András Tárnok

Incidence, Paris Classification, and Follow-up in a Nationwide Incident Cohort of Pediatric Patients With Inflammatory Bowel Disease

Objectives: The aim of the study was to evaluate the incidence, baseline disease characteristics, and disease location based on the Paris classification in pediatric inflammatory bowel disease (IBD) in the Hungarian nationwide inception cohort. In addition, 1-year follow-up with therapy was analyzed. Methods: From January 1, 2007 to December 31, 2009, newly diagnosed pediatric patients with IBD were prospectively registered. Twenty-seven pediatric gastroenterology centers participated in the data collection ensuring the data from the whole country. Newly diagnosed patients with IBD younger than 18 years were reported. Disease location was classified according to the Paris classification. Results: A total of 420 patients were identified. The incidence rate of pediatric IBD was 7.48/105 (95% confidence interval [CI] 6.34/105–8.83/105). The incidence for Crohn disease (CD) was 4.72/105 (95% CI 3.82–5.79), for ulcerative colitis (UC) 2.32/105 (95% CI 1.71–3.09), and for IBD-unclassified 0.45/105 (95% CI 0.22–0.84). Most common location in CD was L3 (58.7%); typical upper gastrointestinal abnormalities (ulcer, erosion and aphthous lesion) were observed in 29.9%. Extensive colitis in patients with UC (E4, proximal to hepatic flexure) was the most common disease phenotype (57%), whereas only 5% of children had proctitis. A total of 18.6% of patients had ever severe disease (S1). Frequency of azathioprine administration at diagnosis was 29.5% in patients with CD, and this rate increased to 54.6% (130/238) at 1-year follow-up. In UC, only 3.3% received azathioprine initially, and this rate elevated to 22.5% (25/111). Use of corticosteroid decreased from 50% to 15.3% in patients with UC. Rate of bowel resection in patients with CD during the first year of follow-up was 5%. Conclusions: The incidence of pediatric IBD in Hungary was among the higher range reported. This is the first large, nationwide incident cohort analyzed according to the Paris classification, which is a useful tool to determine the characteristic pediatric CD phenotype.

Diagnostic yield of upper endoscopy in paediatric patients with Crohn's disease and ulcerative colitis. Subanalysis of the HUPIR registry

BACKGROUND, AIMS According to Porto Criteria upper gastrointestinal (UGI) endoscopy is recommended in patients with suspected inflammatory bowel disease (IBD). Nevertheless, previous studies revealed frequent involvement of UGI tract even in patients with ulcerative colitis (UC). The aim of the present study was to determine the diagnostic role of esophagogastroduodenoscopy (EGD) and assess the prevalence and different aspects of UGI involvement in children registered in the Hungarian Pediatric IBD Registry (HUPIR) from 1st of January 2007 to 31th of December 2009. METHODS Twenty seven institutes provided prospective follow-up data about newly diagnosed IBD patients to HUPIR. The registry was based on detailed questionnaire (76 parameters) involving anamnestic data, laboratory findings, activity indexes, diagnostic procedures, endoscopic examinations (EGD and ileocolonoscopy), and histological data. Localization and phenotype of disease were based on the Montreal classification criteria. RESULTS During the 3-year period 420 children were diagnosed with IBD, 265 (63%) of them had Crohns disease (CD), 130 (31%) UC, and 25 (6%) IBD-unclassified (IBD-U). The mean age at diagnosis was 13.2 years (range: 1.2-18 years). EGD was performed in 237 patients (56%), in most cases in patients suffering from CD. Macroscopic lesions on EGD were noted in 64% of patients with CD and 40% of children with UC. Characteristic lesions for CD (ulcer, erosion, aphthous lesion, and granuloma) were noted in 31% of CD patients, however, EGD helped to establish the final diagnosis in 9% of CD patients (diagnostic yield, 9%). CONCLUSIONS There was a high frequency of UGI involvement in children with CD and UC. One third of CD patients showed significant lesions at upper endoscopy and one patient out of ten had real diagnostic help from EGD.

Gastrointestinal malformations, associated congenital abnormalities, and intrauterine growth.

