New entity of adult ultra-short coeliac disease: the first international cohort and case-control study.

BACKGROUND: Ultra-short coeliac disease (USCD) is defined as villous atrophy only present in the duodenal bulb (D1) with concurrent positive coeliac serology. We present the first, multicentre, international study of patients with USCD. METHODS: Patients with USCD were identified from 10 tertiary hospitals (6 from Europe, 2 from Asia, 1 from North America and 1 from Australasia) and compared with age-matched and sex-matched patients with conventional coeliac disease. FINDINGS: Patients with USCD (n=137, median age 27 years, IQR 21-43 years; 73% female) were younger than those with conventional coeliac disease (27 vs 38 years, respectively, p<0.001). Immunoglobulin A-tissue transglutaminase (IgA-tTG) titres at index gastroscopy were lower in patients with USCD versus conventional coeliac disease (1.8×upper limit of normal (ULN) (IQR 1.1-5.9) vs 12.6×ULN (IQR 3.3-18.3), p<0.001).Patients with USCD had the same number of symptoms overall (median 3 (IQR 2-4) vs 3 (IQR 1-4), p=0.875). Patients with USCD experienced less iron deficiency (41.8% vs 22.4%, p=0.006).Both USCD and conventional coeliac disease had the same intraepithelial lymphocytes immunophenotype staining pattern; positive for CD3 and CD8, but not CD4.At follow-up having commenced a gluten-free diet (GFD) (median of 1181 days IQR: 440-2160 days) both USCD and the age-matched and sex-matched controls experienced a similar reduction in IgA-tTG titres (0.5 ULN (IQR 0.2-1.4) vs 0.7 ULN (IQR 0.2-2.6), p=0.312). 95.7% of patients with USCD reported a clinical improvement in their symptoms. INTERPRETATION: Patients with USCD are younger, have a similar symptomatic burden and benefit from a GFD. This study endorses the recommendation of D1 sampling as part of the endoscopic coeliac disease diagnostic workup.

New approaches to diet therapy for eosinophilic esophagitis.

PURPOSE OF REVIEW: An empiric step-up (2-4-6) elimination diet remains the most common dietary approach in clinical practice when treating eosinophilic esophagitis (EoE). However, research in this field has fallen behind pharmacological therapy. This review aims to summarize novel approaches to dietary therapy for EoE. RECENT FINDINGS: A first prospective multicenter study in 41 pediatric patients (mean age 9 years) has evaluated the efficacy of a cow's milk elimination diet. This dietary approach led to histological remission in 51% of patients, albeit a caveat is that up to 80% of patients were receiving concomitant therapy with proton pump inhibitors. In a series of 18 adult patients with documented milk-induced EoE, ingestión of 400 ml of sterilized milk (boiled for up to 20 min) daily for 8 weeks did not induce histologic relapse in two-thirds of patients. SUMMARY: Milk elimination diet is effective in one-half of pediatric EoE patients and should likely be the first choice in children with EoE (within a step-up dietary approach). Promising data on tolerance of sterilized milk in adults with milk-induced EoE (66%) merit further replication in children, which may radically improve quality of life for patients and their caregivers.

Empirical Second-Line Therapy in 5000 Patients of the European Registry on Helicobacter pylori Management (Hp-EuReg).

BACKGROUND & AIMS: After a first Helicobacter pylori eradication attempt, approximately 20% of patients will remain infected. The aim of the current study was to assess the effectiveness and safety of second-line empiric treatment in Europe. METHODS: This international, multicenter, prospective, non-interventional registry aimed to evaluate the decisions and outcomes of H pylori management by European gastroenterologists. All infected adult cases with a previous eradication treatment attempt were registered with the Spanish Association of Gastroenterology-Research Electronic Data Capture until February 2021. Patients allergic to penicillin and those who received susceptibility-guided therapy were excluded. Data monitoring was performed to ensure data quality. RESULTS: Overall, 5055 patients received empiric second-line treatment. Triple therapy with amoxicillin and levofloxacin was prescribed most commonly (33%). The overall effectiveness was 82% by modified intention-to-treat analysis and 83% in the per-protocol population. After failure of first-line clarithromycin-containing treatment, optimal eradication (>90%) was obtained with moxifloxacin-containing triple therapy or levofloxacin-containing quadruple therapy (with bismuth). In patients receiving triple therapy containing levofloxacin or moxifloxacin, and levofloxacin-bismuth quadruple treatment, cure rates were optimized with 14-day regimens using high doses of proton pump inhibitors. However, 3-in-1 single capsule or levofloxacin-bismuth quadruple therapy produced reliable eradication rates regardless of proton pump inhibitor dose, duration of therapy, or previous first-line treatment. The overall incidence of adverse events was 28%, and most (85%) were mild. Three patients developed serious adverse events (0.3%) requiring hospitalization. CONCLUSIONS: Empiric second-line regimens including 14-day quinolone triple therapies, 14-day levofloxacin-bismuth quadruple therapy, 14-day tetracycline-bismuth classic quadruple therapy, and 10-day bismuth quadruple therapy (as a single capsule) provided optimal effectiveness. However, many other second-line treatments evaluated reported low eradication rates. ClincialTrials.gov number: NCT02328131.

