PP13 ELECTROCARDIOGRAPHIC STUDY OF COELIAC DISEASE IN CHILDREN AND ADOLESCENTS

PP13 ELECTROCARDIOGRAPHIC STUDY OF COELIAC DISEASE IN CHILDREN AND ADOLESCENTS

S208 Abstracts of XVI National Congress of SIGENP / Digestive and Liver Disease 41S (2009), S199–S239 and 60 adults (mean age at diagnosis 35.9±12.6...

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Abstracts of XVI National Congress of SIGENP / Digestive and Liver Disease 41S (2009), S199–S239

and 60 adults (mean age at diagnosis 35.9±12.6 years [range 16-78 years]). All patients fulfilled the ESPGHAN or NASPGHAN criteria for the diagnosis of CD. High-resolution class II HLA genotyping was performed. The subjects were divided into the 5 risk groups according to their genotype. To analyze the correlation between genotypic groups and grade of histological lesions we used a χ2 test. Results: The results of relationship (Table 1) between genotypic groups and histological findings was statistically significant (p=0.0002). In particular the subjects of the G1 and G2 groups had intestinal lesions with more severe atrophy. Moreover all the 5 subjects of the study that encoded DR7-DRx genotype were included among the 6 patients of the G5 with minimal or no intestinal damage. Conclusions: Our results demonstrate a correlation between genotype and histological phenotype in CD. Therefore the finding of high risk genotypes G1 and G2 in patients studied for CD with positive serological markers could be an alternative to intestinal biopsy for the formalization of the diagnosis. Thus would allow for an easier and less invasive diagnostic process. Furthermore, in patients with DR7-DRx genotype (G5), which is associated to minimal lesions, the genetic threshold of developing CD is low and so these patients could undergo a personalized diet not strictly gluten-free but with low quantities of it. Table 1. Correlation between genotypic groups and histological findings

stage III, and 7 with rectal bleeding) and 20 healthy neonates as control matched for age, sex, and gestational age. Stool samples were collected and immediately stored at -80°C before ELISA measurement (ß-Defensin 2 ELISA Kit® , Immundiagnostik, Bensheim, Germany). Statistical analyses were based on Wilkoxon or Sign rank tests and correlation were analysed using the non parametric Spearman test. Results: HBD2 was reproducibly detectable in all stool samples. In full term newborns, faecal HBD2 decreased statistically from day 3 to day 7 (227 ng/g; 14-440 vs 117 ng/g; 30-470; p=0.01) then moderately decreased until day 30 (84 ng/g; 10-500). In contrast, healthy preterms exhibited stable levels between days 15 and 60 (82ng/g; 30-154 and 85ng/g; 26-390, respectively). No correlation with gestational age or mode of feeding was detected. No difference in HBD2 was observed between full term and preterm neonates at either days 12-15 or 30. Faecal HBD2 increased significantly (p=0.04) in preterm neonates with NEC. Indeed, HBD2 levels increased dramatically during Bell’s stage NEC III, median 412 ng/g (range 92-1271) vs 49 ng/g (range 2-1178) in patients with bleeding and 56 ng/g (range 31-164) in controls. Discussion/conclusion: This pilot study shows for the first time the quantification of faecal HBD2 in neonates, providing normal reference values. Comparison with adult values (31±15.4 ng/g), suggests local inflammation in the neonatal period, likely due to bacterial and food antigens. Up-regulation seems to occur during intestinal suffering.