Background In contrast with other malformations, congenital anomalies of the gastrointestinal tract have been scarcely investigated. Methods The prevalence of gastrointestinal malformations with special reference to associated disorders and intrauterine growth was retrospectively analyzed in the newborn infants admitted to the Neonatal Intensive Care Unit of the Department of Pediatrics, University of Pécs, Hungary, in the 14-year period between 1987 and 2000. Results Of 4,241 neonates with gastrointestinal malformations, 241 (5.68%) had a total of 304 malformations (excluding Hirschsprung disease). In 133 patients, the gastrointestinal anomalies were observed as one of multiple malformations; a specific syndrome or association was diagnosed in 36 cases. Skeletal disorders were the most frequently associated anomalies. Intrauterine growth retardation was found in a large number of patients with both isolated and multiple gastrointestinal malformations (38.9% and 30.8%, respectively). Conclusions Gastrointestinal malformations often are complicated by skeletal anomalies and intrauterine growth retardation. The association among these disorders requires further investigation. However, from a practical point of view, this association should be considered in treating affected patients.

Low n-3 long-chain polyunsaturated fatty acids in newly diagnosed celiac disease in children with preexisting type 1 diabetes mellitus.

Objective: Fat malabsorption can occur in celiac disease (CD) owing to villus atrophy and inflammation of small intestinal mucosa. Abnormal fatty acid (FA) status of intestinal mucosa in children with CD was reported earlier. Previously we found significantly reduced availability of n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) in children and young adults with type 1 diabetes mellitus (DM). The aim of this study was to investigate FAs in plasma lipid classes in children with newly diagnosed CD with or without preexisting DM. Methods: FA composition of plasma samples of children with untreated CD only (n = 20) and with preexisting DM (CDDM, n = 8) were compared with those of healthy controls (n = 21). Detailed analysis of phospholipid, triacylglycerol, and sterol ester FAs was performed by high-resolution capillary gas–liquid chromatography. Results: Significantly decreased docosapentaenoic (C22:5n-3), docosahexaenoic (C22:6n-3), n-3 polyunsaturated fatty acids (n-3 PUFA), and n-3 LCPUFA values were found in CDDM group compared with controls and patients with CD. When compared with healthy controls, no significant difference was found in plasma FAs of children with newly diagnosed CD only. Conclusions: Children with CDDM showed marked signs of reduced availability of n-3 PUFA and n-3 LCPUFA in circulating lipids. Although different tissues express membrane FAs differently, our present study suggests that CD on its own does not necessarily lead to detectable disturbances of essential FA metabolism in plasma and supports the concept that DM has significant impact on plasma FA composition in children.

Baseline characteristics and disease phenotype in inflammatory bowel disease

Objectives: Predicting short-term relapses and long-term prognosis is of utmost importance in paediatric inflammatory bowel disease (IBD). Our aim was to investigate the short-term disease outcome and medication during the first year in a paediatric incident cohort from Hungary. In addition, association laboratory markers and disease activity indices with short-term disease outcome and medication were analysed. Methods: From January 1, 2008 to December 31, 2010, demographic data and clinical characteristics of newly diagnosed paediatric patients with IBD <18 years of age were prospectively recorded. Results: A total of 420 patients were identified (Crohn disease [CD] 266 and ulcerative colitis [UC] 124). Initially, 48% (124/256) of the patients with CD had moderate-to-severe disease (Pediatric Crohns Disease Activity Index [PCDAI] >31), and this rate decreased to 2.1% at 1-year follow-up. Proportion of patients with UC with moderate-to-severe disease (Pediatric Ulcerative Colitis Activity Index >35) at diagnosis declined from 57.5% (69/120) to 6.8% at 1-year follow-up. Terminal ileal involvement correlated with higher initial C-reactive protein (CRP) (P = 0.021) and initial PCDAI (P = 0.026). In UC, elevated CRP (P = 0.002) was associated with disease extension. CRP and PCDAI at diagnosis were associated with the need for immunomodulators at 1 year in children with CD. Initial CRP was also associated with the need for immunomodulators in patients with UC at 1-year follow-up. Conclusions: At diagnosis, half of the patients with IBD had moderate-to-severe disease, and this rate decreased to <10% after 1 year. Initial CRP and PCDAI were related to the need for aggressive therapy in CD.

