Radiopaque marker colonic transit study in the pediatric population BSPGHAN Motility Working Group consensus statement.

Functional constipation (FC) is a common condition in childhood in the United Kingdom and worldwide. Various radiological approaches have been established for diagnostic purposes. The radiopaque marker study (ROMS) is universally accepted and used to assess colonic transit time (CTT) in children with FC. Despite being widely used, there is a lack of standardization with various technical protocols, reproducibility of different populations, the purpose for using investigation, variance in the number of markers used, the amount of study days and calculations, the need to empty the colon before performing the test, and whether to perform on medication or off, or the use of specific diets. As part of the British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) motility working group (MWG), we decided to explore further into the evidence, in order to provide guidance regarding the use of ROMS in dealing with FC in the pediatric population.

An ESPGHAN Position Paper on the Use of Low-FODMAP Diet in Pediatric Gastroenterology.

Excluding oligo-, di-, monosaccharides and polyols (FODMAPs) from the diet is increasingly being used to treat children with gastrointestinal complaints. The aim of this position paper is to review the available evidence on the safety and efficacy of its use in children and provide expert guidance regarding practical aspects in case its use is considered . Members of the Gastroenterology Committee, the Nutrition Committee and the Allied Health Professionals Committee of the European Society for Pediatric Gastroenterology Hepatology and Nutrition contributed to this position paper. Clinical questions regarding initiation, introduction, duration, weaning, monitoring, professional guidance, safety and risks of the diet are addressed. A systematic literature search was performed from 2005 to May 2021 using PubMed, MEDLINE and Cochrane Database of Systematic Reviews. In the absence of evidence, recommendations reflect the expert opinion of the authors. The systematic literature search revealed that the low-FODMAP diet has not been comprehensively studied in children. Indications and contraindications of the use of the diet in different pediatric gastroenterological conditions are discussed and practical recommendations are formulated. There is scarce evidence to support the use of a low-FODMAP diet in children with Irritable Bowel Syndrome and no evidence to recommend its use in other gastrointestinal diseases and complaints in children. Awareness of how and when to use the diet is crucial, as a restrictive diet may impact nutritional adequacy and/or promote distorted eating in vulnerable subjects. The present article provides practical safety tips to be applied when the low-FODMAP diet is considered in children.

Prucalopride in intestinal pseudo obstruction, paediatric experience and systematic review.

BACKGROUND: Intestinal pseudo obstruction both acute and chronic is an uncommon severe motility disorder that affect both children and adults, can lead to significant morbidity burden and have no standard management strategy. Prucalopride a highly selective serotonin receptor agonist is an effective laxative with reported extra colon action. We aim to report our experience in children with acute and chronic intestinal pseudo obstruction who responded to prucalopride and systemically review the use of prucalopride in intestinal pseudo obstruction. METHODS: A report of clinical experience and systemic review of the relevant medical databases to identify the outcome of usage of prucalopride in patients with acute and chronic intestinal pseudo obstruction. Studies meeting the selection criteria were reviewed including abstract only and case reports. RESULTS: All reported cases showed clinical response to prucalopride. There were three full text, two abstracts only and three case reports all reporting clinical improvement with prucalopride. CONCLUSION: Prucalopride appears to show promising results in children and adults with acute and chronic intestinal pseudo obstruction.

The evolution of magnetic resonance enterography in the assessment of motility disorders in children.

Gastrointestinal symptoms including constipation, diarrhoea, pain and bloating represent some of the most common clinical problems for patients. These symptoms can often be managed with cheap, widely available medication or will spontaneously resolve. However, for many patients, chronic GI symptoms persist and frequently come to dominate their lives. At one end of the spectrum there is Inflammatory Bowel Disease (IBD) with a clearly defined but expensive treatment pathway. Contrasting with this is Irritable Bowel Syndrome (IBS), likely a collection of pathologies, has a poorly standardised pathway with unsatisfactory clinical outcomes. Managing GI symptoms in adult populations is a challenge. The clinical burden of gastrointestinal disease is also prevalent in paediatric populations and perhaps even harder to treat. In this review we explore some of the recent advances in magnetic resonance imaging (MRI) to study the gastrointestinal tract. Complex in both its anatomical structure and its physiology we are likely missing key physiological markers of disease through relying on symptomatic descriptors of gut function. Using MRI we might be able to characterise previously opaque processes, such as non-propulsive contractility, that could lead to changes in how we understand even common symptoms like constipation. This review explores recent advances in the field in adult populations and examines how this safe, objective and increasingly available modality might be applied to paediatric populations.

