title: Investigation of potential early Histologic markers of pediatric inflammatory bowel disease.
abstract: BACKGROUND
  Early manifestations of pediatric inflammatory bowel disease (IBD) can be relatively nonspecific. Initial mucosal biopsies may not be conclusive, delaying the diagnosis until subsequent biopsies demonstrate typical histologic features of IBD. We hypothesized that certain inflammatory cell types may be utilized as early histologic indicators of IBD in children.
  
  
  METHODS
  A retrospective analysis compared histologic findings from initially inconclusive or negative endoscopic studies in 22 patients who were subsequently diagnosed with IBD (after diagnostic endoscopy) to those of 20 comparison patients with functional abdominal pain matched for age, gender, and study type. A pediatric pathologist, blinded to study group, reviewed biopsies for histologic abnormalities. Eosinophil densities were obtained from the stomach, duodenum, and rectosigmoid areas. Immunohistochemistry (IHC) staining for tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-9 (MMP-9) was performed on the stomach and rectosigmoid areas.
  
  
  RESULTS
  Gastritis and colonic crypt distortion were present in the IBD group at a greater rate (61 % vs. 22 %, p = 0.020; 34 % vs. 4 %, p = 0.008, respectively). Peak and mean eosinophil densities in the rectosigmoid area were greater in the IBD group (17.0/hpf vs. 5.0/hpf, p = 0.0063; 12.3/hpf vs. 4.2/hpf, p = 0.0106, respectively). TNF-α and MMP-9 staining did not reveal any significant differences.
  
  
  CONCLUSIONS
  Our data suggests that significantly greater inflammation in the stomach, crypt distortion in the colon, and eosinophilia in the rectosigmoid distinguished the IBD group from the comparison group at the time of the initial endoscopic evaluation.
authors.affiliation: Division of Gastroenterology, Children's Mercy Hospitals & Clinics, 2401 Gillham Road, Kansas City, MO, 64108, USA. jabass@cmh.edu.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Bass
authors.affiliation: Division of Gastroenterology, Children's Mercy Hospitals & Clinics, 2401 Gillham Road, Kansas City, MO, 64108, USA. cfriesen@cmh.edu.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Friesen
authors.affiliation: Division of Gastroenterology, Children's Mercy Hospitals & Clinics, 2401 Gillham Road, Kansas City, MO, 64108, USA. addeacy@cmh.edu.|Division of Developmental and Behavioral Sciences, Children's Mercy Hospitals & Clinics, 2401 Gillham Road, Kansas City, MO, 64108, USA. addeacy@cmh.edu.
authors.forename: Amanda D
authors.initials: AD
authors.lastname: Deacy
authors.affiliation: Division of Infectious Disease, Children's Mercy Hospitals & Clinics, 2401 Gillham Road, Kansas City, MO, 64108, USA. naneilan@cmh.edu.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Neilan
authors.affiliation: Division of Gastroenterology, Children's Mercy Hospitals & Clinics, 2401 Gillham Road, Kansas City, MO, 64108, USA. jmbracken@cmh.edu.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Bracken
authors.affiliation: Division of Gastroenterology, Children's Mercy Hospitals & Clinics, 2401 Gillham Road, Kansas City, MO, 64108, USA. vshakhnovich@cmh.edu.|Division of Clinical Pharmacology, Toxicology, and Therapeutic Innovation, Children's Mercy Hospitals & Clinics, 2401 Gillham Road, Kansas City, MO, 64108, USA. vshakhnovich@cmh.edu.
authors.forename: Valentina
authors.initials: V
authors.lastname: Shakhnovich
authors.affiliation: Department of Pathology, Children's Mercy Hospitals & Clinics, 2401 Gillham Road, Kansas City, MO, 64108, USA. vsingh@cmh.edu.
authors.forename: Vivekanand
authors.initials: V
authors.lastname: Singh
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D016099:Endoscopy, Gastrointestinal / Q000706:statistics & numerical data; D004804:Eosinophils / Q000473:pathology; D005260:Female; D005756:Gastritis / Q000150:complications / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D015212:Inflammatory Bowel Diseases / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D007422:Intestines / Q000737:chemistry / Q000473:pathology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D012189:Retrospective Studies; D013270:Stomach / Q000737:chemistry / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
chemical_list: D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9