fluticasone and Eosinophilic-Esophagitis

Eosinophilic esophagitis (EoE) is a chronic immune-mediated inflammatory disease of the esophagus that affects an estimated 34.4/100 000 people in Europe and North America. EoE affects both children and adults, and causes dysphagia, food impaction of the esophagus, and esophageal strictures.. EoE is defined by symptoms of esophageal dysfunction, such as vomiting, dysphagia, or feeding difficulties, in a patient with an esophageal biopsy demonstrating at least 15 eosinophils per high-power field in the absence of other conditions associated with esophageal eosinophilia such as gastroesophageal reflux disease or achalasia. Genetic factors and environmental factors, such as exposure to antibiotics early in life, are associated with EoE. Current therapies include proton pump inhibitors; topical steroid preparations, such as fluticasone and budesonide; dietary therapy with amino acid formula or empirical food elimination; and endoscopic dilation. In a systematic review of observational studies that included 1051 patients with EoE, proton pump inhibitor therapy was associated with a histologic response, defined as less than 15 eosinophils per high-power field on endoscopic biopsy, in 41.7% of patients, while placebo was associated with a 13.3% response rate. In a systematic review of 8 randomized trials of 437 patients with EoE, topical corticosteroid treatment was associated with histologic remission in 64.9% of patients compared with 13.3% for placebo. Patients with esophageal narrowing may require dilation. Objective assessment of therapeutic response typically requires endoscopy with biopsy.. EoE has a prevalence of approximately 34.4/100 000 worldwide. Treatments consist of proton pump inhibitors, topical steroids, elemental diet, and empirical food elimination, with esophageal dilation reserved for patients with symptomatic esophageal narrowing.

Topics: Adrenal Cortex Hormones; Adult; Amino Acids; Budesonide; Capsules; Combined Modality Therapy; Deglutition Disorders; Dilatation; Eosinophilic Esophagitis; Eosinophils; Esophagoscopy; Esophagus; Fluticasone; Food Hypersensitivity; Gene-Environment Interaction; Humans; Proton Pump Inhibitors

Topical corticosteroids (TS) have become standard therapy for eosinophilic esophagitis (EoE). However, a variety of drug formulations have been used for which results of histological and clinical responses may be different. We aimed at determining the short-term histologic efficacy of TS for EoE based on randomized placebo-controlled trials and to review clinical response.. We searched MEDLINE, ISI Web of Science, and clinicaltrials.gov for randomized controlled trials (RCTs) on TS versus placebo for active EoE published until June 2019. Treatment effects were calculated as risk ratios (RRs) comparing histologic remission between groups.. Nine RCTs (6 budesonide and 3 fluticasone) involving a total of 483 participants were included. A substantial overall effect of TS on acute histologic remission (RR 12.5, 95% confidence interval 6.0-25.9) was found despite varying definitions of histologic response. Indirect comparisons between drug and formulation types showed a trend for a better histologic efficacy of budesonide (RR 13.5 vs. 10.4 fluticasone) and for the orodispersible tablet (RR 46.2 vs. 11.5 suspension, and 10.4 nebulized formula/spray), but only based on small patient numbers. Scores used for clinical response assessment were different between studies, and short-term clinical results were less impressive: significant differences favoring TS were found in 4/9 RCTs (4/6 budesonide, 0/3 fluticasone).. TS are effective for short-term induction of histological remission in EoE with less impressive clinical response rates. The mode of drug delivery to the esophagus may be a relevant factor for the degree of histologic remission. Further trials should use uniform assessment criteria and long-term patient-centered outcomes.

Topics: Adrenal Cortex Hormones; Budesonide; Eosinophilic Esophagitis; Fluticasone; Humans; Randomized Controlled Trials as Topic

Eosinophilic Esophagitis (EoE) is an immune-mediated, chronic inflammatory disorder of the esophagus. Topical steroids have been used in the management of EoE for over 15 years. However, there are no Food and Drug Administration (FDA) approved drug therapies for EoE.. This review discusses the current understanding of EoE and the role of topical steroids in the induction and maintenance of remission in patients with EoE. We performed a comprehensive review of the literature, summarized randomized control trials from 2006 to 2020, and provided a simplified management algorithm for EoE.. In patients with EoE, topical steroids are effective in inducing clinical and histologic remission. Formulations of topical steroids that maximize the exposure to esophageal mucosa have the highest efficacy. A majority of patients who achieve remission with topical steroids develop clinical and histologic relapse off therapy within a year. Current evidence suggests that maintenance therapy with long-term topical steroids decreases the risk of relapse and progression to fibrostenotic disease. While uncertainty over the dose and duration of maintenance topical steroids and their potential side effects exists, long-term maintenance therapy with topical steroids appears to be the way forward to improve long-term outcomes in patients with EoE.

Topics: Administration, Topical; Anti-Inflammatory Agents; Budesonide; Endpoint Determination; Eosinophilic Esophagitis; Fluticasone; Humans; Maintenance Chemotherapy

Eosinophilic oesophagitis is a unique form of non-IgE-mediated food allergy characterised by oesophageal eosinophilic infiltration. The prevalence of EoE has grown to currently represent the first cause of dysphagia and food impaction in children and young adults. Avoiding food triggers is the only therapy targeting the cause of the disease, but none of the currently available food allergy tests adequately predicts food triggers for EoE. Strategies based on the empirical elimination of food are the most effective and convenient in clinical practice. Proton pump inhibitors constitute an effective first-line therapy in half of patients, through a direct anti-inflammatory effect independent of its action on gastric acid secretion. Topical glucocorticosteroids budesonide and fluticasone reduce eosinophilic inflammation and reverse symptoms. This review includes the most relevant aspects of the epidemiology, diagnosis, treatment and monitoring of eosinophilic oesophagitis.

Topics: Adult; Anti-Inflammatory Agents; Budesonide; Child; Deglutition Disorders; Diet Therapy; Eosinophilic Esophagitis; Evidence-Based Practice; Fluticasone; Humans; Inflammation; Proton Pump Inhibitors; Young Adult

In order to provide a comparative evaluation of available pharmacologic treatments for eosinophilic esophagitis (EoE), we conducted a network meta-analysis.. A variety of pharmacologic treatments for EoE have been reported, however there exists a paucity of direct comparisons.. We searched randomized controlled trials using MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials database through December 2014. Studies were analyzed using a random-effects network meta-analysis to identify the most effective therapy. Subgroup analysis was performed among studies that excluded gastroesophageal reflux disease or proton-pump inhibitor responsive esophageal eosinophilia, and also among pediatric and adult populations. The ranking probability for the efficacy of each treatment was analyzed. Consistency of the included randomized controlled trials was checked by applying inconsistency and node-splitting models.. Eleven studies of a total of 456 patients were identified. Six pharmacologic treatments (budesonide suspension and viscous, fluticasone, prednisone, esomeprazole, and mepolizumab) and placebo were included in our analysis. Meta-analysis showed superiority of budesonide viscous, budesonide suspension, and fluticasone over placebo. Network meta-analysis demonstrated the rank order of efficacy as budesonide viscous, esomeprazole, prednisone, budesonide suspension, fluticasone, mepolizumab, and placebo. The results were consistent from the inconsistency model analysis and node-splitting analysis. Subgroup analysis demonstrated prednisone, budesonide suspension, and esomeprazole were the most effective when network meta-analyses were performed among studies that excluded gastroesophageal reflux disease or proton-pump inhibitor responsive esophageal eosinophilia, and among pediatric and adult populations, respectively.. On the basis of this network meta-analysis, viscous budesonide was shown to be the most effective pharmacologic therapy for EoE among the reported pharmacologic treatments.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Budesonide; Child; Child, Preschool; Eosinophilic Esophagitis; Esomeprazole; Female; Fluticasone; Gastrointestinal Agents; Glucocorticoids; Humans; Infant; Male; Middle Aged; Prednisone; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Remission Induction; Treatment Outcome; Young Adult

Eosinophilic esophagitis (EoE) is defined as a chronic, immune-medicated or antigen-mediated, esophageal disease, characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. Food allergens are identified in most patients. Treatment strategies include elimination diets, drugs, and esophageal dilation. This article focuses on pharmacologic treatment. Currently, there is no pharmacologic treatment that has been approved by regulatory authorities. Established pharmacologic options to treat EoE include proton pump inhibitors and swallowed topical steroids. Several biologic therapies are currently under evaluation and some of them have shown promising results in improving biologic endpoints and patient-reported outcomes.

Topics: Administration, Topical; Anti-Allergic Agents; Anti-Inflammatory Agents; Antibodies, Monoclonal; Budesonide; Eosinophilic Esophagitis; Fluticasone; Histamine Antagonists; Humans; Pregnenediones; Proton Pump Inhibitors

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus, which requires short- and long-term treatment. In addition, patients under long-term treatment for any chronic condition should have a structured follow-up. The mainstays in EoE treatment are drugs (such as swallowed topical corticosteroids [STC] and proton pump inhibitors), dietary exclusions, and endoscopic dilations. STC are the most widely used treatment and have proven efficacy in inducing clinical, endoscopic and histological remission in active EoE. However, data regarding maintaining disease remission and long-term management are limited. Ongoing disease activity and relapses despite STC treatment are frequently observed. This sheds light on the urgent need for adequate maintenance strategies, which have not been well defined. In terms of follow-up concepts, to date neither guidelines nor consensus recommendations have been published. To summarize the current knowledge on long-term diagnostic and therapeutic STC management of EoE, we conducted a literature search using PubMed and Embase applying the following key search items: Eosinophilic esophagitis, eosinophils, esophagus, swallowed topical corticosteroids, fluticasone, budesonide, long-term, treatment, therapy, and follow-up. In addition, we present empirically developed long-term management concepts applied at two large EoE centers, with a special focus on STC treatments. Finally, we highlight areas of future research and perspectives regarding the long-term management of EoE.

Topics: Administration, Oral; Adrenal Cortex Hormones; Budesonide; Chronic Disease; Eosinophilic Esophagitis; Eosinophils; Esophagoscopy; Esophagus; Fluticasone; Humans; Maintenance Chemotherapy; Randomized Controlled Trials as Topic; Remission Induction; Treatment Outcome

The goal of this Review is to discuss the clinical approach to patients who do not respond to treatment for eosinophilic oesophagitis (EoE). Refractory EoE is challenging to manage as there are limited data to guide decision-making. In this Review, refractory EoE is defined as persistent eosinophilia in the setting of incomplete resolution of the primary presenting symptoms and incomplete resolution of endoscopic findings following a PPI trial, and after treatment with either topical steroids or dietary elimination. However, this definition is controversial. This Review will examine these controversies, explore how frequently non-response is observed, and highlight potential explanations and predictors of non-response. Non-response is common and affects a large proportion of patients with EoE. It is important to systematically assess multiple possible causes of non-response, as well as consider treatment complications and an incorrect diagnosis of EoE. If non-response is confirmed, second-line treatments are required. Although the overall response rate for second-line therapy is disappointing, with only half of patients eventually responding, there are several promising agents that are currently under investigation, and the future is bright for new treatment modalities for refractory EoE.

Topics: Anti-Inflammatory Agents; Eosinophilic Esophagitis; Esophagoscopy; Fluticasone; Humans; Patient Compliance; Proton Pump Inhibitors; Recurrence

Eosinophilic oesophagitis is a diagnosis that is being made more frequently in the assessment of dysphagia in both adults and children. It is unclear whether this is a result of increased prevalence or improved diagnostic methods. Children present commonly to paediatric institutions with foreign body impaction. Research indicates that food impaction may predispose to eosinophilic oesophagitis. This article presents eosinophilic oesophagitis from an otolaryngologist's point of view. It details the clinical features present in the disease as well as how it is diagnosed and managed. It illustrates early signs of eosinophilic oesophagitis so that primary physicians and emergency physicians know when to refer on to otolaryngologists.

Topics: Administration, Topical; Anti-Inflammatory Agents; Budesonide; Child; Deglutition Disorders; Diet Therapy; Eosinophilic Esophagitis; Esophagoscopy; Esophagus; Fluticasone; Foreign Bodies; Humans; Otolaryngology

Eosinophilic esophagitis (EoE) is a clinicopathologic condition characterized by symptoms of esophageal dysfunction in the presence of eosinophil-predominant inflammation of esophageal mucosa. Topical steroids are recommended as first line pharmacologic therapy in EoE. We aimed to determine the efficacy of topical steroids in inducing histologic and clinical remission in children and adults with EoE.. We performed a systematic search of the MEDLINE, EMBASE, Scopus, and Cochrane library databases for studies investigating the efficacy of topical steroids in EoE. We collected data on the number of patients, dose and duration of therapy, complete and partial histological response, and clinical improvement. We performed meta-analysis of placebo-controlled randomized clinical trials using Review Manager version 5.2. We used funnel plots to evaluate for publication bias.. Five studies that included 174 patients with EoE were included in the meta-analysis. Topical fluticasone was administered in three studies involving 114 patients, and topical budesonide in two studies involving 60 patients. Patients treated with topical steroids, as compared with placebo, had higher complete histological remission (odds ratio [OR] 20.81, 95% confidence interval [CI] 7.03, 61.63) and partial histological remission (OR 32.20, 95% CI 6.82, 152.04). There was a trend towards improvement in clinical symptoms with topical steroids as compared with placebo but it did not reach statistical significance (OR 2.72, 95 %CI 0.90, 8.23).. Topical corticosteroids seem to be effective in inducing histological remission but may not have similar significant impact in improving clinical symptoms of EoE. Studies with large sample size are needed to uniformly validate symptom improvement in EoE.

