Pilar Navarro, Ángel Arias, Laura Arias-González, Emilio J Laserna-Mendieta, Miriam Ruiz-Ponce, Alfredo J Lucendo
Systematic review with meta-analysis: the growing incidence and prevalence of eosinophilic oesophagitis in children and adults in population-based studies.
Aliment Pharmacol Ther. 2019 May;49(9):1116-1125. doi: 10.1111/apt.15231. Epub 2019 Mar 18.
Abstract/Text
BACKGROUND: The frequency of eosinophilic oesophagitis (EoE) occurrence is escalating. Current diagnostic criteria recently proposed for the disease, determine that previous estimates of incidence and prevalence are outdated.
AIM: To gauge the current incidence and prevalence of EoE by performing a systematic review of population-based studies.
METHODS: Three electronic databases were searched from their inception dates to September 2018. A total of 2386 documents were screened; 29 studies reported on the prevalence and incidence of EoE in the general population.
RESULTS: The pooled prevalence of EoE was 34.4 cases per 100 000 inhabitants (95% CI, 23.1-47.5), and was higher for adults (42.2; 95% CI, 31.1-55) than for children (34; 95% CI, 22.3-49.2). The pooled EoE incidence rates were 6.6/100 000 person-years (95% CI, 3-11.7) in children and 7.7/100 000 (95% CI, 1.8-17.8) in adults. No differences were found between North American and European studies using varied sources of data (insurance and administrative databases compared to hospital-bases case series). Subgroup analysis according to risk of bias did not change results significantly. A steady rise in EoE incidence and prevalence rates was observed over time, comparing studies conducted under subsequent definitions for EoE. No significant publication bias was found.
CONCLUSIONS: In a systematic review and meta-analysis, we found a sharp increase, higher than previous estimates, in the incidence and prevalence of EoE in population based studies. Results from studies carried out in developed countries show broad consistency and provide evidence of increasing pooled prevalence and incidence of EoE rates over time.
© 2019 John Wiley & Sons Ltd.
Diagnosis and treatment of eosinophilic esophagitis in Japan. Esophagus. 2017 14: 66-75. doi: 10.1007/s10388-016-0550-8.
Norihisa Ishimura, Eiko Okimoto, Kotaro Shibagaki, Nahoko Nagano, Shunji Ishihara
Similarity and difference in the characteristics of eosinophilic esophagitis between Western countries and Japan.
Dig Endosc. 2020 Jul 5;. doi: 10.1111/den.13786. Epub 2020 Jul 5.
Abstract/Text
Over the past two decades, the incidence and prevalence of eosinophilic esophagitis (EoE) have risen rapidly, especially in Western countries, with cases in Japan also showing a gradual increase in recent years. However, similarities and differences regarding the characteristics of EoE between Western countries and Japan remain to be clearly elucidated. The current clinical guidelines for diagnosis include symptoms related to esophageal dysfunction and dense eosinophilic infiltration in the esophageal epithelium. Most affected patients in Japan are diagnosed incidentally during a medical health check-up and asymptomatic cases with typical endoscopic findings suggestive of EoE are frequently encountered. Clinical characteristics of EoE in Japanese are similar to those seen in Western populations. The predominant symptom is dysphagia, with food impaction extremely rare in Japanese cases. Linear furrows are the most frequently reported characteristic endoscopic finding, while an esophageal stricture or narrow caliber is rarely observed. Treatment strategies for EoE include drugs, dietary restrictions, and endoscopic dilation when the disease is advanced with stricture formation. Although single therapy using a proton-pump inhibitor has been shown to achieve symptomatic and histological response in the majority of patients in Japan, no prospective randomized control studies that evaluated drug or elimination diet therapy have been presented. Overall, EoE has similar clinical characteristics between Japanese and Western populations, while disease severity seems to be milder in Japan. Additional studies are necessary to determine genetic factors, natural history of the disease, and treatment efficacy of drugs and elimination diet as compared to Western populations.
© 2020 Japan Gastroenterological Endoscopy Society.
Eiko Okimoto, Norihisa Ishimura, Shunji Ishihara
Clinical Characteristics and Treatment Outcomes of Patients with Eosinophilic Esophagitis and Eosinophilic Gastroenteritis.
Digestion. 2020 Nov 17;:1-8. doi: 10.1159/000511588. Epub 2020 Nov 17.
Abstract/Text
BACKGROUND: Eosinophilic esophagitis (EoE) and eosinophilic gastroenteritis (EGE), part of the spectrum of eosinophilic gastrointestinal disorders (EGID), share pathogenic similarities. We examined differences regarding clinical characteristics and treatment outcomes between EoE and EGE cases.
