Skip to main content
SpringerLink
Log in

Duodenal bulb biopsy in the diagnostic work-up of coeliac disease

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Coeliac disease (CD) is an autoimmune enteropathy which can present with patchy mucosal lesions. The aim of the present study is to investigate the significance of duodenal bulb biopsy in the diagnostic work-up of CD in both pediatric and adult patients, and to highlight the key points for pathologists. D1 (duodenal bulb) and D2 (distal duodenum) biopsies of 153 newly diagnosed serology-positive CD patients were evaluated for villous/crypt ratio and intraepithelial lymphocyte (IEL) counts on CD3-stained slides and were classified according to Marsh. Mucosal pathology was patchy in 15% (13% only D1 and 2% only D2) of patients, and 85% of patients had diffuse mucosal pathology involving both D1 and D2 biopsies which showed concordant histology in 60% and discordant in 25% of the cases. Though majority of the patients (75%) with only D1 involvement were pediatric cases, no significant difference was found between pediatric and adult patients when all cases were considered (17 vs 14%). Our results clearly indicate that without D1 sampling, diagnosis of CD would have been missed in a significant number of cases (13%), thereby highlighting the importance of taking duodenal biopsies from multiple sites in the diagnostic work-up of CD. We, therefore, conclude that every biopsy piece from both D1 and D2 should be carefully evaluated for the whole spectrum of mucosal changes caused by gluten ingestion and classified using a scheme based on Marsh to allow recognition of mild lesions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Bonamico M, Mariani P, Thanasi E, Ferri M, Nenna R, Tiberti C, Mora B, Mazzilli MC, Magliocca FM (2004) Patchy villous atrophy of the duodenum in childhood celiac disease. J Pediatr Gastroenterol Nutr 38:204–207

    Article  Google Scholar 

  2. Bonamico M, Thanasi E, Mariani P, Nenna R, Luparia RP, Barbera C, Morra I, Lerro P, Guariso G, De Giacomo C, Scotta S, Pontone S, Carpino F, Magliocca FM, Societa Italiana di Gastroenterologica EeNP (2008) Duodenal bulb biopsies in celiac disease: a multicenter study. J Pediatr Gastroenterol Nutr 47:618–622

    Article  Google Scholar 

  3. Caruso R, Marafini I, Del Vecchio BG, Fina D, Paoluzi OA, Colantoni A, Sedda S, Pallone F, Monteleone G (2014) Sampling of proximal and distal duodenal biopsies in the diagnosis and monitoring of celiac disease. Dig Liver Dis 46:323–329. https://doi.org/10.1016/j.dld.2013.12.005

    Article  PubMed  Google Scholar 

  4. Dhandhu BS, Gupta GK, Wanjari SJ, Sharma N, Nijhawan S (2018) A prospective study to evaluate the role of duodenal bulb biopsy in the diagnosis of celiac disease. Indian J Gastroenterol 37:98–102. https://doi.org/10.1007/s12664-018-0821-5

    Article  PubMed  Google Scholar 

  5. Downey L, Houten R, Murch S, Longson D, Guideline Development G (2015) Recognition, assessment, and management of coeliac disease: summary of updated NICE guidance. BMJ 351:h4513. https://doi.org/10.1136/bmj.h4513

    Article  CAS  PubMed  Google Scholar 

  6. Doyev R, Cohen S, Ben-Tov A, Weintraub Y, Amir A, Galai T, Moran-Lev H, Yerushalmy-Feler A (2019) Ultra-short celiac disease is a distinct and milder phenotype of the disease in children. Dig Dis Sci 64:167–172. https://doi.org/10.1007/s10620-018-5323-x

    Article  CAS  PubMed  Google Scholar 

  7. Ensari A (2010) Gluten-sensitive enteropathy (celiac disease): controversies in diagnosis and classification. Arch Pathol Lab Med 134:826–836. https://doi.org/10.1043/1543-2165-134.6.826

    Article  PubMed  Google Scholar 

  8. Evans KE, Aziz I, Cross SS, Sahota GR, Hopper AD, Hadjivassiliou M, Sanders DS (2011) A prospective study of duodenal bulb biopsy in newly diagnosed and established adult celiac disease. Am J Gastroenterol 106:1837–1742. https://doi.org/10.1038/ajg.2011.171

    Article  PubMed  Google Scholar 

  9. Feakins A, Campbell, Mears, Scott (2016) Tissue pathways for gastrointestinal and pancreatobiliary pathology. The Royal College of Pathologists. https://www.rcpath.org/uploads/assets/4593f557-d75c-4ca6-9307a9d688e02a2d/g085-tp-giandp-jan16.pdf

