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Image of herpes labialis (cold sores) caused by reactivation of herpes simplex virus type 1 (HSV-1) from Wikimedia Commons | Speifensender. [Creative Commons Attribution-Share Alike 3.0 Unported License.]

Herpes Simplex Viruses: Test Your Knowledge

Lars Grimm, MD, MHS; Michael J. Payette, MD, MBA; Kristen Russomanno, MD | February 10, 2023 | Contributor Information

Herpes Simplex Virus 1 and 2

Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2, respectively) are double-stranded DNA viruses of the family Herpesviridae. Primary infection occurs via direct contact with infected skin and subsequent inoculation of mucous membranes or defects in the skin's surface. The virus then reaches sensory and autonomic nerve endings and remains latent in the nerve cell bodies of ganglion neurons. This allows for reactivation, which explains the recurrent signs and symptoms characteristic of HSV infection.[1]

HSV-1 is traditionally associated with orofacial disease; it causes vesicular lesions commonly referred to as cold sores when present in the oral cavity (shown). HSV-1 is typically acquired in childhood, but reactivation can occur in adolescence and later.

HSV-2, however, is most commonly associated with genital herpes, a well-known sexually transmitted infection (STI). Note that in rare cases, HSV-2 can be isolated from oral lesions, just as HSV-1 can be isolated from genital lesions.

Image courtesy of Medscape.

Herpes Simplex Viruses: Test Your Knowledge

Lars Grimm, MD, MHS; Michael J. Payette, MD, MBA; Kristen Russomanno, MD | February 10, 2023 | Contributor Information

Many HSV infections may be subclinical or mild, and up to 88.1% of HSV-2-infected individuals between ages 14 and 49 years have never received a clinical diagnosis.[2] However, symptomatic infections can be severe and present with a sudden onset of systemic signs, including fevers, regional lymphadenopathy, and painful vesicular lesions (shown). Recurrent infections manifest similarly, although they are typically less severe and have a shorter duration; they also tend to lack systemic signs such as fevers. In immunocompromised hosts, infections can cause life-threatening complications.

Image courtesy of Medscape.

Herpes Simplex Viruses: Test Your Knowledge

Lars Grimm, MD, MHS; Michael J. Payette, MD, MBA; Kristen Russomanno, MD | February 10, 2023 | Contributor Information

Genital Herpes

Genital herpes lesions typically appear as one or more vesicles in the genital and/or rectal area and can mimic other STIs.

The most common symptoms of primary genital HSV infection include painful genital ulcers (shown), dysuria, fever, tender lymphadenopathy, and headache. Men who have sex with men are also at risk for proctitis. The typical incubation period following exposure is 2-12 days, and ulcers usually resolve after 19 days.[3]

Following a primary outbreak, intermittent asymptomatic viral shedding occurs, with an increased risk of viral transmission to sexual partners. The risk is greater when the male partner has been initially infected and the female is susceptible (ie, not previously infected). Primary genital HSV-2 infections tend to shed from the genital tract for a more prolonged period than HSV-1 infections do.[3]

Image courtesy of Medscape.

Herpes Simplex Viruses: Test Your Knowledge

Lars Grimm, MD, MHS; Michael J. Payette, MD, MBA; Kristen Russomanno, MD | February 10, 2023 | Contributor Information

Recurrent genital herpes infections are common, with most cases caused by HSV-2. However, HSV-1 has been associated with an increasing prevalence of genital outbreaks.[2]

Recurrent genital herpes infections are typically less severe and have a shorter duration than primary infections (average of 10 days vs 19 days, respectively). Prodromal tingling or pain in the area of outbreak may occur prior to a vesicular eruption; however, systemic symptoms are uncommon with recurrent herpes outbreaks.[3]

Image from Wikimedia Commons | Kapitainekavern. [Creative Commons Attribution-Share Alike 4.0 International License.]