METHODS: Two-hundred fifteen EGID patients, including 181 with EoE and 34 with EGE, diagnosed at Shimane University Hospital between February 2011 and March 2019 were enrolled. Information regarding clinical parameters and treatment outcomes was reviewed.
RESULTS: EoE showed significant male predominance (82.3%) as compared with EGE (50.0%) (p < 0.001). Furthermore, patients with EoE were significantly older and had a higher body mass index (24.8 ± 4.0 vs. 22.2 ± 4.3, p < 0.05). Over 90% of the EoE patients were initially given proton pump inhibitor (PPI) treatment, of whom 73.2% showed clinical and histological remission. Vonoprazan, a more potent acid inhibitor than PPI, was effective in two-thirds of the nonresponsive EoE patients initially treated with a PPI. In contrast, oral glucocorticoid administration was mainly given to patients with EGE (58.8%). Of 13 EGE patients treated with a food-elimination diet, responsible foods were successfully identified in 9, with 7 controlled in a state of remission without glucocorticoid therapy.
CONCLUSIONS: We found different clinical characteristics and treatment strategies in the present EoE and EGE cases. Most of the EoE patients responded to and were maintained by acid suppressive therapy, using PPI or vonoprazan. For EGE patients, glucocorticoid administration was mainly used though food-elimination diet therapy also showed beneficial effects.
© 2020 The Author(s) Published by S. Karger AG, Basel.
Xiang Zhu, Meiqin Wang, Parm Mavi, Madhavi Rayapudi, Akhilesh K Pandey, Ajay Kaul, Philip E Putnam, Marc E Rothenberg, Anil Mishra
Interleukin-15 expression is increased in human eosinophilic esophagitis and mediates pathogenesis in mice.
Gastroenterology. 2010 Jul;139(1):182-93.e7. doi: 10.1053/j.gastro.2010.03.057. Epub 2010 Apr 8.
Abstract/Text
BACKGROUND & AIMS: Quantitative microarray analyses have shown increased expression of interleukin-15 (IL-15) messenger RNA in the esophagus of patients with eosinophilic esophagitis (EoE), a recently recognized allergic disorder with poorly understood pathogenesis.
METHODS: Quantitative polymerase chain reaction and enzyme-linked immunosorbent assay analyses were performed to examine protein and transcript levels in tissue samples from patients with EoE. Tissues from IL-15Ra-deficient and wild-type (control) mice were also examined. Tissue eosinophilia was determined by immunostaining for major basic protein and flow cytometry for cell-surface receptors.
RESULTS: Quantitative polymerase chain reaction analyses showed that levels of IL-15 and its receptor IL-15Ra were increased approximately 6- and approximately 10-fold, respectively, in tissues from patients with EoE and approximately 3- and approximately 4-fold, respectively, in mice with allergen-induced EoE. A >2-fold increase in serum IL-15 protein levels was also detected in human EoE samples compared with those from healthy individuals. Human IL-15 messenger RNA levels correlated with esophageal eosinophilia (P < .001). IL-15Ra-deficient mice were protected from allergen-induced esophageal eosinophilia compared with controls (P < .001), even though similar levels of airway eosinophilia were observed in all mice. IL-15 activated STAT5 and CD4(+) T cells to produce cytokines that act on eosinophils. Incubation of primary esophageal epithelial cells from mice and humans with IL-15 caused a dose-dependent increase in the mRNA expression and protein levels of eotaxin-1, -2, and -3.
CONCLUSIONS: IL-15 mediates in the pathogenesis of EoE. IL-15 activates CD4(+) T cells to produce cytokines that act on eosinophils.
Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
Carine Blanchard, Melissa K Mingler, Maria Vicario, J Pablo Abonia, Yi Ying Wu, Thomas X Lu, Margaret H Collins, Philip E Putnam, Susanne I Wells, Marc E Rothenberg
IL-13 involvement in eosinophilic esophagitis: transcriptome analysis and reversibility with glucocorticoids.
J Allergy Clin Immunol. 2007 Dec;120(6):1292-300. doi: 10.1016/j.jaci.2007.10.024.
Abstract/Text
BACKGROUND: Eosinophilic esophagitis (EE) is an emerging worldwide disease that mimics gastroesophageal reflux disease. Early studies have established that esophageal eosinophilia occurs in association with T(H)2 allergic responses, and we recently identified an EE-specific esophageal transcriptome that included eotaxin-3.
