Pediatric Patients with Eosinophilic Esophagitis and Their Parents Identify Symptoms as the Most Important Treatment Outcome.

INTRODUCTION: Given the lack of data, we aimed to explore which therapeutic endpoints pediatric patients with eosinophilic esophagitis (EoE) and their parents consider to be relevant. METHODS: We created an educational brochure on EoE and a questionnaire, both of which were content-validated by pediatric patients and parents. Validated documents were sent to 112 patients and parents. They ranked the importance (5 levels) of short (during next 3 months) and long-term (≥1 year) treatment effect on symptoms, quality of life, endoscopic inflammation, stricture formation, histological inflammation, and fibrosis. RESULTS: A total of 45 parents and 30 pediatric patients ≥11 years completed the questionnaires. Pediatric patients identified improvement in the following domains as most important in the short- and long-term, respectively: symptoms (73% vs. 77%), QoL (53% vs. 57%), histologic inflammation (47% vs. 50%), histologic fibrosis (40% vs. 33%), endoscopic inflammation (47% vs. 40%), and strictures (33% vs. 40%). Parents of children ≥11 years old classified improvement in the following domains as most important in the short- and long-term, respectively: symptoms (70% vs. 83%), QoL (63% vs. 80%), histologic inflammation (67% vs. 77%), histologic fibrosis (47% vs. 63%), endoscopic inflammation (77% vs. 80%), and strictures (40% vs. 53%). Agreement between caregiver and children on the short-term importance of treatment outcomes was as follows: symptoms (77%), QoL (40%), histologic inflammation and fibrosis (47% and 43%), endoscopic inflammation and strictures (50% and 40%). CONCLUSION: Pediatric patients and parents attributed most importance to improvement in symptoms and QoL. Agreement between parents and patients regarding therapy goals is limited.

Outcome in pediatric celiac disease is independent of the diagnostic approach in patients with high antibody levels.

OBJECTIVES: European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines enable the diagnosis of celiac disease (CD) without biopsies in patients with immunoglobulin A (IgA)-antibodies against tissue transglutaminase (TGA-IgA) ≥ 10× the upper limit of normal (ULN) and positivity of endomysial antibodies in a second blood sample. Limited data exist comparing the biopsy versus the nonbiopsy diagnostic approach regarding long-term outcomes in CD patients. Our study aimed to investigate the influence of the diagnostic approach on adherence to gluten-free diet (GFD), serological remission (defined as normalization of TGA-IgA during follow-up (FU)) and clinical remission in CD patients with TGA-IgA ≥ 10× ULN. METHODS: Retrospective multicenter study. Patients with CD and TGA-IgA ≥ 10× ULN at diagnosis were included in the study. Patients with confirmed diagnosis by biopsy were compared to patients diagnosed by nonbiopsy approach using univariate analysis, Kaplan-Meier survival curve, and logistic regression models. RESULTS: A total of 282 CD patients (192 [68.1%] in the biopsy group; 90 [31.9%] in the nonbiopsy group) were analyzed. The median time to normalization of TGA-IgA was 16.5 months [interquartile range, IQR: 13, 28] in the biopsy and 15 months [IQR: 12, 26] in the nonbiopsy group; p = 0.14). Rates of normalized TGA-IgA at first to third-year FU were comparable between both groups. Adherence to GFD did not seem to be influenced by the diagnostic approach. CONCLUSIONS: The nonbiopsy approach is not inferior to the biopsy approach in terms of adherence to GFD and serological remission in patients with CD.

Drug-Related Adverse Events Necessitating Treatment Discontinuation in Pediatric Inflammatory Bowel Disease Patients.

