Fibrostenotic Eosinophilic Esophagitis Research Articles

Dupilumab in adolescent eosinophilic esophagitis: Experience with fibrostenosis and EGID with esophageal involvement.

We evaluated patients aged 12-20 on dupilumab 300 mg weekly for treatment of eosinophilic esophagitis (EoE) who had ≥1 follow-up endoscopy at a tertiary care pediatric hospital (n = 18). Fifty percent had inflammatory EoE (n = 9), 22% had fibrostenotic EoE (n = 4), and 28% had non-EoE eosinophilic gastrointestinal disease (EGID) with esophageal involvement (n = 5). Ninety-four percent discontinued topical corticosteroids (TCS) 2-4 weeks after starting dupilumab. Eighty-nine percent of inflammatory EoE patients had histological response (<15 eosinophils/high-powered field) after an average of 19.1 weeks. One hundred percent of patients with fibrostenotic disease exhibited histological response after 16.8 weeks. Of patients with non-EoE EGID, 60% achieved esophageal histological response after an average of 40.1 weeks. In a small cohort, dupilumab was very effective for adolescent inflammatory and fibrostenotic EoE despite rapid weaning of TCS. Dupilumab was also somewhat effective for non-EoE EGID with esophageal involvement; however, a longer duration of therapy was required.

Real-World Efficacy of Dupilumab in Severe, Treatment-Refractory, and Fibrostenotic Patients With Eosinophilic Esophagitis

Dupilumab is approved for treatment of eosinophilic esophagitis (EoE), but real-world data are lacking. We aimed to determine the real-world efficacy of dupilumab in patients with severe, treatment-refractory, and fibrostenotic EoE. We conducted a retrospective cohort study of EoE patients prescribed dupilumab and who were treatment-refractory to standard modalities. Patient demographics, clinical characteristics, EoE history, and procedural data (including the histologically worst, predupilumab, and postdupilumab endoscopies) were extracted from medical records. Symptomatic, endoscopic, and histologic responses were assessed for the worst and predupilumab endoscopies compared with the postdupilumab endoscopy. We identified 46 patients with refractory fibrostenotic EoE who were treated with dupilumab. Patients showed endoscopic, histologic, and symptomatic improvement on dupilumab compared with both the worst and the predupilumab esophagogastroduodenoscopies. The peak eosinophil counts decreased markedly, and postdupilumab histologic response rates were 80% and 57% for fewer than 15 eosinophils per high-power field and 6 or fewer eosinophils per high-power field, respectively, and the Endoscopic Reference Score decreased from 5.01 to 1.89 (P < .001 for all). Although the proportion of strictures was stable, there was a significant increase in the predilation esophageal diameter (from 13.9 to 16.0 mm; P < .001). Global symptom improvement was reported in 91% (P < .001). In this population of severe, refractory, and fibrostenotic EoE patients, most achieved histologic, endoscopic, and symptom improvement with a median of 6 months of dupilumab, and esophageal stricture diameter improved. Dupilumab has real-world efficacy for a severe EoE population, most of whom would not have qualified for prior clinical trials.

A role for age-associated alterations in esophageal epithelium in eosinophilic esophagitis-associated fibrosis.

Subepithelial fibrosis occurs in a subset of eosinophilic esophagitis (EoE) patients and is associated with esophageal stricture. While mechanisms driving EoE fibrosis remain incompletely understood, findings from experimental systems support roles for epithelial-fibroblast crosstalk in this type of tissue remodeling. The current paradigm presents EoE as a progressive fibrostenotic disease in which aged patients develop fibrosis as a function of disease chronicity. In the current study we provide evidence that altered epithelial biology in the aging esophagus may also contribute to EoE-associated fibrosis. We find that induction of EoE inflammation in young and aged mice using the MC903/Ovalbumin protocol for the same time period results in increased lamina propria thickness uniquely in aged animals. Additionally, epithelial cells from aged mice less efficiently limit fibroblast contractility in collagen plug contraction assays compared to those from their young counterparts. Finally, to identify potential mechanisms through which aged esophageal epithelial cells may stimulate fibrotic remodeling, we perform cytokine array experiments in young and aged mice. These studies are significant as identification of age-associated factors that contribute to fibrotic remodeling may aid in the design of strategies toward early detection, prevention, and therapy of fibrostenotic EoE.

