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Background: Swallowed topical corticosteroids (tC) are common therapy for patients with eosinophilic esophagitis (EoE). Widely heterogeneous results have occurred due to their active ingredients, formulations and doses., Objective: To assess the effectiveness of topical corticosteroid therapy for EoE in real-world practice., Methods: Cross-sectional study analysis of the multicentre EoE CONNECT registry. Clinical remission was defined as a decrease of ≥50% in dysphagia symptom scores; histological remission was defined as a peak eosinophil count below 15 per high-power field. The effectiveness in achieving clinico-histological remission (CHR) was compared for the main tC formulations., Results: Overall, data on 1456 prescriptions of tC in monotherapy used in 866 individual patients were assessed. Of those, 904 prescriptions with data on formulation were employed for the induction of remission; 234 reduced a previously effective dose for maintenance. Fluticasone propionate formulations dominated the first-line treatment, while budesonide was more common in later therapies. A swallowed nasal drop suspension was the most common formulation of fluticasone propionate. Doses ≥0.8 mg/day provided a 65% CHR rate and were superior to lower doses. Oral viscous solution prepared by a pharmacist was the most common prescription of budesonide; 4 mg/day provided no benefit over 2 mg/day (CHR rated being 72% and 80%, respectively). A multivariate analysis revealed budesonide orodispersible tablets as the most effective therapy (OR 18.9, p < 0.001); use of higher doses (OR 4.3, p = 0.03) and lower symptom scores (OR 0.9, p = 0.01) were also determinants of effectiveness., Conclusion: Reduced symptom severity, use of high doses, and use of budesonide orodispersible tablets particularly were all independent predictors of tC effectiveness., (© 2024 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: Direct comparisons of childhood- and adulthood-onset eosinophilic esophagitis (EoE) are scarce., Aim: To compare disease characteristics, endoscopic and histological features, allergic concomitances and therapeutic choices across ages., Methods: Cross-sectional analysis of the EoE CONNECT registry., Results: The adulthood-onset cohort (those diagnosed at ≥18y) comprised 1044 patients and the childhood-onset cohort (patients diagnosed at <18 y), 254. Vomiting, nausea, chest and abdominal pain, weight loss, slow eating and food aversion were significantly more frequent in children; dysphagia, food bolus impaction and heartburn predominated in adults. A family history of EoE was present in 16% of pediatric and 8.2% of adult patients (p<0.001). Concomitant atopic diseases did not vary across ages. Median±IQR diagnostic delay (years) from symptom onset was higher in adults (2.7 ± 6.1) than in children (1 ± 2.1; p<0.001). Esophageal strictures and rings predominated in adults (p<0.001), who underwent esophageal dilation more commonly (p = 0.011). Inflammatory EoE phenotypes were more common in children (p = 0.001), who also presented higher eosinophil counts in biopsies (p = 0.015) and EREFS scores (p = 0.017). Despite PPI predominating as initial therapy in all cohorts, dietary therapy and swallowed topical corticosteroids were more frequently prescribed in children (p<0.001)., Conclusions: Childhood-onset EoE has differential characteristics compared with adulthood-onset, but similar response to treatment., Competing Interests: Conflict of Interest AJ Lucendo has served as a speaker, and/or has received research and/or education funding and/or consulting fees from Adare/Ellodi, Dr. Falk Pharma, Regeneron, Dr. Falk Pharma and EsoCap. C. Santander received honoraria as consultant and trainer at Laborie/MMS and Medtronic Covidien AG, and received research funding from AstraZeneca, EsoCap Biotech, Regeneron Pharmaceuticals Inc., Adare Pharmaceuticals Inc., and Dr. Falk Pharma GmbH. J. Alcedo has served as a speaker, consultant and advisory member for or has received research funding from Adare Pharmaceuticals Inc, Abbvie, MSD, Allergan, and Shire Pharmaceuticals. C Gutiérrez-Junquera has received research funding from Dr. Falk Pharma. The remaining authors have no conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Background: The growing prevalence of eosinophilic esophagitis (EoE) represents a considerable burden to patients and health care systems. Optimizing cost-effective management and identifying mechanisms for disease onset and progression are required. However, the paucity of large patient cohorts and heterogeneity of practice hinder the defining of optimal management of EoE., Methods: EoE CONNECT is an ongoing, prospective registry study initiated in 2016 and currently managed by EUREOS, the European Consortium for Eosinophilic Diseases of the Gastrointestinal Tract. Patients are managed and treated by their responsible specialists independently. Data recorded using a web-based system include demographic and clinical variables; patient allergies; environmental, intrapartum, and early life exposures; and family background. Symptoms are structurally assessed at every visit; endoscopic features and histological findings are recorded for each examination. Prospective treatment data are registered sequentially, with new sequences created each time a different treatment (active principle, formulation, or dose) is administered to a patient. EoE CONNECT database is actively monitored to ensure the highest data accuracy and the highest scientific and ethical standards., Results: EoE CONNECT is currently being conducted at 39 centers in Europe and enrolls patients of all ages with EoE. In its aim to increase knowledge, to date EoE CONNECT has provided evidence on the effectiveness of first- and second-line therapies for EoE in clinical practice, the ability of proton pump inhibitors to induce disease remission, and factors associated with improved response. Drug effects to reverse fibrous remodeling and endoscopic features of fibrosis in EoE have also been assessed., Conclusion: This prospective registry study will provide important information on the epidemiological and clinical aspects of EoE and evidence as to the real-world and long-term effectiveness and safety of therapy. These data will potentially be a vital benchmark for planning future EoE health care services in Europe., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Alfredo J. Lucendo has served as a speaker, and/or has received research and/or education funding and/or consulting fees from Adare/Ellodi, Dr. Falk Pharma, Regeneron, and EsoCap. Cecilio Santander has received training and consultant fees from Laborie/MMS. The rest of the authors have no conflict of interest., (© The Author(s), 2022.)