OBJECTIVES: Inflammatory bowel disease (IBD) requires long-term drug therapy in most patients, posing a risk for adverse drug events with the need for discontinuation. In this study, we investigated adverse events (AE) necessitating drug discontinuation in pediatric and adolescent IBD patients. METHODS: We used data prospectively collected from IBD patients below the age of 18 enrolled in the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS), namely demographic variables, medical characteristics, drug treatments, and related AE. We analyzed the frequency, type, and risk factors for AE necessitating drug discontinuation. RESULTS: A total of 509 pediatric IBD patients fulfilled the inclusion criteria of which 262 (51.5%) were diagnosed with Crohn disease (CD), 206 (40.5%) with ulcerative colitis (UC), and 41 (8%) with IBD-unclassified (IBD-U). In total, 132 (25.9%) presented with at least 1 drug-related AE that required drug cessation. Immunomodulators [methotrexate 29/120 (24.2%), azathioprine 57/372 (15.3%)] followed by tumor necrosis factor (TNF)-alpha antagonists [adalimumab 8/72 (11.1%), infliximab 22/227 (9.7%)] accounted for the highest proportions of AE necessitating treatment discontinuation. Treatment schemes with at least 3 concomitant drugs significantly amplified the risk for development of drug-related AE [odds ratio = 2.50, 95% confidence interval (1.50-4.17)] in all pediatric IBD patients. CONCLUSIONS: Drug-related AE necessitating discontinuation are common in pediatric and adolescent IBD patients. Caution needs to be taken in the case of concomitant drug use.

The Use of 5-Aminosalicylic Acid in Children and Adolescents With Inflammatory Bowel Disease.

BACKGROUND: In ulcerative colitis (UC) 5-aminosalicylic acid (5-ASA) is recommended as primary therapy for mild to moderate disease. Topical 5-ASA has been proven especially effective. In Crohn's disease (CD) the evidence for a beneficial role of 5-ASA is weak. We investigated the use of topical and systemic 5-ASA therapy in children and adolescents with inflammatory bowel disease. MATERIALS AND METHODS: Data of patients younger than 18 years, registered between April 2008 and December 2015 in the Swiss Inflammatory Bowel Disease Cohort, were analyzed. RESULTS: Three hundred twenty pediatric inflammatory bowel disease patients were included; 189 with CD and 131 with UC. Over one third of UC patients [51 (39%)] received topical 5-ASA therapy and 43 (33%) received combination therapy during their disease course. UC patients with left-sided colitis or proctitis were more likely to receive topical or combination therapy as compared with patients with pancolitis (P<0.001 and <0.001, respectively). An increase in the use of topical 5-ASA therapy in UC patients was noted over time from 5% to 38%. Forty-seven percent of CD patients were treated with oral 5-ASA during their disease course. The usage was stable over time at approximately 15% to 20%. CONCLUSIONS: In recent years a very positive trend showing an increase in topical 5-ASA therapy in children and adolescents with UC has been observed. However topical therapy is still used with relative low frequency, especially in patients with a more extensive disease. Conversely, despite weak evidence supporting 5-ASA use in CD patients it has been frequently prescribed. Physicians should continue to encourage their UC patients to use topical therapy.

Extraintestinal Manifestations of Pediatric Inflammatory Bowel Disease: Prevalence, Presentation, and Anti-TNF Treatment.

BACKGROUND: There is a paucity of data on extraintestinal manifestations (EIM) and their treatment in pediatric patients with inflammatory bowel disease (IBD). METHODS: Since 2008, the Pediatric Swiss IBD Cohort Study has collected data on the pediatric IBD population in Switzerland. Data on 329 patients were analyzed retrospectively. RESULTS: A total of 55 patients (16.7%) experienced 1-4 EIM (39 Crohn disease, 12 ulcerative colitis, and 4 IBD-unclassified patients). At IBD onset, presence of EIM was more frequent than in the adult population (8.5% vs 5.0%, P = 0.014). EIM were more frequent in Crohn disease when compared to ulcerative colitis/IBD-unclassified (22.5% vs 10.3%, P = 0.003). The most prevalent EIM were peripheral arthritis (26/329, 7.9%) and aphthous stomatitis (24/329, 7.3%). Approximately 27.6% of all EIM appeared before IBD diagnosis. Median time between IBD diagnosis and occurrence of first EIM was 1 month (-37.5-149.0). Thirty-one of the 55 patients (56.4%) were treated with 1 or more anti-tumor necrosis factor (TNF) agents. IBD patients with EIM were more likely to be treated with anti-TNF compared to those without (56.4% vs 35.0%, P = 0.003). Response rates to anti-TNF depended on underlying EIM and were best for peripheral arthritis (61.5%) and uveitis (66.7%). CONCLUSIONS: In a cohort of pediatric patients with IBD, EIM were frequently encountered. In up to 30%, EIM appeared before IBD diagnosis. Knowledge of these findings may translate into an increased awareness of underlying IBD, thereby decreasing diagnostic delay. Anti-TNF for the treatment of certain EIM is effective, although a substantial proportion of new EIM may present despite ongoing anti-TNF therapy.

