Megacystis-microcolon-intestinal hypoperistalsis syndrome: don't forget the bladder.

PURPOSE: Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a well described clinical condition, but reports are focused on microcolon and intestinal hypoperistalsis, while data on bladder management are scant. Aim of the study is to present urological concerns in MMIHS. METHODS: Retrospective evaluation of clinical data on urological management of MMIHS patients treated in the last 10 years. RESULTS: Six patients were enrolled (3 male, 3 female). Three girls had prenatal diagnosis of megacystis (1 vesicoamniotic shunt was placed). All patients had genetic diagnosis: 5 had ACTG2 gene mutations and 1 MYH11 mutation. All patients were addressed to our attention for urinary symptoms, such as urinary retention, urinary tract infections, acute renal injury. Two patients presented frequent stoma prolapses. All children underwent a complete urological evaluation, and then started a bladder management protocol (clean intermittent catheterization, via urethra or cystostomy-tube placement), with improvement of urinary infections, upper urinary tract dilation and stoma prolapses, if present. All patients had good renal function at last follow-up. CONCLUSION: We believe that MMIHS patients must be addressed soon and before onset of symptoms for a multidisciplinary evaluation, including an early assessment by a pediatric urologist expert in functional disorder, to preserve renal function at its best.

Italian guidelines for the management of irritable bowel syndrome in children and adolescents : Joint Consensus from the Italian Societies of: Gastroenterology, Hepatology and Pediatric Nutrition (SIGENP), Pediatrics (SIP), Gastroenterology and Endoscopy (SIGE) and Neurogastroenterology and Motility (SINGEM).

The irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID), whose prevalence has widely increased in pediatric population during the past two decades. The exact pathophysiological mechanism underlying IBS is still uncertain, thus resulting in challenging diagnosis and management. Experts from 4 Italian Societies participated in a Delphi consensus, searching medical literature and voting process on 22 statements on both diagnosis and management of IBS in children. Recommendations and levels of evidence were evaluated according to the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus was reached for all statements. These guidelines suggest a positive diagnostic strategy within a symptom-based approach, comprehensive of psychological comorbidities assessment, alarm signs and symptoms' exclusion, testing for celiac disease and, under specific circumstances, fecal calprotectin and C-reactive protein. Consensus also suggests to rule out constipation in case of therapeutic failure. Conversely, routine stool testing for enteric pathogens, testing for food allergy/intolerance or small intestinal bacterial overgrowth are not recommended. Colonoscopy is recommended only in patients with alarm features. Regarding treatment, the consensus strongly suggests a dietary approach, psychologically directed therapies and, in specific conditions, gut-brain neuromodulators, under specialist supervision. Conditional recommendation was provided for both probiotics and specific fibers supplementation. Polyethylene glycol achieved consensus recommendation for specific subtypes of IBS. Secretagogues and 5-HT4 agonists are not recommended in children with IBS-C. Certain complementary alternative therapies, antispasmodics and, in specific IBS subtypes, loperamide and rifaximin could be considered.

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.

Diagnostic and therapeutic approach to children with chronic refractory constipation: Consensus report by the SIGENP motility working group.

Constipation is a common problem in children, accounting for about 3% of all primary care visits and up to 25% of referrals to paediatric gastroenterologists. Although polyethylene glycol often proves effective, most children require prolonged treatment and about 50% of them have at least one relapse within the first 5 years after initial recovery. When conventional treatment fails, children are considered to have refractory constipation. Children with refractory constipation deserve specialist management and guidance. Over the last decades, there has been a remarkable increase in our knowledge of normal and abnormal colonic and anorectal motility in children, and a number of different techniques to measure transit and motility have been developed. The present review analyses the possible diagnostic investigations for children with refractory constipation, focusing on their actual indications and their utility in clinical practice. Moreover, we have also analytically reviewed medical and surgical therapeutic options, which should be considered in selected patients in order to achieve the best clinical outcome.

Isoperistaltic gastric tube for long gap esophageal atresia (LGEA) in newborn, infants, and toddlers: a case-control study from a tertiary center.

