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The present document constitutes Part 2 of the EoETALY Consensus Statements guideline on the diagnosis and management of eosinophilic esophagitis (EoE) developed by experts in the field of EoE across Italy (i.e., EoETALY Consensus Group). Part 1 was published as a different document, and included three chapters discussing 1) definition, epidemiology, and pathogenesis; 2) clinical presentation and natural history and 3) diagnosis of EoE. The present work provides guidelines on the management of EoE in two final chapters: 4) treatment and 5) monitoring and follow-up, and also includes considerations on knowledge gaps and a proposed research agenda for the coming years. The guideline was developed through a Delphi process, with grading of the strength and quality of the evidence of the recommendations performed according to accepted GRADE criteria.This document has received the endorsement of three Italian national societies including the Italian Society of Gastroenterology (SIGE), the Italian Society of Neurogastroenterology and Motility (SINGEM), and the Italian Society of Allergology, Asthma, and Clinical Immunology (SIAAIC). The guidelines also involved the contribution of members of ESEO Italia, the Italian Association of Families Against EoE., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Eosinophilic esophagitis (EoE) is a chronic type 2-mediated inflammatory disease of the esophagus that represents the most common eosinophilic gastrointestinal disease. Experts in the field of EoE across Italy (i.e., EoETALY Consensus Group) including gastroenterologists, endoscopists, allergologists/immunologists, and paediatricians conducted a Delphi process to develop updated consensus statements for the management of patients with EoE and update the previous position paper of the Italian Society of Gastroenterology (SIGE) in light of recent evidence. Grading of the strength and quality of the evidence of the recommendations was performed using accepted GRADE criteria. The guideline is divided in two documents: Part 1 includes three chapters, namely 1) definition, epidemiology, and pathogenesis; 2) clinical presentation and natural history, and 3) diagnosis, while Part 2 includes two chapters: 4) treatment and 5) monitoring and follow-up. This document has received the endorsement of three Italian national societies including the SIGE, the Italian Society of Neurogastroenterology and Motility (SINGEM), and the Italian Society of Allergology, Asthma, and Clinical Immunology (SIAAIC). With regards to patients' involvement, these guidelines involved the contribution of members of ESEO Italia, the Italian Association of Families Against EoE., Competing Interests: Declaration of competing interest Nicola de Bortoli: Advisory board member for: AlfaSigma, Sanofi Genzyme, Dr Falk; Lecture grants from Reckitt-Benkiser, Malesci, Dr. Flak, Sofar, Alfa-Sigma, Pharma-Line. Pierfrancesco Visaggi: Has served as speaker for Dr Falk, JB Pharmaceuticals, Malesci. Roberto Penagini: Has served as speaker for Dr Falk, Sanofi. Edda Battaglia: has served as consultant for NZP, GUNA Gaia Pellegatta has served as speaker for Dr Falk, Sanofi Genzyme, Malesci. Paola Iovino: Has served as consultant for Dr Falk Giovanni Marasco: Served as an advisory board member for AlfaSigma, EG Pharma, Monteresearch srl, Recordati, Cineca. Received lecture grants from Agave, AlfaSigma, Bromatech, Clorofilla, Echosens, Ferring, Mayoly Spindler, Menarini and Schwabe Pharma. Salvatore Oliva: Has served as speaker for Sanofi, Medtronic; Has served as consultant for: Sanofi, Medtronic, Brystol; Has received research support from Alfa Sigma, Medtronic. Francesca Racca: has served as speaker for Sanofi; has served as consultant for Dr Falk, Sanofi, GSK Erminia Ridolo: has served as consultant for Dr Falk Edoardo Vincenzo Savarino: has served as speaker for Abbvie, Agave, AGPharma, Alfasigma, Aurora Pharma, CaDiGroup, Celltrion, Dr Falk, EG Stada Group, Fenix Pharma, Fresenius Kabi, Galapagos, Janssen, JB Pharmaceuticals, Innovamedica/Adacyte, Malesci, Mayoly Biohealth, Omega Pharma, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Tillots, Unifarco; has served as consultant for Abbvie, Agave, Alfasigma, Biogen, Bristol-Myers Squibb, Celltrion, Diadema Farmaceutici, Dr. Falk, Fenix Pharma, Fresenius