Natural History of Pediatric Crohn's Disease: A Population-Based Cohort Study

Vernier‐Massouille, Gwénola; Baldé, Mamadou; Salleron, Julia; Turck, Dominique; Dupas, Jean Louis; Mouterde, O.; Merle, V.; Salomez, Jean Louis; Branche, Julien; Marti, Raymond; Lerebours, Éric; Cortot, Antoine; Gower‐Rousseau, Corinne; Colombel, Jean Fréd́eric

doi:10.1053/j.gastro.2008.06.079

Cited by 539 publications

(464 citation statements)

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“…17 Despite increased use of anti-tumor necrosis factor-α therapy, a population-level decline in rates of surgeries for CD strictures has not been observed. 18,19 This suggests that alternate inflammatory and molecular pathways drive stricturing complications.…”

Section: Discussionmentioning

confidence: 99%

Genetic and Transcriptomic Variation Linked to Neutrophil Granulocyte–Macrophage Colony-Stimulating Factor Signaling in Pediatric Crohn’s Disease

Denson

Jurickova

Karns

et al. 2018

Inflammatory Bowel Diseases

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Background: Granulocyte-macrophage colony-stimulating factor auto-antibodies (GMAbs) suppress neutrophil-extrinsic GM-CSF signaling and increase risk for stricturing behavior in Crohn's disease (CD). We aimed to define clinical, genomic, and functional associations with neutrophil-intrinsic GM-CSF signaling. Methods:Missense mutations in CSF2RA, CSF2RB, JAK2, STAT5A, and STAT5B were identified using whole-exome sequencing in 543 pediatric inflammatory bowel disease (IBD) patients. Neutrophil-intrinsic GM-CSF signaling was defined using the GM-CSF-induced STAT5 stimulation index (GMSI) in 180 pediatric IBD patients and 26 non-IBD controls. Reduced GM-CSF signaling (GMSI-Lo) was defined as the 20th percentile within the control group. Variation in neutrophil phospho-protein abundance, bacterial killing, and the global pattern of gene expression with the GMSI was determined. Results:We validated 18 potentially damaging missense mutations in CSF2RA and CSF2RB. CSF2RA A17G carriage increased from 10% in those with intact neutrophil GMSI to 32% in those with low GMSI (P = 0.02). Conflicts of interest:The authors have no financial arrangements with any company whose product figures prominently in the submitted manuscript or with a company making a competing product. Dr. Denson has received grant support from Janssen and holds a patent for the use of GM-CSF auto-antibodies as a diagnostic doi: 10.1093/ibd/izy265 Published online 13 August 2018 test in inflammatory bowel disease. Dr. Dubinsky has served as a consultant for Abbvie, Takeda, Janssen, and Pfizer and has received research support from Abbvie, Janssen, and Prometheus. Dr. Guthery has received research support in the last year from Regeneron Pharmaceuticals. Dr. Leleiko or his immediate family have equity interests in Celgene, Vericel, Ionis, Vertex, and Alnylam, and he has served as a consultant for CRICO. The remaining authors have nothing to declare. 2Denson et al from 17% in those with intact neutrophil GMSI to 35% in GMSI-Lo neutrophils (P = 0.043). Crohn's disease neutrophils with low GMSI exhibited specific alterations in phospho-protein networks and genes regulating cytokine production, wound healing, and cell survival and proliferation. Stricturing behavior increased from 7% in patients with both low GMAb and intact GMSI to 64% in patients with both elevated GMAb and low GMSI (P < 0.0001).Conclusions: Low/normal neutrophil-intrinsic GM-CSF signaling is associated with CSF2RA missense mutations, alterations in gene expression networks, and higher rates of disease complications in pediatric CD.

