Vernal keratoconjunctivitis and eosinophilic esophagitis: A rare combination?

Vernal keratoconjunctivitis (VKC) is a bilateral ocular inflammatory disease with a conjunctival and corneal involvement and typical onset during childhood. Eosinophilic esophagitis (EoE) is a chronic disease characterized by eosinophilic inflammation of the mucosa (≥15 eosinophils/HPF) and symptoms of esophageal dysfunction. EoE and VKC are both immune-mediated diseases sharing a similar pathogenetic mechanism and a high association with other allergic diseases. Nevertheless, no data are currently available about their clinical association. We present 4 cases of concomitant diagnosis of vernal keratoconjunctivitis and eosinophil esophagitis suggesting that these conditions may coexist in the same patient more frequently than expected. Health care providers should be aware of the possibility of co-occurrence in their daily practice.

Foreign body ingestion in children: Definition of a nomogram to predict surgical or endoscopic intervention.

BACKGROUND AND AIMS: Foreign body ingestion (FBI) in children requires early identification to prevent adverse outcomes and may necessitate endoscopic or surgical intervention. This study aims to develop a nomogram that identifies children who require urgent surgical or endoscopic intervention by using the patient's medical history and clinical parameters collected at admission. METHODS: This study is a retrospective review (01/2015-12/2020) of a multicenter case series of children admitted for FBI. Data from 5864 records from 24 hospitals in Italy were analyzed. Logistic regression models were used to establish the probability of requiring surgical or endoscopic intervention based on patient history and clinical characteristics. The nomogram representing the results from the multivariable model was reported to examine the propensity for surgery/endoscopy. RESULTS: The study identified a significant association between intervention and various factors, including type of foreign body (blunt: reference category, disk battery (odds ratio OR:4.89), food bolus (OR:1.88), magnets (OR:2.61), sharp-pointed (OR:1.65), unknown (OR:1.02)), pre-existing diseases or conditions (OR 3.42), drooling (OR 10.91), dysphagia (OR 5.58), vomiting (OR 3.30), retrosternal pain (OR 5.59), abdominal pain (OR 1.58), hematemesis (OR 2.82), food refusal/poor feeding (OR 2.99), and unexplained crying (OR 2.01). The multivariable regression model showed good calibration and discrimination ability, with an area under the ROC curve of 0.77. CONCLUSIONS: This study developed the first nomogram to predict the probability of the need for surgical or endoscopic intervention in children with FBI, based on the information collected at admission. The nomogram will aid clinicians in identifying children who require early intervention to prevent adverse outcomes.

Oral Viscous Budesonide in Children With Eosinophilic Esophagitis After Repaired Esophageal Atresia: A Clinical Trial.

OBJECTIVES: A high prevalence of eosinophilic esophagitis (EoE) has been reported in children with repaired esophageal atresia (EA). Topical steroids proved to be an effective and safe therapy in EoE, although not approved in pediatrics. We report the results of the first clinical trial of oral viscous budesonide (OVB) performed in children with EoE after repaired esophageal atresia (EoE-EA). METHODS: This open-label, single-arm, phase 2 clinical trial with randomized pharmacokinetic sampling, was conducted at the Bambino Gesù Children's Hospital between September 2019 and June 2021. EoE-EA patients received an age-banded dose of OVB twice daily for 12 weeks and were endoscopically evaluated. The primary endpoint was the rate of patients achieving histological remission. Secondary endpoints included clinical and endoscopic benefit after treatment, and safety assessments. RESULTS: Eight consecutive EA-EoE patients were enrolled (median age 9.1 years, interquartile range 5.5). Of these, 5 received 0.8 mg and 3 received 1.0 mg twice daily of OVB. Histological remission was obtained in all but 1 patient (87.5%). The clinical score showed significant improvement at the end of treatment in all patients. No endoscopic features of EoE were found after treatment. No treatment-emergent adverse event occurred. CONCLUSION: OVB is an effective, safe, and well-tolerated formulation of budesonide for use in pediatric patients with EoE-EA.

Characterization of Eosinophilic Esophagitis From the European Pediatric Eosinophilic Esophagitis Registry (pEEr) of ESPGHAN.

