New 2020 Eosinophilic Esophagitis Guidelines

Full text (I Hirano et al. Gastroenterol 2020; 158: 1776-86)AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters Clinical Guidelines for the Management of Eosinophilic Esophagitis

Full text: PDF

This guideline was developed through a collaboration between AGA and the Joint Task Force for Allergy-Immunology Practice Parameters, which comprises the American Academy of Allergy, Asthma & Immunology and the American College of Allergy, Asthma & Immunology. This guideline is jointly published in Gastroenterology and Annals of Allergy, Asthma and Immunology.

Technical review article (MA Rank et al. Gastroenterol 2020; 158: 1789-1810): Technical Review on the Management of Eosinophilic Esophagitis: A Report From the AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters

 

Link: Clinical Decision Support Tool

Link: Treatment of EoE Spotlight Poster

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Head-to-Head: Budesonide vs Fluticasone for Eosinophilic Esophagitis

A recent double-blind, double-dummy study (ES Dellon et al. Gastroenterol 2019; 157: 65-73) found similar efficacy between budesonide and fluticasone for newly-diagnosed eosinophilic esophagitis. They had hypothesized that an oral viscous budesonide would be more effective due to increased esophageal contact time.

Methods: The authors compared an oral viscous budesonide OVB) at 1 mg BID (n=56) to fluticasone (swallowed) MDI dosed at 880 mcg BID (n=55).  Patients aged 16-80 years, with mean of 37 years.

Baseline characteristics:

  • ~95% in both groups with dysphagia
  • ~75% with any atopic condition
  • ~50% with dilatation required at baseline

Key findings:

  • Similar drop in eosinophil count: 73 (OVB) and 77 (MDI) eos/hpf at baseline to 15 and 21 respectively
  • Histologic response (<15 eos/hpf) rates of 71% (OVB) and 64% (MDI).
  • Response to <5 eos/hpf occurred in 61% OVB and 49% MDI; response to <1 eos/hpf was noted in 41% and 35% respectively
  • Symptom scores (DSQ) responded similarly as well
  • Similar degree of candidiasis 12% for OVB and 16% for MDI

In the associated editorial, the authors speculate that one reason for similar efficacy was the detailed instructions given for patients taking the MDI.

My take: This study supports both topical steroid therapies; practical issues like cost and insurance coverage could be influential in selecting the specific treatment for an individual patient.

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From AGA twitter feed

Safety of Fluticasone for Eosinophilic Esophagitis (Abstract)

Doerthe A Andreae et al. The American Journal of Gastroenterology 111, 1187-1197 (August 2016) | doi:10.1038/ajg.2016.238

METHODS:

In an open-label, prospective, single-center study, we offered pediatric patients with active EoE fluticasone 2 puffs to swallow twice a day (strengths in μg/puff: 2–4 years: 44, 5–11 years: 110, ≥12 years: 220). Clinical, endoscopic, and histological assessments were performed at baseline and shortly after therapy. If histological remission was seen, fluticasone was continued with clinical follow-ups every 4 months and endoscopic and histological follow-ups yearly. Clinical scores were derived from eight symptoms (abdominal pain, nausea, vomiting, regurgitation, chest pain, dysphagia, food impaction, and early satiety). Endoscopic scores were derived from six features (rings, exudates, furrows, edema, stricture, and shearing). Scores were expressed as ratio (features present/total). In addition to peak eosinophils/high power field (HPF) (primary outcome), histological features (eosinophilic microabscesses, degranulation, superficial layering, basal zone hyperplasia, dilated intercellular spaces, and lamina propria fibrosis) were assessed. Median clinical and endoscopic scores and individual histologic features were compared over 4 time intervals: <4 months, 4–12 months, 13–24 months, and >24 months. Growth and adverse effects were monitored.

RESULTS:

We enrolled 54 patients, 80% male, median age 6.5 years (range 2–17 years), 85% atopic (57% asthma, 68% allergic rhinitis, and 31% atopic dermatitis), and 74% with food allergy. Mean follow-up was 20.4 months, the longest being 68 months (5.7 years). Esophageal eosinophil counts significantly decreased (median peak eosinophils/HPF at baseline 72, <4 months: 0.5, 4–12 months: 1.75, 13–24 months: 10, and >24 months: 12, all P<0.01). All histological features significantly decreased from baseline to all follow-up time points (all P<0.01). Lamina propria fibrosis significantly decreased (% patients with fibrosis at baseline 92, <4 months: 41, 4–12 months: 50, 13–24 months: 45, and >24 months: 39, all P<0.01). Endoscopic features improved (score at baseline 0.37, <4 months: 0.17, 4–12 months: 0.17, 13–24 months: 0, and >24 months: 0.1, all P<0.01, except at >24 months: P<0.05). Symptoms improved (score at baseline 0.22, <4 months: 0, 4–12 months: 0.11, 13–24 months: 0.11, and >24 months: 0.11, all P<0.05 except at >24 months: P=0.05). In a mixed linear regression model that accounts for correlation of repeated observations in the patient in a per-patient analysis, we found that treatment with swallowed fluticasone led to a statistically significant and sustained decrease in peak esophageal eosinophil counts. Asymptomatic esophageal candidiasis was seen in three children but resolved with anti-fungal therapy. Height and weight z-scores followed expected growth curves.