Kabi, Janssen, JB Pharmaceuticals, Merck & Co, Nestlè, Reckitt Benckiser, Regeneron, Sanofi, SILA, Sofar, Synformulas GmbH, Tssakeda, Unifarco; he received research support from Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco, Zeta Farmaceutici. Bruno Annibale, Federica Baiano Svizzero, Giovanni Barbara, Brigida Barberio, Ottavia Bartolo, Antonio Di Sabatino, Ludovico Docimo, Marzio Frazzoni, Manuele Furnari, Matteo Ghisa, Andrea Iori, Marco Vincenzo Lenti, Elisa Marabotto, Aurelio Mauro, Marcella Pesce, Antonino Carlo Privitera, Ilaria Puxeddu, Mentore Ribolsi, Salvatore Russo, Giovanni Sarnelli, Salvatore Tolone, Patrizia Zentilin, Fabiana Zingone: None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The Lyon Consensus proposed a hierarchical approach to GERD diagnosis based on conventional and new impedance-pH metrics, namely acid exposure time (AET), number of reflux episodes, post-reflux swallow-induced peristaltic wave (PSPW) index, and mean nocturnal baseline impedance (MNBI)., Aims: To define the value of conventional and new impedance-pH parameters as predictors of response to label-dose PPI in typical GERD., Methods: Consecutive adult patients with typical esophageal symptoms were prospectively studied with impedance-pH monitoring and treated with 8-week label-dose PPI. At the end of the PPI course, symptoms response was assessed., Results: Among 255 patients who entered the study, 168 (65.9%) reported symptom remission. At ROC analysis, both MNBI and PSPW index were significantly associated to PPI responsiveness with AUC of 0.783 and 0.801, respectively. Cut-off values of 1747Ω for MNBI and 50% for PSPW index were identified as discriminators between response and non-response to label-dose PPI. At multivariate analysis, MNBI, PSPW index, and AET >6% were efficient predictors of PPI responses (OR 3, 5.4 and 2.3, respectively). Number of reflux episodes did not predict PPI response., Conclusions: The novel MII-pH variables together with pathological are highly predictive of response of the typical GERD syndrome to label-dose PPI., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Eosinophilic oesophagitis (EoE) may lead to severe complications if not promptly recognised., Aims: To assess the diagnostic delay in patients with EoE and to explore its risk factors., Methods: EoE patients followed-up at eight clinics were included via retrospective chart review. Diagnostic delay was estimated as the time lapse occurring between the appearance of the first likely symptoms indicative of EoE and the final diagnosis. Patient-dependent and physician-dependent diagnostic delays were assessed. Multivariable regression models were computed., Results: 261 patients with EoE (mean age 34±14 years; M:F ratio=3:1) were included. The median overall diagnostic delay was 36 months (IQR 12-88), while patient- and physician-dependent diagnostic delays were 18 months (IQR 5-49) and 6 months (IQR 1-24). Patient-dependent delay was greater compared to physician-dependent delay (95% CI 5.1-19.3, p<0.001). A previous misdiagnosis was formulated in 109 cases (41.8%; gastro-oesophageal reflux disease in 67 patients, 25.7%). The variables significantly associated with greater overall diagnostic delay were being a non-smoker, >1 episode of food impaction, previous endoscopy with no biopsies, regurgitation, and ≥2 assessing physicians. Being single was significantly associated with lower overall and patient-dependent diagnostic delay., Conclusion: EoE is burdened by substantial diagnostic delay, depending on both patient-related and physician-related factors., Competing Interests: Declaration of Competing Interest None to disclose for all authors., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave (PSPW) index are able to increase the diagnostic yield of impedance-pH and are associated to proton pump inhibitor (PPI) response. Few data concerning these variables in patients with extra-esophageal symptoms (EES) are available., Aims: To evaluate, in EES patients, the role of the conventional and new impedance-pH variables in diagnosing GERD and the predictive value of impedance-pH variables for PPI response., Methods: Consecutive patients presenting suspected GERD-related EES underwent impedance-pH. Patients treated in the last six months with double dose PPI therapy were enrolled. The presence of concomitant typical symptoms was assessed., Results: 239 EES patients were studied; 102 responders and 137 non-responders. Eighty-one (34%) were affected by non-erosive reflux disease (NERD), 61 (26%) presented reflux hypersensitivity (RH) and 97 (40%) were non-GERD. In NERD and RH groups, a significantly higher proportion of patients with pathological PSPW index or MNBI values compared to non-GERD group was observed. 