Changes in health-related quality of life over a 1-year follow-up period in children with inflammatory bowel disease.

PURPOSE: Little is known about disease-specific health-related quality-of-life (HRQoL) changes over time in paediatric patients with inflammatory bowel disease (IBD), and about their associations with baseline medical characteristics. METHODS: In this study, 153 paediatric patients with IBD from the multicentre prospective Swiss IBD cohort study were included at baseline. Of these, 90 patients were analysed at a 1-year follow-up. Medical data were extracted from hospital records, while HRQoL data were measured using the standardized, self-report disease-specific IMPACT-III questionnaire. RESULTS: The IBD diagnosis of the included children was made an average of 2.0 years before their baseline assessment. Over the 1-year follow-up period, a significant increase in overall HRQoL and in the HRQoL domain 'physical functioning' was evident. On multivariate analysis, overall HRQoL changes over time were predicted by baseline HRQoL, baseline disease activity, and disease activity changes over time. HRQoL improvements were significantly associated with decreases in physician-assessed disease activity. Children reporting a low baseline HRQoL and children with inactive or mildly-active disease experienced greater improvements. CONCLUSIONS: Children with more severe baseline disease activity had the greatest risk for HRQoL deterioration over the 1-year follow-up period. However, among possible factors that might influence HRQoL changes over time, the child's medical characteristics explained only a small proportion of their variability in our sample. We, therefore, recommend that researchers and clinicians focus on factors that are not incorporated within the multidimensional HRQoL concept if they seek to gain better insights into factors that influence HRQoL changes over time in children with IBD.

Pulse wave velocity measurement as a marker of arterial stiffness in pediatric inflammatory bowel disease: a pilot study.

In adults with inflammatory bowel disease (IBD), the incidence of cardiovascular events is increased, leading to long-term morbidity. Arterial stiffness (AS) measured by pulse wave velocity (PWV) is a validated early precursor of cardiovascular disease (CVD), and measurement of PWV was shown to be a feasible test in children. The aim of this study was to assess AS in children with IBD. In this prospective study, we determined PWV between the carotid and femoral artery (PWVcf) in 25 children and adolescents with IBD (11 females, median age 14.1 years, median disease duration 2.8 years). The majority (68%) of the subjects were in clinical remission, and 48% received anti-tumor necrosis factor alpha (TNFα) treatment. AS was not increased in this cohort of children and adolescents with IBD, who did not have signs of cardiovascular disease, such as arterial hypertension. CONCLUSION: PWV seems to be normal in children with IBD in remission or with mild disease activity. Larger studies should assess its potential role as a valid and non-invasive follow-up marker in children with IBD, to avoid cardiovascular complications. What is Known : • Inflammatory bowel disease (IBD) is a risk factor of cardiovascular disease (CVD). • Pulse wave velocity (PWV) measurement is the current gold standard to assess arterial stiffness (AS), which is an early predictor of CVD. What is New: • This is the first study using PWV measurements to determine AS in children with IBD. • In children with IBD in remission or only mild disease activity AS is not increased.

Type of CFTR mutation determines risk of pancreatitis in patients with cystic fibrosis.

BACKGROUND & AIMS: Different mutations in the cystic fibrosis gene (CFTR) are associated with different functional status of the exocrine pancreas. We investigated whether CFTR genotypes determine the risk of pancreatitis in patients with cystic fibrosis (CF). METHODS: Patients with pancreatic-sufficient CF were identified from 2 CF population-based databases (N = 277; 62 with pancreatitis and 215 without pancreatitis); patients' genotypes and clinical characteristics were analyzed. The loss of pancreatic function associated with each CFTR genotype was determined based on the pancreatic insufficiency prevalence (PIP) score. RESULTS: Patients with pancreatitis were more likely to have genotypes associated with mild (70%) than moderate-severe (30%) PIP scores (P = .004). The cumulative proportion of patients who developed pancreatitis through to the age of 50 years was significantly greater for genotypes associated with mild (50%) than moderate-severe (27%) PIP scores (P = .006). The genotype associated with mild PIP scores had a hazard ratio of 2.4 for pancreatitis (95% confidence interval, 1.3-4.5; P = .006). Patients with pancreatitis were diagnosed with CF at an older median age than those without pancreatitis (14.9 years [interquartile range, 9.5-27.7] vs 9.3 years [interquartile range, 1.5-21.4]; P = .003) and had lower mean levels of sweat chloride than patients without pancreatitis (74.5 ± 26.2 mmol/L vs 82.8 ± 25.2 mmol/L; P = .03). CONCLUSIONS: Specific CFTR genotypes are significantly associated with pancreatitis. Patients with genotypes associated with mild phenotypic effects have a greater risk of developing pancreatitis than patients with genotypes associated with moderate-severe phenotypes. This observation provides further insight into the complex pathogenesis of pancreatitis.