Introduction: To compare Engerix-B and Fendrix hepatitis B virus for primo vaccination in inflammatory bowel disease (IBD)., Methods: Patients with IBD were randomized 1:1 to receive Engerix-B double dose or Fendrix single dose at months 0, 1, 2, and 6. Anti-HBs titers were measured 2 months after the third and fourth doses. Response to vaccination was defined as anti-HBs ≥100 UI/L. Anti-HBs titers were measured 2 months after the third and fourth doses and again at 6 and 12 months after the fourth dose., Results: A total of 173 patients were randomized (54% received Engerix-B and 46% Fendrix). Overall, 45% of patients responded (anti-HBs ≥100 IU/L) after 3 doses and 71% after the fourth dose. The response rate after the fourth dose was 75% with Fendrix vs 68% with Engerix-B (P = 0.3). Older age and treatment with steroids, immunomodulators, or anti-tumor necrosis factor were associated with a lower probability of response. However, the type of vaccine was not associated with the response. Anti-HBs titer negativization occurred in 13% of patients after 6 months and 20% after 12 months. Anti-HBs ≥100 IU/L after vaccination was the only factor associated with maintaining anti-HBs titers during follow-up., Discussion: We could not demonstrate a higher response rate of Fendrix (single dose) over Engerix-B (double dose). A 4-dose schedule is more effective than a 3-dose regimen. Older age and treatment with immunomodulators or anti-tumor necrosis factors impaired the success. A high proportion of IBD patients with protective anti-HBs titers after vaccination loose them over time. The risk of losing protective anti-HBs titers is increased in patients achieving anti-HBs <100 IU/L after the vaccination.

Background and Aims: Steroid-refractoriness is a common and unpredictable phenomenon in ulcerative colitis [UC], but there are no conclusive studies on the molecular functions involved. We aimed to assess the mechanism of action related to steroid failure by integrating transcriptomic data from UC patients, and updated molecular data on UC and glucocorticoids., Methods: MicroRNA [miRNA] and mRNA expression were evaluated by sequencing and microarrays, respectively, from rectal biopsies of patients with moderately-to-severe active UC, obtained before and on the third day of steroid treatment. The differential results were integrated into the mathematical models generated by a systems biology approach., Results: This computational approach identified 18 proteins that stand out either by being associated with the mechanism of action or by providing a means to classify the patients according to steroid response. Their biological functions have been linked to inflammation, glucocorticoid-induced transcription and angiogenesis. All the selected proteins except ANP32E [a chaperone which has been linked to the exchange of H2A.z histone and promotes glucocorticoid receptor-induced transcription] had previously been related to UC and/or glucocorticoid-induced biological actions. Western blot and immunofluorescence assays confirmed the implication of this chaperone in steroid failure in patients with active UC., Conclusions: A systems biology approach allowed us to identify a comprehensive mechanism of action of steroid-refractoriness, highlighting the key role of steroid-induced transcription and the potential implication of ANP32E in this phenomenon., (Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aim: Intravenous corticosteroids remain the first line therapy for severe attacks of ulcerative colitis although up to 30-40% of patients do not respond to treatment. The availability of alternative therapies to colectomy and the knowledge of early predictors of response to corticosteroids should have improved the clinical outcomes of patients with severe refractory ulcerative colitis. The aim of the study is to describe the current need, way of use, and efficacy of rescue therapies, as well as colectomy rates in patients with severe ulcerative colitis flares., Methods: Between January 2005 and December 2011, all patients admitted in three referral centres for a severe ulcerative colitis flare who received intravenous corticosteroids were identified and clinical and biological data were accurately collected. Patients were followed-up until colectomy, death, or date of data collection., Results: Sixty-two flares were included. Initial efficacy of