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High Dose Vitamin D Therapy in Paediatric IBD
AGA Abstracts
and 8 of 22 patients. In the cases with negative MRE in the colon but positive endoscopy and/or histology, subtle endoscopic lesions such as erosions were described. Findings in the ileum were concordant in 16/17 patients and MRE describes the length of ileal involvement. In 5 cases the ileocaecal valve could not be intubated. In all those patients MRE findings were abnormal. MRE detected ileal stenosis with prestenotic dilatation in 4/22 patients. The jejunum was affected in 3/22 patients and fistula were described in 2/22 children. CONCLUSIONS: In this cohort, MRE fails to detect subtle endoscopic and histologic colonic lesions. In contrast, good concordance was seen at the level of the ileum.. MRE describes the extent of ileal involvement, the (non)occurrence of ileal stenosis and is of additional diagnostic use in case of failure of intubation of the ileocaecal valve. It also describes jejunal involvement and the occurrence of fistula, enabling a better classification according to the Montreal criteria. MRE was not widely used in Belcro at diagnosis but is now increasingly in the prospective part of the registry.
(96.2%) controls. Conclusion: Campylobacter spp. and Sutterella wadsworthensis are commonly identified in the paediatric colon. C. concisus appears more prevalent in CD although this was not significant. Helicobacter spp. are uncommon. PCR and culture methodology have revealed no significant distinction between the microaerophilic microbiota of paediatric IBD versus controls. It is unlikely that these organisms have a role in the initiation of paediatric IBD. Su1924 PANCA Status and Its Relationship to Psychological Profile in Children With Ulcerative Colitis Ninfa Candela, Toba A. Weinstein, Jeremiah J. Levine, Louise Maranda, James Markowitz Background: In adults with UC, pANCA status has been shown to be important in distinguishing psychobiological subtypes of disease, such that an absence of pANCA was associated with an interaction between psychological factors and disease activity that was not present in the pANCA positive subjects (Maunder et al, 2006). We investigated the interaction between biological and psychological factors in UC by focusing on the relationship of depression, anxiety and disease activity in children with UC and its relationship to pANCA. Methods: Consecutive children with previously established, biopsy proven UC who presented to the pediatric GI clinic were recruited for participation in the study. All underwent evaluation using the following tests: current UC disease activity (Pediatric Ulcerative Colitis Activity Index [PUCAI]), depression (Children's Depression Inventory [CDI-S]), anxiety (Revised Child Manifest Anxiety Scale [RCMAS]), quality of life (IMPACT-III [QOL]) and pANCA status (Prometheus Labs, San Diego, CA). Comparisons between pANCA+ and pANCA- subjects were performed. Strength of relationships between actual scores was measured using Pearson's correlation coefficient, r. Significance was set at p < 0.05. Results: 51 children (13.5±2.7yrs old at time of recruitment, 4.9±2.6 yrs total duration of UC, 49% with active disease, 51% male, 60% pANCA+) with UC were evaluated. Demographic characteristics were comparable in the two pANCA groups. No significant differences were found between the pANCA groups in terms of mean disease activity, depression or anxiety scores (Table 1), although QOL scores appeared somewhat better in the pANCA+ group. In the pANCA- subjects no relationship was found between disease activity and depression (r =0.003, p = 0.990), and there was only a weak positive association between disease activity and anxiety scores (r = 0.301, p = 0.225). In pANCA+ subjects there were moderate, statistically significant associations between disease activity and depression scores (r = 0.459, p = 0.012) and between disease activity and total anxiety (r = 0.590, p = 0.001). Conclusion: While psychological profiles do not differ between pANCA+ and pANCA- children with UC, disease activity appears to correlate with both depression and anxiety scores only in the pANCA+ subjects. These results appear diametrically opposite to those previously reported in adults. Larger studies with a more diverse disease activity population are necessary to better explore this interaction in children. In addition, differences between our results and published adult literature suggest that further investigations are required to understand and determine the role (if any) of pANCA as it relates to psychological profile and disease activity in UC. Table 1: Psychological Evaluations and QOL Stratified by pANCA Status
