Cytomegalovirus Colitis

Updated: Jan 08, 2017
  • Author: Douglas M Heuman, MD, FACP, FACG, AGAF; Chief Editor: BS Anand, MD  more...
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Overview

Background

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.

Gross specimen of bowel showing ulceration seconda Gross specimen of bowel showing ulceration secondary to cytomegalovirus colitis.
Giant cell with inclusion body characteristic of c 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 the 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).

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Pathophysiology

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 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.

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Etiology

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
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Epidemiology

United States data

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]

International data

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]

Race-, sex-, and age-related demographics

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]

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Prognosis

Morbidity/mortality

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

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 affected colon is indicated to avert perforation and sepsis.
  • Perforation
  • Sepsis
  • Peritonitis
  • Death
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