CONCLUSIONS:

We demonstrate that swallowed fluticasone is effective as a long-term maintenance therapy for children with EoE, without growth impediment or serious side effects.

My take: This post, from an abstract, shows a single-center’s experience with fluticasone. This study provides some reassurance regarding safety & efficacy when used as a maintenance medication. However, as noted in links below, higher doses of fluticasone have been associated with adrenal insufficiency.

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Adrenal Insufficiency due to Fluticasone in Eosinophilic Esophagitis

A recent study (MC Golekoh et al. J Pediatr 2016; 170: 240-5) shows that adrenal insufficiency developed in 10% of patients on chronic (>6 months) swallowed corticosteroid therapy for Eosinophilic Esophagitis (EoE).

Background: 58 patients with 67% receiving fluticasone and 33% receiving budesonide.  Median age: 13.7, median fluticasone dose 1320 mcg/day, median treatment duration: 4 yrs.  For budesonide, median dose was 1000 mcg/day and median age 10.7 yrs.

Key findings with low-dose ACTH stimulation:

  • Abnormal peak cortisol (≤ 20 mcg/dL) present in 15% and adrenal insufficiency (< 18 mcg/dL)  (n=6) noted in 10%
  • Only patients receiving >440 mcg/day of fluticasone had adrenal insufficiency
  • No patients taking budesonide had an abnormal cortisol level

Commentary:

  • Higher doses of fluticasone, particularly early in treatment, has been shown to have an improved inflammatory response.  However, as with asthma therapy, higher doses increase the risk of adrenal insufficiency.
  • Adrenal insufficiency can be asymptomatic but pose a risk for life-threatening adrenal crisis.
  • Strengths of study: Fairly large cohort, endoscopic/pathologic reports available, and ACTH stimulation testing which has better sensitivity than random cortisol.
  • Limitations: Lower number of patients receiving budesonide, particularly at a higher dose.  No indication of adherence.

My take: If higher doses of fluticasone are needed for prolonged period, consider screening (endocrinology consultation) for adrenal insufficiency.

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Farjado, Puerto Rico

Farjado, Puerto Rico

Predicting Response to Topical Steroids in Eosinophilic Esophagitis

A recent study (Wolf WA, et al. Clin Gastroenterol Hepatol 2015; 13: 45-58) examined 221 patients in a retrospective cohort study to determine how effective topical steroids were in the treatment of eosinophilic esophagitis (EoE).  The authors studied these patients from 2006-2013; the majority received budesonide (63%) and the remainder received fluticasone; the typical dosing was 0.5 mg-1 mg twice daily and 440-880 mcg twice daily, respectively. 129 (58%) of the participants were >18 years.

Key findings:

  • 57% had histologic response with <15 eos/hpf
  • Refractory patients “were difficult to treat with dietary and second-line pharmacologic therapies, with less than half responding even after multiple second-line therapies.” The most successful second-line approach was diet: 6 of 16 (38%) had improved histology (<15 eos/hpf).  Higher doses of topical agents were effective in 2 of 14 (14%) and alternative topical agent was effective in 2 of 7 patients (29%).
  • Dilatation at the time of disease presentation (25% of the study cohort) correlated with poor clinical outcome.  Only 40% (20 of 50) had a histologic response.
  • High tissue levels of tryptase and eotaxin-3 increased the likelihood of a steroid response.

As this was a retrospective study, there were several weaknesses.

Take-home message: The findings from this large cohort show that more than 40% of patients did not have a favorable histologic response.  Some recent studies indicate that higher doses of steroids may be effective, but this may be influenced by the proportion of individuals with advanced fibrostenotic disease.

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Chicago's Bean

Chicago’s Bean

Nexium versus Fluticasone for EoE

As noted in previous blog posts (EoEDrugsDietsDilatation and PPI-REE | gutsandgrowthEoE –Journal Club (Part 1) | gutsandgrowth, and EoE –Journal Club (Part 2) | gutsandgrowth), proton pump inhibitors are recommended as 1st line therapy in suspected eosinophilic esophagitis (EoE) for several reasons.  Besides the potential for gastroesophageal reflux to cause esophageal eosinophilia, there has been recognition of PPI-responsive eosinophilic esophagitis (PPI-REE).  In adults, the response to proton pump inhibitors, both clinically and histologically, is likely higher than in children; nevertheless, in children it is anticipated that 20-40% of patients with suspected EoE will have a histological remission with PPI therapy.