OBJECTIVES: Few pediatric data on phenotypic aspects of eosinophilic esophagitis (EoE) are available. The pEEr registry was developed to prospectively characterize children with EoE from Europe and Israel. METHODS: pEEr is an ongoing prospective registry enrolling children with esophageal eosinophilia (≥15 eos/HPF). Anonymized data were collected from 19 pediatric centers. Data regarding demographics, clinical manifestations, endoscopy, histology, and therapies were collected. RESULTS: A total of 582 subjects (61% male) were analyzed. The median age at diagnosis was 10.5 years [interquartile range (IQR): 5.7-17.7], whereas the age at symptom onset was 9.2 years (IQR: 4.3-16.4), resulting in a median diagnostic delay of 1.2 years (IQR: 0.7-2.3). The diagnostic delay was longer below age <6 years. Shorter diagnostic delays were associated with the presence of food allergy or a family history for EoE. Symptoms varied by age with dysphagia and food impaction more common in adolescents, while vomiting and failure to thrive more common in younger children ( P < 0.001). Among endoscopic findings, esophageal rings were more common in adolescents, whereas exudates were more frequent in younger children( P < 0.001). Patients who responded to proton pump inhibitors (PPIs) were more likely to be older, males, and less often presented severe endoscopic findings. Patients unresponsive to PPIs received topical steroids (40%), elimination diet (41%), or a combined therapy (19%). CONCLUSIONS: EoE findings vary according to age in pediatric EoE. Young children are commonly characterized by non-specific symptoms, atopic dermatitis, food allergy, and inflammatory endoscopic lesions. Adolescents usually have dysphagia or food impaction, fibrostenotic lesions, and a better PPI response.

Hematemesis in Infants: The First Evidence-Based Score to Predict the Need for Timely Endoscopy.

OBJECTIVES: Infantile acute upper gastrointestinal bleeding involves a decision for therapeutic intervention that most pediatricians first coming into contact with the patient are, not unreasonably, unable to objectively provide. Therefore, some objective tools of individual risk assessment would seem to be crucial. The principal aim of the present study was to investigate the anamnestic and clinical parameters of infants with hematemesis, together with laboratory and instrumental findings, to create a scoring system that may help identify those infants requiring an appropriate and timely application of upper gastrointestinal (GI) endoscopy. METHODS: Clinical data of infants admitted for hematemesis to the participating centers over the study period were systematically collected. According to the outcome dealing with rebleeding, need for blood transfusion, mortality, finding of GI bleeding lesions, or need for surgical intervention, patients were blindly divided into a group with major clinical severity and a group with minor clinical severity. Univariate and multivariate logistic regressions were conducted to investigate significant prognostic factors for clinical severity. RESULTS: According to our findings, we drafted a practical diagnostic algorithm and a clinical score able to predict the need for timely upper GI endoscopy (BLOVO infant score). Our clinical scoring system was created by incorporating anamnestic factors, clinical parameters, and laboratory findings that emerged as predictors of a worst outcome. CONCLUSIONS: We provided the first objective tool of individual risk assessment for infants with hematemesis, which could be very useful for pediatricians first coming into contact with the patient in the emergency department.

Point-of-Care Ultrasound Training Programs Across Italian Pediatric Residency Schools: A National Survey.

INTRODUCTION: The role of point-of-care ultrasound (POCUS) in routine clinical practice is rapidly growing, whereas adult specialties have already included training programs regarding this topic; pediatric residency schools are still late on this topic, particularly in Italy. METHODS: We performed an online anonymous survey to Italian residents. The online survey has been submitted to the resident representatives of each pediatric residency school in Italy by the Italian Observatory of Pediatric Residents; each representative in turn distributed it to the pediatric residents of his own school. RESULTS: Three sixty-one residents responded to the survey. Only 7.8% of residents declared that in their residency school, an official training program on POCUS exists, although more than 95% of respondents declared that such a training would be of primary importance for their future practice. Most residents do not know how to use an ultrasound machine nor the differences between different probes. CONCLUSIONS: Our results demonstrate that POCUS training is still missing in Italy. Given the growing number of evidences of the benefits from including POCUS in clinical practice and patient evaluation, efforts are needed to fill this gap, in Italy and, probably, in most European countries. Such a training will definitely help the new generation of pediatricians improve their curriculum and, therefore, child health.

