Advertisement

Diagnosis and Management of CMV Colitis

  • Anat Yerushalmy-Feler
  • Jacqueline Padlipsky
  • Shlomi CohenEmail author
Intra-Abdominal Infections, Hepatitis and Gastroenteritis (T. Steiner, Section Editor)
  • 744 Downloads
Part of the following topical collections:
  1. Topical Collection on Intra-abdominal Infections, Hepatitis, and Gastroenteritis

Abstract

Purpose of Review

Cytomegalovirus (CMV) colitis is a relatively common end-organ infectious complication in immunocompromised hosts which negatively affects clinical outcomes. This paper presents the contemporary approaches to the diagnosis and management of CMV colitis and discusses some of the controversies of this condition, focusing on methods of diagnosis.

Recent Findings

While certain risk factors for CMV colitis are well recognized, the clinical as well as endoscopic features of this condition are nonspecific. Rapid diagnosis and management are usually needed, especially in critically ill patients, which necessitate invasive diagnostic procedures. Hematoxylin and eosin staining of colonic mucosal tissue may show the typical viral inclusions associated with CMV colitis that are highly specific for this condition. However, the staining has low sensitivity compared to immunohistochemistry, which is considered the gold standard for diagnosis of CMV colitis. Tissue polymerase chain reaction (PCR) is highly sensitive for diagnosis, but is controversial for many reasons, detailed in this paper.

Summary

A high index of suspicion is needed, and once diagnosis is made, treatment should be highly considered to improve the outcome of these severely ill patients. Noninvasive diagnostic tests will be available in the future and will hopefully improve the diagnosis and care of patients with CMV colitis.

