A meta-analytic review of the psychosocial adjustment of youth with inflammatory bowel disease.

OBJECTIVE: To conduct a meta-analytic review of psychosocial adjustment of youth with inflammatory bowel disease (IBD). METHODS: Nineteen studies with a total of 1167 youth with IBD (M age = 14.33, 50% female) were included. Effect size (ES) estimates were calculated for anxiety symptoms & disorders, depressive symptoms & disorders, internalizing symptoms & disorders, externalizing symptoms, quality of life (QOL), social functioning, and self-esteem. Separate ESs were calculated for comparisons between IBD and youth with chronic illnesses versus healthy youth. RESULTS: Youth with IBD had higher rates of depressive disorders and internalizing disorders than youth with other chronic conditions. Youth with IBD had higher parent-reported internalizing symptoms, lower parent- and youth-reported QOL, and lower youth-reported social functioning compared to healthy youth. CONCLUSIONS: Clinical attention to depressive disorders, QOL, and social functioning may be particularly salient in the context of pediatric IBD.

Increased immune reactivity predicts aggressive complicating Crohn's disease in children.

BACKGROUND & AIMS: The ability to identify children with CD who are at highest risk for rapid progression from uncomplicated to complicated phenotypes would be invaluable in guiding initial therapy. The aims of this study were to determine whether immune responses and/or CARD15 variants are associated with complicated disease phenotypes and predict disease progression. METHODS: Sera were collected from 796 pediatric CD cases and tested for anti-Cbir1 (flagellin), anti-outer membrane protein C, anti-Saccharomyces cerevisiae, and perinuclear antineutrophil cytoplasmic antibody by using enzyme-linked immunosorbent assay. Genotyping (Taqman MGB) was performed for 3 CARD15 variants (single nucleotide polymorphisms 8, 12, and 13). Associations between immune responses (antibody sum and quartile sum score, CARD15, and clinical phenotype were evaluated. RESULTS: Thirty-two percent of patients developed at least 1 disease complication within a median of 32 months, and 18% underwent surgery. The frequency of internal penetrating, stricturing, and surgery significantly increased (P trend < .0001 for all 3 outcomes) with increasing antibody sum and quartile sum score. Nine percent of seropositive groups had internal penetrating/stricturing versus 2.9% in the seronegative group (P = .01). Twelve percent of seropositive groups underwent surgery versus 2% in the seronegative group (P = .0001). The highest antibody sum group (3) and quartile sum score group (4) demonstrated the most rapid disease progression (P < .0001). Increased hazard ratio was observed for antibody sum group 3 (7.8; confidence interval, 2.2-28.7), P < .002 and quartile sum score group 4 (11.0; confidence interval, 1.5-83.0, P < .02). CONCLUSIONS: The rate of complicated CD increases in children as the number and magnitude of immune reactivity increase. Disease progression is significantly faster in children expressing immune reactivity.

Body mass index in children with newly diagnosed inflammatory bowel disease: observations from two multicenter North American inception cohorts.

OBJECTIVE: To conduct a systematic review of children with newly diagnosed inflammatory bowel disease (IBD) from 2 prospective inception cohorts to examine body mass index (BMI) status at presentation. STUDY DESIGN: Clinical, demographic, and BMI data were obtained from 783 patients with newly diagnosed IBD. National Health and Nutrition Examination Survey data for 2748 healthy children were used as a control. RESULTS: Most children with Crohn's disease and ulcerative colitis had a BMI in the normative range (5%-84%). Low BMI (<5%) was seen in 22% to 24% of children with Crohn's disease and 7% to 9% of children with ulcerative colitis. Ten percent of children with Crohn's disease and 20% to 30% of children with ulcerative colitis had a BMI at diagnosis consistent with overweight or risk for overweight. CONCLUSION: Children with IBD are affected by current population trends toward overweight. A significant subgroup of children with newly diagnosed IBD has a BMI categorized as overweight or at risk for overweight. Clinicians should be aware of possible IBD diagnosis in the presence increased BMI.

Comparative phenotypic and CARD15 mutational analysis among African American, Hispanic, and White children with Crohn's disease.

