Review Shows Evolution, Current Thinking on Managing Eosinophilic Esophagitis

A recent review for clinicians provides an overview of current therapies and possible options for eosinophilic esophagitis (EoE).

EoE is chronic inflammatory disorder marked by symptoms of eosinophil-predominant inflammation and esophageal dysfunction. Without treatment, it progresses to fibrous remodeling and stricture formation that impairs quality of life, as patients are unable to eat freely, have heavily restricted diets, or must used prescription formulas for nutrition.

Diagnostic delays are common, although awareness of the disorder is increasing, noted the authors, writing in Therapeutic Advances in Gastroenterology. Diagnosis of EoE requires the finding of more than 15 eosinophils per high power field (eos/HPF) in esophageal biopsies.

In younger children and infants, symptoms mainly consist of reflux-like symptoms, vomiting, abdominal pain, food refusal, and failure to thrive. Older children and adults with EoE most commonly report solid food dysphagia, food impaction, and nonswallowing associated chest pain.

Changing dietary approaches

After EoE was discovered to be a distinct type of food allergy, studies showed that it could be treated with a total elimination diet, which consists of removing all food proteins capable of causing an allergic reaction and exclusively relying on an amino-acid based elemental formula. In clinical practice, however, this proves difficult; the formula taste is unappealing when consumed directly and very young children require a nasogastric tube in order to ensure adequate intake. Moreover, in children under the age of 2, avoiding solid food may lead to delayed oral-motor skill development, the authors noted.

In addition, relying on an elemental diet creates significant psychological and social difficulties and negative health-related quality of life. These liquid medical foods are often expensive, as the formulas not universally reimbursed by payers.

The process to reintroduce foods one at a time in order to identify allergenic triggers is long and complex even after remission is achieved, requiring multiple endoscopies with biopsies and continued liquid nutrition and other support.

Although EoE is triggered by food, it is not a disorder based on a response to immuneoglobulin E (IgE), and the usual blood and skin tests used for IgE allergies (skin prick test, prick-prick test, atopic patch testing) were discovered to have no utility in managing these patients.

The difficulties with a total elimination diet and the lack of diagnostics led to the next phase of managing EOE, by eliminating a reduced number of foods.

The first approach, developed in 2006, pulled the 6 most common food allergens (milk, wheat, egg, soy, nuts, and fish and seafood) for 6 weeks; 75% of patients attained remission at results on par with total elimination diets, studies showed. Specific food triggers were identified by reintroduction of each food followed by endoscopy with biopsy after each reintroduction.

Several studies pointed to milk as the main trigger, followed by gluten, eggs, and soy or legumes; therefore, the next dietary approach removed these 4 foods from patients’ diets (the 4-FED diet). This was followed by removing just milk and gluten (the 2-FED diet).

In a US assessment of childen with EoE, 4-FED achieved a 54% to 64% effectiveness at inducing remission. In a multicenter study of children and adults using a 2-FED diet, 43% achieved remission; nonresponders moved on to a 4-FED approach, for an overall combined efficacy of 60%. Those who did not respond to either of these less restrictive diets moved up to a 6-FED, for an overall efficacy of 80%. There were no differences seen in terms of efficacy between children and adults.

Drug therapies—corticosteroids and proton pump inhibtors

After EOE was recognized, various randomized contolled trials showed that systemic steroids had no advantage over topical corticosteroids and had worse adverse affects. Swallowed topical corticosteroids (STCs) are the most drug class in EoE, the authors said.

“The superiority of fluticasone propionate over placebo to induce clinical and histological remission of EoE, and of any other formulation of STC, has been corroborated in numerous systematic reviews and meta-analyses that involve RCTs carried out in children and adults over the last two decades,” they wrote.

More recently, proton pump inhibitors (PPIs) have been shown to induce remission in multipe observational studies, athough no randomized trial has compared the effectiveness or safety of PPI with other treatment options, and none are expected, the authors said. Initially, PPIs were used to rule out GERD but are now considered to be anti-inflammatory therapies in their own right.

For patients whe respond to them, they restore the damaged esophageal mucosa, reverse the inflammatory transcriptome, and reverse fibrous remodeling, and the effects are independent of blocking gastric acid.

Dilation procedures

Esophageal strictures are one of the most severe complications of EoE and may be caused by untreated EoE. Patient age and delayed diagnosis are factors for a fibrotic and stricturing EoE phenotype and are less likely to be seen in pediatric patients. It does not have an effect on underlying inflammation and should be reserved for 3 clinical scenarios, the authors said:

• Those with fibrostenosing EoE at the time of diagnosis
• Patients with continued symptoms such as dysphagia and food impaction and persistent esophageal strictures after other measures have failed
• Cases of persistent dysphagia in the presence of endoscopic and histological remission with medical or dietary therapy

Future therapies

The authors pointed out that there “is no single strategy that has a clear advantage as the primary therapy for EoE, and, therefore, the choice of therapy needs to be individually discussed with the patients and their families.”

Clinicans might consider using PPIs, diet, or topical steroids as first-line anti-inflammatory therapy.

Novel treatments in late-stage studies and possibly on the horizon include biologics, which are used in asthma and atopic dermatitis. These include monoclonal antibodies targeting interleukein (IL)-4 (dupilumab); IL-13 (cendakimab); the alpha subunit of the IL-5 receptor (IL-5Rα; benralizumab); and Siglec-8 blockers (lirentelimab).

Other possibilities include nonbiologic, oral therapies, including modulators of the sphingosine-1-phosphate receptors, which are being evaluated in other immune-mediated diseases. In addition, there has been a successful case report of a Janus kinase inhibitor used for a treatment-resistant adult patient.

Reference

Feo-Ortega S, Lucendo AJ. Evidence-base d treatments for eosinophilic esophagitis: insights for the clinician. Therap Adv Gastroenterol. Published online January 19, 2022. doi: 10.1177/17562848211068665.