Keywords

Colitis Cytomegalovirus Immunodeficiency Inflammatory bowel disease 

Abbreviations

CMV

Cytomegalovirus

IBD

inflammatory bowel disease

UC

ulcerative colitis

ICU

intensive care unit

HIV

human immunodeficiency virus

GVHD

graft-versus-host-disease

H&E

hematoxylin and eosin

IHC

immunohistochemistry

PCR

polymerase chain reaction

FFPE

formalin-fixed, paraffin-embedded tissue

Notes

Compliance with Ethical Standards

Conflict of Interest

All authors have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by anyof the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Goodman AL, Murray CD, Watkins J, Griffiths PD, Webster DP. CMV in the gut: a critical review of CMV detection in the immunocompetent host with colitis. Eur J Clin Microbiol Infect Dis. 2015;34(1):13–8.CrossRefGoogle Scholar
  2. 2.
    Yerushalmy-Feler A, Kern-Isaacs S, Cohen S. CMV infection in pediatric IBD. Curr Gastroenterol Rep. 2018;20(4):13.CrossRefGoogle Scholar
  3. 3.
    Liu PY, Cheng SB, Lin CC, Lin CH, Chang SN, Cheng CY, et al. Cytomegalovirus disease after liver transplantation: a nationwide population-based study. Transplant Proc. 2014;46(3):832–4.Google Scholar
  4. 4.
    Bhutani D, Dyson G, Manasa R, Deol A, Ratanatharathorn V, Ayash L, et al. Incidence, risk factors, and outcome of cytomegalovirus viremia and gastroenteritis in patients with gastrointestinal graft-versus-host disease. Biol Blood Marrow Transplant. 2015;21(1):159–64.Google Scholar
  5. 5.
    Bontà J, Zeitz J, Frei P, Biedermann L, Sulz MC, Vavricka SR, et al. Cytomegalovirus disease in inflammatory bowel disease: epidemiology and disease characteristics in a large single-centre experience. Eur J Gastroenterol Hepatol. 2016;28:1329–34.Google Scholar
  6. 6.
    do Carmo AM, Santos FM, Ortiz-Agostinho CL, Nishitokukado I, Frota CS, Gomes FU, et al. Cytomegalovirus infection in inflammatory bowel disease is not associated with worsening of intestinal inflammatory activity. PLoS One. 2014;9(11):e111574.CrossRefGoogle Scholar
  7. 7.
    • Levin A, Yaari S, Stoff R, Caplan O, Wolf DG, Israeli E. Diagnosis of Cytomegalovirus infection during exacerbation of ulcerative colitis. Digestion. 2017;96(3):142–8. This study provides a clinical model to detect the presence of CMV infection in patients hospitalized with UC exacerbation.CrossRefGoogle Scholar
  8. 8.
    Gauss A, Rosenstiel S, Schnitzler P, Hinz U, Rehlen T, Kadmon M, et al. Intestinal cytomegalovirus infection in patients hospitalized for exacerbation of inflammatory bowel disease: a 10-year tertiary referral center experience. Eur J Gastroenterol Hepatol. 2015;27(6):712–20.Google Scholar
  9. 9.
    Lee HS, Park SH, Kim SH, Kim J, Choi J, Lee HJ, et al. Risk Factors and clinical outcomes associated with Cytomegalovirus colitis in patients with acute severe ulcerative colitis. Inflamm Bowel Dis. 2016;22(4):912–8.CrossRefGoogle Scholar
  10. 10.
    Galiatsatos P, Shrier I, Lamoureux E, Szilagy A. Meta-analysis of outcome of cytomegalovirus colitis in immunocompetent hosts. Dig Dis Sci. 2005;50:609–16.CrossRefGoogle Scholar
  11. 11.
    Siciliano RF, Castelli JB, Randi BA, Vieira RD, Strabelli TMV. Cytomegalovirus colitis in immunocompetent critically ill patients. Int J Infect Dis. 2014;20:71–3.CrossRefGoogle Scholar
  12. 12.
    Bernard S, Germi R, Lupo J, Laverrière MH, Masse V, Morand P, et al. Symptomatic cytomegalovirus gastrointestinal infection with positive quantitative real-time PCR findings in apparently immunocompetent patients: a case series. Clin Microbiol Infect. 2015;21(12):1121.e1-e7.CrossRefGoogle Scholar
  13. 13.
    Jain R, Trehan A, Mishra B, Singh R, Saud B, Bansal D. Cytomegalovirus disease in children with acute lymphoblastic leukemia. Pediatr Hematol Oncol. 2016;33(4):239–47.CrossRefGoogle Scholar
  14. 14.
    Nierenberg NE, Poutsiaka DD, Chow JK, Cooper J, Price LL, Freeman RB, et al. Pretransplant lymphopenia is a novel prognostic factor in CMV and non-CMV invasive infection after liver transplantation. Liver Transpl. 2014;20(12):1497–507.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Zhang WX, Ma CY, Zhang JG, He F, Liu QM, Cheng A, et al. Effects of cytomegalovirus infection on the prognosis of inflammatory bowel disease patients. Exp Ther Med. 2016;12(5):3287–93.Google Scholar
