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.

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.

Prospective longitudinal study: use of faecal gluten immunogenic peptides to monitor children diagnosed with coeliac disease during transition to a gluten-free diet.

BACKGROUND: Treatment for coeliac disease is a lifelong strict gluten-free diet. Although guidelines recommend regular follow-up with dietary interviews and coeliac serology, these methods may be inaccurate. AIM: To evaluate the usefulness of faecal gluten immunogenic peptides to support the diagnosis and to determine the adherence to the gluten-free diet in coeliac children. METHODS: Multicentre prospective observational study including 64 coeliac children. Faecal gluten peptides, and tissue transglutaminase and deamidated gliadin peptide antibodies were analyzed at diagnosis, and 6, 12 and 24 months thereafter. Gluten consumption was estimated from gluten peptide levels. RESULTS: Most children (97%) had detectable gluten peptides at diagnosis. On a gluten-free diet, the rate of gluten peptides increased from 13% at 6 months to 25% at 24 months. Mean estimated gluten exposure dropped from 5543 mg/d at diagnosis to 144 mg/d at 6 months, then increased to 606 mg/d by 24 months. In contrast, deamidated gliadin peptide antibodies normalised and only 20% had elevated tissue transglutaminase antibody by 24 months. The elevation of tissue transglutaminase antibody was more prolonged in patients with detectable gluten peptides (P < 0.05). Nevertheless, absolute levels of tissue transglutaminase antibody had low sensitivity to identify patients with detectable gluten peptides (P > 0.1). Dietitian assessment was only moderately correlated with gluten peptide detection (κ = 0.5). CONCLUSIONS: Faecal gluten peptides testing may guide treatment of coeliac disease prior to diagnosis and during the assessment diet adherence. Further studies could determine if early identification of gluten exposure reduces the need for expensive/invasive investigations for non-responsive coeliac disease. ClinicalTrials.gov Number: NCT02711397.

Long-term Treatment With Proton Pump Inhibitors Is Effective in Children With Eosinophilic Esophagitis.

OBJECTIVES: Proton pump inhibitor (PPI)-responsive eosinophilic esophagitis (EoE) is frequently observed in children, but data on long-term treatment are scarce. The objective of this study is to evaluate the long-term efficacy and safety of PPIs in children with EoE. METHODS: This prospective study enrolled children with EoE and histological remission to an 8-week esomeprazole trial (1 mg/kg/dose, twice daily). Esomeprazole was maintained at 1 mg/kg/day for 1 year. Symptom recurrence and adverse events were monitored and a follow-up endoscopy was performed at 12 months. Complete histological remission was defined as ≤5 eosinophils/high-power field (eos/hpf), and partial histological remission as >5 and <15 eos/hpf. Patients had no concomitant dietary restrictions or topical steroid. RESULTS: Fifty-seven children were included. Histological remission on maintenance PPI therapy was present in 40 children (70.1%; 95% CI 56.5-81.5). Long-term remission rate was higher in children with initial complete histological remission than in those with partial remission (81% vs 50%, P = 0.014). Forty-nine children (86%) remained asymptomatic. Pretreatment clinical and histological findings and median PPI dose/kg/day were similar between relapsers and nonrelapsers. Eleven out of 12 children (91.6%) receiving esomeprazole 0.5 mg ·â€Škg ·â€Š day for 12 additional months remained in remission. Mild and transient side effects without requiring PPI avoidance were observed in 5 children. CONCLUSIONS: Up to 70% of children with PPI-responsive EoE remain in histological and clinical remission on a low-dose maintenance treatment at 1-year follow-up, with adequate safety profile. Complete histological remission to an 8-week PPI trial was associated with higher probability of histological remission on maintenance therapy.

High Prevalence of Response to Proton-pump Inhibitor Treatment in Children With Esophageal Eosinophilia.

