Efficacy of Bismuth Therapy in Eradicating Helicobacter pylori in Children-Data From the RENIHp Registry.

OBJECTIVES: To evaluate the efficacy of colloidal bismuth subcitrate (CBS) therapy for the eradication of H. pylori in patients from a national pediatric registry of H. pylori infection. METHODS: The Spanish Registry of Children with H. pylori Infection (RENIHp) is a national, multi-center, prospective, non-interventional registry that includes children aged 5-18 years with H. pylori infection diagnosed by endoscopy. All patients in the registry who were treated with CBS between the period 2020 and 2023 were included in this study. The primary outcome was the eradication rate, which was assessed using a 13C-urea breath test or monoclonal antigen in the stool 6-8 weeks post-treatment. RESULTS: The registry included 682 patients, 38 (5.6%) of whom underwent treatment with CBS. Fifty percent (19/38) of patients had previously undergone unsuccessful eradication treatment. In 78.9% (30/38) of patients, treatment was guided by an antibiotic sensitivity test. In the remaining patients, an empirical approach was employed. The CBS therapies used were as follows: quadruple therapy with proton pump inhibitors (PPIs), CBS, amoxicillin, and metronidazole (MET) [18/38 (47.3%)]; quadruple therapy with PPIs, CBS, tetracycline, and MET [13/38 (34.2%)]; and other therapies [7/38 (18.4%)]. Thirty-two patients (84.2%) treated with CBS were followed-up with eradication monitoring. The overall eradication rate in patients treated with CBS was 93.8% (30/32, [95% CI: 85.4%-100%]), whereas it was 86.7% in patients in the registry who were not on CBS treatment (430/496, [95% CI: 83.3%-89.5%], p = 0.208). In the six patients with dual resistance to clarithromycin (CLA) and MET who were treated with quadruple therapy with CBS, the eradication rate was 100% (n = 6/6, [95% CI: 61.0%-100%]). CONCLUSION: CBS therapies in our registry, although only used in selected cases and at lower than recommended levels, were very effective and showed an eradication rate of > 90%.

Factors Associated With Decision to Treat or Not to Treat Helicobacter pylori Infection in Children: Data From the EuroPedHp Registry.

BACKGROUND: European and North-American guidelines on management of H. pylori infection in children provide the option not to treat even if the infection is endoscopically confirmed. We used data from the EuroPedHp Registry to identify factors associated with therapy decisions. METHODS: We included treatment-naïve patients reported between 2017 and 2020 from 30 centers in 17 European countries. Multivariable logistic regression identified factors including comorbidities within and outside the gastrointestinal (GI) tract influencing the decision for or against therapy. RESULTS: Of 1165 patients (52% females, median age 12.8), 28% (321/1165) reported any alarm symptom, 26% (307/1165) comorbidities, and 16% (192/1165) did not receive eradication treatment. Therapy was initiated less often in children having any GI comorbidity (57%, n = 181), particularly in those with eosinophilic esophagitis (60%, n = 35), inflammatory bowel disease (54%, n = 28), and celiac disease (43%, n = 58), compared to those with non-GI (86%, n = 126) or no comorbidity (89%, n = 858), despite similar frequencies of alarm and non-alarm symptoms, ulcers, erosions, and nodular gastritis. Patients with GI and without comorbidities remained more likely untreated in high versus low H. pylori prevalence countries (p < 0.0001). In children without comorbidities, factors favoring therapy included older age, being overweight, having symptoms, erosions, antral nodularity, and available antibiotic susceptibility results. CONCLUSION: In this cohort, H. pylori-infected children with GI comorbidities compared to no comorbidity showed 75% reduced chance of receiving eradication therapy. We found no evidence supporting different management strategies in infected patients with GI comorbidities compared to all pediatric patients with endoscopically proven H. pylori infection.

Helicobacter pylori infection found during upper endoscopy performed for the diagnosis of celiac, inflammatory bowel diseases, and eosinophilic esophagitis: A multicenter pediatric European study.