Genotype Marsh 0 Marsh 1 Marsh 2 Marsh 3a Marsh 3b Marsh 3c Total group G1 G2 G3 G4 G5

N % N % N % N % N %

– – – – 1 2.7 – – 5 35.7

– – 1 8.3 3 8.1 – – 1 7.1

1 3.2 – – 2 5.4 – – – –

4 12.9 1 8.3 14 37.8 1 33.3 2 14.3

11 35.5 8 66.7 13 35.1 2 66.7 3 21.4

15 48.4 2 16.7 4 10.8 – – 3 21.4

31 100 12 100 37 100 3 100 14 100

PP13 ELECTROCARDIOGRAPHIC STUDY OF COELIAC DISEASE IN CHILDREN AND ADOLESCENTS M. Montuori a , P. Versacci a , A. Turchetti a , R.P.L. Luparia a , R. Nenna a , A. Torre b , M. Mennini a , L. Petrarca a , S. Anaclerio a , M. Bonamico a a Departments b CNR-INMM,

References [1] Bourgey M, Calcagno G, Tinto N. HLA related genetic risk for coeliac disease. Gut 2007;56(8):1054-9.

PP12 QUANTIFICATION OF FAECAL ß-DEFENSIN 2 LEVELS IN NEONATES: UP-REGULATION DURING DIGESTIVE EVENTS? M.E. Baldassarre a , F. Campeotto b , N. Kapel c , L. Amati d , M. Fanelli e , A. Laneve a , A. Filannino a , M.R. Falcone a , N. Laforgia a a Dipartimento di Ginecologia, Ostetricia e Neonatologia, U.O di Neonatologia e T.I.N., Università di Bari, Italy; b Néonatologie et Gastroentérologie Pédiatrique, APHP, Groupe Hospitalier Cochin-Saint Vincent de Paul, Université Paris Descartes, Paris, France; c Coprologie fonctionnelle, APHP, Groupe hospitalier Pitié-Salpêtrière, Paris, France; d Ospedale IRCCS "De Bellis", Castellana Grotte, Italy; e Dipartimento di Medicina Preventiva e Salute Pubblica, Università di Bari, Italy

Aim Newborns display high intestinal permeability and a naive adaptive immune system, but infections are rare, indicating strong innate defence mechanisms. We measured faecal ß-defensin 2 (HBD2), an inducible endogenous antibiotic peptide produced by intestinal epithelial cells, in healthy full term and preterm neonates and in preterm neonates with intestinal symptoms. Patients and methods: A first study enrolled 30 full terms (mean gestational age 39 weeks, range: 36-41) and 20 preterms (30 weeks, 25-33). Faecal samples were collected at day 3, 7 12 and 30 for full term neonates and at days 15, 30 and 60 for preterms. A second study enrolled 10 neonates with intestinal distress (3 with NEC, Bell’s

of Paediatrics, “Sapienza” University of Rome, Italy; Italy

Objective: Several diseases may be associated with coeliac disease (CD) such as osteoporosis, dermatitis herpetiforme, chronic hepatitis, insulin-dependent diabetes and autoimmune thyroiditis. In adult patients idiopathic dilated cardiomiopathy myocarditis and prolonged QT interval have been described. However, up to now, no study has been performed in order to evaluate heart abnormalities after a gluten free diet (GFD). The aim of this study was to perform an electrocardiographic study in a series of CD children and adolescents at CD diagnosis on a gluten-containing diet. Methods: We studied 60 CD children and adolescent (24 males, aged from 6-17 years), collected in the Paediatric Department of “Sapienza” University of Rome. Coeliac disease was diagnosed according to the North American Society for Pediatric Gastroenterology Hepatology and Nutrition criteria. Before the endoscopy, all patients underwent ECG. All electrocardiograms were reviewed by the same observer and QT interval, as corrected for heart rate (QTc), was calculated according to Bazzett’s formula and compared with the generally accepted upper normal limit for QTc (440 ms). No patient had a history of taking drugs known to induce QT prolongation. Patients with abnormalities were re-tested for ECG after 12 months of GFD. Results: QTc interval was significantly more prolonged in 3 CD females out of 60 children (5%), showing normal electrolytes concentration. After 12 months of GFD, abnormal QTc interval was found normalized in all 3 patients. No other electrocardiographic abnormalities were found in children investigated. Conclusions: Our results demonstrate that not only in adults but also in children a significant QTc prolongation could be found, and it reverses on a GFD. Although the QTc abnormality was mild, it should not be overlooked since the long QTc syndrome is associated with an increased risk of ventricular arrhythmias, syncope and sudden heart. This risk should be taken into account in subjects who undergo narcosis for endoscopy. The exact mechanism of QTc prolongation in CD patients

