.
6. **Regular Monitoring:**
- Keep regular follow-up appointments with a healthcare provider to monitor the condition and adjust treatment as needed.
Making these lifestyle changes can help control the symptoms and improve overall management of eosinophilic esophagitis. - Medication
-
For eosinophilic esophagitis (EoE), common medications include:
1. **Proton Pump Inhibitors (PPIs)**: These are often used as a first-line treatment to reduce acid and assess for any acid-related component of the disease.
2. **Topical Corticosteroids**: Medications like fluticasone or budesonide can be swallowed to reduce inflammation in the esophagus.
3. **Systemic Corticosteroids**: Used in severe cases, although they are generally avoided due to potential side effects.
4. **Biologics**: Emerging treatments that target specific pathways in the immune response, such as dupilumab.
Always consult with a healthcare provider for the most appropriate treatment plan. - Repurposable Drugs
-
Currently, there are some drugs primarily approved for other conditions that are being studied for their potential in treating eosinophilic esophagitis (EoE). Examples include:
1. **Proton Pump Inhibitors (PPIs)**: Originally used for acid reflux (GERD), PPIs can help some EoE patients by reducing inflammation.
2. **Budesonide**: An inhaled steroid for asthma that can be formulated into a slurry to treat esophageal inflammation in EoE.
3. **Fluticasone**: Another asthma inhaler medication that can be used off-label for EoE when sprayed and swallowed to reduce esophageal eosinophils.
These drugs are not always approved specifically for EoE but may be repurposed under medical supervision to manage symptoms and inflammation. Always consult a healthcare provider for clinical decisions. - Metabolites
-
For eosinophilic esophagitis (EoE), specific metabolites directly associated with the condition are not well-defined. However, eosinophil activation in EoE can lead to the release of various substances, including:
1. **Eosinophil-derived neurotoxin (EDN)**
2. **Major basic protein (MBP)**
3. **Eosinophil cationic protein (ECP)**
4. **Leukotrienes**
5. **Interleukins such as IL-5 and IL-13**
These substances contribute to inflammation and tissue remodeling in the esophagus. Research into specific metabolic pathways and biomarkers in EoE is ongoing. - Nutraceuticals
- Nutraceuticals have not been widely studied or conclusively proven effective for treating eosinophilic esophagitis (EoE). Current management primarily involves dietary modification, pharmacological treatment such as proton pump inhibitors, topical corticosteroids, and elimination diets, or in some cases, endoscopic dilation. Always consult with a healthcare provider for personalized advice and treatment options.
- Peptides
- Eosinophilic Esophagitis (EoE) is a chronic immune/antigen-mediated esophageal disease characterized by eosinophil infiltration in the esophagus. Peptides, especially food-derived, can act as antigens in genetically predisposed individuals, triggering an immune response that leads to inflammation and tissue damage. Management often involves dietary modifications to eliminate these antigenic peptides, as well as the use of medications such as proton pump inhibitors (PPIs) and topical corticosteroids.