Mind the gut: probiotics in paediatric neurogastroenterology.

The gut-brain axis has recently emerged as a key modulator of human health and the intestinal microbiome has a well-recognised pivotal role in this strong connection. The aim of this narrative review is to update and summarise the effect and clinical applicability of probiotics in paediatric neurogastroenterology. The Cochrane Database and PubMed were searched using keywords relating to different subtypes of functional gastrointestinal disorders (FGIDs) and their symptoms, those relating to the CNS and related neurological or behavioural dysfunction as well as 'probiotic' OR 'probiotics'. Included papers were limited to those including children (aged 0-18 years) and using English language. Although significant effects of specific strains have been reported in infants with FGIDs, heterogeneity amongst the studies (different products and concentrations used and FGID subtypes), has limited the ability to draw an overall conclusion on the clinical value of probiotics. According to different meta-analyses of randomised controlled trials, the use of Lactobacillus reuteri (DSM 17938) was associated with a significant decrease in average crying time in infantile colic. There is moderate evidence for this strain and LGG and limited evidence (based on one study each) for the beneficial effect of VSL#3 and a three-strain bifidobacteria mix in abdominal pain FGIDs, particularly in the irritable bowel disease subgroup of children, but not in functional dyspepsia. There is currently no clear evidence of positive effects of oral probiotics in autistic spectrum disorder. Efficacy and safety of other strains or beneficial effects in other conditions still need to be proven, as probiotic properties are strain-specific, and data cannot be extrapolated to other brain-gut or mood diseases or to other probiotics of the same or different species. To transform the use of probiotics from a tempting suggestion to a promising treatment modality in neurogastroenterological disorders more accurate differentiation of the efficacy-proven strains, clarification of dose, duration, and outcome and a careful selection of the target patients are still necessary.

Overlap between functional abdominal pain disorders and organic diseases in children. / Sobreposición entre los trastornos funcionales de dolor abdominal y enfermedades orgánicas en niños.

Functional abdominal pain disorders are highly prevalent in children. These disorders can be present in isolation or combined with organic diseases, such as celiac disease and inflammatory bowel diseases. Intestinal inflammation (infectious and non-infectious) predisposes children to the development of visceral hypersensitivity that can manifest as functional abdominal pain disorders, including irritable bowel syndrome. The new onset of irritable bowel syndrome symptoms in a patient with an underlying organic disease, such as inflammatory bowel disease, is clinically challenging, given that the same symptomatology may represent a flare-up of the inflammatory bowel disease or an overlapping functional abdominal pain disorder. Similarly, irritable bowel syndrome symptoms in a child previously diagnosed with celiac disease may occur due to poorly controlled celiac disease or the overlap with a functional abdominal pain disorder. There is little research on the overlap of functional abdominal disorders with organic diseases in children. Studies suggest that the overlap between functional abdominal pain disorders and inflammatory bowel disease is more common in adults than in children. The causes for these differences in prevalence are unknown. Only a handful of studies have been published on the overlap between celiac disease and functional abdominal pain disorders in children. The present article provides a review of the literature on the overlap between celiac disease, inflammatory bowel disease, and functional abdominal pain disorders in children and establish comparisons with studies conducted on adults.

Sequential incremental doses of bisacodyl increase the diagnostic accuracy of colonic manometry.

BACKGROUND: Colonic manometry is the standard diagnostic modality for evaluating colonic motility in children. Intraluminal bisacodyl is routinely used to trigger high-amplitude propagating contractions (HAPCs), a feature of normal colonic motility. Usually, only a single dose (0.2 mg/kg) is suggested. We retrospectively explored whether the use of an additional higher (0.4 mg/kg) dose of bisacodyl increases the yield of colonic manometry. METHODS: In 103 children (median age: 8.8 years, range 3.2-15.7 years) with a diagnosis of slow transit constipation, colonic motility was recorded for 1 h before and 1 h after each of two incremental doses of bisacodyl (low, L, dose: 0.2 mg/kg, max 10 mg; high, H, dose: 0.4 mg/kg, max 20 mg) and the characteristics of HAPCs analyzed. KEY RESULTS: High-amplitude propagating contractions were seen in 85 children. H dose significantly increased the proportion of patients with fully propagated HAPCs (H dose: 57/103 [55%], L dose: 27/103 [26%], p < 0.001), paralleling the significant decrease in the proportion with partially propagated HAPCs (H dose: 29/103 [28%], L dose: 47/103 [46%], p < 0.01). Mean HAPC number significantly increased throughout the colon at H compared to L dose (7.2 ± 5.05 vs 5.6 ± 5.1, p < 0.05). Finally, the proportion of patients with normal pressure wave morphology of HAPCs significantly increased with higher dose (H dose: 55/85 [65%], L dose: 27/85 [32%], p < 0.001). CONCLUSIONS & INTERFERENCES: An additional higher dose of bisacodyl during colonic manometry improves colonic neuromuscular function suggesting its use might improve interpretation and decision making in children with slow transit constipation.