Background: Limited evidence exists about outcomes after gastric tube formation as "rescue" technique to avoid esophageal replacement in long gap esophageal atresia (LGEA). The last ERNICA Consensus Conference on the Management of LGEA has placed the techniques of gastric tubulization among the priorities for future research. Aims: Evaluate personal experience with Isoperistaltic Gastric Tube (IGT) and compare its outcomes with other more popular techniques for LGEA. Methods: A case-control study has been conducted. A retrospective monocentric analysis of LGEA patients (period: 2010-19) has been conducted in all consecutive IGT patients and each of these has been type matched with two cases of LGEA treated with other techniques. The follow-up (FU) considered was 24-months. Results: IGT and controls showed no statistically significant differences regarding preoperative variables like sex, gestational age, birth weight, syndromes, and EA type. However, IGT patients had a significantly longer esophageal GAP under boost pressure (4.5 vertebral bodies vs. 3.6, p = 0.019) at time of surgery. The analysis showed no statistical difference among the two groups about perioperative outcomes, ICU, or overall postoperative stay. No differences have been shown between IGT and controls during the follow-up regarding GERD, esophagitis, fundoplication, dysphagia, vocal cord paralysis, stenosis, and dilatations, auxologic data, need for anastomosis revision, oral aversion, and death. Conclusions: Isoperistaltic Gastric Tube is safe and effective even in LGEA patients with longer gaps, with good perioperative, post-operative and middle-term outcomes. This procedure may be considered as an alternative to avoid esophageal substitution when a primary anastomosis seems impossible for a residual gap after traction and growth techniques.

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.

Prevalence of Non-erosive Esophageal Phenotypes in Children: A European Multicenter Study.

Background/Aims: Since available data on pediatric non-erosive esophageal phenotypes (NEEPs) are scant, we investigated their prevalence and the phenotype-dependent treatment response in these children. Methods: Over a 5-year period, children with negative upper endoscopy, who underwent esophageal pH-impedance (off-therapy) for persisting symptoms not responsive to proton pump inhibitor (PPI)-treatment, were recruited. Based on the results of acid reflux index (RI) and symptom association probability (SAP), patients were categorized into: (1) abnormal RI (non-erosive reflux disease [NERD]), (2) normal RI and abnormal SAP (reflux hypersensitivity [RH]), (3) normal RI and normal SAP (functional heartburn [FH]), and (4) normal RI and not-reliable SAP (normal-RI-not otherwise-specified [normal-RI-NOS]). For each subgroup, treatment response was evaluated. Results: Out of 2333 children who underwent esophageal pH-impedance, 68 cases, including 18 NERD, 14 RH, 26 FH, and 10 normal-RI-NOS were identified as fulfilling the inclusion criteria and were analyzed. Considering symptoms before endoscopy, chest pain was more reported in NERD than in other cases (6/18 vs 5/50, P = 0.031). At long-term follow-up of 23 patients (8 NERD, 8 FH, 2 RH, and 5 normal-RI-NOS): 17 were on PPIs and 2 combined alginate, 1 (FH) was on benzodiazepine + anticholinergic, 1 (normal-RI-NOS) on citalopram, and 3 had no therapy. A complete symptom-resolution was observed in 5/8 NERD, in 2/8 FH, and in 2/5 normal-RI-NOS. Conclusions: FH may be the most common pediatric NEEP. At long-term follow-up, there was a trend toward a more frequent complete symptom resolution with PPI-therapy in NERD patients while other groups did not benefit from extended acid-suppressive-treatment.

Enteral formula compared to Nissen-Fundoplication: Data from a retrospective analysis on tolerance, utility, applicability, and safeness in children with neurological diseases.

