1/17/2021 Herpes simplex virus infections - AMBOSS

REGISTER / LOG IN

Written and peer-reviewed by physicians—but use at your own risk. Read our
disclaimer.

AMBOSS

Trusted medical answers—in

seconds.
Get access to 1,000+ medical articles
with instant search
and clinical tools.

TRY FREE FOR 5 DAYS

Herpes simplex virus infections Last updated: August 10, 2020

Summary

Herpes simplex virus infections may be caused by two virus genotypes:

herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2). Worldwide
seroprevalence is high, with antibodies detectable in over 90% of the population. Of these
cases, approx. 60% are caused by HSV-1. The most common infections are labial and
genital herpes, which present with painful ulcerations. Two further conditions, seen
especially in children, are herpetic gingivostomatitis and herpetic whitlow. While
herpetic gingivostomatitis is characterized by painful lesions of the oral and pharyngeal
mucosa, herpetic whitlow causes blisters on the ngers with pronounced regional
lymphadenopathy. In individuals with underlying dermatological conditions, infection with
HSV can cause eczema herpeticum, resulting in painful erosions spread diffusely over the

https://www.amboss.com/us/knowledge/Herpes_simplex_virus_infections 1/10
1/17/2021 Herpes simplex virus infections - AMBOSS

head and upper body. However, the majority of primary infections remain asymptomatic,
REGISTER / LOG IN
while recurrent infections present with the typical manifestations. The diagnosis of HSV
infections is usually con rmed through viral cultures, but may also be based on detection of
HSV DNA in PCR, or multinucleated giant cells in Tzanck smears. Treatment consists mainly
of topical or oral acyclovir; IV administration may be needed in critical cases, such as HSV
infection in immunocompromised patients.

General information
Prevalence: More than 90% of the world's population over the age of 40 carries HSV.

Types
Herpes simplex virus type 1 (HSV-1), human herpes virus type 1 (HHV-1)

Herpes simplex virus type 2 (HSV-2), human herpes virus type 2 (HHV-2)

Transmission

Direct contact with mucosal tissue or secretions of another infected person

Infection with HSV-1 usually is acquired in childhood via saliva.

HSV-2 is mostly spread through genital contact and should, therefore, raise suspicion for
sexual abuse if found in children.

Perinatal transmission (e.g., during childbirth if the mother is symptomatic) is more

common for HSV-2.

Type of infection

Primary infection

Mostly asymptomatic (up to 80% of cases, but virus is still shed)

If symptomatic, the infection is often sudden and severe with systemic symptoms (e.g.,
fever, malaise, myalgias, and headaches)[1]

Reactivation of infection

Frequency and severity vary individually; symptoms are usually less severe than in
primary infection.

https://www.amboss.com/us/knowledge/Herpes_simplex_virus_infections 2/10
1/17/2021 Herpes simplex virus infections - AMBOSS

Often at the same site as primary infection

REGISTER / LOG IN

Pathophysiology
Inoculation: The virus enters the body through mucosal surfaces or small dermal lesions.

Neurovirulence: The virus invades, spreads, and replicates in nerve cells.

Latency: After primary infection, the virus remains dormant in the ganglion neurons.

Trigeminal ganglion: HSV-1

Sacral ganglion: HSV-2

Reactivation: triggered by various factors (e.g., immunode ciency, stress, trauma) → clinical
manifestations

Dissemination: infection spreads to unusual sites (e.g., lungs, gastrointestinal tract, eyes)

May occur in pregnant patients or patients with severe immunode ciency (e.g.,
malnutrition, recipients of organ transplants, patients with AIDS)

Labial herpes (herpes labialis)

Pathogen: mostly HSV-1 (HSV-2 in 10–20% of cases)

Most common recurrent HSV-1 infection in adults

Clinical features
Prodromal symptoms (∼ 24 hours): pain, tingling, burning

Recurring, erythematous vesicles that turn into painful ulcerations, also known as
cold sores; (primarily affecting the oral mucosa and lip borders)

Differential diagnoses

Shingles (Herpes zoster)

Aphthous ulcers

Herpangina

Hand, foot, and mouth disease

Candidiasis

https://www.amboss.com/us/knowledge/Herpes_simplex_virus_infections 3/10
1/17/2021 Herpes simplex virus infections - AMBOSS

Syphilitic chancre or chancroid

REGISTER / LOG IN
See “Diagnostics” and "Treatment" below.