OBJECTIVE: We sought to determine the mechanism by which this T(H)2 response leads to EE.
METHODS: Real-time PCR and microarray analysis were performed on RNA extracted from esophageal biopsy specimens and primary esophageal epithelial cell cultures stimulated with IL-13 (0-100 ng/mL). Transient transfections in esophageal cell lines were performed with plasmids containing the luciferase gene driven by eotaxin-3 promoter fragments and modified forms of signal transducer and activator of transcription 6.
RESULTS: The IL-13 mRNA level was markedly increased (16-fold) in esophageal biopsy specimens from patients with EE compared with those from healthy individuals. Furthermore, IL-13 treatment of primary esophageal epithelial cells was sufficient to induce a global-expression transcript profile that remarkably overlapped with the EE-specific esophageal transcriptome. In addition, esophageal epithelial cells markedly produce eotaxin-3 after IL-13 stimulation through a transcriptional mechanism dependent on signal transducer and activator of transcription 6. Lastly, increased IL-13 mRNA levels and the EE transcriptome were largely reversible with glucocorticoid treatment in vivo.
CONCLUSIONS: Taken together, we propose that the pathogenesis of EE is mediated by an IL-13-stimulated keratinocyte-derived transcriptome that is largely reversible with corticosteroid treatment. Furthermore, we identify an in vivo IL-13-induced transcriptome that has potential utility for target assessment after anti-IL-13 therapeutics.
CLINICAL IMPLICATIONS: IL-13-induced pathways and genes are fundamental processes in the cause and manifestations of EE; as such, therapeutic agents that interfere with IL-13 might be particularly useful for disease treatment.
Li Zuo, Patricia C Fulkerson, Fred D Finkelman, Melissa Mingler, Christine A Fischetti, Carine Blanchard, Marc E Rothenberg
IL-13 induces esophageal remodeling and gene expression by an eosinophil-independent, IL-13R alpha 2-inhibited pathway.
J Immunol. 2010 Jul 1;185(1):660-9. doi: 10.4049/jimmunol.1000471. Epub 2010 Jun 11.
Abstract/Text
Eosinophilic esophagitis (EE) is an emerging disease associated with both food and respiratory allergy characterized by extensive esophageal tissue remodeling and abnormal esophageal gene expression, including increased IL-13. We investigated the ability of increased airway IL-13 to induce EE-like changes. Mice with pulmonary (but not esophageal) overexpression of IL-13 evidenced esophageal IL-13 accumulation and developed prominent esophageal remodeling with epithelial hyperplasia, angiogenesis, collagen deposition, and increased circumference. IL-13 induced notable changes in esophageal transcripts that overlapped with the human EE esophageal transcriptome. IL-13-induced esophageal eosinophilia was dependent on eotaxin-1 (but not eotaxin-2). However, remodeling occurred independent of eosinophils as demonstrated by eosinophil lineage-deficient, IL-13 transgenic mice. IL-13-induced remodeling was significantly enhanced by IL-13Ralpha2 deletion, indicating an inhibitory effect of IL-13Ralpha2. In the murine system, there was partial overlap between IL-13-induced genes in the lung and esophagus, yet the transcriptomes were divergent at the tissue level. In human esophagus, IL-13 levels correlated with the magnitude of the EE transcriptome. In conclusion, inducible airway expression of IL-13 results in a pattern of esophageal gene expression and extensive tissue remodeling that resembles human EE. Notably, we identified a pathway that induces EE-like changes and is IL-13-driven, eosinophil-independent, and suppressed by IL-13Ralpha2.
Carine Blanchard, Emily M Stucke, Karen Burwinkel, Julie M Caldwell, Margaret H Collins, Annette Ahrens, Bridget K Buckmeier, Sean C Jameson, Allison Greenberg, Ajay Kaul, James P Franciosi, Jonathan P Kushner, Lisa J Martin, Philip E Putnam, J Pablo Abonia, Suzanne I Wells, Marc E Rothenberg
Coordinate interaction between IL-13 and epithelial differentiation cluster genes in eosinophilic esophagitis.
J Immunol. 2010 Apr 1;184(7):4033-41. doi: 10.4049/jimmunol.0903069. Epub 2010 Mar 5.