Efficacy of the neurokinin-1 receptor antagonist aprepitant in children with cyclical vomiting syndrome.

BACKGROUND: Aprepitant (Emend, Merck Sharp & Dohme Ltd, Haarlem, the Netherlands), a neurokinin-1 receptor antagonist, prevents vomiting in a range of conditions. No data are available on its use in children with cyclical vomiting syndrome (CVS). AIM: We investigated the efficacy of aprepitant as prophylactic treatment or acute intervention in CVS children refractory to conventional therapies. METHODS: Forty-one children (median age: 8 years) fulfilling NASPGHAN criteria treated acutely (RegA) or prophylactically (RegP) with aprepitant were retrospectively reviewed. Primary outcome was the clinical response (decrease in frequency and intensity of CVS episodes). Secondary outcomes were: number of CVS episodes/year, number of hospital admissions/year, CVS episode duration, number of vomits/h, symptom-free interval length (days), and school attendance percentage. The follow-up period was 18-60 months. RESULTS: Sixteen children received RegP and 25 RegA. One child on RegP stopped treatment due to severe migraine. At 12-months on intention-to-treat analysis, 13 children on RegP (81%) achieved either complete (3/16, 19%) or partial (10/16, 62%) clinical response. On RegA, 19 children (76%) had either complete (3/25, 12%) or partial (16/25, 64%) response (P = 0.8 vs. RegP). In both RegP and RegA, there was a significant decrease in CVS episodes/year, hospital admission number/year, CVS episode length, number of vomits/h, as well as an increase in symptom-free interval duration and school attendance percentage. Side effects were reported only in RegP (5/16, 31%) including hiccough (3/16, 19%), asthenia/fatigue (2/16, 12.5%), increased appetite (2/16, 12.5%), mild headache (1/16, 6%) and severe migraine (1/16, 6%). CONCLUSION: Aprepitant appears effective for both acute and prophylactic management of paediatric cyclical vomiting syndrome refractory to conventional therapies.

Extraintestinal manifestations in children with gastrointestinal food allergy.

OBJECTIVES: The presence of extraintestinal manifestations (EIM) in children with gastrointestinal (GI) food allergy (GIFA) is greatly debated. In the present study we assessed the prevalence of EIM in children with GIFA and investigated whether their presence is helpful in the allergy-focused history-taking process. METHODS: The medical records of all children with a proven diagnosis of GIFA were reviewed along with those of children diagnosed as having inflammatory bowel disease (IBD) as controls. Data regarding age at onset, age at diagnosis, atopic family history, atopic comorbidities, GI symptoms, and EIM were recorded. RESULTS: Data from 436 children with GIFA and 74 children with IBD were included in the analysis. EIM were documented in 368 children with GIFA, including fatigue (53.0%), allergic shiners (49.1%), mouth ulcers (39.0%), joint pain/hypermobility (35.8%), poor sleep (34.4%), night sweats (34.4%), headache (22.7%), and bed-wetting (17.7%). The proportion of patients with EIM was higher in the GIFA group compared with that in the IBD group (368/436 [84.4%] vs 40/74 [54.1%]; P < 0.001). Segregating the GIFA group into children with and without atopic comorbidities, both atopic (276/30; 89.9%) and nonatopic (93/130; 71.5%) children showed higher proportion of EIM than children with IBD ([40/74; 54.1%], P < 0.01 and <0.05, respectively). CONCLUSIONS: GIFA are commonly associated with a wide range of EIM, which appear to represent important and specific clinical features of this group of conditions. Their recognition in taking an allergy-focused history may play an important role for both diagnosis and management.

