Cytomegalovirus Colitis

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Cytomegalovirus (CMV) is a member of the Herpesviridae family, along with herpes simplex viruses 1 and 2, Epstein-Barr virus, and varicella-zoster virus. It is a double-stranded DNA virus with a protein coat and lipoprotein envelope. Similar to other herpesviruses, CMV is icosahedral and replicates in the host’s nucleus. Replication in the host cell typically manifests pathologically with large intranuclear inclusion bodies and smaller cytoplasmic inclusions, and is accompanied by the presence of CMV viral particles in the plasma. See the images below.

Between 50% and 80% of the world’s population is seropositive for CMV. The initial CMV infection in the immunocompetent host typically is mild and goes undetected clinically. This is followed by a chronic latent state, during which the virus remains present within the host cells, but viral proliferation is prevented by the host cell-mediated immunity. Failure of immune containment may lead to reactivation with viral proliferation and severe systemic illness. Systemic CMV disease is characterized by fever, pancytopenia, and inflammatory changes in multiple organs including the liver and lungs, and in the retina. Colitis is a frequent manifestation of this acute systemic illness.

Patients are rendered susceptible to systemic CMV disease by treatment with immunosuppressive medications, or by illnesses that reduce cellular immunity, such as human immunodeficiency virus (HIV) infection. Acute systemic illness caused by CMV is particularly common following initial exposure in an immune compromised individual (in particular, in a CMV-negative transplant recipient who receives an organ from a CMV-positive donor).

Cytomegalovirus (CMV) has 3 major patterns of infection.

The first is primary infection, in which a patient who has never been exposed to the pathogen becomes infected, either by contact with another patient who is actively infected or by transfer of blood or tissue from a seropositive individual with latent virus. The second pattern, reactivation, occurs in a patient who is seropositive with a latent virus when the host’s immune system becomes compromised. The third, superinfection, occurs when a patient who is CMV-seropositive receives latently infected cells from another patient who is seropositive. The resulting CMV infection is from the latent donor cells, not from the recipient cells.

Regardless of the pattern of infection, resolution of an active infection results in a latent state in which CMV persists indefinitely in the host tissues. Viral proliferation is absent, and viral antigen and DNA are undetectable in plasma. If the host’s T-cell response becomes compromised by disease or by immunosuppressive therapy, latent virus reactivation can occur.

CMV infection can cause a variety of syndromes. Most primary infections in immunocompetent individuals go undetected. Nonspecific fever, sometimes accompanied by pancytopenia, characterizes uncomplicated CMV infection. Severe cases of tissue-invasive CMV disease may produce a bewildering array of clinical syndromes, depending on the particular organs involved.

When the colon becomes affected by tissue-invasive CMV, ulcerative changes can be seen. As the body mounts an inflammatory response, watery diarrhea may begin to develop. As ulcers increase in depth, erosion into blood vessels can cause profuse bloody diarrhea. Over time, inflammatory polyps may develop, which, rarely, may obstruct the colon. Severe inflammation and vasculitis may lead to ischemia and transmural necrosis of the bowel, resulting in perforation and peritonitis.

Any factor that causes a decrease in a patient’s immunity increases the risk for cytomegalovirus (CMV) colitis, including the following:

Adults older than 70 years, especially if nutritionally depleted

Human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS)

High- and low-dose steroid therapy and therapy with other immunosuppressive medications

Transplantation patients (especially patients receiving CMV-positive organs)

Hemodialysis

Neoplasia

Inflammatory bowel disease

Alcoholism

Collagen-vascular disease (seems to be related to immunosuppressive therapy)

Blood transfusions

Malnutrition

Cytomegalovirus (CMV) colitis is rare in immunocompetent patients. It occurs in 2-16% of patients who have received solid organ transplants and in 3-5% of patients with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS). A study documented CMV infection in 27.3% of patients with steroid-refractory ulcerative colitis and 9.1% of patients with nonrefractory colitis. ^{[1, 2]}

In a systematic review of published studies on HIV and CMV coinfection in Africa, investigators found a high CMV seroprevalence throughout the continent, (>90% in the majority of the population). ^[3] Of those with gastrointestinal manifestations, CMV was found in 0% to 14%. ^[3]

No racial or sexual predilection has been& recognized.

Reports of patients who are not immunocompromised contracting CMV colitis indicate that the illness tends to occur in patients older than 70 years. In immunocompromised patients, CMV can occur at any age, including the newborn period.

CMV reactivation has a reported 4.5-16.6% prevalence in patients with severe colitis; it can reach 25% in those who require colectomy for severe colitis. ^[4]

With rapid diagnosis and proper antiviral therapy, the prognosis of patients with cytomegalovirus (CMV) colitis is good if the underlying disease itself is controllable.

In patients without immunocompromised status, the prognosis appears to be age dependent, with patients older than 55 years having a higher mortality. Males and patients who need surgery also have a poorer prognosis.

Since the introduction of effective antiviral agents, morbidity and mortality have been reduced.

CMV reactivation has been known to occur in patients with inflammatory bowel disease-related colitis, particularly in those who have steroid-refractory colitis. ^[5] In cases of CMV reactivation that give rise to true CMV colitis (on the basis of histology and immunohistochemistry findings), antiviral agents may provide benefit. ^[5]

Complications include the following:

Toxic megacolon and necrotizing colitis: Once diagnosed, patients with these complications usually have diffuse disease and a poor prognosis. In these patients, generous resection of all the affected colon is indicated to avert perforation and sepsis.

