Longitudinal Perspective on Managing Refractory Eosinophilic Esophagitis

Abstract

Background One third of patients with eosinophilic esophagitis (EoE) do not achieve histological remission with standard medical or dietary treatment. The outcome of these patients undergoing various rescue treatments is not known and whether these patients constitute a distinct subset remains unclear. Objective To analyze EoE treatment outcomes in a predominantly pediatric population, including after initial treatment failure (rescue treatment) for differences in outcomes and clinical presentation. Methods We identified 100 serial cases of confirmed EoE from our REDCap® database established at Massachusetts General Hospital starting from January 2007. Demographic data, clinical symptoms, treatment regimens, endoscopic findings, skin testing results, food triggers and clinical outcome of various rescue treatment strategies were presented. We defined clinical response as histological remission with peak eosinophil count of at least 6 biopsies less than 10 per high power field. RESULTS Ninety-seven EoE patients underwent initial treatments. Eighty-one elected dietary treatment (7 elemental diet, 54 multiple food elimination diet, and 20 milk-free diet and 16 elected medical treatment (15 swallowed fluticasone and 1 budesonide). Initial response rate to dietary and medical treatment was 67% (54/81) and 56% (9/16) respectively. Of the 34 who failed initial treatment, 24 of them elected various second treatment regimens (3 medical therapy, 2 milk-free diet, 14 multiple food elimination diet and 5 elemental diet) and 54% (13/24) achieved histological remission. Eight of the remaining 11 who failed second treatment underwent additional treatments and 2 ultimately achieved histological remission. The overall response rate by intention-to-treat analysis increased from 65% (63/97) with initial treatment to 78% (76/97) with rescue treatment, and further to 80% (78/97) with multiple rescue treatments. On a per-protocol basis, the overall response rate was 93% (78/84); however, patients who failed the first two rounds of therapy had only a 20% response rate. Patients who responded to initial treatment were found to have more symptoms and endoscopic abnormalities. In contrast, comparison of patients who failed both initial and rescue therapy to those who responded to rescue therapy did not identify any differentiating clinical features. CONCLUSION More than half of the patients who failed initial EoE treatment could still achieve histological remission with rescue treatments. Elemental diet is the most effective initial and rescue therapy in achieving histological remission. No clinical features could not identified to reliably predict response to rescue treatment.

Assessing the Risk Factors for Refractory Eosinophilic Esophagitis in Children and Adults

“…Patients' demographic data confirmed the findings reported in the literature: predominance in male sex, occurrence in both children and adults, and association between EoE and personal history of allergy, with frequent sensitization to inhalant and food allergens [11, 15, 18, 19]. With regard to incidence of refractory EoE, our data are also in line with those previously reported [16, 20], corresponding to one-third of all patients affected by EoE, at least in our pediatric population. Indeed, it was higher (57%) in our adult group.…”

“…Different approaches and combination of these treatments have been applied during the brief history of EoE, with variable results. The available data demonstrated that up to 30% of patients have a refractory disease [16]. The term refractory EoE, in fact, identifies those patients with EoE who are not responsive to therapy neither in clinical nor endoscopic or histological level.…”

Six-Food Elimination Diet and Topical Steroids are Effective for Eosinophilic Esophagitis: A Meta-Regression

“…Of these, 193 full articles were considered pertinent based on the title or abstract, and 51 were selected for inclusion: 33 articles describing therapy with topical fluticasone [20–52], 17 articles describing therapy with topical budesonide [28,32–34,36,44,51,53–62], and 9 articles describing therapy with SFED [60,63–70]. Manuscripts started in year of publication in 2003 among studies of topical fluticasone, 2007 among studies of topical budesonide, and 2006 among studies of SFED.…”

“…Very little is known about the longitudinal course of EoE patients under treatment, especially among patients on SFED, and what is known suggests relapse is common if treatments are stopped. Only two retrospective studies examined the effectiveness of second-line therapies, though at least a fifth to a third of patients fail to respond to first line therapies [34,51]. …”

Illuminating Elimination Diets: Controversies Regarding Dietary Treatment of Eosinophilic Esophagitis

“…32,22 Most importantly, it has been repeatedly demonstrated that removal of an offending food allergen or allergens results in clinical remission of EoE. [26][27][28]30,[33][34][35][36][37][38][39] There are three major approaches to dietary elimination in EoE: elemental formula, targeted elimination, and empiric elimination. 40 The goal of elimination diets is not to indefinitely limit the diets of patients to highly-restricted regimens, but to induce clinicopathologic remission, after which foods can be added back sequentially in order to identify food triggers of esophageal eosinophilia and to establish a less restrictive, long-term, therapeutic diet for effective and least restrictive disease management.…”