Elżbieta Krzesiek

Epidemiology of inflammatory bowel disease among children in Poland. A prospective, population-based, 2-year study, 2002-2004.

Background/Aims: The incidence of pediatric inflammatory bowel disease (IBD) in Western countries is on the rise. No prospective studies have been conducted on the epidemiology of pediatric IBD in Poland. The aim of the study was to define the characteristics of new pediatric IBD and assess the incidence of new IBD among children in Poland between 2002 and 2004. Methods: Patient records from 24 pediatric gastroenterology centers servicing the whole population of Poland were collected. IBD diagnosis was based on clinical, radiological, endoscopic and histological features. Results: There were 491 new IBD patients, representing an overall incidence of IBD of 2.7 cases/100,000 children/year. The incidence of Crohn’s disease (CD) was 0.6, ulcerative colitis (UC) 1.3, and indeterminate colitis (IC) 0.8. The age-related incidence of IBD was 1.8 in the 0- to 10-year-old age group, rising to 3.7 for the 11- to 18-year age group. Conclusions: The overall incidence of IBD (as well as CD, UC and IC) in Poland is lower than that in Western countries. The relative contribution of UC and IC to the overall IBD incidence is higher in Poland than in most Western countries. These findings may suggest a tendency towards under- or misdiagnosis.

Monotherapy with infliximab versus combination therapy in the maintenance of clinical remission in children with moderate to severe Crohn disease.

Objectives: The aim of the present study was to compare the efficacy and safety of 2 protocols of maintenance therapy with infliximab (IFX) and an immunomodulatory agent in pediatric patients with Crohn disease (CD): withdrawal of immunomodulators versus continuation of immunosuppressants. Methods: The present multicenter randomized open-label trial included 99 patients with CD (ages 14.5 ± 2.6 years) who were administered IFX (5 mg/kg body weight) along with an immunomodulatory agent (azathioprine 1.5–3 mg/kg body weight per day, methotrexate 10–25 mg/week). After 10 weeks of the induction therapy, 84 responders were centrally randomized into 1 of the following groups: group I (n = 45) in which IFX and an immunomodulatory agent were continued up to week 54 and group II (n = 39) in which the immunomodulatory agent was discontinued after 26 weeks. Results: The induction therapy was reflected by a significant decrease in Pediatric Crohns Disease Activity Index (PCDAI) and Simplified Endoscopic Activity Score for Crohns Disease (SES-CD) values. After the maintenance phase, the analyzed groups did not differ significantly in terms of the clinical response loss rates and final PCDAI and SES-CD scores. Furthermore, no significant intragroup differences were documented between mean PCDAI scores determined at the end of induction and maintenance phases. Intensification/modification of the treatment was required in 13 of 45 (29%) and 11 of 39 (28%) patients of groups I and II, respectively. A total of 9 serious adverse events were documented; none of the patients died during the trial. Conclusions: Twenty-six weeks likely represent the safe duration of combined IFX/immunomodulatory therapy in our sample of pediatric patients with CD.

Hepatic Vein Thrombosis as a Complication of Ulcerative Colitis in a 12-Year-Old Patient

More than a hundred various extraintestinal complications of ulcerative colitis and Crohn’s disease have been found and described so far [1, 2]. Vein thrombosis, which in most cases occurs in pelvic, pulmonary, cerebral, lower extremities, and portal and splenic veins, seems to be well recognized as coexisting with inflammatory bowel disease (IBD). In his necropsy studies of patients with IBD, Graef et al. [3] noted vein thrombosis in 39% of cases compared with 14% in a control group. Although vein thrombosis, especially visceral vein thrombosis, has been rather common in IBD, hepatic vein thrombosis (Budd–Chiari syndrome) in IBD is rare. Parker [4] performed necropsy on 164 hepatic vein thrombosis patients and only two of them were positive for the ulcerative colitis.

Genetic architecture differences between pediatric and adult-onset inflammatory bowel diseases in the Polish population.

Most inflammatory bowel diseases (IBDs) are classic complex disorders represented by common alleles. Here we aimed to define the genetic architecture of pediatric and adult-onset IBDs for the Polish population. A total of 1495 patients were recruited, including 761 patients with Crohn’s disease (CD; 424 pediatric), 734 patients with ulcerative colitis (UC; 390 pediatric), and 934 healthy controls. Allelotyping employed a pooled-DNA genome-wide association study (GWAS) and was validated by individual genotyping. Whole exome sequencing (WES) was performed on 44 IBD patients diagnosed before 6 years of age, 45 patients diagnosed after 40 years of age, and 18 healthy controls. Altogether, out of 88 selected SNPs, 31 SNPs were replicated for association with IBD. A novel BRD2 (rs1049526) association reached significance of P = 5.2 × 10−11 and odds ratio (OR) = 2.43. Twenty SNPs were shared between pediatric and adult patients; 1 and 7 were unique to adult-onset and pediatric-onset IBD, respectively. WES identified numerous rare and potentially deleterious variants in IBD-associated or innate immunity-associated genes. Deleterious alleles in both groups were over-represented among rare variants in affected children. Our GWAS revealed differences in the polygenic architecture of pediatric- and adult-onset IBD. A significant accumulation of rare and deleterious variants in affected children suggests a contribution by yet unexplained genetic components.

Immunogenicity of 13-Valent Pneumococcal Conjugate Vaccine in Pediatric Patients with Inflammatory Bowel Disease.