Perforation

Sepsis

Peritonitis

Death

Maconi G, Colombo E, Zerbi P, et al. Prevalence, detection rate and outcome of cytomegalovirus infection in ulcerative colitis patients requiring colonic resection. Dig Liver Dis. 2005 Jun. 37(6):418-23. [Medline].

Kim YS, Kim YH, Kim JS, et al, for the IBD Study Group of the Korean Association for the Study of Intestinal Diseases(KASID), Korea. Cytomegalovirus infection in patients with new onset ulcerative colitis: a prospective study. Hepatogastroenterology. 2012 Jun. 59(116):1098-101. [Medline].

Gronborg HL, Jespersen S, Honge BL, Jensen-Fangel S, Wejse C. Review of cytomegalovirus coinfection in HIV-infected individuals in Africa. Rev Med Virol. 2017 Jan. 27(1):[Medline].

Sager K, Alam S, Bond A, Chinnappan L, Probert CS. Review article: cytomegalovirus and inflammatory bowel disease. Aliment Pharmacol Ther. 2015 Apr. 41(8):725-33. [Medline].

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Onyeagocha C, Hossain MS, Kumar A, et al. Latent cytomegalovirus infection exacerbates experimental colitis. Am J Pathol. 2009 Nov. 175(5):2034-42. [Medline]. [Full Text].

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Pillet S, Pozzetto B, Jarlot C, Paul S, Roblin X. Management of cytomegalovirus infection in inflammatory bowel diseases. Dig Liver Dis. 2012 Jul. 44(7):541-8. [Medline].

Chan KS, Lee WY, Yu WL. Coexisting cytomegalovirus infection in immunocompetent patients with Clostridium difficile colitis. J Microbiol Immunol Infect. 2016 Dec. 49(6):829-36. [Medline].

Lancini D, Faddy HM, Flower R, Hogan C. Cytomegalovirus disease in immunocompetent adults. Med J Aust. 2014 Nov 17. 201(10):578-80. [Medline].

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 Jan. 34(1):13-8. [Medline].

Kim JW, Boo SJ, Ye BD, et al. Clinical utility of cytomegalovirus antigenemia assay and blood cytomegalovirus DNA PCR for cytomegaloviral colitis patients with moderate to severe ulcerative colitis. J Crohns Colitis. 2014 Jul. 8(7):693-701. [Medline].

Jones A, McCurdy JD, Loftus EV Jr, et al. Effects of antiviral therapy for patients with inflammatory bowel disease and a positive intestinal biopsy for cytomegalovirus. Clin Gastroenterol Hepatol. 2015 May. 13(5):949-55. [Medline].

Shukla T, Singh S, Loftus EV Jr, Bruining DH, McCurdy JD. Antiviral therapy in steroid-refractory ulcerative colitis with cytomegalovirus: systematic review and meta-analysis. Inflamm Bowel Dis. 2015 Nov. 21(11):2718-25. [Medline].

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Chan KS, Yang CC, Chen CM, et al. Cytomegalovirus colitis in intensive care unit patients: difficulties in clinical diagnosis. J Crit Care. 2014 Jun. 29(3):474.e1-6. [Medline].

Yadegarynia D, Tehrani S, Roohi M, et al. Prevalence of cytomegalovirus infection in patients with ulcerative colitis: a prospective cross-sectional study in Tehran, Iran. Iran J Microbiol. 2018 Oct. 10(5):342-7. [Medline]. [Full Text].

Carpani G, Foresti S, Dell’Oro R, Grassi G, Bombelli M. Severe systemic cytomegalovirus infection in an immunocompetent patient outside the intensive care unit: a case report. BMC Infect Dis. 2019 Jan 9. 19(1):34. [Medline]. [Full Text].

Douglas M Heuman, MD, FACP, FACG, AGAF Chief of Hepatology, Hunter Holmes McGuire Department of Veterans Affairs Medical Center; Professor, Department of Internal Medicine, Division of Gastroenterology, Virginia Commonwealth University School of Medicine

Douglas M Heuman, MD, FACP, FACG, AGAF is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Physicians, American Gastroenterological Association

Disclosure: Received grant/research funds from Novartis for other; Received grant/research funds from Bayer for other; Received grant/research funds from Otsuka for none; Received grant/research funds from Bristol Myers Squibb for other; Received none from Scynexis for none; Received grant/research funds from Salix for other; Received grant/research funds from MannKind for other.

Jasmohan S Bajaj, MD, MSc Assistant Professor of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University Medical Center

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Vivek V Gumaste, MD Associate Professor of Medicine, Mount Sinai School of Medicine of New York University; Adjunct Clinical Assistant, Mount Sinai Hospital; Director, Division of Gastroenterology, City Hospital Center at Elmhurst; Program Director of GI Fellowship (Independent Program); Regional Director of Gastroenterology, Queens Health Network

Vivek V Gumaste, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association

Disclosure: Nothing to disclose.

Jeffrey D Band, MD, FACP, FIDSA Professor of Medicine, Oakland University William Beaumont School of Medicine; Health System Chair, Healthcare Epidemiology and International Medicine, Beaumont Health System; Former Chief of Infectious Diseases, Beaumont Hospital; Clinical Professor of Medicine, Wayne State University School of Medicine

Disclosure: Nothing to disclose.

The authors and editors of Medscape Drugs & Diseases gratefully acknowledge the contributions of previous authors Deron J. Tessier, MD, and Russell A. Williams, MBBS, to the development and writing of this article.

Cytomegalovirus Colitis

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