Abstract/Text
We have previously proposed that the pathogenesis of eosinophilic esophagitis (EE) is mediated by an IL-13-driven epithelial cell response associated with marked gene dysregulation including eotaxin-3 overproduction. In this study, we compared epithelial responses between healthy patients and those with EE, aiming to uncover molecular explanations for EE pathogenesis. Esophageal epithelial cells could be maintained for up to five passages, with 67% and 62% of cell lines reaching confluence in healthy controls and EE cases, respectively. Both sets of epithelial cells avidly responded to IL-13 at similar levels as assessed by eotaxin-3 production. Acidic pH increased cellular release of eotaxin-3 (4.6 +/- 1.98 ng/ml versus 12.46 +/- 2.90 ng/ml at pH 7.4 and 4, respectively; p < 0.05). Numerous epidermal differentiation complex (EDC) genes, such as filaggrin and SPRR3, were downregulated both in IL-13-stimulated esophageal epithelial cells and in EE biopsies specimens compared with healthy controls. Whereas the filaggrin loss of function mutation 2282del4 was overrepresented in EE compared with control individuals (6.1% versus 1.3% respectively; p = 0.0172), the decreased filaggrin expression was uniformly seen in all EE cases in vivo. Indeed, expression of the EDC genes filaggrin and involucrin was strongly decreased directly by IL-13. These results establish that the epithelial response in EE involves a cooperative interaction between IL-13 and expression of EDC genes.
Yugo Suzuki, Toshiro Iizuka, Atsuko Hosoi, Daisuke Kikuchi, Takayuki Okamura, Yorinari Ochiai, Junnosuke Hayasaka, Nobuhiro Dan, Yutaka Mitsunaga, Masami Tanaka, Hiroyuki Odagiri, Kosuke Nomura, Satoshi Yamashita, Akira Matsui, Shu Hoteya
Clinicopathological Differences between Eosinophilic Esophagitis and Asymptomatic Esophageal Eosinophilia.
Intern Med. 2022 May 1;61(9):1319-1327. doi: 10.2169/internalmedicine.8241-21. Epub 2021 Oct 19.
Abstract/Text
Objective According to consensus guidelines, eosinophilic esophagitis (EoE) is defined as a clinicopathological entity whose symptoms and histology must always be considered together. However, endoscopic findings typical of EoE are often seen in asymptomatic esophageal eosinophilia (aEE). We aimed to clarify the clinicopathological features of aEE. Methods We retrospectively compared cases of aEE and those of symptomatic EoE. Materials We reviewed 146 patients who underwent upper gastrointestinal endoscopy and were confirmed histopathologically to have esophageal eosinophil infiltration of at least 15 eosinophils per high-power field. They were divided into the aEE group (n=75) and the EoE group (n=71). Patients' clinicopathological findings were then collected and examined. Results The EoE group experienced dysphagia (47.9%), heartburn (40.8%), food impaction (40.8%), chest pain (16.9%), and other symptoms (8.5%). There was no significant difference between the two groups with regard to age, sex, current smoking status, or alcohol consumption. The aEE group had a significantly higher body mass index (p<0.01) and significantly lower frequency of concurrent allergic diseases (p<0.01) than the EoE group. No significant differences were found between the two groups with regard to the mean peripheral blood eosinophil count, non-specific immunoglobulin E concentration, peak eosinophil infiltration in the biopsy specimens, EoE histology scoring system, phenotype and location of typical endoscopic findings of EoE, or thickness of the esophagus wall or the mucosal and submucosal layer as measured by endoscopic ultrasonography. Two patients in the aEE group who were followed up without treatment subsequently developed esophageal symptoms. Conclusion aEE and EoE may have the same clinicopathological features.
Norihisa Ishimura, Shohei Sumi, Mayumi Okada, Hironobu Mikami, Eiko Okimoto, Nahoko Nagano, Asuka Araki, Yuji Tamagawa, Tsuyoshi Mishiro, Naoki Oshima, Shunji Ishihara, Riruke Maruyama, Yoshikazu Kinoshita
Is Asymptomatic Esophageal Eosinophilia the Same Disease Entity as Eosinophilic Esophagitis?
Clin Gastroenterol Hepatol. 2019 Jun;17(7):1405-1407. doi: 10.1016/j.cgh.2018.08.048. Epub 2018 Aug 23.
Abstract/Text
Eosinophilic esophagitis (EoE) is an allergic inflammatory disorder that is characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation.1,2 Its prevalence has been increasing rapidly in both Western and Asian countries. In Japan, most of the cases of esophageal eosinophilia (EE) are found in an upper endoscopy examination for gastric cancer screening performed during a comprehensive health check-up.3,4 Indeed, we frequently encounter patients with asymptomatic EE showing typical endoscopic findings, such as linear furrows, as well as histologic findings compatible with EoE. However, the current clinical guidelines for EoE diagnosis include symptoms related to esophageal dysfunction, thus patients without symptoms do not fulfill the diagnostic criteria.1,2 The clinical characteristics remain to be fully elucidated,5 thus we aimed to clarify clinical features of asymptomatic EE as compared with those of EoE.
Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.
Hannah P Kim, R Brooks Vance, Nicholas J Shaheen, Evan S Dellon
The prevalence and diagnostic utility of endoscopic features of eosinophilic esophagitis: a meta-analysis.
Clin Gastroenterol Hepatol. 2012 Sep;10(9):988-96.e5. doi: 10.1016/j.cgh.2012.04.019. Epub 2012 May 18.
Abstract/Text
BACKGROUND & AIMS: Endoscopic findings such as esophageal rings, strictures, narrow-caliber esophagus, linear furrows, white plaques, and pallor or decreased vasculature might indicate the presence of eosinophilic esophagitis (EoE). We aimed to determine the prevalence and diagnostic utility of endoscopic features of EoE.
METHODS: We conducted a systematic review and meta-analysis. PubMed, EMBASE, and gastrointestinal meeting abstracts were searched to identify studies that included more than 10 patients with EoE and reported endoscopic findings. Pooled prevalence, sensitivity, specificity, and predictive values were calculated using random- and mixed-effects models.
RESULTS: The search yielded 100 articles and abstracts on 4678 patients with EoE and 2742 without (controls). In subjects with EoE, the overall pooled prevalence was as follows: esophageal rings, 44%; strictures, 21%; narrow-caliber esophagus, 9%; linear furrows, 48%; white plaques, 27%; and pallor/decreased vasculature, 41%. Substantial heterogeneity existed among studies. Results from endoscopy examinations were normal in 17% of patients, but this number decreased to 7% when the analysis was limited to prospective studies (P < .05). Overall levels of sensitivity were modest, ranging from 15% to 48%, whereas levels of specificity were greater, ranging from 90% to 95%. Positive predictive values ranged from 51% to 73% and negative predictive values ranged from 74% to 84%.
CONCLUSIONS: There is heterogeneity among studies in the reported prevalence of endoscopic findings in patients with EoE, but in prospective studies at least 1 abnormality was detected by endoscopy in 93% of patients. The operating characteristics of endoscopic findings alone are inadequate for diagnosis of EoE. Esophageal biopsy specimens should be obtained from all patients with clinical features of EoE, regardless of the endoscopic appearance of the esophagus.
Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.
Yoshikazu Kinoshita, Norihisa Ishimura, Naoki Oshima, Shunji Ishihara
Systematic review: Eosinophilic esophagitis in Asian countries.
World J Gastroenterol. 2015 Jul 21;21(27):8433-40. doi: 10.3748/wjg.v21.i27.8433.
Abstract/Text
AIM: To investigate the prevalence and the clinical characteristics of Asian patients with eosinophilic esophagitis.
METHODS: We conducted a systematic search of the PubMed and Web of Science databases for original studies, case series, and individual case reports of eosinophilic esophagitis in Asian countries published from January 1980 to January 2015. We found 66 and 80 articles in the PubMed and Web of Science databases, respectively; 24 duplicate articles were removed. After excluding animal studies, articles not written in English, and meeting abstracts, 25 articles containing 217 patients were selected for analysis.
RESULTS: Sample size-weighted mean values were determined for all pooled prevalence data and clinical characteristics. The mean age of the adult patients with eosinophilic esophagitis was approximately 50 years, and 73% of these patients were male. They frequently presented with allergic diseases including bronchial asthma, allergic rhinitis, food allergy, and atopic dermatitis. Bronchial asthma was the most frequent comorbid allergic disease, occurring in 24% of patients with eosinophilic esophagitis. Dysphagia was the primary symptom reported; 44% of the patients complained of dysphagia. Although laboratory blood tests are not adequately sensitive for an accurate diagnosis of eosinophilic esophagitis, endoscopic examinations revealed abnormal findings typical of this disease, including longitudinal furrows and concentric rings, in 82% of the cases. One-third of the cases responded to proton pump inhibitor administration.
CONCLUSION: The characteristics of eosinophilic esophagitis in Asian patients were similar to those reported in Western patients, indicating that this disease displays a similar pathogenesis between Western and Asian patients.