Su1922 Terminal Ileal Biopsy, Small Bowel Imaging and Upper-GI Endoscopy - All Required for Efficient Diagnosis of Paediatric Crohn's Disease Robin Dart, Richard K. Russell, Pamela Rogers, Peter M. Gillett, David C. Wilson Introduction: Differentiating Crohn's disease from UC and IBDU is vital for early management, particularly in children. Appreciable phenotypic differences between adult and paediatriconset Crohn's disease (PCD) exist in location extent at diagnosis. Guidelines for diagnosis of PCD recommend assessment by upper-gastrointestinal endoscopy (UGIE), colonoscopy with terminal ileal (TI) biopsy and small-bowel imaging. We aimed to establish the relative contribution of each part of evaluation to PCD diagnosis. Methods: We performed a retrospective case note review on the cohort of PCD (diagnosis <17 years of age) patients from a regional paediatric IBD centre from 1997 to 2009. Patients who underwent full endoscopic examination at first presentation including attempted TI biopsy, UGIE and small-bowel imaging (barium follow-through or small-bowel MRI) were included. Pathology reports were examined and location of PCD defining granulomatous inflammation was recorded. Montreal classification was recorded for all patients. Results: Pathology and endoscopy reports were available for 105/114 (92%) patients with PCD undergoing full GI tract evaluation at initial diagnosis. Terminal ileal biopsy was achieved on 63% (66/105) occasions. Histopathological defining features of PCD in the TI alone were present in 11% (7/66) of cases. Diagnosis of PCD was achieved on the basis of small bowel imaging in 10% of all cases (10/105) with non-specific GI histopathology for PCD including 5% of cases (3/66) where TI biopsy was achieved. Histopathological defining features of PCD were seen in UGIE alone in 8% (8/105) ; 7/8 cases included colonoscopy + TI biopsy where TI biopsy was not diagnostic. Sensitivity of colonoscopy without TI biopsy, UGIE and small bowel imaging for PCD was 77% in our cohort. Sensitivity of colonoscopy + TI biopsy alone was 83%. This improved to 90% when small bowel imaging was added and to 98% when UGIE was added to the evaluation (two patients had non-Crohn's specific intestinal inflammation with exta-intestinal granulomatous inflammation). Conclusions: Differentiation of PCD from UC can be challenging, and requires careful correlation of clinical, endoscopic, pathological and radiological findings. Our data strongly supports the recommendation by BSPGHAN1 that children suspected of IBD should have full endoscopic and radiological evaluation at diagnosis. Many children undergo endoscopic evaluation by adult gastroenterologists, who are more accustomed to the adult distribution of disease, and may be tempted to forgo full ileocolonoscopy (IC) and UGIE. However our data demonstrate the need for both UGIE and IC which significantly improve diagnostic yield in PCD. References: 1. Sandhu et al. Guidelines for the Management of Inflammatory Bowel Disease in Children in the United Kingdom. JPGN 2010;50: S1-S13 Su1923
Su1925
The Role of the Microaerophilic Colonic Microbiota in De-Novo Paediatric Inflammatory Bowel Disease Richard Hansen, Indrani Mukhopadhya, Richard K. Russell, William M. Bisset, Susan H. Berry, John M. Thomson, Emad El-Omar, Georgina L. Hold
High Dose Vitamin D Therapy in Paediatric IBD Andrew S. Day, Daniel A. Lemberg, Rachel Messenger, Helen J. Woodhead Background and Aims: Vitamin D deficiency is commonly seen in children with IBD, requiring supplementation. Intermittent high dose (STOSS) therapy has not previously been evaluated in paediatric IBD. Methods: The records of children with IBD were reviewed to determine those with Vitamin D deficiency managed with STOSS therapy. Children were administered up to 800,000 units of Vitamin D as a single dosage. The background characteristics of the children, response to therapy, side-effects and requirement for repeated dosing were reviewed. Results: Twenty-eight children with IBD were identified to have had a total of 35 STOSS treatments. Seven children required repeat dosing after a mean of 12.6 months. 25OHVit D level prior to treatment was 37.9 (range <12 to 49). Therapy lead to an elevation in Vitamin D levels in all cases: the mean 25OHVit D level 1 week after therapy was 216.6 (range of 89-298) and 144.3 (range 62-253) 4 weeks after therapy. Hypercalcaemia was not seen after dosing. Conclusions: Single high-dose therapy for children with IBD effectively and safely corrects vitamin D deficiency in children with IBD. Clarification of dosage and timing for scheduled repeat dosing requires further evaluation.