Loss of Endothelial TSPAN12 Promotes Fibrostenotic Eosinophilic Esophagitis via Endothelial Cell–Fibroblast Crosstalk

Eosinophilic esophagitis (EoE) can progress to fibrostenosis by unclear mechanisms. Herein, we investigated gene dysregulation in fibrostenotic EoE, its association with clinical parameters and specific pathways, and thefunctional consequences. Esophageal biopsies from subjects with EoE were collected across 11 Consortium of Eosinophilic Gastrointestinal Disease Researchers sites (n= 311) and 2 independent replication cohorts (n= 83). Inclusion criteria for fibrostenotic EoE were endoscopic rings, stricture, and/or a history of dilation. Endoscopic, histologic, and molecular features were assessed by the EoE Endoscopic Reference Score, EoE Histology Scoring System, EoE Diagnostic Panel, and RNA sequencing. Esophageal endothelial TSPAN12 expression and functional effects on barrier integrity and gene expression were analyzed invitro. TSPAN12 was the gene most correlated with fibrostenosis (r=-0.40, P < .001). TSPAN12 was lower in fibrostenotic EoE and correlated with EoE Endoscopic Reference Score, EoE Diagnostic Panel, and EoE Histology Scoring System (r= 0.34-0.47, P < .001). Lower TSPAN12 associated with smaller esophageal diameter (r= 0.44, P= .03), increased lamina propria fibrosis (r=-0.41, P < .001), and genes enriched in cell cycle-related pathways. Interleukin (IL)-13 reduced TSPAN12 expression in endothelial cells. Conversely, anti-IL-13 therapy increased TSPAN12 expression. TSPAN12 gene silencing increased endothelial cell permeability and dysregulated genes associated with extracellular matrix pathways. Endothelial cell-fibroblast crosstalk induced extracellular matrix changes relevant to esophageal remodeling. Patients with fibrostenotic EoE express decreased levels of endothelial TSPAN12. We propose that IL-13 decreases TSPAN12, likely contributing to the chronicity of EoE by promoting tissue remodeling through fibroblast-endothelial cell crosstalk.

Obesity reduces the requirement for subsequent esophageal stricture dilation in adults with eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) causes esophageal narrowing and strictures, but factors that modify the severity of strictures and requirement for subsequent dilation are not well described. The aim of this study was to identify characteristics that impact the need for repeat (> 1) esophageal dilations in EoE patients. This was a single center retrospective cohort study over a 12-year period (September 2005-October 2017). Patients were identified using ICD9, ICD10, and CPT codes for esophageal dilation, eosinophilic esophagitis, and esophageal obstruction. Data for EoE clinical characteristics, treatments, and BMI were extracted and correlated to the number of esophageal dilations and time elapsed between dilations. Of the 21 patients who met inclusion criteria, 11 (52%) had at least two dilations and 9 (43%) had three dilations. There was no differences baseline demographics between patients who needed ≥ 2 vs. those who needed one dilation. However, patients with a BMI > 30 had a significantly longer median time to second dilation compared to non-obese patients (4.9years vs. 1.8years; p = 0.027). Stratification by either high dose PPI or inhaled steroid use did not change this result. EoE patients with strictures who are obese have a reduced requirement for subsequent esophageal dilation. While the mechanism for this is not clear, increased attention of non-obese patients with fibrostenotic EoE is indicated as they are at higher risk for recurrent strictures.

Sudden Chest Pain Due to Esophageal Intramural Dissection

Sudden Chest Pain Due to Esophageal Intramural Dissection

Comorbid Diagnosis of Eosinophilic Esophagitis and Inflammatory Bowel Disease in the Pediatric Population.

