Eosinophilic Esophagitis: The Four D’s of Treatment

Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease of the esophagus. Over the past two decades, EoE has rapidly emerged as a major cause of dysphagia, food impactions, and foregut symptoms in both children and adults. Prevalence rates in Western countries now range from 1 in 2000 to 1 in 1000, with incidence continuing to rise. Both environmental and genetic factors contribute to EoE pathogenesis. Research suggests food allergens like milk, wheat, eggs, and legumes can trigger an inflammatory response in genetically predisposed individuals. EoE is mediated by a T-helper cell 2 (TH2) immune reaction, with key cytokines like interleukin (IL)-5, IL-13, and IL-4 stimulating eosinophil production and activation. Inflammatory cells infiltrate the epithelial layers of the esophagus, releasing toxic granules and pro-inflammatory signals. This leads to chronic tissue inflammation and extracellular matrix remodeling. Hallmark histologic findings include eosinophil-predominant inflammation, basal cell hyperplasia, dilated intercellular spaces, and subepithelial fibrosis. Chronic remodeling causes symptoms of esophageal dysfunction like dysphagia, food impactions, and chest pain. Untreated disease can progress to esophageal strictures.

Diagnosis of EoE requires both characteristic symptoms and histologic evidence of esophageal eosinophilia on endoscopic biopsies. Consensus guidelines define EoE as greater than 15 eosinophils per high power field in the esophageal epithelium after an 8 week trial of high dose proton pump inhibitor (PPI) therapy. PPIs help exclude GERD as an cause. Other disorders that can cause esophageal eosinophilia need exclusion as well, like infections, drug reactions, connective tissue disease, and eosinophilic gastrointestinal disorders.

Once diagnosed, the goals of EoE treatment are to relieve symptoms, resolve inflammatory changes, and prevent complications like strictures. Four main therapies constitute the “four D’s” of treatment: drugs, diet, dilation, and dupilumab.

Drug options include PPIs, topical glucocorticoids, and the monoclonal antibody dupilumab. While they do not address the underlying food allergy, PPIs reduce acid secretion and have anti-inflammatory properties when used at high doses (40-80 mg/day). Up to 50% of EoE patients respond histologically to PPI monotherapy. Topical steroids directly treat the inflammation in a localized manner. Budesonide as a viscous slurry or swallowed fluticasone spray are commonly used. They lead to histologic remission in 50-80% of cases. However, symptoms and eosinophil counts often recur after discontinuation. Maintenance therapy is generally required. The latest drug approved is dupilumab (Dupixent), a subcutaneous injectable biologic targeting the Th2 cytokines IL-4 and IL-13. In the LIBERTY EoE trials, dupilumab 300 mg weekly achieved 60% histologic remission compared to placebo. It significantly improved symptoms as well. Dupilumab represents an important new option, though cost, delivery, and long-term safety remain concerns.

Elimination diets are another effective treatment strategy by removing inciting food allergens. Elemental formula diets are highly efficacious but unpalatable. Empiric elimination of the six most common allergenic foods (milk, wheat, eggs, soy, nuts, fish/shellfish) induces remission in over 70% of patients. This six-food diet is very restrictive, leading many to opt for four-food or two-food eliminations, but with lower efficacy around 50%. Regardless, repeat endoscopies are required during methodical food reintroduction to identify triggers. Dietary therapy has the advantage of addressing the underlying pathogenesis, but practical challenges limit its use.

Esophageal dilation is key for relieving dysphagia and treating advanced strictures in EoE. Using bougie dilators or through-the-scope balloons, the strictures can be sequentially dilated to 15-18 mm diameter. Clinical improvement is often dramatic after dilation, though multiple sessions are typically required. Dilation is sometimes combined with drugs or diet to maximize anti-inflammatory treatment as well. Serious risks like perforation are rare with gradual dilation.

In summary, mainstays of EoE treatment include drugs, diet, dilation, and dupilumab. Optimal therapy is highly individualized, based on disease severity, patient preferences, and local practice patterns. Combination therapy is frequently needed, especially for more severe presentations. Key is shared decision making between patients and their gastroenterologist when mapping out a treatment plan. The group concluded that:

PPIs are a good first-line option given their safety, efficacy and low cost. High dose is key.

Topical steroids are the mainstay drugs with proven histologic and symptom improvement. Budesonide and fluticasone are equally effective.

Dietary elimination can achieve remission in many patients but requires commitment and multiple EGDs.

Esophageal dilation gives rapid relief of dysphagia and treats strictures. Technique is important to minimize risk.

Dupilumab shows great promise as a novel biologic for EoE but cost and delivery may limit use. Further study on long-term impacts is needed.

Overall, exciting progress continues in expanding options to individualize care for EoE patients. I will plan to provide more in-depth looks at each of these treatment approaches in future posts. Please share any questions in the comments!

Frequently Asked Questions about Eosinophilic Esophagitis Treatment

Q: What are the main symptoms of EoE that would prompt someone to seek treatment?

A: The most common symptoms of EoE are dysphagia (difficulty swallowing), food impactions, and choking/chest pain when eating. Acid reflux symptoms can also occur. In children, poor weight gain, feeding difficulties, and abdominal pain may be presenting signs.

Q: How often do I need to repeat endoscopy with biopsies to monitor EoE treatment?

A: After initiating treatment, repeat endoscopy is recommended in 6-12 weeks to assess histologic response. Long term, endoscopy on a periodic basis such as every 1-3 years is advised to monitor inflammation and detect stricture progression.

Q: Are there any diets that can cure EoE?

A: No diet has been proven to permanently “cure” EoE. The elemental diet comes closest but is not sustainable long-term in most patients. Empiric and directed elimination diets are effective for inducing remission in many patients, but EoE usually recurs after discontinuation.

Q: How long do I need to be on medications like topical steroids or dupilumab?

A: Medications do not change the underlying allergic mechanisms in EoE. Most experts recommend continuing maintenance therapy long-term to prevent recurrence of inflammation and symptoms. Periodic trials off medication can assess for possible remission.

Q: Does EoE increase my risk of esophageal cancer?

A: There is no direct causative link between EoE and cancer risk. However, uncontrolled inflammation over time can lead to cellular changes like metaplasia. Optimal treatment to reduce this chronic inflammation is advised.

Q: How successful is esophageal dilation? Will I likely need multiple sessions?

A: Over 90% of patients have symptom relief after dilation. However, EoE is a chronic condition and strictures can recur, so repeat procedures are common. On average patients undergo dilation 1-2 times per year once started.

Q: Are there any alternative medicine or holistic approaches that help EoE?

A: A few complementary approaches like eliminating gluten or non-IgE-mediated foods may have anecdotal benefits. Probiotics have limited data. But allergy testing and naturopathic cures have not shown clear usefulness in EoE.

Q: What should I do if I have an acute food impaction?

A: Try taking small sips of liquid. If unable to clear within a few hours, go to the emergency room for evaluation. Impactions may require endoscopic removal if they do not pass spontaneously. Meat tenderizers should not be used.

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