Abstracts of XVI National Congress of SIGENP / Digestive and Liver Disease 41S (2009), S199–S239 is still unclear. Our study shows that electrolytes imbalance is not responsible of ECG abnormalities. A possible role might be played by nutritional deficiencies or autoimmune processes involved in CD.

PP14 CYCLIC VOMITING SYNDROME (CVS): TEN-YEAR EXPERIENCE IN A REFERRAL CENTER S. Martinazzi, F. Gottardi, C. Monfredini, A. Ravelli University Department of Pediatrics, Children’s Hospital, Brescia, Italy Introduction: CVS is a functional GI disorder characterized by recurrent attacks of unremitting nausea and vomiting separated by periods of well-being. Aim: To describe the features of CVS in a population of pediatric patients referred to our center, thereby helping gastroenterologists to recognize this condition. Methods: Retrospective analysis of all our patients diagnosed as having CVS according to Rome criteria between 1997 and 2008. Results: CVS was diagnosed in 91 patients. In all these patients, known gastrointestinal, neurological, urinary and metabolic abnormalities were excluded by appropriate investigation. F:M ratio was 1.3:1 and age of onset was 2-6 years in 34% and 6-10 years in 25%. Attacks occurred at 5:00-12:00 a.m. in 43% of patients. Vomiting was severe, with a mean 7.4 emeses/hour and 31 emeses/day, and was usually associated with nausea (74%) and profound lethargy (55%). Other GI symptoms such as abdominal pain (53%) and diarrhea (20%) were commonly reported, as were migraine-like symptoms such as headache (40%) and photophobia (27%). Most patients showed autonomic arousal, i.e. pallor (65%), hypersalivation (28%), fever (22%) and tachycardia (14%). Prodromic symptoms were reported by 80% of patients. On average, episodes lasted 40 hours, recurred 10 times per year and were separated by symptom-free intervals of 3.5 months. Triggers were identified in 45% of cases, as positive or negative stress (58%), intercurrent infection (29%), or menses (13%). 47% of patients had a positive family history of migraine, usually along the matrilineage. Erosive esophagitis was reported in 21% and Mallory-Weiss tear in 3.3% of patients. Diagnosis of CVS was made >3 years after the onset of symptoms in 53% of the patients, and after 1-3 years in 34% of them. Clinical improvement or long-term remission, respectively, were achieved using prophylactic drugs such as cyproheptadine (21 and 14 patients), pizotifen (15 and 5 patients) and amytriptiline (8 and 2 patients) without significant side effects. Conclusion: CVS mostly affects pre-school and school-age children, and a thorough clinical assessment is needed to rule out possible albeit uncommon underlying organic disorders. Although it has a rather severe and fairly distinctive pattern of occurrence, CVS is still largely unknown and the diagnosis is considerably delayed in most cases. An appropriate prophylactic therapy using anti-migraine drugs can achieve long-term remission or significant improvement in the majority of patients.

PP15 USEFULNESS OF DUODENAL CULTURES IN CELIAC DISEASE A. Famiani, D. Comito, A. Deak, V. Raffa, R. Gallizzi, P. Rossi, V. Ferrau’, C. Romano Pediatric Department, University of Messina, Italy Background: Diagnostic criteria for celiac disease (CD) are smallbowel biopsy and mucosal villous atrophy with crypt hyperplasia (Marsh 3). Serum determination of endomysal (EMA) and transglutaminase antibodies (tTG) has a very close association (98-100%) with intestinal damage. It has been described that 5% of CD patients can be

