Background and study aims: Conventional histology with hematoxylin and eosin (H&E) staining is the accepted
standard for diagnosing acute intestinal graft-versus-host disease (GvHD). Confocal
endomicroscopy (CEM) is a noninvasive method that allows in vivo histology to be performed
during endoscopy. The aim of this study was to evaluate CEM for the diagnosis of acute
intestinal GvHD.
Patients and methods: This observational pilot study conducted between September 2006 and August 2008 included
patients with acute diarrhea after stem cell transplantation, infectious diarrhea,
or active ulcerative colitis. CEM (EC-3870CIFK, Pentax, Tokyo, Japan) was performed
after intravenous injection of fluorescein 10 % and topical application of acriflavine
0.05 %.
Results: A total of 35 patients with acute diarrhea after stem cell transplantation were examined.
In 16 patients, CEM and histology showed no evidence of GvHD. In 14/19 patients with
histologically confirmed GvHD, the diagnosis could already be established by CEM during
ongoing endoscopy. In GvHD grade IV, near complete destruction of the colonic crypts
(”flat mucosa”) was visible. Control patients with infectious colitis (n = 15) or ulcerative colitis (n = 15) displayed inflammatory changes but no evidence of GvHD. Altogether, sensitivity
of CEM was 74 % and specificity was 100 %.
Conclusions: CEM improves rapid diagnosis of acute intestinal GvHD with high accuracy while performing
endoscopy. Platelet transfusions and unnecessary biopsy acquisition can be avoided
once acute intestinal GvHD has been diagnosed in vivo.
References
- 1
Rieger K, Loddenkemper C, Maul J. et al .
Mucosal FOXP3+ regulatory T cells are numerically deficient in acute and chronic GvHD.
Blood.
2006;
107
1717-1723
- 2
Sale G E, Shulman H M, McDonald G B, Thomas E D.
Gastrointestinal graft-versus-host disease in man: a clinicopathologic study of the
rectal biopsy.
Am J Surg Pathol.
1979;
3
291-293
- 3
Shulman H M, Kleiner D, Lee S J. et al .
Histopathologic diagnosis of chronic graft-versus-host disease: National Institutes
of Health Consensus Development Project on Criteria for Clinical Trials in Chronic
Graft-versus-Host Disease: II. Pathology Working Group Report.
Biol Blood Marrow Transplant.
2006;
12
31-47
- 4
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
- 5
Kiesslich R, Goetz M, Vieth M. et al .
Technology Insight: confocal laser endoscopy for in vivo diagnosis of colorectal cancer.
Nat Clin Pract Oncol.
2007;
4
480-490
- 6
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
- 7
Kitabatake S, Niwa Y, Miyahara R. et al .
Confocal endomicroscopy for the diagnosis of gastric cancer in vivo.
Endoscopy.
2006;
38
1110-1114
- 8
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
- 9
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
- 10
Kiesslich R, Hoffman A, Goetz M. et al .
In vivo diagnosis of collagenous colitis by confocal endomicroscopy.
Gut.
2006;
55
591-592
- 11
Kiesslich R, Gossner L, Goetz M. et al .
In vivo histology of Barrett’s esophagus and associated neoplasia by confocal laser
endomicroscopy.
Clin Gastroenterol Hepatol.
2006;
4
979-987
- 12
Trovato C, Sonzogni A, Ravizza D. et al .
Celiac disease: in vivo diagnosis by confocal endomicroscopy.
Gastrointest Endosc.
2007;
65
1096-1099
- 13
Zambelli A, Villanacci V, Buscarini E. et al .
Collagenous colitis: a case series with confocal laser microscopy and histology correlation.
Endoscopy.
2008;
40
606-608
- 14
Yeh S P, Liao Y M, Hsu C H. et al .
Gastric bleeding due to graft-vs-host disease: discrepancy between endoscopic and
histologic assessment.
Am J Clin Pathol.
2004;
122
919-925
- 15
Cox G J, Matsui S M, Lo R S. et al .
Etiology and outcome of diarrhea after marrow transplantation: a prospective study.
Gastroenterology.
1994;
107
1398-1407
- 16
Nydegger A, Catto-Smith A G, Tiedemann K, Hardikar W.
Diagnosis of gastrointestinal graft-versus-host disease – is rectal biopsy enough?.
Pediatr Blood Cancer.
2007;
48
561-566
- 17
Zeissig S, Bojarski C, Buergel N. et al .
Downregulation of epithelial apoptosis and barrier repair in active Crohn’s disease
by tumour necrosis factor alpha antibody treatment.
Gut.
2004;
53
1295-1302
- 18
Welch D C, Wirth P S, Goldenring J R. et al .
Gastric graft-versus-host disease revisited: does proton pump inhibitor therapy affect
endoscopic gastric biopsy interpretation?.
Am J Sur Pathol.
2006;
30
444-449
- 19
Papadimitriou J C, Cangro C B, Lustberg A. et al .
Histologic features of mycophenolate mofetil-related colitis: a graft-versus-host
disease-like pattern.
Int J Sur Pathol.
2003;
11
295-302
- 20
Kiesslich R, Goetz M, Angus E M. et al .
Identification of epithelial gaps in human small and large intestine by confocal endomicroscopy.
Gastroenterology.
2007;
133
1769-1778
1 equally contributed
C. BojarskiMD
Charité – Campus Benjamin Franklin
Medizinische Klinik I – Gastroenterologie, Infektiologie, Rheumatologie
Hindenburgdamm 30
12200 Berlin
Germany
Fax: +49-30-84454481
Email: christian.bojarski@charite.de