Cytomegalovirus Colitis



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 presence of CMV viral particles in the plasma. See the images below.

View Image

Gross specimen of bowel showing ulceration secondary to cytomegalovirus colitis.

View Image

Giant cell with inclusion body characteristic of cytomegalovirus colitis.

Between 50% and 80% of the world's population is seropositive for CMV. 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 host cells, but viral proliferation is prevented by 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).


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 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 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.



United States

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 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]






Patients may present with the following symptoms:


Patients with CMV colitis may exhibit a wide range of abdominal findings depending on the stage of their disease.


Any factor that causes a decrease in a patient's immunity increases the risk for CMV colitis.

Laboratory Studies

Imaging Studies


Histologic Findings

Affected specimens may show acute and chronic inflammatory changes, vasculitis, and/or mucosal ulceration. Deep biopsy specimens are preferred. Staining with Papanicolaou or hematoxylin and eosin stains may reveal classic findings, which include giant cells (usually 25-35 µm) (see the image below) with cytomegaly and large ovoid or pleomorphic nuclei containing basophilic inclusions (owl's eyes, halo rim). Data suggest that immunohistochemical staining may be more sensitive for detecting CMV.

View Image

Giant cell with inclusion body characteristic of cytomegalovirus colitis.

Medical Care

Surgical Care


Because CMV colitis is usually observed as part of a multisystemic disease, the following consultations should be obtained.



Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Ganciclovir (Cytovene)

Clinical Context:  Acyclic nucleoside analogue of 2'deoxyguanasine. Phosphorylates first to monophosphate form by CMV-encoded protein kinase homologue, then to diphosphate and triphosphate forms by cellular kinases, allowing for a 100-fold greater concentration in CMV-infected cells. Thought to inhibit CMV replication by competitive inhibition of viral DNA polymerases and by incorporating itself into viral DNA, causing termination of viral DNA elongation. Like acyclovir, ganciclovir is virostatic and only exerts its effect on replicating virus.

Foscarnet (Foscavir)

Clinical Context:  Organic analogue of inorganic pyrophosphate that inhibits replication of herpes simplex viruses, including CMV. Selectively inhibits at pyrophosphate binding site on virus-specific DNA polymerases at concentrations that do not affect cellular polymerases. Unlike ganciclovir, does not require activation by a kinase and is active in vitro.

Class Summary

Inhibit replication of target virus.

Further Inpatient Care

Further Outpatient Care

Inpatient & Outpatient Medications



In CMV-naive patients receiving solid organ transplants from CMV-positive donors, risk of CMV disease exceeds 40%. Prophylactic administration of ganciclovir or valganciclovir for 100 days post transplant markedly reduces the incidence of tissue invasive CMV infection. However, after prophylaxis is discontinued, some patients develop delayed CMV disease.

An alternative approach is weekly monitoring of CMV DNA with preemptive antiviral treatment when viremia is detected. The preemptive approach has theoretical appeal, as it may encourage activation of endogenous immune responses to CMV while arresting infection before tissue invasive disease can develop. Preemption also avoids the cost and toxicity of antiviral medications in those patients who achieve spontaneous immunity to CMV. Prophylaxis versus preemption is currently an area of controversy in the transplant literature.

Prophylaxis is also commonly administered in CMV-seropositive transplant patients during periods when intensified immunosuppression is required for treatment of acute or chronic rejection.




Douglas M Heuman, MD, FACP, FACG, AGAF, Chief of GI, Hepatology, and Nutrition at North Shore University Hospital/Long Island Jewish Medical Center; Professor, Department of Medicine, Hofstra North Shore-LIJ School of Medicine

Disclosure: Novartis Grant/research funds Other; Bayer Grant/research funds Other; Otsuka Grant/research funds None; Bristol Myers Squibb Grant/research funds Other; Scynexis None None; Salix Grant/research funds Other; MannKind 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.

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

Disclosure: Nothing to disclose.

Specialty Editors

Jeffrey D Band, MD, Professor of Medicine, Oakland University William Beaumont School of Medicine; Director, Division of Infectious Diseases and International Medicine, Corporate Epidemiologist, William Beaumont Hospital; Clinical Professor of Medicine, Wayne State University School of Medicine

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: Medscape Salary Employment

James L Achord, MD, Professor Emeritus, Department of Medicine, Division of Digestive Diseases, University of Mississippi School of Medicine

Disclosure: Nothing to disclose.