Genital herpes (herpes genitalis)

Pathogen: HSV-2, HSV-1 (less common)

Incubation period: 2–7 days

Clinical ndings
Most patients are asymptomatic

Genitals: redness, swelling, tingling, pain, pruritus

Possibly unusual vaginal discharge

Painful lymphadenopathy in the groin area

After several days, “punched-out” lesions may appear that later ulcerate.

Lesions may appear as single or disseminated, painful red bumps or white vesicles.

They are typically located on or around the genitals and anus.

Recurrence is common.

See “Diagnostics” and "Treatment" below.

For genital herpes during pregnancy, see congenital herpes simplex virus infection

Herpetic gingivostomatitis
Etiology: severe manifestation of an (often primary) HSV-1 infection
https://www.amboss.com/us/knowledge/Herpes_simplex_virus_infections 4/10
1/17/2021 Herpes simplex virus infections - AMBOSS

Mainly in children (∼ 1–6 years), but also immunocompromised patients (e.g., agranulocytosis,
REGISTER / LOG IN
HIV)

Clinical features
Prodrome (fever, malaise) often mistaken for teething in children.

Pharyngitis, cervical lymphadenopathy

Gingivitis; erythema and painful ulcerations on perioral skin and oral mucosa, especially on
the inner cheek, soft palate, and tongue
Differential diagnoses

The same as for labial herpes

Herpetic pharyngotonsillitis: pharyngitis and tonsillitis caused by HSV-1

See “Diagnostics” and "Treatment" below.

Eczema herpeticum
Also known as Kaposi varicelliform eruption (KVE)

Pathogen: most commonly HSV-1 and HSV-2

Etiology: associated with preexisting skin conditions, most often atopic dermatitis

Clinical features
Fever, malaise, lymphadenopathy

Extensive disseminated and painful eruptions on the head and upper body; :
erythematous skin with multiple, round, umbilicated vesicles that may progress to
punched-out erosions

See “Diagnostics” and "Treatment" below.

Eczema herpeticum is considered a dermatological emergency and treatment

with oral or IV acyclovir must be initiated quickly!

https://www.amboss.com/us/knowledge/Herpes_simplex_virus_infections 5/10
1/17/2021 Herpes simplex virus infections - AMBOSS

REGISTER / LOG IN

Herpetic whitlow
Pathogen: HSV-1 in 60% of cases; HSV-2 in 40% of cases (in the adult population)

Etiology

Direct contact with infected secretions through a break in the skin, e.g., torn cuticle

Main groups:

Children; (via sucking of thumb/ ngers (may have a history of labial herpes)

Health care workers exposed to oral secretions (e.g., dentists)

Incubation period: 2–20 days

Clinical features

Possibly history of fever and malaise

Infection of the dermal and subcutaneous tissue

One or more ngers involved; (especially the thumb and index ngers); mostly found on
terminal phalanx

Pain, tingling, and burning in infected nger

Finger edema

Grouped, non-purulent vesicles on an erythematous base for up to 10 days

Vesicles may rupture or ulcerate

Axillary and epitrochlear lymphadenopathy

Differential diagnoses: paronychia, cellulitis, felon

See “Diagnostics” and "Treatment" below.

Surgical treatment is not indicated because it may cause severe complications

(e.g., bacterial superinfection, systemic spread, herpes encephalitis)!

https://www.amboss.com/us/knowledge/Herpes_simplex_virus_infections 6/10
1/17/2021 Herpes simplex virus infections - AMBOSS

REGISTER / LOG IN

Other HSV infections

HHV-1

Herpes simplex encephalitis

HSV-1 is the most common pathogen causing sporadic encephalitis in the US.

Most commonly involves the temporal lobe

Manifests with altered mental status and focal neurologic de cits (e.g., seizures, aphasia)

Herpes conjunctivitis
Viral keratitis

Herpes esophagitis

Epidemiology: typically occurs in patients who are immunocompromised.