Evaluation of Gastroesophageal Reflux Disease 1 Year after Esophageal Atresia Repair: Paradigms Lost from a Single Snapshot?

OBJECTIVE: To analyze the findings of both multichannel intraluminal impedance with pH (MII-pH) and endoscopy/histopathology in children with esophageal atresia at age 1 year, according to current recommendations for the evaluation of gastroesophageal reflux disease (GERD) in esophageal atresia. STUDY DESIGN: We retrospectively reviewed both MII-pH and endoscopy/histopathology performed in 1-year-old children with esophageal atresia who were followed up in accordance with international recommendations. Demographic data and clinical characteristics were also reviewed to investigate factors associated with abnormal GERD investigations. RESULTS: In our study cohort of 48 children with esophageal atresia, microscopic esophagitis was found in 33 (69%) and pathological esophageal acid exposure on MII-pH was detected in 12 (25%). Among baseline variables, only the presence of long-gap esophageal atresia was associated with abnormal MII-pH. Distal baseline impedance was significantly lower in patients with microscopic esophagitis, and it showed a very good diagnostic performance in predicting histological changes. CONCLUSIONS: Histological esophagitis is highly prevalent at 1 year after esophageal atresia repair, but our results do not support a definitive causative role of acid-induced GERD. Instead, they support the hypothesis that chronic stasis in the dysmotile esophagus might lead to histological changes. MII-pH may be a helpful tool in selecting patients who need closer endoscopic surveillance and/or benefit from acid suppression.

The not-so-rare absent RAIR: Internal anal sphincter achalasia in a review of 1072 children with constipation undergoing high-resolution anorectal manometry.

BACKGROUND: Our objective is to describe the prevalence of patients with internal anal sphincter achalasia (IASA) without Hirschsprung disease (HD) among children undergoing anorectal manometry (ARM) and their clinical characteristics. METHODS: We performed a retrospective review of high-resolution ARM studies performed at our institution and identified patients with an absent rectoanal inhibitory reflex (RAIR). Clinical presentation, medical history, treatment outcomes, and results of ARM and other diagnostic tests were collected. We compared data between IASA patients, HD patients, and a matched control group of patients with functional constipation (FC). KEY RESULTS: We reviewed 1,072 ARMs and identified 109 patients with an absent RAIR, of whom 28 were diagnosed with IASA. Compared to patients with FC, patients with IASA had an earlier onset of symptoms and were more likely to have abnormal contrast enema studies. Compared to patients with HD, patients with IASA were more likely to have had a normal timing of meconium passage, a later onset of symptoms, and were diagnosed at an older age. At the latest follow-up, the majority of patients diagnosed with IASA (54%) were only using oral laxatives. Over half of patients with IASA had been treated with anal sphincter botulinum toxin injection, and 55% reported a positive response. CONCLUSIONS AND INFERENCES: Patients diagnosed with IASA may represent a more severe patient population compared to patients with FC, but have a later onset of symptoms compared to patients with HD. They may require different treatments for their constipation and deserve further study.

Point of view of the Italians pediatric scientific societies about the pediatric care during the COVID-19 lockdown: what has changed and future prospects for restarting.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is currently rare in children and they seem to have a milder disease course and better prognosis than adults. However, SARS-Cov-2 pandemic has indirectly caused problems in pediatric medical assistance. In view of this we wanted to draw a picture of what happened during health emergency and analyze future prospects for restarting. METHODS: We involved the Italian pediatric scientific societies institutionally collected in the Italian Federation of Associations and Scientific Societies of the Pediatric Area (FIARPED); We sent a questionnaire to all scientific societies about the pediatric care activity during the COVID-19 emergency and future perspectives for the phase of post-containment. RESULTS: The analysis of the questionnaires showed significant decrease of:admission, outpatient visits and specialist consultancy activities during the COVID-19 emergency, primarily linked to the fear of infection. Instead it was increased the serious degree of diseases admitted. Most of scientific societies maintained the relationship with chronic patients through some form of telemedicine, reporting a strong positive opinion about this modality. Finally showed the need to give life a new approach for hospitalizations and outpatient visits through a greater use of telemedicine, educational programs on families and a more decisive role of family pediatricians. CONCLUSIONS: Our study highlighted many aspects that can be improved in pediatric care. We think that It will be necessary a new shared strategy to improve the management and continuity of care for pediatric patients, primarily developing a network of collaboration between families, family pediatrician and hospitals and by enhancing the use of new methods of telecommunications.