Topics: Administration, Topical; Budesonide; Chi-Square Distribution; Eosinophilic Esophagitis; Esophageal Mucosa; Esophagus; Fluticasone; Humans; Odds Ratio; Randomized Controlled Trials as Topic; Remission Induction; Steroids; Treatment Outcome

Controversy surrounds the clinical and histological response to topical steroids in patients with eosinophilic oesophagitis (EoE).. To perform a systematic review and network meta-analysis of randomised controlled trials to assess the efficacy of topical steroids compared with placebo or proton pump inhibitor (PPIs) for the management of eosinophilic oesophagitis.. Cochrane Central Register of Controlled Trials and MEDLINE from inception to 1 July 2015 was searched. Data were extracted independently by two authors. Methodological quality was assessed using the Cochrane risk of bias tool. A network meta-analysis was performed using the Bayesian methods under random-effects multiple treatment comparisons. Results were summarised as odds ratio along with credibility intervals. We also calculated the ranking probability for each treatment based on surface under the cumulative ranking curve (SUCRA).. The overall methodological quality of included studies was low. SUCRA ranking probability indicated that PPI had the highest probability of being the best treatment for achieving histological remission and mean change in eosinophils (0.81 and 0.85, respectively), followed by budesonide (0.74 and 0.63, respectively) and fluticasone (0.5 and 0.5, respectively). None of the comparisons indicated a statistically signicant difference.. The results from network meta-analysis show that there is no statistically significant difference between PPI, budesonide and fluticasone for the treatment of EoE as assessed by the histological and clinical response. The evidence is limited by serious risk of bias and imprecision, which emphasises the urgent need for large RCTs with adequate sample size and methodological rigour to provide conclusive evidence.

Topics: Bayes Theorem; Budesonide; Drug Administration Routes; Eosinophilic Esophagitis; Fluticasone; Humans; Proton Pump Inhibitors; Steroids

Esophagitis is the end result of a variety of insults to epithelial homeostasis. Eosinophilic esophagitis is a manifestation of non-IgE-mediated food allergy that most commonly affects the esophagus of males who have other atopic phenomena. Reflux esophagitis reflects repeated exposure to acidic gastric contents because of failure of the normal protections afforded by the LES. Because certain histologic features can be present in either condition, endoscopic biopsy alone does not distinguish them. Their symptoms overlap, but the treatment options are very different, such that making a formal diagnosis by following consensus guidelines is essential. A treatment protocol designed to manage the inflammation by controlling the provocative factors (acid for GERD and food antigens for EoE) or suppressing the inflammation (ie, topical steroids for EoE) should result in normalization of the mucosa and resolution of symptoms. Eosinophilic esophagitis is a chronic condition that rarely remits spontaneously, so any therapeutic modality will need to be continued indefinitely.

Topics: Adolescent; Budesonide; Diet Therapy; Eosinophilic Esophagitis; Esophageal pH Monitoring; Esophagitis, Peptic; Fluticasone; Fundoplication; Gastroesophageal Reflux; Glucocorticoids; Histamine H2 Antagonists; Humans; Proton Pump Inhibitors

Eosinophilic oesophagitis is a chronic immune-mediated inflammatory disorder of the oesophagus, characterized by symptoms of dysphagia or food bolus obstruction. Diagnosis is supported by typical histological findings. This article covers pertinent aspects of the disease, pathogenic explanations and treatment options.

Topics: Administration, Topical; Anti-Inflammatory Agents; Budesonide; Cytokines; Deglutition Disorders; Diet Therapy; Eosinophilic Esophagitis; Esophageal Stenosis; Esophagoscopy; Fluticasone; Humans; Proton Pump Inhibitors; Th2 Cells

Eosinophilic esophagitis (EoE) is a chronic, immune/antigen-mediated disease characterized clinically by symptoms related to esophageal dysfunction and histologically by a marked eosinophilic infiltrate in the esophageal mucosa. What was once considered a rare disease has nowadays become one of the most frequent esophageal diseases in the Western countries, occupying a place just next to the gastroesophageal reflux disease. EoE etiology and pathogenesis remain largely unknown, although most studies consider that allergic and genetic factors play the most important role.. We report the case of EoE in an elderly male (octogenarian), giving a brief review of the current data related to epidemiology, pathogenesis, diagnosis, and treatment of the disease.. Dysphagia to solid foods was the leading symptom, and endoscopic findings included white exudates, longitudinal furrows, and concentric mucosal rings, all suggestive for EoE. Diagnosis relied on histological findings in esophageal mucosal biopsies (>30 eosinophils per high power field).He was treated with topical steroids for 8 weeks, symptoms improved gradually and the patient remained in remission at the 8-month follow-up.. This case emphasizes that EoE may occur in very old patients and gastroenterologists should have a high index of suspicion of this disorder in any elderly with dysphagia and endoscopic relevant features.

Topics: Administration, Inhalation; Aged, 80 and over; Anti-Inflammatory Agents; Biopsy; Deglutition Disorders; Eosinophilic Esophagitis; Esophagoscopy; Esophagus; Fluticasone; Follow-Up Studies; Humans; Male

Eosinophilic esophagitis (EoE) is a relatively common chronic immune-mediated disease of the esophagus characterized clinically by symptoms of esophageal dysfunction that vary by age. Histologically, EoE results in marked esophageal eosinophilia despite treatment with high-dose proton pump inhibition. The cornerstone of treatment is dietary restriction and/or pharmacologic therapy, mainly with topical steroids. This review briefly describes dietary therapy, but focuses on the various medical options in the treatment of EoE, with an emphasis on steroid-based therapy. Numerous landmark studies are reviewed describing the symptomatic and histologic endpoints as well as safety data. The literature strongly supports the use of topical steroid therapy as a means of significantly decreasing eosinophilic mucosal disease. Specifically, high-dose fluticasone propionate appears to be very effective, and has been shown to result in the resolution of mucosal eosinophilia in a large percentage of treated patients. Long-term studies over many years will need to determine whether mucosal healing will change the natural history of this stricture-causing disease. In addition to topical therapy, various other drug-based therapies are reported, including newer immune-based monoclonal antibodies.

Topics: Animals; Child; Eosinophilic Esophagitis; Fluticasone; Humans; Proton Pump Inhibitors

Eosinophilic esophagitis (EoE) is defined as a chronic immune/antigen-mediated esophageal disease characterized by clinical symptoms of esophageal dysfunction and histologically by eosinophil-predominant infiltration of the esophagus mucosa. Treatment of EoE should therefore lead to improvement of clinical symptoms and a histological decrease of eosinophilic inflammation. Topical corticosteroids (tCS; fluticasone, budesonide) have been demonstrated to be effective in treating EoE and therefore represent first-line therapy. To date, there is no approved therapy in the world for EoE. This is the reason why EoE patients are treated with medication such as inhalers or aqueous nebulizer solutions, which have to be swallowed. After administration, patients are not allowed to eat or drink for 45 min in order for the esophagus to become well coated so that the topical anti-inflammatory effect is maximized. For adults there are different dose ranges: fluticasone propionate 440-880 μg/day twice daily, budesonide 2 mg/day divided dose for inducing remission over a period of 4 to 8 weeks. Since EoE is a chronic disease known to relapse after termination of medication, maintenance therapy seems to be valuable, but there is no evidence from controlled studies with long-term follow-up. In several randomized trials, both tCS have been able to show a good safety profile. Candida esophagitis and oral candidiasis present the most common side effects of topical steroid therapy. At the moment, no data about tCS and long-term safety in EoE are available.

Topics: Adrenal Cortex Hormones; Androstadienes; Animals; Budesonide; Eosinophilic Esophagitis; Fluticasone; Humans

Eosinophilic esophagitis is a clinicopathologic disease that can present with a constellation of upper gastrointestinal symptoms and endoscopic findings in conjunction with significant infiltration of the esophageal tissue with eosinophils. Clinical and histologic resolution of the disease can be seen with dietary restriction therapies and systemic and topical corticosteroids. Because most patients have an atopic background and the disease seems to have an underlying T-helper type 2 pathogenesis, allergists and gastroenterologists need to be familiar with the diagnosis and management of this disease. In this review, clinical characteristics, endoscopic and histologic findings, and available therapy options are discussed.

Topics: Age Factors; Androstadienes; Budesonide; Eosinophilic Esophagitis; Eosinophils; Esophagus; Fluticasone; Food; Food Hypersensitivity; Humans; Sex Factors

Eosinophilic oesophagitis is a clinicopathological disease characterized by oesophageal eosinophilia and gastrointestinal symptoms. Currently, the optimal treatment regimens remain unclear. The pathogenesis of eosinophilic oesophagitis appears to involve immune dysregulation, while acid reflux may have a secondary role; the mainstays in treatment are aimed principally at these dual processes. While a trial of a PPI is worthwhile it is likely that PPI therapy is treating concurrent acid reflux rather than true eosinophilic oesophagitis. Dietary elimination with elemental feed is safe but poorly tolerated. Swallowed topical steroids are the mainstay of commercially available therapies. Both fluticasone and budesonide have been proven to be beneficial both symptomatically and in reducing oesophageal eosinophil counts in the short and medium term. Basic studies have determined a role for IL-5 in oesophageal remodelling in eosinophilic esophagitis. Initial clinical studies have shown single or multiple infusions of monoclonal antibody to IL-5 to be well tolerated and to cause a long-term decrease in both peripheral and sputum eosinophil count in these eosinophil driven conditions. At present, swallowed corticosteroids are the mainstay of treatment for patients with eosinophilic oesophagitis in patients failing PPI therapy. Studies have been heterogenous in their diagnostic criteria for eosinophilic oesophagitis and in the definition of response to therapy, making comparison of results difficult.

Topics: Adrenal Cortex Hormones; Androstadienes; Budesonide; Diet Therapy; Eosinophilic Esophagitis; Fluticasone; Humans; Proton Pump Inhibitors

Empirical elimination diets are effective for achieving histological remission in eosinophilic oesophagitis, but randomised trials comparing diet therapies are lacking. We aimed to compare a six-food elimination diet (6FED) with a one-food elimination diet (1FED) for the treatment of adults with eosinophilic oesophagitis.. We conducted a multicentre, randomised, open-label trial across ten sites of the Consortium of Eosinophilic Gastrointestinal Disease Researchers in the USA. Adults aged 18-60 years with active, symptomatic eosinophilic oesophagitis were centrally randomly allocated (1:1; block size of four) to 1FED (animal milk) or 6FED (animal milk, wheat, egg, soy, fish and shellfish, and peanut and tree nuts) for 6 weeks. Randomisation was stratified by age, enrolling site, and gender. The primary endpoint was the proportion of patients with histological remission (peak oesophageal count <15 eosinophils per high-power field [eos/hpf]). Key secondary endpoints were the proportions with complete histological remission (peak count ≤1 eos/hpf) and partial remission (peak counts ≤10 and ≤6 eos/hpf) and changes from baseline in peak eosinophil count and scores on the Eosinophilic Esophagitis Histology Scoring System (EoEHSS), Eosinophilic Esophagitis Endoscopic Reference Score (EREFS), Eosinophilic Esophagitis Activity Index (EEsAI), and quality of life (Adult Eosinophilic Esophagitis Quality-of-Life and Patient Reported Outcome Measurement Information System Global Health questionnaires). Individuals without histological response to 1FED could proceed to 6FED, and those without histological response to 6FED could proceed to swallowed topical fluticasone propionate 880 μg twice per day (with unrestricted diet), for 6 weeks. Histological remission after switching therapy was assessed as a secondary endpoint. Efficacy and safety analyses were done in the intention-to-treat (ITT) population. This trial is registered on ClinicalTrials.gov, NCT02778867, and is completed.. Between May 23, 2016, and March 6, 2019, 129 patients (70 [54%] men and 59 [46%] women; mean age 37·0 years [SD 10·3]) were enrolled, randomly assigned to 1FED (n=67) or 6FED (n=62), and included in the ITT population. At 6 weeks, 25 (40%) of 62 patients in the 6FED group had histological remission compared with 23 (34%) of 67 in the 1FED group (difference 6% [95% CI -11 to 23]; p=0·58). We found no significant difference between the groups at stricter thresholds for partial remission (≤10 eos/hpf, difference 7% [-9 to 24], p=0·46; ≤6 eos/hpf, 14% [-0 to 29], p=0·069); the proportion with complete remission was significantly higher in the 6FED group than in the 1FED group (difference 13% [2 to 25]; p=0·031). Peak eosinophil counts decreased in both groups (geometric mean ratio 0·72 [0·43 to 1·20]; p=0·21). For 6FED versus 1FED, mean changes from baseline in EoEHSS (-0·23 vs -0·15; difference -0·08 [-0·21 to 0·05]; p=0·23), EREFS (-1·0 vs -0·6; difference -0·4 [-1·1 to 0·3]; p=0·28), and EEsAI (-8·2 vs -3·0; difference -5·2 [-11·2 to 0·8]; p=0·091) were not significantly different. Changes in quality-of-life scores were small and similar between the groups. No adverse event was observed in more than 5% of patients in either diet group. For patients without histological response to 1FED who proceeded to 6FED, nine (43%) of 21 reached histological remission; for patients without histological response to 6FED who proceeded to fluticasone propionate, nine (82%) of 11 reached histological remission.. Histological remission rates and improvements in histological and endoscopic features were similar after 1FED and 6FED in adults with eosinophilic oesophagitis. 6FED had efficacy in just less than half of 1FED non-responders and steroids had efficacy in most 6FED non-responders. Our findings indicate that eliminating animal milk alone is an acceptable initial dietary therapy for eosinophilic oesophagitis.. US National Institutes of Health.