Objectives and study: Approximately 46-90% of children with neurological disorders (NDs) suffer from gastrointestinal diseases, such as gastro-esophageal reflux disease (GERD), constipation, or malnutrition. Therefore, enteral feeding is often necessary to achieve nutritional requirements. The treatment of GERD could be based on pharmacological therapy, nutritional treatment (changing the type of formula), or surgical treatment (Nissen Fundoplication, NF). The aim of this study was to describe and compare resource consumption between NE based on different formulas and NF in patients with ND. Methods: We performed a retrospective analysis on all children with neurological damage (age: 29 days-17 years) treated from January 2009 to January 2019 due to nutritional problems and food and/or gastrointestinal intolerances. For all patients, demographic and anthropometric characteristics, symptoms, type of nutrition (formula and enteral access), and number and type of outpatient or emergency room visits were collected. Patients with <24 months of age at the closing of the database and with <24 months of follow-up were excluded. Results: Out of 376 children, 309 children (M: 158; median age: 4 IQR 1-10) were enrolled, among which, 65 patients (NF group M: 33; median age: 5.3 IQR 1.8-10.7) underwent NF. Vomit, GERD, and dysphagia were more represented in the NF group (p < 0.05). Our analysis shows that the NF group seems to present a lower number of hospitalization and a lower number of visits for non-GI disorders, but a higher number of visits for GI disorders compared to non-NF. In the NF group, a higher prevalence of the use of amino-acid-based formula and free diet is observed, with a trend for the lower prevalence of casein-based or whey+casein-based formula (Fisher test p = 0.072). The median cost of a patient enrolled in the database is € 19,515 ± 540 ($ 20,742.32 ± 573.96) per year, with no significant difference between the two groups. Regarding formula, at baseline, 76 children consumed a free diet, 24 a casein-based formula, 139 a whey+casein-based formula, 46 a whey-based formula, and 24 an amino-acid-based formula. Conclusions: In conclusion, compared to EN, NF may not improve the clinical aspect and related costs in children with NDs. Considering the psychological and QoL burden for patients, in a "step-up" strategy, EN could be proposed as an efficient alternative to NF.

Pediatric Gastroenterology and Hepatology in Italy before and after the COVID-19: Lessons learned and management changes by SIGENP.

Around the world, the 2019 Coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has raised serious public health problems and major medical challenges. The Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) published several papers on the impact of COVID-19 on the current management, diagnosis, and treatment of acute and chronic gastrointestinal, hepatic, immune-mediated, and functional disorders. The present article summarizes the most relevant SIGENP reports and consensus during and after the peak of the COVID-19 outbreak, including the diagnosis and treatment of inflammatory bowel disease (IBD), indications and timing of digestive endoscopy, and insights into the novel hepatitis.

Role of inflammation in pediatric irritable bowel syndrome.

BACKGROUND: IBS affects a large number of children throughout the world and is thought to be the result of disturbed neuroimmune function along with the brain-gut axis. Although the underlying pathophysiologic mechanisms are not clear, the role of low-grade inflammation and mucosal immune activation in IBS symptom generation has become evident also in subsets of pediatric patients. Animal models provided meaningful insight in the causal relationship between abnormal mucosal immune activation and changes in gastrointestinal (GI) sensory-motor function. Likewise, the development of long-standing GI symptoms fulfilling the current criteria for functional GI disorders after infection gastroenteritis and in patients with IBD or celiac disease in remission further supports this hypothesis. Immune activation, its impact on gut sensory-motor function, and potential implications for symptom generation emerged in both children and adults with IBS. PURPOSE: The aim of this review is to summarize the main evidence on the presence of low-grade inflammation and immune activation in children with IBS, its possible role in symptom generation, and its potential implication for new therapeutic strategies.

Cyclic vomiting syndrome in children: a nationwide survey of current practice on behalf of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) and Italian Society of Pediatric Neurology (SINP).

BACKGROUND: Cyclic Vomiting Syndrome (CVS) is a rare functional gastrointestinal disorder, which has a considerable burden on quality of life of both children and their family. Aim of the study was to evaluate the diagnostic modalities and therapeutic approach to CVS among Italian tertiary care centers and the differences according to subspecialties, as well as to explore whether potential predictive factors associated with either a poor outcome or a response to a specific treatment. METHODS: Cross-sectional multicenter web-based survey involving members of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) and Italian Society of Pediatric Neurology (SINP). RESULTS: A total of 67 responses were received and analyzed. Most of the respondent units cared for less than 20 patients. More than half of the patients were referred after 3 to 5 episodes, and a quarter after 5 attacks. We report different diagnostic approaches among Italian clinicians, which was particularly evident when comparing gastroenterologists and neurologists. Moreover, our survey demonstrated a predilection of certain drugs during emetic phase according to specific clinic, which reflects the cultural background of physicians. CONCLUSION: In conclusion, our survey highlights poor consensus amongst clinicians in our country in the diagnosis and the management of children with CVS, raising the need for a national consensus guideline in order to standardize the practice.

