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)
  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

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. Intrauterine adverse effects to fetus
    1. CMV is a TORCH Virus
    2. Risk of Intrauterine Growth Retardation
  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 with suspected CMV infection

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. 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

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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Related Studies

Ontology: Cytomegalovirus Infections (C0010823)

Definition (MEDLINEPLUS)

Cytomegalovirus (CMV) is a virus found around the world. It is related to the viruses that cause chickenpox and infectious mononucleosis (mono). Between 50 percent and 80 percent of adults in the United States have had a CMV infection by age 40. Once CMV is in a person's body, it stays there for life.

CMV is spread through close contact with body fluids. Most people with CMV don't get sick and don't know that they've been infected. But infection with the virus can be serious in babies and people with weak immune systems. If a woman gets CMV when she is pregnant, she can pass it on to her baby. Usually the babies do not have health problems. But some babies can develop lifelong disabilities.

A blood test can tell whether a person has ever been infected with CMV. Most people with CMV don't need treatment. If you have a weakened immune system, your doctor may prescribe antiviral medicine. Good hygiene, including proper hand washing, may help prevent infections.

Centers for Disease Control and Prevention
Definition (NCI) A herpesvirus infection caused by Cytomegalovirus. Healthy individuals generally do not produce symptoms. However, the infection may be life-threatening in affected immunocompromised patients. The virus may cause retinitis, esophagitis, gastritis, and colitis. Morphologically, it is characterized by the presence of intranuclear inclusion bodies.
Definition (MSH) Infection with CYTOMEGALOVIRUS, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults.
Concepts Disease or Syndrome (T047)
MSH D003586
ICD9 078.5
ICD10 B25 , B25.9
SnomedCT 266203007, 243578002, 186699001, 186695007, 187456009, 154371005, 28944009
English Cytomegalovirus, Cytomegalic Inclusion Disease, Cytomegalic Inclusion Diseases, Cytomegalovirus Infection, Cytomegalovirus Infections, Diseases, Cytomegalic Inclusion, Inclusion Disease, Inclusion Disease, Cytomegalic, Inclusion Diseases, Inclusion Diseases, Cytomegalic, Infections, Cytomegalovirus, Salivary Gland Virus Disease, Disease, Cytomegalic Inclusion, Infection, Cytomegalovirus, CMV - Cytomegalovirus infec, Cytomegaloviral dis,unspec, Cytomegaloviral disease, unspecified, [X]Cytomegaloviral dis,unspec, [X]Cytomegaloviral disease, unspecified, Cytomegaloviral Infection, CYTOMEGALUS VIRUS INFECTION, CYTOMEGALIC INCLUSION DIS, CYTOMEGALOVIRUS INFECT, INFECT CYTOMEGALOVIRUS, INCLUSION DIS, SALIVARY GLAND VIRUS DIS, cytomegalovirus disease, cytomegalovirus disease (diagnosis), CMV infection, Cytomegaloviral infections, Cytomegalus virus infection, Cytomegalovirus Infections [Disease/Finding], cmv cytomegalovirus infection, cytomegalovirus infections, cytomegalovirus infection, cmv infection, cytomegaloviral infections, cytomegaloviral infection, cmv infections, cytomegalic inclusion disease, CMV Infections, CMV, Cytomagalovirus infection, [X]Cytomegaloviral disease, unspecified (disorder), Cytomegalovirus infections, Cytomegalic inclusion disease, Salivary gland virus disease, CMV - Cytomegalovirus infection, Cytomegalovirus infection, Cytomegalovirus infection (disorder), Disease due to Cytomegalovirus, inclusion disease, cytomegaloviral disease, disease (or disorder); inclusion disease (cytomegaloviral), disease (or disorder); inclusion disease, salivary gland, inclusion disease; salivary gland, salivary gland; inclusion disease, Cytomegalovirus infection, NOS, Cytomegaloviral disease, cytomegalovirus