The incidence and prevalence of eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD) are rising with similar patterns. Co-occurrence of both diseases in the same patient has been increasingly reported. We sought to examine the pediatric population with both EoE and IBD to better understand the epidemiology and clinical implications of this overlap. We conducted a retrospective case-control study at 2 tertiary care children's hospitals. Subjects with both EoE and IBD were identified and compared with randomly selected controls with EoE and IBD alone in terms of: demographics, atopic conditions, IBD classification, location and phenotype of Crohn disease (CD), IBD medications, endoscopic findings, and histopathology. Descriptive statistics summarized the data. Sixty-seven subjects with dual-diagnosis were identified across both institutions. The prevalence of IBD in the EoE population was 2.2% and EoE in IBD was 1.5%. Subjects with both diseases were more likely to have IgE-mediated food allergy compared with IBD alone (36% vs 7%, P < 0.001). Subjects with CD-EoE were less likely to have perianal disease than CD alone (2% vs 20%, P = 0.004). There was no difference in fibrostenotic EoE between the dual-diagnosis group and EoE alone. Treatment with a TNF-alpha inhibitor (anti-TNF) for management of preexisting IBD was protective against development of EoE with a relative risk of 0.314 [95% confidence interval [CI] 0.159-0.619]. This is a unique population in whom the underlying pathway leading to dual-diagnosis is unclear. Concomitant atopic conditions, especially IgE-mediated food allergy, and medication exposures, particularly anti-TNFs, may help predict likelihood of developing dual-diagnosis.

Fibrostenotic eosinophilic esophagitis might reflect epithelial lysyl oxidase induction by fibroblast-derived TNF-α

Fibrosis and stricture are major comorbidities in patients with eosinophilic esophagitis (EoE). Lysyl oxidase (LOX), a collagen cross-linking enzyme, has not been investigated in the context of EoE. We investigated regulation of epithelial LOX expression as a novel biomarker and functional effector of fibrostenotic disease conditions associated with EoE. LOX expression was analyzed by using RNA-sequencing, PCR assays, and immunostaining in patients with EoE; cytokine-stimulated esophageal 3-dimensional organoids; and fibroblast-epithelial cell coculture, the latter coupled with fluorescence-activated cell sorting. Gene ontology and pathway analyses linked TNF-α and LOX expression in patients with EoE, which was validated in independent sets of patients with fibrostenotic conditions. TNF-α-mediated epithelial LOX upregulation was recapitulated in 3-dimensional organoids and coculture experiments. We find that fibroblast-derived TNF-α stimulates epithelial LOX expression through activation of nuclear factor κB and TGF-β-mediated signaling. In patients receiver operating characteristic analyses suggested that LOX upregulation indicates disease complications and fibrostenotic conditions in patients with EoE. There is a novel positive feedback mechanism in epithelial LOX induction through fibroblast-derived TNF-α secretion. Esophageal epithelial LOX might have a role in the development of fibrosis with substantial translational implications.

Eosinophilic Esophagitis (EoE) - Successful Treatment With PPI Therapy in a Single-Center - Education and Engagement Are Key

Introduction: Recently, the international EoE consensus eliminated the cumbersome terminology of PPI-responsive esophageal eosinophilia. This supports our practice over the last 7 years of using PPI’s as first line therapy for EoE patients because of convenience, cost, and ease of administration. Here we present our single-center experience in treating EoE. Keys to success involve intense education on appropriate drug dosing, the mechanism of PPIs being anti-eosinophilic, and the key role of strict adherence to a proper PPI trial. Methods: From 2011 to 2017, patients at our institution with confirmed EoE were enrolled sequentially into a database. EoE diagnosis required the combination of clinical symptoms, endoscopic features, and histologic confirmation. In a retrospective manner, data was analyzed as outlined in Figure 1.379 Figure 1 No Caption available.Results: 77 patients (mean age 37, range 17-71, 69% male) with confirmed EoE were treated at our center. A PPI trial was completed on 71/77 (92%) patients with 50/71 (70%) patients having response. Complete response was seen in 44/50 (88%) and partial response in 6/50 (12%). Of those with a complete response, 27/32 (84%) were able to be reduced to once daily PPI maintenance therapy, but 5/32 (16%) relapsed. Of 33 patients with fibrostenotic EoE, an average of 2.3 dilatations were needed to reach a final average esophageal diameter of 17mm. Symptom relief was achieved in 85%; no perforations occurred. Ten patients (13%) were treated with topical steroids. Overall, 7/10 (70%) were steroid responsive. Selective diet elimination based on food allergy testing was successful in 7/8 (88%). Six-food elimination diet as primary therapy in one patient received a complete response. Conclusion: Our 70% response to PPI therapy in our EoE population over 7 years is on the high end of the reported range of 33-80%. The reason for our success in this unselected population may be due to intense education and engagement fostered in our patients. Our patients understand the drug mechanism of action/dosing, are very compliant with the PPI trial, and often rewarded by not needing topical steroids or diet restriction. In addition, the 85% with complete response were decreased to once daily PPIs, thereby lessening concern over potential side effects of long term high dose PPIs. Conclusion In our practice, PPIs have a 70% response rate in unselected EoE patients. Our excellent success may be related to intense education and engagement with our patients.