24 (25%) non-GERD patients presented a pathological PSPW index and/or MNBI. Pathological PSPW index, MNBI and presence of typical symptoms were associated to PPI response., Conclusions: MNBI and PSPW index measurement increases the diagnostic yield of impedance-pH; abnormal values are associated with a satisfactory response to acid-suppressive therapy in EES patients., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Altered body composition is frequently observed in Crohn's disease (CD) patients., Aims: To investigate the nutritional status, and the effect of different therapeutic regimes in adult CD patients., Methods: Fat free mass (FFM) and BIA-derived phase angle (PhA) were assessed in 45 CD patients, 22 on conventional therapy (CT) and 23 on maintenance therapy with infliximab (MT). Nutritional status was also assessed in 12 CD patients before and following the induction protocol with infliximab. BIA data of CD patients were compared with those of 20 healthy asymptomatic volunteers. In CD patients C Reactive Protein (CRP) and albuminaemia dosage were obtained., Results: The mean values of PhA and of FFM were significantly lower in CT patients when compared with control group and MT patients. Following infliximab treatment FFM increased, although not significantly, while mean phase angle value significantly increased from 4.6±0.3 to 6.2±0.4 (p<0.05). CRP was significantly lower in MT patients compared to that in CT patients., Conclusion: CD patients on conventional therapy showed a lower FFM and a lower mean phase angle score compared to those on infliximab therapy. Following infliximab treatment the mean phase angle score normalized. PhA is a reliable nutritional indicator in IBD patients and could be considered as an additional tool for assessing response to treatment., (Copyright © 2016. Published by Elsevier Ltd.)

Patients with esophageal symptoms potentially associated to esophageal motor disorders such as dysphagia, chest pain, heartburn and regurgitation, represent one of the most frequent reasons for referral to gastroenterological evaluation. The utility of esophageal manometry in clinical practice is: (1) to accurately define esophageal motor function, (2) to identify abnormal motor function, and (3) to establish a treatment plan based on motor abnormalities. With this in mind, in the last decade, investigations and technical advances, with the introduction of high-resolution esophageal manometry, have enhanced our understanding and management of esophageal motility disorders. The following recommendations were developed to assist physicians in the appropriate use of esophageal manometry in modern patient care. They were discussed and approved after a comprehensive review of the medical literature pertaining to manometric techniques and their recent application. This position statement created under the auspices of the Gruppo Italiano di Studio per la Motilità dell'Apparato Digerente (GISMAD), Società Italiana di Gastroenterologia ed Endoscopia Digestiva (SIGE) and Associazione Italiana Gastroenterologi ed Endoscopisti Digestivi Ospedalieri (AIGO) is intended to help clinicians in applying manometric studies in the most fruitful manner within the context of their patients with esophageal symptoms., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: We sought to compare intercellular space diameter in children with non-erosive and erosive reflux disease, and a control group. We also aimed to characterize the reflux pattern in erosive and non-erosive reflux disease patients, and to explore the relationship between intercellular space diameter values and reflux parameters., Methods: Twenty-four children with non-erosive reflux disease, 20 with erosive reflux disease, and 10 controls were prospectively studied. All patients and controls underwent upper endoscopy. Biopsies were taken at 2-3 cm above the Z-line, and intercellular space diameter was measured using transmission electron microscopy. Non-erosive