Background:There are only a few studies on immune response to pneumococcal vaccines in patients with inflammatory bowel disease (IBD); all of them assessed polysaccharide vaccines only. The aim of the study was to evaluate the immunogenicity and safety of 13-valent pneumococcal conjugate vaccine (PCV13) in IBD pediatric patients compared with healthy controls. Methods:This was a multicenter, prospective, and controlled study on children and adolescents aged 5 to 18 years with IBD with no history of pneumococcal immunization. The subjects for the study belonged to one of the following groups: patients with IBD on no immunosuppressive therapy (group A), those on tumor necrosis factor agents or immunomodulators (group B), and healthy controls (group C). The study population received 1 intramuscular injection of PCV13. The primary outcome measure was adequate vaccine response defined as postvaccination titer ≥0.35 &mgr;g/mL to all 13 serotypes. Geometric mean titers and geometric mean titer rises were measured for all serotypes. The evidence of local and systemic adverse effects for 5 days after the vaccine was registered. Results:A total of 178 subjects (122 patients and 56 controls) completed the study course. There was no significant difference in the rate of adequate vaccine response between patients with IBD and controls measured 4 to 8 weeks after vaccination (90.4% versus 96.5%, P = 0.5281). Children in group A had higher geometric mean titer rises than children in group B (P = 0.0369). There were no serious adverse events related to PCV13 during the study. Conclusions:PCV13 is both immunogenic and safe in pediatric patients with IBD.

Assessment of Magnetic Resonance Enterography in the Diagnosis of Small Bowel Diseases in Children with Crohn’s Disease

BACKGROUND In pediatric patients Crohns disease most commonly involves the colon and the ileocecal part of the intestine. MR enterography, a new method of small bowel imaging with magnetic resonance, has been introduced in the last decade. OBJECTIVES The aim of this study was to assess the usefulness of the MR enterography in the diagnosis of small bowel lesions in children with Crohns disease. MATERIAL AND METHODS The study included 37 children (18 girls and 19 boys) aged from 5.5 to 18 years (average age, 13.3), diagnosed with Crohns disease according to the Porto criteria. The disease duration ranged from 1 month to 12 years, on average 3 years. MR eterography was performed according to the Giles et al. protocol. The obtained results were compared with the location and the manifestation of the disease according to the Paris classification. RESULTS In 13 children (35.1%), the disease began prior to 10 years of age, and in the remaining 24 children (64.9%) between 10 and 17 years of age. The gastrointestinal endoscopy confirmed Crohns disease in the colon (45.9%) and in the colon and ileum (27.1%). An incomplete colonoscopy examination which did not reveal the location of the disease was conducted in 7 children (18.9%). A comparison of the location of Crohns disease with the location of lesions in the small bowel as indicated by MR enterography revealed that the most common changes can be found in the final part of ileum, in ileum, and in 4 children in jejunum. MR enterography demonstrated, that 16 children (43.2%) had inflammation, 7 children (18.9%) stenosis, and 14 children (37.8%) had no lesions at all. CONCLUSIONS MR enterography is a non-invasive and safe procedure well tolerated by children that allows the visualization of lesions in the small bowel in children with Crohns disease.

Demographic characteristics of children with early clinical manifestation of inflammatory bowel disease.

Introduction Inflammatory bowel disease (IBD), which includes Crohns disease (CD) and ulcerative colitis (UC), is a chronic condition of the colon and small intestine. The disease is common in young people (children and young adults), but it is rare in children younger than five years of age. Therefore, IBD developing during the first years of life (under the age of 5) is known as an early-onset IBD (EO-IBD), and it is considered to be a specific entity with a distinct phenotype. However, the available data on that issue are still insufficient. Aim To determine the characteristics and clinical course of children with early-onset IBD. Material and methods We performed a retrospective database analysis of 47 infants younger than 5 years old diagnosed with IBD. Patients demographic data, including age, sex, and age at disease onset, were collected in 6 paediatric hospitals in Poland. Disease location was established on the basis of the review of all endoscopic, colonoscopic, histopathological, and radiological records. All possible complications were reported, as well as any treatment and its efficacy. Since the diagnosis was established all patients have been on follow up. Results Among 47 children registered in the database, 23 (49%) had a diagnosis of CD, 16 (34%) had UC, and 8 (17%) had IC (indeterminate colitis). The mean age at diagnosis was 28.5 ±27.5 months; 57.4% were male. The most common location/type of disease was ileocolonic disease (L3). The most common complication of IBD was anaemia, found in 30 (63.8%) children. The observed course of the disease was either severe or moderate. In 4 children younger than 2 years old, surgery was performed. Conclusions Inflammatory bowel disease in children younger than 5 years old includes UC, CD, and a relatively high proportion of IC. In early-onset IBD severe and moderate course of the disease is usually observed. Disease manifestation in these patients is predominantly ileocolonic.

Deep Vein Thrombosis of the Left Lower Limb in a 12 Year-Old Female Child with Ulcerative Colitis - Case Report.

Summary Background Inflammatory bowel disease includes ulcerative colitis and Crohn’s disease. Case Report This case report presents a patient with ulcerative colitis, with thrombotic complication of the left common iliac vein that occurred at the age of 11, two years after diagnosis. After a year of anticoagulation and compression therapy, although exacerbations of underlying disease occurred in the first 6 months of treatment, there was no recurrence of deep venous thrombosis, partial recanalization within affected venous system has been achieved and the patient is remission of ulcerative colitis for the last six months. Conclusions In children, thromboembolic complications occur about 7 times less often than in adults, but increases in the case of hospitalized children. In children with IBD this complication can occur independently og disease activity even in patients with any other risk factors.