  10. Force USPST, Bibbins-Domingo K, Grossman DC, Curry SJ, Barry MJ, Davidson KW, Doubeni CA, Ebell M, Epling JW Jr, Herzstein J, Kemper AR, Krist AH, Kurth AE, Landefeld CS, Mangione CM, Phipps MG, Silverstein M, Simon MA, Tseng CW (2017) Screening for celiac disease: US Preventive Services Task Force recommendation statement. JAMA 317:1252–1257. https://doi.org/10.1001/jama.2017.1462

    Article  Google Scholar 

  11. Gonzalez S, Gupta A, Cheng J, Tennyson C, Lewis SK, Bhagat G, Green PH (2010) Prospective study of the role of duodenal bulb biopsies in the diagnosis of celiac disease. Gastrointest Endosc 72:758–765. https://doi.org/10.1016/j.gie.2010.06.026

    Article  PubMed  Google Scholar 

  12. Hopper AD, Cross SS, Sanders DS (2008) Patchy villous atrophy in adult patients with suspected gluten-sensitive enteropathy: is a multiple duodenal biopsy strategy appropriate? Endoscopy 40:219–224. https://doi.org/10.1055/s-2007-995361

    Article  CAS  PubMed  Google Scholar 

  13. Husby S, Koletzko S, Korponay-Szabo IR, Mearin ML, Phillips A, Shamir R, Troncone R, Giersiepen K, Branski D, Catassi C, Lelgeman M, Maki M, Ribes-Koninckx C, Ventura A, Zimmer KP, Diagnosis EWGoCD, Committee EG, European Society for Pediatric Gastroenterology H, Nutrition (2012) European society for pediatric gastroenterology, hepatology, and nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 54:136–160. https://doi.org/10.1097/MPG.0b013e31821a23d0

    Article  CAS  PubMed  Google Scholar 

  14. Husby S, Koletzko S, Korponay-Szabo I, Kurppa K, Mearin ML, Ribes-Koninckx C, Shamir R, Troncone R, Auricchio R, Castillejo G, Christensen R, Dolinsek J, Gillett P, Hrobjartsson A, Koltai T, Maki M, Nielsen SM, Popp A, Stordal K, Werkstetter K, Wessels M (2020) European society paediatric gastroenterology, hepatology and nutrition guidelines for diagnosing coeliac disease 2020. J Pediatr Gastroenterol Nutr 70:141–156. https://doi.org/10.1097/MPG.0000000000002497

    Article  PubMed  Google Scholar 

  15. Husnoo N, Ahmed W, Shiwani MH (2017) Duodenal biopsies for the diagnosis of coeliac disease: are we adhering to current guidance? BMJ Open Gastroenterol 4:e000140. https://doi.org/10.1136/bmjgast-2017-000140

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kirmizi A, Kalkan C, Yuksel S, Gencturk Z, Savas B, Soykan I, Cetinkaya H, Ensari A (2018) Discriminant value of IEL counts and distribution pattern through the spectrum of gluten sensitivity: a simple diagnostic approach. Virchows Arch 473:551–558. https://doi.org/10.1007/s00428-018-2430-1

    Article  CAS  PubMed  Google Scholar 

  17. Kurien M, Evans KE, Hopper AD, Hale MF, Cross SS, Sanders DS (2012) Duodenal bulb biopsies for diagnosing adult celiac disease: is there an optimal biopsy site? Gastrointest Endosc 75:1190–1196. https://doi.org/10.1016/j.gie.2012.02.025

    Article  PubMed  Google Scholar 

  18. Lebwohl B, Kapel RC, Neugut AI, Green PH, Genta RM (2011) Adherence to biopsy guidelines increases celiac disease diagnosis. Gastrointest Endosc 74:103–109. https://doi.org/10.1016/j.gie.2011.03.1236

    Article  PubMed  PubMed Central  Google Scholar 

  19. Levinson-Castiel R, Hartman C, Morgenstern S, Avitzur Y, Hirsch A, Rosenbach Y, Shapiro R, Zevit N, Fleischaker H, Niv Y, Shamir R (2011) The role of duodenal bulb biopsy in the diagnosis of celiac disease in children. J Clin Gastroenterol 45:26–29. https://doi.org/10.1097/MCG.0b013e3181e04d26

    Article  PubMed  Google Scholar 

  20. Ludvigsson JF, Bai JC, Biagi F, Card TR, Ciacci C, Ciclitira PJ, Green PH, Hadjivassiliou M, Holdoway A, van Heel DA, Kaukinen K, Leffler DA, Leonard JN, Lundin KE, McGough N, Davidson M, Murray JA, Swift GL, Walker MM, Zingone F, Sanders DS, Group BSGCDGD (2014) Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology. Gut 63:1210–1228. doi: https://doi.org/10.1136/gutjnl-2013-306578

