A Blinded Pilot Comparison of Capsule Endoscopy and Small Bowel Histology in Unresponsive Celiac Disease

  • L. Maiden
  • T. Elliott
  • S. D. McLaughlin
  • P. Ciclitira
Original Article


This study compares video capsule endoscopy (VCE) with histological specimens of proximal small bowel in patients with celiac disease who have failed to respond to a gluten-free diet. Patients with nonresponsive celiac disease underwent capsule endoscopy, and concordance between endoscopy and histology was then calculated using the kappa statistic. In 19 patients, endoscopy videos were reported as normal in ten (53%) case, as having mild changes in three (16%) cases, and as having moderate-severe changes in six (31%) cases. Two (11%) had acute ulcers. No small bowel tumors were seen. Endoscopy demonstrated concordance with histological changes in 14 of the 18 patients with histology available (78% concordance). The kappa statistic suggested a substantial degree of concordance between histology and endoscopic findings. Endoscopy with distal duodenal biopsies is superior to VCE in detecting proximal, nonresponsive celiac disease, but more distal lesions may be missed such that the strength of VCE lies in its ability to visualize the entire small bowel.


Capsule endoscopy Refractory celiac disease Refractory celiac sprue 


  1. 1.
    Pink IJ, Creamer B. Response to a gluten-free diet of patients with the coeliac syndrome. Lancet. 1967;1:300–304. doi: 10.1016/S0140-6736(67)91238-X.PubMedCrossRefGoogle Scholar
  2. 2.
    O’Mahony S, Howdle PD, Losowsky MS. Review article: management of patients with non-responsive coeliac disease. Aliment Pharmacol Ther. 1996;10:671–680. doi: 10.1046/j.1365-2036.1996.66237000.x.PubMedCrossRefGoogle Scholar
  3. 3.
    Daum S, Cellier C, Mulder CJ. Refractory coeliac disease. Best Pract Res Clin Gastroenterol. 2005;19:413–424. doi: 10.1016/j.bpg.2005.02.001.PubMedCrossRefGoogle Scholar
  4. 4.
    Trier JS. Celiac sprue. N Engl J Med. 1991;325:1709–1719.PubMedGoogle Scholar
  5. 5.
    Gomez J, Moran C, Maurino E, Bai J. Exocrine pancreatic insufficiency in celiac disease. Gastroenterology. 1998;114:621–623; letter. doi: 10.1016/S0016-5085(98)70562-1.Google Scholar
  6. 6.
    Carroccio A, Lacono G, Montalto G, et al. Exocrine pancreatic function in children with coeliac disease before and after a gluten free diet. Gut. 1991;32:796–799. doi: 10.1136/gut.32.7.796.PubMedCrossRefGoogle Scholar
  7. 7.
    Fine K, Meyer R, Lee E. The prevalence and causes of chronic diarrhea in patients with celiac sprue treated with a gluten-free diet. Gastroenterology. 1997;112:1830–1838. doi: 10.1053/gast.1997.v112.pm9178673.PubMedCrossRefGoogle Scholar
  8. 8.
    Roufail W, Ruffin J. Effect of antibiotic therapy on gluten sensitive enteropathy. Am J Dig Dis. 1966;11:587–593. doi: 10.1007/BF02233506.PubMedCrossRefGoogle Scholar
  9. 9.
    Kitis G, Holmes G, Cooper B, Thompson H, Allan R. Association of coeliac disease and inflammatory bowel disease. Gut. 1980;21:636–641. doi: 10.1136/gut.21.7.636.PubMedCrossRefGoogle Scholar
  10. 10.
    McCashland T, Donovan J, Strobach R, Linder J, Quigley E. Collagenous colitis: a manifestation of gluten-sensitive enteropathy. J Clin Gastroenterol. 1992;15:45–51. doi: 10.1097/00004836-199207000-00011.PubMedCrossRefGoogle Scholar
  11. 11.
    DuBois R, Lazenby A, Yardley J, Hendrix T, Bayless T, Giardiello F. Lymphocytic enterocolitis in patients with ‘refractory sprue’. JAMA. 1989;262:935–937. doi: 10.1001/jama.262.7.935.PubMedCrossRefGoogle Scholar
  12. 12.
    Howdle PD, Jalal PK, Holmes GK, et al. Primary small-bowel malignancy in the UK and its association with coeliac disease. QJM. 2003;96:345–353. doi: 10.1093/qjmed/hcg058.PubMedCrossRefGoogle Scholar
  13. 13.
    Freeman HJ. Lymphoproliferative and intestinal malignancies in 214 patients with biopsy-defined celiac disease. J Clin Gastroenterol. 2004;38:429–434. doi: 10.1097/01.mcg.0000135363.12794.2b.PubMedCrossRefGoogle Scholar
  14. 14.
    Cellier C, Delabesse E, Helmer C, et al. Refractory sprue, coeliac disease, and enteropathy-associated T-cell lymphoma. French Coeliac Disease Study Group. Lancet. 2000;356:203–208. doi: 10.1016/S0140-6736(00)02481-8.PubMedCrossRefGoogle Scholar
  15. 15.
    Isaacson PG, O’Connor NT, Spencer J, et al. Malignant histiocytosis of the intestine: a T-cell lymphoma. Lancet. 1985;2:688–691. doi: 10.1016/S0140-6736(85)92930-7.PubMedCrossRefGoogle Scholar
  16. 16.
    Ciclitira PJ, King AL, Fraser JS. AGA technical review on Celiac Sprue. American Gastroenterological Association. Gastroenterology. 2001;120:1526–1540.PubMedCrossRefGoogle Scholar