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negative for EMA and tTG. Specific CD autoantibodies against TG2 are deposited in the normal duodenal mucosa before they can be detected in circulation. Their deposition precedes the gluten-induced duodenal damage. Aim: To evaluate the sensibility and specificity of EMA detection in supernatant culture of biopsy specimens in first-grade relatives. Patients and Methods: The latter EMA assay was performed on specimens from 15 pts (age 28-38 yrs) who presented clinical symptoms suggestive for CD, high risk for class II HLA and negative for serology. The histological pattern was characterized by minimal infiltrative changes (Marsh I). The Group 2 was formed by 15 EMA negative pts who had undergone EGDS with duodenal biopsy. Two specimens of duodenal mucosa were cultured for 72 h at 37°C with a commercial reagent set (anti-Endomysium-biopsy, Eurospital, Italy). Culture supernatant was stored for determination of EMA with the same commercial reagent set used for serum EMA. Results: 10 (66%) Group 1 pts presented EMA in the supernatant culture of duodenal biopsy specimens respect to 1 patient only from Group 2 (p <0.05). Conclusions: EMA assay for cultured intestinal biopsy specimens can be an important diagnostic tool in suspected latent CD. Mild enteropaty is more frequent in first-degree relatives and negative serum EMA. Early gluten free diet can have a role in the prevention of intestinal lymphoma.

PP16 WIRELESS CAPSULE ENDOSCOPY (WCE) IS HELPFUL IN THE DIAGNOSTIC WORK-UP FOR PEDIATRIC INFLAMMATORY BOWEL DISEASE (IBD) PATIENTS V. Mancini a , G. Di Nardo a , A. Staiano c , G. Lombardi b , E. Miele c , S. Oliva a , N. Cavallari a , G. Bevivino a , F. Conte a , C. Alessandri a , S. Cucchiara a a Sapienza University of Rome, Pediatric Gastroenterology & Liver Unit, Rome; b Pescara Hospital, Pediatric Gastroenterology Unit, Pescara; c Federico II University of Naples, Pediatric Gastroenterology Unit, Naples

Aim: WCE has gained wide acceptance in gastrointestinal GI endoscopy by revealing lesions of the small bowel (SB) not seen with other imaging tools. The usefulness of WCE in the diagnostic work-up of pediatric IBD is rarely reported. We determined the diagnostic yield of WCE for children with IBD, either with a definite diagnosis, Crohn’s disease (CD), ulcerative colitis (UC), as well as for children with suspected or unclassified IBD (IBDU). Methods: Seventy patients, mean age (SD) 13.5 (4.37), recruited in 3 Italian Pediatric Gastroenterology Centres underwent PillCam SB2 WCE (Given Imaging Inc.) examination after an overnight fast and a mini-bowel preparation with not more than 1 L of PEG 4000 oral solution, administered in 200 ml increments every 10 minutes in the early morning of the examination. Indications included: 1) determination of SB involvement in 31 CD patients and in 18 UC patients; 2) work-up of suspected IBD (14 patients); 3) diagnostic definition in 7 patients with IBDU. WCE findings were classified as diagnostic (> 3 ulcerations, also in incomplete studies); suspicious (≤ 3 ulcerations or erosions); non specific or normal. Incomplete studies were defined as the capsule not reaching the cecum. All patients previously underwent upper and lower GI endoscopy and IBD was diagnosed according to widely agreed criteria (J Pediatr Gastroenterol Nutr 2007;44:653). Results: WCE disclosed typical SB lesions in 20 out of 31 CD patients (64.5%) and allowed to relate their abnormal clinical and biochemical features to the SB involvement. In 3/18 (16.6%) patients previously diagnosed as UC, typical ileal lesions of CD were detected and diagnosis was switch on CD, in the remaining 15 UC patients (83.3%) SB was unaffected or showed non specific findings and UC diagnosis was confirmed. Of the 14 patients with suspected IBD and in whom