Molecular and Histological Profiling Reveals an Innate-Shaped Immune Microenvironment in Solitary Juvenile Polyps.

INTRODUCTION: Solitary juvenile polyps (JP) are characterized by a benign disease course with low recurrence rate but present with signs of intestinal inflammation. To better understand the underlying pathogenesis, we performed histological and molecular evaluation targeting distinct immune mechanisms. METHODS: Pediatric patients with JP (n = 12), with treatment-naïve inflammatory bowel disease (IBD; [n = 41]) as inflammatory control, and non-IBD controls (n = 14) were investigated. For a comparative analysis of infiltrating immune cells, a next-generation tissue microarray of biopsies was assembled, immunostained, and scored. Targeted transcriptional profiling was performed using a customized immunology panel. RESULTS: In JP, a predominant accumulation of neutrophils and eosinophils was observed. RNA expression profiles revealed increased levels of CXCL8, CXCL5, and CCL11 transcripts in JP, indicating an enhanced recruitment of neutrophils and eosinophils. Moreover, messenger RNA levels of the proinflammatory cytokine IL1b and the inflammation-amplifying receptor TREM1 were higher in JP, whereas we could not find signs of a functionally polarized Tcell response in JP when compared with IBD. DISCUSSION: Patients with JP and patients with treatment-naïve IBD have distinct cell infiltrates during active disease. The ample presence of eosinophils in JP supports neutrophil accumulation, which is responsible for the elevated release of calprotectin. Intriguingly, however, we were not able to identify a functionally polarized T-cell response in JP, which indicates that during the acute onset of inflammation in JP, a potent adaptive immune memory is not established. This may explain the low reoccurrence rate of JP.

The erroneous perception of a clinical sign: Cholestasis preceding sepsis mimicking hepatitis in an adolescent patient.

Jaundice should be considered as a first clinical sign preceding severe invasive bacterial infection or sepsis in patients of all ages including childhood and adolescence. Early laboratory investigations and MR imaging studies for osteomyelitis or myositis are paramount to avoid progression to life-threatening sepsis and significant morbidity and mortality.

Evidence of a generalized defect of acinar cell function in Shwachman-Diamond syndrome.

BACKGROUND: : Because the acinar cells of the exocrine pancreas in patients with Shwachman-Diamond syndrome (SDS) are severely depleted, we hypothesized that a similar deficiency may be present in acinar cells of the parotid gland. PATIENTS AND METHODS: : We determined serum pancreatic isoamylase and parotid amylase activities in 16 patients with SDS, 13 healthy controls, and 13 disease controls (cystic fibrosis or fibrosing pancreatitis). Parotid amylase and electrolyte concentrations were measured in stimulated parotid gland secretions. Starch digestion was assessed by breath hydrogen testing in patients with SDS (with and without enzyme supplements) and healthy controls. RESULTS: : Serum pancreatic and parotid isoamylase values were lower in the patients with SDS than in the healthy controls (P < 0.0001 and P = 0.0002, respectively). Serum pancreatic isoamylase, but not parotid isoamylase, was significantly lower in the disease controls than in the healthy controls (P < 0.0001 and P = 0.17, respectively). Secreted parotid gland amylase concentration (units per milligram of protein) in patients with SDS was lower than that in the healthy controls (P = 0.04), whereas the disease controls were comparable to the healthy subjects (P = 0.09). Secreted parotid chloride concentration was inversely correlated with amylase concentration in the patients with SDS (P = 0.01), but no correlation was seen in the healthy controls or disease controls. When patients with SDS ingested starch without enzyme supplementation, their breath hydrogen excretion was significantly higher than that in the healthy controls (P = 0.009). Following starch ingestion with enzymes, breath hydrogen in the patients with SDS was lower (P < 0.05) than with no enzyme treatment, and no different from controls (P = 0.37). CONCLUSIONS: : Mutations in the SBDS gene cause a generalized functional abnormality of exocrine acinar cells.

