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Published in: Virchows Archiv 5/2015

01-05-2015 | Original Article

Diagnosing cytomegalovirus in patients with inflammatory bowel disease—by immunohistochemistry or polymerase chain reaction?

Authors: Nina Zidar, Ivan Ferkolj, Katja Tepeš, Borut Štabuc, Nika Kojc, Tina Uršič, Miroslav Petrovec

Published in: Virchows Archiv | Issue 5/2015

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Abstract

Cytomegalovirus (CMV) reactivation is a common complication in patients with inflammatory bowel diseases (IBD), particularly in those with steroid-resistant ulcerative colitis. It is usually diagnosed by histopathologic and immunohistochemical examination of the colon biopsy. The introduction of quantitative, real-time polymerase chain reaction (qPCR) has been recommended to improve the sensitivity, but there is little consensus on how to use it. We compared the two methods in samples from resected bowel of patients with IBD. Twelve patients with IBD who had undergone bowel resection were analysed for CMV, using qPCR and immunohistochemistry. In all cases, tissue samples from the base and the edge of ulcers and from uninvolved mucosa were obtained. The highest densities of CMV-positive cells were found in samples from the base of ulcers (immunohistochemistry 0–0.47 positive cells/mm2; qPCR 10–3809 viral copies/mg) or the edge of ulcers (immunohistochemistry 0.06–0.32 positive cells/mm2; qPCR 35–1049 viral copies/mg). In samples of uninvolved mucosa, immunohistochemistry was negative, whereas qPCR was either negative or showed very low values (0–3 viral copies/mg). We conclude that both immunohistochemistry and qPCR can be successfully used for diagnosing CMV reactivation in patients with IBD. The base and the edge of ulcers are the optimal sites for endoscopic biopsies. The density of CMV-positive cells was low and their distribution within the colon uneven. It therefore seems that the number of sampled biopsies and/or the number of investigated levels is more important that the choice of diagnostic method.
Literature
1.
go back to reference Landolfo S, Gariglio M, Gribaudo G, Lembo D (2003) The human cytomegalovirus. Pharmacol Ther 98:269–297CrossRefPubMed Landolfo S, Gariglio M, Gribaudo G, Lembo D (2003) The human cytomegalovirus. Pharmacol Ther 98:269–297CrossRefPubMed
3.
go back to reference Ljungman P, Griffiths P, Paya C (2002) Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis 34:1094–1097CrossRefPubMed Ljungman P, Griffiths P, Paya C (2002) Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis 34:1094–1097CrossRefPubMed
4.
go back to reference You DM, Johnson MD (2012) Cytomegalovirus infection and the gastrointestinal tract. Curr Gastroenterol Rep 14:334–342CrossRefPubMed You DM, Johnson MD (2012) Cytomegalovirus infection and the gastrointestinal tract. Curr Gastroenterol Rep 14:334–342CrossRefPubMed
5.
go back to reference Kambham N, Vij R, Cartwright CA, Longacre T (2004) Cytomegalovirus infection in steroid-refractory ulcerative colitis: a case-control study. Am J Surg Pathol 28:365–373CrossRefPubMed Kambham N, Vij R, Cartwright CA, Longacre T (2004) Cytomegalovirus infection in steroid-refractory ulcerative colitis: a case-control study. Am J Surg Pathol 28:365–373CrossRefPubMed
6.
go back to reference Kandiel A, Lashner B (2006) Cytomegalovirus colitis complicating inflammatory bowel disease. Am J Gastroenterol 101:2857–2865CrossRefPubMed Kandiel A, Lashner B (2006) Cytomegalovirus colitis complicating inflammatory bowel disease. Am J Gastroenterol 101:2857–2865CrossRefPubMed
7.
go back to reference Domènech E, Vega R, Ojanguren I, Hernández A, Garcia-Planella E, Bernal I, Rosinach M, Boix J, Cabré E, Gassull MA (2008) Cytomegalovirus infection in ulcerative colitis: a prospective, comparative study on prevalence and diagnostic strategy. Inflamm Bowel Dis 14:1373–1379CrossRefPubMed Domènech E, Vega R, Ojanguren I, Hernández A, Garcia-Planella E, Bernal I, Rosinach M, Boix J, Cabré E, Gassull MA (2008) Cytomegalovirus infection in ulcerative colitis: a prospective, comparative study on prevalence and diagnostic strategy. Inflamm Bowel Dis 14:1373–1379CrossRefPubMed
8.
