title: Distinctive histopathologic phenotype in resection specimens from patients with Crohn's disease receiving anti-TNF-α therapy.
abstract: Anti-tumor necrosis factor α (anti-TNF-α) therapy can result in endoscopic healing, reduction of symptoms, and reduced need for surgery and hospitalization in many patients with Crohn's disease (CD). Earlier data suggested that anti-TNF-α therapy may be associated with fibrosis and stricturing. We sought to determine whether anti-TNF-α therapy affects histologic inflammation, fibrosis, and granuloma formation. Hematoxylin and eosin sections from 62 patients with CD treated with either infliximab or adalimumab and 80 controls undergoing the same surgery but without prior exposure to anti-TNF-α therapy were compared. All patients with CD had undergone surgery within 6 months of therapy; CD controls were matched for steroid exposure, procedure, and indication for surgery and were subcategorized and case matched. Blinded histologic assessment of all slides was performed using a semiquantitative scoring system to assess inflammatory changes and fibrosis in all bowel layers. Compared with controls, the group treated with anti-TNF-α showed a reduction in mucosal and submucosal inflammation (P < .05), a decrease in granuloma formation (P < .05), and an increase in duplication of the muscularis mucosae (P < .05). A notable feature was a distinct pattern of hyalinizing submucosal fibrosis that was often devoid of inflammatory cells and that started directly below the muscularis mucosae; this pattern was not observed in the control group (P < .05). Resection specimens from patients with CD treated with anti-TNF-α therapy showed (a) reduced mucosal and submucosal inflammation; (b) a decrease in granuloma formation; and (c) a distinct pattern of submucosal hyaline fibrosis, with increased fibrosis in the muscularis mucosae and muscularis propria.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mount Sinai Hospital, Toronto, ON, Canada Joseph and Wolf Lebovic Health Complex 600 University Avenue Toronto, Ontario, Canada M5G 1X5; Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada 910 W. 10th Avenue, Vancouver, British Columbia, Canada V5Z 1M9. Electronic address: david.schaeffer@vch.ca.
authors.forename: David F
authors.initials: DF
authors.lastname: Schaeffer
authors.affiliation: Department of Laboratory Medicine and Pathology, Mount Sinai Hospital, Toronto, ON, Canada Joseph and Wolf Lebovic Health Complex 600 University Avenue Toronto, Ontario, Canada M5G 1X5.
authors.forename: Joanna C
authors.initials: JC
authors.lastname: Walsh
authors.affiliation: Department of Laboratory Medicine and Pathology, Mount Sinai Hospital, Toronto, ON, Canada Joseph and Wolf Lebovic Health Complex 600 University Avenue Toronto, Ontario, Canada M5G 1X5.
authors.forename: Richard
authors.initials: R
authors.lastname: Kirsch
authors.affiliation: Division of Gastroenterology, Department of Medicine, Mount Sinai Hospital, Toronto, ON, Canada Joseph and Wolf Lebovic Health Complex 600 University Avenue Toronto, Ontario, Canada M5G 1X5; Zane Cohen Centre for Digestive Diseases, Toronto, ON, Canada 60 Murray Street Toronto, Ontario, Canada M5T 3L9.
authors.forename: Matti
authors.initials: M
authors.lastname: Waterman
authors.affiliation: Division of Gastroenterology, Department of Medicine, Mount Sinai Hospital, Toronto, ON, Canada Joseph and Wolf Lebovic Health Complex 600 University Avenue Toronto, Ontario, Canada M5G 1X5; Zane Cohen Centre for Digestive Diseases, Toronto, ON, Canada 60 Murray Street Toronto, Ontario, Canada M5T 3L9.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Silverberg
authors.affiliation: Department of Laboratory Medicine and Pathology, Mount Sinai Hospital, Toronto, ON, Canada Joseph and Wolf Lebovic Health Complex 600 University Avenue Toronto, Ontario, Canada M5G 1X5; Zane Cohen Centre for Digestive Diseases, Toronto, ON, Canada 60 Murray Street Toronto, Ontario, Canada M5T 3L9.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Riddell
mesh_terms: D000068879:Adalimumab; D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D003424:Crohn Disease / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D005260:Female; D005355:Fibrosis / Q000139:chemically induced / Q000473:pathology; D006099:Granuloma / Q000139:chemically induced / Q000473:pathology; D006801:Humans; D006965:Hyperplasia / Q000139:chemically induced / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology; D010641:Phenotype; D016037:Single-Blind Method; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab
keywords: Adalimumab; Anti–TNF-α therapy; Crohn’s disease; Fibrosis; Fibrotic strictures; Infliximab