Evaluation of Safety and Immunogenicity of BNT162B2 mRNA COVID-19 Vaccine in IBD Pediatric Population with Distinct Immune Suppressive Regimens.

Patients affected by Inflammatory Bowel Disease (IBD) present higher risk for infection and suboptimal response upon vaccination. The immunogenicity of SARS-CoV2 vaccination is still largely unknown in adolescents or young adults affected by IBD (pIBD). We investigated the safety and immunogenicity of the BNT162B2 mRNA COVID-19 vaccine in 27 pIBD, as compared to 30 healthy controls (HC). Immunogenicity was measured by anti-SARS-CoV2 IgG (anti-S and anti-trim Ab) before vaccination, after 21 days (T21) and 7 days after the second dose (T28). The safety profile was investigated by close monitoring and self-reported adverse events. Vaccination was well tolerated, and short-term adverse events reported were only mild to moderate. Three out of twenty-seven patients showed IBD flare after vaccination, but no causal relationship could be established. Overall, pIBD showed a good humoral response upon vaccination compared to HC; however, pIBD on anti-TNFα treatment showed lower anti-S Ab titers compared to patients receiving other immune-suppressive regimens (p = 0.0413 at first dose and p = 0.0301 at second dose). These data show that pIBD present a good safety and immunogenicity profile following SARS-CoV-2 mRNA vaccination. Additional studies on the impact of specific immune-suppressive regimens, such as anti TNFα, on immunogenicity should be further investigated on larger cohorts.

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.

New therapies for esophageal strictures in children.

PURPOSE OF REVIEW: The present review aims at describing recent advances in therapeutic strategies for the treatment of benign esophageal strictures in children. We discuss current knowledge and practice on esophageal dilations, which are still the mainstream of treatment. We present new evidence about adjuvant treatments for recurrent and refractory strictures, including endoscopic incisional therapy, esophageal stenting, intralesional or topical mytomicin C and intralesional, systemic or topical steroids. RECENT FINDINGS: Current evidence on esophageal dilations is not sufficient to establish superiority of one of the available techniques, especially the use of balloon or bougie dilators, but a prospective international cohort study on anastomotic stricture in esophageal atresia is underway to address this issue. Recurrent and refractory strictures still represent a challenge, since none of the adjuvant pharmacological and mechanical interventions has shown to be enough feasible, effective and safe to revolutionize clinical practice. SUMMARY: In the last couple of years, several encouraging results have been published on management of esophageal strictures in children. Further research is needed, hopefully directed toward secure, easily reproducible and minimally invasive measures.

Eosinophilic Esophagitis and Microbiota: State of the Art.

Eosinophilic esophagitis (EoE) is a chronic, food-triggered, immune-mediated disease of the oesophagus, clinically characterized by symptoms referred to oesophagal dysfunction, and histologically defined by an eosinophil productive inflammation of the oesophagal mucosa, among other cell types. The involvement of an adaptive Th2-type response to food antigens in EoE was known since 2000; several cytokines and chemokines promote food-specific responses, during which local production of IgE, but also IgG4 derived from plasma cells in lamina propria of oesophagal mucosa might play an important role. Evidence pointing towards a possible role for the innate immunity in EoE has arisen recently. Together, this evidence gives rise to a potential role that the innate immune system in general, and also the microbial pattern recognition receptors (PRRs) might play in EoE pathogenesis. Among PRRs, Toll-like receptors (TLRs) are type-I transmembrane receptors expressed both on epithelial and lamina propria cells with the capacity to distinguish between pathogen and commensal microbes. As TLRs in the different intestinal epithelia represent the primary mechanism of epithelial recognition of bacteria, this evidence underlines that oesophagal TLR-dependent signaling pathways in EoE support the potential implication of microbiota and the innate immune system in the pathogenesis of this disease. The oesophagal mucosa hosts a resident microbiota, although in a smaller population as compared with other districts of the gastrointestinal tract. Few studies have focused on the composition of the microbiota of the normal oesophagus alone. Still, additional information has come from studies investigating the oesophagal microbiota in disease and including healthy patients as controls. Our review aims to describe all the evidence on the oesophagal and intestinal microbiota in patients with EoE to identify the specific features of dysbiosis in this condition.