OBJECTIVES: Proton-pump inhibitor-responsive esophageal eosinophilia is a newly recognized entity with an unclear prevalence in children, as only retrospective data are available. The aim of this study was to determine the prevalence and clinical features of proton-pump inhibitor-responsive esophageal eosinophilia in children. METHODS: This prospective study enrolled patients with esophageal symptoms and esophageal eosinophilic counts as 15 or more than 15 eos/hpf (eosinophils per high-power field). Children received treatment with esomeprazole 1 mg ·â€Škg per dose twice daily for 8 weeks and the endoscopy was repeated. Complete response to proton-pump inhibitor (PPI) was defined as 5 or less than 5 eos/hpf, and a partial response as >5 and <15 eos/hpf in post-treatment biopsies. RESULTS: Fifty-one children (74.5% boys) were included. Histological response was observed in 35 children (68.6%): 24 children (47%) had a complete response and 11 children (21.6%) had a partial response. Only 16 children (31.4%) were diagnosed with eosinophilic esophagitis (EoE). There were no differences in history of atopy, allergy tests, pH study results, and endoscopic scores. Clinical symptoms were similar, with the exception of food impaction, which was more frequent in children with EoE (56.2% vs 20%, P = 0.01). The mean pretreatment peak eosinophil count was higher in patients with EoE (74.8 ±â€Š36.2 vs 46.3 ±â€Š30.7, P = 0.007). Eleven of the 14 patients (78.6%) on a lower PPI treatment maintenance dose remained in clinicopathologic remission at 1-year follow-up. CONCLUSIONS: A significant proportion of children with esophageal eosinophilia responded to high dose PPI treatment. Clinical, endoscopic, and pH study results were similar, with exception of patients with EoE, who were more likely to experience food impaction and have higher esophageal eosinophil counts.

Normal values of spleen stiffness in healthy children assessed by acoustic radiation force impulse imaging (ARFI): comparison between two ultrasound transducers.

BACKGROUND: Portal hypertension, a major complication of hepatic fibrosis, can affect the stiffness of the spleen. OBJECTIVE: To suggest normal values of spleen stiffness determined by acoustic radiation force impulse imaging in healthy children and to compare measurements using two different US probes. MATERIALS AND METHODS: In a prospective study, 60 healthy children between 1 day and 14 years of age were assigned to four age groups with 15 children in each. Measurements were performed using two transducers (convex 4C1 and linear 9L4), and 10 measurements were obtained in each child, 5 with each probe. RESULTS: The mean splenic shear wave velocities were 2.17 m/s (SD 0.35, 95% CI 2.08-2.26) with the 4C1 probe and 2.15 m/s (SD 0.23, 95% CI 2.09-2.21) with the 9L4 probe (not significant). CONCLUSION: We found normal values for spleen stiffness with no difference in the mean values obtained using two types of US transducers, but with higher variability using a convex compared to a linear transducer.

Normal values of liver shear wave velocity in healthy children assessed by acoustic radiation force impulse imaging using a convex probe and a linear probe.

Acoustic radiation force impulse (ARFI) is an image-guided ultrasound elastography method that allows quantification of liver stiffness by measurement of shear wave velocity. One purpose of the work described in this article was to determine the normal liver stiffness values of healthy children using ARFI with two different probes, 4 C1 and 9 L4. Another purpose was to evaluate the effects of site of measurement, age, gender and body mass index on liver stiffness values. This prospective study included 60 healthy children (newborn to 14 y) divided into four age groups. One thousand two hundred ARFI measurements were performed, that is, 20 measurements per patient (5 measurements in each lobe, with each probe). Means, standard deviations (SD) and confidence intervals for velocity were calculated for each hepatic lobe and each probe in each age group and for the whole group. Mean shear wave velocity measured in the right lobe was 1.19 ± 0.04 m/s (SD = 0.13) with the 4 C1 transducer and 1.15 ± 0.04 m/s (SD = 0.15) with the 9 L4 transducer. Age had a small effect on shear wave measurements. Body mass index and sex had no significant effects on ARFI values, whereas site of measurement had a significant effect, with lower ARFI values in the right hepatic lobe. ARFI is a non-invasive technique that is feasible to perform in children with both the 4 C1 and 9 L4 probes. The aforementioned velocity values obtained in the right lobe may be used as reference values for normal liver stiffness in children.

Acute viral gastroenteritis: proportion and clinical relevance of multiple infections in Spanish children.

Dual infections associated with acute infectious diarrhoea and its microbiological, epidemiological and clinical findings have been evaluated in patients selected from a comprehensive survey of children under 4 years old, admitted to hospital emergency rooms from October 1996 to November 1997. A total of 820 children (433 males and 387 females) were enrolled. Stools were tested for rotavirus, adenovirus, astrovirus and bacterial enteropathogens. Patients were grouped according to age, and the seasonality of mixed infections was evaluated. Clinical trends and severity of gastrointestinal disease by Ruuska's score were also analysed. Mixed infections were identified in 39 cases (5 %), of which 23 were males and 16 were females. The majority of cases were in the 7-18-month age group (26 cases) and occurred in autumn (67 %). Virus-virus co-infections were more frequent (26/39) than virus-bacteria co-infections (13/39). More than two infectious agents were detected in only four cases. The most common viral co-infections were rotavirus-astrovirus (13/26) and rotavirus-adenovirus (10/26). The present report is the first prospective analysis of clinical-epidemiological trends of dual infections in young Spanish children with acute viral gastroenteritis. Our results emphasize the clinical importance of mixed infections as a cause of severe diarrhoea in children.