Italian Infezione da citomegalovirus, Malattia citomegalica, Infezione da Cytomegalovirus, Infezioni da Cytomegalovirus
Dutch cytomegalie-inclusieziekte, CMV-infectie, aandoening; inclusion disease (cytomegalie), aandoening; inclusion disease, speekselklier, inclusion disease; speekselklier, speekselklier; aandoening, insluitlichaampje, Ziekten door cytomegalovirus, niet gespecificeerd, cytomegalovirusinfecties, cytomegalovirusinfectie, Cytomegalovirusziekte, Cytomegalo-inclusieziekte, Cytomegalovirus-infectie, Cytomegalovirus-infecties, Inclusieziekte, Infectie, cytomegalovirus-, Infecties, cytomegalovirus-, Speekselklierziekte, virale, Virusinfectie, cytomegalo-, Virusinfecties, cytomegalo-
French Infection par CMV, Infection à cytomegalovirus, Maladie des inclusions cytomégaliques, INFECTION A CMV, Infection à Cytomégalovirus, Infections à Cytomégalovirus, Infections à cytomégalovirus, Infections à CMV
German Einschlusskoerperchenkrankheit, Cytomegalus-Virusinfektion, CMV Infektion, ZYTOMEGALOVIRUSINFEKTION, Zytomegalie, nicht naeher bezeichnet, Zytomegalievirus-Infektionen, Zytomegalievirus-Infektion, Zytomegalievirusinfektionen, Zytomegalie, Einschlußkörperchenkrankheit, Speicheldrüsenviruskrankheit
Portuguese Infecção por CMV, Doença de inclusão citomegálica, INFECCAO POR CITOMEGALOVIRUS, Infecção a citomegalovírus, Infecções a citomegalovírus, Doença de Inclusão Citomegálica, Doença de Inclusão, Doença Viral das Glândulas Salivares, Infecções por Citomegalovirus
Spanish Infección por CMV, Enfermedad citomegálica de inclusión, [X]enfermedad por citomegalovirus, no especificada (trastorno), [X]enfermedad por citomegalovirus, no especificada, enfermedad por inclusión citomegálica, enfermedad virósica de las glándulas salivales, infección por CMV, infección por citomegalovirus (trastorno), infección por citomegalovirus, Infecciones por citomegalovirus, Infección por citomegalovirus, Enfermedad de Inclusión Citomegálica, Enfermedad de Inclusión, Enfermedad Viral de la Glándula Salival, Infecciones por Citomegalovirus
Swedish Cytomegalovirusinfektioner
Japanese ｻｲﾄﾒｶﾞﾛｳｲﾙｽｶﾝｾﾝ, ｷｮｻｲﾎﾞｳﾌｳﾆｭｳﾀｲﾋﾞｮｳ, サイトメガロウイルス感染症, Cytomegalovirus感染症, 唾液腺ウイルス疾患, 封入体病, 封入病, 巨細胞封入体病, 巨細胞性封入体病, サイトメガロウイルス感染, 巨細胞封入体症
Czech cytomegalie inkluzní, Infekce způsobené cytomegaloviry, Infekce způsobená cytomegaloviry, Cytomegalovirová infekce, Cytomegalovirová inkluzní nemoc, Infekce cytomegalovirem, infekce CMV, cytomegalovirové infekce, Cytomegalovirus - infekce, cytomegalovirová infekce, infekce cytomegalovirem
Finnish Sytomegalovirusinfektiot
Russian INKLIUZIONNAIA BOLEZN', TSITOMEGALOVIRUSNYE INFEKTSII, SLIUNNYKH ZHELEZ VIRUSNAIA BOLEZN', TSITOMEGALIIA, TSITOMEGALIIA LOKALIZOVANNAIA, ИНКЛЮЗИОННАЯ БОЛЕЗНЬ, СЛЮННЫХ ЖЕЛЕЗ ВИРУСНАЯ БОЛЕЗНЬ, ЦИТОМЕГАЛИЯ, ЦИТОМЕГАЛИЯ ЛОКАЛИЗОВАННАЯ, ЦИТОМЕГАЛОВИРУСНЫЕ ИНФЕКЦИИ
Korean 상세불명의 거대세포바이러스병, 거대세포바이러스병
Croatian CITOMEGALOVIRUSNE INFEKCIJE
Polish Cytomegalia, Zakażenia cytomegaliawirusowe
Hungarian Cytomegaliás inclusiós betegség, Cytomegalovírus okozta fertőzések, Cytomegalovirus fertőzés, CMV fertőzés
Norwegian Cytomegalovirussykdom, Cytomegalovirusinfeksjoner
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Cytomegalovirus (C0010825)

