Korean J Gastroenterol.  2022 Aug;80(2):60-65. 10.4166/kjg.2022.094.

Cytomegalovirus Infection in Patients with Inflammatory Bowel Disease

• Lee J

• KMID: 2532679
• DOI: http://doi.org/10.4166/kjg.2022.094

Abstract

A diagnostic evaluation for cytomegalovirus (CMV) infection is required in patients with inflammatory bowel disease (IBD) who do not respond to steroid or immunomodulatory treatment. However, there is no consensus on an accurate diagnostic method for CMV infection in patients with IBD, and it is difficult to clearly distinguish the exacerbation of ulcerative colitis from CMV colitis. According to several recent studies, the most accurate test method for CMV colitis is quantitative tissue DNA-quantitative PCR, which is recommended as the first-line diagnostic technique along with an immunohistochemistry stain. The benefit of antiviral therapy for CMV infection in patients with IBD is also controversial. Although the definition of viral load is unclear, antiviral therapy can lower the rate of colectomy in CMV infections with a high viral load in patients with IBD. This review presents the latest findings about CMV infections in IBD, based on recently reported studies.

Keyword

Cytomegalovirus; Inflammatory bowel diseases; Opportunistic infections

Figure

• 

  Fig. 1 Endoscopic findings of cytomegalovirus infection in inflammatory bowel disease. (A) Diffuse erythematous mucosal change with erosion. (B) Multiple small erosions with exudate. (C) Diffuse subepithelial hemorrhage with edema. (D) Punched-out ulcer with clear demarcation from surrounding tissues. (E) Diffuse geographic ulcer.

• 

  Fig. 2 Histopathologic findings of cytomegalovirus infection in ulcerative colitis. (A) Characteristic viral cytopathic effects such as nuclear enlargement and intranuclear inclusion are identified (hematoxylin and eosin stain [H&E], ×40). (B) Several scattered stromal cells are reactive for cytomegalovirus by immunohistochemical staining (×40).

Reference

1. Kandiel A, Lashner B. 2006; Cytomegalovirus colitis complicating inflammatory bowel disease. Am J Gastroenterol. 101:2857–2865. DOI: 10.1111/j.1572-0241.2006.00869.x. PMID: 17026558.

2. Powell RD, Warner NE, Levine RS, Kirsner JB. 1961; Cytomegalic inclusion disease and ulcerative colitis; report of a case in a young adult. Am J Med. 30:334–340. DOI: 10.1016/0002-9343(61)90105-X. PMID: 13737621.

3. Kucharzik T, Ellul P, Greuter T, et al. 2021; ECCO guidelines on the prevention, diagnosis, and management of infections in inflammatory bowel disease. J Crohns Colitis. 15:879–913. DOI: 10.1093/ecco-jcc/jjab052. PMID: 33730753.

4. Choi CH, Moon W, Kim YS, et al. 2017; Second Korean guideline for the management of ulcerative colitis. Korean J Gastroenterol. 69:1–28. DOI: 10.4166/kjg.2017.69.1.1. PMID: 28135789.

5. Rubin DT, Ananthakrishnan AN, Siegel CA, Sauer BG, Long MD. 2019; ACG clinical guideline: ulcerative colitis in adults. Am J Gastroenterol. 114:384–413. DOI: 10.14309/ajg.0000000000000152. PMID: 30840605.

6. Kim YS. 2021; Does cytomegalovirus load predict the outcome of acute severe ulcerative colitis? Intest Res. 19:357–359. DOI: 10.5217/ir.2021.00120. PMID: 34731562. PMCID: PMC8566827.

7. Jain S, Namdeo D, Sahu P, et al. 2021; High mucosal cytomegalovirus DNA helps predict adverse short-term outcome in acute severe ulcerative colitis. Intest Res. 19:438–447. DOI: 10.5217/ir.2020.00055. PMID: 33147897. PMCID: PMC8566826.

8. Römkens TE, Bulte GJ, Nissen LH, Drenth JP. 2016; Cytomegalovirus in inflammatory bowel disease: a systematic review. World J Gastroenterol. 22:1321–1330. DOI: 10.3748/wjg.v22.i3.1321. PMID: 26811669. PMCID: PMC4716042.

9. Lv YL, Han FF, Jia YJ, et al. 2017; Is cytomegalovirus infection related to inflammatory bowel disease, especially steroid-resistant inflammatory bowel disease? A meta-analysis. Infect Drug Resist. 10:511–519. DOI: 10.2147/IDR.S149784. PMID: 29276397. PMCID: PMC5733908.