In Celiac Disease Patients the In Vivo Challenge with the Diploid Triticum monococcum Elicits a Reduced Immune Response Compared to Hexaploid Wheat.

SCOPE: Gluten from the diploid wheat Triticum monococcum (TM) has low content of immunostimulatory sequences and a high gastro-intestinal digestibility. Gluten-reactive T cells elicited by diploid and hexaploid (Triticum aestivum-TA) wheat in celiac disease (CD) patients upon a brief oral challenge are analyzed. METHODS AND RESULTS: Seventeen patients with CD (median age 13 years) consumed for 3 days sandwiches made with TM (cultivar Norberto-ID331, N=11), or TA (cultivar Sagittario, N=11) flours, corresponding to 12 gr of gluten/die. Immunostimulatory properties are assessed in blood by measuring the IFN-γ-secreting T cells by EliSpot and the expression of inflammatory cytokines/receptors (IL-12A, IL-15, IL-18RAP, IFN-γ) by qPCR. TA mobilizes a remarkable number of gliadin-specific, IFN-γ-secreting T cells (p<0.05), while no significant cell mobilization is induced by TM (p=ns). Similar results are obtained in response to five immunogenic peptides from α-, ω-, and γ-gliadins, although with a large individual variability. An increased mRNA expression for IL-12A and IFN-γ is detected in the group eating TA compared to those consuming TM (p<0.05). CONCLUSIONS: Although T. monococcum is a cereal not suitable for the diet of celiacs, this diploid wheat elicits a reduced in vivo T-cell response compared to T. aestivum in celiac patients.

Eosinophilic esophagitis in esophageal atresia: Tertiary care experience of a "selective" approach for biopsy sampling.

BACKGROUND: A high prevalence (9.5-30%) of eosinophilic esophagitis (EoE) in patients with esophageal atresia (EA) has been reported. The application of the EoE criteria to EA patients might be problematic. To date, only studies using a "routine" biopsy approach, even in asymptomatic patients, have been performed. The aim of the study was to establish the prevalence of EoE among symptomatic EA patients (EA/EoE group) without anastomotic stricture (AS) and to compare their characteristics with those of EoE patients from general population (EoE group). METHODS: From 2005 to 2018, we reviewed charts of children with EA and EoE. "Selective" biopsy approach only in EA children without AS and/or endoscopic feature of EoE was performed. Characteristics of EA/EoE and EoE groups were compared. RESULTS: Among 370 EA and 118 EoE, 15 EA/EoE patients were detected (4.0% of EA patients). Male predominance and a high prevalence of allergy without differences between EA/EoE and EoE groups was observed. EA/EoE children were significantly younger (p < 0.0001). PPI-responder patients were significantly more prevalent in EA/EoE group (p = 0.045). CONCLUSION: Our data confirm that EA patients are at high risk for developing EoE. High incidence, early onset, and high prevalence of PPI-responders might suggest that esophageal motility disorders interact to increase propensity to EoE in EA patients. However, our study also suggests that overdiagnosis of EoE may occur in EA and that adapted criteria for EoE diagnosis should be developed for EA patients. TRIAL REGISTRATION: Not applicable for this retrospective study.

Diagnostic Approach to Monogenic Inflammatory Bowel Disease in Clinical Practice: A Ten-Year Multicentric Experience.