Ultra-short celiac disease exhibits differential genetic and immunophenotypic features compared to conventional celiac disease.

BACKGROUND: Ultra-short coeliac disease (USCD) is a novel celiac disease (CD) subtype limited to the duodenal bulb (D1). HLA haplotypes and flow cytometry have not been assessed yet. AIMS: To compare genetic, clinical, serologic, histopathologic and inmmunophenotypic parameters between USCD and conventional celiac disease (CCD) patients. METHODS: Prospective single-center study in children and adult patients undergoing duodenal biopsies on a gluten-containing diet. Biopsies for histology and flow cytometry were taken separately from D1 and distal duodenum. Biopsies in seronegative patients with celiac lymphogram were repeated after 2 years on a gluten-free diet. RESULTS: Among 505 included patients, 127 were diagnosed with CD, of whom 7 (5.5%) showed USCD. HLADQ2 was significantly less common in USCD compared to CCD (71% vs. 95%, p 0.003). Likewise, USCD patients showed more frequent non-significant seronegativity (28% vs. 8%, p 0.07) and significantly lower titrations (7-15IU/ml) of tissue transglutaminase antibodies (tTG-IgA) (60% vs. 13%, p<0.001). Biopsies from D1 revealed significant less NK cells down-expression in USCD patients (1.4 vs. 5, p 0.04). CONCLUSIONS: Up to 5.5% of CD patients showed USCD. A lower frequency of HLADQ2, along with less serum tTG-IgA titration and duodenal NK cell suppression, were differential features of USCD.

V Spanish Consensus Conference on Helicobacter pylori infection treatment. / V Conferencia Española de Consenso sobre el tratamiento de la infección por Helicobacter pylori.

Helicobacter pylori infection is very common in the Spanish population and represents the main cause of chronic gastritis, peptic ulcer, and gastric cancer. The last iteration of Spanish consensus guidelines on H. pylori infection was conducted in 2016. Recent changes in therapeutic schemes along with increasing supporting evidence were key for developing the V Spanish Consensus Conference (May 2021). Fourteen experts performed a systematic review of the scientific evidence and developed a series of recommendations that were subjected to an anonymous Delphi process of iterative voting. Scientific evidence and the strength of the recommendation were classified using GRADE guidelines. An eradication therapy, when prescribed empirically, is considered acceptable when it reliably achieves, or preferably surpass, 90% cure rates. Currently, only quadruple therapies (with or without bismuth) and generally lasting 14 days, accomplish this goal in first- and second-line therapies. A non-bismuth quadruple concomitant regimen (proton pump inhibitor, clarithromycin, amoxicillin, and metronidazole) or a quadruple bismuth-based combination (proton pump inhibitor, bismuth, tetracycline, and metronidazole), are recommended as first-line regimens. Rescue therapies after eradication failure and management of H. pylori infection in peptic ulcer disease were also reviewed.

European Registry on Helicobacter pylori management (Hp-EuReg): patterns and trends in first-line empirical eradication prescription and outcomes of 5 years and 21 533 patients.

