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好酸球性食道炎

著者: 石村典久 島根大学 第2内科

監修: 木下芳一 兵庫県立姫路循環器病センター/製鉄記念広畑病院

著者校正/監修レビュー済:2021/02/10
参考ガイドライン:
  1. 厚生労働省好酸球性消化管疾患研究班:幼児・成人好酸球性消化管疾患診療ガイドライン(2020年9月14日)
  1. Guidelines on eosinophilic esophagitis:evidence-based statements and recommendations for diagnosis and management in children and adults. United European Gastroenterol J. 2017;5:335-358.
  1. Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis:Proceedings of the AGREE Conference. Gastroenterology. 2018;155:1022-1033.
患者向け説明資料

概要・推奨   

  1. 上部消化管内視鏡検査で縦走溝、白斑リング状変化(輪状溝)の所見を認めた場合は好酸球性食道炎が疑われる(推奨度1JG
  1. 食事のつかえ感など食道に起因すると考えられる症状を主訴に来院した患者では、上部消化管内視鏡検査で異常を認めない場合でも好酸球性食道炎は否定できない。食道粘膜の生検を行い、食道上皮への好酸球の浸潤の有無を確認することが推奨される(推奨度1G
  1. 好酸球性食道炎の組織診断には、食道の複数の部位から組織を採取することが推奨される(推奨度1JG
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
石村典久 : 特に申告事項無し[2021年]
監修:木下芳一 : 講演料(アストラゼネカ,武田,大塚,第一三共)[2021年]

改訂のポイント:
  1. 定期レビューを行い、2017年以降のガイドラインの改訂に基づいて概要・推奨、疾患情報、診断、治療について加筆修正を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 好酸球性食道炎とは、食道の上皮層中に多数の好酸球を中心とした炎症細胞浸潤が持続する慢性アレルギー疾患であり、嚥下障害や食事のつかえ感を生じる。好酸球の上皮内浸潤を中心とした慢性炎症に伴い食道粘膜下層の浮腫や線維化が起こり、食道運動機能異常や食道狭窄などを合併する。
  1. 欧米では2000年代より有病率の増加が認められており、最近の報告では人口10万人あたり30~50人程度と報告されている[1]。日本では一般住民を対象とした大規模な疫学調査の報告はないが、内視鏡検査施行例を対象とした頻度調査では、最近10年間で増加傾向にあることが指摘されており、内視鏡検査約300例に1例程度の頻度で診断されると報告されている[2][3]。患者の半数以上に喘息、アトピー性皮膚炎、アレルギー性鼻炎などのアレルギー性疾患の合併がみられる[4]。食物抗原や空気中の抗原で刺激された食道粘膜上皮中の樹状細胞が、IL-15の産生を介して、またTh2系の免疫反応を誘導してリンパ球にIL-5、13を大量に産生させる[5]
  1. IL-13は扁平上皮のeotaxin-3産生を増加させ上皮内への好酸球の浸潤を促進するとともに、扁平上皮のバリア機能に関与するfilaggrinやinvolucrinの発現を低下させる[6][7][8]
  1. 好酸球性消化管疾患は指定難病であり、中等症以上の場合などでは、申請し認定されると、診療費用の自己負担分の一部が公費負担として助成される。(平成27年1月1日施行
  1. Disease:4001 [難病法に基づく医療費助成制度]
問診・診察のポイント  
  1. 自覚症状に関して詳細に問診する。つかえ感が軽度の場合には、他の人より食事に時間がかかる、食事の際に水分を多く摂取しないと食べにくい、などを訴えることが多い。症状の出現時期やつかえやすい食事についても確認する。

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文献 

著者: Pilar Navarro, Ángel Arias, Laura Arias-González, Emilio J Laserna-Mendieta, Miriam Ruiz-Ponce, Alfredo J Lucendo
雑誌名: 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.
PMID 30887555  Aliment Pharmacol Ther. 2019 May;49(9):1116-1125. doi: ・・・
著者: Norihisa Ishimura, Eiko Okimoto, Kotaro Shibagaki, Nahoko Nagano, Shunji Ishihara
雑誌名: 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.
PMID 32623781  Dig Endosc. 2020 Jul 5;. doi: 10.1111/den.13786. Epub 2・・・
著者: Eiko Okimoto, Norihisa Ishimura, Shunji Ishihara
雑誌名: 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.
PMID 33202408  Digestion. 2020 Nov 17;:1-8. doi: 10.1159/000511588. Ep・・・
著者: Xiang Zhu, Meiqin Wang, Parm Mavi, Madhavi Rayapudi, Akhilesh K Pandey, Ajay Kaul, Philip E Putnam, Marc E Rothenberg, Anil Mishra
雑誌名: 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.
PMID 20381491  Gastroenterology. 2010 Jul;139(1):182-93.e7. doi: 10.10・・・
著者: 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
雑誌名: 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.

PMID 18073124  J Allergy Clin Immunol. 2007 Dec;120(6):1292-300. doi: ・・・
著者: Li Zuo, Patricia C Fulkerson, Fred D Finkelman, Melissa Mingler, Christine A Fischetti, Carine Blanchard, Marc E Rothenberg
雑誌名: 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.

PMID 20543112  J Immunol. 2010 Jul 1;185(1):660-9. doi: 10.4049/jimmun・・・
著者: 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
雑誌名: 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.

PMID 20208004  J Immunol. 2010 Apr 1;184(7):4033-41. doi: 10.4049/jimm・・・
著者: Hannah P Kim, R Brooks Vance, Nicholas J Shaheen, Evan S Dellon
雑誌名: 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.
PMID 22610003  Clin Gastroenterol Hepatol. 2012 Sep;10(9):988-96.e5. d・・・
著者: Yoshikazu Kinoshita, Norihisa Ishimura, Naoki Oshima, Shunji Ishihara
雑誌名: 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.

PMID 26217096  World J Gastroenterol. 2015 Jul 21;21(27):8433-40. doi:・・・
著者: 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
雑誌名: 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.
PMID 30009819  Gastroenterology. 2018 Oct;155(4):1022-1033.e10. doi: 1・・・
著者: 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
雑誌名: 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.

PMID 28507746  United European Gastroenterol J. 2017 Apr;5(3):335-358.・・・
著者: Kyoichi Adachi, Tomoko Mishiro, Shino Tanaka, Yoshikazu Kinoshita
雑誌名: 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.
PMID 26418844  Dig Endosc. 2016 Mar;28(2):139-44. doi: 10.1111/den.125・・・
著者: Ikuo Hirano, Nelson Moy, Michael G Heckman, Colleen S Thomas, Nirmala Gonsalves, Sami R Achem
雑誌名: 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.

PMID 22619364  Gut. 2013 Apr;62(4):489-95. doi: 10.1136/gutjnl-2011-30・・・
著者: Alfredo J Lucendo, Ángel Arias, Javier Molina-Infante
雑誌名: 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.
PMID 26247167  Clin Gastroenterol Hepatol. 2016 Jan;14(1):13-22.e1. do・・・
著者: 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
雑誌名: 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.

PMID 18237866  Clin Gastroenterol Hepatol. 2008 Feb;6(2):165-73. doi: ・・・

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