Definition (NCI) A genus of the family herpesviridae, subfamily betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions.
Definition (NCI_NCI-GLOSS) A virus that may be carried in an inactive state for life by healthy individuals. It is a cause of severe pneumonia in people with a suppressed immune system, such as those undergoing bone marrow transplantation or those with leukemia or lymphoma.
Definition (NCI_CDISC) Any viral organism that can be assigned to the genus Cytomegalovirus.
Definition (MSH) A genus of the family HERPESVIRIDAE, subfamily BETAHERPESVIRINAE, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS.
Definition (CSP) widely occurring intracellular herpesvirus characterized by narrow host specificity and slow reproduction (latency); causes a variety of pathologies in mammals, including AIDS related oculopathy in humans.
Concepts Virus (T005)
MSH D003587
SnomedCT 407444007, 243577007, 243578002, 16609001, 243579005
LNC LP14255-1, MTHU033986, LA20066-9
English Cytomegalovirus, Salivary Gland Viruses, Virus, Salivary Gland, Viruses, Salivary Gland, Salivary Gland Virus, salivary gland virus, CMV - Cytomegalovirus, Cytomegalovirus group virus, Genus Cytomegalovirus, cytomegalovirus group, salivary gland viruses, cmv cytomegalovirus, cytomegalovirus (CMV), Cytomegalovirus group virus (organism), Cytomegalovirus group, Cytomegalovirus (living organism) (organism), Cytomegaloviruses, CMV, CYTOMEGALOVIRUS, CMV, CYTOMEGALOVIRUS, cytomegalovirus, Salivary gland virus, Genus Cytomegalovirus (organism), Cytomegalovirus group, NOS, Cytomegalovirus, NOS, Salivary gland virus, NOS, Cytomegalovirus (living organism) [Ambiguous]
French Cytomegalovirus, CMV, Virus des glandes salivaires
Swedish Cytomegalovirus
Spanish género Cytomegalovirus, Cytomegalovirus, citomegalovirus, citomegalovirus (organismo vivo), virus de la glándula salival, virus del grupo de CMV, grupo citomegalovirus, grupo Cytomegalovirus, virus del grupo de citomegalovirus, virus del grupo de citomegalovirus (organismo), CMV, citomegalovirus (concepto no activo), virus de las glándulas salivales, género Cytomegalovirus (organismo), Citomegalovirus, Virus de la Glándula Salival
Czech Cytomegalovirus, CMV infekce
Finnish Sytomegalovirus
Italian Virus della ghiandola salivare, Cytomegalovirus
Russian GERPESVIRUS 5 (BETA) CHELOVEKA, TSITOMEGALOVIRUS, GERPESVIRUS 5 CHELOVEKA, SLIUNNYKH ZHELEZ BOLEZNI VIRUSY, ГЕРПЕСВИРУС 5 (БЕТА) ЧЕЛОВЕКА, ГЕРПЕСВИРУС 5 ЧЕЛОВЕКА, СЛЮННЫХ ЖЕЛЕЗ БОЛЕЗНИ ВИРУСЫ, ЦИТОМЕГАЛОВИРУС
Japanese ヒトヘルペスウイルス5(ベータ), ヒトヘルペスウイルス5型, ヒトヘルペスウイルス5, 唾液腺ウイルス, サイトメガロウイルス, ヘルペスウイルス5型-ヒト, ｻｲﾄﾒｶﾞﾛｳｲﾙｽ
Portuguese CMV, Cytomegalovirus, Citomegalovirus, Vírus das Glândulas Salivares
German CMV, Zytomegalievirus, Speicheldrüsenviren
Dutch CMV, Cytomegalievirus, Cytomegalovirus, Virus, Cytomegalo-, Speekselkliervirus
Croatian CITOMEGALOVIRUS
Polish Wirusy ślinianek, CMV, Cytomegalowirusy, Wirus cytomegalii, Cytomegalowirus
Hungarian CMV
Derived from the NIH UMLS (Unified Medical Language System)

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