BACKGROUND: Helicobacter pylori may be found during upper gastrointestinal endoscopy (UGE) performed to diagnose celiac disease (CeD), inflammatory bowel disease (IBD), and eosinophilic esophagitis (EoE). We aimed to describe the frequency of H. pylori in children undergoing UGE for CeD, IBD, and EoE and the number of children receiving eradication treatment. MATERIALS AND METHODS: A retrospective multicenter study from 14 countries included pediatric patients diagnosed with CeD, IBD, and EoE between January 2019 and December 2021. DATA COLLECTED: age, gender, hematologic parameters, endoscopic, histologic, and H. pylori culture results, and information on eradication treatment. RESULTS: H. pylori was identified in 349/3890 (9%) children [167 (48%) male, median 12 years (interquartile range 8.1-14.6)]. H. pylori was present in 10% (173/1733) CeD, 8.5% (110/1292) IBD and 7.6% (66/865) EoE patients (p = NS). The prevalence differed significantly between Europe (Eastern 5.2% (28/536), Southern 3.8% (78/2032), Western 5.6% (28/513)) and the Middle East 26.6% (215/809) [odds ratio (OR) 7.96 95% confidence interval (CI) (6.31-10.1) p < 0.0001]. Eradication treatment was prescribed in 131/349 (37.5%) patients, 34.6% CeD, 35.8% IBD, and 56.1% EoE. Predictors for recommending treatment included erosions/ulcers [OR 6.45 95% CI 3.62-11.47, p < 0.0001] and nodular gastritis [OR 2.25 95% CI 1.33-3.81, p 0.003]. Treatment rates were higher in centers with a low H. pylori prevalence (<20%) [OR 3.36 95% CI 1.47-7.66 p 0.004]. CONCLUSIONS: Identifying H. pylori incidentally during UGE performed for the most common gastrointestinal diseases varies significantly among regions but not among diseases. The indications for recommending treatment are not well defined, and less than 40% of children received treatment.

Transcultural adaptation to Spain of the CDPQOL questionnaire specific for coeliac children.

This study aimed to translate, cross-culturally adapt, and validate the CDPQOL questionnaire, a coeliac disease (CD)-specific paediatric health-related quality of life (HRQoL) instrument (CDPQOL), in Spanish children with CD. The CDPQOL questionnaire has two versions for children aged 8-12 and 13-18. Translation and linguistic validation were performed following an international consensus process. Internal consistency was calculated using Cronbach's alpha and McDonald's omega coefficients, and convergent validity was assessed with average variance extracted (AVE). Confirmatory factor analysis (CFA) and exploratory factor analysis (EFA), when necessary, were carried out to assess the construct validity. A total of 235 children were included. In the 8-12 age group, a change in the distribution of items to a new structure of three dimensions (negative emotions, food feelings and social interaction) was required. In this new model, CFA supported the fit of the model (χ2/gl = 1.79, RMSEA = 0.077 (IC 95% 0.05-0.100), CFI = 0.969, TLI 0.960, SRMR = 0.081) and Cronbach's alpha and McDonald's omega coefficients were > 0.7 in all three dimensions. In the 13-18 age group, CFA showed that all fit indexes were acceptable (χ2/gl = 1.702, RMSEA = 0.102 (IC 95% 0.077-0.127), p < 0.001, CFI = 0.956, TLI = 0.947, SRMR = 0.103) and Cronbach's alpha and McDonald's omega coefficients were > 0.7 in all three dimensions, except for uncertainty dimension. Conclusions: The Spanish version of the CDPQOL questionnaire is a useful instrument to assess quality of life in coeliac children whose native language was Spanish spoken in Spain, with changes in item distribution in the younger age group questionnaire. What is Known: • The first specific questionnaire for coeliac children, Dutch Coeliac Disease Questionnaire (CDDUX), which focuses on diet, was translated into Spanish and validated allowing to evaluate the HRQoL of Spanish coeliac children. • Spanish Children and parents feel the disease had no substantial negative impacts on patient HRQoL using this questionnaire, similar to that observed with other countries. What is New: • The age specific for CD children (CDPQOL) was elaborated in the USA and focuses on other aspects not evaluated by CDDUX such as emotional and social issues related to living with CD. • The CDPQOL was translated into Spanish and validated allowing it to be used to assess Spanish coeliac children's QoL.