Topics: Animals; Elimination Diets; Eosinophilic Esophagitis; Female; Fluticasone; Humans; Male; Quality of Life; United States

Endoscopic features of eosinophilic esophagitis (EoE) are measured using the validated EoE Endoscopic Reference Score (EREFS); however, a threshold for treatment response has not been defined. We aimed to determine a cut-point for endoscopic response as measured by EREFS.. We performed a secondary analysis of a randomized clinical trial comparing budesonide slurry with swallowed fluticasone multidose inhaler for initial treatment of EoE. In the parent trial, EREFS was determined before and after treatment (score range 0-9), as were histologic findings and dysphagia symptoms. We performed tabular, flexible trend, and dependent mixture analyses of measures of treatment response to select the best clinical EREFS threshold.. In the 111 included patients (mean age 39 years; 67 % male; 96 % white), an EREFS threshold of ≤ 2 was 80 % sensitive (95 % confidence interval [CI] 69 % to 88 %) and 83 % specific (95 %CI 67 % to 94 %) for histologic response (peak of < 15 eosinophils per high-power field). Flexible trend analysis and dependent mixture modeling similarly suggested that a threshold of ≤ 2 best captured the correlation of EREFS with histologic and symptomatic measures. Dependent mixture modeling found near-total membership in the response class at EREFS of 0 or 1 and > 75 % at EREFS of 2 or 3.. An EREFS of ≤ 2 was the best clinical threshold for endoscopic response to topical steroid treatment, and was consistent with clinical and histologic response. Therefore, future studies can report a binary outcome of endoscopic response when EREFS is 2 or less.

Topics: Adult; Deglutition Disorders; Eosinophilic Esophagitis; Eosinophils; Esophagoscopy; Female; Fluticasone; Humans; Male

Topical steroids are effective treatments for eosinophilic esophagitis (EoE). The FLUTE (Fluticasone in EoE) trial evaluated safety and efficacy of APT-1011 (fluticasone propionate oral disintegrating tablet) vs placebo for treatment of EoE.. In this randomized, double-blind, placebo-controlled, dose-finding, phase 2b trial, 106 adults with EoE received 1 of 4 APT-1011 doses or placebo for a 12-week induction period and 40 weeks of maintenance. Primary outcome was histologic response (≤6 eosinophils per high-power field) at Week 12. Secondary outcomes included endoscopic features and dysphagia frequency.. Histologic response rates were 0% for placebo, 80% for APT-1011 3 mg twice daily (BID), 67% for 3 mg at bedtime (HS), 86% for 1.5 mg BID, 48% for 1.5 mg HS (P < .001 for all groups vs placebo). At Week 12, mean Edema/Rings/Exudates/Furrows/Strictures (EoE Endoscopic Reference Score) total score (max, 9.0) improved from 4.5 to 2.3 for 3 mg BID, 5.3 to 2.1 for 3 mg HS, 4.6 to 1.7 for 1.5 mg BID, 5.3 to 2.9 for 1.5 mg HS vs 5.2 to 4.5 for placebo. Mean dysphagia frequency over 14 days improved from baseline to Week 12 with all active groups improving more than placebo. Improvements were sustained to Week 52. APT-1011 was safe and well-tolerated, with higher incidence of candidiasis noted at the higher twice daily doses.. APT-1011 dosing regimens were superior for histologic and endoscopic responses, and for reduction in dysphagia frequency vs placebo. Based on the symptom improvement and assessment of adverse events together with the histologic response rate, 3 mg once daily at bedtime dose showed the most favorable risk-benefit profile.. gov, Number: NCT03191864.

Topics: Adult; Deglutition Disorders; Double-Blind Method; Eosinophilic Esophagitis; Esophagoscopy; Fluticasone; Humans; Tablets; Treatment Outcome

APT-1011, a fluticasone propionate orally disintegrating tablet formulation, is under investigation for the treatment of eosinophilic oesophagitis (EoE).. To evaluate the safety and tolerability of APT-1011 administered to patients with EoE and to assess the effect on clinical symptoms of EoE, endoscopic appearance and oesophageal eosinophilia.. A randomised, double-blind, placebo-controlled, multicentre, phase 1b/2a study was conducted at seven medical centres in the US to evaluate the safety and tolerability of APT-1011 over 8 weeks in adults and adolescents with EoE. Participants were randomised to placebo (n = 8), 1.5 mg APT-1011 BID (n = 8) or 3.0 mg APT-1011 QD (n = 8). Safety and tolerability were assessed as the primary outcome; histologic and endoscopic measures were assessed as exploratory outcomes.. There were no deaths, serious treatment-emergent adverse events (TEAEs), severe TEAEs or discontinuations from the study related to a TEAE. In one participant randomised to 1.5 mg APT-1011 BID, a reduction in cortisol was observed, but without evidence of adrenal insufficiency. Compared with placebo, treatment with APT-1011 resulted in greater reductions in oesophageal eosinophil counts, EoE Endoscopic Reference Score, patient global assessment and symptom-based EoE activity index from baseline to end of treatment (Week 8).. APT-1011 was safe and well tolerated in adolescents and adults with EoE. Exploratory efficacy outcomes demonstrated improvement in histologic and endoscopic findings as well evidence of symptom improvement. The results of this study support the continued development of APT-1011 for the treatment of EoE (NCT-01386112).

Topics: Administration, Oral; Adolescent; Adult; Child; Dose-Response Relationship, Drug; Double-Blind Method; Drug Compounding; Eosinophilic Esophagitis; Female; Fluticasone; Humans; Male; Middle Aged; Placebos; Severity of Illness Index; Tablets; Treatment Outcome; United States; Young Adult

Eosinophilic esophagitis (EoE) is assessed endoscopically (endoscopic activity), based on grades of edema, rings, exudates, furrows, and strictures (EREFS). We examined variations in endoscopic assessments of severity, developed and validated 3 EREFS-based scoring systems, and assessed responsiveness of these systems using data from a randomized placebo-controlled trial of patients with EoE.. For the development set, 5 gastroenterologists reviewed EREFS findings from 266 adults with EoE and provided endoscopist global assessment scores (EndoGA, scale of 0 to 10); variation (ΔEndoGA) was assessed using linear regression. We evaluated simple scores (features given arbitrary values from 0 to 3) and developed 2 scoring systems (adjusted score range, 0-100). We then fitted our linear regression model with mean EndoGA to data from 146 adults recruited in centers in Switzerland and the United States between April 2011 and December 2012. For the validation set, we collected data from 120 separate adults (recruited in centers in Switzerland and the United States between May 2013 and July 2014), assessing regression coefficient-based scores using Bland-Altman method. We assessed the responsiveness of our scoring systems using data from a randomized trial of patients with EoE given fluticasone (n=16) or placebo (n=8).. The distribution of EndoGA values differed among endoscopists (mean ΔEndoGA, 2.6±1.8; range 0-6.6). We developed 2 regression-based scoring systems to assess overall and proximal and distal esophageal findings; variation in endoscopic features accounted for more than 90% of the mean EndoGA variation. In the validation group, differences between mean EndoGA and regression-based scores were small (ranging from -4.70 to 2.03), indicating good agreement. In analyses of data from the randomized trial, the baseline to end of study change in patients given fluticasone was a reduction of 24.3 in simple score (reduction of 4.6 in patients given placebo, P=.052); a reduction of 23.5 in regression-based overall score (reduction of 6.56 in patients given placebo, P=.12), and a reduction of 23.8 (reduction of 8.44 in patients given placebo, P=.11).. Assessments of endoscopic activity in patients with EoE vary among endoscopists. In an analysis of data from a randomized controlled trial, we found that newly developed scoring systems are no better than simple scoring system in detecting changes in endoscopic activity. These results support the use of a simple scoring system in evaluation of endoscopic activity in patients with EoE. clinicaltrials.gov no: NCT00939263 and NCT01386112.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Dose-Response Relationship, Drug; Eosinophilic Esophagitis; Esophagoscopy; Esophagus; Female; Fluticasone; Humans; Male; Middle Aged; Prognosis; Severity of Illness Index; Young Adult

Topical steroid treatments for eosinophilic esophagitis (EoE) include swallowed fluticasone from a multi-dose inhaler (MDI) or oral viscous budesonide (OVB) slurry, but the 2 have never been compared. We assessed whether OVB was more effective than MDI for initial treatment of patients with EoE.. In a double-blind, double-dummy trial, patients with a new diagnosis of EoE were randomly assigned to groups given 8 weeks of either OVB (1 mg/4 mL) twice daily plus a placebo inhaler (n = 56) or fluticasone MDI (880 μg) twice daily plus a placebo slurry (n = 55). Primary outcomes were post-treatment maximum eosinophil counts per high-power field (eos/hpf) and a validated dysphagia score (dysphagia symptom questionnaire [DSQ]) at week 8. Secondary outcomes included endoscopic severity (validated EoE endoscopic reference score), histologic response (<15 eos/hpf), and safety.. In a modified intention-to-treat analysis, the subjects had baseline peak eosinophil counts of 73 and 77 eos/hpf in the OVB and MDI groups, respectively, and DSQ scores of 11 and 8. Post-treatment eosinophil counts were 15 and 21 in the OVB and MDI groups, respectively (P = .31), with 71% and 64% achieving histologic response (P = .38). DSQ scores were 5 and 4 in the OVB and MDI groups (P = .70). Similar trends were noted for post-treatment total EoE endoscopic reference scores (2 vs 3; P = .06). Esophageal candidiasis developed in 12% of patients receiving OVB and 16% receiving MDI; oral thrush was observed in 3% and 2%, respectively.. In a randomized clinical trial, initial treatment of EoE with either OVB or fluticasone MDI produced a significant decrease in esophageal eosinophil counts and improved dysphagia and endoscopic features. However, OVB was not superior to MDI, so either is an acceptable treatment for EoE. ClinicalTrials.gov ID NCT02019758.

Topics: Administration, Oral; Administration, Topical; Adolescent; Adult; Budesonide; Eosinophilic Esophagitis; Esophagoscopy; Female; Fluticasone; Glucocorticoids; Humans; Male; Metered Dose Inhalers; Middle Aged; Treatment Outcome; Vascular Ring; Young Adult

Non-dysphagia symptoms, such as heartburn and dyspepsia, are poorly characterized in adults with eosinophilic esophagitis (EoE). It is unclear if treatment improves these symptoms. The aim of this paper was to assess (i) heartburn and dyspepsia symptom severity in adult EoE patients using validated symptom measures; (ii) change in symptoms after treatment; and (iii) symptom association with endoscopic and histologic features. In a prospective cohort of adult EoE patients who were not responsive to proton pump inhibitor therapy, non-dysphagia symptoms were assessed with heartburn items from the validated GERD-HRQL (gastroesophageal reflux disease health-related quality of life) and SODA (severity of dyspepsia assessment) instruments. Subjects completed the questionnaires at baseline and after treatment. Association of baseline symptoms with endoscopic and histologic features, and before and after treatment with diet or topical steroids, was assessed. Eighty-six EoE patients (mean age 39 years, 57% male, 95% white) completed a baseline questionnaire and 62 completed the follow-up questionnaire. The mean baseline GERD-HRQL score was 4.5 ± 6.5 and the mean total SODA score was 41.0 ± 12.6. At baseline, there was a weak but significant correlation between peak eosinophils and the SODA score (r = 0.28; p = 0.03) and no association between heartburn and SODA scores and endoscopic or other histologic findings. After treatment, there was a decrease in GERD-HRQL heartburn (4.3 vs. 2.6; p = 0.04) and SODA (49.5 vs. 35.5; p = 0.04) scores in histologic responders, but not in nonresponders. In a prospective cohort of EoE patients, baseline eosinophils positively correlated with dyspepsia severity. Heartburn and dyspepsia symptoms improved after treatment in histologic responders.

Topics: Adult; Anti-Inflammatory Agents; Budesonide; Combined Modality Therapy; Diet Therapy; Dyspepsia; Eosinophilic Esophagitis; Esophagoscopy; Female; Fluticasone; Follow-Up Studies; Heartburn; Humans; Male; Middle Aged; Prospective Studies; Quality of Life; Severity of Illness Index; Treatment Outcome

The role of esophageal dilation in patients with esophageal eosinophilia with dysphagia remains unknown. The practice of dilation is currently based on center preferences and expert opinion. The aim of this study is to determine if, and to what extent, dysphagia improves in response to initial esophageal dilation followed by standard medical therapies. We conducted a randomized, blinded, controlled trial evaluating adult patients with dysphagia and newly diagnosed esophageal eosinophilia from 2008 to 2013. Patients were randomized to dilation or no dilation at time of endoscopy and blinded to dilation status. Endoscopic features were graded as major and minor. Subsequent to randomization and endoscopy, all patients received fluticasone and dexlansoprazole for 2 months. The primary study outcome was reduction in overall dysphagia score, assessed at 30 and 60 days post-intervention. Patients with severe strictures (less than 7-mm esophageal diameter) were excluded from the study. Thirty-one patients were randomized and completed the protocol: 17 randomized to dilation and 14 to no dilation. Both groups were similar with regard to gender, age, eosinophil density, endoscopic score, and baseline dysphagia score. The population exhibited moderate to severe dysphagia and moderate esophageal stricturing at baseline. Overall, there was a significant (P < 0.001) but similar reduction in mean dysphagia score at 30 and 60 days post-randomization compared with baseline in both groups. No significant difference in dysphagia scores between treatment groups after 30 (P = 0.93) or 60 (P = 0.21) days post-intervention was observed. Esophageal dilation did not result in additional improvement in dysphagia score compared with treatment with proton pump inhibitor and fluticasone alone. In patients with symptomatic esophageal eosinophilia without severe stricture, dilation does not appear to be a necessary initial treatment strategy.

Topics: Adult; Deglutition Disorders; Dexlansoprazole; Dilatation; Eosinophilic Esophagitis; Esophageal Stenosis; Esophagoplasty; Esophagoscopy; Esophagus; Female; Fluticasone; Glucocorticoids; Humans; Male; Proton Pump Inhibitors; Single-Blind Method; Treatment Outcome; Young Adult

To establish the prevalence of adrenal insufficiency (AI) in children with eosinophilic esophagitis treated with swallowed fluticasone propionate (FP) or budesonide.. Children treated with FP or budesonide for ≥ 6 months underwent a low-dose adrenocorticotropin stimulation test. Patients using systemic, inhaled, intranasal, or topical glucocorticoids were excluded. The primary outcome is AI, defined as peak serum cortisol <18 μg/dL (≤ 495 nmol/L).. Of 58 patients (81% male), 67% were on FP (median age 13.7 years [range 4.3-19.1], dose 1320 μg/d [440-1760], treatment duration 4.0 years [0.6-13.5]). Thirty-three percent were on budesonide (median age 10.7 years [range 3.2-17.2], dose 1000 μg/d [500-2000], treatment duration 3.4 years [0.6-7.7]). The overall prevalence of abnormal peak cortisol response (≤ 20 μg/dL) was 15% (95% CI 6%-25%) (indeterminate [18-20 μg/dL] 5% [n = 3] vs AI [<18 μg/dL] 10% [n = 6]). All patients on budesonide had a normal response vs only 77% of patients on FP (P = .02), all of whom were taking FP at a dose >440 μg/d.. AI was present in 10% of children treated with swallowed glucocorticoids for ≥ 6 months and was found only in those treated with FP >440 μg/d. We recommend low-dose adrenocorticotropin stimulation testing in children treated long term with high dose FP to allow early detection of AI.