Evan S Dellon, Chris A Liacouras, Javier Molina-Infante, Glenn T Furuta, Jonathan M Spergel, Noam Zevit, Stuart J Spechler, Stephen E Attwood, Alex Straumann, Seema S Aceves, Jeffrey A Alexander, Dan Atkins, Nicoleta C Arva, Carine Blanchard, Peter A Bonis, Wendy M Book, Kelley E Capocelli, Mirna Chehade, Edaire Cheng, Margaret H Collins, Carla M Davis, Jorge A Dias, Carlo Di Lorenzo, Ranjan Dohil, Christophe Dupont, Gary W Falk, Cristina T Ferreira, Adam Fox, Nirmala P Gonsalves, Sandeep K Gupta, David A Katzka, Yoshikazu Kinoshita, Calies Menard-Katcher, Ellyn Kodroff, David C Metz, Stephan Miehlke, Amanda B Muir, Vincent A Mukkada, Simon Murch, Samuel Nurko, Yoshikazu Ohtsuka, Rok Orel, Alexandra Papadopoulou, Kathryn A Peterson, Hamish Philpott, Philip E Putnam, Joel E Richter, Rachel Rosen, Marc E Rothenberg, Alain Schoepfer, Melissa M Scott, Neil Shah, Javed Sheikh, Rhonda F Souza, Mary J Strobel, Nicholas J Talley, Michael F Vaezi, Yvan Vandenplas, Mario C Vieira, Marjorie M Walker, Joshua B Wechsler, Barry K Wershil, Ting Wen, Guang-Yu Yang, Ikuo Hirano, Albert J Bredenoord
Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the AGREE Conference.
Gastroenterology. 2018 Oct;155(4):1022-1033.e10. doi: 10.1053/j.gastro.2018.07.009. Epub 2018 Sep 6.
Abstract/Text
BACKGROUND & AIMS: Over the last decade, clinical experiences and research studies raised concerns regarding use of proton pump inhibitors (PPIs) as part of the diagnostic strategy for eosinophilic esophagitis (EoE). We aimed to clarify the use of PPIs in the evaluation and treatment of children and adults with suspected EoE to develop updated international consensus criteria for EoE diagnosis.
METHODS: A consensus conference was convened to address the issue of PPI use for esophageal eosinophilia using a process consistent with standards described in the Appraisal of Guidelines for Research and Evaluation II. Pediatric and adult physicians and researchers from gastroenterology, allergy, and pathology subspecialties representing 14 countries used online communications, teleconferences, and a face-to-face meeting to review the literature and clinical experiences.
RESULTS: Substantial evidence documented that PPIs reduce esophageal eosinophilia in children, adolescents, and adults, with several mechanisms potentially explaining the treatment effect. Based on these findings, an updated diagnostic algorithm for EoE was developed, with removal of the PPI trial requirement.
CONCLUSIONS: EoE should be diagnosed when there are symptoms of esophageal dysfunction and at least 15 eosinophils per high-power field (or approximately 60 eosinophils per mm2) on esophageal biopsy and after a comprehensive assessment of non-EoE disorders that could cause or potentially contribute to esophageal eosinophilia. The evidence suggests that PPIs are better classified as a treatment for esophageal eosinophilia that may be due to EoE than as a diagnostic criterion, and we have developed updated consensus criteria for EoE that reflect this change.
Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.
Alfredo J Lucendo, Javier Molina-Infante, Ángel Arias, Ulrike von Arnim, Albert J Bredenoord, Christian Bussmann, Jorge Amil Dias, Mogens Bove, Jesús González-Cervera, Helen Larsson, Stephan Miehlke, Alexandra Papadopoulou, Joaquín Rodríguez-Sánchez, Alberto Ravelli, Jukka Ronkainen, Cecilio Santander, Alain M Schoepfer, Martin A Storr, Ingrid Terreehorst, Alex Straumann, Stephen E Attwood
Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults.
United European Gastroenterol J. 2017 Apr;5(3):335-358. doi: 10.1177/2050640616689525. Epub 2017 Jan 23.
Abstract/Text
INTRODUCTION: Eosinophilic esophagitis (EoE) is one of the most prevalent esophageal diseases and the leading cause of dysphagia and food impaction in children and young adults. This underlines the importance of optimizing diagnosys and treatment of the condition, especially after the increasing amount of knowledge on EoE recently published. Therefore, the UEG, EAACI ESPGHAN, and EUREOS deemed it necessary to update the current guidelines regarding conceptual and epidemiological aspects, diagnosis, and treatment of EoE.
