Childhood-onset Inflammatory Bowel Disease Research Articles

Pediatric inflammatory bowel diseases: coming of age

Inflammatory bowel diseases (IBD) comprise a heterogeneous group of distinct intestinal disorders. Here, we discuss the concept of childhood-onset IBD as separate disease forms within a larger multifactorial disease category. There are excellent epidemiological data indicating that the incidence of pediatric IBD, mainly Crohn's disease, is still increasing over the last decades, with indicators of more extensive and more severe disease presentations in children compared to adults, also reflected by higher levels of humoral immune responses. Recent genetic scans allowed to identify particular susceptibility genes for pediatric IBD forms, such as IL27 or probably DcR3. Early postnatal onset forms of IBD might reflect monogenetic causes, as suggested with the finding of IL10 signaling defects that may define a new form of IBD. There are good epidemiological, genetic and clinical data to distinguish different forms of IBD, particularly forms starting early in life. Profound insights in the molecular basis of immune dysregulation in IBD have been gained over the last few years. These recent discoveries will nourish and substantially stimulate the future search for precise cause(s) responsible for life-long intestinal inflammation and it will help to explain the still ongoing rise in incidence in childhood IBD.

Increasing incidence of paediatric inflammatory bowel disease in Ontario, Canada: evidence from health administrative data

Objective:Health administrative databases can be used to track chronic diseases. The aim of this study was to validate a case ascertainment definition of paediatric-onset inflammatory bowel disease (IBD) using administrative...

Long-term health outcomes in pediatric inflammatory bowel disease: A population-based study

The long-term sequelae of inflammatory bowel disease (IBD) may differ between children and adults. We evaluated the health status of patients with pediatric onset of IBD and controls in early adulthood. A questionnaire on the current health status and disease history was mailed to patients with childhood onset IBD diagnosed during 1987-2003 in 2 university hospitals in Finland. Matched controls were randomly selected from the Population Register Centre. A total of 368 (67%) of the 550 patients and 646 (37%) controls responded (median age 20 years). Ulcerative colitis (UC) was the most common primary diagnosis (58%) reclassified as Crohn's disease (CD) in 8.5%. Of the patients, 80% had been on glucocorticoids at some point (median duration of the disease 8.3 years). One-third of CD patients had undergone intestinal resection. In UC, total colectomy was common (24%). The frequency of joint diseases (5.4% versus 0.2%) and biliary duct diseases (2.7% versus 0.3%) was higher in patients than in controls (P < 0.001). Overall quality of life was decreased in the patients (mean score 5.7 versus 6.0 in controls, P < 0.001). Further, some impediment on adult height and weight was observed among male patients. IBD in children may have a more aggressive disease course than in adults, since most pediatric patients need glucocorticoids, and abdominal surgery is frequent. At 8 years from diagnosis, most patients have active disease and quality of life is slightly lower than in the rest of the population.

Definition of Phenotypic Characteristics of Childhood-Onset Inflammatory Bowel Disease

Childhood-onset inflammatory bowel disease (IBD) might be etiologically different from adult-onset IBD. We analyzed disease phenotypes and progression of childhood-onset disease and compared them with characteristics of adult-onset disease in patients in Scotland. Anatomic locations and behaviors were assessed in 416 patients with childhood-onset (276 Crohn's disease [CD], 99 ulcerative colitis [UC], 41 IBD type unclassified [IBDU] diagnosed before seventeenth birthday) and 1297 patients with adult-onset (596 CD, 701 UC) IBD using the Montreal classification. At the time of diagnosis in children, CD involved small bowel and colon (L3) in 51% (138/273), colon (L2) in 36%, and ileum (L1) in 6%; the upper gastrointestinal (GI) tract (L4) was also affected in 51%. In 39%, the anatomic extent increased within 2 years. Behavioral characteristics progressed; 24% of children developed stricturing or penetrating complications within 4 years (vs 9% at diagnosis; P < .0001; odds ratio [OR], 3.32; 95% confidence interval [CI], 1.86-5.92). Compared with adults, childhood-onset disease was characterized by a "panenteric" phenotype (ileocolonic plus upper GI [L3+L4]; 43% vs 3%; P < .0001; OR, 23.36; 95% CI, 13.45-40.59) with less isolated ileal (L1; 2% vs 31%; P < .0001; OR, 0.06; 95% CI, 0.03-0.12) or colonic disease (L2; 15% vs 36%; P < .0001; OR, 0.31; 95% CI, 0.21-0.46). UC was extensive in 82% of the children at diagnosis, versus 48% of adults (P < .0001; OR, 5.08; 95% CI, 2.73-9.45); 46% of the children progressed to develop extensive colitis during follow-up. Forty-six percent of children with CD and 35% with UC required immunomodulatory therapy within 12 months of diagnosis. The median time to first surgery was longer in childhood-onset than adult-onset patients with CD (13.7 vs 7.8 years; P < .001); the reverse was true for UC. Childhood-onset IBD is characterized by extensive intestinal involvement and rapid early progression.

