Correlation between biomarkers (calprotectin, seromucoid, metalloproteinase-3 and CRP) and clinical and endoscopic activity of ulcerative colitis in children.

PURPOSE: The aim of the study was to compare the clinical activity and inflammatory markers with the endoscopic activity of ulcerative colitis (UC) and mucosal healing. PATIENTS AND METHODS: The study included 50 children aged 2-18 years (27 girls, 23 boys) diagnosed with UC at various stages of the disease; 8 children were assessed twice. In 20 children, colonoscopy revealed pancolitis, in 24 - left-sided colitis, and in 6 - ulcerative proctitis. The clinical activity of UC was assessed according to the Pediatric Ulcerative Colitis Activity Index (PUCAI). Endoscopic index of the colon inflammation was assessed according to the Rachmilewitz scoring. We assessed the clinical activity of UC, the concentration of fecal calprotectin (FC), seromucoid, metalloproteinase-3 (MMP-3) and C-reactive protein (CRP). RESULTS: The study demonstrated significant decrease in the clinical activity, FC, seromucoid and MMP-3 in endoscopic remission. We found a strong positive correlation between PUCAI, FC, serum seromucoid and serum MMP-3 with the endoscopic activity. However, we found no relationship between the concentration of CRP and the endoscopic activity of the disease. Among the studied markers, seromucoid exhibited the best performance in distinguishing between patients with endoscopic remission and endoscopically active disease. CONCLUSIONS: The examined inflammatory markers such as FC, as well as serum seromucoid and MMP-3 levels may be helpful in the assessment of large intestine mucosal healing.

Value of magnetic resonance enterography in diagnosis and treatment follow up in Crohn's disease in children.

PURPOSE: Crohn's disease (CD) is a chronic inflammatory disease which can affect all parts of the gastrointestinal tract. Magnetic resonance enterography (MRE) enables detection of pathologic changes in the small intestine, which are not accessible by conventional endoscopy. The aim of the study was to assess the value of MRE in imaging of small bowel lesions, their location and extent, in CD patients and its correlation with clinical and endoscopic activity. MATERIALS AND METHODS: MRE was performed in 108 children with CD, aged 5.5 to 18 years. The diagnosis was based on the Porto criteria. Location and clinical manifestation was evaluated according to the Paris classification. Clinical CD activity was assessed with PCDAI and endoscopic activity with SES-CD. In 36 children, control MRE was performed. RESULTS: The most common endoscopic location of the disease was the colon (41.7%), terminal ileum and colon (24.1%). Inflammation as the main clinical manifestation was dominant (81.5%). In MRE, inflammatory changes were found in 40.8% of children, strictures in 11.1%. The EIA value (activity in MRE) increased along with PCDAI score and SES-CD. MRE performed during follow up, showed transmural healing in 16.7% of patients and improvement in 55.5%. CONCLUSIONS: MRE is an efficient diagnostic tool in proper characterization of disease location in pediatric CD. As positive correlation of the results of MRE with the endoscopic and clinical activity has been found, taking into account good tolerance and non-invasiveness of the procedure it can be recommended to be used in reassessment.

[Intramural duodenal hematoma and acute pancreatitis as a complication of diagnostic biopsy of a duodenal 6-year-old boy]. / Krwiak sródscienny dwunastnicy I ostre zapalenie trzustki jako powiklanie diagnostycznej biopsji dwunastnicy u 6-letniego chlopca.

Hematoma duodenum is a very rare complication of diagnostic endoscopy of the upper gastrointestinal tract when biopsy of the duodenum is performed (average frequency is estimated as 1:1,250 biopsies). Most often, it affects children and young adults without any risk factors. Symptoms result from obstruction of the duodenum and compression of the adjacent structures. Conservative treatment, which consists of parenteral nutrition and aspiration of gastric contents until the absorption of hematoma and patency of the gastrointestinal tract returns, is preferred. This paper describes a 6-year-old boy diagnosed due to short stature and low weight in whom the diagnostic biopsy of the duodenum caused formation of a hematoma in the descending duodenum and led to total ileus and acute pancreatitis. The boy was treated conservatively with good result and complete resolution of symptoms was achived.

