Pediatric IBD-unclassified Is Less Common than Previously Reported; Results of an 8-Year Audit of the EUROKIDS Registry

Winter, D.A.; Karolewska-Bochenek, Katarzyna; Łazowska-Przeorek, Izabella; Lionetti, Paolo; Chong, Sonny K. F.; Roma-Giannikou, Eleftheria; Malý, Jan; Kolho, Kaija‐Leena; Shaoul, Ron; Staiano, Annamaria; Damen, Gerard; Meij, Tim de; Hendriks, D.; George, Elvira K.; Turner, Dan; Escher, Johanna C.

doi:10.1097/mib.0000000000000483

Cited by 41 publications

(43 citation statements)

References 26 publications

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“…By our new 'prevalent' IBD subtype definition, the prevalence of pediatric IBD-U was 18%, which is still higher than in adults, and higher than reported in a large European cohort study at end of follow-up: 5.6% [32]. The distinction between CD and UC can at times be more challenging in pediatric populations since colonic CD is a more common [60].…”

Section: Discussionmentioning

confidence: 67%

“…In other studies, 23-84% of patients with an initial diagnosis of IBD-U were later classified as UC or CD [9,12,24,[31][32][33]55]. In pediatric patients, a systematic review found an increase in diagnosis of CD over time, and a decrease in IBD-U [7].…”

Section: Discussionmentioning

confidence: 95%

“…The frequency of IBD-U is usually reported to be higher among pediatric patients compared to that of the adult population: 13 versus 6% in a meta-analysis [6], and to be decreasing over disease course [7]. In well characterized IBD cohorts, the proportion of IBD-U has been reported to range from 1 to 20% in adults [8][9][10][11][12][13][14][15][16][17][18][19][20] and from 4 to 22% in pediatric patients [21][22][23][24][25][26][27][28][29][30][31][32][33]) (Table 1).…”

Section: Introductionmentioning

confidence: 99%

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Changes in inflammatory bowel disease subtype during follow-up and over time in 44,302 patients

Everhov

Sachs

Malmborg

et al. 2019

Scandinavian Journal of Gastroenterology

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Aim: To investigate inflammatory bowel disease (IBD) register-based subtype classifications over a patient's disease course and over time. Methods: We examined International Classification of Diseases coding in patients with !2 IBD diagnostic listings in the National Patient Register 2002Register -2014. Results: 18% of the patients changed diagnosis (17% of adults, 29% of children) during a median follow-up of 3.8 years. Of visits with diagnoses of Crohn's disease (CD) or ulcerative colitis (UC), 97% were followed by the same diagnosis, whereas 67% of visits with diagnosis IBD-unclassified (IBD-U) were followed by another IBD-U diagnosis. Patients with any diagnostic change changed mostly once (47%) or twice (31%), 39% from UC to CD, 33% from CD to UC and 30% to or from IBD-U. Using a classification algorithm based on the first two diagnoses ('incident classification'), suited for prospective cohort studies, the proportion adult patients with CD, UC, and IBD-U 2002-2014 were 29%, 62%, and 10% (43%, 45%, and 12% in children). A classification model incorporating additional information from surgeries and giving weight to the last 5 years of visits ('prevalent classification'), suited for description of a study population at end of follow-up, classified 31% of adult cases as CD, 58% as UC and 11% as IBD-U (44%, 38%, and 18% in children). Conclusions: IBD subtype changed in 18% during follow-up. The proportion with CD increased and UC decreased from definition at start to end of follow-up. IBD-U was more common in children.

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Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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Changes in inflammatory bowel disease subtype during follow-up and over time in 44,302 patients

Everhov

Sachs

Malmborg

et al. 2019

Scandinavian Journal of Gastroenterology

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“…UC and IBD-unclassified (IBD-U) account for 30-40 percent of pediatric IBD in the United States and Europe. 5-7 Furthermore, approximately 80 percent of children with CD have colonic involvement with 25 percent exhibiting a colon-only phenotype with no small intestinal involvement. 8,9 Colon-only CD phenotype is even more common with younger age, occurring in about 40 percent of children under 10 years of age.…”

mentioning

confidence: 99%

Mucosal Expression of Type 2 and Type 17 Immune Response Genes Distinguishes Ulcerative Colitis From Colon-Only Crohn’s Disease in Treatment-Naive Pediatric Patients

