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International Journal of Colorectal Disease

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01-02-2019 | Original Article

Accuracy of diagnostic tests and a new algorithm for diagnosing cytomegalovirus colitis in inflammatory bowel diseases: a diagnostic study

Authors: Lea I. Kredel, Pamela Mundt, Linda van Riesen, Korinna Jöhrens, Jörg Hofmann, Christoph Loddenkemper, Britta Siegmund, Jan C. Preiß

Published in: International Journal of Colorectal Disease | Issue 2/2019

Abstract

Purpose

The optimal method for detecting CMV colitis in patients with inflammatory bowel disease (IBD) has not been established. We wanted to investigate which diagnostic test would be most accurate when defining CMV colitis rather by the further clinical course than by using another diagnostic modality.

Methods

All consecutive patients with moderately or severely active IBD who had been tested for CMV by PCR, histology, or antigenemia assay at the two campuses CBF and CCM of the Charité - Universitätsmedizin Berlin between September 2006 and September 2009 were included in this retrospective study. During that time, in patients with a positive CMV test, immunosuppressive treatment of any kind was immediately reduced and antiviral treatment was started. This allowed identifying patients who responded to antiviral treatment and those who only responded to later escalation of immunosuppressive therapy.

Results

One hundred and nine patients were identified, out of whom nine were considered to have clinically relevant CMV colitis. Sensitivity and specificity were 1 and 0.94 for CMV PCR and 0.5 and 1 for pp65 antigen immunofluorescence assay from peripheral blood, 0.67 and 0.98 for immunohistochemistry, and 0.17 and 0.98 for hematoxylin-eosin staining. When using absence of leukocytosis, splenomegaly, and steroid refractory disease as clinical parameters to test for CMV colitis, blood CMV PCR and immunohistochemistry were able to exclude CMV colitis in negative patients with a 75% likelihood of positive patients to have clinically relevant CMV colitis.

Conclusions

Blood-based CMV PCR together with simple clinical parameters can exclude clinically relevant CMV colitis at a high specificity.

Pillet S, Pozzetto B, Roblin X (2016) Cytomegalovirus and ulcerative colitis: place of antiviral therapy. World J Gastroenterol 22:2030–2045. https://doi.org/10.3748/wjg.v22.i6.2030 CrossRefPubMedPubMedCentral

Siegmund B (2017) Cytomegalovirus infection associated with inflammatory bowel disease. Lancet Gastroenterol Hepatol 2:369–376. https://doi.org/10.1016/S2468-1253(16)30159-5 CrossRefPubMed

Cottone M, Pietrosi G, Martorana G, Casa A, Pecoraro G, Oliva L, Orlando A, Rosselli M, Rizzo A, Pagliaro L (2001) Prevalence of cytomegalovirus infection in severe refractory ulcerative and Crohn’s colitis. Am J Gastroenterol 96:773–775. https://doi.org/10.1111/j.1572-0241.2001.03620.x CrossRefPubMed

Domènech E, Vega R, Ojanguren I, Hernández Á, 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 14:1373–1379. https://doi.org/10.1002/ibd.20498 CrossRefPubMed

Maher MM, Nassar MI (2009) Acute cytomegalovirus infection is a risk factor in refractory and complicated inflammatory bowel disease. Dig Dis Sci 54:2456–2462. https://doi.org/10.1007/s10620-008-0639-6 CrossRefPubMed

Criscuoli V, Casà A, Orlando A, Pecoraro G, Oliva L, Traina M, Rizzo A, Cottone M (2004) Severe acute colitis associated with CMV: a prevalence study. Dig Liver Dis 36:818–820. https://doi.org/10.1016/j.dld.2004.05.013 CrossRefPubMed

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 and 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 8:443–468. https://doi.org/10.1016/j.crohns.2013.12.013 CrossRefPubMed

Jones A, McCurdy JD, Loftus EV et al (2015) Effects of antiviral therapy for patients with inflammatory bowel disease and a positive intestinal biopsy for cytomegalovirus. Clin Gastroenterol Hepatol 13:949–955. https://doi.org/10.1016/j.cgh.2014.09.042 CrossRefPubMed

Shukla T, Singh S, Loftus EV et al (2015) Antiviral therapy in steroid-refractory ulcerative colitis with cytomegalovirus: systematic review and meta-analysis. Inflamm Bowel Dis 21:2718–2725. https://doi.org/10.1097/MIB.0000000000000489 CrossRefPubMed

10.

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 39:712–720. https://doi.org/10.1111/apt.12650 CrossRefPubMed

11.

