Colon
Infectious colitis
CMV
Author: Nalini Bansal, M.D.
Editorial Board Member: Raul S. Gonzalez, M.D.
Topic Completed: 1 November 2017
Minor changes: 21 July 2021
Copyright: 2002-2021, PathologyOutlines.com, Inc.
PubMed Search: CMV colitis[TI] OR cytomegalovirus colitis[TI] colon
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2 | Board review style question #3 | Board review style answer #3 | Board review style question #4 | Board review style answer #4Cite this page: Bansal N. CMV. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/colonCMV.html. Accessed September 21st, 2021.
Definition / general
- Cytomegalovirus (CMV) is a double stranded DNA virus belonging to the herpesvirus group (World J Gastroenterol 2009;15:4327)
- Infection is usually seen in immunocompromised and debilitated patients, usually due to reactivation of latent infection
- In immunocompetent patients, disease is related to primary infection
- Infection in immunocompetent hosts is generally asymptomatic or may present as a mononucleosis syndrome
- Tissue invasive CMV results from the hematogenous spread of CMV
- Gastrointestinal (GI) CMV disease is the most common manifestation of tissue invasive CMV (Am J Transplant 2013;13:93)
Essential features
- Cytomegalovirus (CMV) is a double stranded DNA virus belonging to the herpesvirus group
- Infection is usually seen in immunocompromised and debilitated patients in setting of transplant, use of immunosuppressive drugs, AIDS
- Infection mainly occurs due to reactivation of latent infection
- Most common sites of involvement are esophagus and colon
- Gastrointestinal bleeding is most common clinical presentation
- Gold standard for diagnosis is histological diagnosis with immunohistochemistry (IHC)
- Computed tomography scan and barium enema are considered the best imaging modalities for diagnosing CMV colitis
- Microscopy shows cytomegalic cells with basophilic intranuclear inclusions, usually of endothelial / mesenchymal cells
- Treatment consists of induction and maintenance therapy with antiviral drugs, such as ganciclovir or valganciclovir
Terminology
- CMV infection: refers to presence of detectable CMV levels in the human body
- CMV disease: CMV disease relates to symptoms due to CMV
ICD coding
- B25.8: other cytomegaloviral diseases
Epidemiology
- Virus is prevalent in adults, with 50 - 80% of the general population possessing an antibody to CMV by age 35 (Dis Colon Rectum 2004;47:722)
- Seroprevalence is highest in developing countries throughout Africa and Asia (Rev Infect Dis 1990;12:S701)
- Seroprevelance also varies by race and ethnicity; infection seen at early age among non-Hispanic blacks (16.3 years) and Mexican Americans (17.5 years) compared with non-Hispanic whites (29.3 years) (BMC Infect Dis 2007;7:71)
- Infection can be acquired during birth, breast feeding, close contact, sexual contact, transfusion or with organ transplant (Scand J Gastroenterol 2010;45:1295)
Sites
- Most common sites of CMV related gastrointestinal involvement are the esophagus and colon
Pathophysiology
- Infection is usually seen in immunocompromised and debilitated patients, usually due to reactivation of latent infection; hematogenous spread of virus favors tissue invasive CMV infection
- CD4+ and CD8+ T cells play an important role in controlling viral replication
- CD4 cell counts of < 50 cells/µL in AIDS patients predispose to tissue invasive CMV disease (Arch Intern Med 1998;158:957)
Etiology
- CMV virus
Clinical features
- Gastrointestinal bleeding is the most common initial presentation of CMV colitis (Hepatogastroenterology 2012;59:2137)
- Other features, including diarrhea, fever and abdominal pain, are common presenting symptoms (Scand J Infect Dis 1998;30:559)
- Can mimic common colitides (Arch Pathol Lab Med 2016;140:854)
- Patients with extraocular CMV disease often have concurrent CMV retinitis; thus, any patient diagnosed with CMV gastrointestinal disease should have a formal ophthalmologic examination
- Classic mononucleosis can occur due to CMV in immunocompetent patients, and presents as protracted fevers and lassitude in the setting of absolute lymphocytosis and atypical lymphocytes (Am J Med Sci 1978;276:325)
Diagnosis
- Gold standard for CMV colitis is histological diagnosis
- Diagnosis based upon the following triad: clinical symptoms of gastrointestinal disease, visualization of characteristic lesions on endoscopy and intranuclear or cytoplasmic inclusions on pathology (AIDSinfo: Guidelines for Prevention and Treatment of Opportunistic Infections in HIV Infected Adults and Adolescents [Accessed 6 November 2017])
Laboratory
- Histology:
- Gold standard test
- Inclusions on histology with positive immunohistochemistry for CMV
- Serology:
- Detection of CMV IgM antibodies: indicates acute infection
- Fourfold increase in titer of CMV IgG specific antibodies 2 - 4 weeks apart indicates acute infection
