HLA-DQA1*05 Associates with Extensive Ulcerative Colitis at Diagnosis: An Observational Study in Children.

The human leukocyte antigen (HLA) allele group HLA-DQA1*05 predisposes to ulcerative colitis (UC) and is associated with the development of antibodies against infliximab in patients with inflammatory bowel disease (IBD). Therefore, we hypothesized that the presence of HLA-DQA1*05 correlates with characteristics of pediatric IBD. Within a multi-center cohort in Poland, the phenotype at diagnosis and worst flare was established and HLA-DQA1*05 status was assessed enabling genotype-phenotype analyses. HLA-DQA1*05 was present in 221 (55.1%) out of 401 children with IBD (UC n = 188, Crohn's disease n = 213). In UC, the presence of HLA-DQA1*05 was moderately associated with a large extent of colonic inflammation at diagnosis (E4 55% more frequent in HLA-DQA1*05-positive patients, p = 0.012). PUCAI at diagnosis (p = 0.078) and the time from UC diagnosis to the first administration of biologic treatment (p = 0.054) did not differ depending on HLA-DQA1*05 status. The number of days of hospitalization for exacerbation was analyzed in 98 patients for whom sufficient follow-up was available and did not differ depending on HLA-DQA1*05 carriership (p = 0.066). HLA-DQA1*05 carriers with CD were less likely to present with both stenosing and penetrating disease (B2B3, p = 0.048) and to have active disease proximal to the ligament of Treitz (L4a) at the worst flare (p = 0.046). Future research focusing on explaining and preventing anti-TNF immunogenicity should take into account that ADA may develop not only as an isolated reaction to anti-TNF exposure but also as a consequence of intrinsic differences in the early course of UC.

Frequency of gastroesophageal reflux disease in children with adenoid hypertrophy.

OBJECTIVES: Recent studies have suggested that the reflux of gastric contents can cause adenoid hypertrophy (AH). The frequency of gastro-oesophageal reflux disease (GERD) in this AH population is unknown, but according to studies using pH-metry it may be as high as 65%. The aim of this study was to estimate the frequency of GERD among children with AH. METHODS: This was a cross-sectional, multicentre, prospective study of children with AH selected for adenoidectomy. The diagnosis of AH was made by a single laryngologist using a flexible fiberscope. All children had 24-hr multichannel intraluminal pH-impedance (MII/pH) assessment. A GERD diagnosis was made using BioVIEW software analysis after manual review by a single investigator. RESULTS: 38 consecutive patients (21 males, mean age 6.58 years) were enrolled in the study. GERD was diagnosed in 5 (13.2%) patients. A total of 1462 gastro-oesophageal reflux events (GERs) were detected by MII/pH and the majority (60.9%) were acidic. The only significant differences between the GERD-positive and GERD-negative groups were the total number of GERs, and the number of acid GERs. CONCLUSION: It is first study using MII/pH to assess the frequency of GERD in children with AH. The data suggest that GERD in children with AH seems to be not as common as it was previously raised. Further studies are needed to confirm these results.

A Two-Week Fecal Microbiota Transplantation Course in Pediatric Patients with Inflammatory Bowel Disease.

Dysbiosis plays a major role in the etiology of inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) is a new promising option for IBD treatment. We aimed to assess the effectiveness of a two-week FMT course in children with IBD. Ten patients, 10-17 years of age with moderate to severe IBD received a course of eight doses of freshly prepared FMT via a naso-duodenal tube or gastroscopy. All of the patients had pancolitis. There were eight cases of ulcerative colitis (UC) and two of Crohn's disease (CD). Disease activity was evaluated using the Pediatric UC Activity Index (PUCAI) and Pediatric CD Activity Index (PCDAI) for UC and CD, respectively, CRP, and fecal calprotectin on the day before the first infusion and then on the day before the next course of FMT. Clinical response, defined as a decrease of 15 points in either index, was observed in 9/10 patients (seven UC and two CD). Clinical remission, defined as a PCDAI score ≤ 10 and PUCAI score < 10 measured at the same time point, was observed in 3/8 UC patients and 2/2 CD patients. Side effects observed were self-limiting and benign. We conclude that a short, intensive course of FMT has a beneficial effect on UC and CD colitis. FMT was well-tolerated and safe. Nonetheless, an optimal protocol of FMT administration is crucial for treatment efficacy.