Introduction: Helicobacter species can initiate animal colitis similar to human ulcerative colitis (UC). Campylobacter concisus has been linked to paediatric Crohn's disease (CD). Microaerophilic organisms such as Helicobacter and Campylobacter may be involved in the initiation of IBD. Aim: To establish the prevalence of Helicobacter and Campylobacter in treatment naïve, de-novo paediatric IBD and controls. Methods: Paediatric patients undergoing colonoscopy were recruited to two groups: those with a new diagnosis of IBD at their first presentation and controls with a macroscopically normal colon and no evidence of IBD on biopsy. All subjects were free from systemic antibiotics, steroids and immunosuppression for 3 months. 24 IBD patients and 26 controls were studied. The IBD cohort comprised 12 (50%) CD, 8 (33.3%) UC and 4 (16.7%) IBD unspecified (IBD-U) patients. 15 (62.5%) of the IBD and 20 (77.8%) of the control group were male with median ages of 12.4 and 11.0 years respectively. 5-6 colonic mucosal biopsies were taken: in controls largely from the sigmoid/rectum and in IBD from the most distal inflamed site. 3 biopsies were stored at -80C for subsequent DNA extraction and PCR. 1-2 biopsies were used for culture. 5 selective plates were used alongside blood agar. Cultures were incubated in microaerophilic conditions (Anoxomat) at 37C. Plates were reviewed twice weekly for up to one month. Isolates deemed Gram-negative and microaerophilic underwent PCR of the 16S rRNA gene for phylogenetic identification. Results: No Helicobacter were cultured. 3 Campylobacter species were cultured: C. concisus from a subject with CD, Campylobacter curvus and Campylobacter showae from controls. Sutterella wadsworthensis was isolated from 13 subjects: 8 controls and 5 IBD. All biopsies were positive for bacterial DNA with universal eubacterial primers. Nested PCR for Helicobacter genus was positive in 5 (10%) subjects, comprising 3 (12.5%) IBD and 2 (7.7%) controls. PCR for Campylobacter genus was positive in 38 (76%) subjects, comprising 19 (79.2%) IBD and 19 (73.1%) controls. Nested PCR for C. concisus was positive in 25 (50%) subjects, comprising 14 (58.3%) IBD (8/12 CD, 3/8 UC and 3/4 IBDU) and 11 (42.3%) controls. In response to frequent isolation of the organism, PCR for S. wadsworthensis was positive in 48 (96%) subjects, comprising 23 (95.8%) IBD and 25
AGA Abstracts
Su1926 The Natural History of Ulcerative Colitis in Pediatric Population: A 20 Year Population-Based Study Hoda M. Malaty, Bincy P. Abraham, Seema Mehta, Carolyn Thibodeaux, George D. Ferry OBJECTIVES: The natural history of ulcerative colitis (UC) has not been well studied in pediatric populations. METHODS: We performed a retrospective investigation on a cohort of children diagnosed with UC between 1989 and 2003 and registered in the IBD center at Texas Children's Hospital. We included the demographics (i.e., age, sex, and age at diagnosis). The diagnosis of IBD was based on clinical, radiological, endoscopic, and histological examinations. Disease diagnosis and distribution was identified on the basis of a review of all endoscopic, colonoscopic, pathological, and radiological records. We estimated the occurrence colectomy, presence of proctitis and extra intestinal manifestations (EIMs) at the
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and 8 of 22 patients. In the cases with negative MRE in the colon but positive endoscopy and/or histology, subtle endoscopic lesions such as erosions were described. Findings in the ileum were concordant in 16/17 patients and MRE describes the length of ileal involvement. In 5 cases the ileocaecal valve could not be intubated. In all those patients MRE findings were abnormal. MRE detected ileal stenosis with prestenotic dilatation in 4/22 patients. The jejunum was affected in 3/22 patients and fistula were described in 2/22 children. CONCLUSIONS: In this cohort, MRE fails to detect subtle endoscopic and histologic colonic lesions. In contrast, good concordance was seen at the level of the ileum.. MRE describes the extent of ileal involvement, the (non)occurrence of ileal stenosis and is of additional diagnostic use in case of failure of intubation of the ileocaecal valve. It also describes jejunal involvement and the occurrence of fistula, enabling a better classification according to the Montreal criteria. MRE was not widely used in Belcro at diagnosis but is now increasingly in the prospective part of the registry.