OBJECTIVE: The best approach for Helicobacter pylori management remains unclear. An audit process is essential to ensure clinical practice is aligned with best standards of care. DESIGN: International multicentre prospective non-interventional registry starting in 2013 aimed to evaluate the decisions and outcomes in H. pylori management by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap. Variables included demographics, previous eradication attempts, prescribed treatment, adverse events and outcomes. Data monitoring was performed to ensure data quality. Time-trend and geographical analyses were performed. RESULTS: 30 394 patients from 27 European countries were evaluated and 21 533 (78%) first-line empirical H. pylori treatments were included for analysis. Pretreatment resistance rates were 23% to clarithromycin, 32% to metronidazole and 13% to both. Triple therapy with amoxicillin and clarithromycin was most commonly prescribed (39%), achieving 81.5% modified intention-to-treat eradication rate. Over 90% eradication was obtained only with 10-day bismuth quadruple or 14-day concomitant treatments. Longer treatment duration, higher acid inhibition and compliance were associated with higher eradication rates. Time-trend analysis showed a region-dependent shift in prescriptions including abandoning triple therapies, using higher acid-inhibition and longer treatments, which was associated with an overall effectiveness increase (84%-90%). CONCLUSION: Management of H. pylori infection by European gastroenterologists is heterogeneous, suboptimal and discrepant with current recommendations. Only quadruple therapies lasting at least 10 days are able to achieve over 90% eradication rates. European recommendations are being slowly and heterogeneously incorporated into routine clinical practice, which was associated with a corresponding increase in effectiveness.

Persistent Villous Atrophy in De Novo Adult Patients With Celiac Disease and Strict Control of Gluten-Free Diet Adherence: A Multicenter Prospective Study (CADER Study).

INTRODUCTION: A substantial proportion of adult patients with celiac disease on a gluten-free diet exhibit persistent villous atrophy, and inadvertent gluten exposure may be one of the causes. The aim of the present study was to evaluate villous atrophy persistence after 2 years on a gluten-free diet in de novo adult patients with celiac disease with strict control of gluten exposure. METHODS: Symptomatic de novo adult patients with celiac disease were prospectively included. Clinical visits and dietary surveillance were scheduled every 6 months during a 2-year follow-up period. At each visit, fecal samples were collected and stored at -20 °C until analysis for gluten immunogenic peptides (f-GIPs). A follow-up duodenal biopsy was performed at 2 years. We evaluated the variables associated with persistent villous atrophy. RESULTS: Seventy-six patients completed the study (36.5 ± 1.6 years, 73% women); persistent villous atrophy was observed in 40 (53%), whereas 72.5% were asymptomatic and 75% had negative serology. Detectable f-GIP >0.08 µg/g in at least 1 fecal sample was seen in 69% of patients. There were no significant differences in the median f-GIP at each visit and median area under the curve over the serial measurements between patients with persistent villous atrophy and those who recovered. On multivariate analysis, only older age was associated with persistent villous atrophy (32% for 16-30 years; 67% for >30 years; P = 0.016). DISCUSSION: The rate of persistent villous atrophy after 2 years was high in adult patients with celiac disease on an intentionally strict gluten-free diet. Low-level ongoing inadvertent gluten exposure could be a contributing factor to persistent villous atrophy.

V Spanish Consensus Conference on Helicobacter pylori infection treatment.

Helicobacter pylori infection is very common in the Spanish population and represents the main cause of chronic gastritis, peptic ulcer, and gastric cancer. The last iteration of Spanish consensus guidelines on H. pylori infection was conducted in 2016. Recent changes in therapeutic schemes along with increasing supporting evidence were key for developing the V Spanish Consensus Conference (May 2021). Fourteen experts performed a systematic review of the scientific evidence and developed a series of recommendations that were subjected to an anonymous Delphi process of iterative voting. Scientific evidence and the strength of the recommendation were classified using GRADE guidelines. An eradication therapy, when prescribed empirically, is considered acceptable when it reliably achieves, or preferably surpass, 90% cure rates. Currently, only quadruple therapies (with or without bismuth) and generally lasting 14 days, accomplish this goal in first- and second-line therapies. A non-bismuth quadruple concomitant regimen (proton pump inhibitor, clarithromycin, amoxicillin, and metronidazole) or a quadruple bismuth-based combination (proton pump inhibitor, bismuth, tetracycline, and metronidazole), are recommended as first-line regimens. Rescue therapies after eradication failure and management of H. pylori infection in peptic ulcer disease were also reviewed.

Efficacy of Budesonide Orodispersible Tablets as Induction Therapy for Eosinophilic Esophagitis in a Randomized Placebo-Controlled Trial.