- CMV DNA test: polymerase chain reaction (PCR) or hybrid capture is used to detect viral DNA in blood, plasma, leucocytes, tissue or stool
- Kandiel et al. propose that a CMV DNA cutoff level of 25,000 copies/mL in whole blood is a reasonable level for initiating antiviral treatment, with quantification by real time PCR (Am J Gastroenterol 2006;101:2857)
- CMV culture: time consuming (1 - 3 weeks) and has lower sensitivity than newer techniques (antigen testing, PCR)
Radiology description
- Computed tomography (CT) scan and barium enema are considered the best imaging modalities for diagnosing CMV colitis
- CT scan may reveal colonic wall thickening
- "Accordion sign" may be seen, defined as alternating edematous haustral folds separated by transverse mucosal ridges filled with oral contrast material
- "Target" and "double / fat halo" signs can also be seen
- Both these signs signify edema with surrounding hyperemia
- Barium enema may reveal stricture, mucosal irregularity and ulceration or thumbprinting (Arch Pathol Lab Med 2016;140:854)
Prognostic factors
- Despite aggressive clinical manifestations, the prognosis of CMV colitis is good if diagnosed and treated early
Case reports
- 65 year old immunocompetent man with acute colonic obstruction secondary to CMV induced colonic stricture (BMJ Case Rep 2013 Sep 10;2013)
Treatment
- Antiviral drugs: given as induction and maintenance therapy
- Induction therapy: ganciclovir or valganciclovir
- Intravenous ganciclovir is dosed as 5 mg/kg/dose every 12 hours or oral valganciclovir (900 mg twice daily) for 3 - 6 weeks
- Maintenance therapy: is required if there is concurrent retinitis or recurrent gastrointestinal disease after induction therapy has been discontinued
- Consists of valganciclovir, 900 mg given once daily (AIDSinfo: Guidelines for Prevention and Treatment of Opportunistic Infections in HIV Infected Adults and Adolescents [Accessed 6 November 2017])
Clinical images
Images hosted on other servers:
Diffuse inflammation
Ulcerating mass
Gross description
- Well demarcated ulcerations, ulceroinfiltrative changes and pseudomembrane formation (Hepatogastroenterology 2012;59:2137)
Gross images
Images hosted on other servers:
Ulceration and erythema
Ulceration secondary to CMV colitis
Terminal ileum
Caecum
Multiple, small punctate ulcers in the mucosa
Microscopic (histologic) description
- CMV infected cells are cytomegalic cells, typically two to fourfold larger than normal, containing basophilic intranuclear inclusion bodies (Cowdry bodies) surrounded by a clear halo, giving the appearance of an owl's eye
- Cells show a thickened nuclear membrane and smaller granular intracytoplasmic inclusions
- Many of these infected cells can be seen surrounding blood vessels, as the most commonly infected cells are endothelial cells and mesenchymal cells (World J Gastroenterol 2009;15:4327)
- Other features include architectural distortion with shortening of the crypts and glandular branching, cryptitis, crypt abscesses, basal lymphoplasmacytic cellular infiltrates and focal mucin depletion with reactive epithelial atypia, which can simulate inflammatory bowel disease (IBD) (Am Surg 2007;73:58)
- Submucosal vasculitis, thrombus of microvessels and necrosis may also be seen
Microscopic (histologic) images
Contributed by Nalini Bansal, M.D.
Cytomegalovirus inclusions in endothelial cells
Cytomegalovirus immunohistochemistry positive
Images hosted on other servers:
Cytomegalovirus inclusions
CMV inclusions - immunocompetent patient
Superficial ulceration
Enlarged nuclei containing basophilic inclusions
Giant cell with inclusion body
Crypt with multiple apoptotic cells
Mass-like lesion
Epithelial cytomegalic cells
CMV+ cells
Positive cells in ascending and sigmoid colon
Positive stains
- Immunohistochemistry for CMV
Negative stains
- Other viral marker immunohistochemistry, such as adenovirus
Molecular / cytogenetics description
- Polymerase chain reaction (PCR) DNA amplification
- Note: PCR DNA levels in the colon are not related to viremia levels measured in the blood
- Detection of viral mRNAs coding for the pp67 protein has been proposed for quantifying CMV viremia (Hum Pathol 2014;45:48)
Differential diagnosis
- Graft versus host disease: no viral inclusions
- Inflammatory bowel disease: no viral inclusions
- Ischemic colitis: no viral inclusions
Board review style question #1
What type of virus is CMV?
- dsDNA virus
- dsRNA virus
- ssDNA virus
- ssRNA virus
Board review style answer #1
Board review style question #2
What is the most common site for CMV induced GI infection?
- Colon
- Duodenum
- Ileum
- Stomach
Board review style answer #2
Board review style question #3
When does tissue invasive CMV disease usually occur?
- CD4 count is < 50 cells/µL
- CD4 count is > 50 cells/µL
- Patients are immunocompetent
- None of the above
Board review style answer #3
Board review style question #4
What is the most common clinical presentation of CMV GI disease?
- Abdominal pain
- Diarrhea
- Fever
- GI bleeding
Board review style answer #4