(96.2%) controls. Conclusion: Campylobacter spp. and Sutterella wadsworthensis are commonly identified in the paediatric colon. C. concisus appears more prevalent in CD although this was not significant. Helicobacter spp. are uncommon. PCR and culture methodology have revealed no significant distinction between the microaerophilic microbiota of paediatric IBD versus controls. It is unlikely that these organisms have a role in the initiation of paediatric IBD. Su1924 PANCA Status and Its Relationship to Psychological Profile in Children With Ulcerative Colitis Ninfa Candela, Toba A. Weinstein, Jeremiah J. Levine, Louise Maranda, James Markowitz Background: In adults with UC, pANCA status has been shown to be important in distinguishing psychobiological subtypes of disease, such that an absence of pANCA was associated with an interaction between psychological factors and disease activity that was not present in the pANCA positive subjects (Maunder et al, 2006). We investigated the interaction between biological and psychological factors in UC by focusing on the relationship of depression, anxiety and disease activity in children with UC and its relationship to pANCA. Methods: Consecutive children with previously established, biopsy proven UC who presented to the pediatric GI clinic were recruited for participation in the study. All underwent evaluation using the following tests: current UC disease activity (Pediatric Ulcerative Colitis Activity Index [PUCAI]), depression (Children's Depression Inventory [CDI-S]), anxiety (Revised Child Manifest Anxiety Scale [RCMAS]), quality of life (IMPACT-III [QOL]) and pANCA status (Prometheus Labs, San Diego, CA). Comparisons between pANCA+ and pANCA- subjects were performed. Strength of relationships between actual scores was measured using Pearson's correlation coefficient, r. Significance was set at p < 0.05. Results: 51 children (13.5±2.7yrs old at time of recruitment, 4.9±2.6 yrs total duration of UC, 49% with active disease, 51% male, 60% pANCA+) with UC were evaluated. Demographic characteristics were comparable in the two pANCA groups. No significant differences were found between the pANCA groups in terms of mean disease activity, depression or anxiety scores (Table 1), although QOL scores appeared somewhat better in the pANCA+ group. In the pANCA- subjects no relationship was found between disease activity and depression (r =0.003, p = 0.990), and there was only a weak positive association between disease activity and anxiety scores (r = 0.301, p = 0.225). In pANCA+ subjects there were moderate, statistically significant associations between disease activity and depression scores (r = 0.459, p = 0.012) and between disease activity and total anxiety (r = 0.590, p = 0.001). Conclusion: While psychological profiles do not differ between pANCA+ and pANCA- children with UC, disease activity appears to correlate with both depression and anxiety scores only in the pANCA+ subjects. These results appear diametrically opposite to those previously reported in adults. Larger studies with a more diverse disease activity population are necessary to better explore this interaction in children. In addition, differences between our results and published adult literature suggest that further investigations are required to understand and determine the role (if any) of pANCA as it relates to psychological profile and disease activity in UC. Table 1: Psychological Evaluations and QOL Stratified by pANCA Status
