Mark Furman

Joint BSPGHAN and Coeliac UK guidelines for the diagnosis and management of coeliac disease in children

The revised BSPGHAN guidelines for the diagnosis and management of coeliac disease represent an important shift in diagnostic strategy, aimed at simplifying and shortening the diagnostic process in selected cases. Guidance is given concerning the indications for testing for coeliac disease, which is still significantly underdiagnosed in the UK. While screening data suggest a likely incidence of 1 in 100 persons, only 10%–20% of this figure is currently being diagnosed.The BSPGHAN guidelines follow the new ESPGHAN guidelines in overall diagnostic strategy, while providing more didactic stratagems, which should be of assistance for paediatricians in specialties other than gastroenterology.

Wireless capsule endoscopy in children: a study to assess diagnostic yield in small bowel disease in paediatric patients.

Background and Aim:Small bowel disease in the paediatric population is varied and to date has relied on indirect l modalities such as small bowel follow-through with attendant radiation exposure. Wireless capsule endoscopy (WCE) has the potential to provide a safer and more effective means of investigating the paediatric small bowel. The aim of our study was to prospectively assess the diagnostic yield of WCE compared with standard investigation in children with suspected small bowel disease. Methods:Twenty-eight consecutive patients, median age 12.5 y (range, 9.4–15.9) with suspected small bowel disease were investigated with WCE. This included 16 patients with suspected small bowel Crohn disease (CD) (10 newly diagnosed; 6 known cases), 6 with obscure or occult gastrointestinal bleeding (GIB), 3 with Peutz-Jegher polyposis (PJP), 2 with protein-losing enteropathy and 1 with recurrent abdominal pain. All of the patients had preceding upper gastrointestinal endoscopy (OGD) and ileocolonoscopy, and 24 had a barium meal and follow-through (BMFT). Images were downloaded and analysed and results compared with the endoscopic and radiological findings. Results:Three patients were unable to swallow the capsule (1 CD, 1 PJP and 1 GIB). Two of these patients (1 GIB, 1 PJP) had the capsule placed in the stomach endoscopically and completed the WCE uneventfully thereafter. In 3 patients (CD group) the capsule remained in the stomach and/or proximal duodenum and no small bowel images were obtained. Hence, 24 patients had successful completion of the WCE through the small bowel, 23 of whom had clinically relevant findings identified. In all patients with CD who had successful WCE studies (12/16), small bowel disease was identified (11/12 active disease, 1/12 chronic disease). A possible small bowel bleeding source was identified in all 6 patients with GIB. Two patients with GIB also underwent push enteroscopy and 1 of these had a bleeding source identified. The 2 patients with protein-losing enteropathy had extensive patchy lymphangiectasia of the jejunum and ileum, not detected at OGD. The patient with abdominal pain had an intussusception of the upper jejunum. The 2 PJP patients had small bowel polyps identified, which were not detected at BMFT. WCE was more sensitive for small bowel pathology than both BMFT (19 vs 5; 26% sensitivity compared with WCE) and endoscopic investigations (23 vs 10; 43.4% sensitivity compared with WCE). Two patients with CD had delayed capsule transit. Conclusions:WCE led to a positive alteration in management in 18/24 (75%) of patients whose small bowel was examined by WCE and in 18/28 (64.3%) who were admitted to the study. WCE was safe, well tolerated, and more sensitive than radiological and standard endoscopic modalities in the detection of small bowel CD distribution, GIB source, and presence of polyps in children.