go back to reference Roblin X, Pillet S, Oussalah A, Berthelot P, Del Tedesco E, Phelip JM, Chambonnière ML, Garraud O, Peyrin-Biroulet L, Pozzetto B (2011) Cytomegalovirus load in inflamed intestinal tissue is predictive of resistance to immunosuppressive therapy in ulcerative colitis. Am J Gastroenterol 106:2001–2008CrossRefPubMed Roblin X, Pillet S, Oussalah A, Berthelot P, Del Tedesco E, Phelip JM, Chambonnière ML, Garraud O, Peyrin-Biroulet L, Pozzetto B (2011) Cytomegalovirus load in inflamed intestinal tissue is predictive of resistance to immunosuppressive therapy in ulcerative colitis. Am J Gastroenterol 106:2001–2008CrossRefPubMed
9.
go back to reference Maher MM, Nassar MI (2009) Acute cytomegalovirus infection is a risk factor in refractory and complicated inflammatory bowel disease. Dig Dis Sci 54:245662CrossRef Maher MM, Nassar MI (2009) Acute cytomegalovirus infection is a risk factor in refractory and complicated inflammatory bowel disease. Dig Dis Sci 54:245662CrossRef
10.
go back to reference Kim JJ, Simpson N, Klipfel N, Debose R, Barr N, Laine L (2010) Cytomegalovirus infection in patients with active inflammatory bowel disease. Dig Dis Sci 55:1059–1065CrossRefPubMed Kim JJ, Simpson N, Klipfel N, Debose R, Barr N, Laine L (2010) Cytomegalovirus infection in patients with active inflammatory bowel disease. Dig Dis Sci 55:1059–1065CrossRefPubMed
11.
go back to reference Nakase H, Yoshino T, Honzawa Y, Chiba T (2010) Low prevalence of CMV infection in patients with Crohn’s disease in comparison with ulcerative colitis: effect of different immune response on prevalence of CMV infection. Dig Dis Sci 55:1498–1499CrossRefPubMed Nakase H, Yoshino T, Honzawa Y, Chiba T (2010) Low prevalence of CMV infection in patients with Crohn’s disease in comparison with ulcerative colitis: effect of different immune response on prevalence of CMV infection. Dig Dis Sci 55:1498–1499CrossRefPubMed
12.
go back to reference Lawlor G, Moss AC (2010) Cytomegalovirus in inflammatory bowel disease: pathogen or innocent bystander? Inflamm Bowel Dis 16:1620–1627CrossRefPubMed Lawlor G, Moss AC (2010) Cytomegalovirus in inflammatory bowel disease: pathogen or innocent bystander? Inflamm Bowel Dis 16:1620–1627CrossRefPubMed
13.
go back to reference Hamlin PJ, Shah MN, Scott N, Wyatt JI, Howdle PD (2004) Systemic cytomegalovirus infection complicating ulcerative colitis: a case report and review of the literature. Postgrad Med J 80:233–235CrossRefPubMedCentralPubMed Hamlin PJ, Shah MN, Scott N, Wyatt JI, Howdle PD (2004) Systemic cytomegalovirus infection complicating ulcerative colitis: a case report and review of the literature. Postgrad Med J 80:233–235CrossRefPubMedCentralPubMed
14.
go back to reference Hommes DW, Sterringa G, van Deventer SJ, Tytgat GN, Weel J (2004) The pathogenicity of cytomegalovirus in inflammatory bowel disease: a systematic review and evidence-based recommendations for future research. Inflamm Bowel Dis 10:245–250CrossRefPubMed Hommes DW, Sterringa G, van Deventer SJ, Tytgat GN, Weel J (2004) The pathogenicity of cytomegalovirus in inflammatory bowel disease: a systematic review and evidence-based recommendations for future research. Inflamm Bowel Dis 10:245–250CrossRefPubMed
15.