Topics: Administration, Oral; Adolescent; Adrenal Insufficiency; Anti-Inflammatory Agents; Budesonide; Child; Child, Preschool; Drug Administration Schedule; Eosinophilic Esophagitis; Female; Fluticasone; Follow-Up Studies; Humans; Male; Prevalence; Prospective Studies; Treatment Outcome; Young Adult

The esophageal mucosal integrity is impaired in patients with eosinophilic esophagitis (EoE). We aimed to evaluate the effect of fluticasone propionate on inflammation and functional and structural markers of esophageal mucosal barrier integrity in adult patients with EoE.. In this prospective study, we included 15 EoE patients (median age (IQR), 43 (30-45) years). Patients underwent upper endoscopy before and after an 8-week course of swallowed fluticasone propionate 500 μg BID. Several parameters of esophageal mucosal barrier integrity were evaluated: esophageal electrical tissue impedance in vivo during endoscopy, transepithelial electrical resistance (TER) and transepithelial molecule flux in Ussing chambers using esophageal biopsy specimens, and intercellular spaces as a structural marker of permeability using electron microscopy. Esophageal eosinophils and mast cells were counted, and expression of inflammatory cytokines and barrier integrity proteins was investigated using qPCR. Esophageal symptoms and signs were also assessed.. Peak eosinophil and mast cell counts decreased significantly after fluticasone propionate treatment. The esophageal mucosal integrity increased substantially during treatment, as shown by increased extracellular impedance and TER (both P<0.01) and decreased transepithelial molecule flux in Ussing chambers (P<0.05). Whereas expression of genes encoding for inflammatory cytokines (IL5, IL13, eotaxin-3, periostin, TSLP) decreased after treatment, expression of genes encoding for barrier integrity proteins (filaggrin and desmoglein-1) increased.. Fluticasone propionate treatment decreases eosinophilic inflammation and improves the esophageal mucosal barrier integrity in adult EoE patients. Improvement of the mucosal barrier integrity correlates with normalization of expression of desmoglein-1 and filaggrin marker genes.

Topics: Adult; Anti-Inflammatory Agents; Biopsy; Cytokines; Deglutition; Dose-Response Relationship, Drug; Electric Impedance; Eosinophilic Esophagitis; Eosinophils; Esophagoscopy; Female; Filaggrin Proteins; Fluticasone; Follow-Up Studies; Gene Expression Regulation; Humans; Intestinal Mucosa; Leukocyte Count; Male; Microscopy, Electron; Middle Aged; Prospective Studies; Real-Time Polymerase Chain Reaction; Recovery of Function; RNA; Treatment Outcome

We evaluated the efficacy and safety of high-dose swallowed fluticasone propionate (FP) and dose reduction in patients with eosinophilic esophagitis (EoE) and analyzed esophageal transcriptomes to identify mechanisms.. We conducted a randomized, multisite, double-blind, placebo-controlled trial of daily 1760 mcg FP in participants age 3-30 years with active EoE. Twenty-eight participants received FP, and 14 participants received placebo. After 3 months, participants given FP who were in complete remission (CR) received 880 mcg FP daily, and participants in the FP or placebo groups who were not in CR continued or started, respectively, 1760 mcg FP daily for 3 additional months. The primary end point was histologic evidence for CR. Secondary end points were partial remission (PR), symptoms, compliance, esophageal gene expression, esophageal eosinophil count, and the relationship between clinical features and FP responsiveness.. After 3 months, 65% of subjects given FP and no subjects given placebo were in CR (P = .0001); 12% of those given FP and 8% of those given placebo were in PR. In the FP group, 73% of subjects remained in CR, and 20% were in PR after the daily dose was reduced by 50%. Extending FP therapy in FP-resistant participants did not induce remission. FP decreased heartburn severity (P = .041). Compliance, age, sex, atopic status, or anthropomorphic features were not associated with response to FP. Gene expression patterns in esophageal tissues of FP responders were similar to those of patients without EoE; there was evidence for heterogeneous steroid signaling in subjects who did not respond to FP and preliminary evidence for transcripts predictive of FP responsiveness.. Daily administration of a high dose of FP induces histologic remission in 65%-77% of patients with EoE after 3 months. A 50% dose reduction remained effective in 73%-93% of patients who initially responded to FP. Nonresponders had evidence of steroid resistance; histologic and molecular markers may predict resistance. Clinicaltrials.gov number: NCT00426283.

Topics: Administration, Oral; Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Child; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Drug Resistance; Eosinophilic Esophagitis; Fluticasone; Gene Expression Profiling; Gene Expression Regulation; Humans; Remission Induction; Severity of Illness Index; Time Factors; Treatment Outcome; United States; Young Adult

Patients with clinical symptoms of esophageal dysfunction and dense eosinophilic infiltration of the esophageal mucosa are suspected to have eosinophilic esophagitis (EoE). Topical steroids are often used as first-line therapy for EoE, although some patients respond clinically to proton pump inhibitors (PPIs). The purpose of this study was to compare the histological and clinical response of patients with esophageal eosinophilia treated with aerosolized swallowed fluticasone propionate vs. esomeprazole.. This prospective single-blinded randomized controlled trial enrolled newly diagnosed patients with suspected EoE, defined as having clinical symptoms related to esophageal dysfunction with at least 15 eosinophils/high power field (hpf). Patients underwent 24-h pH/impedance monitoring to establish gastroesophageal reflux disease (GERD). Patients were stratified by the presence of GERD and randomized to receive fluticasone 440 mcg twice daily or esomeprazole 40 mg once daily for 8 weeks followed by repeat endoscopy with biopsies. The primary outcome was histological response of esophageal eosinophilia, defined as <7 eosinophils/hpf. Secondary outcomes included clinical change in symptoms using the validated Mayo dysphagia questionnaire (MDQ) and interval change in endoscopic findings following treatment.. Forty-two patients (90% male, 81% white, mean age 38 ± 10 years) were randomized into fluticasone (n = 21) and esomeprazole (n = 21) treatment arms. In all, 19% (8/42) of patients had coexisting GERD and were equally stratified into each arm (n = 4). Overall, there was no significant difference in resolution of esophageal eosinophilia between fluticasone and esomeprazole (19 vs. 33%, P = 0.484). In patients with established GERD, resolution of esophageal eosinophilia was noted in 0% (0/4) of the fluticasone group compared with 100% (4/4) of the esomeprazole group (P = 0.029). In GERD-negative patients, there was no significant difference in resolution of esophageal eosinophilia between treatment arms with fluticasone and esomeprazole (24 vs.18%, P = 1.00). The MDQ score significantly decreased after treatment with esomeprazole (19 ± 21 vs. 1.4 ± 4.5, P<0.001), but not with fluticasone (17 ± 18 vs. 12 ± 16, P = 0.162). Improvement in endoscopic findings and other histological markers were similar between treatment groups.. Fluticasone and esomeprazole provide a similar histological response for esophageal eosinophilia. With regard to clinical response, esomeprazole was superior to fluticasone, particularly in patients with established GERD.

Topics: Adult; Androstadienes; Anti-Inflammatory Agents; Anti-Ulcer Agents; Eosinophilic Esophagitis; Esomeprazole; Female; Fluticasone; Humans; Male; Middle Aged; Single-Blind Method; Treatment Outcome

We evaluated the effect of aerosolized fluticasone therapy on symptomatic dysphagia and histologic eosinophilia in adults with eosinophilic esophagitis (EoE).. We performed a double-blind, randomized, placebo-controlled trial of fluticasone in 42 adult patients with a new diagnosis of EoE (30 men; mean age, 37.5 y). Participants were assigned randomly to groups that swallowed 880 μg of aerosolized fluticasone twice daily (n = 21), or took a placebo inhaler twice daily (n = 15) for 6 weeks. End points of the study were symptomatic and histologic response.. A complete histologic response (>90% decrease in mean eosinophil count) was observed in 11 of 15 subjects who received 6 weeks of fluticasone (62%), compared with none of the 15 subjects who received placebo (P < .001), based on intention-to-treat analysis; histologic responses were observed in 68% of subjects who received fluticasone (13 of 19) compared with none of those who received placebo (0 of 15) by per-protocol analysis (P < .001). Intracellular staining for eosinophil-derived neurotoxin was reduced in 81% of subjects who received fluticasone (13 of 16) compared with 8% who received placebo (1 of 13) (P < .001). Dysphagia was reduced in 57% of subjects who received fluticasone (12 of 21) compared with 33% who received placebo (7 of 21) (P = .22) by intention-to-treat analysis; dysphagia was reduced in 63% of patients who received fluticasone (12 of 19) and 47% of those who received placebo (7 of 15) (P = .49) based on per-protocol analysis. Esophageal candidiasis developed in 26% of subjects who received fluticasone (5 of 19), but in none of the subjects in the placebo group (P = .05).. Aerosolized, swallowed fluticasone leads to a histologic but not a symptomatic response in adults with EoE.

Topics: Administration, Oral; Adolescent; Adult; Aerosols; Aged; Androstadienes; Anti-Allergic Agents; Double-Blind Method; Eosinophilic Esophagitis; Female; Fluticasone; Histocytochemistry; Humans; Male; Microscopy, Fluorescence; Middle Aged; Placebos; Treatment Outcome; Young Adult

Recent research shows that both pediatric and adult patients with eosinophilic esophagitis (EoE) experience esophageal remodeling marked by increased collagen deposition in which TGF-β plays an important role. However, limited data are available on the intensity and reversibility of fibrous remodeling in adults with EoE.. We sought to analyze differences in collagen deposition in the lamina propria (LP) and profibrogenic cytokine gene expression along with other changes induced by prolonged treatment with fluticasone propionate in adults with EoE.. Ten adults given consecutive diagnoses of EoE were studied prospectively. Deep esophageal biopsy specimens were obtained before and after 1 year of treatment with fluticasone propionate. Collagen deposition in the LP was assessed in tissue sections with the aid of the Masson trichrome technique. IL5, TGFB1, fibroblast growth factor 9 (FGF9), and CCL18 gene expression was quantified through real-time PCR. EoE results were compared among samples from 10 adult patients with gastroesophageal reflux disease and 10 control subjects with healthy esophagi.. Patients with EoE showed a significant increase in subepithelial collagen deposition; this correlated positively with eosinophil density in the LP and the patient's age. Prolonged steroid treatment induced a nonsignificant reduction in subepithelial fibrosis, which remained significantly higher than in control subjects. Profibrogenic cytokine gene expression also increased in patients with EoE, with IL5 (P < .001), FGF9 (P = .005), and CCL18 (P = .008) all significantly upregulated. After 1 year of treatment, a reduction was observed in gene expression; for CCL18 expression, this decrease was statistically significant (P < .001).. Esophageal remodeling is associated with upregulated gene expression of profibrogenic cytokines in adults with EoE. Prolonged treatment with fluticasone propionate leads to a nonsignificant reduction in subepithelial collagen deposition accompanied by downregulation of profibrogenic cytokine gene expression, with that of CCL18 being especially significant.

Topics: Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Collagen; Cytokines; Eosinophilic Esophagitis; Female; Fibrosis; Fluticasone; Gene Expression; Humans; Male; Middle Aged; Real-Time Polymerase Chain Reaction; Young Adult

Given the variety of preparations and lack of standardization of swallowed topical corticosteroids (STC) for treatment of eosinophilic esophagitis (EoE), we sought to better understand STC prescribing practices of pediatric gastroenterologists. A 12-question survey was distributed to members of North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Eosinophilic Gastrointestinal Disease Special Interest Group and responses were analyzed. Forty-two of 68 physicians responded. Oral viscous budesonide (OVB) was overall first choice STC in 31 (74%) survey respondents, with OVB most frequently utilized in patients under 5 years old and fluticasone propionate in patients 13-18 years old. Nineteen types of mixing vehicles were used for OVB preparation, the 3 most frequent being sucralose, honey, and artificial maple syrup. Insurance coverage, cost, and patient compliance were most frequently cited barriers to STC use. Highly variable STC prescribing practices reported by this group highlights the need for standardization of STC treatment in EoE.

Topics: Adolescent; Budesonide; Child; Child, Preschool; Eosinophilic Esophagitis; Fluticasone; Glucocorticoids; Humans

Although swallowed topical steroids are effective in inducing histological remission in eosinophilic esophagitis (EoE), their efficacy is limited by treatment nonadherence. In this study, we objectively measured adherence rates to swallowed topical steroids in adolescents with EoE over the course of 8 weeks and analyzed the association between adherence rate, disease and demographic features, symptom severity, and medication-taking habit strength. We found that approximately 20% of adolescents with EoE were over-dosing on their medications. After excluding these patients, mean adherence rate was 67.0% (±19.4%) and median adherence rate was 63% (interquartile range 53%-88%). Adherence was not associated with demographic features, disease history, symptom severity, or quality of life but was associated with habit strength (Pearson r = 0.48, P = 0.04). These findings suggest that habit strength may serve as a potential target for interventions aimed at improving adherence in adolescents with EoE.