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

INTRODUCTION: Inflammatory bowel disease (IBD), which includes Crohn's 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. Patient's 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.

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

BACKGROUND: In pediatric patients Crohn's 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 Crohn's 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 Crohn's 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 Crohn's 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 Crohn's 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 Crohn's disease.

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 µg/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.

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 ±â€Š2.6 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 Crohn's Disease Activity Index (PCDAI) and Simplified Endoscopic Activity Score for Crohn's 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.

Fecal Calprotectin as an Activity Marker of Inflammatory Bowel Disease in Children.

BACKGROUND: Children constitute 20% of patients with inflammatory bowel diseases (IBD). Still there is a search for a perfect marker for this group of patients which would help in the diagnosis of the disease, in determinating its activity and in monitoring the treatment. OBJECTIVES: Evaluate the usefulness of the application of calprotectin measurement in stool samples from children with IBD, as a marker of the severity of inflammation. MATERIAL AND METHODS: We analysed 156 patients: 58 with ulcerative colitis (UC), 67 with Crohn's disease (CD), and 31 from the control group. In all patients the concentration of calprotectin in the sample of feces, markers of inflammation and hemoglobin were measured. RESULTS: Concentration of calprotectin in feces of patients with IBD was above the normal range in all patients with moderate and severe disease and in the majority with mild disease or in remission, but it was normal in all patients from the control group. CONCLUSIONS: Elevated concentration of fecal calprotectin (FC) was observed in the majority of patients with IBD, but in none from the control group. The number of patients with elevated FC concentration increased together with the disease activity. FC concentration was higher in patients with severe and moderate disease activity. FC concentration in patients with IBD was associated with the increase of inflammatory markers and decreased haemoglobin. Percentage of laboratory abnormalities in children with Crohn's disease and perianal changes was higher. FC concentration can be a noninvasive marker of disease activity in IBD.

[Biological treatment of inflammatory bowel diseases in children in the years 2004-2013 in Poland]. / Leczenie biologiczne nieswoistych zapalen jelit u dzieci w latach 2004-2013 w Polsce.

UNLABELLED: In the last years an increase in Crohn's disease morbidity in children is observed together with constant morbidity of ulcerative colitis. The course of these diseases is severe, younger children are affected and the diseases are resistant to conventional treatment. Biological drugs are a chance for a longer remission and healing of the intestinal mucosa. OBJECTIVE OF THE WORK: Assessment of the use of biological drugs in treatment of inflammatory bowel disease in Poland was the objective of the work. MATERIAL AND METHODS: Gastroenterological centers treating inflammatory bowel disease during the years 2004-2013 were invited to a questionnaire retrospective study. RESULTS: The questionnaires of biological treatment of Crohn's disease and ulcerative colitis in children were received from 12 centers. In the years 2004-2013 the number of children aged 4 months to 18 years with Crohn's disease treated with biological drugs was 424. In the years 2004-2008--69 children were treated with infliximab and in the years 2009-2013--299 children, which was a four-fold increase. 56 children were treated with adalimumab in the years 2008-2013. In the years 2005-2013--72 children with ulcerative colitis were treated with infliximab and 11 with adalimumab. The age of the children ranged from 2 years to 18 years. The higher number of children treated was in the years 2009-2013: 59 with infliximab and 10 with adalimumab. CONCLUSIONS: In the last decade a significant increase on the number of children with Crohn's disease and ulcerative colitis treated with biological drugs was observed. It is connected not only to greater morbidity but above all to the introduction of a treatment program by the National Health Insurance Fund for children with Crohn's disease. There is an expectation that the introduction of biological treatment in inflammatory bowel disease will prolong clinical and endoscopic remission and diminish the number of surgeries.

[Blue rubber bleb naevus syndrome--a rare cause of bleeding from the gastrointestinal tract--case report]. / Zespól naczyniaków gumiastych--rzadka przyczyna krwawienia z przewodu pokarmowego--opis przypadku.