intravenous corticosteroids (mild activity or inactive disease without rescue treatment, at day 7 after starting intravenous corticosteroids) was achieved in 50% of flares, and rescue therapies were used in 27 episodes (43%). After a median follow-up of 18 months, the colectomy rate was 6.5%. Failed oral corticosteroids for the index flare were the only baseline feature that predicted the need for rescue therapy and colectomy., Conclusions: There is a marked reduction in the colectomy rate and an increased use of medical rescue therapies as compared to historical series. Patients worsening while on oral corticosteroids for a moderate flare are at high risk of rescue therapy and colectomy and, therefore, should be directly treated with rescue therapies instead of attempting intravenous corticosteroids., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Oral corticosteroids remain the mainstay of treatment for moderately active ulcerative colitis (UC). In patients who fail to respond to oral corticosteroids, attempting the intravenous route before starting rescue therapies is an alternative, although no evidence supports this strategy., Aim: To evaluate clinical outcomes after a course of intravenous corticosteroids for moderate attacks of UC according to the failed oral corticosteroids or not., Methods: All episodes of active UC admitted to three university hospitals between January 2005 and December 2011 were identified and retrospectively reviewed. Only moderately active episodes treated with intravenous corticosteroids were included. Treatment outcome was compared between episodes which failed to outpatient oral corticosteroids for the index flare and those directly treated by intravenous corticosteroids., Results: 110 episodes were included, 45% of which failed to outpatient oral corticosteroids (median dose 60mg/day [IQR 50-60], median length of course 10days [IQR 7-17]). Initial response (defined as mild severity or inactive disease at day 7 after starting intravenous corticosteroids, without rescue therapy) was achieved in 75%, with no between-group differences (78% vs. 75%). After a median follow-up of 12months (IQR 4-24), 35% of the initial responders developed steroid-dependency and up to 13% required colectomy. Unsuccessful response to oral corticosteroids was the only factor associated with steroid-dependency in the long term (P=0.001)., Conclusions: Intravenous corticosteroids are efficient for inducing remission in moderately active UC unresponsive to oral corticosteroids, but almost half of these patients develop early steroid-dependency. Alternative therapeutic strategies should be assessed in this clinical setting., (Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background: The short-term efficacy of infliximab (IFX) and cyclosporine A (CsA) in steroid-refractory ulcerative colitis (SRUC) has been recently shown to be similar, but long-term outcomes are still unclear. Moreover, the need for further rescue therapies in patients treated with IFX or CsA for SRUC has not been reported. The aims of our study were to compare short-term and long-term efficacy between 2 different strategies based on initial treatment with CsA or IFX for SRUC attacks., Patients and Methods: Between January 2005 and December 2011, all patients admitted for SRUC who required medical rescue therapy were identified from the electronic databases of 3 referral centers and grouped according to whether they received CsA or IFX as first-line rescue therapy, and retrospectively reviewed., Results: Among 50 SRUC attacks, 20 were treated with CsA as first-line rescue therapy and 30 with IFX. The CsA group had a higher proportion of patients with severe UC activity immediately before rescue therapy (P = 0.03) and a shorter median time from intravenous corticosteroids to rescue therapy (P = 0.03). A higher proportion of patients in the CsA group received second-line drug therapy (switch) as compared with the IFX group (P = 0.04). Fifteen patients (30%) were colectomized during the study period, with no between-group differences. Previous thiopurine exposure (P = 0.004; odds ratio = 6.1 [1.7-20.9]) was the only independent predictor of colectomy., Conclusions: CsA- and IFX-based strategies for SRUC seem similarly effective in preventing colectomy in the short and long term, although second-line drug therapy is more often required with CsA-based strategies.