BACKGROUND & AIMS: Swallowed topical-acting corticosteroids are recommended as first-line therapy for eosinophilic esophagitis (EoE). Asthma medications not optimized for esophageal delivery are sometimes effective, although given off-label. We performed a randomized, placebo-controlled trial to assess the effectiveness and tolerability of a budesonide orodispersible tablet (BOT), which allows the drug to be delivered to the esophagus in adults with active EoE. METHODS: We performed a double-blind, parallel study of 88 adults with active EoE in Europe. Patients were randomly assigned to groups that received BOT (1 mg twice daily; n = 59) or placebo (n = 29) for 6 weeks. The primary end point was complete remission, based on clinical and histologic factors, including dysphagia and odynophagia severity ≤2 on a scale of 0-10 on each of the 7 days before the end of the double-blind phase and a peak eosinophil count <5 eosinophils/high power field. Patients who did not achieve complete remission at the end of the 6-week double-blind phase were offered 6 weeks of open-label treatment with BOT (1 mg twice daily). RESULTS: At 6 weeks, 58% of patients given BOT were in complete remission compared with no patients given placebo (P < .0001). The secondary end point of histologic remission was achieved by 93% of patients given BOT vs no patients given placebo (P < .0001). After 12 weeks, 85% of patients had achieved remission. Six-week and 12-week BOT administration were safe and well tolerated; 5% of patients who received BOT developed symptomatic, mild candida, which was easily treated with an oral antifungal agent. CONCLUSIONS: In a randomized trial of adults with active EoE, we found that budesonide oral tablets were significantly more effective than placebo in inducing clinical and histologic remission. Eudra-CT number 2014-001485-99; ClinicalTrials.gov ID NCT02434029.

Combination of Bismuth and Standard Triple Therapy Eradicates Helicobacter pylori Infection in More than 90% of Patients.

BACKGROUND & AIMS: Due to the poor eradication rates of standard triple therapy, the addition of bismuth salts has been proposed for first-line eradication of Helicobacter pylori. We assessed the effectiveness and safety of the combination of bismuth and the standard, clarithromycin-containing triple therapy in eradication of H pylori infection, using data from a large multi-center registry. METHODS: We performed an interim analysis of data from the European Registry on H pylori Management, a prospective trial registering clinical data and outcomes from infected patients from 27 countries in Europe since 2013. We extracted data on 1141 treatment-naïve patients who received first-line treatment with bismuth salts (240 mg) and a proton pump inhibitor (57% received esomeprazole, 18% received omeprazole, 11% received pantoprazole, and 14% received rabeprazole), amoxicillin (1 g), and clarithromycin (500 mg), all taken twice daily. RESULTS: Intention to treat and per-protocol rates of eradication were 88% and 94%, respectively. Intention to treat eradication increased to 93% in patients who received 14-day treatments. Adverse events occurred in 36% of patients; 76% of these events were mild, with a mean duration of 6 days. In multivariate analysis, eradication was associated with treatment compliance (odds ratio [OR], 13.0), a double dose (equivalent to 40 mg omeprazole) of proton pump inhibitor (OR, 4.7), and 14-day duration of treatment (OR, 2.0). CONCLUSIONS: In an analysis of data from a large multi-center registry, we found the addition of bismuth to 14-day standard triple therapy with clarithromycin and amoxicillin to eradicate H pylori infection in more than 90% of patients, based on intention to treat analysis, with an acceptable safety profile and level of adherence. ClinicalTrials.gov no: NCT02328131.

Approaches to diet therapy for eosinophilic esophagitis.

PURPOSE OF REVIEW: The aim of this review is to highlight recent advances in dietary therapy for eosinophilic esophagitis (EoE). RECENT FINDINGS: An empiric elimination diet step-up strategy is now well established as the initial approach for dietary treatment. The most common food triggers are by far cow's milk, followed by wheat and egg. Legumes seem to be important solely in Spain and other Mediterranean countries, where they are regularly consumed. Retrospective efficacy data on cow's milk elimination diet in children vary from 25 to 65%. The recently described esophageal prick test did not detect local reaction to the most common food triggers described for EoE. SUMMARY: Within the step-up approach, the specific food group or groups to be first eliminated and whether if it will depend on the geographical setting and food consumption habits remain unknown. Prospective studies on cow's milk elimination diet in children and adults are definitely warranted. Better food allergy testing, identifying specific antigens involved in each food group, should be developed for an individualized therapy. As for disease prevention, we undoubtedly need to understand why foods we have been consuming since the Neolithic age have caused EoE just over the past few decades.