  21. Mangiavillano B, Masci E, Parma B, Barera G, Viaggi P, Albarello L, Tronconi GM, Mariani A, Testoni S, Santoro T, Testoni PA (2010) Bulb biopsies for the diagnosis of celiac disease in pediatric patients. Gastrointest Endosc 72:564–568. https://doi.org/10.1016/j.gie.2010.05.021

    Article  PubMed  Google Scholar 

  22. Mansfield-Smith S, Savalagi V, Rao N, Thomson M, Cohen MC (2014) Duodenal bulb histological analysis should be standard of care when evaluating celiac disease in children. Pediatr Dev Pathol 17:339–343. https://doi.org/10.2350/14-03-1451-OA.1

    Article  PubMed  Google Scholar 

  23. Marsh MN (1992) Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity (‘celiac sprue’). Gastroenterology 102:330–354

    Article  CAS  Google Scholar 

  24. McCarty TR, O’Brien CR, Gremida A, Ling C, Rustagi T (2018) Efficacy of duodenal bulb biopsy for diagnosis of celiac disease: a systematic review and meta-analysis. Endosc Int Open 6:E1369–E1378. https://doi.org/10.1055/a-0732-5060

    Article  PubMed  PubMed Central  Google Scholar 

  25. Mooney PD, Kurien M, Evans KE, Rosario E, Cross SS, Vergani P, Hadjivassiliou M, Murray JA, Sanders DS (2016) Clinical and immunologic features of ultra-short celiac disease. Gastroenterology 150:1125–1134. https://doi.org/10.1053/j.gastro.2016.01.029

    Article  CAS  PubMed  Google Scholar 

  26. Murray JA, Rubio-Tapia A, Van Dyke CT, Brogan DL, Knipschield MA, Lahr B, Rumalla A, Zinsmeister AR, Gostout CJ (2008) Mucosal atrophy in celiac disease: extent of involvement, correlation with clinical presentation, and response to treatment. Clin Gastroenterol Hepatol 6:186–193; quiz 125. https://doi.org/10.1016/j.cgh.2007.10.012

    Article  PubMed  Google Scholar 

  27. Nenna R, Pontone S, Pontone P, Petrarca L, Mennini M, Standoli M, Mastrogiorgio G, Bonamico M, Magliocca FM (2012) Duodenal bulb in celiac adults: the “whether biopsying” dilemma. J Clin Gastroenterol 46:302–307. https://doi.org/10.1097/MCG.0b013e31822d31da

    Article  PubMed  Google Scholar 

  28. Nenna R, Tiberti C, Petrarca L, Mennini M, Mastrogiorgio G, Lucantoni F, Panimolle F, Pontone S, Bavastrelli M, Magliocca FM, Bonamico M (2013) Anti-transglutaminase immunoreactivity and histological lesions of the duodenum in coeliac patients. Int Immunol 25:389–394. https://doi.org/10.1093/intimm/dxs159

    Article  CAS  PubMed  Google Scholar 

  29. Pais WP, Duerksen DR, Pettigrew NM, Bernstein CN (2008) How many duodenal biopsy specimens are required to make a diagnosis of celiac disease? Gastrointest Endosc 67:1082–1087. https://doi.org/10.1016/j.gie.2007.10.015

    Article  PubMed  Google Scholar 

  30. Prasad KK, Thapa BR, Nain CK, Singh K (2009) Assessment of the diagnostic value of duodenal bulb histology in patients with celiac disease, using multiple biopsy sites. J Clin Gastroenterol 43:307–311. https://doi.org/10.1097/MCG.0b013e31815b9d11

    Article  PubMed  Google Scholar 

  31. Rashid M, MacDonald A (2009) Importance of duodenal bulb biopsies in children for diagnosis of celiac disease in clinical practice. BMC Gastroenterol 9:78. https://doi.org/10.1186/1471-230X-9-78

    Article  PubMed  PubMed Central  Google Scholar 

  32. Ravelli A, Bolognini S, Gambarotti M, Villanacci V (2005) Variability of histologic lesions in relation to biopsy site in gluten-sensitive enteropathy. Am J Gastroenterol 100:177–185. https://doi.org/10.1111/j.1572-0241.2005.40669.x

    Article  PubMed  Google Scholar 

  33. Robert ME, Crowe SE, Burgart L, Yantiss RK, Lebwohl B, Greenson JK, Guandalini S, Murray JA (2018) Statement on best practices in the use of pathology as a diagnostic tool for celiac disease: a guide for clinicians and pathologists. Am J Surg Pathol 42:e44–e58. https://doi.org/10.1097/PAS.0000000000001107