Omeprazole for gastroesophageal reflux disease in the first 2 years of life : A dose-finding study with dual-channel pH monitoring

Background and Aim: Gastroesophageal reflux occurs in the majority of infants, with severity ranging from asymptomatic to severe esophagitis and failure to thrive. Omeprazole is recognized as a safe and effective treatment of gastroesophageal reflux in older children, at an initial dosage of 0.7 mg · kg−1 · day−1. To our knowledge, no dose-finding studies have been carried out in children under 2 years of age. The aim of the present study was to prospectively determine the dosage of omeprazole required to treat symptomatic gastroesophageal reflux in children younger than 2 years. Patients and Methods: Children under 2 years with clinical suspicion of gastroesophageal reflux underwent 24-hour dual-channel intraesophageal/gastric pH monitoring. A reflux index above 10% in children under 1 year and above 6% in children older than 1 year was deemed significant. Treatment with omeprazole at an initial dosage of 0.7 mg · kg−1 · day−1 (in 2 divided doses) was followed by dual-channel pH study after 14 days. The dosage was increased in increments of 0.7 mg · kg−1 · day−1, and pH studies were repeated until the gastroesophageal reflux was controlled. Results: Ten children (5 male, 5 female), mean age 7.75 months (range, 1.25–20 months), were investigated. The initial median reflux index was 18.5% (range, 6.5%–56.3%). Follow-up median reflux index was improved at 1.6% (0.1%–8.1%) (P < 0.05). The median dosage required was 1.05 mg · kg−1 · day−1. Four children required 1.4 mg · kg−1 · day−1, and 1 required 2.8 mg · kg−1 · day−1. Corrected reflux index improved from 34.8% (16.8%–90.8%) to 20.1% (0.4%–100%) but did not achieve statistical significance. There were no serious complications or side effects. Conclusions: Omeprazole is an effective treatment for gastroesophageal reflux in children younger than 2 years. The majority respond to a dosage of 0.7 mg · kg−1 · day−1, but increased dosages up to 2.8 mg · kg−1 · day−1 may be required.

Enterotoxin-producing staphylococci cause intestinal inflammation by a combination of direct epithelial cytopathy and superantigen-mediated T-cell activation

Background: Enterotoxin‐producing Staphylococcus aureus may cause severe inflammatory intestinal disease, particularly in infants or immunodeficient or elderly patients. They are also recognized to be associated with sudden infant death syndrome. Little is known, however, about mucosal responses to staphylococci. Methods: The mucosal lesion in three infants with staphylococcal enterocolitis was assessed by immunohistochemistry and electron microscopy. The organisms underwent extensive molecular analysis. Their toxins were assessed for capacity to induce T‐cell activation and host mucosal responses examined by in vitro organ culture. Epithelial responses were studied by coculture with HEp‐2 and Caco‐2 cells. Results: Intestinal biopsies from the patients showed marked epithelial damage with mucosal inflammation. The three staphylococci, representing two distinct clones, were methicillin‐sensitive, producing SEG/I enterotoxins and Rho‐inactivating EDIN toxins. Their enterotoxins potently activated T cells, but only whole organisms could induce in vitro enteropathy, characterized by remarkable epithelial desquamation uninhibited by tacrolimus. EDIN‐producing staphylococci, but not their supernatants, induced striking cytopathy in HEp‐2 epithelial cells but not in Caco‐2 cells. Although HEp‐2 and Caco‐2 cells produced similar IL‐8, CCL20, and cathelicidin LL37 responses upon bacterial exposure, only Caco‐2 cells expressed mRNA for the &bgr;‐defensins HBD2 and HBD3, while HEp‐2 cells were unable to do so. Conclusions: Staphylococci induce enterocolitis by a combination of direct enterocyte cytopathy mediated by EDIN toxins, disrupting the epithelial barrier, and enterotoxin superantigen‐induced mucosal T‐cell activation. Gut epithelial production of &bgr;‐defensins may contribute to host defense against invasive staphylococcal disease. (Inflamm Bowel Dis 2011;)