Bismuth quadruple regimen with tetracycline or doxycycline versus three-in-one single capsule as third-line rescue therapy for Helicobacter pylori infection: Spanish data of the European Helicobacter pylori Registry (Hp-EuReg).

BACKGROUND: Different bismuth quadruple therapies containing proton-pump inhibitors, bismuth salts, metronidazole, and a tetracycline have been recommended as third-line Helicobacter pylori eradication treatment after failure with clarithromycin and levofloxacin. AIM: To evaluate the efficacy and safety of third-line treatments with bismuth, metronidazole, and either tetracycline or doxycycline. METHODS: Sub-study with Spanish data of the "European Registry on H pylori Management" (Hp-EuReg), international multicenter prospective non-interventional Registry of the routine clinical practice of gastroenterologists. After previous failure with clarithromycin- and levofloxacin-containing therapies, patients receiving a third-line regimen with 10/14-day bismuth salts, metronidazole, and either tetracycline (BQT-Tet) or doxycycline (BQT-Dox), or single capsule (BQT-three-in-one) were included. Data were registered at AEG-REDCap database. Univariate and multivariate analyses were performed. RESULTS: Four-hundred and fifty-four patients have been treated so far: 85 with BQT-Tet, 94 with BQT-Dox, and 275 with BQT-three-in-one. Average age was 53 years, 68% were women. Overall modified intention-to-treat and per-protocol eradication rates were 81% (BQT-Dox: 65%, BQT-Tet: 76%, BQT-three-in-one: 88%) and 82% (BQT-Dox: 66%, BQT-Tet: 77%, BQT-three-in-one: 88%), respectively. By logistic regression, higher eradication rates were associated with compliance (OR = 2.96; 95% CI = 1.01-8.84) and no prior metronidazole use (OR = 1.96; 95% CI = 1.15-3.33); BQT-three-in-one was superior to BQT-Dox (OR = 4.46; 95% CI = 2.51-8.27), and BQT-Tet was marginally superior to BQT-Dox (OR = 1.67; 95% CI = 0.85-3.29). CONCLUSION: Third-line H pylori eradication with bismuth quadruple treatment (after failure with clarithromycin and levofloxacin) offers acceptable efficacy and safety. Highest efficacy was found in compliant patients and those taking 10-day BQT-three-in-one or 14-day BQT-Tet. Doxycycline seems to be less effective and therefore should not be recommended.

Prospective, study comparing the accuracy of two different stool antigen tests (Premier Platinum HpSA and novel ImmunoCard STAT! rapid test) for the diagnosis of Helicobacter pylori infection.

BACKGROUND: At present only monoclonal EIA (enzyme-immunoassay) stool antigen-tests have obtained optimal accuracy in the diagnosis of Helicobacter pylori. Our aim was to evaluate the accuracy of two stool antigen-tests, the validated Premier Platinum HpSA PLUS (EIA test) and the newly available ImmunoCard STAT! HpSA HD (rapid test) for the initial diagnosis and the confirmation of eradication of H. pylori infection. PATIENTS AND METHODS: Patients with indication of H. pylori diagnosis, or confirmation after treatment were included. Data were coded to protect personal data and ensure blindness between tests. Accuracy was considered as coincident diagnosis with the gold standard (13C-urea breath test, UBT). The EIA was used as a bench standard. All stool tests were performed in duplicate. RESULTS: 264 patients completed the protocol (100 naïve, 164 post-eradication). Average age was 52 years, 61% women, 11% ulcer. Positive diagnoses by UBT were 41% for naïve and 17% for post-eradication. Overall ImmunoCard and EIA accuracies were respectively 91% (95%C.I.=88-94%) and 89% (86-93%), sensitivities 72% (67-78%) and 72% (67-78%), and specificities 98% (96-100%), and 95% (92-97%). Concordance between ImmunoCard and EIA was 95% (93-98%). DISCUSSION: Our results indicate that the newly available ImmunoCard rapid stool antigen-test achieves 90% accuracy, with high specificity but suboptimal sensitivity. The ImmunoCard attained equivalent accuracies as the EIA bench standard, with 95% concordance.

Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the AGREE Conference.

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.

Dietary therapy for eosinophilic esophagitis.

