Optimization of Differential Diagnosis of Inflammatory Bowel Diseases Based on an Integrated Assessment of Oral Mucosa Status

The objective of the investigation was to improve the differential diagnosis of inflammatory bowel diseases, on the basis of an integrated assessment of morphological data, the findings of optical imaging of tissues, and immunohistochemical examinations of the oral mucosa.

Materials and Methods. We studied morphological and immunohistochemical characteristics of the oral mucosae in each of 26 patients with Crohn’s disease (CD) and 17 patients with ulcerative colitis (UC). We performed both visual comparisons and quantitative assessments of cross-polarization optical coherence tomography (CP OCT) images and morphological data on collagen fibers obtained from polarization microscopy using picrosirius red staining.

Results. We suggest a new and objective differential diagnostic criterion for CD and UC which makes use of the condition of the oral mucosa, based on a quantitative assessment of CP OCT images (by calculation of the integral depolarization factor). In accordance with the results of immunohistochemical studies, we have revealed the most significant indices, and that these can be used as differential diagnostic criteria in CD and UC. We have developed a mathematical model including the four most immunohistochemical significant attributes (relative area of staining, the degree of CD16 expression, CD31 staining intensity and the degree of CD57 expression). We have determined a threshold level for the area of tryptase expression by the mast cells of the buccal mucosa, which achieves the maximum differential diagnostic accuracy for the CD and UC indices. The most significant characteristics of the immunohistochemical method exceed the diagnostic efficiency parameters of CP OCT.

Conclusion. Given that CP OCT is non-invasive and has high diagnostic accuracy, we recommend using a quantitative assessment of CP OCT images as the first stage of an operational differential diagnosis of the diseases, based on the condition of the oral mucosa. In the case of inconclusive results, an oral mucosa biopsy, followed by morphological and immunohistochemical examination, would be expedient.