Paneth cell metaplasia in newly diagnosed inflammatory bowel disease in children

BackgroundPaneth cell metaplasia (PCM) is well described in adults but little is known about the distribution of colonic Paneth cells and the occurrence of PCM in a paediatric population. The aim of this study is to determine whether Paneth cell hyperplasia or metaplasia characteristically occurs in the colons of children with newly diagnosed idiopathic inflammatory bowel disease (IBD).MethodsWe retrospectively reviewed colonic series from 28 new diagnoses of paediatric IBD at a tertiary referral centre, and from a further 14 children with IBD-like symptoms whose colonic biopsies and ancillary investigations were normal. Paneth cells were counted at 6 anatomical sites in the colon, and at each site acute and chronic inflammation were assessed semi-quantitatively and the presence or absence of crypt architectural distortion and eosinophilia was documented.ResultsIn control, ulcerative colitis (UC) and Crohn’s disease (CD) groups there was a gradient of decreasing Paneth cell numbers from caecum to rectum. Paneth cells were not seen in the distal colon in the control group, but they were present there in 11 of 13 patients with ulcerative colitis and 14 of 15 with Crohn’s disease. Only patients with IBD showed Paneth cell hyperplasia, assessed as more than 10 Paneth cells per 10 well-oriented crypts at any site. There was a statistically significant increase in Paneth cells in the caecum, ascending, transverse and descending colon in UC and in the ascending, transverse, descending and sigmoid colon in CD compared with controls. There was no significant difference between UC and CD. There was no correlation between the site of PCM and acute or chronic inflammation, crypt distortion or eosinophilia.ConclusionPaneth cells are found in the proximal but not the distal colon in otherwise normal paediatric colonic series. A high proportion of UC and CD patients show PCM in the distal colon. This is present early in the disease and does not correlate with histological features of chronicity.

Management of Crohn's disease

Crohns disease (CD) is rapidly increasing in children so an up to date knowledge of diagnosis, investigation and management is essential. Exclusive enteral nutrition is the first line treatment for active disease. The vast majority of children will need immunosuppressant treatment and around 20% will need treatment with biologics. Recent guidelines have helped make best use of available therapies.

Standard versus rapid food reintroduction after exclusive enteral nutritional therapy in paediatric Crohn’s disease

Background In paediatric Crohn’s disease (PCD), 6–8 weeks of exclusive enteral nutrition (EEN) is effective in 60–80% cases. EEN is followed by gradual food reintroduction over variable (1–5 weeks) periods. Currently, there is no recommended duration or method for food reintroduction. The rationale for slow reintroduction is unclear and may be because of concerns about food intolerance or to maintain longer remission. Aims The aims of this study were as follows: to compare relapse rates following standard and rapid reintroduction of food after EEN in PCD and to determine the duration of maintained remission in two groups of PCD patients. Materials and methods Two groups with PCD were compared: group A received standard food reintroduction over 5 weeks and group B received rapid reintroduction over 3 days. Data were collected over two consecutive time periods: group A (2005–2009) and group B (2009–2011). Only patients with a new diagnosis of PCD were included. Those with strictures and those on steroids or biologicals during EEN were excluded. The minimum duration of follow-up was 1 year. Results Group A included 20 patients and group B included 19 patients. In these groups, EEN led to clinical remission in 80% of the patients in group A and in 76% of the patients in group B. At 6 months, one-third of the patients from each group had developed relapse and a year after EEN, 50% of the patients in group A and 47% of the patients in group B developed relapse. Time to first relapse was 188 days (group A) and 136 days (group B). None of these results were statistically significant. Conclusion In PCD, rapid food reintroduction following 6-week EEN is safe and equally effective as longer food reintroduction. We propose that a rapid food reintroduction schedule be recommended as the most tolerable approach for food reintroduction. Relapse rate and duration of remission are uninfluenced by the type of food reintroduction.