METHODS: General methodology according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used in order to comply with current standards of evidence assessment in formulation of recommendations. An extensive literature search was conducted up to August 2015 and periodically updated. The working group consisted of gastroenterologists, allergists, pediatricians, otolaryngologists, pathologists, and epidemiologists. Systematic evidence-based reviews were performed based upon relevant clinical questions with respect to patient-important outcomes.
RESULTS: The guidelines include updated concept of EoE, evaluated information on disease epidemiology, risk factors, associated conditions, and natural history of EoE in children and adults. Diagnostic conditions and criteria, the yield of diagnostic and disease monitoring procedures, and evidence-based statements and recommendation on the utility of the several treatment options for patients EoE are provided. Recommendations on how to choose and implement treatment and long-term management are provided based on expert opinion and best clinical practice.
CONCLUSION: Evidence-based recommendations for EoE diagnosis, treatment modalities, and patients' follow up are proposed in the guideline.
Kyoichi Adachi, Tomoko Mishiro, Shino Tanaka, Yoshikazu Kinoshita
Suitable biopsy site for detection of esophageal eosinophilia in eosinophilic esophagitis suspected cases.
Dig Endosc. 2016 Mar;28(2):139-44. doi: 10.1111/den.12555. Epub 2015 Oct 26.
Abstract/Text
BACKGROUND AND AIM: Esophageal eosinophilia (EE) is the most important finding for the diagnosis of eosinophilic esophagitis. We conducted the present retrospective study to clarify the most suitable site of the esophagus to examine for EE detection.
METHODS: We enrolled 4999 subjects who underwent upper gastrointestinal endoscopy screening examinations as part of a detailed health check-up. When endoscopic esophageal abnormalities characteristic of eosinophilic esophagitis were observed, two or three biopsy specimens were obtained from the middle or lower esophagus, and endoscopic findings of fixed rings, exudates, furrows, edema, stricture, and crepe paper esophagus in biopsied sites were analyzed.
RESULTS: Thirty-five subjects underwent histological examination for EE, of whom 20 showed positive findings in biopsied specimens. Higher grade endoscopic findings of exudates, furrows, and edema were observed in cases with EE in comparison to the 15 without EE, whereas statistically significant higher grade endoscopic findings of exudates, furrows, and edema were also observed in biopsied sites with EE in comparison to those without EE. In addition, a positive finding of EE in biopsied specimens from the lower esophagus was significantly more frequently noted as compared to those from the middle esophagus. Multiple logistic regression analysis showed that a lower esophagus biopsy site and severe exudates were significant factors related to a positive EE finding in biopsied specimens.
CONCLUSION: The most suitable conditions for detection of EE are a lower esophagus biopsy site and the presence of exudates in cases suspicious of eosinophilic esophagitis shown by endoscopy.
©2015 Japan Gastroenterological Endoscopy Society.
Ikuo Hirano, Nelson Moy, Michael G Heckman, Colleen S Thomas, Nirmala Gonsalves, Sami R Achem
Endoscopic assessment of the oesophageal features of eosinophilic oesophagitis: validation of a novel classification and grading system.
Gut. 2013 Apr;62(4):489-95. doi: 10.1136/gutjnl-2011-301817. Epub 2012 May 22.
Abstract/Text
OBJECTIVE: Abnormalities are commonly identified during endoscopy in eosinophilic oesophagitis (EoE). There is no standardised classification to describe these features. This study aimed to evaluate the interobserver agreement of a grading system for the oesophageal features of EoE.
METHOD: The proposed system incorporated the grading of four major oesophageal features (rings, furrows, exudates, oedema) and the presence of additional features of narrow calibre oesophagus, feline oesophagus, stricture and crepe paper oesophagus. Endoscopic videos from 25 patients with EoE and controls were reviewed by 21 gastroenterologists. Interobserver agreement was assessed by estimating multi-rater κ and the proportion of pairwise agreement.
RESULTS: Using the original grading system, agreement for rings, furrows and exudates was moderate (κ=0.38-0.46, 56-65% agreement) but poor for oedema (κ=0.23, 51% agreement). Identification of narrow calibre oesophagus had fair agreement (κ=0.30, 74% agreement) while feline oesophagus had poor agreement (κ=0.15, 68% agreement). After collapsing the severity grading for oedema and furrows and eliminating poorly performing features of feline oesophagus and narrow calibre oesophagus, a modified grading system demonstrated good agreement for the four major features of EoE (κ=0.40-0.54, 71-81% agreement) and additional features of stricture and crepe paper oesophagus (κ=0.52 and 0.58, 79% and 92% agreement).
