Updated Consensus Guidelines for Eosinophilic Esophagitis

Full text: ES Dellon, CA Liacouras,  J Molina-Infante, GT Furuta et al. Gastroenterol 2018; 155: 1022-33.

This article provides a thorough review of EoE -including clinical features, differential diagnosis, diagnostic criteria, and treatments.

Key point: “The evidence suggests that PPIs are better classified as a treatment for esophageal eosinophilia that may be due to EoE than as a diagnostic criterion, and we have developed updated consensus criteria for EoE that reflect this change.”

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Eosinophilic Esophagitis -Update

At a recent morning clinical conference, Dr. Seth Marcus provided a terrific update on eosinophilic esophagitis (EoE).  I am placing some of the slides below and the following is a link to the full lecture: The Evolution of EoE -Seth Marcus

During this part of the presentation, there was a discussion regarding the role of  allergists. Due to the poor predictive value (negative and positive) of allergy testing (skin tests and blood tests), the consensus is that routine allergy evaluation is NOT needed for children with EoE.  However, IgE-mediated food allergies along with other atopic diseases are common in children with EoE and selected patients could benefit from allergy referral.

The slide above reviews the main treatment options: topical corticosteroids, proton pump inhibitor therapy, and elimination diet.  While all of these are reasonable as first-line approaches, many in the group favored proton pump inhibitor (PPI) treatment as initial therapy.  In those with a very good response (<5 eos/hpf at followup), this would allow lower dose PPI as a maintenance option.  Another point of discussion was the fact that PPI responders tend to more favorably metabolize the PPIs to achieve higher therapeutic levels.  It is anticipated that future treatment could be influenced by knowing the individual’s CYP2C19*17 Polymporphisms (#NASPGHAN17 EoE Session)

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Reslizumab (recombinant anti-IL-5) for Eosinophilic Esophagitis

Reslizumab, a monoclonal recombinant antibody to interleukin-5 did not receive FDA approval for eosinophilic esophagitis.  However, a recent report (J Markowitz et al. Journal of Pediatric Gastroenterology and Nutrition: June 2018 – Volume 66 – Issue 6 – p 893–897)  describes the outcomes of patients who entered the randomized control trial and continued to receive subsequently via open label extension (OLE, n=6) or through compassionate use (CU, n=4. This study provides data over 9 years of treatment.

Key findings:

  • Median eosinophil count dropped from 35 to 3
  • No serious adverse events were noted
  • Clinical features improved.  For example, dysphagia dropped from 42% to 0% and vomiting dropped from 67% to 17%

My take: Though this is a small study, it shows that in selected patients disruption of the inflammatory pathways can result in significant clinical improvement.

Pics from Ameila Island and thereabouts -Not sure whose dog  (not ours)

Impedance Measurements with Eosinophilic Esophagitis

Briefly noted: MA Lowry et al. JPGN 2018; 67: 198-203.  This study showed that active eosinophilic esophagitis (EoE) was associated with much lower impedance values that inactive EoE, NERD, and controls.  At 2, 5 and 10 cm above the squamo-columnar junction, median values of impedance with active EoE were 1069, 1368, and 1707 respectively.  In comparison, inactive EoE had median values were 3663, 3657, and 4494, respectively.  My take: Since impedance was also performed during endoscopy with sedation, this does not represent a significant advance in current management.

Sunrise at Amelia Island

Long-term Use of Proton Pump Inhibitors for Eosinophilic Esophagitis

A prospective pediatric eosinophilic esophagitis (EoE) study (C Gutierrez-Junquera et al. JPGN 2018; 67: 210-6) examines the use of proton pump inhibitors (PPIs) for long-term management for this disorder.

After diagnosis of EoE, children received esomeproazole (1 mg/kg/dose BID).  For those with a response (<15 eos/hpf), they were maintained on 1 mg/kg/day for one year.