Objective analysis of centromere separation.

Centromere separation sequence and premature centromere division have gained increasing interest; however, inaccuracy and subjectivity in their investigation have often been criticized. We describe a simple computerized image analysis system that makes an objective and exact staging of centromere division possible.

Blount disease (tibia vara) in Bardet–Biedl syndrome

Bardet–Biedl syndrome [OMIM 209900] characterized by hypogenitalism, mental retardation, obesity, polydactyly, pigmentary retinopathy, and renal abnormalities was first described in 1922 [Biedl, 1922]. The association of the hepatic, renal, and cardiac abnormalities and skeletal deformities, such as hip dysplasia, brachydactyly, syndactyly, or short stature is well known. The genetic heterogeneity of the syndrome is well established; seven loci have been reported so far [Carmi et al., 1995; Bruford et al., 1997; Beales et al., 1999]. To our knowledge, only one case of tibia vara in a patient with Bardet–Biedl syndrome has been published [Motzkin et al., 1992]. We will document another. An 11-year-old roma boy was born at 39 weeks of gestation (birth weight 2,600 g, length 50 cm) by spontaneous vaginal delivery after an uneventful pregnancy. He was the first child of the parents who are not known to be consanguineous. There was no family history of hexadactyly, blindness, mental retardation, extreme obesity, malformation, stillbirth, or miscarriage. Postaxial hexadactyly of both feet and right hand were diagnosed at birth. Their surgical correction was carried out at the age of 17 months. At this time, Bardet– Biedl syndrome was suspected because of polydactyly, psychomotor delay, and retinal pigmentation. The child was lost for follow-up until the age of 10 years when he attended a special school because of moderate mental retardation. Bowing of the left leg was noticed by his parents at the age of 5 years. This deformity increased gradually during the next years and the patient developed pain in the medial side of the knee joint. This resulted in limping and impaired walking ability. On admission, at the age of 10 years, he was extremely obese with a body weight of 75.5 kg (BMI 35.1). Purple abdominal striae and patchy hypopigmentation of the skin were seen. His penis was 2.5 cm, his testicles were found to be hypoplastic too, 1 ml each. An extreme varus deformity of the left knee with the medial rotation of the leg, tenderness of the medial side of the knee joint, and a functional shortening of 4.5 cm with consequent limp were found (Fig. 1). Radiographs of the left knee and leg showed 40 degrees of varus angulation of the left tibia (Fig. 2). No other skeletal malformations were observed. Abdominal ultrasound showed several gallstones, but failed to find structural changes of the liver and kidneys. Electroretinography revealed pigmentary retinopathy. No hypertension could be demonstrated. Bone age was advanced (12.5 years). Oral glucose tolerance test showed impaired glucose tolerance. The patient underwent a valgization osteotomy of the left proximal tibia. The wedge removed from the lateral side was transferred into the medial part of the osteotomy. Two crossed K-wires were used for temporary fixation of the osteotomy. The leg was immobilized in a plaster cast for 12 weeks. Partial weight bearing was allowed from the 4th postoperative week. Postoperative radiographs showed that the varus deformity decreased

P-030: Triple increase in incidence of inflammatory bowel disease under 5 years in a 6 year follow-up based on a nationwide, prospective incidence cohort (HUPIR)

Introduction: The incidence of paediatric IBD (PIBD) has never been reported in New South Wales (NSW), Australia. We describe our experience in PIBD over 45 years at the Children’s Hospital at Westmead (CHW), the largest tertiary paediatric centre in NSW. Methods: Cases of PIBD from 1968 to 2013 were ascertained from lists kept prospectively by clinicians. Clinical notes were reviewed for demographic and clinical details. NSW periodic census data were used for the catchment population denominator in the assessment of incidence. We estimate that two thirds of the PIBD patients in NSW were managed at CHW based on published hospital activity data. Results: During the study period, 684 cases of IBD (CD 404, UC 238, IBD-U 42) were managed in CHW. Age of diagnosis range from 6 weeks old to 17 years old (mean 10.68, median 11.33). At diagnosis, 67% were older than 10 and 10% were younger than 5. Male to female ratio was 1.3:1. In the 1970s, 1980s, 1990s, 2000s, and 201