10. Lopes S, Andrade P, Conde S, et al. 2017; Looking into enteric virome in patients with IBD: defining guilty or innocence? Inflamm Bowel Dis. 23:1278–1284. DOI: 10.1097/MIB.0000000000001167. PMID: 28617757.

11. Cottone M, Pietrosi G, Martorana G, et al. 2001; Prevalence of cytomegalovirus infection in severe refractory ulcerative and Crohn's colitis. Am J Gastroenterol. 96:773–775. DOI: 10.1111/j.1572-0241.2001.03620.x. PMID: 11280549.

12. Lee HS, Park SH, Kim SH, et al. 2016; Risk factors and clinical outcomes associated with cytomegalovirus colitis in patients with acute severe ulcerative colitis. Inflamm Bowel Dis. 22:912–918. DOI: 10.1097/MIB.0000000000000675. PMID: 26829410.

13. Kim YS, Kim YH, Kim JS, et al. 2012; The prevalence and efficacy of ganciclovir on steroid-refractory ulcerative colitis with cytomegalovirus infection: a prospective multicenter study. J Clin Gastroenterol. 46:51–56. DOI: 10.1097/MCG.0b013e3182160c9c. PMID: 21552140.

14. 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. DOI: 10.1007/s10620-008-0639-6. PMID: 19093204.

15. Iida T, Ikeya K, Watanabe F, et al. 2013; Looking for endoscopic features of cytomegalovirus colitis: a study of 187 patients with active ulcerative colitis, positive and negative for cytomegalovirus. Inflamm Bowel Dis. 19:1156–1163. DOI: 10.1097/MIB.0b013e31828075ce. PMID: 23619714.

16. Yang H, Zhou W, Lv H, et al. 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. DOI: 10.1097/MIB.0000000000001095. PMID: 28426459.

17. McCurdy JD, Enders FT, Jones A, et al. 2015; Detection of cytomegalovirus in patients with inflammatory bowel disease: where to biopsy and how many biopsies? Inflamm Bowel Dis. 21:2833–2838. DOI: 10.1097/MIB.0000000000000556. PMID: 26273816.

18. Gauss A, Rosenstiel S, Schnitzler P, et al. 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. DOI: 10.1097/MEG.0000000000000361. PMID: 25919654.

19. Kishore J, Ghoshal U, Ghoshal UC, et al. 2004; Infection with cytomegalovirus in patients with inflammatory bowel disease: prevalence, clinical significance and outcome. J Med Microbiol. 53:1155–1160. DOI: 10.1099/jmm.0.45629-0. PMID: 15496396.

20. Okahara K, Nagata N, Shimada T, et al. 2017; Colonic cytomegalovirus detection by mucosal PCR and antiviral therapy in ulcerative colitis. PLoS One. 12:e0183951. DOI: 10.1371/journal.pone.0183951. PMID: 28886066. PMCID: PMC5590814.

21. Nowacki TM, Bettenworth D, Meister T, et al. 2018; Novel score predicts risk for cytomegalovirus infection in ulcerative colitis. J Clin Virol. 105:103–108. DOI: 10.1016/j.jcv.2018.06.002. PMID: 29940421.

22. Qin Y, Wang G, Kong D, et al. 2021; Risk factors of cytomegalovirus reactivation in ulcerative colitis patients: a meta-analysis. Diagnostics (Basel). 11:1952. DOI: 10.3390/diagnostics11111952. PMID: 34829298. PMCID: PMC8625464.

23. Liu CC, Ji S, Ding Y, Zhou L, Liu X, Li W. 2018; Cytomegalovirus infection and steroid-refractory inflammatory bowel disease: possible relationship from an updated meta-analysis. Ir J Med Sci. 187:935–942. DOI: 10.1007/s11845-018-1752-y. PMID: 29392650.

24. Kim YS, Kim YH, Kim JS, et al. 2014; Long-term outcomes of cytomegalovirus reactivation in patients with moderate to severe ulcerative colitis: a multicenter study. Gut Liver. 8:643–647. DOI: 10.5009/gnl13427. PMID: 25368753. PMCID: PMC4215451.

25. Roblin X, Pillet S, Oussalah A, et al. 2011; Cytomegalovirus load in inflamed intestinal tissue is predictive of resistance to immunosuppressive therapy in ulcerative colitis. Am J Gastroenterol. 106:2001–2008. DOI: 10.1038/ajg.2011.202. PMID: 21788989.