  17. 17.
    Remedios ML, Appleyard M. Capsule endoscopy: current indications and future prospects. Intern Med J. 2005;35:234–239. doi: 10.1111/j.1445-5994.2005.00808.x.PubMedCrossRefGoogle Scholar
  18. 18.
    Culliford A, Daly J, Diamond B, et al. The value of wireless capsule endoscopy in patients with complicated celiac disease. Gastrointest Endosc. 2005;62:55–61. doi: 10.1016/S0016-5107(05)01566-X.PubMedCrossRefGoogle Scholar
  19. 19.
    Marsh MN, Crowe PT. Morphology of the mucosal lesion in gluten sensitivity. Baillieres Clin Gastroenterol. 1995;9:273–293. doi: 10.1016/0950-3528(95)90032-2.PubMedCrossRefGoogle Scholar
  20. 20.
    Maiden L, Thjodleifsson B, Theodors A, et al. A quantitative analysis of NSAID-induced small bowel pathology by capsule enteroscopy. Gastroenterology. 2005;128:1172–1178. doi: 10.1053/j.gastro.2005.03.020.PubMedCrossRefGoogle Scholar
  21. 21.
    Brocchi E, Tomassetti P, Misitano B, et al. Endoscopic markers in adult coeliac disease. Dig Liver Dis. 2002;34:172–174. doi: 10.1016/S1590-8658(02)80190-6.CrossRefGoogle Scholar
  22. 22.
    Toth E, Ohlsson B, Ljungberg O, et al. Celiac disease diagnosed using video capsule endoscopy in a patient with Crohn’s disease. Endoscopy. 2006;38:548. doi: 10.1055/s-2006-925342.Google Scholar
  23. 23.
    Green PH, Rubin M. Capsule endoscopy in celiac disease: diagnosis and management. Gastrointest Endosc Clin N Am. 2006;16:307–316. doi: 10.1016/j.giec.2006.03.003.PubMedCrossRefGoogle Scholar
  24. 24.
    Hopper AD, Sidhu R, Hurlstone DP, et al. Capsule endoscopy: an alternative to duodenal biopsy for the recognition of villous atrophy in coeliac disease? Dig Liver Dis. 2007;39:145–147. doi: 10.1016/j.dld.2006.07.017.CrossRefGoogle Scholar
  25. 25.
    Petroniene R, Dubcenco E, Baker JP, et al. Given capsule endoscopy in celiac disease. Gastrointest Endosc Clin N Am. 2004;14:115–127. doi: 10.1016/j.giec.2003.10.005.PubMedCrossRefGoogle Scholar
  26. 26.
    Kimchi NA, Broide E, Zehavi S, et al. Capsule endoscopy diagnosis of celiac disease and ileal tumors in a patient with melena of obscure origin. Isr Med Assoc J. 2005;7:412–413.PubMedGoogle Scholar
  27. 27.
    Daum S, Weiss D, Hummel M, et al. Frequency of clonal intraepithelial T lymphocyte proliferatios in enteropathy-type intestinal T cell lymphoma, coeliac disease, and refractory sprue. Gut. 2001;49:804–812. doi: 10.1136/gut.49.6.804.PubMedCrossRefGoogle Scholar
  28. 28.
    Hara AK, Leighton JA, Heigh RI, et al. Crohn disease of the small bowel: preliminary comparison among CT enterography, capsule endoscopy, small-bowel follow-through, and ileoscopy. Radiology. 2006;238:128–134. doi: 10.1148/radiol.2381050296.PubMedCrossRefGoogle Scholar
  29. 29.
    Eliakim R, Fischer D, Suissa A, et al. Wireless capsule video endoscopy is a superior diagnostic tool in comparison to barium follow-through and computerized tomography in patients with suspected Crohn’s disease. Eur J Gastroenterol Hepatol. 2003;15:363–367. doi: 10.1097/00042737-200304000-00005.PubMedCrossRefGoogle Scholar
  30. 30.
    Albert JG, Martiny F, Krummenerl A, et al. Diagnosis of small bowel Crohn’s disease: a prospective comparison of capsule endoscopy with magnetic resonance imaging and fluoroscopic enteroclysis. Gut. 2005;54:1721–1727. doi: 10.1136/gut.2005.069427.PubMedCrossRefGoogle Scholar
  31. 31.
    Voderholzer W, Beinhoelzl J, Rogalla P, et al. Small bowel involvement in Crohn’s disease: a prospective comparison of wireless capsule endoscopy and computed tomography enteroclysis. Gut. 2005;54:369–373. doi: 10.1136/gut.2004.040055.PubMedCrossRefGoogle Scholar
  32. 32.
    Holmes GK. Coeliac disease and malignancy. Dig Liver Dis. 2002;34:229–237. doi: 10.1016/S1590-8658(02)80198-0.PubMedCrossRefGoogle Scholar
  33. 33.
    Smedby KE, Akerman M, Hildebrand H, et al. Malignant lymphomas in coeliac disease: evidence of increased risks for lymphoma types other than enteropathy-type T cell lymphoma. Gut. 2005;54:54–59. doi: 10.1136/gut.2003.032094.PubMedCrossRefGoogle Scholar
  34. 34.
    Pennazio M. Capsule endoscopy: where are we after 6 years of clinical use? Dig Liver Dis. 2006;38:867–878. doi: 10.1016/j.dld.2006.09.007.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • L. Maiden
    • 1
  • T. Elliott
    • 1
  • S. D. McLaughlin
    • 2
  • P. Ciclitira
    • 2
  1. 1.Department of GastroenterologyGuy’s & St. Thomas’ NHS Foundation TrustLondonUK
  2. 2.Division of Nutritional SciencesRayne Institute, King’s College London, St. Thomas’ HospitalLondonUK

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