Herpesvirus Infections

Question 1

general characteristics of herpesviruses

Answer 1

large, dsDNA viruses with 4 structural features:
1. outer envelope
2. tegument
3. nucleocapsid
4. inner DNA core
Surface and integument proteins mediate cell entry and viral replication.

Question 2

alpha subfamily

Answer 2

includes HSV1+2, VZV. (Alpha causes ulcers)

Question 3

beta subfamily

Answer 3

includes CMV, HHV6, HHV7.

Question 4

gamma subfamily

Answer 4

includes EBV, HHV8. (Gamma causes cancer)

Question 5

tzanck smear

Answer 5

immunohistochemistry test for herpesviruses, especially HSV1+2, usually shows multinucleated giant cells

Question 6

HSV1 primary infection

Answer 6

primary infection: usually in childhood, mostly asymptomatic, incubation 2-12 days. Children: gingivostomatitis; adults: exudative pharyngitis.

Resolves in 10-14 days, establishes latency in the sensory ganglia, usually trigeminal nerve (cranial nerve 5 - face sensation)

HSV1 can also cause Herpetic whitlow, herpes gladitorum, and genital HSV1 infections.

Question 7

herpetic whitlow

Answer 7

caused by HSV1 - usually looks like a bacterial infection on the finger but is actually a herpetic lesion. Often spread by primary oral lesions and higher prevalence in dentists/pathologists, etc who have come into contact with a lesion.

Question 8

herpes gladitorum

Answer 8

HSV1 infection from wrestling mat/rugby players. Involves face, neck, chest, arms.

Question 9

recurrent HSV1 infections

Answer 9

due to reactivation - clinical episodes of productive viral replication with spread from neural cell to axon and then skin.
Prodromal symptoms are frequent (tingling).
Provoked by stress, fever, sun, trauma, decreased immunity, steroids.
Causes cold sores.

Question 10

HSV2 primary infection

Answer 10

painful grouped vesicles on erythematous base - progress to pustules and then ulcers. Usually infecting the external genitalia, cervix, urethra, anus, oral/skin, and rarely the meninges.

• Incubation 2-12 days.
• Systemic sx may occur in first episodes.
• viral shedding usually 11 days, heals in 2-4 weeks.

Question 11

HSV2 recurrence

Answer 11

88% will recur within 1 year. Less severe and less frequent over time.

• immunocomp have more recurrences and may be severe.
• treatment early (during prodrome) may prevent outbreaks

Question 12

HSV1+2 treatment

Answer 12

acyclovir, or famciclovir, or valacyclovir

-suppressive therapy usually reserved for immunocompromised

Question 13

herpes encephalitis

Answer 13

Due to HSV1 reactivation in the trigeminal ganglion- virus extends into temporal lobe.
Symptoms: HA, fever, behavioral changes, seizures.
CSF: shows mixed pleocytosis (increased cell count) with increased protein and RBCs in the CSF. RBCS***** important!
DX: HSV PCR of CSF or brain bx
RX: IV acyclovir
mortality 20% despite treatment

Question 14

other HSV complications

Answer 14

neonatal herpes - meningoencephalitis, disseminated or local infection in baby.

ocular herpes - keratitis or retinitis

reactivation in immunocompromised - can cause esophagitis or organ involvement

eczema herpeticum - HSV occurs alongside active skin disease (atopic dermatitis, eczema)

Question 15

primary varicella (VZV)

Answer 15

• chicken pox in children, more serious in adults
• disseminated disease in immunocompromised
• transmission: respiratory or contact with lesions
• incubation: 10-14 days
• prodrome: 1-2 days of fever, HA, malaise
• rash: begins on trunk, occurs in crops due to cyclic viremia; lesions progress: vesicle -> pustule -> crusted ulcer
• rash is pruritic and contagious until all lesions crust over

Question 16

VZV reactivation

Answer 16

can cause shingles (herpes zoster) usually in dermatomes, or disseminated zoster in immunocompromised

