Endoscopy 2010; 42(3): 197-202
DOI: 10.1055/s-0029-1243937
Original article

© Georg Thieme Verlag KG Stuttgart · New York

Diagnostic value of confocal endomicroscopy in celiac disease

U.  Günther1 [*] , S.  Daum1 [*] , F.  Heller1 , M.  Schumann1 , C.  Loddenkemper2 , M.  Grünbaum2 , M.  Zeitz1 , C.  Bojarski1
  • 1Medizinische Klinik I Gastroenterologie, Charité – Campus Benjamin Franklin, Berlin, Germany
  • 2Institut für Pathologie, Charité – Campus Benjamin Franklin, Berlin, Germany
Further Information

Publication History

submitted 19 September 2009

accepted after revision 4 January 2010

Publication Date:
01 March 2010 (online)

Background: Improved endoscopic screening with targeted biopsies might enhance diagnostic yield in celiac disease. Confocal endomicroscopy (CEM) allows high-resolution in vivo histological analysis. We compared the endomicroscopic findings during ongoing endoscopy with the histological findings graded according to the Marsh classification.

Methods: Twenty-four patients with celiac disease and six patients with celiac disease that was refractory on a gluten-free diet were examined using CEM. The duodenal mucosa was evaluated by CEM and by conventional histological analysis in respect of villous atrophy, crypt hyperplasia, and increased numbers of intraepithelial lymphocytes (IELs > 40 / 100 enterocytes). The CEM results were assessed as to sensitivity, specificity, and interobserver variability. A Marsh classification score determined by CEM was compared to that obtained by histology. Thirty patients undergoing routine upper gastrointestinal endoscopy were used as controls.

Results: Conventional histology showed villous atrophy and crypt hyperplasia in 23 and increased numbers of IELs in 27 of the 30 patients with celiac disease. With CEM, villous atrophy, crypt hyperplasia, and increased IELs were respectively identified in 17, 12, and 22 of the 30 patients. The agreement of the findings on CEM with those of conventional histology was good in relation to villous atrophy (sensitivity 74 %) and increased numbers of IELs (sensitivity 81 %), but inadequate in relation to crypt hyperplasia (sensitivity 52 %). The κ values for determination of interobserver variability were 0.90 for villous atrophy, 1.00 for crypt hyperplasia, and 0.84 for IEL detection. In the 30 control patients, normal duodenal architecture was found by both histology and endomicroscopy, indicating an overall specificity of 100 %.

Conclusion: The assessment of duodenal histology by CEM in patients with celiac disease is sensitive and specific in determining increased numbers of IELs and villous atrophy, but insufficient in respect of crypt hyperplasia. For routine use of CEM in patients with celiac disease, the technique would need to be improved.