and erosive reflux disease patients underwent impedance-pH monitoring., Results: Mean intercellular space diameter values were significantly higher in both non-erosive (0.9 ± 0.2 μm) and erosive reflux disease (1 ± 0.2 μm) compared to controls (0.5 ± 0.2 μm, p<0.01). No difference was found between the two patient groups. Acid exposure time, the number of acid, weakly acidic and weakly alkaline reflux events did not differ between the two patient groups. No difference was found in the mean intercellular space diameter between non-erosive reflux disease children with and without abnormal acid exposure time (1 ± 0.3 vs. 0.9 ± 0.2 μm). No correlation was found between any reflux parameter and intercellular space diameter values., Conclusions: Dilated intercellular space diameter seems to be a useful and objective marker of oesophageal damage in paediatric gastro-oesophageal reflux disease, regardless of acid exposure. In childhood, different gastro-oesophageal reflux disease phenotypes cannot be discriminated on the basis of reflux pattern., (Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: The unsatisfactory response to medical treatment in non-erosive patients is becoming a real challenge for gastroenterologists. Non-responder patients, evaluated under treatment, present symptoms which are related to non-acidic, mixed and proximal reflux episodes., Methods: To elucidate the reflux pattern and mechanisms related to persistence of symptoms despite treatment, oesophageal pH-impedance was performed in 55 non-erosive responder and 24 non-responder patients, studied off therapy. Ten responder and 10 non-responder patients underwent a repeated study during proton pump inhibitor treatment., Results: Non-responders were characterised by a higher overall number and larger proportion of symptomatic reflux episodes. Non-responders were also characterised by an enhanced sensitivity to acidic, mixed and proximal refluxes. Weakly acidic reflux accounted for 29% of symptomatic refluxes in non-responders and 34% in responders. Proportions of acidic and weakly acidic reflux episodes were comparable both in responders and non-responders when analysed off and on treatment., Conclusions: An increased overall number of reflux episodes and enhanced sensitivity to reflux are strongly associated with treatment failure. Treatment strategies aimed at decreasing transient lower oesophageal sphincter relaxations, pain modulators or anti-reflux surgery should be considered in non-responders in whom a significant relationship between symptoms and reflux has been confirmed., (Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Dilation of intercellular space diameters of oesophageal epithelium detected at transmission electron microscopy morphometry is a marker of tissue injury in non-erosive reflux disease patients. Semi-quantitative evaluation of intercellular space diameters using light microscopy seems to provide promising results., Aim/methods: To comparatively evaluate intercellular space diameters in the same patients, by means of morphometry and semi-quantitative analysis, both on light microscopy and transmission electron microscopy microphotographs, biopsies were taken in 29 non-erosive reflux disease patients at distal and proximal oesophagus. Twelve asymptomatic controls underwent the same protocol., Results: Morphometric analysis on transmission electron microscopy microphotographs showed mean intercellular space diameter values of patients, at distal and proximal oesophagus, 3- and 2-fold, respectively, higher than those in controls (p<0.001). On light microscopy microphotographs, mean intercellular space diameter values of patients at distal oesophagus were higher than those in controls, an overlap between patients and controls being observed. The semi-quantitative score was positive in 79% of patients and in 25% of controls at distal esophagus., Conclusions: Intercellular space diameter morphometric analysis at light microscopy is widely available, allows intercellular space diameter to be quantitatively measured with good sensitivity and specificity and could represent a useful tool in non-erosive reflux disease diagnosis. Despite satisfactory sensitivity, the semi-quantitative score at light microscopy is hampered by much lower specificity than transmission electron microscopy- and light microscopy-morphometry.