1. Assche G., Dignass A., Reinisch W., van der Woude C.J., Sturm A., De Vos M., et al. The second European evidence-based consensus on the diagnosis and management of Crohn’s disease: special situations. J Crohn’s Colitis 2010; 41(1): 63–101, http://dx.doi.org/10.1016/j.crohns.2009.09.009.
2. Dignass A., Lindsay J.O., Sturm A., Windsor A., Colombel J.F., Allez M., et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis. Part 2: current management. J. Crohn’s Colitis 2012; 6(10): 991–1030, http://dx.doi.org/10.1016/j.crohns.2012.09.002.
3. Stchukina О.B. Indeterminate colitis: current state of the problem. Consilium Medicum 2008; 10(8): 77–79.
4. Bentley E., Jenkins D., Campbell F., Warren B. How could pathologists improve the initial diagnosis of colitis? Evidence from an international workshop. J Clin Pathol 2002; 55(12): 955–960, http://dx.doi.org/10.1136/jcp.55.12.955.
5. Joossens S., Reinisch W., Vermeire S., Sendid B., Poulain D., Peeters M., Geboes K., Bossuyt X., Vandewalle P., Oberhuber G., Vogelsang H., Rutgeerts P., Colombel J.F. The value of serologic markers in indeterminate colitis: a prospective follow-up study. Gastroenterology 2002; 122(5): 1242–1247, http://dx.doi.org/10.1053/gast.2002.32980.
6. Mow W.S., Landers C.J., Steinhart A.H., Feagan B.G., Croitoru K., Seidman E., Greenberg G.R., Targan S.R. High-level serum antibodies to bacterial antigens are associated with antibiotic-induced clinical remission in Crohn’s disease: a pilot study. Dig Dis Sci 2004; 491(7–8): 1280–1286, http://dx.doi.org/10.1023/b:ddas.0000037824.66186.e2.
7. Belousova E.A. Yazvennyy kolit i bolezn’ Krona [Ulcerative colitis and Crohn’s disease]. Tver: OOO Izdatel’stvo “Triada”; 2002.
8. Brown S.J., Mayer L. The immune response in inflammatory bowel disease. Am J Gastroenterol 2007; 102(9): 2058–2069, http://dx.doi.org/10.1111/j.1572-0241.2007.01343.x.
9. Strioga M., Pasukoniene V., Characiejus D. CD8⁺ CD28^– and CD8⁺ CD57⁺ T cells and their role in health and disease. Immunology 2011; 134(1): 17–32, http://dx.doi.org/10.1111/j.1365-2567.2011.03470.x.
10. Geboes K. Crohn’s disease, ulcerative colitis or indeterminate colitis — how important is it to differentiate? Acta Gastroenterol Belg 2001; 64(2): 197–200.
11. Lankarani K.B., Sivandzadeh G.R., Hassanpour S. Oral manifestation in inflammatory bowel disease: a review. World J Gastroenterol 2013; 19(46): 8571–8579.
12. Shen B., Zuccaro G., Gamilich T.L., Gladkova N., Lashner B.A., Delaney C.P., Connor J.T., Remzi F.H., Kareta M., Bevins C.L., Feldchtein F., Strong S.A., Bambrick M.L., Trolli P., Fazio V.W. Ex vivo histology-correlated optical coherence tomography in the detection of transmural inflammation in Crohn’s disease. Clin Gastroenterol Hepatol 2004; 2(9): 754–760, http://dx.doi.org/10.1016/S1542-3565(04)00346-5.
13. Gladkova N., Kiseleva E., Robakidze N., Balalaeva I., Karabut M., Gubarkova E., Feldchtein F. Evaluation of oral mucosa collagen condition with cross-polarization optical coherence tomography. J Biophotonics 2013; 6(4): 321–329, http://dx.doi.org/10.1002/jbio.201200059.
14. Ganganna K., Shetty P., Shroff S.E. Collagen in histologic stages of oral submucous fibrosis: a polarizing microscopic study. J Oral Maxillofac Pathol 2012; 16(2): 162–166, http://dx.doi.org/10.4103/0973-029X.98446.
15. Lee C.K., Tsai M.T., Lee H.C., Chen H.M., Chiang C.P., Wang Y.M., Yang C.C. Diagnosis of oral submucous fibrosis with optical coherence tomography. J Biomed Opt 2009; 14(5): 054008, http://dx.doi.org/10.1117/1.3233653.
16. Feldchtein F.I., Gelikonov V.M., Gelikonov G.V. Polarization-sensitive common path optical coherence reflectometry/tomography device. Patent US 7,728,985 B2. 2010.
17. Gelikonov V.M., Gelikonov G.V. New approach to cross-polarized optical coherence tomography based on orthogonal arbitrarily polarized modes. Laser Phys Lett 2006; 3(9): 445–451, http://dx.doi.org/10.1002/lapl.200610030.
18. Gubarkova E.V., Kirillin M.Y., Sergeeva E.A., Kiseleva E.B., Snopova L.B., Prodanets N.N., Sharabrin E.G., Shakhov Е.B., Nemirova S.V., Gladkova N.D. Cross-polarization optical coherence tomography in evaluation of atherosclerotic plaque structure. Sovremennye Tehnologii v Medicine 2013; 5(4): 45–55.
19. Giattina S.D., Courtney B.K., Herz P.R., Harman M., Shortkroff S., Stamper D.L., Liu B., Fujimoto J.G., Brezinski M.E. Assesment of coronary plaque collagen with polarization sensitive optical coherence tomography (PS-OCT). Int J Cardiol 2006; 107(3): 400–409, http://dx.doi.org/10.1016/j.ijcard.2005.11.036.
20. Vorob’ev G.I., Khalif I.L. Nespetsificheskie vospalitel’nye zabolevaniya kishechnika [Non-specific inflammatory bowel disease]. Moscow: Miklosh; 2008; 400 p.
21. Veloso T.F. Extraintestinal manifestations of inflammatory bowel disease: do they influence treatment and outcome? World J Gastroenterol 2011; 17(22): 2702–2707.
22. Graham M.F., Diegelmann R.F., Elson C.O., Lindblad W.J., Gotschalk N., Gay S., Gay R. Collagen content and types in the intestinal strictures of Crohn’s disease. Gastroenterology 1988; 94(2): 257–265.
23. Walsh L.J. Mast cell and oral inflammation. Crit Rev Oral Biol Med 2003; 14(3): 188–198, http://dx.doi.org/10.1177/154411130301400304.
24. Middel P., Thelen P., Blaschke S., Polzien F., Reich K., Blaschke V., Wrede A., Hummel K.M., Gunawan B., Radzun H.J. Expression of the T-cell chemoattractant chemokine lymphotactin in Crohn’s disease. Am J Pathol 2001; 159(5): 1751–1761, http://dx.doi.org/10.1016/S0002-9440(10)63022-2.
25. Pujari R., Vidya N. Mast cell density in oral submucous fibrosis: a possible role in pathogenesis. Int J Health Sci (Qassim) 2013; 7(1): 23–29.

Robakidze N.S. Optimization of Differential Diagnosis of Inflammatory Bowel Diseases Based on an Integrated Assessment of Oral Mucosa Status. Sovremennye tehnologii v medicine 2015; 7(1): 81, https://doi.org/10.17691/stm2015.7.1.11