Infectious Disease Book

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CytomegalovirusAka: CMV-Induced Mononucleosis, CMV

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  1. See Also
    1. CMV Chorioretinitis
  2. 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
    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
  3. Pathophysiology
    1. Human Herpes Virus (Herpesviridae)
    2. Pathogenesis
      1. CMV remains latent after initial infection
      2. CMV reactivates in immunocompromised patients
    3. 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
  4. Risk factors for infection
    1. Pregnant day care workers (see TORCH Virus)
    2. Organ transplant recipients
    3. Immunocompromised patients (e.g. HIV Infection)
  5. Symptoms and Signs
    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. Intrauterine adverse effects to fetus
      1. CMV is a TORCH Virus
      2. Risk of Intrauterine Growth Retardation
  6. 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
      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. Histology of tissue biopsy (CMV organ involvement)
      1. Owls-eye inclusion body (highly specific for CMV)
    5. CMV-Induced false positive tests
      1. Rheumatoid Factor
      2. Direct Coombs
      3. Cryoglobulinemia
      4. Speckled pattern of Antinuclear Antibody test
  7. Differential Diagnosis
    1. Mononucleosis (nearly identical presentation)
    2. See Mononucleosis Differential Diagnosis
  8. Diagnosis
    1. See Mononucleosis Diagnostic Approach
  9. Complications in Immunocompromised patients
    1. CMV Chorioretinitis (occurs in 15-20% of HIV patients)
    2. Gastrointestinal tract infection (in 5-10% of HIV)
      1. Hepatitis
      2. Pancreatitis
      3. 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
  10. 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
  11. Management: Immunocompromised patients (especially HIV)
    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
        1. Cidofovir 5 mg/kg IV each week for 2 weeks
      2. Chronic maintenance (prevents relapse in 4-8 weeks)
        1. Cidofovir 5 mg/kg every other week
  12. References
    1. de Jong (1998) Antiviral Res 39:141
    2. Taylor (2003) Am Fam Physician 67(3):519
  13. Resources
    1. CDC National Center for Infectious Diseases
      1. http://www.cdc.gov/ncidod/diseases/cmv.htm

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