Blue rubber bleb nevus syndrome (BRBNS or Bean's syndrome) is a rare disease characterized by the interaction of hemangiomas of rubber-like tenacity in the skin and gastrointestinal tract, rarely in other organs. Cutaneous malformations are usually asymptomatic and not require any treatment. The most common symptoms of gastrointestinal tract are iron deficiency anemia and bleeding. Hemangiomas can occur in any organ and cause a wide spectrum of symptoms. BRBNS can cause massive bleeding and even death. In this article we present a case of Bean's syndrome in a 7,5-year-old girl with bleeding from the lower gastrointestinal tract, which has been caused by hemangiomas located in the skin, large intestine, chest and armpit.

[Blue rubber bleb naevus syndrome]. / Zespól naczyniaków gumiastych.

Blue rubber bleb nevus syndrome (Bean syndrome) is a rare disease characterized by the presence of multiple vascular malformation of rubber-like consistence. This disease is of a genetic origin and most often is caused by sporadic mutation, however, exist reports on autosomal dominant type of heritance. Nevi are most frequently met in the skin and alimentary tract but may be present in all organs and tissues. The most frequent symptom of Bean syndrome is anaemia due to ferrum deficiency, which is a result of chronic hemorrhagia from vascular malformations in the alimentary tract. Vascular anomalies on the skin are usually asymptomatic. Other symptoms are less frequent and depend on the localisation of vascular changes and therefore patients with Bean syndrome require meticulous analysis of reported multiple - specialistic medical care.

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.

[Distinct clinical characteristics of inflammatory bowel disease in children younger than 5 years]. / Odrebnosci kliniczne nieswoistych zapalen jelit u najmlodszych dzieci do lat 5.

UNLABELLED: In the last decades an increase in morbidity of inflammatory bowel disease, particularly of Crohn disease, in children has been observed. OBJECTIVE: Assessment of clinical course and activity of inflammatory bowel disease in children younger than 5 years was the goal of the study. MATERIAL AND METHODS: The study comprised 21 children aged 2 to 5 years (13 boys and 8 girls) who were diagnosed with: Lesniowski-Crohn disease (7 children), ulcerative colitis (7 children) and indeterminate colitis (remaining 7 children). RESULTS: Among studied children boys prevailed (61.9%). In 6 children the disease started in the first and second year of life; the average age of disease onset was 26.9 months and the time between the onset of the disease and the diagnosis was 16.6 months. 46% of patients came from the cities with population above 100000 when only 23% lived in the country. Autoimmune diseases were diagnosed in the families of 6 children, food or pollen allergy in the families of 11 children. Abdominal pain, diarrhea, presence of blood and mucous in the stool, fever and lack of thrive were most apparent in the clinical picture. The pathological changes were present mainly in the large intestine and only in one case in the upper part of the alimentary tract and jejunum. The observed course of the disease was severe or moderate. In two children aged 3 years colectomy was performed. CONCLUSIONS: In children younger than 5 years severe and moderate course of the Lesniowski-Crohn disease and ulcerative colitis is apparent. Fever, abdominal pain, diarrhea, presence of blood and mucous in the stool and lack of appetite were the most often seen symptoms. Pathological changes in children younger than 5 years were present mainly in the large intestine and only in single cases in the upper part of the alimentary tract and jejunum. In children with inflammatory bowel disease a frequent occurrence of allergy, bronchitis, pneumonia and urinary tract infection, which required antibiotics, was observed.

[Diagnostic role of upper gastrointestinal endoscopy in pediatric inflammatory bowel diseases]. / Zmiany endoskopowe w górnym odcinku przewodu pokarmowego u dzieci chorych na nieswoiste zapalenia jelit.