An international survey on anastomotic stricture management after esophageal atresia repair: considerations and advisory statements.

BACKGROUND: Endoscopic dilatation is the first-line treatment of stricture formation after esophageal atresia (EA) repair. However, there is no consensus on how to perform these dilatation procedures which may lead to a large variation between centers, countries and doctor's experience. This is the first cross-sectional study to provide an overview on differences in endoscopic dilatation treatment of pediatric anastomotic strictures worldwide. METHODS: An online questionnaire was sent to members of five pediatric medical networks, experienced in treating anastomotic strictures in children with EA. The main outcome was the difference in endoscopic dilatation procedures in various centers worldwide, including technical details, dilatation approach (routine or only in symptomatic patients), and adjuvant treatment options. Descriptive statistics were performed with SPSS. RESULTS: Responses from 115 centers from 32 countries worldwide were analyzed. The preferred approach was balloon dilatation (68%) with a guidewire (66%), performed by a pediatric gastroenterologist (n = 103) or pediatric surgeon (n = 48) in symptomatic patients (68%). In most centers, hydrostatic pressure was used for balloon dilatation. The insufflation duration was standardized in 59 centers with a median duration of 60 (range 5-300) seconds. The preferred first-line adjunctive treatments in case of recurrent strictures were intralesional steroids and topical mitomycin C, in respectively 47% and 31% of the centers. CONCLUSIONS: We found a large variation in stricture management in children with EA, which confirms the current lack of consensus. International networks for rare diseases are required for harmonizing and comparing the procedures, for which we give several suggestions.

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.

Cyclic Vomiting Syndrome in Children.

Cyclic Vomiting Syndrome (CVS) is an underdiagnosed episodic syndrome characterized by frequent hospitalizations, multiple comorbidities, and poor quality of life. It is often misdiagnosed due to the unappreciated pattern of recurrence and lack of confirmatory testing. CVS mainly occurs in pre-school or early school-age, but infants and elderly onset have been also described. The etiopathogenesis is largely unknown, but it is likely to be multifactorial. Recent evidence suggests that aberrant brain-gut pathways, mitochondrial enzymopathies, gastrointestinal motility disorders, calcium channel abnormalities, and hyperactivity of the hypothalamic-pituitary-adrenal axis in response to a triggering environmental stimulus are involved. CVS is characterized by acute, stereotyped and recurrent episodes of intense nausea and incoercible vomiting with predictable periodicity and return to baseline health between episodes. A distinction with other differential diagnoses is a challenge for clinicians. Although extensive and invasive investigations should be avoided, baseline testing toward identifying organic causes is recommended in all children with CVS. The management of CVS requires an individually tailored therapy. Management of acute phase is mainly based on supportive and symptomatic care. Early intervention with abortive agents during the brief prodromal phase can be used to attempt to terminate the attack. During the interictal period, non-pharmacologic measures as lifestyle changes and the use of reassurance and anticipatory guidance seem to be effective as a preventive treatment. The indication for prophylactic pharmacotherapy depends on attack intensity and severity, the impairment of the QoL and if attack treatments are ineffective or cause side effects. When children remain refractory to acute or prophylactic treatment, or the episode differs from previous ones, the clinician should consider the possibility of an underlying disease and further mono- or combination therapy and psychotherapy can be guided by accompanying comorbidities and specific sub-phenotype. This review was developed by a joint task force of the Italian Society of Pediatric Gastroenterology Hepatology and Nutrition (SIGENP) and Italian Society of Pediatric Neurology (SINP) to identify relevant current issues and to propose future research directions on pediatric CVS.