BACKGROUND AND AIMS: Multiple monogenic disorders present as very early onset inflammatory bowel disease (VEO-IBD) or as IBD with severe and atypical features. Establishing a genetic diagnosis may change patients' management and prognosis. In this study, we describe the diagnostic approach to suspected monogenic IBD in a real clinical setting, discussing genetic and phenotypic findings and therapeutic implications of molecular diagnosis. METHODS: Information of patients with VEO-IBD and early onset IBD with severe/atypical phenotypes (EO-IBD s/a) managed between 2008-2017 who underwent a genetic workup were collected. RESULTS: Ninety-three patients were included, and 12 (13%) reached a genetic diagnosis. Candidate sequencing (CS) was performed in 47 patients (50%), and next generation sequencing (NGS) was performed in 84 patients (90%). Candidate sequencing had a good diagnostic performance only when guided by clinical features specific for known monogenic diseases, whereas NGS helped finding new causative genetic variants and would have anticipated one monogenic diagnosis (XIAP) and consequent bone marrow transplant (BMT). Patients with monogenic IBD more frequently were male (92% vs 54%; P = 0.02), had extraintestinal findings (100% vs 34%; P < 0.001), and had disease onset ≤1 month of life (25% vs 1%; P = 0.006). Genetic diagnosis impacted patient management in 11 patients (92%), 7 of whom underwent BMT. CONCLUSION: A genetic diagnosis can be established in a significant proportion of suspected monogenic IBD and has an impact on patients' management. Candidate sequencing may be deployed when clinical findings orientate toward a specific diagnosis. Next generation sequencing should be preferred in patients with nonspecific phenotypes.

Association between body positioning and gastroesophageal reflux in paediatric age.

AIM: Postural measures are frequently recommended for gastroesophageal reflux (GER) symptoms, despite limited evidence. This was the first study to assess the impact of upright and recumbent body positions on GER episodes in children and adolescents, not just infants. METHODS: We retrospectively assessed the pH-impedance parameters of paediatric patients referred for possible GER-related symptoms to two hospitals in Naples and Rome, Italy, from September 2016 to September 2018. Data were separately obtained for the time that the patients spent in upright and recumbent positions. RESULTS: Data from 187 patients under the age of 18 were collected, at a mean age of just over seven years. We found that the acid exposure time was stable irrespective of changes in body position (P > .05). The mean number of reflux episodes per hour was 2.99 during the upright position and 1.21 during the recumbent position (P < .05), and the mean oesophageal acid clearance time was 44.4 and 93.4 seconds, respectively (P < .05). CONCLUSION: Most paediatric patients experienced reflux in the upright rather than recumbent position, probably as a result of frequent transient lower oesophageal sphincter relaxations while they were awake. In particular, our findings provide new insights into postural measures for reflux in children and adolescents.

Pediatric Eosinophilic Esophagitis: Results of the European Retrospective Pediatric Eosinophilic Esophagitis Registry (RetroPEER).

OBJECTIVES: Recommendations for diagnosing and treating eosinophilic esophagitis (EoE) are evolving; however, information on real world clinical practice is lacking. To assess the practices of pediatric gastroenterologists diagnosing and treating EoE and to identify the triggering allergens in European children. METHODS: Retrospective anonymized data were collected from 26 European pediatric gastroenterology centers in 13 countries. Inclusion criteria were: Patients diagnosis with EoE, completed investigations prescribed by the treating physician, and were on stable medical or dietary interventions. RESULTS: In total, 410 patients diagnosed between December 1999 and June 2016 were analyzed, 76.3% boys. The time from symptoms to diagnosis was 12 ±â€Š33.5 months and age at diagnosis was 8.9 ±â€Š4.75 years. The most frequent indications for endoscopy were: dysphagia (38%), gastroesophageal reflux (31.2%), bolus impaction (24.4%), and failure to thrive (10.5%). Approximately 70.3% had failed proton pump inhibitor treatment. The foods found to be causative of EoE by elimination and rechallenge were milk (42%), egg (21.5%), wheat/gluten (10.9%), and peanut (9.9%). Elimination diets were used exclusively in 154 of 410 (37.5%), topical steroids without elimination diets in 52 of 410 (12.6%), both diet and steroids in 183 of 410 (44.6%), systemic steroids in 22 of 410 (5.3%), and esophageal dilation in 7 of 410 (1.7%). Patient refusal, shortage of endoscopy time, and reluctance to perform multiple endoscopies per patient were noted as factors justifying deviation from guidelines. CONCLUSIONS: In this "real world" pediatric European cohort, milk and egg were the most common allergens triggering EoE. Although high-dose proton pump inhibitor trials have increased, attempted PPI treatment is not universal.