Dilated intercellular space diameter as marker of reflux-related mucosal injury in children with chronic cough and gastro-oesophageal reflux disease.

BACKGROUND: The diagnostic corroboration of the relationship between gastro-oesophageal reflux disease (GERD) and chronic cough remains challenging. AIMS: To compare oesophageal mucosal intercellular space diameter (ISD) in children with GERD, children with gastro-oesophageal reflux (GER)-related cough (GrC) and a control group, and to explore the relationship between baseline impedance levels and dilated ISD in children with GER-related cough. METHODS: Forty children with GERD, 15 children with GrC and 12 controls prospectively underwent oesophagogastroduodenoscopy (EGD) with oesophageal biopsies taken 2-3 cm above squamocolumnar junction. ISD were quantified using transmission electron microscopy. Impedance-pH monitoring with evaluation of baseline impedance in the most distal impedance channel was performed in both patient groups. RESULTS: A significant difference in mean ISD values was found between GrC patients (0.9 ± 0.2 µm) and controls (0.5 ± 0.2 µm, P < 0.001), whereas there was no difference between GrC and GERD group (1 ± 0.3 µm, NS). No difference was found in the mean ISD between GrC children with or without pathological oesophageal acid exposure time (1 ± 0.3 vs. 0.9 ± 0.2 µm), and there was no correlation between ISD and any reflux parameter. Finally, there was no correlation between ISD and distal baseline impedance values (r:-0.35; NS). CONCLUSIONS: In children with reflux-related cough, dilated intercellular space diameter appears to be an objective and useful marker of oesophageal mucosal injury regardless of acid exposure, and its evaluation should be considered for those patients where the diagnosis is uncertain. In children with reflux-related cough, baseline impedance levels have no role in identifying reflux-induced oesophageal mucosal ultrastructural changes.

High-resolution colonic manometry accurately predicts colonic neuromuscular pathological phenotype in pediatric slow transit constipation.

BACKGROUND: Severe pediatric slow transit constipation (STC) is commonly due to intrinsic colonic neuromuscular disease. We sought to correlate neuromuscular histological phenotypes in pediatric STC with colonic manometric phenotypes using high-resolution manometry (HRM). We tested the hypothesis that failure of motor quiescence (FQ) between bisacodyl-induced high amplitude propagating sequences (HAPSs) might predict neuromuscular pathology. METHODS: Eighteen children (10 males, median age: 7.5 years) with refractory STC underwent stationary colonic HRM before segmental colonic resection. Six age-matched constipated children with normal colonic transit served as controls. Colonic resection specimens underwent histopathological analysis. Conventional manometric parameters and area under the curve (AUC) during a 1-min period following bisacodyl-induced HAPSs [PBAUC(1) ], as measure of FQ, were calculated. KEY RESULTS: Numbers of postbisacodyl HAPSs in descending and sigmoid segments were lower in patients than controls (P < 0.01, respectively). Low amplitude propagating sequences (LAPSs) were common prebisacodyl in controls and rare in STC (P < 0.001), whereas postbisacodyl LAPS were more common in STC (P < 0.001). Postbisacodyl, both retrograde propagating contractions and bursts of contractions were present in STC patients only (P < 0.001 and P < 0.01). Postbisacodyl simultaneous pressurization was seen only in STC (P < 0.05 and P < 0.001, in descending and rectosigmoid segments). Histological abnormalities were present in 17/18. Fourteen were neurogenic, one neuro-myogenic, and two myogenic. In segments with HAPS, PBAUC(1) was predictive of colonic neuropathy using a cutoff of 205 mmHg.s(-1) (Sensitivity 100%, specificity 86%, PPV92%, NPV100%). CONCLUSIONS & INFERENCES: PBAUC(1) is increased in multiple colonic segments in neuropathic pediatric STC and constitutes a sensitive and specific biomarker of neuropathy.

Relationship between baseline impedance levels and esophageal mucosal integrity in children with erosive and non-erosive reflux disease.

