A Root Cause Medicine Protocol For Patients With Eosinophilic Esophagitis: Testing, Therapeutic Diet, and Supportive Supplements

A large-scale population survey including over 31,000 participants found that one in six adults reported experiencing dysphagia (difficulty swallowing). Gastroesophageal reflux disease (GERD), eosinophilic esophagitis, and esophageal strictures were the most common comorbidities associated with dysphagia. (1) 

Eosinophilic esophagitis is estimated to affect 0.5-1 in 1,000 people. It is the leading cause of food impaction, affecting up to 7% of patients requiring endoscopy for any reason and up to 23% of patients experiencing dysphagia. Diagnosing and treating eosinophilic esophagitis is crucial to alleviate symptoms, prevent complications, and improve the quality of life for individuals affected by this chronic inflammatory condition. Timely intervention can help reduce inflammation, manage discomfort, and prevent long-term damage to the esophageal tissue. (10) 

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What Is Eosinophilic Esophagitis?

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition that affects the esophagus, the portion of the digestive tract that connects the mouth to the stomach. EoE is characterized by the buildup of eosinophils, a type of white blood cell involved in allergic and parasitic immune responses, in the lining of the esophagus. The high number of eosinophils in the esophagus can lead to inflammation, irritation, and damage to the esophageal tissue. This can result in various symptoms and (potentially emergent) health complications. 

Eosinophilic Esophagitis Signs and Symptoms

EoE can manifest with a variety of signs and symptoms, many of which overlap with other gastrointestinal disorders, like GERD. Patients with EoE commonly report a history of chronic seasonal allergies, asthma, atopic dermatitis, or other allergic conditions (24).  

Common symptoms of EoE include:

• Dysphagia, especially with solid foods; this sensation is often described as feeling like food getting stuck in the throat
• Food impaction, where food becomes stuck in the esophagus; this may require emergent medical intervention to remove the obstruction
• Chest pain or discomfort that does not resolve with antacids
• Heartburn and regurgitation 
• Vomiting
• Abdominal pain
• Feeding difficulties and failure to thrive in children 

Untreated and severe EoE can lead to scarring, narrowing, and tearing of the esophagus. This increases the risk of emergent complications, such as obstruction and excessive bleeding. (13) 

What Are the Possible Causes of Eosinophilic Esophagitis?

EoE is a complex condition that likely arises from intricate interplays between genetic susceptibility, environmental triggers, and immune responses.

One of the key factors in the disease process is an abnormal immune response, often linked to allergies. Immediate hypersensitivity reactions (like anaphylaxis) are rare in patients with EoE. Instead, EoE is associated with delayed hypersensitivity reactions, which involve a more gradual immune response to allergens. Exposure to dietary and environmental allergens, like dairy, wheat, soy, eggs, nuts, seafood, pollen, mold, and dust mites, can trigger the immune system to overreact in the esophagus. The result is esophageal eosinophilic infiltration and subsequent chronic inflammation. (26) 

EoE has a strong genetic component, indicated by the increased risk of disease development in patients who have first-degree relatives with the disease. Genome-wide studies have confirmed this genetic influence by identifying 31 genes potentially associated with EoE. However, twin studies suggest that environmental factors beyond genetics play a role in EoE. Cesarean delivery, formula feeding, and antibiotic exposure in infancy have been linked to EoE risk. (23)

These environmental factors are known to be implicated in alterations to the commensal, healthy microbiome. Studies have demonstrated the importance of the microbiota in immune regulation and have implicated dysbiotic patterns in the pathogenesis of atopic diseases like asthma and atopic dermatitis. This begs the question: What role does the intestinal microbiome play in EoE development? While the precise mechanisms linking dysbiosis to EoE remain unclear, current research highlights that dysbiosis in the esophageal microbiota might contribute to EoE by triggering inflammation and eosinophilic accumulation in the esophageal tissue. (19) 

Functional Medicine Labs to Test for Root Cause of Eosinophilic Esophagitis

Diagnosis of EoE typically involves a combination of medical history, physical examination, and endoscopy with a biopsy of the esophageal tissue. EoE is diagnosed when the following three criteria are met:

• Clinical symptoms of esophageal dysfunction are present
• At least 15 eosinophils per high-powered field are present in tissue biopsy
• The patient has a lack of responsiveness to high-dose proton pump inhibitor therapy 

While no diagnostic laboratory tests are available for EoE, functional medicine tests can be helpful tools in evaluating EoE and determining the root causes of the disease.

Allergy & Sensitivity Testing

Three types of allergy tests exist to evaluate for food allergy: skin prick testing, atopy patch testing, and food-specific IgE immunoassays. Food allergy detection through skin prick testing is only 13% effective in predicting successful elimination diets in adults, making serum testing the best option. (3) 

IgG4 (Immunoglobulin G subclass 4) is an antibody produced by the immune system and is often associated with allergic reactions and immune-related disorders, including EoE (4). IgG4 antibodies can also be measured in a blood sample. 