go back to reference Pillet S, Pozzetto B, Jarlot C, Paul S, Roblin X (2012) Management of cytomegalovirus infection in inflammatory bowel diseases. Dig Liver Dis 44:541–548CrossRefPubMed Pillet S, Pozzetto B, Jarlot C, Paul S, Roblin X (2012) Management of cytomegalovirus infection in inflammatory bowel diseases. Dig Liver Dis 44:541–548CrossRefPubMed
16.
go back to reference Garrido E, Carrera E, Manzano R, Lopez-Sanroman A (2013) Clinical significance of cytomegalovirus infection in patients with inflammatory bowel disease. World J Gastroenterol 19:17–25CrossRefPubMedCentralPubMed Garrido E, Carrera E, Manzano R, Lopez-Sanroman A (2013) Clinical significance of cytomegalovirus infection in patients with inflammatory bowel disease. World J Gastroenterol 19:17–25CrossRefPubMedCentralPubMed
17.
go back to reference Matsuoka K, Iwao Y, Mori T, Sakuraba A, Yajima T, Hisamatsu T, Okamoto S, Morohoshi Y, Izumiya M, Ichikawa H, Sato T, Inoue N, Ogata H, Hibi T (2007) Cytomegalovirus is frequently reactivated and disappears without antiviral agents in ulcerative colitis patients. Am J Gastroenterol 102:331–337CrossRefPubMed Matsuoka K, Iwao Y, Mori T, Sakuraba A, Yajima T, Hisamatsu T, Okamoto S, Morohoshi Y, Izumiya M, Ichikawa H, Sato T, Inoue N, Ogata H, Hibi T (2007) Cytomegalovirus is frequently reactivated and disappears without antiviral agents in ulcerative colitis patients. Am J Gastroenterol 102:331–337CrossRefPubMed
18.
go back to reference Delvincourt M, Lopez A, Pillet S, Bourrier A, Seksik P, Cosnes J, Carrat F, Gozlan J, Beaugerie L, Roblin X, Peyrin-Biroulet L, Sokol H (2014) The impact of cytomegalovirus reactivation and its treatment on the course of inflammatory bowel disease. Aliment Pharmacol Ther 39:712–720CrossRefPubMed Delvincourt M, Lopez A, Pillet S, Bourrier A, Seksik P, Cosnes J, Carrat F, Gozlan J, Beaugerie L, Roblin X, Peyrin-Biroulet L, Sokol H (2014) The impact of cytomegalovirus reactivation and its treatment on the course of inflammatory bowel disease. Aliment Pharmacol Ther 39:712–720CrossRefPubMed
19.
go back to reference Rahier JF, Magro F, Abreu C, Armuzzi A, Ben-Horin S, Chowers Y, Cottone M, de Ridder L, Doherty G, Ehehalt R, Esteve M, Katsanos K, Lees CW, Macmahon E, Moreels T, Reinisch W, Tilg H, Tremblay L, Veereman-Wauters G, Viget N, Yazdanpanah Y, Eliakim R, Colombel JF, European Crohn’s Colitis Organisation (ECCO) (2014) Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis 8:443–468CrossRefPubMed Rahier JF, Magro F, Abreu C, Armuzzi A, Ben-Horin S, Chowers Y, Cottone M, de Ridder L, Doherty G, Ehehalt R, Esteve M, Katsanos K, Lees CW, Macmahon E, Moreels T, Reinisch W, Tilg H, Tremblay L, Veereman-Wauters G, Viget N, Yazdanpanah Y, Eliakim R, Colombel JF, European Crohn’s Colitis Organisation (ECCO) (2014) Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis 8:443–468CrossRefPubMed
20.
go back to reference Papadakis KA, Tung JK, Binder SW, Kam LY, Abreu MT, Targan SR, Vasiliauskas EA (2001) Outcome of cytomegalovirus infections in patients with inflammatory bowel disease. Am J Gastroenterol 96:2137–2142CrossRefPubMed Papadakis KA, Tung JK, Binder SW, Kam LY, Abreu MT, Targan SR, Vasiliauskas EA (2001) Outcome of cytomegalovirus infections in patients with inflammatory bowel disease. Am J Gastroenterol 96:2137–2142CrossRefPubMed
21.