Clinical features: odynophagia, dysphagia, and retrosternal chest pain

Diagnostics: see “Diagnostics” and "Treatment" below; endoscopy shows super cial
ulcers in the upper or mid esophagus in the absence of plaques

Erythema multiforme

HHV-2: congenital herpes simplex, neonatal herpes simplex

Both: viral meningitis (more commonly caused by HSV-2 than HSV-1)

Diagnostics

Diagnosis is primarily based on clinical features, with con rmation through the following
tests:

Light microscopy ndings on a Tzanck smear

https://www.amboss.com/us/knowledge/Herpes_simplex_virus_infections 7/10
1/17/2021 Herpes simplex virus infections - AMBOSS

Detects multinucleated giant cells (non-speci c)

REGISTER / LOG IN
Eosinophilic intranuclear Cowdry A inclusion bodies (non-speci c)

Results available within 1 hour

Unable to differentiate between HSV-1 and HSV-2, also commonly positive in VZV

Viral culture

Can be used to con rm the diagnosis in skin and/or mucosal HSV infections.

Results are available in 48 hours.

The culture should be taken from a fresh vesicle, either from skin or genitals.

PCR

Detects HSV DNA (identi cation of virus genotype)

Method of choice for CNS infections (meningitis, encephalitis), as well as for skin and
mucosal lesions

CSF sample is used in patients with suspected herpes encephalitis or meningitis.

Direct uorescent antibody test : identi cation of the virus genotype

Serum antibody testing: shows primary seroconversion

“Smear your herpes all over the TANK”: Herpes is detected by TzANcK
smear.

Resources: [2]

Treatment

Depending on the site, type, and severity of HSV-1 infection, antiviral drugs are administered
either topically or systemically. In most cases of recurrent infection, topical and/or

https://www.amboss.com/us/knowledge/Herpes_simplex_virus_infections 8/10
1/17/2021 Herpes simplex virus infections - AMBOSS

symptomatic treatment is suf cient.

REGISTER / LOG IN

Antiviral treatment

Effect

Decrease in duration and severity of infection; (most effective if therapy is initiated within
72 hours of onset of infection)

Reduction of viral shedding

However, recurrence cannot be prevented.

Agents
First-line: oral acyclovir for mild disease

In severe cases or immunocompromised patients: IV acyclovir

Topical may be helpful if used early

In case of acyclovir-resistant HSV-1: foscarnet

Valacyclovir

Penciclovir

Famciclovir

Duration: 7–10 days

Prophylaxis: indicated in the case of frequent or severe relapses; in patients with prodromal
symptoms

Long-term suppressive therapy with (val)acyclovir

Early treatment of herpes infections is essential to prevent complications

because antiviral drugs only inhibit the virus during its replication phase!

Symptomatic treatment

IV uids
Barrier creams to avoid lip adhesion in cases of lesions on the lips

Pain relief (oral or IV)

Antipyretics

https://www.amboss.com/us/knowledge/Herpes_simplex_virus_infections 9/10
1/17/2021 Herpes simplex virus infections - AMBOSS

Antibiotics for bacterial superinfection (e.g., amoxicillin, clindamycin)

REGISTER / LOG IN

Prevention

Use of condoms, gloves

Consider isolation of hospitalized patients with shedding lesions

References
1. Albrecht MA. Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex
virus infection. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate.
https://www.uptodate.com/contents/epidemiology-clinical-manifestations-and-diagnosis-of-
genital-herpes-simplex-virus-infection?
search=genital%20herpes&source=search_result&selectedTitle=2%E2%88%BC133&usage_
type=default&display_rank=2 .Last updated: December 13, 2018. Accessed: August 6,
2020.

2. Miller JM, Binnicker MJ, Campbell S, et al. A Guide to Utilization of the Microbiology
Laboratory for Diagnosis of Infectious Diseases: 2018 Update by the Infectious Diseases
Society of America and the American Society for Microbiology. Clinical Infectious Diseases.
2018; 67 (6): p.e1-e94. doi: 10.1093/cid/ciy381 . | Open in Read by QxMD

© 2020 AMBOSS Medical Knowledge Terms and Conditions Privacy Legal Notice
Get Support & Contact Us

https://www.amboss.com/us/knowledge/Herpes_simplex_virus_infections 10/10