3D high-definition manometry in evaluation of children after surgery for Hirschsprung's disease: A pilot study.

PURPOSE: Anorectal 3-dimensional high definition manometry (3D HRM) could be the best tool for postoperative assessment of restorative surgical procedures for Hirschsprung's disease. The aim of our study was to evaluate patients after surgery for Hirschsprung's disease using 3D HRM. MATERIALS AND METHODS: Anorectal function was evaluated using solid state 3D HRM. We measured the length of the anal canal, mean resting squeeze pressures, the presence of rectoanal inhibitory reflex, cough reflex, ano-anal reflex and the bear down manoeuvre. RESULTS: We studied 14 children operated on for Hirschsprung's disease. The mean values of pressure asymmetry were higher in patients after the Duhamel procedure than after the TEPT procedure (29.58% vs. 22.26% during resting and 26.1% vs. 14.01% during squeeze, respectively). No difference between the groups was observed in the measurement of all the manometric parameters except the presence of rectoanal inhibitory reflex (87.5% after TEPT vs. 33% after Duhamel). CONCLUSIONS: Anorectal 3D HRM evaluation of patients with Hirschsprung's disease demonstrated that the asymmetry of the anal canal occurred in a similar percentage after both procedures.

Gastroesophageal Reflux Disease in Children with Cystic Fibrosis.

Previously published studies have indicated that gastroesophageal reflux (GER) disease is common in pediatric patients with cystic fibrosis. The aim of the present study was to get insight into the incidence of GER and to characterize the nature of reflux episodes in children with cystic fibrosis. This was a multicenter, prospective study of children with cystic fibrosis older than 18 months. Forty four consecutive patients (22 boys, mean age 10.4 ± 3.6, range 3.0-17.8 years) were enrolled into the study. All patients underwent 24 h pH-impedance monitoring. GER were classified according to the widely recognized criteria as an acid, weakly acid, weakly alkaline, or proximal. The pH-impedance trace was considered abnormal when acid exposure was >6 %. GER was diagnosed in 24/44 (54.5 %) children. A total of 1585 (median 35, range 7-128) reflux episodes were detected; 1199 (75.6 %) were acidic, 382 (24.1 %) weakly acidic, and 4 (0.3 %) weakly alkaline. Six hundred and ninety-one (43.6 %) reflux episodes reached the proximal esophagus. In 14/44 patients typical GER symptoms were present. We conclude that the incidence of GER in children with cystic fibrosis is very high. In the majority of patients typical GER symptoms are absent. Therefore, diagnostic procedures should be considered, regardless of lacking symptoms. Although acid reflux episodes predominate in children with cystic fibrosis, classical pH-metry may not constitute a sufficient diagnostic method in this population because of a relatively high number of proximal reflux episodes. Such episodes also indicate an increased risk for aspiration. The pH-impedance diagnostic measurement is advocated when suspecting GER in children with cystic fibrosis.

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.

Immunisation in children and adolescents with inflammatory bowel disease.

Inflammatory bowel disease (IBD) patients may be at a higher risk for developing infections due to underlying disease, malnutrition, surgery, or immunosuppressive therapy. Therefore, protecting this group against infections is of particular importance. Immunisation against vaccine-preventable diseases is strongly recommended. This article for the first time summarises data on immunogenicity and safety of vaccines in IBD children and provides an update on some important issues regarding immunisation in these group of children.

[Recommendations for prevention of community-acquired pneumonia with bacteremia as the leading form of invasive pneumococcal infections in the population of people over 50 years of age and risk groups above 19 years of age]. / Rekomendacje dotyczace profilaktyki pozaszpitalnego zapalenia pluc z bakteriemia jako wiodacej postaci inwazyjnych zakazen pneumokokowych w populacji osób powyzej 50 roku zycia oraz w grupach ryzyka powyzej 19 roku zycia.

