Herpes simplex

Herpes simplex viruses are ubiquitous, host-adapted pathogens that cause a wide variety of disease states. Two types exist: herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). Both are closely related but differ in epidemiology. HSV-1 is traditionally associated with orofacial disease, while HSV-2 is traditionally associated with genital disease; however, lesion location is not necessarily indicative of viral type.

Up to 80% of herpes simplex infections are asymptomatic. Symptomatic infections can be characterized by significant morbidity and recurrence. In immunocompromised hosts, infections can cause life-threatening complications.

Pathophysiology-

The prevalence of HSV infection worldwide has increased over the last several decades, making it a major public health concern. Prompt recognition of herpes simplex infection and early initiation of therapy are of utmost importance in the management of the disease.

HSV (both types 1 and 2) belongs to the family Herpesviridae and to the subfamily Alphaherpesvirinae. It is a double-stranded DNA virus characterized by the following unique biological properties

• Neurovirulence (the capacity to invade and replicate in the nervous system)
• Latency (the establishment and maintenance of latent infection in nerve cell ganglia proximal to the site of infection): In orofacial HSV infections, the trigeminal ganglia are most commonly involved, while, in genital HSV infection, the sacral nerve root ganglia (S2-S5) are involved.
• Reactivation: The reactivation and replication of latent HSV, always in the area supplied by the ganglia in which latency was established, can be induced by various stimuli (eg, fever, trauma, emotional stress, sunlight, menstruation), resulting in overt or covert recurrent infection and shedding of HSV. In immunocompetent persons who are at an equal risk of acquiring HSV-1 and HSV-2 both orally and genitally, HSV-1 reactivates more frequently in the oral rather than the genital region. Similarly, HSV-2 reactivates 8-10 times more commonly in the genital region than in the orolabial regions. Reactivation is more common and severe in immunocompromised individuals.

Dissemination of herpes simplex infection can occur in people with impaired T-cell immunity, such as in organ transplant recipients and in individuals withAIDS.

HSV is distributed worldwide. Humans are the only natural reservoirs, and no vectors are involved in transmission. Endemicity is easily maintained in most human communities owing to latent infection, periodic reactivation, and asymptomatic virus shedding.

HSV is transmitted by close personal contact, and infection occurs via inoculation of virus into susceptible mucosal surfaces (eg, oropharynx, cervix, conjunctiva) or through small cracks in the skin. The virus is readily inactivated at room temperature and by drying; hence, aerosol and fomitic spread are rare.

HSV-1 infections transmitted via saliva are common in children, although primary herpes gingivostomatitis can be observed at any age.

Clinical presentation-

The clinical course of herpes simplex infection depends on the age and immune status of the host, the anatomic site of involvement, and the antigenic virus type. Primary herpes simplex virus (HSV)–1 and HSV-2 infections are accompanied by systemic signs, longer duration of symptoms, and higher rate of complications. Recurrent episodes are milder and shorter. Both HSV-1 and HSV-2 can cause similar genital and orofacial primary infections after contact with infectious secretions containing either HSV-1 (usually oral secretions) or HSV-2 (usually genital secretions).

• Acute herpetic gingivostomatitis
  

  • This is a manifestation of primary HSV-1 infection that occurs in children aged 6 months to 5 years. Adults may also develop acute gingivostomatitis, but it is less severe and is associated more often with a posterior pharyngitis.
  • Infected saliva from an adult or another child is the mode of infection. The incubation period is 3-6 days.
  • Clinical features include the following:
    • Abrupt onset
    • High temperature (102-104°F)
    • Anorexia and listlessness
    • Gingivitis (This is the most striking feature, with markedly swollen, erythematous, friable gums.)
    • Vesicular lesions (These develop on the oral mucosa, tongue, and lips and later rupture and coalesce, leaving ulcerated plaques.)
    • Tender regional lymphadenopathy
    • Perioral skin involvement due to contamination with infected saliva
  • Course: Acute herpetic gingivostomatitis lasts 5-7 days, and the symptoms subside in 2 weeks. Viral shedding from the saliva may continue for 3 weeks or more.
• Acute herpetic pharyngotonsillitis
  

