Monday, September 14, 2015

Histologic Diagnosis of Cytomegalovirus Infection

Cytomegalovirus (CMV) is a double-stranded DNA virus that is a member of the Herpesviridae family. CMV is prevalent (90 percent) in high-risk groups (e.g. human immunodeficiency virus [HIV] patients and unborn babies whose mothers become infected with CMV during pregnancy).  Roughly 60 percent of the United States population has been exposed to cytomegalovirus.

The virus is transmitted through the respiratory tract, GI tract, parenterally, or sexually with the incubation period lasting approximately two weeks. CMV attacks non-keratinocytic cells, primarily endothelial cells and fibroblasts.

Signs and symptoms of CMV are not typically apparent, but the few clinical findings on physical examination include:
  •         Fever of unknown origin
  •         Pharyngitis
  •         Crackles in the lung fields
  •         Enlarged lymph nodes and spleen
  •         Mononucleosis syndrome symptoms 

Symptomatic CMV disease can affect the majority of organs in the body, resulting in pneumonia, hepatitis, encephalitis, myelitis, colitis, uveitis, chorioretinitis, adrenalitis, and neuropathy. In patients with HIV infection, cytomegalovirus affects the entire GI tract and the eyes (resulting in chorioretinitis). Additional manifestations of CMV may include Guillain-Barré syndrome, meningoencephalitis, pericarditis, myocarditis, thrombocytopenia, and hemolytic anemia.

Mucutaneous manifestations of CMV involve:
  •         Perianal ulcers: usually secondary to CMV proctocolitis, but are often co-infected with herpes simplex virus (HSV)
  •         Palpable purpuric papules: may be a manifestation of vasculitis, but in neonates the papules represent extramedullary hematopoiesis
  •         Nonspecific ulcers
  •         Unusual hyperpigmentation (“suntan”) associated with adrenal infection

Laboratory diagnosis of CMV includes:
  •         Direct visualization microscopically of virally infected cells
  •         Viral culture of human fibroblasts
  •          Direct immunofluorescence
  •          DNA in situ hydridization
  •          Immunoperoxidase staining
  •          Polymerase chain reaction (PCR)
  •          Nota bene:  Demonstration of the virus is not synonymous with the cause of the lesion, but is evidence that the patient has a viral infection.

Most hospital labs stock antibody directed to CMV just as they do with HSV for direct immunofluroscopy (IF) of CMV. A smear of the ulcer or tissue biopsy on a slide is taken to the lab and IF is performed on the smear. This process can provide a rapid diagnosis of cytomegalovirus.


References
Cockerell, C. (2015). The Role of the Dermatopathologist in the Diagnosis of Infectious Diseases. Cytomegalovirus. [PowerPoint Presentation]

Medscape (2015). Cytomegalovirus. Retrieved September 10, 2015, from http://emedicine.medscape.com/article/215702-overview.


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