Oesophagitis dissecans in a child with vomiting.

p JP Oesophagitis dissecans superficialis (ODS), referred to as ‘‘sloughing oesophagitis,’’ is a rare finding of unknown aetiology and unclear significance. Some cases have been vomited tubular casts of oesophageal mucosa (1), but often ODS is an unsuspected finding. The endoscopist notices whitish strips of peeling oesophageal mucosa, similar to those seen in eosinophilic oesophagitis. Histology shows intraepithelial splitting of squamous epithelium above the basal layer, typically with no or minimal inflammation (2). Superficial fragments may have fungal or bacterial colonies (2). Multiple small bullae and neutrophil microabscesses involving the middle layers of the epithelium have been described (2). Bullous skin disorders and bisphosphonate therapy are associated with ODS; however, most cases remain unexplained (2–4).

A New Look at Familial Risk of Inflammatory Bowel Disease in the Ashkenazi Jewish Population

Background and AimsThe inflammatory bowel diseases (IBD) are particularly common among the Ashkenazi Jewish (AJ) population. Population-specific estimates of familial risk are important for counseling; however, relatively small cohorts of AJ IBD patients have been analyzed for familial risk to date. This study aimed to recruit a new cohort of AJ IBD patients, mainly from the UK, to determine the familial occurrence of disease.MethodsA total of 864 AJ IBD patients were recruited through advertisements, hospital clinics, and primary care. Participants were interviewed about their Jewish ancestry, disease phenotype, age of diagnosis, and family history of disease. Case notes were reviewed.ResultsThe 864 probands comprised 506 sporadic and 358 familial cases, the latter with a total of 625 affected relatives. Of the UK cases, 40% had a positive family history with 25% having at least one affected first-degree relative. These percentages were lower among those recruited through hospital clinics and primary care (33% for all relatives and 22% among first-degree relatives). Examining all probands, the relative risk of IBD for offspring, siblings, and parents was 10.5, 7.4, and 4, respectively. Age of diagnosis was significantly lower in familial versus sporadic patients with Crohn’s disease.ConclusionsThis study reports familial risk estimates for a significant proportion of the AJ IBD population in the UK. The high rate of a positive family history in this cohort may reflect the greater genetic burden for IBD among AJs. These data are of value in predicting the likelihood of future recurrence of IBD in AJ families.

Improved Medical Treatment and Surgical Surveillance of Children and Adolescents with Ulcerative Colitis in the United Kingdom.

Background Pediatric ulcerative colitis (UC) presents at an earlier age and increasing prevalence. Our aim was to examine morbidity, steroid sparing strategies, and surgical outcome in children with active UC. Methods A national prospective audit was conducted for the inpatient period of all children with UC for medical or surgical treatment in the United Kingdom (UK) over 1 year. Thirty-two participating centers recruited 224 children in 298 admissions, comparisons over 6 years were made with previous audits. Results Over 6 years, recording of Paediatric Ulcerative Colitis Activity Index (PUCAI) score (median 65)(23% to 55%, P < 0.001), guidelines for acute severe colitis (43% to 77%, P < 0.04), and ileal pouch surgery registration (4% to 56%, P < 0.001) have increased. Corticosteroids were given in 183/298 episodes (61%) with 61/183 (33%) not responding and requiring second line therapy or surgery. Of those treated with anti-TNFalpha (16/61, 26%), 3/16 (18.8%) failed to respond and required colectomy. Prescription of rescue therapy (26% to 49%, P = 0.04) and proportion of anti-TNFalpha (20% to 53%, P = 0.03) had increased, colectomy rate (23.7% to 15%) was not significantly reduced (P = 0.5). Subtotal colectomy was the most common surgery performed (n = 40), and surgical complications from all procedures occurred in 33%. In 215/224 (96%) iron deficiency anemia was detected and in 51% treated, orally (50.2%) or intravenously (49.8%). Conclusions A third of children were not responsive to steroids, and a quarter of these were treated with anti-TNFalpha. Colectomy was required in 41/298 (13.7%) of all admissions. Our national audit program indicates effectiveness of actions taken to reduce steroid dependency, surgery, and iron deficiency. 10.1093/ibd/izy042_video1izy042.video15769503407001.