Invasive pneumococcal disease (IPD) is a main cause of mortality associated with pneumococcal infections. Although, IPD is regarding mainly small children and persons in the age > 65 years, the investigations showed that because of IPD exactly sick persons are burdened with the greatest mortality in the older age, rather than of children. The most frequent form of IPD is community acquired pneumonia (CAP) with the bacteremia. The presence of even a single additional risk factor is increasing the probability of the unfavorable descent of pneumococcal infection. The risk factors for IPD and/or pneumonia with bacteremia apart from the age are among others asthma (> 2 x), chronic obstructive pulmonary disease (COPD), sarcoidosis (4 x), idiopathic pulmonary fibrosis (5 x), bronchiectases (2 x), allergic alveolitis (1.9 x) and pneumoconiosis (2 x), type 1 diabetes (4.4 x), type 2 diabetes (1.2 x), autoimmune diseases (e.g. rheumatoid arthritis (4.2 to 14.9 x), kidney failure with the necessity to dialysis (12 x), immunosuppression, cardiovascular disease, alcoholism and cancers. Examinations show that the best method of IPD and CAP preventing are pneumococcal vaccinations. On the market for ages 23-valent polysaccharide vaccine (PPV23) is available covering close the 90% of IPD triggering stereotypes. Her role in preventing CAP is uncertain and the immunological answer after vaccination at older persons and after revaccination is weak. Widely discussed disadvantageous effects of growing old of the immunological system show on the benefit from applying the immunization inducing the immunological memory, i.e. of conjugated vaccines which are activating the T-dependent reply and are ensuring the readiness for the effective secondary response. Examinations so far conducted with conjugated 7-valent and 13-valent (PCV13) vaccines at persons in the age > 50 years are confirming these expectations. Also sick persons can take benefits from PCV13 applying back from so-called IPD risk groups in the age > 19 years. At these work research findings were described above PPV23 and PCV13 at adults and world recommendations of applying both vaccines in risk groups from 19 years up to the advanced years. Also Polish recommendations of optimum applying of these vaccines were presented. They are recommending applying PCV13 at first in them, while PPV23, if to her readings exist should be given to > or = 8 of weeks from PCV13. In persons > or = 19 years which earlier received 1 or should receive more PPV23 doses first PCV13 dose should be given after the year or later than the last PPV23 dose, and then again PPV23 > or = 8 of weeks from PCV13 and the second PPV23 dose not earlier than 5 years from last PPV23. If the PPV23 application seems to be justified, it is irrespective of the more previous state vaccination against pneumococci, PCV13 should be given to as first.

Enterotoxigenic Clostridium perfringens infection and pediatric patients with inflammatory bowel disease.

BACKGROUND AND AIMS: Clostridium difficile is the major cause of antibiotic-associated diarrhea and is the most well known bacterial pathogen associated with inflammatory bowel disease (IBD). Enterotoxigenic Clostridium perfringens has also been detected in up to 15% of antibiotic-associated diarrhea cases, and it has not been found in healthy people. The aim of this study was to investigate the prevalence of C. perfringens infection in pediatric patients with IBD. METHODS: This was a prospective, controlled study evaluating pediatric IBD patients in the Department of Pediatric Gastroenterology and Nutrition in Warsaw, Poland. All of the patients were diagnosed according to the Porto criteria. There were two control groups: (1) non-IBD patients that were suspected for bacterial diarrhea and (2) healthy children. Stool samples were collected on the day of admission. C. perfringens infection diagnosis was based on a positive stool enzyme immunoassay (C. perfringens enterotoxin test kit TechLab). RESULTS: 91 fecal specimens from patients with IBD were collected. The average patient age was 11.7 years in IBD group, 7.4 years in non-IBD patients with diarrhea, and 7.4 years in healthy children. The prevalence of C. perfringens infection was 9% (8/91; CI 95% 4.6-16.4). There were more Crohn's patients (6/8) in the C. perfringens positive group. There was no C. perfringens infection in the two control groups. CONCLUSION: Our pilot data add evidence to the hypothesis that Clostridia other than C. difficile may play a significant role in the clinical course of IBD. However, further studies are needed to confirm this.

