Paediatric Ulcerative Colitis Is a Fibrotic Disease and Is Linked with Chronicity of Inflammation

Author:

Gordon Ilyssa O1ORCID,Abushamma Suha2,Kurowski Jacob A3,Holubar Stefan D4ORCID,Kou Lei5,Lyu Ruishen5,Rieder Florian6

Affiliation:

1. Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic Foundation, Cleveland, OH, USA

2. Department of Gastroenterology, Washington University School of Medicine, Barnes Jewish Hospital, St Louis, MO,  USA

3. Department of Paediatric Gastroenterology, Hepatology and Nutrition, Cleveland Clinic Foundation, Cleveland, OH, USA

4. Department of Colorectal Surgery, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA

5. Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA

6. Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, and Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA

Abstract

Abstract Background and Aims Intestinal fibrosis has recently been characterised in adult ulcerative colitis and may affect motility, diarrhoea, and the symptom of urgency. We aimed to charactersze the presence of fibrosis in paediatric patients with ulcerative colitis, and its link to severity and chronicity of mucosal inflammation, as well as clinical factors of severity. Methods We performed a single-centre cross-sectional study in children ages 1–18 years with ulcerative colitis, undergoing colectomy or proctocolectomy. Tissue cross-sections were derived from proximal, mid, and distal colon and rectum, and inflammation and fibrosis were graded based on previously developed scores. Clinical data were collected prospectively. Results From 62 patients, 205 intestinal sections were evaluated. Median age at diagnosis was 13 years, 100% had extensive colitis, and all resections were done for refractory disease. The presence, chronicity, and degree of inflammation were linked with the presence of fibrosis. Thickness of the muscularis mucosa was also linked with presence and chronicity of inflammation. The overall submucosal fibrosis burden was associated with prior anti-tumour necrosis factor use. Conclusions Paediatric patients with ulcerative colitis exhibit colorectal submucosal fibrosis and muscularis mucosa thickening, which correlate with the presence, chronicity, and degree of mucosal inflammation. Fibrosis should be recognised as a complication of paediatric ulcerative colitis, and ulcerative colitis should be considered a progressive disease.

Funder

Stenosis Therapy and Anti-Fibrotic Research

Crohn’s and Colitis Foundation

National Institutes of Health

Cleveland Clinic Intramural Funding

Publisher

Oxford University Press (OUP)

Subject

Gastroenterology,General Medicine

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