Successful Esophageal Dilation of Eosinophilic Esophagitis (EoE) Patients With a Previous Postdilation Complication: Start Low and Go Slow.

Esophageal dilation is an effective and safe treatment option for fibrostenotic eosinophilic esophagitis (EoE). Despite the safety, adverse events occur, yet there is scarce literature on the best treatment postcomplications. Patients with diagnosis of EoE (≥15 eosinophils per high-power field) from 2011 to 2015 treated at our center were included. Thirty patients with fibrostenotic disease had records available regarding serial dilation therapy. Eight patients previously experienced complications by outside providers. Groups were created based on history of complication before our dilation versus a group without. Mean difference and odds ratio with 95% confidence interval (CI) were calculated. There were 8 complications, 7 occurred during dilation and 1 during passage of the endoscope. Esophageal diameter at initial dilation was lower in patients with prior complications 9.0±1.51 versus 11.73±2.98 mm (95% CI: -4.44, -1.02; P=0.003). However, end-esophageal diameter was similar across both groups 15.8±1.8 versus 16.1±2.0 mm. Total number of dilation sessions: 4.0±1.8 versus 2.32±1.0 (95% CI: 0.17, 3.19; P=0.03), as well as sessions to reach 17 mm diameter 3.8±1.0 versus 2.3±1.0 (95% CI: -0.08, 2.89; P=0.04), were higher in the patients with complications. The length of time in months to reach an esophageal diameter of 17 mm was longer in patients with complications, but the difference was not statistically significant 3.50±0.6 versus 2.3±2.3 months (P=0.09). Esophageal dilation is a safe and effective modality to treat severe fibrostenotic EoE in patients with prior history of complications. The keys to success are: (1) start with lower diameter bougies and (2) dilate slowly over a longer time course to reach targeted diameter and symptom resolution.

Intrabolus Pressure Has Better Correlation Than Eosinophilia with Dysphagia Severity in Fibrostenotic Eosinophilic Esophagitis: A Pilot Study

Eosinophilic esophagitis is characterized by dysphagia with esophageal eosinophilia. We sought to determine if intrabolus pressure measurements on high-resolution manometry had any correlation with dysphagia improvement following standard therapy for patients with fibrostenotic eosinophilic esophagitis. Consecutive patients were prospectively enrolled at our swallowing center. Dysphagia scores, esophageal eosinophil counts, endoscopic reference scores, and intrabolus pressure measurements were compared at baseline and following therapy with 8 weeks of a proton-pump inhibitor and serial bougie dilation to a luminal diameter of 17 mm. Five patients were included in the study. The median age was 38 years. The average endoscopic reference score improved from 5.0 to 2.4 (p = 0.007). The mean esophageal diameter improved from 10.8 mm to 17.2 mm (p = 0.001). Dysphagia severity scores improved from a mean value of 34.2 to 10.8 (p = 0.004). Mucosal eosinophilia had no correlation with dysphagia severity. Mean intrabolus pressure improved from 21.8 mmHg to 11 mmHg (p = 0.001). There was strong correlation between a decrease in intrabolus pressure and improvement in dysphagia severity; however, this was not significant (p = 0.108). Intrabolus pressure has strong correlation with dysphagia severity following therapy for fibrostenotic eosinophilic esophagitis. Bougie dilation provides improvement in dysphagia despite persistent mucosal eosinophilia.

Dilation of Pediatric Eosinophilic Esophagitis: Adverse Events and Short-term Outcomes.

