Ulcerative Colitis: Gold BD

Gold BD, Westra SJ, Graeme-Cook FM. · Department of Pediatrics, Emory University, Atlanta, USA. · N Engl J Med. · Pubmed #14695415 No free full text.

This publication has no abstract.

Heyman MB, Garnett EA, Shaikh N, Huen K, Jose FA, Harmatz P, Winter HS, Baldassano RN, Cohen SA, Gold BD, Kirschner BS, Ferry GD, Stege E, Holland N. · Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143-0136, USA. · Am J Clin Nutr. · Pubmed #19116333 No free full text.

Abstract: BACKGROUND: Folate is postulated to protect against cell injury and long-term risk of cancer. Folate deficiency has been shown to be associated with inflammatory bowel disease (IBD). However, folate concentrations are poorly delineated in children with IBD. OBJECTIVE: The objective was to compare folate concentrations between children with newly diagnosed IBD and healthy controls. DESIGN: Red blood cell folate (RBCF) and whole-blood folate (WBF) concentrations were measured in 78 children (mean age: 12.8 +/- 2.7 y): 22 patients with newly diagnosed untreated Crohn disease, 11 patients with ulcerative colitis, 4 patients with indeterminate colitis, and 41 controls. Vitamin supplementation and dietary intakes determined by food-frequency questionnaire were recorded for 20 IBD patients and 28 controls. RESULTS: RBCF concentrations were 19.4% lower in controls (587.0 +/- 148.6 ng/mL) than in patients (728.7 +/- 185.8 ng/mL; P = 0.0004), and WBF concentrations were 11.1% lower in controls (218.2 +/- 49.7 ng/mL) than in patients (245.3 +/- 59.1 ng/mL; P = 0.031). Total folate intake was 18.8% higher in controls (444.7 +/- 266.7 microg/d) than in IBD patients (361.1 +/- 230.6 microg/d), but this difference was not statistically significant (P = 0.264). Folate intakes were below the Recommended Dietary Allowance (200-400 microg/d), adjusted for age and sex, in 35.4% of study subjects. CONCLUSIONS: In contrast with previous evidence of folate deficiency in adult IBD patients, our data indicate higher folate concentrations in children with newly diagnosed untreated IBD than in controls. This finding was unexpected, especially in light of the higher dietary folate intakes and hematocrit values in children without IBD. The influence of IBD therapy on folate metabolism and the long-term clinical implications of high RBCF and WBF concentrations at the time of IBD diagnosis should be explored further.

White JM, O'Connor S, Winter HS, Heyman MB, Kirschner BS, Ferry GD, Cohen SA, Baldassano RN, Smith T, Clemons T, Gold BD. · Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA. · Clin Gastroenterol Hepatol. · Pubmed #18848910 No free full text.

Abstract: BACKGROUND & AIMS: Few epidemiologic investigations characterize inflammatory bowel disease (IBD) in non-Caucasian children. Our study compared IBD characteristics between African Americans and non-African Americans enrolled in a multicenter pediatric IBD registry with endoscopic- and pathology-based diagnosis. METHODS: The study retrieved data entered from January 2000 to October 2003 on children 1 to 17 years old, inclusive, followed by a consortium of academic and community US pediatric gastroenterology practices. Analyses examined racial/ethnic differences by comparing the proportions of African Americans and non-African Americans in the following categories: each diagnostic disease classification (any IBD, Crohn's disease, ulcerative colitis, indeterminate colitis); age group (<6 y, 6-12 y, or >12 y) at diagnosis or symptom onset; presence of extraintestinal manifestations, Z-scores for height and weight, immunomodulatory therapy, anatomic disease location, and abnormal hemoglobin, albumin, or sedimentation rate at diagnosis. RESULTS: A total of 1406 patients had complete data, 138 (10%) of whom were African American. African Americans more often were older than 12 years of age at diagnosis (52% vs 37%; odds ratio [OR], 1.82; 95% confidence interval [95% CI], 1.28-2.59) and symptom onset (46% vs 30%; OR, 1.99; 95% CI, 1.40-2.84); had Crohn's disease (78% vs 59%; OR, 2.36; 95% CI, 1.56-3.58); and had a low hemoglobin level at diagnosis (39% vs 17%; OR, 3.15; 95% CI, 1.92-5.17). CONCLUSIONS: IBD in African American children and adolescents presents more commonly with Crohn's disease and at older ages compared with non-African Americans. Racial/ethnic differences in the epidemiology of IBD, particularly Crohn's disease, among American youths require further investigation.