et al. 2017

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BACKGROUND & AIMS There is controversy over the role of the type 2 immune response in pathogenesis of ulcerative colitis (UC)—few data are available from treatment-naïve patients. We investigated whether genes associated with a type 2 immune response in the intestinal mucosa are upregulated in treatment-naïve pediatric patients with UC, compared to patients with Crohn’s disease (CD)-associated colitis or without inflammatory bowel disease (IBD), and whether expression levels associate with clinical outcomes. METHODS We used a real-time reverse transcription quantitative PCR array to analyze mRNA expression patterns in rectal mucosal samples from 138 treatment-naïve pediatric patients with IBD and macroscopic rectal disease, as well as those from 49 children without IBD (controls), enrolled in a multicenter prospective observational study from 2008 and 2012. Results were validated in real-time reverse transcription quantitative PCR analyses of rectal RNA from and independent cohort of 34 pediatric patients with IBD and macroscopic rectal disease and 17 controls from Cincinnati Children’s Hospital Medical Center. RESULTS We measured significant increases in mRNAs associated with a type 2 immune response (interleukin 5 gene [IL5], IL13, and IL13RA2) and a type 17 immune response (IL17A and IL23) in mucosal samples from patients with UC compared to patients with colon-only CD. In a regression model, increased expression of IL5 and IL17A mRNAs distinguished patients with UC from patients with colon-only CD (P=.001; area under the receiver operating characteristic curve, 0.72). We identified a gene expression pattern in rectal tissues of patients with UC, characterized by detection of IL13 mRNA, that predicted clinical response to therapy after 6 months (OR, 6.469; 95% CI, 1.553–26.94), clinical response after 12 months (OR, 6.125; 95% CI, 1.330–28.22), and remission after 12 months (OR, 5.333; 95% CI, 1.132–25.12). CONCLUSION In an analysis of rectal tissues from treatment-naïve pediatric patients with IBD, we observed activation of a type 2 immune response during the early course of UC. We were able to distinguish patients with UC from those with colon-only CD based on increased mucosal expression of genes that mediate type 2 and type 17 immune responses. Increased expression at diagnosis of genes that mediate a type 2 immune response is associated with response to therapy and remission in pediatric patients with UC.

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“…Increasing prevalence and hospitalization rates have been reported [1][2][3]. Early diagnosis and monitoring of disease are important to prevent progression, but complicated by highly variable disease manifestations, which may not only affect the gastrointestinal tract but also the skin and eyes [4][5][6]. Therefore, there is a great need for reliable biomarkers for early diagnosis and disease monitoring [7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Meta-Analysis of Expression Profiling Data Indicates Need for Combinatorial Biomarkers in Pediatric Ulcerative Colitis

Lee

Gawel

et al. 2020

Journal of Immunology Research

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Background. Unbiased studies using different genome-wide methods have identified a great number of candidate biomarkers for diagnosis and treatment response in pediatric ulcerative colitis (UC). However, clinical translation has been proven difficult. Here, we hypothesized that one reason could be differences between inflammatory responses in an inflamed gut and in peripheral blood cells. Methods. We performed meta-analysis of gene expression microarray data from intestinal biopsies and whole blood cells (WBC) from pediatric patients with UC and healthy controls in order to identify overlapping pathways, predicted upstream regulators, and potential biomarkers. Results. Analyses of profiling datasets from colonic biopsies showed good agreement between different studies regarding pathways and predicted upstream regulators. The most activated predicted upstream regulators included TNF, which is known to have a key pathogenic and therapeutic role in pediatric UC. Despite this, the expression levels of TNF were increased in neither colonic biopsies nor WBC. A potential explanation was increased expression of TNFR2, one of the membrane-bound receptors of TNF in the inflamed colon. Further analyses showed a similar pattern of complex relations between the expression levels of the regulators and their receptors. We also found limited overlap between pathways and predicted upstream regulators in colonic biopsies and WBC. An extended search including all differentially expressed genes that overlapped between colonic biopsies and WBC only resulted in identification of three potential biomarkers involved in the regulation of intestinal inflammation. However, two had been previously proposed in adult inflammatory bowel diseases (IBD), namely, MMP9 and PROK2. Conclusions. Our findings indicate that biomarker identification in pediatric UC is complicated by the involvement of multiple pathways, each of which includes many different types of genes in the blood or inflamed intestine. Therefore, further studies for identification of combinatorial biomarkers are warranted. Our study may provide candidate biomarkers for such studies.

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Pediatric IBD-unclassified Is Less Common than Previously Reported; Results of an 8-Year Audit of the EUROKIDS Registry

Cited by 41 publications

References 26 publications

Changes in inflammatory bowel disease subtype during follow-up and over time in 44,302 patients

Changes in inflammatory bowel disease subtype during follow-up and over time in 44,302 patients

Mucosal Expression of Type 2 and Type 17 Immune Response Genes Distinguishes Ulcerative Colitis From Colon-Only Crohn’s Disease in Treatment-Naive Pediatric Patients

Meta-Analysis of Expression Profiling Data Indicates Need for Combinatorial Biomarkers in Pediatric Ulcerative Colitis

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