Review shows evolution and current thinking on management of eosinophilic esophagitis

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

EoE is a chronic inflammatory disorder marked by symptoms of eosinophil-predominant inflammation and esophageal dysfunction. Without treatment, it progresses to fibrous remodeling and the formation of strictures that impair quality of life, as patients are unable to eat freely, have a severely restricted diet, or must use prescription formulas for nutrition.

Diagnostic delays are common, although awareness of the disorder is increasing, the authors noted, 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 young children and infants, symptoms consist mainly of reflux-like symptoms, vomiting, abdominal pain, refusal to feed, and growth retardation. Older children and adults with EoE most commonly report solid food dysphagia, food impaction, and chest pain associated with non-swallowing.

Changing dietary approaches

After EoE was discovered as a distinct type of food allergy, studies showed that it could be treated with a total elimination diet, which involves eliminating all food proteins capable of causing an allergic reaction and to rely exclusively on an elementary formula based on amino acids. . In clinical practice, however, this proves difficult; the taste of the formula is unpleasant when consumed directly and very young children require a nasogastric tube to ensure adequate intake. Additionally, in children younger than 2 years old, avoiding solid foods may delay the development of oral-motor skills, the authors noted.

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

The process of reintroducing foods one at a time to identify allergenic triggers is long and complex even after achieving remission, requiring multiple endoscopies with biopsies and continued liquid feeding and other forms of support.

Although EoE is triggered by food, it is not a disorder based on an immunoglobulin E (IgE) response, and the usual blood and skin tests used for IgE allergies (prick test cutaneous, prick-prick test, atopic patch testing) have been found to be of no use in the management of these patients.

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

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

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

In an American evaluation of children with EoE, 4-FED achieved 54% to 64% efficacy in inducing remission. In a multicenter study of children and adults using a 2-FED regimen, 43% achieved remission; non-responders switched to a 4-FED approach, for a combined overall efficacy of 60%. Those who did not respond to any of these less restrictive diets switched to a 6-FED, for an overall effectiveness of 80%. No difference was observed in terms of effectiveness between children and adults.

Drug treatments – corticosteroids and proton pump inhibitors

After recognition of EOE, various randomized controlled trials showed that systemic steroids had no benefit over topical corticosteroids and had worse side effects. Topical swallowed corticosteroids (TSCs) are the most common drug class in EoE, the authors said.

“The superiority of fluticasone propionate over placebo in inducing clinical and histological remission of EoE, and any other STC formulation, has been supported in numerous systematic reviews and meta-analyses involving RCTs performed in children and adults over the past two decades,” they wrote.

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

For patients who respond, they restore damaged esophageal lining, reverse the inflammatory transcriptome, and reverse fibrous remodeling, and the effects are independent of gastric acid blockade.

Dilation procedures

Esophageal strictures are one of the most serious complications of EoE and can be caused by untreated EoE. Patient age and late diagnosis are factors of fibrotic and stenosing EoE phenotype and are less likely to be seen in pediatric patients. It has no effect on underlying inflammation and should be reserved for 3 clinical scenarios, the authors said:

  • Those with fibrostenosing EoE at diagnosis
  • Patients with persistent symptoms such as food dysphagia and impaction and persistent esophageal strictures after failure of other measures
  • Case of persistent dysphagia in the presence of endoscopic and histological remission with medical or dietary treatment

Future therapies

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

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

New 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); IL-5 receptor alpha subunit (IL-5Rα; benralizumab); and Siglec-8 blockers (lirentelimab).

Other possibilities include non-biologic oral therapies, including sphingosine-1-phosphate receptor modulators, which are being evaluated in other immune-mediated diseases. Additionally, there was a successful case report of a Janus kinase inhibitor used for a treatment-resistant adult patient.

Reference

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

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