Topics: Administration, Oral; Adolescent; Eosinophilic Esophagitis; Fluticasone; Humans; Quality of Life; Steroids

Topics: Eosinophilic Esophagitis; Fluticasone; Humans; Microbiota; Steroids

No approved medication exists for the treatment of eosinophilic esophagitis (EoE) in the United States, which forces patients to utilize off-label drugs and/or create their own formulations. We assessed the efficacy of a standardized compounded fluticasone suspension. To do this, we performed a retrospective cohort study identifying all EoE patients treated with compounded fluticasone. Compounded fluticasone was prescribed during routine clinical care and dispensed by a specialty compounding pharmacy. Clinical data were extracted from medical records. Outcomes (symptomatic, endoscopic, and histologic) were assessed after the initial and last compounded fluticasone treatment in our system. There were 27 included patients (mean age 34.2; 67% male; 96% white) treated for a mean length of 5.4 ± 4.4 months. The majority (89%) previously utilized dietary elimination or topical corticosteroids, and many (75%) had primary non-response or secondary loss of response to these treatments. After starting compounded fluticasone, symptoms and endoscopic findings improved [dysphagia (89 vs. 56%, P = 0.005), food impaction (59 vs. 4%, P = 0.003), heartburn (26 vs. 4%, P = 0.01), chest pain (26 vs. 8%, P = 0.05), white plaques (63 vs. 32%; P = 0.005), furrows (81 vs. 60%; P = 0.06), and edema (15 vs. 4%; P = 0.16)]. The median of the peak eosinophil counts decreased from 52 to 37 eos/hpf (P = 0.10) and 35% of patients achieved <15 eos/hpf. In conclusion, compounded fluticasone provided a significant improvement in symptoms and endoscopic findings, with more than a third achieving histologic response in a treatment refractory EoE population. Compounded fluticasone should be considered as an EoE management option.

Topics: Adult; Eosinophilic Esophagitis; Esophagoscopy; Female; Fluticasone; Humans; Male; Retrospective Studies; Treatment Outcome

Topics: Adrenal Cortex Hormones; Adrenal Insufficiency; Child; Eosinophilic Esophagitis; Fluticasone; Humans; Steroids

Topics: Administration, Oral; Eosinophilic Esophagitis; Fluticasone; Humans; Tablets

Topics: Administration, Oral; Eosinophilic Esophagitis; Fluticasone; Humans; Tablets

Few factors have been identified that can be used to predict response of patients with eosinophilic esophagitis (EoE) to topical steroid treatment. We aimed to determine whether baseline clinical, endoscopic, histologic, and molecular features of EoE can be used to predict histologic response.. We collected data from 97 patients with EoE, from 2009 through 2015, treated with a topical steroid for 8 weeks; 59 patients had a histologic response to treatment. Baseline clinicopathologic features and gene expression patterns were compared between patients with a histologic response to treatment (<15 eos/hpf) and non-responders (≥15 eos/hpf). We performed sensitivity analyses for alternative histologic response definitions. Multivariate logistic regression was performed to identify predictive factors associated with response to therapy, which were assessed with area under the receiver operator characteristic (AUROC) curves.. Baseline dilation was the only independent predictor of non-response (odds ratio [OR], 0.30; 95% CI, 0.10-0.89). When an alternate response (<1 eos/hpf) and non-response (<50% decrease in baseline eos/hpf) definition was used, independent predictors of response status were age (OR, 1.08; 95% CI, 1.02-1.14), food allergies (OR, 12.95; 95% CI, 2.20-76.15), baseline dilation (OR, 0.17; 95% CI, 0.03-0.88), edema or decreased vascularity (OR, 0.20; 95% CI, 0.04-1.03), and hiatal hernia (OR, 0.07; 95% CI, 0.01-0.66). Using these 5 factors, we developed a predictive model that discriminated complete responders from non-responders with an AUROC of 0.88. Baseline gene expression patterns were not associated with treatment response and did not change with different histologic response thresholds.. In an analysis of 97 patients with EoE, we found dilation to be the only baseline factor associated with non-response to steroid treatment (<15 eos/hpf). However, a model comprising 5 clinical, endoscopic, and histologic factors identified patients with a complete response (<1 eos/hpf). A baseline gene expression panel was not predictive of treatment response at any threshold.

Topics: Administration, Topical; Adult; Biomarkers; Biopsy; Budesonide; Eosinophilic Esophagitis; Esophagoscopy; Esophagus; Female; Fluticasone; Follow-Up Studies; Glucocorticoids; Humans; Male; Prospective Studies; Treatment Outcome

Eosinophilic esophagitis (EoE) is a chronic immune/antigen-mediated disorder defined by eosinophilic-predominant inflammation and esophageal dysfunction.

Topics: Administration, Topical; Adult; Budesonide; Combined Modality Therapy; Diet Therapy; Eosinophilic Esophagitis; Female; Fluticasone; Glucocorticoids; Humans; Male; Retrospective Studies; Treatment Outcome

Topics: Adult; Eosinophilic Esophagitis; Fluticasone; Follow-Up Studies; Goals; Humans; Steroids

Topics: Adrenal Cortex Hormones; Adrenal Insufficiency; Adrenocorticotropic Hormone; Child; Eosinophilic Esophagitis; Fluticasone; Humans

Topics: Budesonide; Eosinophilic Esophagitis; Fluticasone; Humans; Steroids

Eosinophilic esophagitis (EoE) is treated with dietary modification and/or pharmacologic management with swallowed topical steroids. Swallowed fluticasone propionate (FP) and oral viscous budesonide (OVB) have proven to be effective in resolving symptoms and reversing histologic changes in children and adults with EoE. There are minimal comparative studies between the 2 agents.. The aim of the study was to retrospectively compare endoscopic and histologic outcomes after FP versus OVB therapy in children with EoE in our center.. We performed a retrospective chart review of subjects diagnosed with EoE at a tertiary care center between 2010 and 2015. Inclusion criteria were FP or OVB therapy for ≥8 weeks along with pre- and post-treatment endoscopic evaluation. Demographic and clinical features and endoscopic and histologic assessment were recorded for comparative analysis. Histologic response was defined as <15 eos/hpf and remission as <5 eos/hpf.. The study included 68 EoE patients (20 FP and 48 OVB) with a mean age of 10.6 ± 5.2 years (range 1-20 years); 81% were boys and 68% were Caucasian. No significant demographic or clinical differences were noted between the 2 study groups. Overall histologic response to topical steroids was seen in 44 of 68 (65%) patients. A significantly greater number of patients achieved histologic response with OVB (36/48, 75%) than with FP (8/20, 40%) (P = 0.0059). Mean pretreatment peak eos/hpf was 46 ± 19 in the FP group versus 45 ± 23 in the OVB group. Mean post-treatment peak eos/hpf was 20 ± 29 in the FP group versus 12 ± 16 in the OVB group (P = 0.002). There was also a significantly greater difference in the change of absolute eos/hpf from pre- to post-treatment in the OVB group (-33) versus FP (18) (P = 0.047). A greater number of OVB-treated patients without asthma had a histologic response compared to those with asthma (P = 0.031). The response to OVB was not affected by the delivery vehicle, namely sucralose (Splenda) versus Neocate Duocal.. Our data suggest that treatment with OVB leads to better endoscopic and histologic outcomes than FP. Adherence to treatment and history of asthma are major determining factors in the response to treatments. Using Neocate Duocal as the OVB delivery vehicle is just as effective as sucralose.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Anti-Inflammatory Agents; Budesonide; Child; Child, Preschool; Drug Administration Schedule; Eosinophilic Esophagitis; Esophagoscopy; Female; Fluticasone; Humans; Infant; Male; Retrospective Studies; Treatment Outcome; Young Adult

Few studies have examined combined or alternating treatment algorithms in eosinophilic esophagitis.. We conducted a retrospective cohort study to ascertain the efficacy and adherence to a combined and alternating treatment approach with topical corticosteroids and 2-food elimination diet for pediatric EoE.. Patients were prescribed a 2-food elimination diet (milk and soy) and topical corticosteroid (fluticasone or oral viscous budesonide) for 3 months, after which the steroid was discontinued and 2-food elimination diet continued for 3 months. An EGD was performed at baseline, 3 and 6 months. Clinical, endoscopic, and histologic data were extracted from electronic medical records. Nonparametric tests assessed adherence and outcomes.. Twenty-nine eosinophilic esophagitis cases were included (mean age 11.5 years, 61% male). Complete adherence to combined therapy and 2-food elimination diet alone was 75 and 79%, respectively. Median eosinophil counts decreased from 51 to 2 eosinophils/hpf (p < 0.001) after combined treatment and rebounded to 31 (p = 0.07) after 2FED alone. Dysphagia improved after both the combined and 2-food elimination diet alone treatment approaches (52 vs. 11% and 10%; p = 0.001, 0.005). Nonsignificant improvements in endoscopic findings were documented across the length of follow-up.. An initial combined treatment approach resulted in significant improvements in symptoms and histologic findings. While symptomatic improvements continued with 2-food elimination diet alone, the histologic improvement was not maintained. While loss to follow-up may obscure the efficacy of 2-food elimination diet alone, a combined/alternating treatment approach merits assessment in a larger prospective study.

Topics: Administration, Oral; Administration, Topical; Adrenal Cortex Hormones; Budesonide; Child; Child, Preschool; Combined Modality Therapy; Deglutition Disorders; Eosinophilic Esophagitis; Eosinophils; Esophagoscopy; Female; Fluticasone; Humans; Leukocyte Count; Male; Medication Adherence; Retrospective Studies; Time Factors; Treatment Outcome

Topics: Administration, Oral; Adult; Budesonide; Deglutition Disorders; Eosinophilic Esophagitis; Esophagoscopy; Female; Fluticasone; Glucocorticoids; Humans; Intestinal Obstruction; Male; Proton Pump Inhibitors

Topical steroids are the primary medical therapy for eosinophilic esophagitis (EoE). Current steroid formulations are used off-label and designed for airway delivery. It is known that the efficacy of topical steroids depends on drug-mucosal contact time, which is related to its formulation. The purpose of this study is to examine the effectiveness of fluticasone administered by means of an orally administered powder formulation. We conducted a retrospective analysis of patients diagnosed with EoE based on current guidelines and who were treated with orally administered fluticasone powder. The primary outcome was histologic response (peak eosinophil density (eos/hpf)). Secondary outcomes included patient-reported symptoms (EoEQ) and endoscopic features measured by a validated instrument (EoE endoscopic reference score, EREFS). Forty patients were treated with fluticasone powder with doses of 500 to 1000 mcg b.i.d. A significant difference was found between pre- and posttreatment levels of eosinophilia (P < 0.0001). Seventy-five percent of patients achieved peak densities of <15 eos/hpf. Improvement was also demonstrated in dysphagia symptoms (P = 0.031) and endoscopic findings of furrows (P = 0.0001) and exudates (P = 0.0001). Oral fluticasone powder induced significant improvement in histopathology, symptoms, and endoscopic features of inflammation in adults with EoE. It offers an easy-to-administer formulation of a topical steroid that circumvents concerns with esophageal delivery of commonly used, aerosolized inhaler preparations.

Topics: Adult; Anti-Inflammatory Agents; Eosinophilic Esophagitis; Esophagus; Female; Fluticasone; Humans; Inflammation; Male; Middle Aged; Powders; Retrospective Studies; Treatment Outcome

Focal dermal hypoplasia (FDH) is a rare disorder of the mesodermal and ectodermal tissues. Here we present an eight-year-old female known to have FDH who presents with poor weight gain and dysphagia. She was diagnosed with multiple esophageal papillomas and eosinophilic esophagitis. She was successfully treated with argon plasma coagulation and ingested fluticasone propionate, which has not been described previously in a child.

Topics: Argon; Carcinoma, Squamous Cell; Child; Eosinophilic Esophagitis; Esophageal Neoplasms; Female; Fluticasone; Focal Dermal Hypoplasia; Humans; Papilloma; Polyps

It is unknown if successful control of esophageal inflammation in eosinophilic esophagitis (EoE) decreases the need for subsequent esophageal dilation. We aimed to determine whether histologic response to topical steroid treatment decreases the likelihood and frequency of subsequent esophageal dilation. We conducted a retrospective cohort study. Patients with an incident diagnosis of EoE were included if they had an initial esophageal dilation, received topical steroids, and had a subsequent endoscopy with biopsies. The number of dilations performed in each group was determined, and histologic responders (<15 eos/hpf) were compared to nonresponders. The 55 EoE patients included (27 responders and 28 nonresponders) underwent a mean of 3.0 dilations over a median follow-up of 19 months. Responders required fewer dilations than nonresponders (1.6 vs. 4.6, P = 0.03), after adjusting for potential confounders. Despite undergoing significantly fewer dilations, responders achieved a similar increase in esophageal diameter with dilation (4.9 vs. 5.0 mm; P = 0.92). In EoE patients undergoing esophageal dilation at baseline, control of inflammation with topical steroids was associated with a 65% decrease in the number of subsequent dilations to maintain the same esophageal caliber. This suggests that inflammation control is an important goal in patients with fibrostenotic changes of EoE.

Topics: Administration, Topical; Adult; Anti-Inflammatory Agents; Biopsy; Budesonide; Dilatation; Eosinophilic Esophagitis; Esophageal Stenosis; Esophagus; Female; Fluticasone; Humans; Male; Middle Aged; Young Adult

Eosinophilic esophagitis is a chronic immunogenic-antigen mediated disease of the esophagus, characterized by symptoms related to esophagus dysfunction, histologically defined by over 15 eosinophil counts seen in high-power microscopic field, without gastroesophageal reflux disease. In adults, the most common clinical manifestations are dysphagia, reflux, chest pain, regurgitation and bolus impaction.. We presented the case of a female patient, hospitalized for a serious form of pancreatitis with complications, which required artificial ventilation and enteral feeding, after the initial esophagoscopy verified reflux esophagitis. Further treatment cured the primary illness, and peroral feeding was reintroduced. However, dysphagia with regurgitation occurred, and endoscopic and radiological tests verified esophagus stenosis, which histopathologically corresponded to erosive esophagitis. Two months of treatment by a double dosage of proton pump inhibitors led to no regression of disorders, and the repeated biopsies from the stenotic segments resulted in over 30 eosinophil counts in the high-power microscopic field, which histologically corresponds to eosinophilic esophagitis. Subsequent therapy included fluticasone 880 μg/day orally for a period of eight weeks, which led to complete regression of disorders, and endoscopic and histopathologic remission.. In case of irresponsiveness to the conventional therapy by proton pump inhibitors, repeated esophagoscopy and histopathological analyses of esophagus mucosa biopsy can point to the diagnosis of eosinophilic esophagitis, and a good therapeutic response to topical corticosteroids can be regarded as the clinical confirmation of the diagnosis.