Alex J Mechaber, MD, FACP, Senior Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine

Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

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


  1. 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. Jun 2005;37(6):418-23. [View Abstract]
  2. Kim YS, Kim YH, Kim JS, Cheon JH, Ye BD, Jung SA, et al. Cytomegalovirus infection in patients with new onset ulcerative colitis: a prospective study. Hepatogastroenterology. Jun 2012;59(116):1098-101. [View Abstract]
  3. Onyeagocha C, Hossain MS, Kumar A, et al. Latent cytomegalovirus infection exacerbates experimental colitis. Am J Pathol. Nov 2009;175(5):2034-42. [View Abstract]
  4. Al-Zafiri R, Gologan A, Galiatsatos P, Szilagyi A. Cytomegalovirus complicating inflammatory bowel disease: a 10-year experience in a community-based, university-affiliated hospital. Gastroenterol Hepatol (N Y). Apr 2012;8(4):230-9. [View Abstract]
  5. Pillet S, Pozzetto B, Jarlot C, Paul S, Roblin X. Management of cytomegalovirus infection in inflammatory bowel diseases. Dig Liver Dis. Jul 2012;44(7):541-8. [View Abstract]
  6. Aukrust P, Moum B, Farstad IN, et al. Fatal cytomegalovirus (CMV) colitis in a patient receiving low dose prednisolone therapy. Scand J Infect Dis. 1991;23(4):495-9. [View Abstract]
  7. Baumgart DC, Targan SR, Dignass AU, et al. Prospective randomized open-label multicenter phase I/II dose escalation trial of visilizumab (HuM291) in severe steroid-refractory ulcerative colitis. Inflamm Bowel Dis. Aug 27 2009;epub ahead of print. [View Abstract]
  8. Buckner FS, Pomeroy C. Cytomegalovirus disease of the gastrointestinal tract in patients without AIDS. Clin Infect Dis. Oct 1993;17(4):644-56. [View Abstract]
  9. Dieterich DT, Kotler DP, Busch DF, et al. Ganciclovir treatment of cytomegalovirus colitis in AIDS: a randomized, double-blind, placebo-controlled multicenter study. J Infect Dis. - Busch DF;167(2):278-82. [View Abstract]
  10. Dieterich DT, Poles MA, Lew EA, et al. Concurrent use of ganciclovir and foscarnet to treat cytomegalovirus infection in AIDS patients. J Infect Dis. May 1993;167(5):1184-8. [View Abstract]
  11. Drew WL. Cytomegalovirus infection in patients with AIDS. J Infect Dis. Aug 1988;158(2):449-56. [View Abstract]
  12. Drew WL. Diagnosis of cytomegalovirus infection. Rev Infect Dis. Jul-Aug 1988;10 Suppl 3:S468-76. [View Abstract]
  13. Esforzado N, Poch E, Almirall J, et al. Cytomegalovirus colitis in chronic renal failure. Clin Nephrol. May 1993;39(5):275-8. [View Abstract]
  14. Falagas ME, Griffiths J, Prekezes J, Worthington M. Cytomegalovirus colitis mimicking colon carcinoma in an HIV-negative patient with chronic renal failure. Am J Gastroenterol. Jan 1996;91(1):168-9. [View Abstract]
  15. Frager DH, Frager JD, Wolf EL, et al. Cytomegalovirus colitis in acquired immune deficiency syndrome: radiologic spectrum. Gastrointest Radiol. 1986;11(3):241-6. [View Abstract]
  16. Galiatsatos P, Shrier I, Lamoureux E. Meta-analysis of outcome of cytomegalovirus colitis in immunocompetent hosts. Dig Dis Sci. Apr 2005;50(4):609-16. [View Abstract]
  17. Harbison MA, De Girolami PC, Jenkins RL, Hammer SM. Ganciclovir therapy of severe cytomegalovirus infections in solid-organ transplant recipients. Transplantation. Jul 1988;46(1):82-8. [View Abstract]
  18. Henderson JR. Use of ganciclovir in the treatment of cytomegalovirus infections. Br J Clin Pract. Jul 1989;43(7):233-7. [View Abstract]