Gupta N, Bostrom AG, Kirschner BS, Cohen SA, Abramson O, Ferry GD, Gold BD, Winter HS, Baldassano RN, Smith T, Heyman MB. · UCSF Children's Hospital, University of California, San Francisco, California 94143-0136, USA. · Am J Gastroenterol. · Pubmed #18796101 No free full text.

Abstract: BACKGROUND: The relationship between the age at diagnosis and disease course is poorly defined in children with Crohn's disease (CD). We examined the presentation and course of disease in patients 0-5 compared to 6-17 yr of age at diagnosis. METHODS: We analyzed uniform data from 989 consecutive CD patients collected between January 2000 and November 2003, and stored in the Pediatric IBD Consortium Registry. The statistical tests account for the length of follow-up of each patient. RESULTS: In total, 98 patients (9.9%) were of 0-5 yr of age at diagnosis. The mean follow-up time was 5.6 +/- 5.0 yr in the younger group and 3.3 +/- 2.8 yr in the older group (P < 0.001). Race/ethnicity differed by the age group (P= 0.015); a larger proportion of the younger group was Asian/Pacific Islander or Hispanic, and a larger proportion of the older group was African American. The initial classification as ulcerative colitis or indeterminate colitis was more common among the 0-5 yr of age group (P < 0.001). The 6-17 yr of age patients presented with more abdominal pain (P < 0.001), weight loss (P= 0.001), or fever (P= 0.07), while the 0-5 yr of age patients presented with more rectal bleeding (P= 0.008). The 6-17 yr of age patients were more likely to be treated with antibiotics (P < 0.001), 6-mercaptopurine/azathioprine (P < 0.001), infliximab (P= 0.001), or corticosteroids (P= 0.0006). The 6-17 yr of age patients had a higher cumulative incidence of treatment with 5-aminosalicylates (P= 0.009) or methotrexate (P= 0.04). The risk for developing an abscess (P= 0.001), a fistula (P= 0.02), a stricture (P= 0.05), or a perianal fissure (P= 0.06) was greater in the 6-17 yr of age patients. CONCLUSIONS: The 6-17 yr of age patients with CD appear to have a more complicated disease course compared to 0-5 yr of age children. The 0-5 yr of age group may represent a unique disease phenotype and benefit from different approaches to management. Long-term prospective studies are required to validate these findings.

Jose FA, Garnett EA, Vittinghoff E, Ferry GD, Winter HS, Baldassano RN, Kirschner BS, Cohen SA, Gold BD, Abramson O, Heyman MB. · Department of Pediatric Gastroenterology Hepatology and Nutrition, San Francisco, California 94143, USA. · Inflamm Bowel Dis. · Pubmed #18626963 No free full text.

Abstract: BACKGROUND: Extraintestinal manifestations (EIMs) in pediatric patients with inflammatory bowel disease (IBD) are poorly characterized. We examined the prevalence of EIMs at diagnosis, subsequent incidence, and risk factors for EIMs. METHODS: Data for 1649 patients from the PediIBD Consortium Registry, diagnosed with IBD before 18 years of age (1007 [61%] with Crohn's disease, 471 [29%] with ulcerative colitis, and 171 [10%] with indeterminate colitis), were analyzed using logistic regression, Kaplan-Meier, log rank tests, and Cox models. RESULTS: EIMs were reported prior to IBD diagnosis in 97 of 1649 patients (6%). Older children at diagnosis had higher rates compared with younger children, and arthritis (26%) and aphthous stomatitis (21%) were most common. Among the 1552 patients without EIM at diagnosis, 290 developed at least 1 EIM. Kaplan-Meier estimates of cumulative incidence were 9% at 1 year, 19% at 5 years, and 29% at 15 years after diagnosis. Incidence did not differ by IBD type (P = 0.20), age at diagnosis (P = 0.22), or race/ethnicity (P = 0.24). Arthritis (17%) and osteopenia/osteoporosis (15%) were the most common EIMs after IBD diagnosis. CONCLUSIONS: In our large cohort of pediatric IBD patients, 6% had at least 1 EIM before diagnosis of IBD. At least 1 EIM will develop in 29% within 15 years of diagnosis. The incidence of EIMs both before and after diagnosis of IBD differs by type of EIM and may be slightly higher in girls, but is independent of the type of IBD, age at diagnosis, and race/ethnicity.