Systematic Review and Meta-analysis of Histological Gastric Biopsy Aspects According to the Updated Sydney System in Children.

OBJECTIVES: A descriptive and comparative study of gastric histological aspects according to the updated Sydney classification (USC), obtained from Helicobacter pylori-positive versus H pylori-negative children referred for upper gastrointestinal endoscopy. METHODS: The Prisma method was used to perform a systematic review and meta-analysis. Selection criteria were based on following key words USC, H pylori, children, endoscopy, or biopsy. Publication biases were assessed according to the Newcastle-Ottawa Scale, and a meta-regression analysis was done. The study was registered on the PROSPERO platform. RESULTS: Between 1994 and 2017, 1238 references were found; 97 studies were retained for the systematic review with a total number of 25,867 children; 75 studies were selected for the meta-analysis concerning 5990 H pylori-infected and 17,782 uninfected children.H pylori-positive versus H pylori-negative children, according to the USC, showed significantly higher relative risk for gastric antral and corpus chronic inflammation, presence of neutrophils, and of lymphoid follicles, and gastric mucosa atrophy, whereas, intestinal metaplasia showed a significantly higher RR only in antral biopsies. The meta-regression analysis showed that H pylori-positive versus H pylori-negative children had significantly higher risk only for corpus activity according to age, recurrent abdominal pain, and geographical area of low H pylori prevalence. CONCLUSIONS: H pylori infection in children was associated with higher relative risk for gastric antral and corpus chronic inflammation, presence of neutrophils, lymphoid follicles, and rare gastric mucosa atrophy, whereas, rare intestinal metaplasia was only significantly higher in the antral area.

STAT6 Variants Associate With Relapse of Eosinophilic Esophagitis in Patients Receiving Long-term Proton Pump Inhibitor Therapy.

BACKGROUND & AIMS: Based on histologic features, variants in STAT6 are associated with a poor initial response to proton pump inhibitor (PPI) therapy in pediatric patients with eosinophilic esophagitis (EoE). We investigated whether these genetic variants are associated with a poor long-term response in children with EoE who initially responded to PPI therapy. METHODS: We performed a prospective longitudinal cohort study of children ages 2 to 16 years who met the diagnostic criteria for EoE (≥15 eosinophils/high-power field [eos/hpf]), responded to 8 weeks of treatment with 2 mg/kg/d PPI (<15 eos/hpf), and whose dose then was reduced to 1 mg/kg/d PPI (maintenance therapy) for 1 year, at which point biopsy specimens were collected by endoscopy. Genomic DNA was isolated from formalin-fixed paraffin-embedded biopsy tissue and was genotyped for variants of STAT6. Remission of inflammation was assessed at eos/hpf thresholds of <15 and ≤5. RESULTS: Among 73 patients who received 1 mg/kg/d PPI maintenance therapy for 1 year, 13 patients (18%) had 6 to 14 eos/hpf, 36 patients (49%) had 5 or fewer eos/hpf, and 24 patients (33%) relapsed to EoE (≥15 eos/hpf). Carriage of any of 3 STAT6 variants in linkage disequilibrium (r2 ≥0.8; rs324011, rs167769, or rs12368672) was associated with a 2.3- to 2.8-fold increase in the odds of EoE relapse, and with a 2.8- to 4.1-fold increase in the odds of having 6 to 14 eos/hpf. For rs324011, the odds ratio [95% CI] for relapse was 2.77 [1.11, 6.92]; P = .029, and the odds ratio [95% CI] for having 6 to 14 eos/hpf was 3.06 [1.27, 7.36]; P = .012. CONCLUSIONS: Pediatric EoE patients who initially respond to PPI therapy and carry STAT6 variants rs324011, rs167769, or rs12368672 are at increased risk of relapse after 1 year of PPI maintenance therapy.

Health-related quality of life using specific and generic questionnaires in Spanish coeliac children.