Low prevalence of pulmonary involvement in children with inflammatory bowel disease.

BACKGROUND: Since extraintestinal sites of inflammation have been demonstrated in patients with Crohn's disease (CD) and ulcerative colitis (UC), both entities are regarded as systemic disorders. There are only scarce data on the prevalence of inflammatory bowel disease (IBD)-associated lung involvement in children. OBJECTIVES: The aim of our study was to investigate pulmonary involvement in pediatric patients with IBD. MATERIAL AND METHODS: Fifty children with IBD (25 UC and 25 CD, mean age 14.2 ± 3.2 yrs) and 39 age-matched, healthy, control subjects were included in the study. Pulmonary function testing, methacholine bronchial challenge, fractional exhaled nitric oxide (FeNO) and high resolution computed tomography (HRCT) were used to detect functional and/or structural pulmonary involvement. RESULTS: There were no differences in spirometric parameters, lung volumes or lung diffusion capacity for carbon monoxide between IBD patients and control subjects. Highly significant differences were found in FeNO between CD, UC and control patients (mean 9.3 ± 3.3, 27.7 ± 14.8 and 16.6 ± 9.28, respectively; p = 0.000). Bronchial hyperresponsiveness was diagnosed in six IBD cases (14.6%). HRCT (performed in 32 patients from the study group) revealed mild bilateral bronchiectasis in one patient. CONCLUSIONS: The prevalence of pulmonary involvement in children with IBD is low. Screening for pulmonary involvement in children and young adults with IBD may enable early detection of IBD-related pulmonary diseases which, seems to be notably more common in adult patients. Elevated FeNO could probably be regarded as a marker of airway involvement in non-smoking UC pediatric patients. This requires further studies.

Clostridium difficile infection in newly diagnosed pediatric patients with inflammatory bowel disease: prevalence and risk factors.

BACKGROUND: Epidemiological and microbiological data suggest that Clostridium difficile infection (CDI) plays a substantial role in the clinical initiation of inflammatory bowel disease (IBD). The aim of the present study was to investigate the prevalence and risk factors of CDI in newly diagnosed pediatric patients with IBD. METHODS: The current investigation was a retrospective study. All patients newly diagnosed with IBD in the pediatric gastroenterology clinic in Warsaw between 2007 and 2010 were included in the present study. The patients were diagnosed according to Porto criteria and microbiology evaluation screening tests for CDI were conducted. Risk factors including prior hospitalization, use of antibiotics within 2 months of CDI detection, colonic involvement, and the duration of symptoms were evaluated. CDI diagnosis was based on a positive stool enzyme immunoassay. RESULTS: In the present study, 134 patients were evaluated (54 patients with Crohn's disease, and 80 with ulcerative colitis; 87% of the patients had colonic disease). The average age of the patients was 12.3 years, and the prevalence of CDI was 47% (95% confidence interval [CI], 38%-56%). Significant differences in the prevalence of CDI between patients with Crohn's disease and ulcerative colitis (P = 0.72; odds ratio [OR] = 1.187, 95% CI, 0.56-2.52) were not observed. The risk of CDI was associated with an increase in the age of the patient and the severity of the disease. CONCLUSIONS: The prevalence of CDI in newly diagnosed IBD patients was high and was independent of the type of disease.

Immunogenecity of hepatitis A vaccine in pediatric patients with inflammatory bowel disease.