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 102:331–337. https://doi.org/10.1111/j.1572-0241.2006.00989.x CrossRefPubMed

12.

Humar A, Michaels M, on behalf of the AST ID Working Group on Infectious Disease Monitoring (2006) American Society of Transplantation recommendations for screening, monitoring and reporting of infectious complications in immunosuppression trials in recipients of organ transplantation. Am J Transplant 6:262–274. https://doi.org/10.1111/j.1600-6143.2005.01207.x CrossRefPubMed

13.

Tandon P, James P, Cordeiro E, Mallick R, Shukla T, McCurdy JD (2017) Diagnostic accuracy of blood-based tests and histopathology for cytomegalovirus reactivation in inflammatory bowel disease: a systematic review and meta-analysis. Inflamm Bowel Dis 23:551–560. https://doi.org/10.1097/MIB.0000000000001073 CrossRefPubMed

14.

Kopylov U, Papamichael K, Katsanos K, Waterman M, Bar-Gil Shitrit A, Boysen T, Portela F, Peixoto A, Szilagyi A, Silva M, Maconi G, Har-Noy O, Bossuyt P, Mantzaris G, Barreiro de Acosta M, Chaparro M, Christodoulou DK, Eliakim R, Rahier JF, Magro F, Drobne D, Ferrante M, Sonnenberg E, Siegmund B, Muls V, Thurm T, Yanai H, Dotan I, Raine T, Levin A, Israeli E, Ghalim F, Carbonnel F, Vermeire S, Ben-Horin S, Roblin X (2017) Impact of infliximab and cyclosporine on the risk of colectomy in hospitalized patients with ulcerative colitis complicated by cytomegalovirus—a multicenter retrospective study. Inflamm Bowel Dis 23:1605–1613. https://doi.org/10.1097/MIB.0000000000001160 CrossRefPubMed

15.

Magro F, Gionchetti P, Eliakim R, Ardizzone S, Armuzzi A, Barreiro-de Acosta M, Burisch J, Gecse KB, Hart AL, Hindryckx P, Langner C, Limdi JK, Pellino G, Zagórowicz E, Raine T, Harbord M, Rieder F, for the European Crohn’s and Colitis Organisation [ECCO] (2017) Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 1: definitions, diagnosis, extra-intestinal manifestations, pregnancy, cancer surveillance, surgery, and ileo-anal pouch disorders. J Crohns Colitis 11:649–670. https://doi.org/10.1093/ecco-jcc/jjx008 CrossRefPubMed

16.

Storch GA, Buller RS, Bailey TC, Ettinger NA, Langlois T, Gaudreault-Keener M, Welby PL (1994) Comparison of PCR and pp65 antigenemia assay with quantitative shell vial culture for detection of cytomegalovirus in blood leukocytes from solid-organ transplant recipients. J Clin Microbiol 32:997–1003PubMedPubMedCentral

17.

R Core Team (2018) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL: https://www.R-project.org/

18.

Marill KA, Chang Y, Wong KF, Friedman AB (2017) Estimating negative likelihood ratio confidence when test sensitivity is 100%: a bootstrapping approach. Stat Methods Med Res 26:1936–1948. https://doi.org/10.1177/0962280215592907 CrossRefPubMed

19.

Rychert J, Danziger-Isakov L, Yen-Lieberman B, Storch G, Buller R, Sweet SC, Mehta AK, Cheeseman JA, Heeger P, Rosenberg ES, Fishman JA (2014) Multicenter comparison of laboratory performance in cytomegalovirus and Epstein-Barr virus viral load testing using international standards. Clin Transpl 28:1416–1423. https://doi.org/10.1111/ctr.12473

20.

Zagórowicz E, Bugajski M, Wieszczy P, Pietrzak A, Magdziak A, Mróz A (2016) Cytomegalovirus infection in ulcerative colitis is related to severe inflammation and a high count of cytomegalovirus-positive cells in biopsy is a risk factor for colectomy. J Crohns Colitis 10:1205–1211. https://doi.org/10.1093/ecco-jcc/jjw071 CrossRefPubMed

21.

Nguyen M, Bradford K, Zhang X, Shih DQ (2011) Cytomegalovirus reactivation in ulcerative colitis patients. Ulcers 2011:1–7. https://doi.org/10.1155/2011/282507 CrossRef

22.

Kuwabara A, Okamoto H, Suda T, Ajioka Y, Hatakeyama K (2007) Clinicopathologic characteristics of clinically relevant cytomegalovirus infection in inflammatory bowel disease. J Gastroenterol 42:823–829. https://doi.org/10.1007/s00535-007-2103-3 CrossRefPubMed

23.