Su1922 Terminal Ileal Biopsy, Small Bowel Imaging and Upper-GI Endoscopy - All Required for Efficient Diagnosis of Paediatric Crohn's Disease Robin Dart, Richard K. Russell, Pamela Rogers, Peter M. Gillett, David C. Wilson Introduction: Differentiating Crohn's disease from UC and IBDU is vital for early management, particularly in children. Appreciable phenotypic differences between adult and paediatriconset Crohn's disease (PCD) exist in location extent at diagnosis. Guidelines for diagnosis of PCD recommend assessment by upper-gastrointestinal endoscopy (UGIE), colonoscopy with terminal ileal (TI) biopsy and small-bowel imaging. We aimed to establish the relative contribution of each part of evaluation to PCD diagnosis. Methods: We performed a retrospective case note review on the cohort of PCD (diagnosis <17 years of age) patients from a regional paediatric IBD centre from 1997 to 2009. Patients who underwent full endoscopic examination at first presentation including attempted TI biopsy, UGIE and small-bowel imaging (barium follow-through or small-bowel MRI) were included. Pathology reports were examined and location of PCD defining granulomatous inflammation was recorded. Montreal classification was recorded for all patients. Results: Pathology and endoscopy reports were available for 105/114 (92%) patients with PCD undergoing full GI tract evaluation at initial diagnosis. Terminal ileal biopsy was achieved on 63% (66/105) occasions. Histopathological defining features of PCD in the TI alone were present in 11% (7/66) of cases. Diagnosis of PCD was achieved on the basis of small bowel imaging in 10% of all cases (10/105) with non-specific GI histopathology for PCD including 5% of cases (3/66) where TI biopsy was achieved. Histopathological defining features of PCD were seen in UGIE alone in 8% (8/105) ; 7/8 cases included colonoscopy + TI biopsy where TI biopsy was not diagnostic. Sensitivity of colonoscopy without TI biopsy, UGIE and small bowel imaging for PCD was 77% in our cohort. Sensitivity of colonoscopy + TI biopsy alone was 83%. This improved to 90% when small bowel imaging was added and to 98% when UGIE was added to the evaluation (two patients had non-Crohn's specific intestinal inflammation with exta-intestinal granulomatous inflammation). Conclusions: Differentiation of PCD from UC can be challenging, and requires careful correlation of clinical, endoscopic, pathological and radiological findings. Our data strongly supports the recommendation by BSPGHAN1 that children suspected of IBD should have full endoscopic and radiological evaluation at diagnosis. Many children undergo endoscopic evaluation by adult gastroenterologists, who are more accustomed to the adult distribution of disease, and may be tempted to forgo full ileocolonoscopy (IC) and UGIE. However our data demonstrate the need for both UGIE and IC which significantly improve diagnostic yield in PCD. References: 1. Sandhu et al. Guidelines for the Management of Inflammatory Bowel Disease in Children in the United Kingdom. JPGN 2010;50: S1-S13 Su1923
Su1925
The Role of the Microaerophilic Colonic Microbiota in De-Novo Paediatric Inflammatory Bowel Disease Richard Hansen, Indrani Mukhopadhya, Richard K. Russell, William M. Bisset, Susan H. Berry, John M. Thomson, Emad El-Omar, Georgina L. Hold
High Dose Vitamin D Therapy in Paediatric IBD Andrew S. Day, Daniel A. Lemberg, Rachel Messenger, Helen J. Woodhead Background and Aims: Vitamin D deficiency is commonly seen in children with IBD, requiring supplementation. Intermittent high dose (STOSS) therapy has not previously been evaluated in paediatric IBD. Methods: The records of children with IBD were reviewed to determine those with Vitamin D deficiency managed with STOSS therapy. Children were administered up to 800,000 units of Vitamin D as a single dosage. The background characteristics of the children, response to therapy, side-effects and requirement for repeated dosing were reviewed. Results: Twenty-eight children with IBD were identified to have had a total of 35 STOSS treatments. Seven children required repeat dosing after a mean of 12.6 months. 25OHVit D level prior to treatment was 37.9 (range <12 to 49). Therapy lead to an elevation in Vitamin D levels in all cases: the mean 25OHVit D level 1 week after therapy was 216.6 (range of 89-298) and 144.3 (range 62-253) 4 weeks after therapy. Hypercalcaemia was not seen after dosing. Conclusions: Single high-dose therapy for children with IBD effectively and safely corrects vitamin D deficiency in children with IBD. Clarification of dosage and timing for scheduled repeat dosing requires further evaluation.