BACKGROUND: We aimed to compare the perception of health-related quality of life (HRQOL) and related factors in Spanish coeliac children and their parents, using two questionnaires, the generic KIDSCREEN-52 and the specific the Celiac Disease DUX (CDDUX), and to assess the correlation between them. METHODS: Coeliac children, aged 8-18, who are members of the Madrid Coeliac Association (MCA) and their parents, answered the Spanish version of the CDDUX and KIDSCREEN-52 questionnaires via e-mail. CDDUX was answered by 266 children and 428 parents and KIDSCREEN-52 by 255 children and 387 parents. Linear regression models were fitted to evaluate the association of demographic and clinical factors with HRQOL scores. CDDUX scores were compared with the subjective perception of health status assessed by the first question of KIDSCREEN-52. The correlation between the questionnaires was analysed. RESULTS: We found that the main factors that negatively affected HRQOL were having social or economic difficulties associated with following the diet and having transgression-related symptoms. The maximum correlation between the questionnaires was 0.309 and - 0.254 in parents and children respectively. CONCLUSIONS: Although there is a poor correlation between the two questionnaires, both agreed that the main concerns of the respondents were related to the social and economic difficulties of following the diet. It would be interesting to use both types of questionnaires in order to perform a more complete assessment of HRQOL in coeliac children. TRIAL REGISTRATION: Not applicable.

Influence of the 2012 European Guidelines in Diagnosis and Follow-up of Coeliac Children With Selective IgA Deficiency.

OBJECTIVES: The aim of the study was to describe diagnostic criteria used in children with coeliac disease (CD) and selective IgA deficiency; to determine if the publication of the 2012 ESPGHAN criteria prompted any changes; to evaluate the evolution of serological markers. METHODS: Multicenter, retrospective, descriptive study of a cohort of children under 15 years with selective IgA deficiency diagnosed with CD (January 2006 to December 2016). Demographic, clinical, genetic, histological and IgG-based antibodies were collected at diagnosis and follow-up. RESULTS: Eighty-six children were included, 60 diagnosed after the guide. Two groups were established: G1 (n = 63) and G2 (n = 23) with or without diagnostic biopsy respectively. In G1: 87.3% were symptomatic, 87.3% had human leukocyte antigan (HLA) DQ2/DQ8 typing (all positive), all had IgG serology positive (71.5% ATG, 35% EMA, 19% DPG, 9.5% AGA), and all had villous atrophy (Marsh-Oberhuber 2-3). Follow-up data were available in 58 children, 34 after 2 years on a gluten-free diet. Fifty-two percentage remained ATG IgG-positive despite good dietary adherence and symptom remission. Regarding G2: all were diagnosed post-2012, had typical symptoms, HLA DQ2/DQ8 positive and ATG IgG × 10 ULN. Additionally, EMA IgG was performed in 14 (60%), all positive. CONCLUSIONS: In our cohort of children with selective IgA deficiency and diagnosed with CD, children without a diagnostic biopsy suggests that IgG serology was considered the equivalent as IgA isotype, even when this is not addressed in the aforementioned guidelines. Great heterogeneity was observed in the IgG serology used at diagnosis. After 2 years of a gluten-free diet, half of children remained with a positive serology.

CYP2C19 and STAT6 Variants Influence the Outcome of Proton Pump Inhibitor Therapy in Pediatric Eosinophilic Esophagitis.

