Dermatologic Manifestations of Herpes Simplex 

Herpes simplex viruses (HSVs) are DNA viruses that cause acute skin infections and present as grouped vesicles on an erythematous base. Rarely, these viruses can cause serious illness and can affect pregnancy, leading to significant harm to the fetus. Most infections are recurrent and tend to reappear at or near the same location. Herpes labialis is the most common infection caused by HSV type 1 (HSV-1), whereas genital herpes is usually caused by HSV type 2 (HSV-2). Other clinical manifestations of HSV infection are less common.

Intimate contact between a susceptible person (without antibodies against the virus) and an individual who is actively shedding the virus or with body fluids containing the virus is required for HSV infection to occur. Contact must involve mucous membranes or open or abraded skin.

HSV invades and replicates in neurons as well as in epidermal and dermal cells. Virions travel from the initial site of infection on the skin or mucosa to the sensory dorsal root ganglion, where latency is established. Viral replication in the sensory ganglia leads to recurrent clinical outbreaks. These outbreaks can be induced by various stimuli, such as trauma, ultraviolet radiation, extremes in temperature, stress, immunosuppression, or hormonal fluctuations. Viral shedding, leading to possible transmission, occurs during primary infection, during subsequent recurrences, and during periods of asymptomatic viral shedding.

HSV-1 reactivates most efficiently from trigeminal ganglia (affecting the face and the oropharyngeal and ocular mucosae), while HSV-2 has a more efficient reactivation in the lumbosacral ganglia (affecting the hips, buttocks, genitalia, and lower extremities). The clinical difference in site-specific reactivation between HSV-1 and HSV-2 appears to be due, in part, to each virus establishing latent infection in different populations of ganglionic neurons.^[1]

Frequency

United States

HSV-1 infection is acquired by early childhood, and evidence of serologic infection with HSV-1 approaches 80% in the general adult population. Only about 30% of these individuals have clinically apparent outbreaks. In the United States, approximately 1 in 4-5 adults (21-25%) is serologically positive for HSV-2. For adolescents in the United States, studies have found rates up to 49-53% for HSV-1 and 12-15% for HSV-2. More than half the seropositive individuals do not experience clinically apparent outbreaks, but these individuals still have episodes of viral shedding and can transmit the virus. The incidence of HSV-2 infection is one of the most rapidly increasing rates among sexually transmitted diseases in this country. Independent predictors of HSV-2 seropositivity include female sex, black race, older age, lower education, more lifetime sex partners, prior diagnosis of sexually transmitted disease, and lack of HSV-1 antibody.

International

Serologic evidence of HSV-1 infection by early adulthood ranges from 56-85%, varying by country. HSV-2 seroprevalence has been reported to vary from 13-40% worldwide. More than one third of the world's population has recurrent clinical HSV infections.

In the developing world, HSV-2 is becoming a common cause for genital ulcer disease, especially in countries with a high prevalence of HIV infection. International studies show seroprevalence in people co-infected with HIV being close to 90% for HSV-1 and up to 77% for HSV-2.^[2]

Mortality/Morbidity

Severe complications may be associated with herpes simplex. This is especially true in females who are pregnant and in individuals with immunosuppression who may develop disseminated infection and encephalitis.

The most common complication of primary HSV-2 genital infection is bacterial superinfection. In women, systemic complications, such as urinary retention and aseptic meningitis (seen in up to 25% of women), can occur. The associated pain, paresthesia, and discomfort, as well as the psychosocial impact, of herpes simplex outbreaks cause significant morbidity to the individuals who are affected.

Individuals co-infected with HSV and HIV and who have herpetic mucosal lesions are more likely to transmit HIV during sexual contact. In studies, despite being compliant with highly active antiretroviral therapy (HAART) for treatment of HIV-1 infection, 30-50% of women co-infected with HSV-2 and HIV-1 were shown to have genital HIV-1 shedding at least once in a 3-month period. Studies also suggest that co-infection with HSV-2 may accelerate HIV disease progression by elevating the HIV viral load. However, a 2008 study by Baeten et al found that HSV suppressive therapy decreased genital and plasma HIV levels in women with HSV-2/HIV co-infection.^[3]

Organ transplant recipients and patients with HIV/AIDS may develop herpetic lesions that exhibit an unusual morphology. Moreover, patients with Darier disease, severe atopic dermatitis, or mycosis fungoides may develop life-threatening disseminated Kaposi varicelliform eruption.

Another serious consequence of HSV infection is the transmission of the virus to a neonate by a mother who is infected. Asymptomatic maternal shedding occurs approximately 7% of the time and is responsible for most neonatal HSV infections. The risk of HSV transmission to the newborn is as high as 30-50% from a mother who acquired a new HSV infection near the time of delivery. Among women who have acquired HSV infection before their third trimester of pregnancy, the risk of transmission is less than 1%. HSV infections in neonates are most commonly due to HSV-2 and most are acquired peripartum from exposure to lesions (or shedding virus) in the birth canal, although in utero and postpartum transmission rarely can occur. Transmission is estimated to occur at a rate of 1 case in 3500-5000 deliveries in the United States. Neonatal infection can cause long-term sequelae and even death.

Race

African Americans have a higher prevalence of antibodies against HSV-1 than whites. Nonwhite race has been reported as a risk factor for HSV-2 seropositivity.

Sex

The frequency of HSV-1 and HSV-2 antibodies is slightly higher in females than in males. However, women are more likely than men to be protected from genital HSV infection by the use of barrier methods.

In a study of more than 600 pregnant women, 63% were seropositive for HSV-1, 22% for HSV-2, and 13% for both, and 28% were seronegative. Nonwhite race and having had 4 or more sex partners independently correlated with increased HSV-2 infection. Non-Hispanic white pregnant women had the highest percentage of seronegativity for both HSV-1 and HSV-2. However, this group had the highest risk of having a child with neonatal herpes, indicating their susceptibility for new HSV infection during their third trimester of pregnancy (when a mother is most likely to transmit infection to her neonate).^[4]

Age

The frequency of HSV-1 infection in children varies with the socioeconomic status. Approximately, one third of children from lower socioeconomic families exhibit some evidence of HSV-1 infection by age 5 years. The frequency increases to 70-80% by early adolescence/adulthood. In contrast, only 20% of children from middle-class families seroconvert. The frequency of infection remains fairly stable until the second to third decade of life when it increases to 40-60%. The rate of HSV-2 seroconversion is highest in sexually active young adults.