Acceptability and efficacy of a gel hypotonic oral rehydration solution in children with acute gastroenteritis.

OBJECTIVE: Oral rehydration solution remains the mainstay of acute gastroenteritis therapy. The aim of this study was to investigate the acceptability of a new zinc-containing hypotonic super-oral rehydration solution (ORS) in a gel formulation and its efficacy in reducing the duration and severity of diarrhea in children. METHODS: This was a randomized-controlled trial of children (5-36 months of age) observed for diarrhea lasting less than 24 h. Children were randomized to receive standard hypotonic ORS (group 1) or a gel hypotonic super-ORS containing zinc (group 2). The main study outcome was ORS intake in the first 24 h. ORS intake at 4 h, rate of diarrhea resolution at 72 h of treatment, total duration and severity of diarrhea, hospitalization, and adverse effects were also evaluated. RESULTS: Eighty-three children were enrolled (group 1: 40; group 2: 43). The amount of ORS consumed at 24 h was significantly higher in group 2 than in group 1. A similar result was observed at 4 h. The number of children who refused ORS (<10 ml/kg/day) was lower in group 2 versus group 1 (P=0.001). The number of children presenting diarrhea after 72 h of treatment was lower in group 2 versus group 1 (P=0.028). Also, the mean duration of diarrhea was shorter in group 2 than in group 1 (P=0.001). The hypotonic super-ORS containing zinc in a gel formulation had a positive effect on the severity of diarrhea. No patient required hospitalization. No adverse events were observed in either of the two study groups. CONCLUSION: The new zinc-containing hypotonic super-ORS in a gel formulation is effective in the management of childhood acute gastroenteritis.

Possible impact of comorbid conditions on the persistence of nocturnal enuresis: results of a long-term follow-up study.

PURPOSE: To describe the natural history of patients with nocturnal enuresis (NE) during a 10-year period and to evaluate possible impact of comorbid conditions on the persistence of NE. MATERIALS AND METHODS: Ninety-five children (male to female ratio [M:F] 65:30), aged at first visit between 6 and 21 years were included in this study. Of study subjects 75 had primary monosymptomatic nocturnal enuresis (PMNE), 3 had secondary monosymptomatic nocturnal enuresis (SMNE) and 17 had non-mono­symptomatic nocturnal enuresis (NMNE). Demographic and NE-related details were assessed from electron­ic medical records and by telephone interview at the times 3, 6, 12 months and 3, 5, 10 years after the first examination. Sixty-seven of 95 patients were enrolled, of whom 57 had PMNE (M:F ratio 39:18, mean age 9.35 ± 2.81 years, mean age at improvement 11.5 ± 4.08 years), 8 had NMNE (M:F ratio 4:4, mean age 10.1 ± 2.64 years, mean age at improvement 12.6 ± 1.68 years) and 2 had SMNE (M:F ratio 1:1, mean age 12 years, mean age at improvement 13.5 ± 2.12 years). RESULTS: The mean duration of follow up was 7.2 ± 2.5 years. All of the 67 children had 5 years follow up. Only 29 of 67 patients (19 with PMNE, 8 with NMNE and 2 with SMNE) had 10 years follow up and 4 of 19 with PMNE were still affected by NE. Out of 57 patients with PMNE 12 (2/12 with language disorders, 1/12 varicocele and 1/12 cryptorchidism) and out of 8 patients with NMNE 1 were still enuretic while all patients with SMNE were in remission. CONCLUSION: We observed that language disorders and testicular pathology in NE children could be comor­bidities associated with persistence of NE and treatment resistance.

A focus on recent cases of suicides among Italian children and adolescents and a review of literature.

Suicidal behaviors are among the leading causes of death worldwide. The large spread of suicide suggests that educational programs and literature to parents or guardians should include information about the potential risks and potential consequences of the onset of the idea of suicide in children. We identified 55 cases of suicide among children and young adults <18-year-old occurring in Italy between 1st January, 2011 and 31st December, 2013. The results point to the need to increase our understanding of the dramatic rise in suicidal behaviors during childhood/adolescence and of the causal pathways linking these behaviors to child-adolescent mental disorders. During routine care visits, pediatricians should be skilled to recognize risk factors for adolescent suicide in order to intervene appropriately.