References

  • 1 Gutschmidt S, Sandforth F, Janicke I. et al . Incidence of endemic sprue in Berlin (West). A retrospective study based on biopsy findings.  Z Gastroenterol. 1987;  25 662-667
  • 2 Henker J, Lösel A, Conrad K. et al . Prevalence of asymptommatic coeliac disease in children and adults in the Dresden region of Germany.  Dtsch Med Wochenschr. 2002;  127 1511-1515
  • 3 Ravelli A, Bolognini S, Gambarotti M. et al . Variability of histologic lesions in relation to biopsy site in gluten-sensitive enteropathy.  Am J Gastroenterol. 2005;  100 177-185
  • 4 Cammarota G, Fedeli P, Gasbarrini A. Emerging technologies in upper gastrointestinal endoscopy and celiac disease.  Nat Clin Pract Gastroenterol Hepatol. 2009;  6 47-56
  • 5 Banerjee R, Shekharan A, Ramji C. et al . Role of magnification endoscopy in the diagnosis and evaluation of suspected celiac disease: correlation with histology.  Indian J Gastroenterol. 2007;  26 67-69
  • 6 Banerjee R, Reddy D N. High-resolution narrow-band imaging can identify patchy atrophy in celiac disease: targeted biopsy can increase diagnostic yield.  Gastrointest Endosc. 2009;  69 984-985
  • 7 Kiesslich R, Canto M I. Confocal laser endomicroscopy.  Gastrointest Endosc Clin N Am. 2009;  19 261-272
  • 8 Trovato C, Sonzogni A, Ravizza D. et al . Celiac disease: in vivo diagnosis by confocal endomicroscopy.  Gastrointest Endosc. 2007;  65 1096-1099
  • 9 Zambelli A, Villanacci V, Buscarini E. et al . Confocal laser endomicroscopy in celiac disease: description of findings in two cases.  Endoscopy. 2007;  39 1018-1020
  • 10 Leong R W, Nguyen N Q, Meredith C G. et al . In vivo confocal endomicroscopy in the diagnosis and evaluation of celiac disease.  Gastroenterology. 2008;  135 1870-1876
  • 11 Daum S, Cellier C, Mulder C J. Refractory coeliac disease.  Best Pract Res Clin Gastroenterol. 2005;  19 413-424
  • 12 Kiesslich R, Burg J, Vieth M. et al . Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo.  Gastroenterology. 2004;  127 706-713
  • 13 Marsh M N, Crowe P T. Morphology of the mucosal lesion in gluten sensitivity.  Baillieres Clin Gastroenterol. 1995;  9 273-293
  • 14 Oberhuber G, Caspary W F, Kirchner T. et al . Study Group of Gastroenterological Pathology of the German Society of Pathology. Recommendations for celiac disease/sprue diagnosis [in German].  Z Gastroenterol. 2001;  39 157-166
  • 15 Deinert K, Kiesslich R, Vieth M. et al . In-vivo microvascular imaging of early squamous-cell cancer of the esophagus by confocal laser endomicroscopy.  Endoscopy. 2007;  39 366-368
  • 16 Liu H, Li Y Q, Yu T. et al . Confocal laser endomicroscopy for superficial esophageal squamous cell carcinoma.  Endoscopy. 2009;  41 99-106
  • 17 Kakeji Y, Yamaguchi S, Yoshida D. et al . Development and assessment of morphologic criteria for diagnosing gastric cancer using confocal endomicroscopy: an ex vivo and in vivo study.  Endoscopy. 2006;  38 886-890
  • 18 Kiesslich R, Goetz M, Lammersdorf K. et al . Chromoscopy-guided endomicroscopy increases the diagnostic yield of intraepithelial neoplasia in ulcerative colitis.  Gastroenterology. 2007;  132 874-882
  • 19 Kiesslich R, Hoffman A, Goetz M. et al . In vivo diagnosis of collagenous colitis by confocal endomicroscopy.  Gut. 2006;  55 591-592
  • 20 Bojarski C, Günther U, Rieger K. et al . In vivo diagnosis of acute intestinal graft-versus-host disease by confocal endomicroscopy.  Endoscopy. 2009;  41 433-438
  • 21 Kiesslich R, Goetz M, Burg J. et al . Diagnosing Helicobacter pylori in vivo by confocal laser endoscopy.  Gastroenterology. 2005;  128 2119-2123
  • 22 Günther U, Epple H J, Heller F. et al . In vivo diagnosis of intestinal spirochaetosis by confocal endomicroscopy.  Gut. 2008;  57 1331-1333
  • 23 Catassi C, Fabiani E, Iacono G. et al . A prospective, double-blind, placebo-controlled trial to establish a safe gluten threshold for patients with celiac disease.  Am J Clin Nutr. 2007;  85 160-166
  • 24 Mariné M, Fernández-Bañares F, Alsina M. et al . Impact of mass screening for gluten-sensitive enteropathy in working population.  World J Gastroenterol. 2009;  15 1331-1338
  • 25 Ojetti V, Nucera G, Migneco A. et al . High prevalence of celiac disease in patients with lactose intolerance.  Digestion. 2005;  71 106-110
  • 26 Ferenc T, Janik-Spiechowicz E, Bratkowska W. et al . Genotoxicity assessment of new synthesized acridine derivative – 3,6-diamino-10-methyl-9,10-dihydroacridine.  Mutat Res. 1999;  444 463-470
  • 27 Wainwright M. Dyes in the development of drugs and pharmaceuticals.  Dyes Pigments. 2008;  76 582-589
  • 28 Lo A, Guelrud M, Essenfeld H. et al . Classification of villous atrophy with enhanced magnification endoscopy in patients with celiac disease and tropical sprue.  Gastrointest Endosc. 2007;  66 377-382
  • 29 Pais W P, Duerksen D R, Pettigrew N M. et al . How many duodenal biopsy specimens are required to make a diagnosis of celiac disease?.  Gastrointest Endosc. 2008;  67 1082-1087

1 U. Günther and S. Daum contributed equally to this work.

C. BojarskiMD 

Medizinische Klinik I – Gastroenterology, Infectious Diseases, Rheumatology
Charité – University Medicine Berlin
Campus Benjamin Franklin

Hindenburgdamm 30
12200 Berlin, Germany

Fax: +49-30-84454481

Email: christian.bojarski@charite.de

    >