Herpes Simplex Viruses: Test Your Knowledge

Lars Grimm, MD, MHS; Michael J. Payette, MD, MBA; Kristen Russomanno, MD | February 10, 2023 | Contributor Information

Neonatal Herpes Simplex Infection

There may be vertical transmission of genital herpes from mothers to infants during childbirth. Factors that influence perinatal transmission include maternal HSV antibody status, type of infection (primary vs recurrent), duration of ruptured membranes, and mode of delivery (cesarean vs vaginal). The risk of neonatal transmission rises if vaginal delivery occurs during an active HSV outbreak; thus, cesarean delivery is preferred in this setting. The highest risk for transmission occurs when a primary genital HSV infection is acquired close to the time of delivery.[4]

Neonatal HSV can be classified into three main categories: (1) skin, eye, and mouth (SEM) disease (shown); (2) central nervous system (CNS) disease, with or without SEM disease; and (3) disseminated disease.

Image of herpes skin lesions on the face, torso, arm, and legs of an infant, from the Centers for Disease Control and Prevention (CDC) [public domain].

Herpes Simplex Viruses: Test Your Knowledge

Lars Grimm, MD, MHS; Michael J. Payette, MD, MBA; Kristen Russomanno, MD | February 10, 2023 | Contributor Information

SEM disease usually presents within the first 2 weeks of life and is characterized by localized vesicular eruptions. Left untreated, SEM disease has a high risk of progression to CNS or disseminated disease. Neonates with HSV CNS disease may present with seizures, lethargy, tremors, poor feeding, temperature instability, and/or a full anterior fontanelle within the first 6 postnatal weeks.

Disseminated disease generally presents in the first week of life with neonatal sepsis and multisystem organ failure. Mortality exceeds 80% if disseminated disease is not promptly addressed and treated.[5] Of note, SEM symptoms may not be present in neonates who present with later stage CNS or disseminated disease.

Image courtesy of Medscape.

Herpes Simplex Viruses: Test Your Knowledge

Lars Grimm, MD, MHS; Michael J. Payette, MD, MBA; Kristen Russomanno, MD | February 10, 2023 | Contributor Information

Herpes Simplex Meningitis

Neural penetration of HSV along nerve roots, where it lies dormant, can lead to meningitis and encephalitis.[6]

HSV meningitis is generally caused by HSV-2, and patients present with photophobia, meningismus, and headache. About 13-36% of patients with primary genital herpes present with clinical findings of meningeal involvement. In approximately 85% of patients with HSV-2 meningitis, genital lesions precede the onset of CNS symptoms by approximately 1 week.[7]

Diagnosis of herpes meningitis is via cerebrospinal fluid (CSF) polymerase chain reaction (PCR) assay.[6] Magnetic resonance imaging (MRI) of the brain typically shows diffuse enhancement of the meninges (shown).

Image from MedPix | courtesy of James G Smirniotopoulos, MD, Uniformed Services University.

Herpes Simplex Viruses: Test Your Knowledge

Lars Grimm, MD, MHS; Michael J. Payette, MD, MBA; Kristen Russomanno, MD | February 10, 2023 | Contributor Information

Herpes Simplex Encephalitis

HSV encephalitis is the most common cause of sporadic fatal encephalitis in the world and is usually caused by HSV-1.[8] Encephalitis manifests with abnormal cerebral function, and common presenting symptoms include fever, headache, psychiatric symptoms, seizures, vomiting, focal weakness and neurologic deficits, and/or memory loss.[7] MRI abnormalities involving the temporal lobe (shown) are found in 90% of patients with herpes simplex encephalitis (HSE).

The neuronal damage in HSE is thought to be due to the ability of HSV-1 to induce cell death, a property not characteristic of HSV-2.[9,10] Diagnosis of HSE is via PCR assay detection of HSV in the CSF. The diagnosis can be confirmed by CSF PCR assay or brain biopsy.

Treatment of HSE often involves admission to an intensive care unit to manage increased intracranial pressure and seizures, as well as early administration of intravenous acyclovir.[8] HSE is a neurologic emergency, and nearly two thirds of survivors will have significant neurologic deficits, including cognitive deficits, recurrent seizures, amnesia, dysnomia, and behavioral abnormalities.[8]

Images courtesy of Medscape.