Key findings:

  • Of the initial cohort of 109, 72 (66%) had response to esomeprazole.
  • 57 of these responders were subsequently followed in this study.  At the lower daily esomeprazole dose, 70.1% (n=40) continued with <15 eos/hpf and 29.9% (n=17) had relapse.
  • Maintaining response was more common among those who achieved an initial response (with BID esomeprazole) of <5 eos/hpf compared to those who had achieved an initial response of 6-14 eos/hpf.  At 1 year, in those with who had a more complete response, 81% maintained eosinophil count <15/hpf compared with only 50% in those with a lesser initial response.
  • Adverse events with prolonged treatment were uncommon and included self-resolving diarrhea in three, headache in one and urticaria in one; the latter two adverse effects responded to change to lansoprazole

My takes: 

  1. PPI treatment is effective in probably 40-50% of individuals with EoE (though higher response in this study)
  2. Some individuals need higher doses of PPIs
  3. Due to the high response rate, this underscores the need to diagnose EoE prior to using PPIs or after they have been discontinued.

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Eosinophilic Esophagitis -Three Subtypes

Eosinophilic oesophagitis endotype classification by molecular, clinical, and histopathological analyses: a cross-sectional study

T Shoda et al. The Lancet Gastroenterology & Hepatology, published online May 2, 2018. DOI: https://doi.org/10.1016/S2468-1253(18)30096-7

Abstract:

Background

Eosinophilic oesophagitis is understood in terms of quantifiable histological, endoscopic, and molecular features. Data are scant for inter-relations of these features and their potential to identify distinct disease endotypes. We aimed to identify clinical–pathological correlations between endoscopic and histological disease variables by transcription profiling of the oesophagus of patients with eosinophilic oesophagitis of varying severity and disease activity states.

Methods

We did a cross-sectional study across ten hospital sites in the USA associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers. We analysed oesophageal biopsy specimens taken from paediatric and adult patients with eosinophilic oesophagitis (discovery cohort), using the eosinophilic oesophagitis diagnostic panel (EDP), a set of 96 informative transcripts. Histological and endoscopic features were assessed by quantification of oesophageal eosinophils and use of the eosinophilic oesophagitis histology scoring system (HSS) and the eosinophilic oesophagitis endoscopic reference score (EREFS). Associations among the various histological, endoscopic, and molecular features were analysed by Spearman correlation. Results were replicated in a biologically independent, single-centre, validation cohort of patients with active eosinophilic oesophagitis.

Findings

The discovery cohort contained 185 samples and the validation cohort comprised 100 specimens. In the discovery cohort, EDP showed intersite consistency, significant correlation with oesophageal eosinophils (p<0·0001), and similar findings between paediatric and adult patients. Of eight HSS domains, basal zone hyperplasia correlated with the EDP (median Spearman ρ 0·47 [IQR 0·36–0·60]). Of five EREFS features, distal furrows correlated with the EDP (median Spearman ρ 0·42 [0·32–0·50]). By analysing active eosinophilic oesophagitis in the discovery cohort, the EDP identified three clusters associated with distinct endotypes (termed EoEe1–3) despite similar eosinophil levels. EoEe1 was associated with a normal-appearing oesophagus (risk ratio [RR] 3·27, 95% CI 1·04–10·27; p=0·0443), an inverse association with a history of oesophageal dilation (0·27, 0·09–0·82; p=0·0105) and showed relatively mild histological, endoscopic, and molecular changes. EoEe2 showed an inflammatory and steroid-refractory phenotype (RR 2·77, 95% CI 1·11–6·95; p=0·0376) and had the highest expression of inflammatory cytokines and steroid-responding genes. EoEe3 was associated with a narrow-calibre oesophagus (RR 7·98, 95% CI 1·84–34·64; p=0·0013) and adult onset (2·22, 1·19–4·12; p=0·0155), and showed the highest degree of endoscopic and histological severity and the lowest expression of epithelial differentiation genes. These endotypes were replicated in the validation cohort by clustering and with an eosinophilic oesophagitis endotype-prediction algorithm.

Interpretation

Our new disease classification stratifies patients with eosinophilic oesophagitis into subgroups with potential clinical and therapeutic significance and provides a framework for a precision medicine approach to eosinophilic oesophagitis.

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