Although several studies report on the experience with adult eosinophilic esophagitis (EoE)-related stricture, outcomes for pediatric patients with EoE-associated fibrostenosis and stricture is more limited. To address this, we aim to identify the adverse event (AE) rate and short-term outcomes of the largest reported cohort of children with EoE to undergo esophageal dilation for management of symptomatic esophageal narrowing. A retrospective assessment of all children, 18 years and younger, who underwent esophageal dilation at an academic children's hospital during a 5-year period was conducted. Clinical, endoscopic, histologic, and outcomes of dilation were extracted from the medical record. AEs were captured within a standardized endoscopic AE database. Grade 2 AEs (requiring unanticipated medical intervention) were termed significant. Dilation-related events were compared between patients with EoE, without EoE, and those undergoing standard upper endoscopy. Of the 451 total dilations, 68 dilations were performed in 40 EoE patients (mean age 13.8 years, standard deviation 3.3 years [4.6-18.9 years]). Forty-three percent (17/40) had repeat dilation during the study period. Dilation-related grade 2 AE rates in EoE and in non-EoE patients were 2.9% and 3.1%, respectively (P > 0.5). Chest pain (any grade AE) was reported in 14.7% of EoE dilations. No significant associations were found between postprocedural pain and dilation method, final dilator size, medical therapy, or esophageal eosinophilia. No perforations or significant hemorrhage were reported. We conclude that dilation can be performed safely in children with EoE. In the appropriate clinical setting, cautious dilation may be considered in the management of fibrostenotic EoE.

Tu1093 - Improvement of Dysphagia in Patients with Fibrostenotic Eosinophilic Esophagitis Correlates Better with Fall in Intrabolus Pressure than Decrease in Mucosal Eosinophil Count

Tu1093 - Improvement of Dysphagia in Patients with Fibrostenotic Eosinophilic Esophagitis Correlates Better with Fall in Intrabolus Pressure than Decrease in Mucosal Eosinophil Count

Early Comparison of Inflammatory vs. Fibrostenotic Phenotype in Eosinophilic Esophagitis in a Multicenter Longitudinal Study.

OBJECTIVES:Eosinophilic esophagitis (EoE) is a chronic inflammatory condition that causes esophageal remodeling and stricture formation. We compared the clinical course of symptoms, endoscopic findings, histology, and changes in phenotype over time in EoE patients with inflammatory and fibrostenotic phenotypes.METHODS:Data were obtained from EoE patients from three medical centers and followed prospectively. Endoscopic features and histology from index and follow-up endoscopies were recorded. Behavior was classified as inflammatory if endoscopic findings demonstrated furrows or white plaques and as fibrostenotic if endoscopic findings included fixed rings or strictures.RESULTS:Two hundred and fifty-six EoE patients were included in the analysis. The mean age was 32±18 years, 25% of patients were <18 years, 89% of patients were Caucasians, and 74% of patients were male. The mean duration of symptoms before diagnosis was 6.8±7.2 years with a follow-up of 1.7±1.9 years (maximum follow-up of 12 years). Fifty-four percent of patients presented with fibrostenotic EoE, whereas 46% presented with inflammatory EoE. Patients with inflammatory disease were younger than those with fibrostenotic disease (24±19 vs. 39±15 years, P<0.001). Patients with fibrostenotic disease had a longer duration of symptoms than those with inflammatory disease (8.1±7.7 vs. 5.3±6.3 years, P=0.002). Over the study period, 47 (18%) had remission of inflammatory EoE, 68 (27%) continued to have inflammatory disease, 74 (29%) continued to have fibrostenotic disease, 65 (25%) fibrostenotic patients had regression of fibrosis, and 2 patients (1%) progressed from inflammatory disease to fibrostenotic disease. Patients who had regression from their fibrostenosis were more likely than patients who continued to demonstrate fibrostenosis to have a decrease in proximal (54% vs. 32%, P<0.001) and distal (70% vs. 38%, P<0.001) eosinophilia.CONCLUSIONS:Most EoE patients maintained their phenotype or had an improvement with <1% progressing from inflammatory to fibrostenosis. This suggests that early therapeutic strategies aimed at controlling inflammation may interrupt, decrease, or prevent the remodeling fibrosis in EoE.

The changing faces of eosinophilic esophagitis: the impact of consensus guidelines at the University of South Florida.