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Section: Discussionmentioning

confidence: 99%

Genetic and Transcriptomic Variation Linked to Neutrophil Granulocyte–Macrophage Colony-Stimulating Factor Signaling in Pediatric Crohn’s Disease

Denson

Jurickova

Karns

et al. 2018

Inflammatory Bowel Diseases

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“…This agedependent phenotypic clinical expression probably reflects the dynamic nature of the disorder [21] . Disease developing earlier in children and adolescents tends to be much more severe, often resulting in significant disease complications, including strictures or fistulae, or both [22][23][24][25] . It is also more extensive, often involving multiple sites in the small and large intestine, with a higher frequency of involvement of the upper gastrointestinal tract [22][23][24][25] .…”

Section: Age-related Phenotypic Expressionmentioning

confidence: 99%

“…Disease developing earlier in children and adolescents tends to be much more severe, often resulting in significant disease complications, including strictures or fistulae, or both [22][23][24][25] . It is also more extensive, often involving multiple sites in the small and large intestine, with a higher frequency of involvement of the upper gastrointestinal tract [22][23][24][25] . Comparative studies also show significant differences in clinical expression for children and adults [21,22] , as well as the elderly [26] .…”

Section: Age-related Phenotypic Expressionmentioning

confidence: 99%

Long-term natural history of Crohn’s disease

Freeman¹

2009

WJG

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“…While surgery is often delayed in pediatric IBD patients to avoid aggressive medical intervention, researchers have estimated rates of surgery in this population ranging between 20% to 34% at 3 and 5 years post-diagnosis, respectively [40]. Surgical interventions for IBD typically include resecting diseased portions of the GI tract, partial colectomy and ostomy (e.g., a temporary "resting" ostomy), or total colectomy and ostomy (e.g., a permanent ostomy) [40].…”

Section: Ed Risk Factors Associated With Ibdmentioning

confidence: 99%

Adolescents with Diet-Related Chronic Health Conditions (DRCHCs) and Unique Risk for Development of Eating Pathology

David¹,

Culnan²,

Эрнст³

2017

J Child Adolesc Behav

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Diet-Related Chronic Health Conditions (DRCHCs) are a subset of chronic health illnesses, which presently includes Inflammatory Bowel Disease (IBD), Type 1 Diabetes (T1D), Cystic Fibrosis (CF), and Celiac Disease (CD). Food and diet play integral roles in the management and progression of each condition. The diversity of treatments for DRCHCs encompass therapies that impact diet, weight, and body shape, such as steroids, insulin, and special and/or restrictive diets. Often with efforts to control unwanted side effects of the myriad of treatments, there is poor adherence to prescribed therapies. Given the psychosocial burden of DRCHCs, and the high degree of focus on weight and diet involved in managing each disorder, it is not surprising that those living with DRCHCs may be at risk for developing body image concerns, including poor body image and weight concerns, which may increase the risk for the development of eating pathology. In addition to summarizing current eating pathology risk factors present in DRCHCs, the proposed article builds on previous research by recommending an expansion of the category of DRCHCs to include Type II Diabetes and serious/anaphylactic food allergies, and hypothesizes DRCHC-specific eating pathology risk factors, such as hyper focus on weight, medically-related food restriction, and societal acceptance of thinness despite health issues. The article concludes with clinical recommendations for pediatric medical providers to potentially minimize the negative impact of DRCHC on pediatric patients' medical and psychosocial outcomes.

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Natural History of Pediatric Crohn's Disease: A Population-Based Cohort Study

Cited by 539 publications

References 45 publications

Genetic and Transcriptomic Variation Linked to Neutrophil Granulocyte–Macrophage Colony-Stimulating Factor Signaling in Pediatric Crohn’s Disease

Genetic and Transcriptomic Variation Linked to Neutrophil Granulocyte–Macrophage Colony-Stimulating Factor Signaling in Pediatric Crohn’s Disease

Long-term natural history of Crohn’s disease

Adolescents with Diet-Related Chronic Health Conditions (DRCHCs) and Unique Risk for Development of Eating Pathology

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