go back to reference Maconi G, Colombo E, Zerbi P, Sampietro GM, Fociani P, Bosani M, Cassinotti A, Casini V, Russo A, Ardizzone S, Porta M, Bianchi Porro G (2005) Prevalence, detection rate and outcome of cytomegalovirus infection in ulcerative colitis patients requiring colonic resection. Dig Liver Dis 37:418–423CrossRefPubMed Maconi G, Colombo E, Zerbi P, Sampietro GM, Fociani P, Bosani M, Cassinotti A, Casini V, Russo A, Ardizzone S, Porta M, Bianchi Porro G (2005) Prevalence, detection rate and outcome of cytomegalovirus infection in ulcerative colitis patients requiring colonic resection. Dig Liver Dis 37:418–423CrossRefPubMed
22.
go back to reference Al-Zafiri R, Gologan A, Galiatsatos P, Szilagyi A (2012) Cytomegalovirus complicating inflammatory bowel disease: a 10-year experience in a community-based, university-affiliated hospital. Gastroenterol Hepatol (N Y) 8:230–239 Al-Zafiri R, Gologan A, Galiatsatos P, Szilagyi A (2012) Cytomegalovirus complicating inflammatory bowel disease: a 10-year experience in a community-based, university-affiliated hospital. Gastroenterol Hepatol (N Y) 8:230–239
23.
go back to reference Muir SW, Murray J, Farquharson MA, Wheatley DJ, McPhaden AR (1998) Detection of cytomegalovirus in upper gastrointestinal biopsies from heart transplant recipients: comparison of light microscopy, immunocytochemistry, in situ hybridisation, and nested PCR. J Clin Pathol 51:807–811CrossRefPubMedCentralPubMed Muir SW, Murray J, Farquharson MA, Wheatley DJ, McPhaden AR (1998) Detection of cytomegalovirus in upper gastrointestinal biopsies from heart transplant recipients: comparison of light microscopy, immunocytochemistry, in situ hybridisation, and nested PCR. J Clin Pathol 51:807–811CrossRefPubMedCentralPubMed
24.
go back to reference Yoshino T, Nakase H, Ueno S, Uza N, Inoue S, Mikami S, Matsuura M, Ohmori K, Sakurai T, Nagayama S, Hasegawa S, Sakai Y, Chiba T (2007) Usefulness of quantitative real-time PCR assay for early detection of cytomegalovirus infection in patients with ulcerative colitis refractory to immunosuppressive therapies. Inflamm Bowel Dis 13:1516–1521CrossRefPubMed Yoshino T, Nakase H, Ueno S, Uza N, Inoue S, Mikami S, Matsuura M, Ohmori K, Sakurai T, Nagayama S, Hasegawa S, Sakai Y, Chiba T (2007) Usefulness of quantitative real-time PCR assay for early detection of cytomegalovirus infection in patients with ulcerative colitis refractory to immunosuppressive therapies. Inflamm Bowel Dis 13:1516–1521CrossRefPubMed
25.
go back to reference Magro F, Langner C, Driessen A, Ensari A, Geboes K, Mantzaris GJ, Villanacci V, Becheanu G, Borralho Nunes P, Cathomas G, Fries W, Jouret-Mourin A, Mescoli C, de Petris G, Rubio CA, Shepherd NA, Vieth M, Eliakim R, European Society of Pathology (ESP); European Crohn’s and Colitis Organisation (ECCO) (2013) European consensus on the histopathology of inflammatory bowel disease. J Crohns Colitis 7:827–851CrossRefPubMed Magro F, Langner C, Driessen A, Ensari A, Geboes K, Mantzaris GJ, Villanacci V, Becheanu G, Borralho Nunes P, Cathomas G, Fries W, Jouret-Mourin A, Mescoli C, de Petris G, Rubio CA, Shepherd NA, Vieth M, Eliakim R, European Society of Pathology (ESP); European Crohn’s and Colitis Organisation (ECCO) (2013) European consensus on the histopathology of inflammatory bowel disease. J Crohns Colitis 7:827–851CrossRefPubMed
26.