A recent study in adults suggests that PPIs may in fact outperform topical steroids (Am J Gastroenterol 2013; 108: 366-72).  Thanks to Ben Gold and Seth Marcus for identifying this reference.  This study enrolled 42 patients: 90% male, 81% white, mean age 38 years. It was a prospective single-blinded, randomized controlled trial with newly suspected EoE; half of the patients received esomeprazole 40 mg daily and half fluticasone swallowed aerosol 440 mcg twice a day.  After 8 weeks, all patients had repeat endoscopy; a total of eight biopsies were obtained –four at two locations: 15 cm above LES and 3 cm above LES.  In addition, at the start of the study, patients also underwent 24-h pH/impedance monitoring.  4 of the 21 patients in each group had abnormal degrees of gastroesophageal reflux/gastroesophageal reflux disease (GERD).

Study characteristics note that 62% of patients had coexisting atopic disorders.

Results:

  • There was no significant difference in esophageal eosinophilia response with 19% of the fluticasone and 33% of the esomeprazole achieving an eosinophil count < 5/hpf (P=0.484)
  • In patients with coexisting GERD, all 4 esomeprazole patients achieved histologic remission  compared with none of the fluticasone-treated patients.
  • When the GERD patients were excluded, the histological remission was quite similar: 24% with fluticasone and 18% for esomeprazole.

Overall, this study population had a lower rate of response to topical steroids than in multiple previous studies.  More typically, response rates of ~50% have been reported; however, studies have shown lower responses in some adult studies.  Variability in response could be related to multiple factors included dosage, duration, delivery, and definition of response.  In addition, population characteristics included disease duration and frequency of underlying atopic disease and GERD play a role.

Take-home points: Although this is a small study, it reinforces the fact that PPIs induce a histological response and clinical response in some patients suspected of having EoE regardless of whether GERD is present.  PPIs are considered 1st line therapy.  Topical fluticasone had a lower response rate in this study.  However, in clinical pediatric practice, topical steroids are effective in about 50% of patients.

Additional related blog entries:

Looking better or feeling better in EoE?

When seeing a new diagnosis of eosinophilic esophagitis (EoE), I often try to explain that there are two potential goals of treatment: clinical remission (improvement in symptoms) and histologic remission (improvement in appearance of esophagus with microscope).  Unfortunately, these two outcomes are not always synchronous; more proof of this comes from a recent study (Clin Gastroenterol Hepatol 2012; 10: 742-49, 750-52 [editorial]).

In this double-blind, randomized, placebo-controlled study of fluticasone in adult patients with a new diagnosis of EoE, 19 patients were treated with fluticasone (880 μg BID) and 15 patients were treated with placebo inhaler –for six weeks.  Initially, 21 patients were assigned to each group; 2 dropped out of treatment group and 6 dropped out of placebo group before completion of followup EGD.   The average age in the treatment group was 37 years versus 38 years in the placebo group.  A complete histologic response was defined as >90% reduction in mean eosinophil count; this occurred in 62% of fluticasone patients and in none of the placebo group, based on an intention-to-treat analysis.  Another measure of eosinophil activity, eosinophil-derived neurotoxin (EDN), was reduced by 81% on intracellular staining in the treatment group compared with 8% in the placebo group.  Figures 1 through 3 show this staining –it’s pretty cool!

Yet, the clinical response was not statistically different.  Dysphagia was reduced by 57% in the treated subjects compared to 33% in the placebo subjects in an intention-to-treat analysis.  Results were improved modestly in those who actually were treated: 63% (12 of 19) compared to 47% of placebo patients.  A complete response for dysphagia was noted in 42.9% of fluticasone group compared with 28.6% of control group based on an intention-to-treat analysis.  A fairly high rate of candidiasis was noted in treated patients 26%;  no placebo patients developed candida.

Another interesting finding was that among those who continued PPIs for heartburn symptoms the response to fluticasone was not improved.  40% of PPI users had a complete histologic response compared with 79% of non-PPI users.

So what are the reasons for the discrepancy between clinical and histologic response?

  • Established strictures and small-caliber esophagus may require dilation rather than medicines to relieve dysphagia
  • Esophageal fibrosis and subsequent esophageal compliance may not respond to topical therapy or take a lot longer to improve
  • Secondary candidiasis may reduce clinical response –though in this study, 5 of 6 patients with candida did in fact have symptom resolution
  • Compensatory behaviors may improve clinical symptoms –chewing food, cutting up food better, drinking more fluids, and avoiding some foods.  This may make it harder to detect important differences.

Patient information link: (Eosinophilic esophagitis – CCDHC Home)

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Look of improvement on an EoE diet

Guidelines for Eosinophilic Esophagitis

Eosinophilic Esophagitis -Six Food Group Diet

The undiscovered country

MicroRNA signature for eosinophilic esophagitis