Topics: Administration, Oral; Adrenal Cortex Hormones; Aged; Biopsy; Diagnosis, Differential; Drug Administration Schedule; Eosinophilic Esophagitis; Esophagoscopy; Female; Fluticasone; Humans; Predictive Value of Tests; Remission Induction; Tomography, X-Ray Computed; Treatment Outcome

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease in which food antigens play a key role. Current therapeutic options are limited to long-term steroid medication and dietary elimination of multiple foods, each of which is challenging. Our objective was to compare single food elimination of cow's milk to swallowed fluticasone in pediatric EoE patients. This is a prospective, comparative effectiveness trial of newly diagnosed EoE patients (ages 2-18 years) treated with swallowed fluticasone (n = 24) or elimination of cow's milk (n = 20). The dual outcome measures of repeat esophageal biopsy (6-8 weeks) and change in Pediatric Quality of Life Inventor (PedsQL) EoE Module and Symptoms Scales were used to assess response to treatment. After 6-8 weeks of treatment, peak esophageal eosinophil counts decreased to below the threshold of 15 eosinophils/high-power field in 64% of patients treated with cow's milk elimination and 80% of patients treated with swallowed fluticasone (P = 0.4). Mean PedsQL EoE Module total scores (69 vs. 82; P < 0.005) and Total Symptoms scores (58 vs. 75; P = 0.001) showed significant improvement with cow's milk elimination. Among children treated with swallowed fluticasone, mean PedsQL EoE Module total scores (64 vs. 75; P < 0.05) and Total Symptoms scores (58 vs. 69; P < 0.01) were also significantly improved after 6-8 weeks of therapy. Removal of cow's milk from the diet is an effective single food elimination treatment for pediatric patients with EoE as assessed by statistically significant histologic and symptomatic improvement. Cow's milk elimination may be more desirable for EoE patients who do not want to take chronic, long-term steroid medications.

Topics: Adolescent; Animals; Anti-Allergic Agents; Biopsy; Child; Child, Preschool; Diet Therapy; Eosinophilic Esophagitis; Eosinophils; Esophagus; Female; Fluticasone; Humans; Male; Milk; Milk Hypersensitivity; Prospective Studies; Quality of Life; Symptom Assessment; Treatment Outcome

Eosinophilic esophagitis (EoE) has been reported to be more prevalent in patients with esophageal atresia/tracheoesophageal fistula (EA-TEF). To date, there is limited data on the management of EoE in this group of patients. The aim of this study is to evaluate the treatment outcomes of EoE in children with EA-TEF. A retrospective chart review was performed on all EA-TEF children who were diagnosed with and treated for EoE between January 2000 and September 2013 at the Sydney Children's Hospital. Data collected included details of the patient's treatment, post-treatment endoscopy, symptoms and nutrition. Twenty patients were included in the study. Median age at diagnosis was 26 months (8-103 months), and median time from diagnosis to last follow-up was 23 months (2-132 months). Patients were treated with budesonide slurry, swallowed fluticasone, elimination diet alone or in combination. All patients were on proton pump inhibitors at time of diagnosis of EoE which was continued. Six out of seven patients who had furrowing/exudate in endoscopy at diagnosis had complete resolution at a median follow-up period of 26 months (P = 0.031). Median peak intraepithelial eosinophil count reduced significantly from 30/high-powered field (HPF) (19-80/HPF) to 8/HPF (0-85/HPF) (median time for improvement = 24 months) (P = 0.015). There was a significant reduction in symptoms of dysphagia and reflux post-treatment (P < 0.001). Prevalence of strictures significantly decreased (P = 0.016), as did need for dilatations (P = 0.004). In four out of six patients with gastrostomies at baseline, the feeding improved on treatment of EoE and the gastrostomy could be closed. There was also a nonsignificant trend towards improvement in weight and height 'z scores' of the patients. Treatment of EoE in children with EA-TEF was found to significantly reduce intraepithelial eosinophil count, symptoms, strictures and need for dilatations.

Topics: Administration, Oral; Administration, Topical; Budesonide; Child; Child, Preschool; Deglutition Disorders; Diet Therapy; Eosinophilic Esophagitis; Esophageal Atresia; Esophageal Stenosis; Esophagoscopy; Female; Fluticasone; Gastroesophageal Reflux; Glucocorticoids; Humans; Infant; Male; Retrospective Studies; Tracheoesophageal Fistula; Treatment Outcome

Esophageal biopsy specimens from patients with eosinophilic esophagitis (EoE) can feel firm, with resistance felt when pulling the forceps to obtain the tissue sample. We aimed to assess the diagnostic utility of the esophageal biopsy "pull" sign and determine its histologic associations and response to treatment.. This was a prospective cohort study of adults undergoing outpatient upper endoscopy. Cases of EoE were diagnosed per consensus guidelines, and patients were subsequently treated with either topical steroids or dietary elimination. Control subjects were individuals who did not have EoE. The frequency of the esophageal biopsy "pull" sign was assessed in EoE patients and controls, and diagnostic metrics were calculated. The "pull" sign was also reassessed in patients after therapy.. A total of 83 EoE patients and 121 control subjects were included. Sixty-three EoE patients (76%) were "pull" sign positive compared with just 2 control subjects (2%; P < .001), corresponding to a sensitivity and specificity of 76% and 98%, positive and negative predictive values of 97% and 86%, and positive and negative likelihood ratios of 45.9 and 0.245, respectively. The "pull" sign was the strongest endoscopic predictor of EoE case status at baseline and was less frequent after successful treatment (20% vs 79%; P < .001).. The "pull" sign is highly specific for EoE and is rarely seen in non-EoE control subjects. In patients with EoE who respond to treatment, the "pull" sign often resolves. The "pull" sign may be a simple and easily obtained measure of esophageal remodeling.

Topics: Administration, Oral; Administration, Topical; Adult; Biopsy; Budesonide; Case-Control Studies; Cohort Studies; Diet Therapy; Eosinophilic Esophagitis; Esophagoscopy; Female; Fluticasone; Glucocorticoids; Humans; Male; Middle Aged; Prognosis; Prospective Studies; Sensitivity and Specificity; Young Adult

Topics: Deglutition; Eosinophilic Esophagitis; Eosinophils; Female; Fluticasone; Humans; Intestinal Mucosa; Male; Recovery of Function

Topics: Deglutition; Eosinophilic Esophagitis; Eosinophils; Female; Fluticasone; Humans; Intestinal Mucosa; Male; Recovery of Function

Topics: Adrenal Insufficiency; Androstadienes; Anti-Inflammatory Agents; Budesonide; Deglutition; Eosinophilic Esophagitis; Fluticasone; Humans

Topical steroids are first-line treatment agents for eosinophilic esophagitis; however, some studies have demonstrated modest efficacy in inducing histologic remission.. The aim of this study was to determine response to two topical steroids (fluticasone and budesonide), compare their efficacy, and examine patient characteristics which could predict non-response to topical steroids.. We performed a retrospective review of an established EoE registry. Inclusion criteria were patients >1 year of age who were diagnosed with EoE as defined by the most recent consensus guidelines. All patients were treated with an 8-week course of either swallowed fluticasone or viscous budesonide. Responders were defined as achieving <15 eosinophils per high-power field (eos/hpf) in both proximal and distal esophageal biopsies. Demographic, clinical, endoscopic, and histologic features were examined.. The study cohort included 75 EoE patients with a median age of 33 years (range 2-64 years), 71 % adults, 84 % male, and 76 % Caucasian. Overall histologic response rate to topical steroids was 51 %, while clinical response was 71 %. There was no significant differences in histologic response to treatment between children and adults (68 vs. 44 %, p = 0.111). There was no significant difference in response between males and females (47 vs. 73 %, p = 0.191) and between the two types of steroids (48 vs. 56 %, p = 0.632). Responders and non-responders were similar in clinical presentation and baseline endoscopic findings. Following treatment, responders had significantly less peak proximal (4.0 ± 4.4 vs. 46 ± 53, p < 0.001) and distal eosinophil counts (3.5 ± 3.8 vs. 60 ± 47, p < 0.001) compared to non-responders. There were no predictors of response to steroids identified.. Histologic response to treatment was observed in approximately half the cohort, while more than two-thirds experienced clinical response to topical steroids. Response was similar between fluticasone and budesonide. Given the lack of differences in clinical presentation or endoscopic features, predictors of non-response were not seen.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Budesonide; Child; Child, Preschool; Eosinophilic Esophagitis; Female; Fluticasone; Humans; Male; Middle Aged; Retrospective Studies; Young Adult

Although effective in the treatment of eosinophilic esophagitis (EoE) in children, limited data exist on long-term safety and efficacy of swallowed topical corticosteroids. We investigated whether long-term use of swallowed fluticasone in children with EoE leads to sustained reduction in esophageal eosinophils, and endoscopic and clinical improvement.. 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.. 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.. We demonstrate that swallowed fluticasone is effective as a long-term maintenance therapy for children with EoE, without growth impediment or serious side effects.

Topics: Abdominal Pain; Administration, Oral; Adolescent; Anti-Inflammatory Agents; Chest Pain; Child; Child, Preschool; Deglutition Disorders; Eosinophilic Esophagitis; Eosinophils; Esophageal Stenosis; Esophagoscopy; Esophagus; Female; Fibrosis; Fluticasone; Humans; Maintenance Chemotherapy; Male; Mucous Membrane; Nausea; Prospective Studies; Remission Induction; Treatment Outcome; Vomiting

Eosinophilic esophagitis (EoE) is an increasingly diagnosed disease, especially in the western world. Although its pathogenesis remains poorly understood, there is strong evidence that the eosinophilic inflammation in EoE is primarily triggered by immune dysregulation secondary to allergic sensitization to dietary or aero-allergens. Recent studies have reported a higher prevalence of EoE in children with congenital gastrointestinal malformations, i.e. esophageal atresia and/or tracheoesophageal fistula.. We present the case history of a 2-year-old boy who developed EoE in the aftermath of congenital diaphragmatic hernia (CDH) repair.. To the best of our knowledge, the following case report describes for the first time the possible association between CDH and EoE. Given the increasing reported prevalence of EoE in children with congenital gastrointestinal malformations, EoE should be rule out also in CDH survivors.

Topics: Anti-Inflammatory Agents; Biopsy; Diagnosis, Differential; Eosinophilic Esophagitis; Fluticasone; Food Hypersensitivity; Hernias, Diaphragmatic, Congenital; Humans; Infant; Male; Skin Tests

Noninvasive biomarkers would be valuable for diagnosis and monitoring of eosinophilic esophagitis (EoE). The aim of this study was to determine the utility of a panel of serum biomarkers for the diagnosis and management of EoE.. We conducted a prospective cohort study of consecutive adults undergoing outpatient esophagogastroduodenoscopy. Incident cases of EoE were diagnosed per consensus guidelines; controls had gastroesophageal reflux disease (GERD) or dysphagia and did not meet the EoE criteria. EoE cases were treated with topical steroids and had repeat endoscopy. Pre- and post-treatment serum samples were analyzed in a blinded manner for interleukin (IL)-4, IL-5, IL-6, IL-9, IL-13, transforming growth factor (TGF)-α, TGF-β, tumor necrosis factor-α, eotaxin-1, -2, and -3, thymic stromal lymphopoietin (TSLP), major basic protein, and eosinophil-derived neurotoxin. Cases and controls were compared at baseline, and pre- and post-treatment assays were compared in cases.. A total of 61 incident EoE cases and 87 controls were enrolled; 51 EoE cases had post-treatment serum analyzed. There were no significant differences in any of the biomarkers between EoE cases and controls at baseline. IL-13 and eotaxin-3 for cases and controls were 85 ± 160 vs. 43 ± 161 pg/ml (P=0.12) and 41 ± 159 vs. 21 ± 73 (P=0.30). There were no significant differences in assay values among cases before and after treatment. There were also no differences after stratification by atopic status or treatment response.. A panel of inflammatory factors known to be associated with EoE pathogenesis were not increased in the serum, nor were they responsive to therapy. None of these biomarkers are likely candidates for a serum test for EoE. Histologic analysis for diagnosis and management of EoE continues to be necessary, and novel, less invasive, biomarkers are needed.

Topics: Adult; Aged; Androstadienes; Biomarkers; Budesonide; Case-Control Studies; Cohort Studies; Cytokines; Deglutition Disorders; Endoscopy, Digestive System; Eosinophil Major Basic Protein; Eosinophil-Derived Neurotoxin; Eosinophilic Esophagitis; Esophagus; Female; Fluticasone; Gastroesophageal Reflux; Glucocorticoids; Humans; Male; Middle Aged; Prospective Studies; Transforming Growth Factors

Limited data are available on eosinophilic oesophagitis in Italy.. To evaluate typical features of eosinophilic oesophagitis patients in a tertiary centre.. 973 consecutive patients with dysphagia and/or bolus impaction were prospectively enrolled and underwent upper endoscopy for eosinophilic oesophagitis (≥15 eosinophils in at least one high-power field [hpf] and no response to acid suppressants). Demographic and multiple clinical factors were collected.. 45 patients (80% males, mean age 35±16) with incident eosinophilic oesophagitis (mean eosinophil peak count 57.2±40.6/hpf) were enrolled. 32 patients complained of solids dysphagia (71%), and 29 of bolus impaction (64%). Endoscopy found rings in 20 (44%), furrows in 9 (20%), whitish exudates/plaques in 12 (27%), crêpe paper in 7 (13%) and normal findings in 14 patients (31%). Endoscopic and radiologic stenosis occurred in 20 (44%) and 23 (51%), respectively. Ten patients had proton pump inhibitor-oesophageal eosinophilia (22%). Topic fluticasone was effective in 28 of the remaining cases (62%), while 7 required additional treatments (16%).. Eosinophilic oesophagitis prevalence was 12% in patients with dysphagia and/or bolus impaction, emphasizing the importance of this disease in Italy. Despite different environmental factors and dietary habits, Italian patients with eosinophilic oesophagitis present similar characteristics to those of other Western counties.