go back to reference Boeckh M (2011) Complications, diagnosis, management, and prevention of CMV infections: current and future. Hematol Am Soc Hematol Educ Program 2011:305–309CrossRef Boeckh M (2011) Complications, diagnosis, management, and prevention of CMV infections: current and future. Hematol Am Soc Hematol Educ Program 2011:305–309CrossRef
27.
go back to reference Ljungman P, de la Camara R, Cordonnier C, Einsele H, Engelhard D, Reusser P, Styczynski J, Ward K (2008) Management of CMV, HHV-6, HHV-7 and Kaposi-sarcoma herpesvirus (HHV-8) infections in patients with hematological malignancies and after SCT. Bone Marrow Transplant 42:227–240CrossRefPubMed Ljungman P, de la Camara R, Cordonnier C, Einsele H, Engelhard D, Reusser P, Styczynski J, Ward K (2008) Management of CMV, HHV-6, HHV-7 and Kaposi-sarcoma herpesvirus (HHV-8) infections in patients with hematological malignancies and after SCT. Bone Marrow Transplant 42:227–240CrossRefPubMed
28.
go back to reference Ganzenmueller T, Henke-Gendo C, Schlué J, Wedemeyer J, Huebner S, Heim A (2009) Quantification of cytomegalovirus DNA levels in intestinal biopsies as a diagnostic tool for CMV intestinal disease. J Clin Virol 46:254–258CrossRefPubMed Ganzenmueller T, Henke-Gendo C, Schlué J, Wedemeyer J, Huebner S, Heim A (2009) Quantification of cytomegalovirus DNA levels in intestinal biopsies as a diagnostic tool for CMV intestinal disease. J Clin Virol 46:254–258CrossRefPubMed
29.
go back to reference Lemonovich TL, Watkins RR (2012) Update on cytomegalovirus infections of the gastrointestinal system in solid organ transplant recipients. Curr Infect Dis Rep 14:33–40CrossRefPubMed Lemonovich TL, Watkins RR (2012) Update on cytomegalovirus infections of the gastrointestinal system in solid organ transplant recipients. Curr Infect Dis Rep 14:33–40CrossRefPubMed
30.
go back to reference Mills AM, Guo FP, Copland AP, Pai RK, Pinsky BA (2013) A comparison of CMV detection in gastrointestinal mucosal biopsies using immunohistochemistry and PCR performed on formalin-fixed, paraffin-embedded tissue. Am J Surg Pathol 37:995–1000CrossRefPubMed Mills AM, Guo FP, Copland AP, Pai RK, Pinsky BA (2013) A comparison of CMV detection in gastrointestinal mucosal biopsies using immunohistochemistry and PCR performed on formalin-fixed, paraffin-embedded tissue. Am J Surg Pathol 37:995–1000CrossRefPubMed
31.
go back to reference McCoy MH, Post K, Sen JD, Chang HY, Zhao Z, Fan R, Chen S, Leland D, Cheng L, Lin J (2014) qPCR increases sensitivity to detect cytomegalovirus in formalin-fixed, paraffin-embedded tissue of gastrointestinal biopsies. Hum Pathol 45:48–53CrossRefPubMed McCoy MH, Post K, Sen JD, Chang HY, Zhao Z, Fan R, Chen S, Leland D, Cheng L, Lin J (2014) qPCR increases sensitivity to detect cytomegalovirus in formalin-fixed, paraffin-embedded tissue of gastrointestinal biopsies. Hum Pathol 45:48–53CrossRefPubMed
Metadata
Title
Diagnosing cytomegalovirus in patients with inflammatory bowel disease—by immunohistochemistry or polymerase chain reaction?
Authors
Nina Zidar
Ivan Ferkolj
Katja Tepeš
Borut Štabuc
Nika Kojc
Tina Uršič
Miroslav Petrovec
Publication date
01-05-2015
Publisher
Springer Berlin Heidelberg
Published in
Virchows Archiv / Issue 5/2015
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-015-1741-8

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