THE AIM OF THIS STUDY: To evaluate the frequency and type of endoscopic and histopathological changes in upper gastrointestinal tract in children with inflammatory bowel diseases. MATERIAL AND METHODS: The study included 97 patients aged from 3 to 18 years (mean age 12.8 years, 45 girls and 52 boys) with inflammatory bowel diseases (IBD), treated in the 2nd Chair and Department of Pediatrics, Gastroenterology and Feeding of Children from 2005 to 2007. These children were divided into 3 groups depending on the clinical diagnosis: group 1: 38 children with ulcerative colitis (UC), group 2: 26 children with Crohn's disease (CD), and group 3: 33 children with indeterminate colitis (IC). In all patients upper gastrointestinal endoscopy was performed. During endoscopy biopsies were routinely taken from the stomach (antral region), the duodenum and all mucosal changes. H. pylori infection was detected by a positive culture. The obtained results were analyzed using 2 test (p<0.05). RESULTS: Esophageal changes were observed in 27.8% children with IBD, most frequently in CD and IC groups, respectively in 34.6% and 36.3% of children. No endoscopic abnormalities in the esophagus were noted in 72.2% of IBD children and the figure rises to 84.3% in UC children (p<0.05). Endoscopic examination of the stomach revealed no changes in 23.7% of IBD children, in 76.3% of these patients inflammatory lesions were observed. Only in 11.5% of the CD patient were no abnormalities in the stomach observed (p<0.05). In the CD group children mild endoscopic changes were observed in 53.8%, and severe in 34.6% of these patients. Ulceration of the duodenum, often in the descending part was revealed in 23.1% of CD children. Helicobacter pylori infection was found in 10.3% of the IBD children, most frequently in the IC group (12.1%). Histopathological examination confirmed esophageal changes in 31.9% of IBD patients, in the stomach and duodenum respectively in 77.3% and 48.4% of these children. Noncaseating granulomas were noted in 3.1% of the CD patients, partial villus atrophy was noted in 1 child with CD. CONCLUSIONS: In the group of IBD children, various inflammatory changes during the upper endoscopy were observed. Endoscopic examination most frequently revealed inflammatory changes of the stomach, less frequently of the duodenum and of the esophagus. Histopathological examination of IBD patients most frequently confirmed stomach changes. Less frequently histopathological changes were observed of the duodenum and of the esophagus, particularly in CD children. In the group of IBD children H. pylori infection was noted in few of the patients. Upper endoscopy in the IBD children is an important diagnostic tool and should be a part of monitoring the activity of the disease and results of the therapy.

[Intestinal complications and extraintestinal manifestations in children with inflammatory bowel disease]. / Powiklania jelitowe i objawy pozajelitowe w przebiegu nieswoistych zapalen jelit u dzieci.

UNLABELLED: In 15-20% of patients with inflammatory bowel disease (IBD) the disease starts during children period. The often observed consequences of the early start of the IBD are growth delay, undernutrition and pubertal delay. These problems are specific for pediatric population, in comparison with adults IBD patients. AIM: The assessment of the frequency and character of intestinal complications (IC) and extraintestinal manifestations (ElM) in children with IBD (ulcerative colitis - UC and Crohn disease - CD). MATERIAL AND METHODS: The frequency and character of IC and EIM in 184 children with IBD: 158 with UC (76 boys and 82 girls) aged from 2 to 18 years, and 26 with CD (14 boys and 12 girls) aged from 2 to 18 years were assessed. The frequency of IC and EIM in both groups of children Was compared statistically (chi-square test). RESULTS: Massive intestinal haemorrhage was observed in 11 children with UC. Perianal changes were present in 5 children with CD (significantly more often than in children with UC, p<0.05). External intestinal fistulae (p<0.0005), abdominal abscess, intestinal perforation and ileus (p<0.05) were characteristic complications of CD in comparison with UC. 50% of children with UC and 80% those with CD (statistically significant, p<0.005) had experienced, at least one ElM. Secondary anemia and growth delay were observed in 40,5% and 27,8% of children with UC and in 70% (p<0.05) and 80% (p<0.0001) of children with CD respectively. In children with IBD we observed also autoimmunologic hepatitis, primary sclerosing cholangitis, nephrolithiasis, pulmonary interstitial fibrosis, pancreatitis, neurological changes, skin manifestations and arthritis. Osteopenia was observed in 41% of children with CD and in 25% of children with UC. a CONCLUSIONS: A high prevalence of intestinal complications ane extraintestinal manifestations of IBD in pediatric population is observed. In children with IBD extraintestinal manifestations often occur before the onset of gastrointestinal symptoms. The presence of intestinal complications and extraintestinal manifestations in children with IBD should be considered during modification of therapeutic strategies.