Introduction: Helicobacter species can initiate animal colitis similar to human ulcerative colitis (UC). Campylobacter concisus has been linked to paediatric Crohn's disease (CD). Microaerophilic organisms such as Helicobacter and Campylobacter may be involved in the initiation of IBD. Aim: To establish the prevalence of Helicobacter and Campylobacter in treatment naïve, de-novo paediatric IBD and controls. Methods: Paediatric patients undergoing colonoscopy were recruited to two groups: those with a new diagnosis of IBD at their first presentation and controls with a macroscopically normal colon and no evidence of IBD on biopsy. All subjects were free from systemic antibiotics, steroids and immunosuppression for 3 months. 24 IBD patients and 26 controls were studied. The IBD cohort comprised 12 (50%) CD, 8 (33.3%) UC and 4 (16.7%) IBD unspecified (IBD-U) patients. 15 (62.5%) of the IBD and 20 (77.8%) of the control group were male with median ages of 12.4 and 11.0 years respectively. 5-6 colonic mucosal biopsies were taken: in controls largely from the sigmoid/rectum and in IBD from the most distal inflamed site. 3 biopsies were stored at -80C for subsequent DNA extraction and PCR. 1-2 biopsies were used for culture. 5 selective plates were used alongside blood agar. Cultures were incubated in microaerophilic conditions (Anoxomat) at 37C. Plates were reviewed twice weekly for up to one month. Isolates deemed Gram-negative and microaerophilic underwent PCR of the 16S rRNA gene for phylogenetic identification. Results: No Helicobacter were cultured. 3 Campylobacter species were cultured: C. concisus from a subject with CD, Campylobacter curvus and Campylobacter showae from controls. Sutterella wadsworthensis was isolated from 13 subjects: 8 controls and 5 IBD. All biopsies were positive for bacterial DNA with universal eubacterial primers. Nested PCR for Helicobacter genus was positive in 5 (10%) subjects, comprising 3 (12.5%) IBD and 2 (7.7%) controls. PCR for Campylobacter genus was positive in 38 (76%) subjects, comprising 19 (79.2%) IBD and 19 (73.1%) controls. Nested PCR for C. concisus was positive in 25 (50%) subjects, comprising 14 (58.3%) IBD (8/12 CD, 3/8 UC and 3/4 IBDU) and 11 (42.3%) controls. In response to frequent isolation of the organism, PCR for S. wadsworthensis was positive in 48 (96%) subjects, comprising 23 (95.8%) IBD and 25
AGA Abstracts
Su1926 The Natural History of Ulcerative Colitis in Pediatric Population: A 20 Year Population-Based Study Hoda M. Malaty, Bincy P. Abraham, Seema Mehta, Carolyn Thibodeaux, George D. Ferry OBJECTIVES: The natural history of ulcerative colitis (UC) has not been well studied in pediatric populations. METHODS: We performed a retrospective investigation on a cohort of children diagnosed with UC between 1989 and 2003 and registered in the IBD center at Texas Children's Hospital. We included the demographics (i.e., age, sex, and age at diagnosis). The diagnosis of IBD was based on clinical, radiological, endoscopic, and histological examinations. Disease diagnosis and distribution was identified on the basis of a review of all endoscopic, colonoscopic, pathological, and radiological records. We estimated the occurrence colectomy, presence of proctitis and extra intestinal manifestations (EIMs) at the
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