OBJECTIVE: Proton pump inhibitors (PPIs) are an effective treatment for eosinophilic esophagitis (EoE); however, only 30% to 60% of patients respond. Common genetic variants in CYP2C19 and STAT6 associate with PPI plasma concentration and magnitude of inflammatory response, respectively. Our objective was to determine if genetic variation in the genes for CYP2C19 and STAT6 influence differentiation between PPI responsive esophageal eosinophilia versus PPI nonresponsive EoE (PPI-REE, PPI-nonresponsive EoE). METHODS: Genomic DNA was isolated from 92 esophageal tissue biopsies collected from participants of a prospective clinical trial of high-dose PPI therapy for esophageal eosinophilia in children. RESULTS: Of the 92 patients examined, 57 (62%) were PPI-REE and 35 (38%) were PPI-nonresponsive EoE. Forty-six of the 92 patients were further characterized by pH probe monitoring; there was no association between reflux index and carriage of CYP2C1917 (P = 0.35). In children who received a PPI dose between ≥1.54 and ≤2.05 mg/kg/day, binary logistic regression modeling showed that carriage of CYP2C1917 associated with PPI-nonresponsive EoE (odds ratio (OR) [95% confidence interval (CI)] = 7.71 [1.21, 49.11], P = 0.031). Carriage of STAT6 allelic variant rs1059513 predicts PPI-REE (OR [95% CI] = 6.16 [1.44, 26.4], P = 0.028), whereas carriage of STAT6 rs324011 synergizes with CYP2C1917 to predict PPI-nonresponsive EoE (rs324011 OR [95% CI] = 5.56 [1.33, 20.72], P = 0.022; CYP2C1917 OR [95% CI] = 8.19[1.42, 50.57], P = 0.023). CONCLUSIONS: Common variants in CYP2C19 and STAT6 associate with a PPI-nonresponsive EoE outcome of PPI therapy for esophageal eosinophilia suggesting that response rates may be improved by adopting a genotype-guided approach to PPI dosing.

Health-related quality of life in Spanish coeliac children using the generic KIDSCREEN-52 questionnaire.

The aim of this study is to assess the impact of coeliac disease (CD) on health-related quality of life (HRQOL) using the generic KIDSCREEN-52 questionnaire in a group of Spanish children aged 8-18 years and their parents. For this cross-sectional study, coeliac children in the targeted age range, who are members of the Madrid Coeliac Association (MCA), were invited to participate. The Spanish version of the generic KIDSCREEN-52 questionnaire was administered via e-mail. Scores (on a scale from 1 to 100) were expressed as the mean and standard deviation (SD). Demographic and clinical variables related to HRQOL were also assessed. The questionnaire was completed by 434 children and/or their parents. Respondents gave scores of over 50 to seven quality of life domains. Mean scores were significantly higher in children than in their parents for six out of ten domains. In contrast, parents awarded significantly higher scores to the "social support and peers" domain than children did. Significantly lower QOL scores were reported by girls, children aged 16-18 years, children older than 7 years at the time of CD diagnosis, and respondents who did not adhere to the prescribed diet or had difficulty in doing so. CONCLUSION: Overall, the KIDSCREEN-52 questionnaire revealed that CD had no substantial negative impacts on the children's QOL. However, some concerns from the children's perspective were identified, such as issues regarding relationships with their peers. These issues will need to be addressed in order to improve QOL in children with CD. What is Known: • According to the Spanish version of the specific CDDUX, parents and children felt CD had no substantial negative impacts on their HRQOL. What is New: • According to the generic KIDSCREEN-52 questionnaire, QOL in Spanish coeliac children does not seem to be negatively affected by the disease in most general aspects of life. • Parents have a worse perception of their children's HRQOL than their children themselves.

Prevalence and Natural History of Celiac Disease in a Cohort of At-risk Children.

OBJECTIVES: To assess the prevalence and clinical presentation of celiac disease (CD) in a cohort of children with HLA-DQ2 positive and evaluate the risk factors in the development of CD. METHODS: Between July 2004 and July 2005, parents of all healthy full-term newborns in our hospital were invited to participate. HLA-DQ2 was tested in blood sample of the umbilical cord. A point of contact serological test was performed on children between 2 and 3 years of age. Positive results were confirmed by serum anti-transglutaminase 2 and endomysial antibodies. Children with high autoantibody titers underwent an intestinal biopsy. Children of the cohort diagnosed with CD before the screening study were included. Sex, mode of delivery, breast-feeding duration, and age of gluten introduction were studied. RESULTS: Of 1291 children, 362 were HLA-DQ2 positive and 262 participated in the study. CD was diagnosed in 4.1% (95% confidence interval (CI) 1.9-6.3). In the whole cohort, 60% had gastrointestinal symptoms, 7% poor weight gain, and 33% were asymptomatic. Five children with potential CD and 6 with CD autoimmunity became negative (42.3%) and are still negative after 5 to 7 years. Female sex was at-risk factor odds ratio 5.7 (95% CI 1.5-20.9), whereas breast-feeding during gluten introduction had a protective effect odds ratio 0.1 (95% CI 0.01-0.8). CONCLUSIONS: Prevalence of CD in this cohort was 4%, half of whom had digestive symptoms. Because a high proportion of children showed a spontaneous disappearance of antibodies, prevalence studies of CD in young children should be based on intestinal damage so as not to overestimate results.