Prior to the consensus guideline conference in 2007, eosinophilic esophagitis (EoE) was uncommon dominated by the fibrostenotic phenotype, but over the past decade has become a common cause of dysphagia with more inflammatory phenotypes diagnosed. We assessed the impact of guideline definitions on the characteristics of EoE phenotypes over the past 26 years at our institution. We reviewed the electronic health record of 75 consecutive patients meeting guideline definition EoE from 1/1988 to 5/2014. We separated groups based on 5-year intervals of diagnosis and phenotype. For continuous data, results were summarized as mean difference and standard deviation with 95 % confidence intervals. Five groups based on 5-year intervals of diagnosis were identified: group 1-1988-1993 (n = 7), group 2-1994-1999 (n = 7), group 3-2000-2005 (n = 4), group 4-2006-2011 (n = 35), and group 5-2012-2014 (n = 22). Prior to 2000, all patients were diagnosed with fibrostenotic EoE. After the initial 2007 guideline conference, inflammatory EoE has predominated with only one-third diagnosed with fibrostenotic EoE. Prior to 2011, only two were diagnosed with PPI-REE. In the last 3 years, 8 out of 22 patients (32 %) had PPI-REE. Overall, 8 out of 10 (80 %) PPI-REE were the inflammatory phenotype. When comparing pre- (n = 18) and post (n = 57)-consensus definitions, there was a significant difference between age of diagnosis (30.710.2 vs. 41.3 ± 14.3; p = 0.001), age of symptom onset (18.4 +/15.2 vs. 32.4 ± 15.5), and initial esophageal diameter (10.5 ± 2.7 vs. 14.3 ± 4.2; p < 0.0001), respectively. Fibrostenotic EoE has steadily decreased, and inflammatory EoE is now the most recognized form. Across our 26-year experience, there was a decrease in delay in diagnosis and severity of esophageal stricture. The pivotal change occurred around 2007 corresponding to the first EoE guideline emphasizing the impact and importance of early detection of disease.

Mo1842 Comparison of Inflammatory Versus Fibrostenotic Phenotype in Eosinophilic Esophagitis

Background: Eosinophilic esophagitis (EoE) is a chronic inflammatory condition which causes esophageal remodeling and stricture formation over time. Aim: To explore the natural course of symptoms, endoscopic findings to include stricture development, and histology in EoE patients. Methods: EoE adult patients (age > 18 years) were prospectively enrolled from databases of two medical centers (Walter Reed and Mayo Clinic Jacksonville). All EoE patients were diagnosed per recent consensus guidelines. All patients completed index and follow-up symptom surveys. Endoscopic features (rings, furrows, plaques, strictures) and histology from index and follow-up endoscopies were recorded. Disease behavior was classified as inflammatory if endoscopic findings demonstrated furrows or white plaques and classified as fibrostenotic if endoscopic findings included rings or strictures. Results: 165 EoE patients were identified, mean age 42 ± 14 years; 88.5% Caucasian and 70% male. Median (range) duration of symptoms prior to EoE diagnosis was 66 months (0.1-425). Median follow-up time was 19.2 months (0.9-120). At index, the majority (124/165, 75%) presented with fibrostenotic EoE and 25% (41/165) presented with inflammatory disease. Patients who presented with a stricture had a significantly longer duration of symptoms prior to diagnosis (130 vs 86 months, p=0.011). Patients with fibrostenotic features had more food allergies than those with inflammatory disease (23.4% vs. 4.9%, p=0.010); otherwise, other allergic conditions were similar. At index endoscopy, significantly more patients with fibrostenotic disease had dense proximal eosinophilia (>15 eos/hpf) than patients with inflammatory disease (81.1% vs. 64.3%, p=0.015), but were similar in degree of distal eosinophilia (86.4% vs. 85.3%, p=0.415). Over time, disease behavior remained unchanged in the majority (87.3%, 144/165) of patients. Of the 41 patients presenting with inflammatory disease, 21 patients (51%) developed fibrostenotic features with 15 of these developing a stricture at follow-up endoscopy. Patients who developed fibrostenosis had more dense eosinophilia on biopsies (proximal 68.4% vs. 20.0%, p=0.015; distal 68.2% vs. 36.8%, p=0.049) than those who maintained inflammatory features. The majority of patients (68%) reported improved symptoms over time regardless of their disease behavior. Conclusions: The majority of patients with EoE present with or develop fibrostenotic disease. Duration of symptoms was significantly greater in patients presenting with stricture. Dense proximal esophageal eosinophilia is associated with the presence of fibrostenosic disease and higher levels of eosinophilia may predict transformation from inflammatory to fibrostenotic disease.

