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Histopathological findings of extra-ileal manifestations at initial diagnosis of Crohn’s disease-related ileitis

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Abstract

Crohn’s disease is a chronic inflammatory disorder that can affect any part of the gastrointestinal tract. Our objective was to review the histological findings in index biopsies from the terminal ileum and other gastro-intestinal tract sites of Crohn’s disease patients prior any treatment and to compare them with the findings from patients with non-specific ileitis. A total of 111 consecutive Crohn’s disease cases (55 females, median age 27 years) with extra-ileal biopsies were retrospectively selected. Upper gastrointestinal inflammatory changes were found in 68 % of gastric biopsies, 60 % of oesophageal biopsies and 43 % of duodenal biopsies with no significant difference in frequency between paediatric and adult cases. Crohn’s colitis was more common in paediatric cases than adult cases (85 % versus 57 %). Granuloma in at least one extra-ileal site was observed in 40 %, more frequently in paediatric cases than in adults (78 vs 27 %). Compared with Crohn’s disease cases, the group of 151 non-specific ileitis cases (75 females, median age 52 years) were more likely to have normal upper and lower gastrointestinal biopsies and to show less frequent crypt architectural changes in the terminal ileum. In summary, Crohn’s disease ileitis is often associated with inflammation elsewhere in the gastrointestinal tract while non-specific ileitis was infrequently associated with inflammation elsewhere for both paediatric and adult patients. These findings support the role of systematic biopsies in multiple gastrointestinal sites to help distinguishing Crohn’s ileitis from non-specific ileitis in paediatric and adult population.

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References

  1. Magro F, Langner C, Driessen A, Ensari A, Geboes K, Mantzaris GJ, Villanacci V, Becheanu G, Borralho Nunes P, Cathomas G, Fries W, Jouret-Mourin A, Mescoli C, de Petris G, Rubio CA, Shepherd NA, Vieth M, Eliakim R, European Society of P, European Cs, Colitis O (2013) European consensus on the histopathology of inflammatory bowel disease. J Crohns Colitis 7:827–851. doi:10.1016/j.crohns.2013.06.001

    Article  CAS  PubMed  Google Scholar 

  2. Baumgart DC, Sandborn WJ (2012) Crohn’s disease. Lancet 380:1590–1605. doi:10.1016/S0140-6736(12)60026-9

    Article  PubMed  Google Scholar 

  3. Peyrin-Biroulet L, Loftus EV Jr, Colombel JF, Sandborn WJ (2010) The natural history of adult Crohn's disease in population-based cohorts. Am J Gastroenterol 105:289–297. doi:10.1038/ajg.2009.579

    Article  PubMed  Google Scholar 

  4. Dilauro S, Crum-Cianflone NF (2010) Ileitis: when it is not Crohn’s disease. Curr Gastroenterol Rep 12:249–258. doi:10.1007/s11894-010-0112-5

    Article  PubMed  PubMed Central  Google Scholar 

  5. Greaves ML, Pochapin M (2006) Asymptomatic ileitis: past, present, and future. J Clin Gastroenterol 40:281–285. doi:10.1097/01.mcg.0000210104.59370.66

    Article  PubMed  Google Scholar 

  6. Courville EL, Siegel CA, Vay T, Wilcox AR, Suriawinata AA, Srivastava A (2009) Isolated asymptomatic ileitis does not progress to overt Crohn disease on long-term follow-up despite features of chronicity in ileal biopsies. Am J Surg Pathol 33:1341–1347. doi:10.1097/PAS.0b013e3181ad25b6

    Article  PubMed  Google Scholar 

  7. Freeman HJ (2007) Granuloma-positive Crohn’s disease. Can J Gastroenterol 21:583–587

    Article  PubMed  PubMed Central  Google Scholar 

  8. Dixon MF, Genta RM, Yardley JH, Correa P (1996) Classification and grading of gastritis. The updated Sydney system. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol 20:1161–1181

    Article  CAS  PubMed  Google Scholar 

  9. Patterson ER, Shmidt E, Oxentenko AS, Enders FT, Smyrk TC (2015) Normal villous architecture with increased intraepithelial lymphocytes: a duodenal manifestation of Crohn disease. Am J Clin Pathol 143:445–450. doi:10.1309/AJCPBKQND4SHVX9Q