Perrin JM, Kuhlthau K, Chughtai A, Romm D, Kirschner BS, Ferry GD, Cohen SA, Gold BD, Heyman MB, Baldassano RN, Winter HS. · Department of Pediatrics, MassGeneral Hospital for Children, Boston, USA. · J Pediatr Gastroenterol Nutr. · Pubmed #18223375 No free full text.

Abstract: OBJECTIVE: To extend development of a pediatric inflammatory bowel disease (IBD) health-related quality of life (HRQoL) measure by determining its factor structure and associations of factors with generic HRQoL measures and clinical variables. PATIENTS AND METHODS: Cross-sectional survey of children and adolescents ages 8 years to 18 years and their parents attending any of 6 US IBD centers, recruited from either existing registry of age-eligible subjects or visits to participating centers. The survey included generic (Pediatric Quality of Life Inventory) and IBD-specific (Impact Questionnaire) quality of life measures, disease activity, and other clinical indicators. We carried out factor analysis of Impact responses, comparing resulting factors with results on the generic HRQoL and the clinical measures. RESULTS: We included 220 subjects (161 with Crohn disease and 59 with ulcerative colitis). Initial confirmatory factor analysis did not support the 6 proposed Impact domains. Exploratory factor analysis indicated 4 factors with good to excellent reliability for IBD responses: general well-being and symptoms, emotional functioning, social interactions, and body image. Two items did not load well on any factor. The 4 factors correlated well with the Pediatric Quality of Life Inventory and subscales. Children with higher disease activity scores and other indicators of clinical activity reported lower HRQoL. CONCLUSIONS: This study provides further characteristics of a HRQoL measure specific to pediatric IBD and indicates ways to score the measure based on the resulting factor structure. The measure correlates appropriately with generic HRQoL measures and clinical severity indicators.

Anonymous00166, Anonymous00167, Bousvaros A, Antonioli DA, Colletti RB, Dubinsky MC, Glickman JN, Gold BD, Griffiths AM, Jevon GP, Higuchi LM, Hyams JS, Kirschner BS, Kugathasan S, Baldassano RN, Russo PA. · No affiliation provided · J Pediatr Gastroenterol Nutr. · Pubmed #17460505 No free full text.

Abstract: BACKGROUND: Studies of pediatric inflammatory bowel disease (IBD) have varied in the criteria used to classify patients as having Crohn disease (CD), ulcerative colitis (UC), or indeterminate colitis (IC). Patients undergoing an initial evaluation for IBD will often undergo a series of diagnostic tests, including barium upper gastrointestinal series with small bowel follow-through, abdominal CT, upper endoscopy, and colonoscopy with biopsies. Other tests performed less frequently include magnetic resonance imaging scans, serological testing, and capsule endoscopy. The large amount of clinical information obtained may make a physician uncertain as to whether to label a patient as having CD or UC. Nevertheless, to facilitate the conduct of epidemiological studies in children, to allow the entry of children into clinical trials, and to allow physicians to more clearly discuss diagnosis with their patients, it is important that clinicians be able to differentiate between CD and UC. METHODS: A consensus conference regarding the diagnosis and classification of pediatric IBD was organized by the Crohn's and Colitis Foundation of America. The meeting included 10 pediatric gastroenterologists and 4 pediatric pathologists. The primary aim was to determine the utility of endoscopy and histology in establishing the diagnosis of CD and UC. Each member of the group was assigned a topic for review. Topics evaluated included differentiating inflammatory bowel disease from acute self-limited colitis, endoscopic and histological features that allow differentiation between CD and UC, upper endoscopic features seen in both CD and UC, ileal inflammation and "backwash ileitis" in UC, patchiness and rectal sparing in pediatric IBD, periappendiceal inflammation in CD and UC, and definitions of IC. RESULTS: Patients with UC may have histological features such as microscopic inflammation of the ileum, histological gastritis, periappendiceal inflammation, patchiness, and relative rectal sparing at the time of diagnosis. These findings should not prompt the clinician to change the diagnosis from UC to CD. Other endoscopic findings, such as macroscopic cobblestoning, segmental colitis, ileal stenosis and ulceration, perianal disease, and multiple granulomas in the small bowel or colon more strongly suggest a diagnosis of CD. An algorithm is provided to enable the clinician to differentiate more reliably between these 2 entities. CONCLUSIONS: The recommendations and algorithm presented here aim to assist the clinician in differentiating childhood UC from CD. We hope the recommendations in this report will reduce variability among practitioners in how they use the terms "ulcerative colitis," "Crohn disease," and "indeterminate colitis." The authors hope that progress being made in genetic, serological, and imaging studies leads to more reliable phenotyping.