  16. 16.
    Hirayama Y, Ando T, Hirooka Y, Watanabe O, Miyahara R, Nakamura M, et al. Characteristic endoscopic findings and risk factors for cytomegalovirus-associated colitis in patients with active ulcerative colitis. World J Gastrointest Endosc. 2016;8(6):301–9.Google Scholar
  17. 17.
    McCurdy JD, Jones A, Enders FT, Killian JM, Loftus EV, Smyrk TC, et al. A model for identifying cytomegalovirus in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2015;13(1):131–7.CrossRefGoogle Scholar
  18. 18.
    Shukla T, Singh S, Tandon P, McCurdy JD. Corticosteroids and thiopurines, but not tumor necrosis factor antagonists, are associated with cytomegalovirus reactivation in inflammatory bowel disease: a systematic review and meta-analysis. J Clin Gastroenterol. 2017;51(5):394–401.CrossRefGoogle Scholar
  19. 19.
    Ko JH, Peck KR, Lee WJ, Lee JY, Cho SY, Ha YE, et al. Clinical presentation and risk factors for Cytomegalovirus colitis in immunocompetent adult patients. Clin Infect Dis. 2015;60(6):e20–6.Google Scholar
  20. 20.
    Sue PK, Salazar-Austin NM, McDonald OG, Rishi A, Cornish TC, Arav-Boger R. Cytomegalovirus enterocolitis in immunocompetent young children: a report of two cases and review of the literature. Pediatr Infect Dis J. 2016;35(5):573–6.CrossRefGoogle Scholar
  21. 21.
    Novakova V, Hamprecht K, Müller AM, Arellano-Galindo J, Ehlen M, Horneff G. Severe postnatal CMV colitis with an extensive colonic stenosis in a 2-month-old male immunocompetent term infant infected via breast milk. J Clin Virol. 2014;59(4):259–63.CrossRefGoogle Scholar
  22. 22.
    Durand CM, Marr KA, Arnold CA, Tang L, Durand DJ, Avery RK, et al. Detection of cytomegalovirus DNA in plasma as an adjunct diagnostic for gastrointestinal tract disease in kidney and liver transplant recipients. Clin Infect Dis. 2013;57(11):1550–9.Google Scholar
  23. 23.
    Wu XW, Wu L, Ji HZ, Wang FY. Relationship between cytomegalovirus infection and steroid resistance in inflammatory bowel disease: a meta-analysis. Dig Dis Sci. 2015;60(11):3203–8.CrossRefGoogle Scholar
  24. 24.
    • Cohen S, Martinez-Vinson C, Aloi M, et al. Cytomegalovirus infection in pediatric severe ulcerative colitis-a multicenter study from the Pediatric Inflammatory Bowel Disease Porto Group of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition. Pediatr Infect Dis J. 2018;37(3):197–201. This article is the largest cohort of children with UC and CMV.CrossRefGoogle Scholar
  25. 25.
    Zhang C, Krishna SG, Hinton A, Arsenescu R, Levine EJ, Conwell DL. Cytomegalovirus-related hospitalization is associated with adverse outcomes and increased health-care resource utilization in inflammatory bowel disease. Clin Transl Gastroenterol. 2016;7(3):e150.CrossRefGoogle Scholar
  26. 26.
    Grossberg LB, Ezaz G, Grunwald D, Cohen J, Falchuk KR, Feuerstein JD. A national survey of the prevalence and impact of cytomegalovirus infection among hospitalized patients with ulcerative colitis. J Clin Gastroenterol. 2018 Mar;52(3):241–5.PubMedGoogle Scholar
  27. 27.
    Mills AM, Guo FP, Copland AP, Pai RK, Pinsky BA. A comparison of CMV detection in gastrointestinal mucosal biopsies using immunohistochemistry and PCR performed on formalin-fixed, paraffin-embedded tissue. Am J Surg Pathol. 2013;37(7):995–1000.CrossRefGoogle Scholar
  28. 28.
    Matsuda K, Ono S, Ishikawa M, Miyamoto S, Abiko S, Tsuda M, et al. Cecum ulcer is a reliable endoscopic finding in cytomegalovirus colitis concomitant with graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Ann Hematol. 2018;97(5):877–83.CrossRefGoogle Scholar
  29. 29.
    Yang H, Zhou W, Lv H, Wu D, Feng Y, Shu H, et al. The association between CMV viremia or endoscopic features and histopathological characteristics of CMV colitis in patients with underlying ulcerative colitis. Inflamm Bowel Dis. 2017;23(5):814–21.Google Scholar