26. Paul M, Gupta E, Jain P, Rastogi A, Bhatia V. 2018; Diagnostic utility of quantitative cytomegalovirus DNA polymerase chain reaction in intestinal biopsies from patients with inflammatory bowel disease. J Lab Physicians. 10:38–43. DOI: 10.4103/JLP.JLP_94_17. PMID: 29403203. PMCID: PMC5784291.

27. Nguyen M, Bradford K, Zhang X, Shih DQ. 2011; Cytomegalovirus reactivation in ulcerative colitis patients. Ulcers. 2011:282507. DOI: 10.1155/2011/282507. PMID: 21731826. PMCID: PMC3124815.

28. 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. DOI: 10.1007/s00535-007-2103-3. PMID: 17940835.

29. Criscuoli V, Rizzuto MR, Cottone M. 2006; Cytomegalovirus and inflammatory bowel disease: is there a link? World J Gastroenterol. 12:4813–4818. DOI: 10.3748/wjg.v12.i30.4813. PMID: 16937462. PMCID: PMC4087614.

30. Pouw RE, Barret M, Biermann K, et al. 2021; Endoscopic tissue sampling- part 1: upper gastrointestinal and hepatopancreatobiliary tracts. European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 53:1174–1188. DOI: 10.1055/a-1611-5091. PMID: 34535035.

31. Zidar N, Ferkolj I, Tepeš K, et al. 2015; Diagnosing cytomegalovirus in patients with inflammatory bowel disease--by immunohistochemistry or polymerase chain reaction? Virchows Arch. 466:533–539. DOI: 10.1007/s00428-015-1741-8. PMID: 25701481.

32. Garrido E, Carrera E, Manzano R, Lopez-Sanroman A. 2013; Clinical significance of cytomegalovirus infection in patients with inflammatory bowel disease. World J Gastroenterol. 19:17–25. DOI: 10.3748/wjg.v19.i1.17. PMID: 23326158. PMCID: PMC3545225.

33. Boivin G, Handfield J, Toma E, et al. 1998; Evaluation of the AMPLICOR cytomegalovirus test with specimens from human immunodeficiency virus-infected subjects. J Clin Microbiol. 36:2509–2513. DOI: 10.1128/JCM.36.9.2509-2513.1998. PMID: 9705384. PMCID: PMC105154.

34. Kim JW, Boo SJ, Ye BD, et al. 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. DOI: 10.1016/j.crohns.2013.12.014. PMID: 24405983.

35. Lawlor G, Moss AC. 2010; Cytomegalovirus in inflammatory bowel disease: pathogen or innocent bystander? Inflamm Bowel Dis. 16:1620–1627. DOI: 10.1002/ibd.21275. PMID: 20232408.

36. 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. DOI: 10.1097/MIB.0000000000001073. PMID: 28296820.

37. Kopylov U, Eliakim-Raz N, Szilagy A, Seidman E, Ben-Horin S, Katz L. 2014; Antiviral therapy in cytomegalovirus-positive ulcerative colitis: a systematic review and meta-analysis. World J Gastroenterol. 20:2695–2703. DOI: 10.3748/wjg.v20.i10.2695. PMID: 24627606. PMCID: PMC3949279.

38. Shukla T, Singh S, Loftus EV Jr, Bruining DH, McCurdy JD. 2015; Antiviral therapy in steroid-refractory ulcerative colitis with cytomegalovirus: systematic review and meta-analysis. Inflamm Bowel Dis. 21:2718–2725. DOI: 10.1097/MIB.0000000000000489. PMID: 26197450.

39. Jones A, McCurdy JD, Loftus EV Jr, 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. DOI: 10.1016/j.cgh.2014.09.042. PMID: 25283582.

40. Inokuchi T, Kato J, Hiraoka S, et al. 2014; Long-term follow-up of ulcerative colitis patients treated on the basis of their cytomegalovirus antigen status. World J Gastroenterol. 20:509–517. DOI: 10.3748/wjg.v20.i2.509. PMID: 24574719. PMCID: PMC3923025.

41. Mourad FH, Hashash JG, Kariyawasam VC, Leong RW. 2020; Ulcerative colitis and cytomegalovirus infection: from A to Z. J Crohns Colitis. 14:1162–1171. DOI: 10.1093/ecco-jcc/jjaa036. PMID: 32103246.