title: Prognostic significance of granulomas in children with Crohn's disease.
abstract: OBJECTIVE
  Granulomas have long been considered the histological hallmark of Crohn's disease (CD). Currently, there is considerable dispute with regards to their prognostic implications. We aimed to determine the effect of granulomas on phenotypic features and disease's long-term outcomes in a large cohort of pediatric CD patients.
  
  
  METHODS
  Medical records of pediatric CD patients diagnosed at the Schneider Children's Medical Center were reviewed retrospectively. Patients were categorized into two groups based on the presence or absence of granulomas at diagnosis. Baseline characteristics included anthropometric, clinical, laboratory, radiological and endoscopic data. Outcome measures included flares, hospitalizations, biological therapy and surgery.
  
  
  RESULTS
  Of 289 CD patients diagnosed between 2001 and 2015, 99 patients (34%) had granulomas. Median age of the entire cohort at diagnosis was 14.2 years (females, 42.6%), with a median follow-up of 8.5 years. Patients with granulomas had a significantly higher percentage (47.5% vs. 23.7%, p = .001) of upper gastrointestinal involvement and ileo-colonic disease (64.9% vs. 49.5%, p = .01). Extraintestinal manifestations were twice as common in patients without granulomas (16.3% vs. 8.1%, p = .05). Patients with granulomas were more likely to be hospitalized (HR =1.43, 95% CI: 1.0-2.0) and to receive biologic therapy (HR = 1.52, 95% CI: 1.1-2.11). Additionally, both of these disease outcomes occurred significantly earlier (p = .013 and p = .027, respectively). In contrast, patients with granulomas did not exhibit increased risk of flares or bowel resection.
  
  
  CONCLUSIONS
  Patients with granulomas exhibited a distinct phenotype at diagnosis and demonstrated a more severe disease course.
authors.affiliation: a Institute of Gastroenterology, Nutrition and Liver Disease , Schneider Children's Hospital , Petach-Tikva , Israel.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Rothschild
authors.affiliation: a Institute of Gastroenterology, Nutrition and Liver Disease , Schneider Children's Hospital , Petach-Tikva , Israel.
authors.forename: Firas
authors.initials: F
authors.lastname: Rinawi
authors.affiliation: a Institute of Gastroenterology, Nutrition and Liver Disease , Schneider Children's Hospital , Petach-Tikva , Israel.
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Herman
authors.affiliation: b Sackler Faculty of Medicine, Tel-Aviv University , Tel-Aviv , Israel.
authors.forename: Osnat
authors.initials: O
authors.lastname: Nir
authors.affiliation: a Institute of Gastroenterology, Nutrition and Liver Disease , Schneider Children's Hospital , Petach-Tikva , Israel.|b Sackler Faculty of Medicine, Tel-Aviv University , Tel-Aviv , Israel.
authors.forename: Raanan
authors.initials: R
authors.lastname: Shamir
authors.affiliation: a Institute of Gastroenterology, Nutrition and Liver Disease , Schneider Children's Hospital , Petach-Tikva , Israel.|b Sackler Faculty of Medicine, Tel-Aviv University , Tel-Aviv , Israel.
authors.forename: Amit
authors.initials: A
authors.lastname: Assa
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use; D000293:Adolescent; D002648:Child; D003424:Crohn Disease / Q000150:complications* / Q000175:diagnosis* / Q000188:drug therapy; D004724:Endoscopy; D005260:Female; D006099:Granuloma / Q000453:epidemiology* / Q000473:pathology*; D006801:Humans; D000069285:Infliximab / Q000627:therapeutic use; D007557:Israel; D053208:Kaplan-Meier Estimate; D008297:Male; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D041742:Upper Gastrointestinal Tract / Q000473:pathology
chemical_list: D000069285:Infliximab; D000068879:Adalimumab
keywords: Biologic treatment; inflammatory bowel disease; pediatric; phenotype