Hepatocellular carcinoma and regenerating nodule in a 3-year-old child with Alagille syndrome.

In Alagille syndrome, routine follow-up imaging of the liver plays an important role in detecting early parenchymal changes and to evaluate portal hypertension. Modern contrast-enhanced imaging methods not only allow early detection of focal liver lesions, but also enable further characterization of their nature and guide biopsy procedures. We present the US and MR imaging findings of hepatocellular carcinoma and a regenerating nodule in a 3-year-old child with Alagille syndrome.

A Near Miss and Salvage Management of Aortoesophageal Fistula Secondary to Cell Battery Ingestion.

We report a case of an infant surviving aortoesophageal fistula secondary to lithium cell battery ingestion. In the setting of a delayed vascular complication, computed tomography and magnetic resonance imaging are essential to establishing the correct diagnosis and surgical management. Management of children after battery ingestion must be guided by a high index of clinical suspicion.

Clinical presentation of celiac disease and the diagnostic accuracy of serologic markers in children.

There has been growing recognition of a changing clinical presentation of celiac disease (CD), with the manifestation of milder symptoms. Serologic testing is widely used to screen patients with suspected CD and populations at risk. The aim of this retrospective analysis was to evaluate the clinical presentation of CD in childhood, assess the diagnostic value of serologic tests, and investigate the impact of IgA deficiency on diagnostic accuracy. We evaluated 206 consecutive children with suspected CD on the basis of clinical symptoms and positive serology results. Ninety-four (46%) had biopsy-proven CD. The median age at diagnosis of CD was 6.8 years; 15% of the children were <2 years of age. There was a higher incidence of CD in girls (p = 0.003). Iron deficiency and intestinal complaints were more frequent in children with CD than those without CD (61% vs. 33%, p = 0.0001 and 71% vs. 55%, p = 0.02, respectively), while failure to thrive was less common (35% vs. 53%, p = 0.02). The sensitivity of IgA tissue transglutaminase (IgA-tTG) was 0.98 when including all children and 1.00 after excluding children with selective IgA deficiency. The specificity of IgA-tTG was 0.73 using the recommended cut-off value of 20 IU, and this improved to 0.94 when using a higher cut-off value of 100 IU. All children with CD and relative IgA deficiency (IgA levels that are measurable but below the age reference [n = 8]) had elevated IgA-tTG. In conclusion, CD is frequently diagnosed in school-age children with relatively mild symptoms. The absence of intestinal symptoms does not preclude the diagnosis of CD; many children with CD do not report intestinal symptoms. While the sensitivity of IgA-tTG is excellent, its specificity is insufficient for the diagnostic confirmation of a disease requiring life-long dietary restrictions. Children with negative IgA-tTG and decreased but measurable IgA values are unlikely to have CD.

Systematic Analysis of the Impact of Diagnostic Delay on Bowel Damage in Paediatric Versus Adult Onset Crohn's Disease.

BACKGROUND AND AIMS: Length of diagnostic delay is associated with bowel strictures and intestinal surgery in adult patients with Crohn's disease [CD]. Here we assessed whether diagnostic delay similarly impacts on the natural history of paediatric CD patients. METHODS: Data from the Swiss IBD Cohort Study were analysed. Frequency of CD-related complications [bowel stenosis, perianal fistula, internal fistula, any fistula, resection surgery, fistula/abscess surgery, any complication] at diagnosis and in the long term [up to 30 years after CD diagnosis] was compared between paediatric patients [diagnosed <18 years] and adult patients [diagnosed ≥18 years] using multivariate Cox proportional hazard regression modelling. RESULTS: From 2006 to 2016, 387 paediatric and 1163 adult CD patients were included. Median [interquartile range: IQR] diagnostic delay was 3 [1-9] for the paediatric and 6 [1-24] months for the adult group, respectively. Adult onset CD patients presented at diagnosis more frequently with bowel stenosis [p <0.001] and bowel surgery [p <0.001] compared with paediatric CD patients. In the long term, length of diagnostic delay was significantly associated with bowel stenosis [p = 0.001], internal fistula [p = 0.038], and any complication [p = 0.024] in the adult onset CD population. No significant association between length of diagnostic delay and CD-related outcomes in the long term was observed in the paediatric population. CONCLUSIONS: Adult CD patients have longer diagnostic delay compared with paediatric CD patients and present at diagnosis more often with bowel stenosis and surgery. Length of diagnostic delay was found to be predictive for CD-related complications only in the adult but not in the paediatric CD population.