Lawlor G, Moss AC (2010) Cytomegalovirus in inflammatory bowel disease: pathogen or innocent bystander? Inflamm Bowel Dis 16:1620–1627. https://doi.org/10.1002/ibd.21275 CrossRefPubMed

24.

Gauss A, Rosenstiel S, Schnitzler P, Hinz U, Rehlen T, Kadmon M, Ehehalt R, Stremmel W, Zawierucha A (2015) Intestinal cytomegalovirus infection in patients hospitalized for exacerbation of inflammatory bowel disease: a 10-year tertiary referral center experience. Eur J Gastroenterol Hepatol 27:712–720. https://doi.org/10.1097/MEG.0000000000000361 CrossRefPubMed

25.

Kandiel A, Lashner B (2006) Cytomegalovirus colitis complicating inflammatory bowel disease. Am J Gastroenterol 101:2857–2865. https://doi.org/10.1111/j.1572-0241.2006.00869.x CrossRefPubMed

26.

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 13:1516–1521. https://doi.org/10.1002/ibd.20253 CrossRefPubMed

27.

Yang H, Zhou W, Lv H, Wu D, Feng Y, Shu H, Jin M, Hu L, Wang Q, Wu D, Chen J, Qian J (2017) The association between CMV viremia or endoscopic features and histopathological characteristics of CMV colitis in patients with underlying ulcerative colitis. Inflamm Bowel Dis 23:814–821. https://doi.org/10.1097/MIB.0000000000001095 CrossRefPubMed

28.

Kim JW, Boo S-J, Ye BD, Kim CL, Yang SK, Kim J, Kim SA, Park SH, Park SK, Yang DH, Jung KW, Kim KJ, Byeon JS, Myung SJ, Kim JH (2014) Clinical utility of cytomegalovirus antigenemia assay and blood cytomegalovirus DNA PCR for cytomegaloviral colitis patients with moderate to severe ulcerative colitis. J Crohns Colitis 8:693–701. https://doi.org/10.1016/j.crohns.2013.12.014 CrossRefPubMed

29.

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 106:2001–2008. https://doi.org/10.1038/ajg.2011.202 CrossRefPubMed

30.

Ciccocioppo R, Racca F, Paolucci S, Campanini G, Pozzi L, Betti E, Riboni R, Vanoli A, Baldanti F, Corazza GR (2015) Human cytomegalovirus and Epstein-Barr virus infection in inflammatory bowel disease: need for mucosal viral load measurement. World J Gastroenterol 21:1915–1926. https://doi.org/10.3748/wjg.v21.i6.1915 CrossRefPubMedPubMedCentral

31.

Durand CM, Marr KA, Arnold CA, Tang L, Durand DJ, Avery RK, Valsamakis A, Neofytos D (2013) Detection of cytomegalovirus DNA in plasma as an adjunct diagnostic for gastrointestinal tract disease in kidney and liver transplant recipients. Clin Infect Dis 57:1550–1559. https://doi.org/10.1093/cid/cit521 CrossRefPubMedPubMedCentral

32.

Beaugerie L, Cywiner-Golenzer C, Monfort L, Girard PM, Carbonnel F, Ngô Y, Cosnes J, Rozenbaum W, Nicolas JC, Châtelet FP, Gendre JP (1997) Definition and diagnosis of cytomegalovirus colitis in patients infected by human immunodeficiency virus. J Acquir Immune Defic Syndr Hum Retrovirol 14:423–429CrossRefPubMed

33.

McCurdy JD, Jones A, Enders FT et al (2015) A model for identifying cytomegalovirus in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol 13:131–137. https://doi.org/10.1016/j.cgh.2014.05.026 CrossRefPubMed

Title: Accuracy of diagnostic tests and a new algorithm for diagnosing cytomegalovirus colitis in inflammatory bowel diseases: a diagnostic study
Authors: Lea I. Kredel
Pamela Mundt
Linda van Riesen
Korinna Jöhrens
Jörg Hofmann
Christoph Loddenkemper
Britta Siegmund
Jan C. Preiß
Publication date: 01-02-2019
Publisher: Springer Berlin Heidelberg
Published in: International Journal of Colorectal Disease / Issue 2/2019
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI: https://doi.org/10.1007/s00384-018-3170-z

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Springer Medicine

Accuracy of diagnostic tests and a new algorithm for diagnosing cytomegalovirus colitis in inflammatory bowel diseases: a diagnostic study

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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