BACKGROUND: Despite a large body of literature on the subject of Crohn's disease (CD), very little information is available on racial/ethnic differences related to disease presentation, clinical course, and genetics. The first identified CD susceptibility gene, CARD15, seems to be present in up to 40% of white children with CD. However, the frequency of this gene among patients with CD of other racial/ethnic groups in the United States is not known. METHODS: We conducted a multicenter study on African American and Hispanic children with CD to describe the phenotypic and genotypic (CARD15) features in comparison with white children with CD. We also analyzed the frequency of CARD15 mutations in large control samples from white, African American, and Hispanic children. RESULTS: The disease location and behavior were similar among all 3 groups, with inflammatory behavior and the ileocolonic location being the most frequent phenotype. However, significantly lower frequencies of CARD15 mutations were seen in African American (P < 0.0001) and Hispanic (P < 0.0001) children with CD compared with white children with CD. This lower CARD15 frequency among African American patients with CD was also mirrored in the general population. CONCLUSIONS: Phenotypic features of CD are similar among African American and Hispanic children compared with white children. CARD15 mutations are not increased among African American and Hispanic children with CD. CARD15 mutational frequencies among African American and Hispanic children within the general population are lower compared with white children within the general population. Future genetics studies will be required to determine the relationships between genotype and CD phenotype in various ethnic and racial groups.

Incidence, clinical characteristics, and natural history of pediatric IBD in Wisconsin: a population-based epidemiological study.

BACKGROUND: Epidemiological studies of pediatric inflammatory bowel diseases (IBD) are needed to generate etiological hypotheses and inform public policy; yet, rigorous population-based studies of the incidence and natural history of Crohn's disease (CD) and ulcerative colitis (UC) in the United States are limited. METHODS: We developed a field-tested prospective system for identifying all new cases of IBD among Wisconsin children over an 8-year period (2000-2007). Subsequently, at the end of the study period, we retrospectively reconfirmed each case and characterized the clinical course of this incident cohort. RESULTS: The annual incidence of IBD among Wisconsin children was 9.5 per 100,000 (6.6 per 100,000 for CD and 2.4 per 100,000 for UC). Approximately 19% of incident cases occurred in the first decade of life. Over the 8-year study period, the incidence of both CD and UC remained relatively stable. Additionally, (1) childhood IBD affected all racial groups equally, (2) over a follow-up of 4 years, 17% of patients with CD and 13% of patients with patients with UC required surgery, and (3) 85% and 40% of children with CD were treated with immunosuppressives and biologics, respectively, compared with 62% and 30% of patients with UC. CONCLUSIONS: As in other North American populations, these data confirm a high incidence of pediatric-onset IBD. Importantly, in this Midwestern U.S. population, the incidence of CD and UC seems to be relatively stable over the last decade. The proportions of children requiring surgery and undergoing treatment with immunosuppressive and biological medications underscore the burden of these conditions.

Age of diagnosis influences serologic responses in children with Crohn's disease: a possible clue to etiology?

BACKGROUND: Crohn's disease (CD) is often associated with antibodies to microbial antigens. Differences in immune response may offer clues to the pathogenesis of the disease. The aim was to examine the influence of age at diagnosis on the serologic response in children with CD. METHODS: Data were drawn from 3 North American multicenter pediatric inflammatory bowel disease (IBD) research consortia. At or shortly after diagnosis, pANCA, ASCA IgA, ASCA IgG, anti-ompC, and anti-CBir1 were assayed. The results were compared as a function of age at CD diagnosis (0-7 years versus 8-15 years). RESULTS: In all, 705 children (79 <8 years of age at diagnosis, 626 >or=8 years) were studied. Small bowel CD was less frequent in the younger group (48.7% versus 72.6%; P < 0.0001), while colonic involvement was comparable (91.0% versus 86.5%). ASCA IgA and IgG were seen in <20% of those 0-7 years old compared to nearly 40% of those 8-15 years old (P < 0.001), while anti-CBir1 was more frequent in the younger children (66% versus 54%, P < 0.05). Anti-CBir1 detected a significant number of children in both age groups who otherwise were serologically negative. Both age at diagnosis and site of CD involvement were independently associated with expression of ASCA and anti-CBir1. CONCLUSIONS: Compared to children 8-15 years of age at diagnosis, those 0-7 years are more likely to express anti-CBir1 but only half as likely to express ASCA. These age-associated differences in antimicrobial seropositivity suggest that there may be different, and as yet unrecognized, genetic, immunologic, and/or microbial factors leading to CD in the youngest children.