D-lactic Acidosis: Successful Suppression of D-lactate-Producing Lactobacillus by Probiotics.

Intestinal microbiota composition in children with short bowel syndrome (SBS) is an important factor influencing the clinical outcome. An increase of D-lactate-producing bacteria can lead to D-lactic acidosis, also referred to as D-lactate encephalopathy, with severe neurologic impairment. Antibiotic treatments for D-lactic acidosis in children with SBS offer often only short-term relief. Here, we present the case of a boy with SBS who developed recurrent episodes of D-lactic acidosis even under continuous cycling antibiotic treatment. Microbiological analyses were used to detect the presence of D-lactate-producing Lactobacillus species in the stool samples. A probiotic cocktail was introduced to alter the intestinal microbiota. During follow-up under treatment with probiotics, the patient remained stable, and there was no additional need for antibiotic therapy for more than a year. Stool composition of the patient was sequenced regularly over that period. His microbiota profile changed completely in species richness, and a clustering of species according to probiotic usage was seen. Importantly, D-lactate-producing Lactobacillus strains disappeared within a few weeks after probiotic introduction and were no longer detected in the subsequent follow-up specimens.

Change of treatment modalities over the last 10 years in pediatric patients with inflammatory bowel disease in Switzerland.

BACKGROUND AND AIM: During the past decade, several new drugs were approved for the treatment of pediatric inflammatory bowel disease (IBD). We aimed to evaluate if and how pharmacologic treatment options for pediatric IBD in Switzerland have changed over time. PATIENTS AND METHODS: Data from the pediatric Swiss IBD Cohort Study, a national prospective cohort study initiated in 2006, were analyzed. Patients were divided into two groups: patients with IBD diagnosis until 2009 (168 patients) and patients with IBD diagnosis in 2010 and after (210 patients). Both groups were analyzed regarding the past and the current therapies as well as need for surgery. RESULTS: Overall, 378 pediatric patients with IBD were analyzed, of which 51.9% had Crohn's disease (CD) and 48.1% had ulcerative colitis/indeterminate colitis. Median age at diagnosis was 12 years. The majority (65.4%) of the patients with ulcerative colitis experienced pancolitis, whereas 45.4% of patients with CD presented with ileocolonic disease at diagnosis. A decreased use of corticosteroids in pediatric patients with CD can be found after 2010 (P=0.041). Use of 5-aminosalicylic acid for patients with CD was dramatically reduced after the year 2010 (33.5 vs. 67.7% after 6 years of disease). A significant shift toward earlier use of biologicals could be shown after 2010 (P<0.001). However, there was no significant decrease of surgery rate after 5 years of disease. CONCLUSION: In the past decade, a significant earlier use of anti-tumor necrosis factor-α agents in pediatric patients with IBD was observed with steroid-sparing effect in patients with CD. However, this change was not associated with reduction of surgery.

PR3-ANCA and panel diagnostics in pediatric inflammatory bowel disease to distinguish ulcerative colitis from Crohn's disease.