  19. Kambham N, Vij R, Cartwright CA, Longacre T. Cytomegalovirus infection in steroid-refractory ulcerative colitis: a case-control study. Am J Surg Pathol. Mar 2004;28(3):365-73. [View Abstract]
  20. Kanda Y, Yamashita T, Mori T, et al. A randomized controlled trial of plasma real-time PCR and antigenemia assay for monitoring CMV infection after unrelated BMT. Bone Marrow Transplant. Dec 7 2009;epub ahead of print. [View Abstract]
  21. Korzets A, Zevin D, Ori Y, et al. Elevated serum alkaline phosphatase levels in a renal transplant patient precede colitis. Transpl Infect Dis. Sep 2006;8(3):157-60. [View Abstract]
  22. Loftus EV Jr, Alexander GL, Carpenter HA. Cytomegalovirus as an exacerbating factor in ulcerative colitis. J Clin Gastroenterol. Dec 1994;19(4):306-9. [View Abstract]
  23. Maiorana A, Torricelli P, Giusti F, Bellini N. Pseudoneoplastic appearance of cytomegalovirus-associated colitis in nonimmunocompromised patients: report of 2 cases. Clin Infect Dis. Sep 1 2003;37(5):e68-71. [View Abstract]
  24. McCune TR, Nylander WA, Van Buren DH, et al. Colonic screening prior to renal transplantation and its impact on post- transplant colonic complications. Clin Transplant. Apr 1992;6(2):91-6. [View Abstract]
  25. Orloff JJ, Fine MJ, Rihs JD. Acute cardiac tamponade due to cardiac actinomycosis. Chest. Mar 1988;93(3):661-3. [View Abstract]
  26. Orloff JJ, Saito R, Lasky S, Dave H. Toxic megacolon in cytomegalovirus colitis. Am J Gastroenterol. Jul 1989;84(7):794-7. [View Abstract]
  27. Rene E, Marche C, Chevalier T, et al. Cytomegalovirus colitis in patients with acquired immunodeficiency syndrome. Dig Dis Sci. Jun 1988;33(6):741-50. [View Abstract]
  28. San Juan R, Yebra M, Lumbreras C, et al. A new strategy of delayed long-term prophylaxis could prevent cytomegalovirus disease in (D+/R-) solid organ transplant recipients. Clin Transplant. Sep-Oct 2009;23(5):666-71. [View Abstract]
  29. Sommadossi JP, Bevan R, Ling T, et al. Clinical pharmacokinetics of ganciclovir in patients with normal and impaired renal function. Rev Infect Dis. Jul-Aug 1988;10 Suppl 3:S507-14. [View Abstract]
  30. Spiegel JS, Schwabe AD. Disseminated cytomegalovirus infection with gastrointestinal involvement. The role of altered immunity in the elderly. Am J Gastroenterol. Jan 1980;73(1):37-44. [View Abstract]
  31. Teixidor HS, Honig CL, Norsoph E, et al. Cytomegalovirus infection of the alimentary canal: radiologic findings with pathologic correlation. Radiology. May 1987;163(2):317-23. [View Abstract]
  32. Wada Y, Matsui T, Matake H, et al. Intractable ulcerative colitis caused by cytomegalovirus infection: a prospective study on prevalence, diagnosis, and treatment. Dis Colon Rectum. Oct 2003;46(10 Suppl):S59-65. [View Abstract]
  33. Whitley RJ, Jacobson MA, Friedberg DN, et al. Guidelines for the treatment of cytomegalovirus diseases in patients with AIDS in the era of potent antiretroviral therapy: recommendations of an international panel. International AIDS Society-USA. - Feinberg J. May 11 1998;158(9):957-69. [View Abstract]

Gross specimen of bowel showing ulceration secondary to cytomegalovirus colitis.

Giant cell with inclusion body characteristic of cytomegalovirus colitis.

Gross specimen of bowel showing ulceration secondary to cytomegalovirus colitis.

Giant cell with inclusion body characteristic of cytomegalovirus colitis.

Gross specimen of bowel showing ulceration secondary to cytomegalovirus colitis.

Giant cell with inclusion body characteristic of cytomegalovirus colitis.