BACKGROUND: There are only a few studies on immune response to routine vaccinations in children with inflammatory bowel disease (IBD), despite a strong need for this kind of study. The aim of the study was to evaluate the immunogenicity of an inactivated hepatitis A vaccine (HAV) in IBD pediatric patients compared with healthy controls. METHODS: This was an open, prospective, and controlled study on anti-HAV-negative children and adolescents age 2-18 years with IBD. HAV using 720 enzyme-linked immunosorbent assay (ELISA) units were administered at 0 months and at 6-12 months. Seroconversion and geometric mean titers were measured after each vaccine dose. The evidence of local and systemic adverse effects for 3 days after the first and second dose of vaccine was registered. RESULTS: A total of 134 subjects (66 patients and 68 controls) completed the whole study course consisting of two doses of vaccine and six serum samples. There was no significant difference in the rate of seroconversion between IBD patients and controls when measured after the second dose of vaccine (97% versus 100%, P = 0.2407), but the rate was significantly lower in the IBD group when measured after the first dose (39% versus 64%, P = 0.00001). The mean geometric titers were statistically significantly lower in the IBD group than in the control group at all of the measured timepoints. There were no serious adverse events related to HAV during the study. CONCLUSIONS: HAV is both immunogenic and safe in pediatric patients with IBD.

Small intestine bacterial overgrowth does not correspond to intestinal inflammation in cystic fibrosis.

INTRODUCTION: Small intestine bacterial overgrowth (SIBO) has been reported in cystic fibrosis (CF) patients. However, the potential link to intestinal inflammation has not been studied so far. Therefore, we aimed to assess whether SIBO correlates with intestinal inflammation in CF patients. MATERIAL AND METHODS: As a preliminary study, we assessed whether calprotectin is detectable in sputum expectorated by 10 CF patients. Since significant immunoreactivity was documented, in the major study we have included exclusively CF subjects not expectorating sputum for at least two weeks. Fecal calprotectin was measured in 25 CF patients and 30 healthy subjects (HS). All CF subjects were tested for the presence of SIBO using the hydrogen-methane breath test (BT). According to obtained results CF patients were divided into SIBO positive and negative subgroups. Subsequently, the intensity of intestinal inflammation in both subgroups was compared. RESULTS: Fecal calprotectin concentrations in CF patients (range: 1.8-302.5; median 80.0 mg/L) were significantly higher (p < 0.00001) than in HS (not detectable-15.5; 2.5 mg/L). Calprotectin levels were abnormal in 21 (84%) studied CF subjects and none of HS. Abnormal BT results were found in 10 (40.0%) of CF patients. Calprotectin concentrations in SIBO positive and negative patients did not differ. CONCLUSIONS: Gastrointestinal inflammation is a frequent finding in cystic fibrosis patients. However, small intestine bacterial overgrowth does not seem to be the major or at least not the only determinant of intestinal inflammation. Indirect measures of intestinal inflammation in CF patients may give false positive results.

Acid steatocrit determination is not helpful in cystic fibrosis patients without or with mild steatorrhea.

BACKGROUND: Most methods used for the assessment of severe steatorrhea in cystic fibrosis (CF) are sensitive. In fact, the tests show their usefulness in a borderline zone of the results. Yet, the existing data related to acid steatocrit (AS) are still contradictory. Therefore, in the present study we have aimed to assess CF patients without or with mild steatorhea (<10 g/day) and evaluate the applicability of AS in such a subset of patients. PATIENTS AND METHODS: In fifty-five CF patients, AS, fecal fat concentration (FFC) and fecal fat excretion (FFE) in 1-day stool collection were assessed from one to three times (149 samples). In 50 subjects, FFC, FFE, and AS were available for 3 subsequent days. It allowed for the calculations based upon 3-day fecal fat balance study. RESULTS: The correlations between FFE/FFC and AS based upon 1-day stool collection, although statistically significant, were rather weak (r = 0.208, P < 0.011; r = 0.362, P < 0.000006, respectively). The correlations between FFE/FFC and AS based upon the 3-day stool collection, although stronger, did not show values a linear relationship (r = 0.394, P < 0.005; r = 0.454, P < 0.001, respectively). With no regard to the cut-off level for AS (10% and 20%), sensitivity, specificity, negative, and positive predictive values in the determination of abnormal FFC and FFE were not satisfactory. The flow charts describing the accuracy of AS to determine FFE and FC revealed a high level of uncertainty. CONCLUSIONS: AS does not reflect in a reliable way FFE in CF patients without or mild steatorrhea. Its applicability in the assessment of FFC in such patients has therefore limited practical value.

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.