    Article  PubMed  Google Scholar 

  34. Rubio-Tapia A, Hill ID, Kelly CP, Calderwood AH, Murray JA, American College of G (2013) ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol 108:656–676; quiz 677. https://doi.org/10.1038/ajg.2013.79

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Shamban L, Sorser S, Naydin S, Lebwohl B, Shukr M, Wiemann C, Yevsyukov D, Piper MH, Warren B, Green PHR (2017) Factors associated with number of duodenal samples obtained in suspected celiac disease. Endosc Int Open 5:E1220–E1228. https://doi.org/10.1055/s-0043-120522

    Article  PubMed  PubMed Central  Google Scholar 

  36. Sharma A, Mews C, Jevon G, Ravikumara M (2013) Duodenal bulb biopsy in children for the diagnosis of coeliac disease: experience from Perth, Australia. J Paediatr Child Health 49:210–214. https://doi.org/10.1111/jpc.12123

    Article  PubMed  Google Scholar 

  37. Stoven SA, Choung RS, Rubio-Tapia A, Absah I, Lam-Himlin DM, Harris LA, Ngamruengphong S, Vazquez Roque MI, Wu TT, Murray JA (2016) Analysis of biopsies from duodenal bulbs of all endoscopy patients increases detection of abnormalities but has a minimal effect on diagnosis of celiac disease. Clin Gastroenterol Hepatol 14:1582–1588. https://doi.org/10.1016/j.cgh.2016.02.026

    Article  PubMed  Google Scholar 

  38. Tanpowpong P, Broder-Fingert S, Katz AJ, Camargo CA Jr (2012) Predictors of duodenal bulb biopsy performance in the evaluation of coeliac disease in children. J Clin Pathol 65:791–794. https://doi.org/10.1136/jclinpath-2012-200874

    Article  PubMed  Google Scholar 

  39. Thompson H (1974) Necropsy studies on adult coeliac disease. J Clin Pathol 27:710–721. https://doi.org/10.1136/jcp.27.9.710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Valitutti F, Di Nardo G, Barbato M, Aloi M, Celletti I, Trovato CM, Pierdomenico M, Marcheggiano A, Cucchiara S (2014) Mapping histologic patchiness of celiac disease by push enteroscopy. Gastrointest Endosc 79:95–100. https://doi.org/10.1016/j.gie.2013.06.012

    Article  PubMed  Google Scholar 

  41. Vogelsang H, Hanel S, Steiner B, Oberhuber G (2001) Diagnostic duodenal bulb biopsy in celiac disease. Endoscopy 33:336–340. https://doi.org/10.1055/s-2001-13702

    Article  CAS  PubMed  Google Scholar 

  42. Walker MM, Murray JA (2011) An update in the diagnosis of coeliac disease. Histopathology 59:166–179. https://doi.org/10.1111/j.1365-2559.2010.03680.x

    Article  PubMed  Google Scholar 

  43. Weir DC, Glickman JN, Roiff T, Valim C, Leichtner AM (2010) Variability of histopathological changes in childhood celiac disease. Am J Gastroenterol 105:207–212. https://doi.org/10.1038/ajg.2009.557

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Ankara University Medical School, Sihhiye, 06100, Ankara, Turkey

    Hilal Özakıncı, Ayça Kırmızı, Merve Tural, Saba Kiremitçi, Berna Savaş & Arzu Ensari

  2. Department of Paediatric Gastroenterology, Hepatology and Nutrition, Ankara University Medical School, Cebeci, Ankara, Turkey

    Zarife Kuloğlu & Aydan Kansu

Authors
  1. Hilal Özakıncı
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ayça Kırmızı
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Merve Tural
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Saba Kiremitçi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Berna Savaş
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zarife Kuloğlu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Aydan Kansu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Arzu Ensari
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Hilal Özakıncı (HÖ) and Arzu Ensari (AE) designed the study, re-evaluated biopsies, criticized the results, and wrote the manuscript. Merve Tural, Ayça Kırmızı, and Saba Kiremitçi collected pathological, and Zarife Kuloğlu and Aydan Kansu collected clinical data. Berna Savaş and Aydan Kansu edited and criticized the manuscript. All authors gave final approval for publication.

Corresponding author

Correspondence to Arzu Ensari.

Ethics declarations

This retrospective study has been approved by the Institutional Review Board. See supplementary material for the decision in Turkish and translated version in English.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Özakıncı, H., Kırmızı, A., Tural, M. et al. Duodenal bulb biopsy in the diagnostic work-up of coeliac disease. Virchows Arch 477, 507–515 (2020). https://doi.org/10.1007/s00428-020-02832-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-020-02832-6

Keywords

Search

Navigation