BACKGROUND: Baseline impedance measurement has been reported to be related to esophageal acid exposure and hypothesized to be a marker of microscopic changes of the esophageal mucosa. Aims of the study were to establish whether any relationship existed between the magnitude of intercellular space diameter (ISD) of esophageal mucosa and baseline impedance levels in children with gastro-esophageal reflux disease (GERD), and to compare baseline impedance levels between children with non erosive (NERD) and erosive (ERD) reflux disease. METHODS: Fifteen children (median age: 11.2 years) with NERD, and 11 with ERD (median age: 9.6 years) were prospectively studied. All patients underwent upper endoscopy. Biopsies were taken 2-3cm above the Z-line, and ISD was measured using transmission electron microscopy. All patients underwent impedance pH-monitoring, and baseline impedance levels were assessed in the most distal impedance channel. KEY RESULTS: Mean (±SD) ISD did not differ between NERD (1.0±0.3µm) and ERD (1.1 ± 0.3 µm, ns). Considering all patients together, no correlation was found between distal baseline impedance and ISD (r: -0.15; ns). Conversely, negative correlations were found between distal baseline impedance and acid exposure time (r: -0.76; P<0.001), long-lasting reflux episodes (r: -0.78; P<0.001), acid reflux episodes (r: -0.62; P<0.001), and acid clearance time (r: -0.79; P<0.001). Distal baseline impedance was significantly lower in ERD [1455 (947-2338) Ω] than in NERD children [3065 (2253-3771) Ω; P<0.01]. CONCLUSIONS & INFERENCES: In children with GERD baseline impedance levels are not useful in predicting reflux-induced ultrastructural changes in the esophageal mucosa, despite their ability to discriminate between NERD and ERD.

Non-acid gastro-oesophageal reflux in children with suspected pulmonary aspiration.

BACKGROUND & AIMS: In a group of children with suspected pulmonary aspiration, we aimed to describe the type and physical characteristics of gastro-oesophageal reflux (GOR) episodes, and to determine their correlation with the lipid-laden macrophage (LLM) content in bronchoalveolar lavage (BAL). PATIENTS AND METHODS: Twenty-one children with a diagnosis of bronchial asthma, recurrent lung consolidations and recurrent laryngotracheitis underwent 24-h multichannel intraluminal impedance and pH (MII-pH) monitoring, fibreoptic bronchoscopy and BAL. The following parameters were evaluated: total number of reflux episodes, number of acid reflux [AR; pH<4] and non-acid reflux [NAR] episodes [pH>4], height of reflux episodes, LLM content and percentage of neutrophils in the BAL. RESULTS: The number of NAR episodes and the number of those reaching the proximal oesophagus were significantly higher in patients with recurrent lung consolidations than in those with bronchial asthma and laryngotracheitis (p<0.01 and p<0.01). BAL studies showed a significantly higher LLM content in children with recurrent lung consolidations than in those with bronchial asthma and laryngotracheitis (p<0.01). The LLM content correlated significantly with the total number of reflux episodes (r=0.73; p<0.001) and with those reaching the proximal oesophagus (r=0.67; p<0.001). Finally, the LLM content correlated with the number of NAR episodes (r=0.61; p<0.01), with those reaching the proximal oesophagus (r=0.64; p<0.01) and with the percentage of BAL neutrophils (r=0.7; p<0.01). CONCLUSION: NAR episodes reaching the proximal oesophagus correlate with diagnostic marker for pulmonary micro-aspiration. MII-pH monitoring increases the yield in identifying types and proximal extension of reflux episodes, that discriminate between patients with and without pulmonary aspiration.

Role of CARD15, DLG5 and OCTN genes polymorphisms in children with inflammatory bowel diseases.

AIM: To investigate the contribution of variants of CARD15, OCTN1/2 and DLG5 genes in disease predisposition and phenotypes in a large Italian cohort of pediatric patients with inflammatory bowel diseases (IBD). METHODS: Two hundred patients with Crohn's disease (CD), 186 ulcerative colitis (UC) patients, 434 parents (217 trios), and 347 healthy controls (HC) were studied. Polymorphisms of the three major variants of CARD15, 1672C/T and -207G/C SNPs for OCTN genes, IGR2096a_1 and IGR2198a_1 SNPs for the IBD5 locus, and 113G/A variant of the DLG5 gene were evaluated. Potential correlations with clinical sub-phenotypes were investigated. RESULTS: Polymorphisms of CARD15 were significantly associated with CD, and at least one variant was found in 38% of patients (15% in HC, OR = 2.7, P < 0.001). Homozygosis for both OCTN1/2 variants was more common in CD patients (1672TT 24%, -207CC 29%) than in HC (16% and 21%, respectively; P = 0.03), with an increased frequency of the TC haplotype (44.8% vs 38.3% in HC, P = 0.04). No association with the DLG5 variant was found. CD carriers of OCTN1/2 and DLG5 variants more frequently had penetrating disease (P = 0.04 and P = 0.01), while carriers of CARD15 more frequently had ileal localization (P = 0.03). No gene-gene interaction was found. In UC patients, the TC haplotype was more frequent (45.4%, P = 0.03), but no genotype/phenotype correlation was observed. CONCLUSION: Polymorphisms of CARD15 and OCTN genes, but not DLG5 are associated with pediatric onset of CD. Polymorphisms of CARD15, OCTN, and DLG5 genes exert a weak influence on CD phenotype.

