Cytomegalovirus

Aka: Cytomegalovirus, CMV-Induced Mononucleosis, CMV

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II. Epidemiology

  1. General Population
    1. Prior exposure in 40-100% of general population
    2. Many cases occur in childhood and adolescence
    3. May account for 2% of febrile adult cases
      1. Wreghitt (2003) Clin Infect Dis 37:1603-6 [PubMed]
  2. HIV patients
    1. Infects 75-100% of HIV positive patients
    2. Active CMV disease occurs in 20% with CD4 Count <100
    3. CMV disease rarely occurs at CD4 Count > 50 cells

III. Pathophysiology

  1. Human Herpes Virus (Herpesviridae)
    1. Multinucleated giant cells
    2. Intranuclear inclusion bodies
  2. Cytomegalovirus is named for host cell swelling that occurs with infection
  3. Pathogenesis
    1. CMV remains latent after initial infection
    2. CMV reactivates in Immunocompromised patients
  4. Infectivity
    1. Spread by close contact with body fluids
    2. Passed by Saliva, urine, blood, semen, Breast Milk
    3. Also passed by organ tissue transplants

IV. Risk Factors

  1. Pregnant day care workers (see TORCH Virus)
  2. Organ transplant recipients
  3. Immunocompromised patients (e.g. HIV Infection)

V. Findings

  1. Asymptomatic in most immunocompetent patients
  2. CMV-Induced Mononucleosis
    1. Identical to EBV-Induced Mononucleosis
    2. Accounts for up to 7% of Mononucleosis cases
    3. Classic Ampicillin rash also occurs with CMV
  3. Congenital CMV
    1. Intrauterine adverse effects to fetus
    2. CMV is a TORCH Virus and is the most common viral cause of congenital Intellectual Disability
    3. Risk of Intrauterine Growth Retardation, Microcephaly, Deafness and Seizures
  4. CMV Esophagitis or colitis (HIV/AIDS, organ transplant)
    1. Odynophagia
    2. Abdominal Pain
    3. Diarrhea
  5. CMV Retinitis (HIV/AIDS)
    1. Dilated Eye Exam recommended in HIV/AIDS (esp. CD4 Count <100 cells/ml) with suspected CMV infection
    2. Bone Marrow Transplant patients do not typically develop CMV Retinitis
  6. CMV Pneumonitis
    1. Unique to Bone Marrow Transplant patients, and associated with a high mortality
    2. AIDS patients do not typically develop CMV Pneumonitis

VI. Labs

  1. Complete Blood Count
    1. CMV-Induced Mononucleosis changes
      1. Lymphocytes increased >50%
      2. Atypical lymphocytes 10% of total Lymphocytes
    2. Uncommon findings
      1. Anemia
      2. Thrombocytopenia
  2. Liver Function Test abnormalities (in acute infection)
    1. Most common clinical factor to distinguish CMV
      1. Abnormal in 72% of cases
      2. Wreghitt (2003) Clin Infect Dis 37:1603-6 [PubMed]
    2. Aspartate transaminase increased less than 5x normal
    3. Alanine Transaminase increased less than 5x normal
  3. Serology
    1. CMV IgM titer
      1. Best diagnostic test for CMV-Induced Mononucleosis
      2. Indicated if Heterophil Antibody Test negative
    2. CMV PCR
      1. Indications
        1. Immunocompromised patients
        2. Suspected CMV Encephalitis or polyradiculopathy
      2. Not useful in acute infection
        1. Positive test may be transient reactivation
  4. Blood Culture of Buffy Coat
    1. Buffy coat is the layer of White Blood Cells formed in centrifuged blood
    2. Buffy coat culture is of concentrated white cells and higher yield for CMV, which infects WBCs
  5. Histology of tissue biopsy (CMV organ involvement)
    1. Owls-eye inclusion body (highly specific for CMV)
  6. CMV-Induced False Positive tests
    1. Rheumatoid Factor
    2. Direct Coombs
    3. Cryoglobulinemia
    4. Speckled pattern of Antinuclear Antibody test

VII. Differential Diagnosis

  1. Mononucleosis (nearly identical presentation)
  2. See Mononucleosis Differential Diagnosis

VIII. Diagnosis

  1. See Mononucleosis Diagnostic Approach

IX. Complications in Immunocompromised patients

  1. CMV Chorioretinitis (occurs in 15-20% of HIV patients)
  2. Gastrointestinal Tract infection (in 5-10% of HIV; also in transplant patients)
    1. Esophagitis
    2. Hepatitis
    3. Pancreatitis
    4. Enteritis or Colitis
  3. Less common or rare effects
    1. Guillain-Barre Syndrome
    2. Neurologic involvement
      1. Encephalitis
      2. Peripheral Neuropathy
    3. Interstitial Pneumonia
    4. Myocarditis
    5. Epididymitis
    6. Skin changes
      1. Nonspecific rash
      2. Perifollicular papulopustules
      3. Vesiculobullous lesions

X. Management: General

  1. No school or work restrictions in acute infection
    1. Children may continue to attend school or daycare
    2. Healthcare workers may continue to work

XI. Management: Immunocompromised patients (especially HIV, transplant patients)

  1. Highly Active Antiretroviral Therapy (HAART) in HIV
    1. Critical to prevent CMV organ involvement
    2. Risk in HIV highest when CD4 Count <50/mm3
  2. Indications for Viral DNA Polymerase inhibitors
    1. CMV Retinitis (Urgent therapy)
    2. Clinically Significant colitis or other end-organ
    3. Treatment of asymptomatic CMV not indicated
  3. Preparations
    1. Ganciclovir
      1. Granulocytopenia and Anemia risk (25%)
    2. Foscarnet (Foscavir)
      1. Nephrotoxicity (33%)
      2. Neurotoxicity
      3. Electrolyte disturbance (Hypokalemia, Hypocalcemia)
    3. Cidofovir (Vistide)
      1. Nephrotoxicity
      2. Neutropenia
      3. Alopecia
  4. Efficacy
    1. CMV Retinitis responds to 14-21 day in 75-90% cases
    2. Patients failing one drug should move to the other
  5. Dosing
    1. Acute (until CMV PCR undetectable, clinically resolved and at least 3 week course)
      1. Ganciclovir 5 mg/kg IV every 12 hours (preferred) for 3-6 weeks OR
      2. Foscarnet 90 mg/kg IV every 12 hours for 3-6 weeks OR
      3. Cidofovir 5 mg/kg IV weeky for 3-6 weeks
    2. Secondary Prophylaxis (Follows acute management if high risk of relapse)
      1. Valganaciclovir 900 mg orally every 12-24 hours for 1-3 months
    3. References
      1. (2015) Sanford Guide, accessed in IOS app 4/24/2016

XII. Resources

  1. CDC National Center for Infectious Diseases
    1. http://www.cdc.gov/ncidod/diseases/cmv.htm

XIII. References

  1. de Jong (1998) Antiviral Res 39:141-62 [PubMed]
  2. Taylor (2003) Am Fam Physician 67(3):519-26 [PubMed]

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