BACKGROUND: Accurate classification of patients with inflammatory bowel disease into the subtypes ulcerative colitis (UC) and Crohn's disease (CD) is still a challenge, but important for therapy and prognosis. OBJECTIVES: To evaluate the diagnostic utility of anti-neutrophil cytoplasmic antibodies specific for proteinase-3 (PR3-ANCA) for ulcerative colitis (UC) and the value of an antibody panel incorporating PR3-ANCA to differentiate between Crohn's disease (CD) and UC. STUDY DESIGN: In this cohort study, 122 pediatric and adolescent individuals were retrospectively included (61 IBD patients of two clinical centers, 61 non-IBD controls). All subjects had a comprehensive antibody profile done from stored sera taken close to time of diagnosis. By employing quasi-exhaustive logistic regression the best discriminative model for UC and CD,subjects was determined in a training cohort and confirmed in a validation cohort. RESULTS: PR3-ANCA was specifically associated with UC (odds ratio (OR), 17.6; 95% confidence interval (CI); 3.6, 87); P < .001). A four antibody-panel including PR3-ANCA had an AUC of 90.81% (95%CI; 81.93, 99.69) to distinguish between UC and CD in the training cohort. In a smaller external validation cohort, the AUC was 84.13% (95%CI; 64.21, 100) for accurate diagnosis of CD and UC. CONCLUSION: PR3-ANCA is highly specific for UC. The differentiating capability of a panel, which contains PR3-ANCA and weighs broadly available antibodies, is superior and utilization of the panel can support accurate classification in the work-up of pediatric and adolescent patients with IBD patients.

Age at disease onset of inflammatory bowel disease is associated with later extraintestinal manifestations and complications.

INTRODUCTION: A small but increasing number of patients with inflammatory bowel disease are diagnosed during childhood or adolescence, and disease distribution and severity at onset vary according to the age at diagnosis. Clinical factors present at the time of diagnosis can be predictive of the disease course. AIM: The aim of this study was to characterize disease behavior and the cumulative complications and extraintestinal manifestations 10 years after the diagnosis and to assess their association with age at diagnosis. PATIENTS AND METHODS: Data of patients participating with the Swiss IBD cohort study registry, a disease duration of 10 years and a complete data set were analyzed. The outcome was defined as the cumulative change of disease behavior, the occurrence of extra-intestinal manifestations or complications, and the necessity for medical or surgical interventions. RESULTS: A total of 481 patients with Crohn's disease (CD) and 386 patients with ulcerative colitis (UC), grouped according to disease onset before 10, 17, 40, or after 40 years of age, were analyzed. Despite differences in sex, initial disease location, and smoking habits, at 10 years after the diagnosis, no difference was found regarding disease behavior in CD or regarding progression of disease extension in UC. Similarly, no age-of-onset-dependent cumulative need for medical or surgical therapies was found. However, higher rates of anemia and lower rates of arthralgia and osteopenia were found in both pediatric-onset CD and UC, and a tendency toward higher rates of stomatitis in pediatric-onset CD, and of primary sclerosing cholangitis and ankylosing spondylitis in pediatric-onset UC. CONCLUSION: After 10 years of disease evolution, age at disease onset is not anymore associated with disease behavior but only with a small difference in the occurrence of specific extraintestinal manifestations and complications.

Function and Ventilation of Large and Small Airways in Children and Adolescents with Inflammatory Bowel Disease.

BACKGROUND: Extraintestinal manifestations are common among patients with inflammatory bowel disease (IBD), whereas pulmonary involvement is considered rare. However, chronic lung diseases begin with subclinical changes of the small airways and often originate in childhood. Pulmonary involvement, particularly of the small airways, can be assessed using novel inert gas washout tests. METHODS: In this prospective, single-center study, 30 children and adolescents (mean age, 14 years; SD, ±2.6; 13 boys) with IBD (mean disease duration, 3.2 years; SD, ±2.8), and 32 healthy age-matched controls, performed nitrogen multiple-breath washout, double-tracer gas single-breath washout, and diffusion capacity for carbon monoxide. Patients with IBD additionally performed spirometry, plethysmography, and measurement of exhaled nitric oxide. RESULTS: Patients with IBD demonstrated no abnormalities in classical lung function tests. There was no difference between active disease and remission. The lung clearance index, a very sensitive indicator for small airway function, did not differ between patients with IBD and healthy controls (mean difference [95% confidence interval] -0.01 [-0.28 to 0.25]). Specific markers for peripheral lung ventilation (Sacin and Scond) were also within the normal range (0.002 [-0.003 to 0.008] and -0.002 [-0.020 to 0.015], respectively). No association was found between measures of lung function and IBD subtype, clinical disease activity scores, laboratory values, treatment modalities, or disease duration. CONCLUSIONS: In our cohort of pediatric and adolescent patients with IBD without respiratory symptoms, there was no evidence of significant lung disease on extensive screening testing. General screening of asymptomatic patients therefore appears unnecessary and is not recommended in this population.