Headache and recurrent abdominal pain: a controlled study by the means of the Child Behaviour Checklist (CBCL).

Headache and recurrent abdominal pain (RAP) are common disorders in children and adolescents, frequently referred to paediatricians. Both disorders show similarities in trigger and comorbid factors, their burden on family and individual life, and a paroxysmal trend with risks of chronicization over time. However, very few studies have compared directly headache and RAP. The main aim of this study was to compare the psychological profile of headache and RAP patients vs. healthy controls. A total of 210 children and adolescents [99 boys, 111 girls; age range 4-18 years; mean age (m.a.) = 11.04, SD 4.05] were assessed: 70 headache patients (m.a. 12.4 years; SD 2.9; F = 35, M = 35), 70 RAP patients (m.a. 9 years; SD 3.6; F = 30, M = 40) and 70 controls (m.a. 11.7 years; SD 4.6; F = 46, M = 24). The diagnoses had been made according to international systems of classification both for headache (ICHD-II criteria) and RAP (Rome II criteria). The psychological profile had been made according to the Child Behaviour Checklist 4-18 (CBCL). anova one-way analysis was used to compare CBCL scales and subscales between groups. Headache and RAP showed a very similar trend vs. control for the main scales of the CBCL, with a statistically significant tendency to show problems in the Internalizing scale (anxiety, mood and somatic complaints) and no problems in the Externalizing (behavioural) scale. Only for the Attention Problems subscale migraineurs showed a significant difference compared with RAP. In conclusion, headache and RAP show a very similar psychological profile that should be considered not only for diagnostic and therapeutic purposes, but also from the aetiological aspect.

Gut-associated bacterial microbiota in paediatric patients with inflammatory bowel disease.

BACKGROUND: Clinical and experimental observations in animal models indicate that intestinal commensal bacteria are involved in the initiation and amplification of inflammatory bowel disease (IBD). No paediatric reports are available on intestinal endogenous microflora in IBD. AIMS: To investigate and characterise the predominant composition of the mucosa-associated intestinal microflora in colonoscopic biopsy specimens of paediatric patients with newly diagnosed IBD. METHODS: Mucosa-associated bacteria were quantified and isolated from biopsy specimens of the ileum, caecum and rectum obtained at colonoscopy in 12 patients with Crohn's disease, 7 with ulcerative colitis, 6 with indeterminate colitis, 10 with lymphonodular hyperplasia of the distal ileum and in 7 controls. Isolation and characterisation were carried out by conventional culture techniques for aerobic and facultative-anaerobic microorganisms, and molecular analysis (16S rRNA-based amplification and real-time polymerase chain reaction assays) for the detection of anaerobic bacterial groups or species. RESULTS: A higher number of mucosa-associated aerobic and facultative-anaerobic bacteria were found in biopsy specimens of children with IBD than in controls. An overall decrease in some bacterial species or groups belonging to the normal anaerobic intestinal flora was suggested by molecular approaches; in particular, occurrence of Bacteroides vulgatus was low in Crohn's disease, ulcerative colitis and indeterminate colitis specimens. CONCLUSION: This is the first paediatric report investigating the intestinal mucosa-associated microflora in patients of the IBD spectrum. These results, although limited by the sample size, allow a better understanding of changes in mucosa-associated bacterial flora in these patients, showing either a predominance of some potentially harmful bacterial groups or a decrease in beneficial bacterial species. These data underline the central role of mucosa-adherent bacteria in IBD.

Short- and long-term therapeutic efficacy of nutritional therapy and corticosteroids in paediatric Crohn's disease.