Gupta N, Cohen SA, Bostrom AG, Kirschner BS, Baldassano RN, Winter HS, Ferry GD, Smith T, Abramson O, Gold BD, Heyman MB. · UCSF Children's Hospital, University of California, San Francisco, California 94143-0136, USA. · Gastroenterology. · Pubmed #16618401 No free full text.

Abstract: BACKGROUND & AIMS: The cumulative incidence of surgery ranges from 40%-70% at 10 years from the time of diagnosis of Crohn's disease in adults. We retrospectively determined the cumulative incidence of and risk factors for surgery (intestinal resection) in pediatric patients with Crohn's disease. METHODS: Uniform data from 989 consecutive Crohn's disease patients (age 0-17 years at diagnosis), collected from 6 different pediatric centers between January 2000 and November 2003 and stored in the Pediatric IBD Consortium Registry, were analyzed. RESULTS: Median follow-up time was 2.8 years (range, 1 day to 16.7 years). One hundred twenty-eight patients underwent surgery. Kaplan-Meier survival estimates of the cumulative incidence of surgery were 17% at 5 years and 28% at 10 years from the diagnosis of inflammatory bowel disease. Univariate Cox proportional hazards models showed leukocytosis (2.85 [hazard ratio]; P = .02), hypoalbuminemia (3.41; P = .05), and anti-Saccharomyces cerevisiae antibody (ASCA) positivity (3.43; P = .05) were associated with increased risk for surgery. Multivariate Cox models showed female gender (1.49; P = .03), initial diagnosis of ulcerative colitis (3.63; P < .0001), poor growth at presentation (2.16; P = .007), and abscess (1.90; P = .009), fistula (2.30; P = .0005), or stricture (3.41; P < .0001) development were associated with increased risk for surgery. Age 3-5 years (0.26; P = .01) or 6-12 years (0.62; P = .01) at diagnosis, fever at presentation (0.50; P = .03), and treatment with infliximab (0.36; P = .0005) or 5-aminosalicylic acid (0.44; P < .0001) were associated with decreased risk for surgery. CONCLUSIONS: Risk stratification during the course of Crohn's disease in pediatric patients will help to guide therapy that may improve the natural history of disease and decrease the need for surgery.

Heyman MB, Kirschner BS, Gold BD, Ferry G, Baldassano R, Cohen SA, Winter HS, Fain P, King C, Smith T, El-Serag HB. · UCSF Children's Hospital, University of California, San Francisco, CA 94143, USA. · J Pediatr. · Pubmed #15644819 No free full text.

Abstract: OBJECTIVE: To determine the characteristics of inflammatory bowel disease (IBD) in young patients. STUDY DESIGN: Uniform data were collected from a cohort of patients with IBD who were enrolled from January 2000 to November 2002 at six pediatric centers (Pediatric IBD Consortium). RESULTS: Of 1370 children in the registry, the mean age at IBD diagnosis was 10.3 +/- 4.4 years; 54% were male, and 86% were white. Diagnosis was confirmed in 87 (6.1%) under 3 years of age, 211 (15.4%) before 6 years, 654 (47.7%) at 6 to 12 years, and 505 (36.9%) at 13 to 17 years. More than 63% of children younger than 8 years of age had isolated colonic disease, whether Crohn disease, ulcerative colitis (UC), or indeterminate colitis. Conversely, only 35% of those 8 years of age or older had isolated colonic disease ( P < .0001). Overall, 29% had one or more family members with IBD. The subgroup of children younger than 3 years of age with UC had the highest prevalence of first-degree relatives with IBD (44%). CONCLUSIONS: This demographically diverse pediatric IBD cohort revealed age-related variation in the distribution of IBD phenotype, with a high prevalence of isolated colonic disease in young children. Positive family history was especially common in young patients with UC.