Question 17

VZV primary infection treatment

Answer 17

Neonates: VZIG and acyclovir
Age 2-12: No Rx necessary.
Adolescents/adults: acyclovir 800 mg QID x5 days
Pregnancy: acyclovir (IV)

Question 18

herpes zoster (shingles)

Answer 18

• reactivation of latent varicella from a sensory ganglion
• causes painful dysthesia followed by dermatomal vesicular rash, usually in thoracic and lumbar dermatomes
• pain and burning

Treatment: famciclovir or valacyclovir within 3 days of onset. Also pain control/steroids if >50 years.

Prevention: Shingrix, series of 2 injections, 2nd one 2-6 months after 1st

Question 19

EBV primary infection

Answer 19

ubiquitous, most infections subclinical.

• Transmission: oropharynx, primary spread from intimate contact with asymptomatic shedder.
• Virus replicates in oropharyngeal epithelial cells and local susceptible B cells - establishes latency
• Incubation: 30-50 days

Clinical manifestations of MONO: (usually in teens)
Symptoms: malaise, fatigue, sore throat, fever, pharyngitis with palatal petechiae, adenopathy, splenomegaly, hepatomegaly
-extreme tiredness lasts 2-3 weeks.

Labs: atypical lymphocytosis (>10% T CELLS!, T cells have weird shape)
Positive heterophile Ab test.
IgM VCA and EA seen in acute disease.

Treatment: REST, no contact sports, steroids if airway restricted

Question 20

CMV primary infection

Answer 20

mimics EBV mononucleosis. Healthy young adults will have fever, malaise, adenopathy, splenomegaly. Atypical lymphocytosis but negative heterophile ab test. No specific Rx in healthy host.

Question 21

congenital CMV

Answer 21

cytomegalic inclusion disease, caused by primary infection in mother - TORCH syndrome with jaundice, hepatomeg, rash, microcephaly, cerebral calcification, chorioretinitis, seizures.

Question 22

perinatal CMV

Answer 22

due to acquisition at birth or from breast feeding, usually mild or no symptoms but may shed virus in urine/feces for months

Question 23

CMV opportunitic infections

Answer 23

immunosuppressed patients. Reactivation or primary infection.
highest risk: 1-4 months post transplant.
Clinical: fever, leukopenia, direct organ involvement

Question 24

CMV dx and treatment

Answer 24

DX: serology CMV IgM = acute; culture of blood, urine or tissue; quantitative CMV PCR of blood - may allow prediction of reactivation in transplant patients

histopathology: Owl’s eye inclusions

Treatment: ganciclovir IV, valganciclovir oral

Question 25

HHV6

Answer 25

two variants: A and B. Seroprevalence >80% by age 2.
Transmission: saliva, urine, blood, tissue, genital secretions.

• Causes exanthem subitum (roseola) or febrile syndrome without rash in infants.
• Can cause mono-like illness in adults.

Question 26

exanthem subitum (Roseola)

Answer 26

Roseola infantum. Due to HHV6B infection - “Sixth disease”
Incubation: 5-10 days
Acute onset: high fever
Defervescence (decrease fever) and maculopapular rash.
Resolves in 1-2 days. Rarely causes neurologic symptoms - febrile seizures or encephalitis.

Question 27

HHV7

Answer 27

acquired during childhood, transmission via saliva. Similar to HHV6 infection. Exanthem subitum, fver, seizures/encephalitis, reactivation in bone marrow transplant/solid organ transplant patients.

Question 28

HHV8

Answer 28

Kaposi sarcoma associated herpesvirus. Causes vascular multicentric tumor in HIV patients.
Transmission: sexual and likely saliva

Can also cause:

1. primary effusion lymphopenia (PEL) - rare lymphoma seen in HIV involving body cavities
2. multicentric castleman’s disease - rare lymphoproliferative disease - fever, hepato/splenomegaly, adenopathy