CONCLUSIONS: The proposed system for endoscopically-identified oesophageal features of EoE defines common nomenclature and severity scores for the assessment of EoE disease activity. The system has good interobserver agreement among practising and academic gastroenterologists.
Alfredo J Lucendo, Ángel Arias, Javier Molina-Infante
Efficacy of Proton Pump Inhibitor Drugs for Inducing Clinical and Histologic Remission in Patients With Symptomatic Esophageal Eosinophilia: A Systematic Review and Meta-Analysis.
Clin Gastroenterol Hepatol. 2016 Jan;14(1):13-22.e1. doi: 10.1016/j.cgh.2015.07.041. Epub 2015 Aug 3.
Abstract/Text
BACKGROUND & AIMS: Proton pump inhibitor (PPI) therapy might lead to clinical and histologic remission in a significant proportion of patients with symptomatic esophageal eosinophilia (>15 eos/high-power field). We aimed to evaluate systematically the efficacy of PPI therapy for these patients.
METHODS: A search in MEDLINE, EMBASE, and SCOPUS databases, and the American Gastroenterological Association Institute, American College of Gastroenterology, and United European Gastroenterology meetings abstract books, was performed. Primary outcomes were clinical response and histologic remission (<15 eos/high-power field) after PPI therapy. Secondary outcomes were the influence on the response to PPIs of age group, study design/quality, PPI type, doses and interval dosing, and pH monitoring results. Data were pooled using a random-effects model.
RESULTS: Thirty-three studies (11 prospective studies) comprising 619 patients with symptomatic esophageal eosinophilia (188 children and 431 adults) were included. PPI therapy led to a clinical response in 60.8% (95% confidence interval, 48.38%-72.2%; I(2) = 80.2) and histologic remission in 50.5% (95% confidence interval, 42.2%-58.7%; I(2) = 67.5) of patients. No differences were observed regarding the study population (children vs adults), the type of publication, or its quality. PPIs were nonsignificantly more effective in prospective studies (52.6% vs 39.1%) administered twice daily compared with once daily (55.9% vs 49.7%), and with pathologic pH monitoring (65.4% vs 49.3%). A significant publication bias in favor of studies reporting histologic responses to PPIs was observed.
CONCLUSIONS: PPI therapy induces clinicohistologic remission in half of patients with symptomatic esophageal eosinophilia. This finding should be interpreted with caution because of poor-quality evidence, heterogeneity, and publication bias.
Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.
Elizabeth T Schaefer, Joseph F Fitzgerald, Jean P Molleston, Joseph M Croffie, Marian D Pfefferkorn, Mark R Corkins, Joel D Lim, Steven J Steiner, Sandeep K Gupta
Comparison of oral prednisone and topical fluticasone in the treatment of eosinophilic esophagitis: a randomized trial in children.
Clin Gastroenterol Hepatol. 2008 Feb;6(2):165-73. doi: 10.1016/j.cgh.2007.11.008.
Abstract/Text
BACKGROUND & AIMS: Although eosinophilic esophagitis is recognized increasingly, outcome data guiding therapy are limited. We conducted a prospective randomized trial comparing oral prednisone (P) and swallowed fluticasone (F) for histologic and clinical response.
METHODS: Patients were randomized to receive P or F for 4 weeks, followed by an 8-week weaning protocol. Esophageal histology was evaluated at baseline and after 4 weeks of therapy. Clinical assessments were performed at weeks 0, 4, 12, 18, and 24.
RESULTS: Eighty patients with eosinophilic esophagitis were enrolled: 40 in the P arm and 40 in the F arm. Histologic improvement was seen in 30 of 32 P and 34 of 36 F patients, with a greater degree of histologic improvement in the P group. All P and 35 of 36 F patients were free of presenting symptom(s) at week 4. Symptom relapse was seen in 45% of patients by week 24. Kaplan-Meier analysis showed no difference between P and F with regard to relapse rate (P = .7399). No significant difference in time to relapse was found between groups (P = .2529). Systemic adverse effects were noted in 40% of the P arm, whereas esophageal candidal overgrowth was seen in 15% of the F arm.
CONCLUSIONS: Systemic and topical corticosteroids were effective in achieving initial histologic and clinical improvement. P resulted in a greater degree of histologic improvement, without evidence of an associated clinical advantage over F in terms of symptom resolution, relapse rates, or time to relapse. Symptom relapse was common to both groups upon therapy discontinuation, highlighting the need for maintenance treatment protocols.