Topics: Adult; Bronchodilator Agents; Deglutition Disorders; Endoscopy; Eosinophilic Esophagitis; Female; Fluticasone; Humans; Italy; Leukocyte Count; Male; Manometry; Middle Aged; Prospective Studies; Proton Pump Inhibitors; Young Adult

We evaluated the serum levels of eosinophil cationic protein (ECP) and mast cell tryptase (MCT) as surrogate markers for response to treatment in adults with eosinophilic esophagitis (EoE) under topical steroid therapy with fluticasone.. EoE is a chronic disease characterized histologically by eosinophilic inflammation of the esophagus. Esophageal mastocytosis and mast cell activation have been implicated in EoE pathogenesis.. Fifteen patients with EoE completed this prospective observational study. Before and after 3 months of therapy with fluticasone, eosinophilic and mast cell counts were analyzed from histologic samples of the esophagus and were correlated with serum markers ECP and MCT.. Fluticasone-therapy significantly decreased mean eosinophils [from 42.2 to 16.2 eosinophils/high-power field (hpf); P=0.004] and mast cells (from 13.9 to 5.1 mast cells/hpf; P=0.001) in the esophageal epithelium. There was a significant decrease of mean ECP (from 15.6 to 5.5 μg/L; P=0.024) and MCT-serum-values (from 4.7 to 3.8 μg/L; P=0.029) under therapy. Serum-ECP correlated significantly with histologic eosinophilic counts after fluticasone-therapy (r=0.54; P=0.038) in contrast to serum-MCT.. Serum-ECP but not serum-MCT could be a promising noninvasive biomarker to assess response to topical corticosteroid therapy in EoE. These findings should be confirmed by larger studies; ClincialTrials.gov number, NCT01624129.

Topics: Administration, Topical; Adult; Androstadienes; Anti-Inflammatory Agents; Biomarkers; Eosinophil Cationic Protein; Eosinophilic Esophagitis; Eosinophils; Female; Fluticasone; Humans; Leukocyte Count; Male; Middle Aged; Prospective Studies; Tryptases; Young Adult

The allergic response associated with eosinophilic esophagitis (EoE) occurs when food antigens permeate tight junction-mediated epithelial dilated intercellular spaces. We assessed whether levels of tight junction proteins correlate with the dilation of intercellular spaces (spongiosis) and the effects of topical steroids on these parameters.. We assessed esophageal biopsy samples from 10 patients with active EoE treated with topical fluticasone, 10 untreated patients, and 10 patients without esophageal disease (controls) for degree of spongiosis. Immunohistochemical assays were used to determine the levels of the tight junction proteins filaggrin, zonula occludens (ZO)-1, ZO-2, ZO-3, and claudin-1. Histology and immunohistochemistry results were assessed blindly, with levels of tight junction proteins and degree of spongiosis rated on scales of 0 to 3.. The mean degrees of spongiosis in untreated and treated patients with EoE were 1.3 and 0.4, respectively (P = .016). Esophageal epithelia did not stain significantly for ZO-1 or ZO-2. Filaggrin was observed in a predominant cytoplasmic pattern, compared with the cytoplasmic and membranous patterns of ZO-3 and claudin-1. In biopsy specimens from patients with active EoE, the mean staining intensities for filaggrin, ZO-3, and claudin-1 were 1.6, 1.4, and 0.7, respectively. In biopsy specimens from patients treated with fluticasone, levels of filaggrin, ZO-3, and claudin-1 were 2.8 (P = .002 compared with untreated patients), 1.7 (P = .46 compared with untreated patients), and 1.3 (P = .25 compared with untreated patients), respectively. The correlation between the level of filaggrin and the degree of spongiosis was r = 0.23, and between ZO-3 staining and the degree of spongiosis was r = .016 (P = .001 for filaggrin vs ZO-3 staining).. Filaggrin, ZO-3, and claudin-1 (but not ZO-1 or ZO-2) are detected in the esophageal mucosa of patients with EoE treated with steroids and individuals without esophageal disease. Without treatment, spongiosis increases, corresponding with reduced levels of filaggrin, ZO-3, and claudin-1. Loss of tight junction regulators and dilation of intercellular spaces appear to be involved in the pathophysiology of EoE and could be targets for treatment.

Topics: Administration, Topical; Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Child; Eosinophilic Esophagitis; Epithelium; Female; Filaggrin Proteins; Fluticasone; Histocytochemistry; Humans; Immunohistochemistry; Male; Middle Aged; Steroids; Tight Junction Proteins; Tight Junctions; Young Adult

Long-lasting food impactions requiring endoscopic bolus removal occur frequently in patients with eosinophilic esophagitis (EoE) and harbor a risk for severe esophageal injuries. We evaluated whether treatment with swallowed topical corticosteroids is able to reduce the risk of occurrence of this complication.. We analyzed data from the Swiss EoE Cohort Study. Patients with yearly clinic visits, during which standardized assessment of symptoms, endoscopic, histologic, and laboratory findings was carried out, were included.. A total of 206 patients (157 males) were analyzed. The median follow-up time was 5 years with a total of 703 visits (mean 3.41 visits/patient). During the follow-up period, 33 patients (16 % of the cohort) experienced 42 impactions requiring endoscopic bolus removal. We evaluated the following factors regarding the outcome 'bolus impaction' by univariate logistic regression modeling: swallowed topical corticosteroid therapy (OR 0.503, 95%-CI 0.255-0.993, P = 0.048), presence of EoE symptoms (OR 1.150, 95%-CI 0.4668-2.835, P = 0.761), esophageal stricture (OR 2.832, 95%-CI 1.508-5.321, P = 0.001), peak eosinophil count >10 eosinophils/HPF (OR 0.724, 95%-CI 0.324-1.621, P = 0.433), blood eosinophilia (OR 1.532, 95%-CI 0.569-4.118, P = 0.398), and esophageal dilation (OR 1.852, 95%-CI 1.034-3.755, P = 0.017). In the multivariate model, the following factors were significantly associated with bolus impaction: swallowed topical corticosteroid therapy (OR 0.411, 95%-CI 0.203-0.835, P = 0.014) and esophageal stricture (OR 2.666, 95%-CI 1.259-5.645, P = 0.01). Increasing frequency of use of swallowed topical steroids was associated with a lower risk for bolus impactions.. Treatment of EoE with swallowed topical corticosteroids significantly reduces the risk for long-lasting bolus impactions.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Androstadienes; Anti-Inflammatory Agents; Budesonide; Child; Cohort Studies; Eosinophilic Esophagitis; Female; Fluticasone; Humans; Male; Middle Aged; Risk Factors; Young Adult

Eosinophilic esophagitis (EoE) is an increasingly recognized clinical entity. The optimal initial treatment strategy in adults with EoE remains controversial. The aim of this study was to employ a decision analysis model to determine the less costly option between the two most commonly employed treatment strategies in EoE. We constructed a model for an index case of a patient with biopsy-proven EoE who continues to be symptomatic despite proton-pump inhibitor therapy. The following treatment strategies were included: (i) swallowed fluticasone inhaler (followed by esophagogastroduodenoscopy [EGD] with dilation if ineffective); and (ii) EGD with dilation (followed by swallowed fluticasone inhaler if ineffective). The time horizon was 1 year. The model focused on cost analysis of initial treatment strategies. The perspective of the healthcare payer was used. Sensitivity analyses were performed to assess the robustness of the model. For every patient whose symptoms improved or resolved with the strategy of fluticasone first followed by EGD, if necessary, it cost an average of $1078. Similarly, it cost an average of $1171 per patient if EGD with dilation was employed first. Sensitivity analyses indicated that initial treatment with fluticasone was the less costly strategy to improve dysphagia symptoms as long as the effectiveness of fluticasone remains at or above 0.62. Swallowed fluticasone inhaler (followed by EGD with dilation if necessary) is the more economical initial strategy when compared with EGD with dilation first.

Topics: Androstadienes; Anti-Inflammatory Agents; Costs and Cost Analysis; Decision Trees; Deglutition Disorders; Dilatation; Endoscopy, Digestive System; Eosinophilic Esophagitis; Esophageal Stenosis; Fluticasone; Hospitalization; Humans; Metered Dose Inhalers; Tennessee

Interaction with gastroesophageal reflux disease (GERD) has been a fundamental consideration in eosinophilic esophagitis (EoE) since the initial reports of this emerging entity. While studies from the '80s identified the presence of esophageal eosinophilia as being a histologic marker for the diagnosis of GERD, studies in the '90s demonstrated that high levels of esophageal eosinophilia were characteristic for a novel immune/antigen-mediated esophageal disease, EoE, that was seemingly quite distinct from GERD. However, several recent studies have demonstrated the effectiveness of proton pump inhibition (PPI) in reducing symptoms and histopathology in a subset of patients with esophageal eosinophilia and suspected EoE, leading to the terminology "PPI responsive esophageal eosinophilia." It remains uncertain as to whether these patients have EoE, GERD, or a PPI responsive esophageal inflammatory condition that is distinct from either GERD or EoE. Emerging translational research has evidenced mechanisms by which PPI response in patients with esophageal eosinophilia may be a consequence of PPI effects on the immune pathogenesis of EoE. Therefore, a symptom and histologic response to PPI in patients with esophageal eosinophilia does not necessarily "rule in" GERD. Until further studies better define the pathogenesis of PPI responsive esophageal eosinophilia, a trial of PPI therapy remains an important prerequisite to the diagnosis EoE. Following this diagnostic approach allows for the clinical application of available evidence that is derived from research trials in EoE that exclude PPI responsive eosinophilia.

Topics: Androstadienes; Anti-Inflammatory Agents; Anti-Ulcer Agents; Eosinophilic Esophagitis; Esomeprazole; Female; Fluticasone; Humans; Male

Esophageal eosinophilia and eosinophilic esophagitis (EoE) are increasingly recognized and prevalent conditions, which now represent common clinical problems encountered by gastroenterologists, pathologists, and allergists. The study of EoE has become a dynamic field with an evolving understanding of the pathogenesis, diagnosis, and treatment. Although there are limited data supporting management decisions, clinical parameters are needed to guide the care of patients with eosinophilic-esophageal disorders. In this evidence-based review, recommendations developed by adult and pediatric gastroenterologists are provided for the evaluation and management of these patients. New terminology is emphasized, particularly the concepts of esophageal eosinophilia and proton-pump inhibitor-responsive esophageal eosinophilia (PPI-REE) as entities distinct from EoE.

Topics: Adult; Algorithms; Androstadienes; Anti-Inflammatory Agents; Biopsy; Clinical Trials as Topic; Diagnosis, Differential; Endpoint Determination; Eosinophilia; Eosinophilic Esophagitis; Esophagoscopy; Esophagus; Evidence-Based Medicine; Fluticasone; Gastroesophageal Reflux; Humans; Prednisone; Proton Pump Inhibitors

To our knowledge, in Asia, data on utility of allergy tests in management of eosinophilic esophagitis are lacking. The objective of our study was to determine the role of allergy evaluation in management of Saudi children with eosinophilic esophagitis.. Children diagnosed as having eosinophilic esophagitis during the period from 2009 to 2012 were referred to an allergist for allergy evaluation. The allergy evaluation consisted of total IgE level, radio-allergosorbent assay, and skin prick test. Depending on the results of the allergy tests, a restricted or elemental diet was established. Swallowed fluticasone inhaler was prescribed to patients who rejected or failed to respond to the diet. Clinical, endoscopic, and histological evaluation was performed in 8 weeks to assess response.. Eighteen children with eosinophilic esophagitis were included (13 males; mean age 5 years, range 1-11). Sensitization to foods was demonstrated in 14 patients: 4 with a positive test for a single food (28.5%), 1 for 2 food allergens (7%), and 9 for ≥3 food allergens (64.5%). The most common food allergens were milk, soybean, wheat, egg, and nuts. Three young children out of the total 14 patients responded to elemental formula. Four of the 10 older children on the allergy testing guided-dietary restriction achieved partial remission and the remaining 6 did not respond. All 10 patients responded to a swallowed fluticasone inhaler.. Although food sensitizations in Saudi children with eosinophilic esophagitis are common, the allergy tests had limited predictive value for the response to dietary elimination.

Topics: Androstadienes; Anti-Allergic Agents; Child; Child, Preschool; Eosinophilic Esophagitis; Female; Fluticasone; Follow-Up Studies; Food Hypersensitivity; Food, Formulated; Humans; Hypersensitivity; Immunoglobulin E; Infant; Male; Predictive Value of Tests; Radioallergosorbent Test; Retrospective Studies; Skin Tests

Eosinophilic Oesophagitis (EO) is characterised by large numbers of eosinophils in oesophageal mucosa in response to food or inhaled antigens. Treatment with elimination diet or corticosteroids lead to improvement in some children, but their efficacy is not optimal.. of this study is to identify clinical, endoscopic and/or histological features associated with response to treatment with swallowed fluticasone propionate.. In the last 12 years 34 children (M/F 25/9) with EO were treated with fluticasone propionate spray 250 μg/puff by inhaler without spacer, three puffs three times a day for 6 weeks, and returned for a follow-up endoscopy. At histology 25 of them were found to be responders to therapy (73.5%) and 9 were non-responders. Anthropometric characteristics, symptoms at presentation, endoscopic and histological data at baseline between responders and non-responders were compared.. Age, sex, height, duration and type of main symptom at presentation, type of allergy and number of allergens, peripheral eosinophil counts an serum IgE were similar in responders and non-responders. At baseline histology findings responders had a more severe inflammation: median peak eosinophils/high power field was higher (76 vs 44 in non responders p=0.04), eosinophilic microabscesses were present in a significantly higher number of responders (p=0.04) and peak mast cells/ high power field was significantly higher (p=0.001).. Clinical characteristics of children with EO at baseline were similar in responders and non-responders, but a more severe inflammation in oesophageal mucosa was associated with a higher response rate to fluticasone treatment.