S1152 Childhood Onset Inflammatory Bowel Disease Has a More Extensive Disease Phenotype in Comparison to Adult Onset IBD Using the Montreal Classification

S1152 Childhood Onset Inflammatory Bowel Disease Has a More Extensive Disease Phenotype in Comparison to Adult Onset IBD Using the Montreal Classification

393 The Contribution of Germline Variation in the Autophagy Genes ATG16l1 and Irgm to Childhood Onset Inflammatory Bowel Disease

393 The Contribution of Germline Variation in the Autophagy Genes ATG16l1 and Irgm to Childhood Onset Inflammatory Bowel Disease

The Contribution of the DLG5 113A Variant in Early-Onset Inflammatory Bowel Disease

To assess the contribution of the 113 G-->A missense mutation within the discs, large homolog 5 (DLG5) gene in childhood-onset inflammatory bowel disease (IBD) in Scotland. Two-hundred and ninety-six children with IBD were studied. Parental DNA was also collected for transmission disequilibrium testing (TDT) analysis. Genotyping was performed by TaqMan. Genotype-phenotype analysis was also undertaken. Socioeconomic status was assigned using a deprivation category (DepCat) score 1 through 7 (1 = most affluent). TDT analysis demonstrated a significant association with IBD (P = .045). On unifactorial analysis, 113A carriage was associated with: (1) higher social class (DepCat 1 compared with 2-7, and 1-2 compared with 3-7) (66.7% vs 22.6%, P = .0005, OR 6.84 [1.99-23.55] and 37.2% vs 22.2%, P = .03, OR 2.08 [1.04-4.17], respectively); (2) higher height centile (>75th centile vs <75th centile) (42.9% vs 23.1%, P = .01, OR 2.50 [1.18-5.28]); and (3) male sex in Crohn's disease (CD) (29.3% vs 16.9%, P = .04, OR 2.04 [1.01-4.11]). Multifactorial analysis demonstrated that higher social class (DepCat 1) was independently associated with carriage of variants of 113A (P = .001, OR = 6.92 [2.24-21.33]). DLG5 113A is associated with increased susceptibility to IBD in Scottish children. The effect may be most marked for those children living in relative affluence.

Distinct Phenotype of Early Childhood Inflammatory Bowel Disease

Our goals were to answer 2 questions: (1) Is the presentation of early-onset inflammatory bowel disease (IBD) similar to typical adolescent-onset IBD? (2) Is there variability in familial aggregation in childhood IBD? The phenotype of IBD in children under 5 years of age (early-onset) is poorly defined. Clinical and genetic studies of IBD, however, generally assume the phenotype to be homogenous throughout childhood. We analyzed data from 413 consecutive pediatric IBD outpatients attending our center between 1995 and 2000. Disease type, anatomic distribution, and family history were compared between children presenting before (early-onset) and after the age of five (5 to 15 y). Disease presentation was predominantly colonic in early-onset IBD, most patients presenting with ulcerative colitis (UC). Isolated colonic disease was most frequent in early-onset Crohn disease (colonic 76.5%, ileocolic 24%) compared with ileocolic disease (ileocolic 45.5%, colonic 26%, ileal 19.4%, proximal 6.3%) in the older age group. First-degree family history was highest in early-onset UC 26% versus 11% in the older UC group. We describe a distinct phenotype of early childhood onset IBD, with a strikingly high familial aggregation in UC and greater tendency to present with colonic disease. As more genetic heterogeneity is identified in IBD, careful definition of phenotype is required to identify further susceptibility genes. The early-onset form of UC presents an ideal group for further genetic analysis. These phenotype differences also suggest that treatment and outcome may vary in early-onset childhood IBD; prospective studies are required to confirm this.