Medical treatments for eosinophilic esophagitis (a chronic disease associated with increased numbers of eosinophils in the esophagus and symptoms of esophagitis)

Eosinophilic esophagitis (EE) is emerging globally as a significant cause of upper gastrointestinal disease in people with clinical symptoms of esophageal disease including a typical appearance of the esophagus and an increased number of eosinophil white blood cells when the esophagus is examined by an endoscope using high magnification.

The cause of EE is unknown, however dietary and/or environmental factors may be contributing factors. People with EE may have difficulty swallowing, vomiting, regurgitation, chest and/or abdominal pain and frequently fail to respond to treatment with antacids or anti-reflux surgery. Current therapies include steroids, therapies that target specific components of the immune system, such as mast cell inhibitors, leukotriene receptor antagonists, and immune modulators; dietary manipulation and esophageal dilatation, however there is no universal approach to treatment. Our systematic review of the literature identified only three randomised controlled trials evaluating the benefits and harms of medical treatments for EE, two in children and one in adults. One trial compared fluticasone, a steroid spray that is swallowed, with oral steroid (prednisone), one compared fluticasone (a steroid) with placebo and the third compared mepolizumab, a monoclonal antibody, with placebo. In children, fluticasone decreased vomiting more effectively than placebo but did not improve dysphagia. Histological remission was more marked in the fluticasone group compared with the placebo group. Esophageal candidiasis (thrush) was diagnosed in one participant on fluticasone. Another trial showed symptom improvement that was similar with fluticasone and with oral prednisolone. The majority of participants were symptom free at four weeks with no difference between the groups. Symptom relapse usually occurred within six weeks of stopping therapy and had occurred in 45% of all trial participants at six month follow-up with no difference between treatment groups in the rate or timing of relapse. There was improvement as assessed by examining the biopsies taken from the esophagus, in the majority of participants at four weeks, with no difference between the two groups. In the prednisone group, 40% had adverse effects and three withdrew early with severe adverse effects (hyperphagia, weight gain, and the 'moon-shaped' face often seen with steroid treatment (cushingoid features)). In the fluticasone group, 15% were diagnosed with esophageal candidiasis and 45% had a relapse of symptoms at week 24. In the third trial in adults, using monoclonal antibody, there was no difference in symptom response with mepolizumab compared to placebo, but the decrease in esophageal eosinophils was more marked with mepolizumab than placebo.

Authors' conclusions: 

As only three relevant RCTs were identified, we have limited capacity to compare the benefits and harms of medical interventions currently used for treating EE. Further RCTs on therapies for EE are required.

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Background: 

People with eosinophilic esophagitis (EE) have clinical symptoms of esophageal disease, an elevated intraepithelial eosinophil count (15 in one or more high power field at endoscopy), consistent endoscopic findings and failure to respond to gastric acid suppressants. The cause of EE is unknown, however dietary, environmental and immunological factors may contribute. Current medical therapies include steroids, dietary manipulation, mast cell inhibitors, leukotriene receptor antagonists and immune modulators; however there is no universal approach to treatment.

Objectives: 

To evaluate the benefits and harms of medical interventions for EE.

Search strategy: 

We searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group trials register (The Cochrane Library Issue 1, 2009), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2009), MEDLINE (1966 to February 2009) and EMBASE (1980 to February 2009).

Selection criteria: 

Randomised controlled trials (RCTs) comparing a medical or dietary intervention for EE with a placebo or with another medical intervention.

Data collection and analysis: 

Two reviewers independently screened the titles of abstracts.

Main results: 

Three RCTs fulfilled inclusion criteria, two in children and one in adults. In one trial, topical fluticasone decreased vomiting more than placebo (67% versus (vs) 27%, P<0.05) but did not improve dysphagia. Histological remission was reported in fluticasone group compared with placebo group (50% vs 9%, P=0.05; RR 5.5, 95%CI 0.81 to 37.49). One recipient of fluticasone developed oral candidiasis. In trial comparing fluticasone with oral prednisone, symptom resolution and improvement of esophagitis were similar. Majority of participants were symptom free at four weeks with no difference between groups (RR 1.03, 95%CI 0.95 to 1.11). Symptom relapse usually occurred within six weeks of stopping therapy and 45% had symptom relapse at six month follow-up with no difference between groups. With prednisone, 40% suffered adverse effects and three withdrew early from treatment with severe adverse effects (hyperphagia, weight gain, cushingoid features). With fluticasone, 15% developed esophageal candidiasis and 45% had relapse in symptoms at week 24. Histological improvement occurred in majority at four weeks with no difference between groups. In the third trial comparing mepolizumab to placebo, there was no difference in symptom response with mepolizumab compared to placebo, but decrease in esophageal eosinophil count was greater with mepolizumab than placebo (67% vs 25%).

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