BACKGROUND: Comparative data on the therapeutic efficacy of different enteral nutrition formulas and corticosteroids to obtain clinical remission and to induce mucosal healing influencing long-term disease course in paediatric Crohn's disease are still scarce. AIMS: To investigate the efficacy of nutritional therapy using three different formulas versus corticosteroids to achieve clinical remission as well as to induce intestinal mucosal healing in active Crohn's disease children. Duration of remission and effect on growth recovery were also assessed. PATIENTS AND METHODS: Clinical, laboratory, endoscopic and histological data of all new diagnosed active Crohn's disease paediatric cases were retrospectively recorded and reviewed. Thirty-seven children (median age 12.1 years) received nutritional therapy (12 polymeric; 13 semi-elemental; 12 elemental diet) and 10 subjects (median age 12.4 years) received corticosteroids. RESULTS: Similar clinical remission rate were observed after 8 weeks of treatment: 86.5% children receiving nutritional therapy versus 90% treated with corticosteroids. Improvement in mucosal inflammation occurred in 26 out of 37 (64.8%) patients on nutritional therapy and in 4 out of 10 (40%) children on steroids (p < 0.05). Finally, seven subjects on nutritional therapy and none on corticosteroids achieved complete mucosal healing (p < 0.005) at the end of the treatment. Nutritional therapy was more effective than corticosteroids in improving nutritional status and linear growth recovery. Compared to corticosteroids, the duration of clinical remission was longer in the nutritional therapy groups without differences among the three different formulas. CONCLUSIONS: In children with active Crohn's disease, nutritional therapy is more effective than corticosteroids to improve intestinal inflammation and to maintain a more sustained clinical remission.

Chronic intestinal inflammation and seronegative spondyloarthropathy in children.

BACKGROUND: Spondyloarthropathy in adults has been shown to be associated with either clinical or subclinical intestinal inflammation, however this association has rarely been described in children. AIM: To report paediatric patients primarily referred to a paediatric gastroenterology centre for suspected inflammatory bowel disease and found to be affected by a seronegative spondyloarthropathy. Intestinal inflammatory lesions and rheumatological features have been described in them. SUBJECTS: During a 18-month period, 129 children were referred because of symptoms and signs suggesting an inflammatory bowel disease; 31 of them (range age: 5-17 years) were selected because they also had signs of axial and/or peripheral arthropathy and form the basis of our study. METHODS: The investigated patients underwent ileo-colonoscopy with biopsy and rheumatological assessment that also included X-ray and magnetic resonance imaging of the sacroiliac joints. RESULTS: Only seven children had a classical inflammatory bowel disease (four had ulcerative colitis, three had Crohn's disease), 12 had an indeterminate colitis, 12 a lymphoid nodular hyperplasia of the distal ileum as main feature. In the latter two groups, endoscopy and histology revealed an intestinal inflammation of chronic type distinct from the classical pattern found in inflammatory bowel disease. All were HLA B27 negative and fulfilled the European Spondyloarthropathy Study Group criteria for spondyloarthropathy (except five children classified as undifferentiated spondyloarthropathy). CONCLUSIONS: In a group of children primarily investigated for suspected inflammatory bowel disease and also presenting a seronegative spondyloarthropathy we have described both intestinal and rheumatological features. The majority of them exhibited either an indeterminate colitis or a lymphoid nodular hyperplasia of the distal ileum as main feature. These patients may be a population at risk of developing a full inflammatory bowel disease phenotype.

Infliximab heals intestinal inflammatory lesions and restores growth in children with Crohn's disease.