Rational application of the ESPGHAN 2022 recommendations for the follow-up of the paediatric coeliac patient: consensus document of scientific societies (SEGHNP, AEPAP, SEPEAP, SEEC, AEG, SEPD, SEMFYC, SEMG and SEMERGEN).

Coeliac disease is a common condition for which the only current treatment is a gluten-free diet. Adherence to this diet is not always easy and is associated with a reduction in quality of life for the patient and their family. Non-adherence is associated with complications of varying severity. The lack of control at the outpatient care level in a high percentage of these patients evinces the need to improve follow-up protocols and the approach to care delivery with coordination of paediatric gastroenterology units (PGU) and primary care paediatricians. With this aim in mind, the present document was developed by consensus to offer a set of recommendations adapted to our region, based on the recent recommendations published by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), and with participation of the pertinent scientific societies, including those concerning the adult population, for the management and follow-up of adolescents and the transition to adult care.

Drug utilization and off-label drug use in Spanish pediatric gastroenterology outpatients.

BACKGROUND AND OBJECTIVES: The clinical use of medicines outside the conditions authorized in their Summary of Product Characteristics (SPC) (off-label use) is a common practice in pediatrics. The aim of the present study was to describe and quantify the medicines received by children attended in the pediatric gastroenterology department, their off-label use, and compliance with accepted rules for said use. METHODS: A retrospective observational study was performed on all of the patients who had their first consultation in pediatric gastroenterology between January 1 and October 31, 2010. All of the clinical information and medicines prescribed were analyzed. Off-label use was defined as the use of medicines in indications not included in the officially approved SPC or in ages not included or recommended in the SPC as well as the use of doses, intervals, or administration routes different from those considered in the SPC. RESULTS: A total of 695 patients (52.8% male) were included, 48.2% younger than 2 years. Two-hundred seven patients (29.8%) received 331 prescriptions. The most commonly used medicines were anti-H2 and proton pump inhibitors. Of all the prescriptions, 33.2% were considered off-label, and up to 47.3% of the prescribed patients had at least 1 medicine under off-label conditions. The medical records contained no documentation on information given to the parents regarding off-label use. CONCLUSIONS: The study found a high percentage of off-label use of medicines in the Pediatric Gastroenterology outpatient setting, especially in children younger than 2 years. Several initiatives were derived from the present study and implemented in our hospital.

Coeliac Disease Case-Control Study: Has the Time Come to Explore beyond Patients at Risk?

The worldwide prevalence of asymptomatic coeliac disease (CD) is increasing, which is in part due to the routine screening of children with risk factors. Both symptomatic and asymptomatic patients with CD are at risk of long-term complications. The objective of this study was to compare the clinical characteristics of asymptomatic and symptomatic children at the time of CD diagnosis. A case-control study was conducted using data from a cohort of 4838 CD patients recruited from 73 centers across Spain between 2011 and 2017. A total of 468 asymptomatic patients (cases) were selected and matched by age and sex with 468 symptomatic patients (controls). Clinical data, including any reported symptoms, as well as serologic, genetic, and histopathologic data were collected. No significant differences were found between the two groups in most clinical variables, nor in the degree of intestinal lesion. However, the asymptomatic patients were taller (height z-score -0.12 (1.06) vs. -0.45 (1.19), p < 0.001) and were less likely to have anti transglutaminase IgA antibodies ≥ 10 times the upper normal limit (66.2% vs. 758.4%, p = 0.002). Among the 37.1% of asymptomatic patients who were not screened for CD due to the absence of risk factors, only 34% were truly asymptomatic, while the remaining 66% reported non-specific CD-related symptoms. Therefore, expanding CD screening to any child who undergoes a blood test could reduce the burden of care for some children, as many of those considered asymptomatic reported non-specific CD-related symptoms.