Eosinophilic esophagitis is a chronic, immune-mediated esophageal disease triggered predominantly, but not exclusively, by food antigens. Presently, available food allergy tests are suboptimal to predict food triggers for eosinophilic esophagitis, especially in adults. Elemental diets (exclusive feeding with amino acid-based formulas) and empiric 6-food elimination diets (withdrawing milk, wheat, egg, soy, nuts, and fish/seafood for 6 weeks) have consistently shown the best efficacy rates. However, their high level of restriction and need for multiple endoscopies have hampered their implementation in clinical practice. Currently, milk, wheat/gluten, and egg are the most common food triggers in children and adults from the United States, Spain, and Australia. Hence less restrictive empiric schemes, such as a 4-food elimination diet (dairy, gluten-containing cereals, egg, and legumes) or a 2-food elimination diet (dairy and gluten-containing cereals) have been lately developed with good efficacy rates (2-food elimination diet, 43%; 4-food elimination diet in adults, 54%; and 4-food elimination diet in children, 64%). A step-up approach (2-4-6) might result in prompt recognition of a majority of responders with few food triggers, reducing the number of endoscopies and costs and shortening the diagnostic process. Standardization of food reintroduction, novel food allergy testing, and studies evaluating a milk elimination diet in children and the long-term outcomes of dietary interventions are warranted.

Step-up empiric elimination diet for pediatric and adult eosinophilic esophagitis: The 2-4-6 study.

BACKGROUND: Numerous dietary restrictions and endoscopies limit the implementation of empiric elimination diets in patients with eosinophilic esophagitis (EoE). Milk and wheat/gluten are the most common food triggers. OBJECTIVE: We sought to assess the effectiveness of a step-up dietary strategy for EoE. METHODS: We performed a prospective study conducted in 14 centers. Patients underwent a 6-week 2-food-group elimination diet (TFGED; milk and gluten-containing cereals). Remission was defined by symptom improvement and less than 15 eosinophils/high-power field. Nonresponders were gradually offered a 4-food-group elimination diet (FFGED; TFGED plus egg and legumes) and a 6-food-group elimination diet (SFGED; FFGED plus nuts and fish/seafood). In responders eliminated food groups were reintroduced individually, followed by endoscopy. RESULTS: One hundred thirty patients (25 pediatric patients) were enrolled, with 97 completing all phases of the study. A TFGED achieved EoE remission in 56 (43%) patients, with no differences between ages. Food triggers in TFGED responders were milk (52%), gluten-containing grains (16%), and both (28%). EoE induced only by milk was present in 18% and 33% of adults and children, respectively. Remission rates with FFGEDs and SFGEDs were 60% and 79%, with increasing food triggers, especially after an SFGED. Overall, 55 (91.6%) of 60 of the TFGED/FFGED responders had 1 or 2 food triggers. Compared with the initial SFGED, a step-up strategy reduced endoscopic procedures and diagnostic process time by 20%. CONCLUSIONS: A TFGED diet achieves EoE remission in 43% of children and adults. A step-up approach results in early identification of a majority of responders to an empiric diet with few food triggers, avoiding unnecessary dietary restrictions, saving endoscopies, and shortening the diagnostic process.

Helicobacter pylori infection does not protect against eosinophilic esophagitis: results from a large multicenter case-control study.

OBJECTIVES: Rising trends in eosinophilic esophagitis (EoE) have been repeatedly linked to declining Helicobacter pylori (H. pylori) infection, mostly in retrospective studies. We aimed to prospectively evaluate this inverse association. METHODS: Prospective case-control study conducted in 23 centers. Children and adults naïve to eradication therapy for H. pylori were included. Cases were EoE patients, whereas controls were defined by esophageal symptoms and <5 eos/HPF on esophageal biopsies. H. pylori status was diagnosed by non-invasive (excluding serology) or invasive testing off proton pump inhibitor (PPI) therapy for 2 weeks. Atopy was defined by the presence of IgE-mediated conditions diagnosed by an allergist. RESULTS: 808 individuals, including 404 cases and 404 controls (170 children) were enrolled. Overall H. pylori prevalence was 38% (45% children vs. 37% adults, p 0.009) and was not different between cases and controls (37% vs. 40%, p 0.3; odds ratio (OR) 0.97; 95% confidence interval (CI) 0.73-1.30), neither in children (42% vs. 46%, p 0.1) nor in adults (36% vs. 38%, p 0.4). Atopy (OR 0.85; 95%CI 0.75-0.98) and allergic rhinitis (OR 0.81; 95%CI 0.68-0.98) showed a borderline inverse association with H. pylori infection in EoE patients. This trend was not confirmed for asthma or food allergy. CONCLUSIONS: H. pylori infection was not inversely associated with EoE, neither in children nor in adults. A borderline inverse association was confirmed for atopy and allergic rhinitis, but not asthma of food allergy. Our findings question a true protective role of H. pylori infection against allergic disorders, including EoE.