  30. 30.
    Hasegawa T, Aomatsu K, Nakamura M, Aomatsu N, Aomatsu K. Cytomegalovirus colitis followed by ischemic colitis in a non-immunocompromised adult: a case report. World J Gastroenterol. 2015;21(12):3750–4.CrossRefGoogle Scholar
  31. 31.
    Jacob S, Zayyani NR. Cytomegalovirus colitis masquerading as rectal malignancy in an immunocompetent patient. Indian J Pathol Microbiol. 2015;58(1):80–2.CrossRefGoogle Scholar
  32. 32.
    Chidlovskii E, Deroux A, Bernard S, Couturier P. Cytomegalovirus colitis mimicking rectal carcinoma in an immunocompetent elderly woman. BMJ Case Rep. 2016.  https://doi.org/10.1136/bcr-2016-214694
  33. 33.
    Zidar N, Ferkolj I, Tepeš K, Štabuc B, Kojc N, Uršič T, et al. Diagnosing cytomegalovirus in patients with inflammatory bowel disease—by immunohistochemistry or polymerase chain reaction? Virchows Arch. 2015;466(5):533–9.Google Scholar
  34. 34.
    McCoy MH, Post K, Sen JD, Chang HY, Zhao Z, Fan R, et al. qPCR increases sensitivity to detect cytomegalovirus in formalin-fixed, paraffin-embedded tissue of gastrointestinal biopsies. Hum Pathol. 2014;45(1):48–53.CrossRefGoogle Scholar
  35. 35.
    Baniak N, Kanthan R. Cytomegalovirus colitis: an uncommon mimicker of common Colitides. Arch Pathol Lab Med. 2016;140(8):854–8.CrossRefGoogle Scholar
  36. 36.
    Tandon P, James P, Cordeiro E, Mallick R, Shukla T, McCurdy JD. Diagnostic accuracy of blood-based tests and histopathology for cytomegalovirus reactivation in inflammatory bowel disease: a systematic review and meta-analysis. Inflamm Bowel Dis. 2017;23(4):551–60.CrossRefGoogle Scholar
  37. 37.
    Yan Z, Wang L, Dennis J, Doern C, Baker J, Park JY. Clinical significance of isolated Cytomegalovirus-infected gastrointestinal cells. Int J Surg Pathol. 2014;22(6):492–8.CrossRefGoogle Scholar
  38. 38.
    Wong NACS. Gastrointestinal pathology in transplant patients. Histopathology. 2015;66(4):467–79.CrossRefGoogle Scholar
  39. 39.
    Juric-Sekhar G, Upton MP, Swanson PE, Westerhoff M. Cytomegalovirus (CMV) in gastrointestinal mucosal biopsies: should a pathologist perform CMV immunohistochemistry if the clinician requests it? Hum Pathol. 2017;60:11–5.CrossRefGoogle Scholar
  40. 40.
    Rahier JF, Magro F, Abreu C, Armuzzi A, Ben-Horin S, Chowers Y, et al. Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohn's Colitis. 2014;8(6):443–68.Google Scholar
  41. 41.
    Ciccocioppo R, Racca F, Paolucci S, Campanini G, Pozzi L, Betti E, et al. Human cytomegalovirus and Epstein-Barr virus infection in inflammatory bowel disease: need for mucosal viral load measurement. World J Gastroenterol. 2015;21(6):1915–26.CrossRefGoogle Scholar
  42. 42.
    Roblin X, Pillet S, Oussalah A, Berthelot P, Del Tedesco E, Phelip JM, et al. Cytomegalovirus load in inflamed intestinal tissue is predictive of resistance to immunosuppressive therapy in ulcerative colitis. Am J Gastroenterol. 2011;106(11):2001–8.CrossRefGoogle Scholar
  43. 43.
    Fyock C, Gaitanis M, Gao J, Resnick M, Shah S. Gastrointestinal CMV in an elderly, immunocompetent patient. R I Med J. 2014;97(6):53–6.Google Scholar
  44. 44.
    Jones A, McCurdy JD, Loftus EV, Bruining DH, Enders FT, Killian JM, et al. Effects of antiviral therapy for patients with inflammatory bowel disease and a positive intestinal biopsy for Cytomegalovirus. Clin Gastroenterol Hepatol. 2015;13(5):949–55.CrossRefGoogle Scholar
  45. 45.
    Naganuma T, Takemoto Y, Iwai T, Kuwabara N, Uchida J, Nakatani T, et al. Effects of granulocyte and monocyte adsorptive apheresis in renal transplantation recipients with concomitant Cytomegalovirus infection. Transplant Proc. 2016;48(3):929–32.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Anat Yerushalmy-Feler
    • 1
    • 2
  • Jacqueline Padlipsky
    • 2
  • Shlomi Cohen
    • 1
    • 2
    Email author
  1. 1.Pediatric Gastroenterology Unit, Pediatrics Department, “Dana-Dwek” Children’s HospitalTel Aviv Sourasky Medical CenterTel AvivIsrael
  2. 2.Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael

Personalised recommendations