Mo1843 Mast Cell Densities on Esophageal Mucosal Biopsies Were Higher in Eosinophilic Esophagitis Versus Proton Pump Inhibitor-Responsive Esophageal Eosinophilia in Adults

Background: Eosinophilic esophagitis (EoE) is a chronic inflammatory condition which causes esophageal remodeling and stricture formation over time. Aim: To explore the natural course of symptoms, endoscopic findings to include stricture development, and histology in EoE patients. Methods: EoE adult patients (age > 18 years) were prospectively enrolled from databases of two medical centers (Walter Reed and Mayo Clinic Jacksonville). All EoE patients were diagnosed per recent consensus guidelines. All patients completed index and follow-up symptom surveys. Endoscopic features (rings, furrows, plaques, strictures) and histology from index and follow-up endoscopies were recorded. Disease behavior was classified as inflammatory if endoscopic findings demonstrated furrows or white plaques and classified as fibrostenotic if endoscopic findings included rings or strictures. Results: 165 EoE patients were identified, mean age 42 ± 14 years; 88.5% Caucasian and 70% male. Median (range) duration of symptoms prior to EoE diagnosis was 66 months (0.1-425). Median follow-up time was 19.2 months (0.9-120). At index, the majority (124/165, 75%) presented with fibrostenotic EoE and 25% (41/165) presented with inflammatory disease. Patients who presented with a stricture had a significantly longer duration of symptoms prior to diagnosis (130 vs 86 months, p=0.011). Patients with fibrostenotic features had more food allergies than those with inflammatory disease (23.4% vs. 4.9%, p=0.010); otherwise, other allergic conditions were similar. At index endoscopy, significantly more patients with fibrostenotic disease had dense proximal eosinophilia (>15 eos/hpf) than patients with inflammatory disease (81.1% vs. 64.3%, p=0.015), but were similar in degree of distal eosinophilia (86.4% vs. 85.3%, p=0.415). Over time, disease behavior remained unchanged in the majority (87.3%, 144/165) of patients. Of the 41 patients presenting with inflammatory disease, 21 patients (51%) developed fibrostenotic features with 15 of these developing a stricture at follow-up endoscopy. Patients who developed fibrostenosis had more dense eosinophilia on biopsies (proximal 68.4% vs. 20.0%, p=0.015; distal 68.2% vs. 36.8%, p=0.049) than those who maintained inflammatory features. The majority of patients (68%) reported improved symptoms over time regardless of their disease behavior. Conclusions: The majority of patients with EoE present with or develop fibrostenotic disease. Duration of symptoms was significantly greater in patients presenting with stricture. Dense proximal esophageal eosinophilia is associated with the presence of fibrostenosic disease and higher levels of eosinophilia may predict transformation from inflammatory to fibrostenotic disease.

A phenotypic analysis shows that eosinophilic esophagitis is a progressive fibrostenotic disease

Phenotypes of eosinophilic esophagitis (EoE) are not well-characterized. To describe clinical features of patients with EoE with predefined phenotypes, determine predictors of these phenotypes, and make inferences about the natural history of EoE. Retrospective study. Tertiary-care center. Incident EoE cases from 2001 to 2011 that met consensus diagnostic guidelines. Review of records. Endoscopic phenotypes, including fibrostenotic, inflammatory, or mixed. Other groups of clinical characteristics examined included atopy, level of esophageal eosinophilia, and age of symptom onset. Multinomial logistic regression assessed predictors of phenotype status. Of 379 cases of EoE identified, there were no significant phenotypic differences by atopic status or level of eosinophilia. Those with the inflammatory phenotype were more likely to be younger than those with mixed or fibrostenotic (13 vs 29 vs 39 years, respectively; P < .001) and less likely to have dysphagia, food impaction, and esophageal dilation (P < .001 for all). The mean symptom length before diagnosis was shorter for inflammatory (5 vs 8 vs 8 years; P = .02). After multivariate analysis, age and dysphagia independently predicted phenotype. The odds ratio (OR) for fibrostenosis for each 10-year increase in age was 2.1 (95% CI, 1.7-2.7). The OR for dysphagia was 7.0 (95% CI, 2.6-18.6). Retrospective, single-center study. In this large EoE cohort, the likelihood of fibrostenotic disease increased markedly with age. For every 10-year increase in age, the odds of having a fibrostenotic EoE phenotype more than doubled. This association suggests that the natural history of EoE is a progression from an inflammatory to a fibrostenotic disease.