  • In adults, oropharyngeal HSV-1 infection causes pharyngitis and tonsillitis more often than gingivostomatitis.
  • Fever, malaise, headache, and sore throat are presenting features.
  • The vesicles rupture to form ulcerative lesions with grayish exudates on the tonsils and the posterior pharynx.
  • Associated oral and labial lesions occur in fewer than 10% of patients.
  • HSV-2 infection can cause similar symptoms and can be associated with orogenital contact or can occur concurrently with genital herpes.
• Herpes labialis/Cold sore
  

  • This is the most common manifestation of recurrent HSV-1 infection. A prodrome of pain, burning, and tingling often occurs at the site, followed by the development of erythematous papules that rapidly develop into tiny, thin-walled, intraepidermal vesicles that become pustular and ulcerate. In most patients, fewer than two recurrences manifest each year, but some individuals experience monthly recurrences.
  • Maximum viral shedding is in the first 24 hours of the acute illness but may last 5 days.

  
  

  
  

  Physical-

This section describes physical examination findings of the herpetic lesion as it relates to primary and recurrent lesions of cutaneous or mucosal HSV infection. This can be related to either oral or genital infection.

• Primary mucocutaneous HSV infections
  

  • Some primary infections are asymptomatic.
  • Primary (first-episode) infections manifest within several days of exposure to secretions containing viable virus.
  • Often painful, the lesions quickly progress to vesicles and can continue to erupt over 1-2 weeks.
  • The lesions are prominent and are often present internally on the mucosal surface of the oral or genital area, as well as on the surrounding skin.
  • Constitutional symptoms (fever, malaise, myalgias, and anorexia) are often prominent. Weight loss is not uncommon and is due either to illness or dysphagia (in primary gingivostomatitis).
  • Individual vesicles on mucosal surfaces break down rapidly, forming shallow painful ulcers (usually < 8-10 mm in diameter). They may be covered with a white exudate that can be confused with mucosal candidiasis. Those on cutaneous surfaces remain as vesicles longer, only to evolve into crusted ulcers that heal within 5-7 days.
• Recurrent mucocutaneous HSV infections
  

  • Following the establishment of latency in the corresponding sensory nerve ganglion cells, HSV can cause recurrent infection that can be subclinical (manifesting as viral excretion without lesions) or overt (manifesting as mucosal or cutaneous lesions with viral excretion).
  • Oral recurrences are often triggered by recognizable stimuli such as pyrexia (fever blisters and cold sores), stress, or sunburn. Genital recurrences are more likely to be linked to stress rather than to pyrexia. Females may relate a relationship to the menstrual cycle.
  • Localized burning or paraesthesias may precede recurrent lesions. Unlike primary infection, constitutional symptoms are minimal in most cases.
  • Recurrences last 3-7 days and can occur numerous times per year or once or twice in a lifetime. Overall, the number of yearly recurrences tends to decrease over time.
  • Although recurrent HSV infections may last much longer (>30 d) in immunocompromised hosts, such as individuals with AIDS, frequent recurrences are not necessarily a sign of an altered immune system.
  • Because recurrences can be clinically unrecognizable, transmission to susceptible individuals can occur in the absence of overt lesions. In genital HSV infections, barrier protection should be used regardless of existing lesions, even in the absence of a history of genital HSV infection.

  Causes-

  
  

  • HSV is transmitted via close personal contact.
  • HSV infection occurs via inoculation of virus into susceptible mucosal surfaces (eg, oropharynx, cervix, conjunctiva) or through small cracks in the skin.
  • The virus is inactivated readily at room temperature and by drying; hence, aerosol and fomitic spread are rare.
  • HSV-1 is transmitted chiefly by contact with infected saliva, whereas HSV-2 is transmitted sexually or from a mother's genital tract infection to her newborn. However, lesion location does not always indicate viral type.
    Treatment-
    Overall, medical treatment of herpes simplex virus (HSV) infection is centered around specific antiviral treatment. While the same medications are active against HSV-1 and HSV-2, the location of the lesions and the chronicity (primary or reactivation) of the infection dictate the dosage and frequency of medication. It is important to note that life-threatening HSV infections in immunocompromised patients and HSV encephalitis require high-dose intravenous acyclovir, often started empirically.

    When constitutional effects such as fever occur, symptomatic treatment can be used.

    Appropriate wound care is needed, and treatment for secondary bacterial skin infections may be required.

    Fluids can be given to avoid dehydration.