    Article  PubMed  Google Scholar 

  10. Wu TT, Hamilton SR (1999) Lymphocytic gastritis: association with etiology and topology. Am J Surg Pathol 23:153–158

    Article  CAS  PubMed  Google Scholar 

  11. Jenkins D, Goodall A, Drew K, Scott BB (1988) What is colitis? Statistical approach to distinguishing clinically important inflammatory change in rectal biopsy specimens. J Clin Pathol 41:72–79

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Brown IS, Smith J, Rosty C (2012) Gastrointestinal pathology in celiac disease: a case series of 150 consecutive newly diagnosed patients. Am J Clin Pathol 138:42–49. doi:10.1309/AJCPE89ZPVJTSPWL

    Article  PubMed  Google Scholar 

  13. Feakins RM, British Society of G (2013) Inflammatory bowel disease biopsies: updated British Society of Gastroenterology reporting guidelines. J Clin Pathol 66:1005–1026. doi:10.1136/jclinpath-2013-201885

    Article  PubMed  Google Scholar 

  14. Xin W, Greenson JK (2004) The clinical significance of focally enhanced gastritis. Am J Surg Pathol 28:1347–1351

    Article  PubMed  Google Scholar 

  15. Greenson JK, Stern RA, Carpenter SL, Barnett JL (1997) The clinical significance of focal active colitis. Hum Pathol 28:729–733

    Article  CAS  PubMed  Google Scholar 

  16. Rubio CA, Sjodahl K, Lagergren J (2006) Lymphocytic esophagitis: a histologic subset of chronic esophagitis. Am J Clin Pathol 125:432–437

    Article  PubMed  Google Scholar 

  17. Lauwers GY, Fasano A, Brown IS (2015) Duodenal lymphocytosis with no or minimal enteropathy: much ado about nothing? Mod Pathol 28(Suppl 1):S22–S29. doi:10.1038/modpathol.2014.135

    Article  PubMed  Google Scholar 

  18. Mahajan D, Goldblum JR, Xiao SY, Shen B, Liu X (2012) Lymphocytic colitis and collagenous colitis: a review of clinicopathologic features and immunologic abnormalities. Adv Anat Pathol 19:28–38. doi:10.1097/PAP.0b013e31823d7705

    Article  PubMed  Google Scholar 

  19. Satsangi J, Silverberg MS, Vermeire S, Colombel JF (2006) The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut 55:749–753. doi:10.1136/gut.2005.082909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kumarasinghe MP, Quek TP, Chau CY, Mustapha NR, Luman W, Ooi CJ (2010) Endoscopic biopsy features and diagnostic challenges of adult Crohn’s disease at initial presentation. Pathology 42:131–137. doi:10.3109/00313020903494979

    Article  CAS  PubMed  Google Scholar 

  21. Chang HS, Lee D, Kim JC, Song HK, Lee HJ, Chung EJ, Kim TH, Park HW, Byeon JS, Yang SK, Choe JW (2010) Isolated terminal ileal ulcerations in asymptomatic individuals: natural course and clinical significance. Gastrointest Endosc 72:1226–1232. doi:10.1016/j.gie.2010.08.029

    Article  PubMed  Google Scholar 

  22. Goldstein NS (2006) Isolated ileal erosions in patients with mildly altered bowel habits. A follow-up study of 28 patients. Am J Clin Pathol 125:838–846. doi:10.1309/4PK0-G68M-2G1L-6X47

    Article  PubMed  Google Scholar 

  23. Lengeling RW, Mitros FA, Brennan JA, Schulze KS (2003) Ulcerative ileitis encountered at ileo-colonoscopy: likely role of nonsteroidal agents. Clin Gastroenterol Hepatol 1:160–169. doi:10.1053/cgh.2003.50024

    Article  CAS  PubMed  Google Scholar 

  24. Simillis C, Jacovides M, Reese GE, Yamamoto T, Tekkis PP (2010) Meta-analysis of the role of granulomas in the recurrence of Crohn disease. Dis Colon rectum 53:177–185. doi:10.1007/DCR.0b013e3181b7bfb0