Comprehensive Stool Test

Comprehensive stool tests are essential tools in evaluating the intestinal microbiome. While there may be variations in the unique microbial makeups of the esophagus versus the large intestine, patients with EoE have been observed to have altered fecal levels of Fusobacterium, Lactobacillus, Veillonella, Bifidobacterium, and H. pylori compared to healthy controls. Additionally, an elevated fecal eosinophil protein X (EPX) is a marker of increased eosinophilic activity. (15) 

Additional Lab Tests

It can be beneficial to rule out additional gastrointestinal pathologies that present with symptoms similar to EoE. Testing options that may be considered include H. pylori stool antigen testing, SIBO breath testing, and Candida antibodies.

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Conventional Treatment for Eosinophilic Esophagitis

Currently, there is no cure for EoE, making long-term treatment necessary. EoE therapy aims to improve clinical symptoms and patient quality of life, resolve eosinophilic infiltration, optimize esophageal function, and prevent disease progression/complications. Standard treatment modalities to meet these goals include dietary modifications, esophageal dilation, and pharmacologic medications. Corticosteroid, biologic, and proton pump inhibitor medications suppress immunological activity and reduce inflammation in the esophageal tissues. (14)

Integrative Medicine Protocol for Eosinophilic Esophagitis

Understanding the triggers and mediators of EoE, an integrative approach aims to meet the same treatment goals stated above by implementing strategies that target the causative factors of the exaggerated allergenic immune response. 

Therapeutic Diet for Eosinophilic Esophagitis

Because research overwhelmingly shows foods to be the primary trigger of EoE, dietary modifications and elimination diets are the gold-standard treatment. By removing specific food triggers from the diet, dietary therapy aims to maintain long-term clinical remission of the disease. Three main strategies for dietary therapy have evolved for treating EoE:

Elemental Diet

The elemental diet is a liquid, predigested, and hypoallergenic meal replacement that offers a complete nutritional profile. It is the most effective dietary therapy for EoE, resulting in 95-95% resolution of symptoms and histology within one month. However, costliness and emotional considerations pose practical limitations to its long-term use. (11)

Targeted Elimination Diet

A targeted elimination removes allergenic foods identified on IgE allergy testing panels. Foods are generally eliminated from the diet for 4-8 weeks, followed by a reintroduction of each food individual once disease remission has been achieved to confirm food triggers. (11)

Six-Food Elimination Diet

The six-food elimination diet was developed by Kagalwalla et al., in which the six most common allergenic foods in EoE patients are avoided without performing allergy testing. Cow's milk, wheat, tree nuts, egg, soy, and seafood are eliminated for at least 4-8 weeks before a reintroduction challenge is performed. Studies utilizing the six-food elimination diet for six weeks have resulted in 70% of patients with eosinophil counts less than 10 per high-powered field on histology and clinical symptom improvement in 94% of patients. Elimination diets are also associated with better cost profiles and compliance rates than the elemental diet. (11)

Best Supplements for Managing Eosinophilic Esophagitis

Natural supplements can be used as alternatives to, or alongside, pharmacologic medications to reduce inflammation, mediate the immune response, and expedite the healing of esophageal tissues.

Zinc Carnosine

Dilated intercellular spaces are a common finding in EoE, suggestive of a breakdown of tight junction cellular proteins, impaired integrity, and enhanced permeability of the esophageal barrier (7). Zinc carnosine is a chelate of L-carnosine and zinc. It is commonly implemented in gut-healing protocols because it expedites cellular repair and restores the gastrointestinal lining.

Dose: 75 mg twice daily

Duration: 4-8 weeks

Quercetin

Quercetin is a potent antioxidant polyphenol found naturally in onions, broccoli, apples, and tea. It is indicated for treating EoE because of its ability to quench free radicals, inhibit pro-inflammatory cytokines, reduce allergic responses, and modulate the immune system to suppress IgE antibody formation. (20) 

Dose: 500 mg three times daily

Duration: 4-8 weeks

Probiotics

Probiotics have been widely studied and shown to provide health benefits ranging from reducing gastrointestinal symptoms to treating allergic symptoms. Noting variations in the microbiota of patients with EoE and healthy controls, it would be reasonable to assume that restoring a healthy intestinal microbiome can provide value in treating EoE. Studies have noted that synbiotic mixtures of prebiotics and probiotics improve chest pain, appetite, and nausea in patients with EoE. 

Dose: probiotic mix containing Bifidobacterium and Lactobacillus species daily

Duration: 4-8 weeks

When to Retest Labs

With effective treatment strategy and adherence to allergen elimination, histological changes and clinical improvements in symptoms have been observed in patients with EoE as soon as six weeks. Monitoring of symptoms and repeat endoscopy may be recommended at this time. Repeat labs could also be considered as needed to monitor abnormal results noted at baseline. 

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Summary

Eosinophilic esophagitis is an allergy-mediated, inflammatory gastrointestinal disorder that can negatively impact the ability to swallow and lead to life-threatening complications when not managed properly. Obtaining and maintaining remission is possible with the right combination of interventions that modulate the allergic immune response, reduce esophageal inflammation, and promote tissue healing.