Herpes Simplex Viruses: Test Your Knowledge

Lars Grimm, MD, MHS; Michael J. Payette, MD, MBA; Kristen Russomanno, MD | February 10, 2023 | Contributor Information

Herpetic Gingivostomatitis

HSV-1–associated gingivostomatitis is the most common manifestation of primary HSV infection in childhood after levels of passive maternal antibodies have diminished. Transmission occurs via infected saliva from other children or adults who may be asymptomatic. Following an incubation period of 6-8 days, symptoms include fevers, listlessness, gingivitis, and pharyngitis. Painful oral mucosal vesicular lesions (left image) can interfere with eating, drinking, and swallowing. Vesicles eventually crust and reepithelialize, but healing can take up to 3 weeks (right image).[11]

The virus typically remains latent in the trigeminal ganglion and may reactivate to cause recurrent stomatitis or herpes labialis.[11]

Left image courtesy of Medscape; right image from Wikimedia Commons | James Heilman, MD. [Creative Commons Attribution-Share Alike 3.0 Unported License.]

Herpes Simplex Viruses: Test Your Knowledge

Lars Grimm, MD, MHS; Michael J. Payette, MD, MBA; Kristen Russomanno, MD | February 10, 2023 | Contributor Information

Herpetic Whitlow

Herpetic whitlow (shown) develops when HSV infection (usually HSV-1) occurs in breaks in the skin on the nail bed or finger. Typically, lesions present with acute onset of edema, erythema, and localized burning pain and tenderness. Systemic symptoms, such as flulike symptoms and lymphadenopathy, can occur and may be associated with primary infection as a prodrome to the outbreak; subsequent outbreaks are less likely to be associated with systemic symptoms.

Herpetic whitlow can be a complication of primary HSV gingivostomatitis, often occurring in infected children as a result of finger or thumb sucking. It can, however, arise in anyone exposed to HSV, such as healthcare workers who have unprotected contact with infected oropharyngeal secretions.[12]

Image from the CDC [public domain].

Herpes Simplex Viruses: Test Your Knowledge

Lars Grimm, MD, MHS; Michael J. Payette, MD, MBA; Kristen Russomanno, MD | February 10, 2023 | Contributor Information

Herpes Labialis

Reactivation of HSV-1 causes herpes labialis (shown), otherwise known as cold sores or fever blisters. These lesions commonly erupt in response to stressful stimuli such as fevers, infection, or menstruation. They are typically confined to the mucosa of the hard palate and the lips, in contrast to the lesions of primary HSV-1 infection. Most patients develop prodromal symptoms about 1 day prior to the appearance of active lesions.

The condition is harmless, but it is contagious to those who are HSV-1 naive or who are immunocompromised. HSV-1 can also be transmitted from the oral cavity to the genitals through direct contact.[13]

Image courtesy of Medscape.

Herpes Simplex Viruses: Test Your Knowledge

Lars Grimm, MD, MHS; Michael J. Payette, MD, MBA; Kristen Russomanno, MD | February 10, 2023 | Contributor Information

Herpes Gladiatorum

Herpes gladiatorum is caused by skin-to-skin contact, often from sports such as wrestling and rugby.[14]

Vesicular, fluid-filled blisters most commonly occur around the head, neck, and ears. Primary infection may lead to a constellation of symptoms, including fever, lymphadenopathy, headache, and malaise,[14] similar to other primary HSV outbreaks.

Image of erythematous vesicles characteristic of eczema herpeticum with associated impetiginous crust, courtesy of Medscape.

Herpes Simplex Viruses: Test Your Knowledge

Lars Grimm, MD, MHS; Michael J. Payette, MD, MBA; Kristen Russomanno, MD | February 10, 2023 | Contributor Information

Eczema Herpeticum

Eczema herpeticum, or Kaposi varicelliform eruption, is usually caused by HSV-1. It is typically associated with a primary infection, and repeated episodes are unusual.[15] Patients with atopic dermatitis (eczema) are at particularly high risk for developing this condition, thus the name eczema herpeticum.

Eczema herpeticum presents with clusters of painful blisters and erosions, most commonly on the face and neck. Associated symptoms include fever, malaise, and irritability. As with many other herpes infections, recurrence is less severe. Secondary infection with Staphylococcus aureus or Streptococcus pyogenes commonly occurs and may complicate the condition.[16]

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