  25. Heresbach D, Alexandre JL, Branger B, Bretagne JF, Cruchant E, Dabadie A, Dartois-Hoguin M, Girardot PM, Jouanolle H, Kerneis J, Le Verger JC, Louvain V, Politis J, Richecoeur M, Robaszkiewicz M, Seyrig JA, Abermad (2005) Frequency and significance of granulomas in a cohort of incident cases of Crohn’s disease. Gut 54:215–222. doi:10.1136/gut.2004.041715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Idestrom M, Rubio CA, Onelov E, Henter JI, Fagerberg UL, Finkel Y (2014) Pediatric Crohn’s disease from onset to adulthood: granulomas are associated with an early need for immunomodulation. Scand J Gastroenterol 49:950–957. doi:10.3109/00365521.2014.920911

    Article  PubMed  Google Scholar 

  27. Rubio CA, Orrego A, Nesi G, Finkel Y (2007) Frequency of epithelioid granulomas in colonoscopic biopsy specimens from paediatric and adult patients with Crohn’s colitis. J Clin Pathol 60:1268–1272. doi:10.1136/jcp.2006.045336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Oberhuber G, Puspok A, Oesterreicher C, Novacek G, Zauner C, Burghuber M, Vogelsang H, Potzi R, Stolte M, Wrba F (1997) Focally enhanced gastritis: a frequent type of gastritis in patients with Crohn’s disease. Gastroenterology 112:698–706

    Article  CAS  PubMed  Google Scholar 

  29. Ushiku T, Moran CJ, Lauwers GY (2013) Focally enhanced gastritis in newly diagnosed pediatric inflammatory bowel disease. Am J Surg Pathol 37:1882–1888. doi:10.1097/PAS.0b013e31829f03ee

    Article  PubMed  PubMed Central  Google Scholar 

  30. Sonnenberg A, Melton SD, Genta RM (2011) Frequent occurrence of gastritis and duodenitis in patients with inflammatory bowel disease. Inflamm Bowel Dis 17:39–44. doi:10.1002/ibd.21356

    Article  PubMed  Google Scholar 

  31. Shetty S, Anjarwalla SM, Gupta J, Foy CJ, Shaw IS, Valori RM, Shepherd NA (2011) Focal active colitis: a prospective study of clinicopathological correlations in 90 patients. Histopathology 59:850–856. doi:10.1111/j.1365-2559.2011.04019.x

    Article  PubMed  Google Scholar 

  32. Volk EE, Shapiro BD, Easley KA, Goldblum JR (1998) The clinical significance of a biopsy-based diagnosis of focal active colitis: a clinicopathologic study of 31 cases. Mod Pathol 11:789–794

    CAS  PubMed  Google Scholar 

  33. Xin W, Brown PI, Greenson JK (2003) The clinical significance of focal active colitis in pediatric patients. Am J Surg Pathol 27:1134–1138

    Article  PubMed  Google Scholar 

  34. Goldstein NS, Gyorfi T (1999) Focal lymphocytic colitis and collagenous colitis: patterns of Crohn’s colitis? Am J Surg Pathol 23:1075–1081

    Article  CAS  PubMed  Google Scholar 

  35. O'Donnell S, Crotty PL, O'Sullivan M, Breslin N, O'Connor HJ, O'Morain CA, Ryan BM (2013) Isolated active ileitis: is it a mild subtype of Crohn’s disease? Inflamm Bowel Dis 19:1815–1822. doi:10.1097/MIB.0b013e31828dc68b

    PubMed  Google Scholar 

Download references

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Correspondence to Ian S. Brown.

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This study was performed in accordance with institutional ethical guidelines imposed by the local Human Research Ethics Committee.

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Brown, I.S., Miller, G.C., Bettington, M.L. et al. Histopathological findings of extra-ileal manifestations at initial diagnosis of Crohn’s disease-related ileitis. Virchows Arch 469, 515–522 (2016). https://doi.org/10.1007/s00428-016-2009-7

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  • DOI: https://doi.org/10.1007/s00428-016-2009-7

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