Esophageal dilation in eosinophilic esophagitis: risks, benefits, and when to do it.

PURPOSE OF REVIEW: For patients with eosinophilic esophagitis (EoE), endoscopic dilation has been used primarily to provide immediate symptomatic relief of dysphagia. This report reviews the current position of esophageal dilation in the therapeutic algorithm for EoE, including effectiveness and safety issues. RECENT FINDINGS: Esophageal strictures in EoE develop as a consequence of long-lasting esophageal eosinophilia, with patient age and diagnostic delay as well established risk factors. Endoscopic dilation leads to immediate symptomatic improvement in 95% of EoE patients who have strictures or narrow caliber esophagus. As dilation has no effect on the underlying eosinophil inflammation, repeated procedures are usually needed to maintain symptoms in remission. Adding an effective drug or dietary-based EoE therapy reduces the need of further dilation. The high rate of severe complications from dilation reported in early literature has not been reproduced in most recent series, with mild postprocedural chest pain as the most common side effect. Current data suggest that the risk of esophageal perforation is less than 1%. Mucosal tears after dilation should no longer be considered a complication, but rather a marker of procedural success. SUMMARY: Esophageal dilation should be considered in EoE patients with esophageal strictures or narrow caliber esophagus who have persistent dysphagia/food impaction despite an effective anti-inflammatory treatment.

Probiotic supplementation with Lactobacillus plantarum and Pediococcus acidilactici for Helicobacter pylori therapy: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the safety, tolerability and efficacy of a probiotic supplementation for Helicobacter pylori (H. pylori) eradication therapy. DESIGN: Consecutive adult naive patients with a diagnosis of H. pylori infection who were prescribed eradication therapy according to clinical practice (10-day triple or nonbismuth quadruple concomitant therapy) randomly received probiotics (1 × 109 colony-forming units each strain, Lactobacillus plantarum and Pediococcus acidilactici) or matching placebo. Side effects at the end of the treatment, measured through a modified De Boer Scale, were the primary outcome. Secondary outcomes were compliance with therapy and eradication rates. RESULTS: A total of 209 patients (33% triple therapy, 66% non-bismuth quadruple therapy) were included [placebo (n = 106) or probiotic (n = 103)]. No differences were observed regarding side effects at the end of the treatment between groups (ß -0.023, P 0.738). Female gender (P < 0.001) and quadruple therapy (P 0.007) were independent predictors of side effects. No differences in compliance were observed, regardless of the study group or eradication therapy. Eradication rates were similar between groups [placebo 95% (95% confidence interval (CI), 89% to 98%) vs probiotic 97% (95% CI, 92% to 99%), P 0.721]. There were no relevant differences in cure rates (>90% in all cases) between triple and quadruple concomitant therapy. CONCLUSION: Probiotic supplementation containing Lactobacillus Plantarum and Pediococcus acidilactici to H. pylori treatment neither decreased side effects nor improved compliance with therapy or eradication rates.

Eosinophilic oesophagitis: Current evidence-based diagnosis and treatment. / Esofagitis eosinofílica: diagnóstico y tratamiento actual basado en la evidencia.

Eosinophilic oesophagitis (EoE) is a disease caused by an immune response to food antigens in contact with the oesophageal mucosa. Its diagnosis is defined by the combination of oesophageal dysfunction symptoms and inflammation of the oesophageal mucosa predominantly by eosinophils. Its chronic course and frequent progression to subepithelial fibrosis and oesophageal strictures indicate the need for treatment. The information provided by recent clinical trials and systematic reviews has led to the development of new clinical guidelines, endorsed by several European scientific societies. This review includes the most relevant aspects of the new guidelines, updates the EoE concept and reports its epidemiology and risk factors, associated conditions and its natural history in children and adults. Diagnostic criteria are provided, and tests for EoE diagnosis and monitoring and therapeutic options are analysed based on the best scientific evidence and consensus opinion of experts.