Topics: Administration, Inhalation; Adolescent; Androstadienes; Anti-Inflammatory Agents; Child; Eosinophilic Esophagitis; Female; Fluticasone; History, Medieval; Humans; Infant; Male; Nebulizers and Vaporizers; Treatment Outcome

Topics: Aerosols; Androstadienes; Anti-Allergic Agents; Eosinophilic Esophagitis; Eosinophils; Female; Fluticasone; Humans; Male

Although the key features of eosinophilic esophagitis have been increasingly described over recent years, this entity is still often not considered and consequently diagnosis is often either not made or delayed. Typical endoscopic findings may be present. The diagnosis of eosinophilic esophagitis, however, relies on the histological assessment of mucosal biopsies. This case report highlights a common pattern of presentation of eosinophilic esophagitis and demonstrates the importance of considering this diagnosis.

Topics: Adolescent; Androstadienes; Anti-Inflammatory Agents; Anti-Ulcer Agents; Deglutition Disorders; Drug Therapy, Combination; Endoscopy, Gastrointestinal; Eosinophilic Esophagitis; Esophageal Stenosis; Fluticasone; Humans; Male; Omeprazole; Prednisolone

Topics: Androstadienes; Anti-Inflammatory Agents; Budesonide; Diet, Gluten-Free; Eosinophilic Esophagitis; Esophagoscopy; Fluticasone; Food, Formulated; Humans

Topics: Adult; Androstadienes; Anti-Inflammatory Agents; Deglutition Disorders; Eosinophilic Esophagitis; Esophagoscopy; Fluticasone; Food Hypersensitivity; Humans; Male; Proton Pump Inhibitors

Symptoms of vomiting and dysphagia in children with eosinophilic esophagitis may be related to the development of mucosal fibrosis.. Our aims were to (1) investigate esophageal fibrosis in children with EoE compared to patients with gastroesophageal reflux disease and normal individuals, and (2) to assess the degree of mucosal fibrosis in patients with EoE before and after medical treatment.. A retrospective analysis of esophageal biopsies from patients with EoE, GERD, and normal mucosa was performed. Demographic data, clinical information, eosinophil number, and sub-epithelial fibrosis was compared among the groups. A similar comparison was performed in EoE patients, before and after therapy.. Esophageal biopsies from 53 children were included, of which 17 with EoE, 17 GERD, and 19 were normal. A significantly higher number of eosinophils and greater fibrosis was found in EoE patients vs. GERD and normal (fibrosis grade 2: 13 patients in the EoE group vs. one patient for each control group; p=0.0001). After therapy, a significant decrease in fibrosis and eosinophils number was noted in EoE patients [fibrosis grade 2: 10 (71.5%) patients vs. one (7.1%) patient, and eosinophil count was 35.5/HPF vs. 13.4/HPF, pre- and post-therapy, respectively; p<0.05]. The decrease in esophageal fibrosis paralleled the improvement in the related clinical symptoms.. A higher degree of esophageal fibrosis was found in patients with EoE compared to GERD or normal esophagus. Conventional therapy in EoE improved obstructive symptoms, decreased eosinophils count, and reversed the degree of fibrosis. We suggest that appropriate therapy in patients with EoE will improve clinical symptoms and histology.

Topics: Adolescent; Allergens; Androstadienes; Anti-Inflammatory Agents; Biopsy; Case-Control Studies; Child; Child, Preschool; Eosinophilic Esophagitis; Eosinophils; Esophagus; Female; Fibrosis; Fluticasone; Food Hypersensitivity; Gastroesophageal Reflux; Humans; Infant; Male; Mucous Membrane; Retrospective Studies; Treatment Outcome

Eosinophilic esophagitis (EoE) has been a rarely recognized condition in Asian populations, and its clinical manifestation is rarely documented. Our aim was to describe clinically, endoscopically, and pathologically the features of patients with esophageal eosinophilia, including EoE.. Twelve patients histologically proven to have esophageal eosinophilia were investigated. The histological diagnostic cutoff value was defined as a peak of ≥15 eosinophils/high-power field (HPF) in esophageal biopsies. Symptoms, endoscopic and pathological findings, and treatment outcome were evaluated.. Nine of the 12 patients were male and the 12 patients had a mean age of 47.7 years. Allergic conditions were concurrent in a total of 3 patients. Mild peripheral eosinophilia was observed in only 2 patients. The predominant symptom was solid-food dysphagia, but some patients complained of heartburn, or chest, epigastric, or back pain. Three asymptomatic subjects were also incidentally diagnosed during endoscopic screening. Linear furrows, concentric rings, and white exudates in the esophagus were frequently observed. In 4 of 5 patients who were administered a proton pump inhibitor (PPI), esophageal eosinophilia was histologically decreased or disappeared with symptom relief and endoscopic improvement. In 2 patients unresponsive to PPI, topical steroid therapy, administered by the swallowing of fluticasone propionate, led to symptomatic and histological remission.. The endoscopic recognition of linear furrows, concentric rings, and white exudates is important in the diagnosis of eosinophilic esophageal inflammation. In a subset of patients this condition improves clinicopathologically with PPI treatment, and typical EoE, as strictly defined by unresponsiveness to PPI, appears to be a rather rare condition.

Topics: Adult; Aged; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Biopsy; Eosinophilic Esophagitis; Esophagoscopy; Esophagus; Female; Fluticasone; Humans; Japan; Male; Middle Aged; Proton Pump Inhibitors; Retrospective Studies; Treatment Outcome

Topics: Adult; Aged; Aged, 80 and over; Androstadienes; Anti-Inflammatory Agents; Carboxypeptidases A; Chemokine CCL26; Chemokines, CC; Eosinophilic Esophagitis; Female; Fluticasone; Gene Expression; Humans; Male; Mast Cells; Middle Aged; Steroids; Treatment Outcome; Up-Regulation

The population prevalence of eosinophilic esophagitis (EoE) is ~7% in adults. Current American Gastroenterology Association guidelines recommend endoscopic biopsy (Bx) in patients with symptoms of dysphagia. We conducted a cost-effectiveness model to determine if endoscopic Bx is cost effective in patients with refractory gastroesophageal reflux disease (GERD) without dysphagia.. We designed a 5-year Markov model to compare costs and quality-adjusted life years for a cohort of 35-year-old patients with GERD refractory to proton pump inhibitor (PPI) therapy. We compared upper endoscopy (EGD) with and without Bx for EoE. We modeled that patients with EoE who did not undergo initial biopsy would wait 5 years until the diagnosis would be established via a second endoscopy with biopsy.. In patients with refractory GERD without dysphagia, endoscopic Bx for EoE was associated with an incremental cost-effectiveness ratio (ICER) of $51,420 per quality of life year (QALY). The upper endoscopy with biopsy arm cost $12,490 per patient and was associated with 4.080 QALYs, compared with EGD without Bx arm that cost $12,280 and was associated with 4.076 QALYs. The ICER was <$50,000 per QALY when the prevalence of EoE exceeded 8%, or the time of missed diagnosis was 6 years or greater. The biopsy arm was also cost effective if the QALY associated with symptomatic GERD was ≤0.93, cost of 3-month course of PPI therapy ≥$770 cost of fluticasone <$650, probability of EoE resolved on PPI ≤25%, symptom resolution on fluticasone ≥70%, cost endoscopy with biopsy ≤$520, or the cost of endoscopy without biopsy exceeded $300.. Upper endoscopy with Bx for EoE appears to be a cost-effective approach in patients when the prevalence of EoE is 8% or greater.

Topics: Adult; Androstadienes; Anti-Inflammatory Agents; Biopsy; Cohort Studies; Cost-Benefit Analysis; Decision Support Techniques; Decision Trees; Deglutition Disorders; Eosinophilic Esophagitis; Esophagoscopy; Female; Fluticasone; Gastroesophageal Reflux; Humans; Male; Markov Chains; Middle Aged; Proton Pump Inhibitors; Quality of Life; Quality-Adjusted Life Years; Sensitivity and Specificity; Software; Time Factors; United States

Leukotriene D4 is produced by and functions as a chemotactic factor for eosinophils. Eosinophilic esophagitis (EoE) is characterized by esophageal eosinophilic infiltration, determining structural changes and dismotility symptoms. Montelukast, a selective leukotriene D4 receptor antagonist, has gained increasing consideration as a therapeutic agent for EoE. However, limited available information has shown that montelukast is not effective in reducing eosinophilic infiltration. Our paper aims at evaluating whether montelukast could be consider as a steroid-sparing therapy by assessing its efficacy in maintaining both clinical and histopathological remission achieved after topical corticosteroids in adult EoE patients.. Eleven consecutively diagnosed adult EoE patients were prospectively studied. Esophageal biopsies were obtained before and after a 6-month treatment with fluticasone propionate 400 μg/twice a day. Immediately after that, montelukast 10 mg/day was instituted. A new endoscopy was foreseen after a new 3-month period, or as soon as the patients presented esophageal symptoms. Symptoms were assessed by using a questionnaire before and after fluticasone propionate treatment and after montelukast therapy.. Eosinophils density into the esophageal epithelium and lamina propria was significantly reduced after a 6-month treatment with topical steroids (P = 0.003) and increased to levels similar to baseline level into the first 3 months after treatment with montelukast. Baseline symptom scores significantly decreased after treatment with topical steroids (P = 0.003) and increased again after montelukast therapy, but baseline levels improved.. Montelukast was not efficient in maintaining the histopathological or clinical response achieved by topical steroids in adult EoE patients.

Topics: Acetates; Adult; Androstadienes; Anti-Inflammatory Agents; Biopsy; Cyclopropanes; Dose-Response Relationship, Drug; Drug Therapy, Combination; Endoscopy, Gastrointestinal; Eosinophilic Esophagitis; Female; Fluticasone; Follow-Up Studies; Humans; Leukotriene Antagonists; Male; Middle Aged; Patient Satisfaction; Prospective Studies; Quinolines; Remission Induction; Sulfides; Surveys and Questionnaires; Treatment Outcome; Young Adult

Topics: Androstadienes; Anti-Inflammatory Agents; Collagen; Cytokines; Eosinophilic Esophagitis; Female; Fluticasone; Gene Expression; Humans; Male

Some patients with eosinophilic esophagitis (EE) (>15 eosinophils/high-power field on esophageal mucosal biopsies and lack of response to acid suppression and/or normal pH probe study) demonstrate incidental eosinophilic inflammation of the gastric mucosa. It is unclear whether patients with EE and normal gastric biopsies (EE-N) are phenotypically different from patients with EE and gastric mucosal abnormalities (EE-A) (ie, >10 eos/hpf on gastric biopsies). The aim of the study was to compare the clinical features and response to therapy among patients with EE-N and EE-A.. Medical records of all of the EE-A and a random group of patients with EE-N diagnosed during an 8-year period were reviewed. A subgroup analysis of patients treated with swallowed fluticasone with a repeat esophagogastroduodenoscopy within 6 months of starting therapy was also performed.. During the study period, 41 patients had EE-A. When compared to 50 random patients with EE-N, no clinical differences were noted, including sex, age, presenting symptoms, esophageal histology, and atopy history. Eleven (27%) of the 41 EE-A and 14 (28%) of the 50 EE-N patients were treated with swallowed fluticasone, and the response was similar among the groups. The mean esophageal eosinophils/high-power field among the EE-A group dropped from 47 to 8 compared with a 46 to 7 drop among the EE-N group treated with fluticasone therapy (P = 0.91). In 9 (82%) of the 11 patients with EE-A treated with fluticasone, there was resolution (7 of 9) or significant improvement (2 of 9) of gastric eosinophilia.. Patients with EE-A and EE-N have similar clinical presentations. Incidental gastric inflammation does not predict a worse response of esophageal inflammation to fluticasone and should not exclude its use in patients with EE-A. In fact, gastric inflammation responded to swallowed fluticasone in the majority of patients with EE-A. This observation should foster further investigation into pathogenesis of EE and presumed esophagogastric inflammatory axis.

Topics: Adolescent; Androstadienes; Anti-Inflammatory Agents; Child; Child, Preschool; Endoscopy, Digestive System; Eosinophilic Esophagitis; Eosinophils; Female; Fluticasone; Gastric Mucosa; Humans; Infant; Leukocyte Count; Male; Stomach Diseases

Patients with HIV/AIDS are often afflicted with oesophageal disorders. Opportunistic infections such as candidiasis, herpes simplex, cytomegalovirus, mycobacterial infections, Kaposi sarcoma or lymphoma involving the oesophagus, motility disorders and reflux oesophagitis are the usual culprits. Eosinophilic oesophagitis (EE), a recently recognized entity, is an important cause of dysphagia, food impaction and chest discomfort. We report the case of an HIV-infected man who had persistent dysphagia for six months despite treatment with proton pump inhibitor. He was diagnosed with EE after having endoscopic evaluation and biopsy of his oesophagus and was successfully treated with swallowed fluticasone. This case represents the first reported case of EE in an HIV-infected individual.

Topics: Adult; Androstadienes; Anti-Inflammatory Agents; Biopsy; Deglutition Disorders; Endoscopy; Eosinophilic Esophagitis; Fluticasone; Histocytochemistry; HIV Infections; Humans; Male; Proton Pump Inhibitors