Background: The association between inflammatory bowel disease (IBD) and synovitis, acne, pustulosis, hyperostosis, osteitis syndrome (SAPHO syndrome) was first reported in 1992. To date, only case reports and short series have been published., Aims: The purpose of this study was to report new cases and systematically review the literature on this association., Materials and Methods: All patients with concomitant diagnosis of SAPHO syndrome and IBD were identified from the databases of the rheumatology and gastroenterology departments of our institution. In addition, we systematically searched for published full articles in Medlars Online International Literature via PubMed. Relevant information of each positive match was collected and all authors were contacted for additional clinical data., Results: Three patients sharing both SAPHO syndrome and IBD were identified among the 62 patients with SAPHO syndrome (4.8 % of the SAPHO cohort) and the 1,309 patients with IBD (0.2 % of the IBD cohort) from our hospital database. After a systematic review, a total of 39 reported patients with concomitant diagnosis of SAPHO syndrome and IBD were identified. There was a female predominance and most had Crohn's disease with colonic involvement., Conclusions: The association of SAPHO syndrome and IBD seems to be rare among IBD patients but not so among SAPHO patients. SAPHO could be underdiagnosed because of the similarity of its clinical manifestations and some more common extraintestinal manifestations or drug-related side effects in IBD.

Systemic amyloidosis comprises a group of diseases that develop as a consequence of an abnormal accumulation of different proteins in several organs, altering their function. Secondary amyloidosis develops after the accumulation of serum amyloid A protein (an acute phase reactant), mainly in the course of chronic inflammatory conditions such as rheumatologic diseases, familial Mediterranean fever, or tuberculosis. Inflammatory bowel disease (IBD) may also cause secondary amyloidosis. However, little is known about the true prevalence, risk factors, and clinical outcomes of amyloidosis among IBD patients. A few studies suggest that amyloidosis is more prevalent in Crohn's disease than in ulcerative colitis, mainly occurring in patients with an extensive, long-lasting, and penetrating disease pattern. In this article we review the available data on secondary amyloidosis and IBD, focusing on prevalence, risk factors, clinical presentation and therapeutic measures., (Copyright © 2011 Elsevier España, S.L. y AEEH y AEG. All rights reserved.)

Background and Aims: Skip inflammation of the appendiceal orifice has been described in distal UC (UC-IAO) but long-term clinical outcomes are poorly established. Our aim was to evaluate the long-term clinical outcomes of UC-IAO as compared to classic distal UC., Methods: Patients with UC-IAO were identified from the local IBD database. Disease outcome and therapeutic requirements during follow-up were accurately collected, and compared with a control group of patients with distal UC without peri-appendiceal involvement matched by disease extent (proctitis/distal), smoking habit, and date and age at diagnosis., Results: Fourteen UC patients were found to have UC-IAO, most of them with initial extent of UC limited to the rectum. All patients were initially managed with mesalazine administered orally (28.5%), topically (28.5%), or in combination (43%). After a median follow-up of 78 months (interquartile range--IQR 45-123) most UC-IAO patients were successfully managed with oral and/or topical aminosalicylates. Only one of them developed proximal disease progression. As compared to controls, no differences in clinical outcomes or therapeutic requirements were found., Conclusions: Patients with UC-IAO tend to present a mild course, with a low probability to develop proximal progression of disease extent or to require immunosuppressive therapy or colectomy.

Background: Systemic amyloidosis is a rare but life-threatening complication of inflammatory bowel disease (IBD), most cases being reported among Crohn's disease (CD) patients. The only two available retrospective studies showed a prevalence ranging from 0.9% to 3% among CD patients., Aims: To evaluate the prevalence of secondary systemic amyloidosis in a large IBD cohort of a referral centre, and to describe its clinical characteristics and outcome., Methods: Patients diagnosed with amyloidosis were identified among 1006 IBD patients included in the IBD database of our centre, and their medical records were carefully reviewed., Results: Among a total of 1006 IBD patients, 5 cases of amyloidosis were identified, all of them with CD, resulting in a prevalence of 0.5% for IBD and 1% for CD. Two patients died after developing renal failure. Two patients were treated with anti-TNF agents, showing a clinical improvement of their amyloidosis., Conclusions: Secondary amyloidosis occurs mainly in long-lasting, complicated, Crohn's disease and seems to be as prevalent among IBD patients as previously reported., (Copyright © 2009 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Portal hypertension (PH) is a complication that may occur in patients with inflammatory bowel disease (IBD). In these patients, the etiology of PH may not be alcoholic or viral cirrhosis (which cause 90% of cases in the general population). Consequently, etiologic study of PH in patients with IBD should always include a wide spectrum of possibilities. Moreover, the development of PH in IBD patients often requires a distinct therapeutic approach to IBD (both medical and surgical) as PH may be a contraindication for some drugs and is a risk factor for surgical morbidity and mortality. We present the cases of two patients with IBD who developed PH and review the most likely causes of PH in IBD, as well as preventive and therapeutic strategies., (Copyright 2009 Elsevier España, S.L. All rights reserved.)