BACKGROUND: Infliximab has recently emerged as an efficacious agent for patients with severe Crohn's disease. There are only few studies on the use of infliximab in children with Crohn's disease: most of them are retrospective and deal only with the clinical response to the drug. AIM: We aimed at assessing the efficacy of infliximab in children and adolescents with severe Crohn's disease recruited consecutively and followed up prospectively at a single centre. Clinical response, intestinal inflammation and growth pattern were evaluated. PATIENTS: Eighteen patients entered into the trial (median age: 13 years, range: 6-18). They were referred because of severe symptoms with unsatisfactory response to conventional drugs. METHODS: All patients received a baseline schedule of three intravenous infusions of infliximab (0, 2 and 6 weeks), 5 mg/kg. Paediatric Crohn's Disease Activity Index, nutritional and activity serum variables, and ileocolonoscopy (with histology) were evaluated before and 8 weeks after beginning the therapy. All patients had long-term administration of azathioprine (2 mg/kg per day). After the baseline schedule, eight patients had a retreatment infusion of infliximab (5 mg/kg) every 8 weeks. Weight and height Z scores were measured before starting the baseline infusion programme and after 6 months. RESULTS: After 8 weeks of therapy, there was a dramatic improvement in Paediatric Crohn's Disease Activity Index, in nutritional and activity blood parameters, as well as in endoscopic and histological scores; 10 patients had a clinical remission (Paediatric Crohn's Disease Activity Index < or = 10), 12 patients had an inflammatory remission (decrease in both endoscopic and histological scores for > or = 50% as compared to baseline values). In all patients corticosteroids were stopped within 4 weeks after beginning infliximab therapy. After 6 months of therapy, Paediatric Crohn's Disease Activity Index was markedly lower than the pre-treatment value; however, it was significantly lower in patients on retreatment than in those who received only three infusions of infliximab. Furthermore, a significant increase in both weight and height Z scores was observed 6 months after beginning of the baseline infusion programme. Moreover, weight and height gain was significantly higher in patients on retreatment rather than in those treated only with three baseline infusions of infliximab. Mild infusion reactions controlled by slowing infusion rate were observed in four patients. No delayed hypersensitivity-like reactions were seen. CONCLUSIONS: In children with severe Crohn's disease, infliximab is a safe and valuable treatment in inducing remission, in healing inflammatory lesions of the gut, as documented by endoscopy and histology, and in promoting growth. Retreatment infusions of infliximab may be suggested in childhood-onset Crohn's disease to maintain remission and reverse growth failure.

Contrast enhanced magnetic resonance imaging of the terminal ileum in children with Crohn's disease.

BACKGROUND AND AIMS: Recently, magnetic resonance imaging (MRI) has been introduced in the diagnosis of patients with inflammatory bowel disease (IBD). However, it is still rarely reported in paediatric IBD. We studied the diagnostic value of gadolinium enhanced MRI in revealing inflammation of the distal ileum in children with Crohn's disease (CD) and in differentiating them from patients with other inflammatory diseases of the gut. MRI was performed using a polyethylene glycol (PEG) solution as oral contrast agent to distend the small bowel (CE-PEG-MRI). SUBJECTS AND METHODS: Seventy five consecutive patients (median age 13.6 years, range 8-17) with suspected CD underwent ileocolonoscopy with biopsy and CE-PEG-MRI. CD activity was measured by the paediatric Crohn's disease activity index (PCDAI). CE-PEG-MRI was evaluated with an overall score calculated, taking into account both wall thickness and contrast enhancement. RESULTS: Active CD with distal ileitis was diagnosed in 26 cases, active ulcerative colitis (UC) in 18, and spondyloarthropathy and indeterminate ileocolitis in 11; 20 children served as controls. In all CD patients, CE-PEG-MRI revealed a marked ileal involvement with increased wall thickness and parietal contrast enhancement and showed a high concordance with endoscopy and histology, whereas the test was negative in all controls. Of the 18 UC patients, CE-PEG-MRI was negative in 15 and showed a mild parietal contrast enhancement of the terminal ileum in only three of seven patients with backwash ileitis. Among the group of spondyloarthropathy patients, six had mucosal erosions and five mild superficial ileitis: CE-PEG-MRI was negative in four and revealed only mild parietal contrast enhancement of the ileal wall in seven. CE-PEG-MRI did not show an increase in wall thickness of the distal ileum in any of the UC or spondyloarthropathy patients. The sensitivity and specificity of CE-PEG-MRI related to the presence of erosive ileitis, as documented by endoscopy, were 84% and 100%, respectively. In addition, the test correlated markedly with endoscopy and histology in the entire population (r=0.94; r=0.95, respectively) as well as with the PCDAI in CD patients (r=0.91). CONCLUSIONS: In children with active CD, CE-PEG-MRI is a very sensitive and specific test for the detection of distal ileitis and for differentiation from other inflammatory diseases of the gut. The test could also be useful for the firstline diagnostic approach in children with suspected CD. The high correlation of CE-PEG-MRI with ileal endoscopy and histology as well as with PCDAI makes this test of great interest for future studies as a tool for monitoring the clinical course and the effect of therapy in CD patients.