• Recurrent small grouped vesicles on an erythematous base, especially in the orolabial and genital areas.

  • May follow minor infections, trauma, stress, or sun exposure; regional lymph nodes may be swollen and tender.

  • Viral cultures and direct fluorescent antibody tests are positive.


1. Mucocutaneous disease

HSV-1 mucocutaneous disease (“herpes labialis” or “gingivostomatitis”).

Digital lesions (whitlows) are an occupational hazard in medicine and dentistry. Contact sports (eg, wrestling) are associated with outbreaks of skin infections (“herpes gladiatorum”).


Risk factors for HSV transmission include black race, female gender, a history of sexually transmitted infections, an increased number of partners, contact with commercial sex workers, lower socioeconomic status, young age at onset of sexual activity, and total duration of sexual activity.


Genital herpes is a viral infection caused by herpes simplex virus (HSV) type 1 or type 2.

Most cases of recurrent genital herpes are caused by HSV-2. Clinically, HSV causes painful vesicles or ulcers.

However, most persons infected with HSV-2 have not been clinically diagnosed because of the presence of mild or unrecognized infection.

These persons may shed virus and therefore may transmit the infection to others while being asymptomatic.

HSV infections may be diagnosed by culture or polymerase chain reaction (PCR) testing of samples from clinically evident lesions. Serologic antibody testing to both HSV-1 and HSV-2 is also available, although both false positive and false negative and cross-reactivity may occur. Testing positive for HSV-1 alone can also be difficult to interpret, as this is a common nonsexually transmitted infection of childhood.

Antiviral therapy is available for HSV infections. Treatment can be used both for the acute management of symptomatic outbreaks and for suppression to reduce the frequency of outbreak or the risk of viral transmission to an uninfected partner. Pregnant women with a history of HSV should be placed on suppressive therapy late in pregnancy to reduce the risk of symptomatic outbreak or viral shedding at the time of delivery, so as to reduce the risk of neonatal herpes in the newborn. Women with clinically evident genital herpes at the time of delivery should be offered cesarean delivery.



Herpes simplex viruses 1 and 2 affect primarily the oral and genital areas, respectively. 

The virus enters through mucosal membranes or breaks in the skin. It replicates in cells at the infection site and then establishes latent infection of the neuron that innervates the primary infection site via retrograde transport.

HSV avoids antibody-mediated defenses by cell-to-cell spread by the formation of syncytia. Cell-mediated immunity is necessary for control of HSV infections, and persons with impaired cellular immunity can get more severe and diffuse disease. The latent infection of neurons also helps the virus to avoid host defenses and provides the potential for recurrent disease. Recurrences can be triggered by many events, including stress and other illnesses. Recurrent HSV disease is usually less severe than primary disease because of the memory response of the host immune system. HSV-1 tends to be transmitted via contact with saliva or direct contact with skin or mucous membrane lesions. It causes gingivostomatitis, cold sores, and pharyngitis. Herpetic whitlow, an infection of the finger with HSV-1, results from direct contact with herpes lesions and is most commonly seen in children who suck their fingers or in health care professionals who care for infected patients.

Seroprevalence of both viruses increases with age, and the seroprevalence of HSV-2 increases with sexual activity.

Among the adult population in the United States, HSV-2 seropositivity is 16.2%. Only 2.5% of women in a Canadian herpes vaccine study were HSV-2 seropositive compared with 29% among women aged 18–34 years in Kenya. In Germany 13.6% were seropositive, but only up to one-quarter of these were symptomatic. Asymptomatic shedding of either virus is common, but it is more common with HSV-2 and from genital areas, with most infected individuals shedding virus at least once a month, which may be responsible for transmission. Asymptomatic HSV-2–infected individuals shed the virus less frequently than those with symptomatic infection. Disease typically indicates reactivation. Total and subclinical shedding of HSV-2 virus decrease after the first year of initial infection, although viral shedding continues for years thereafter. HSV-2 lesions occur at higher than expected rates among women during the postpartum period and among women who have sex with women.


HSV-2 is the most common cause of genital ulcers in the developed world,

HSV-1 is a more common cause of both genital and oral lesions than HSV-2 in young women in the United States.

Over 85% of adults have serologic evidence of herpes simplex type 1 (HSV-1) infections, most often acquired asymptomatically in childhood.

Occasionally, primary infections may be manifested as severe gingivostomatitis. Thereafter, the patient may have recurrent self-limited attacks, provoked by sun exposure, orofacial surgery, fever, or a viral infection.

Most HSV-2–infected persons in the United States are unaware that they are infected. HSV-2.

Genital recurrences are much more frequent with HSV-2 and gradually decrease over time, whereas HSV-1 recurrences of urogenital lesions are rare after infancy but correlate with CMV seropositivity and age. HSV-2 seropositivity increases the risk of HIV acquisition (it is threefold higher among persons who are HSV-2 seropositive than among those who are HSV-2 seronegative), and HSV-2 reactivates more often in advanced HIV infection. HIV replication is increased by interaction with HSV proteins. Suppression of HSV-2 decreases HIV-1 plasma levels and genital tract shedding of HIV, which can contribute to a reduction in the sexual transmission of HIV-1. An association between HSV-2 infection and bacterial vaginosis, which is also associated with increased HIV-1 transmission, is observed. In those with HIV, HSV-2 does not appear to be associated with a more rapid rate of CD4 decline.





Complications of Injecting Drug Use

  • Local problems—Abscess (Figures 240-2 
    Image not available.

    A 32-year-old woman with type 1 diabetes developed large abscesses all over her body secondary to injection of cocaine and heroin. Her back shows the large scars remaining after the healing of these abscesses. (Courtesy of ­Richard P. Usatine, MD.)

    and 240-3; Abscess), cellulitis, septic thrombophlebitis, local induration, necrotizing fasciitis, gas gangrene, pyomyositis, mycotic aneurysm, compartmental syndromes, and foreign bodies (e.g., broken needle parts) in local areas.2
    • IDUs are at higher risk of getting methicillin-resistant Staphylococcus aureus(MRSA) skin infections that the patient may think are spider bites (Figure 240-4).
    • Some IDUs give up trying to inject into their veins and put the cocaine directly into the skin. This causes local skin necrosis that produces round atrophic scars (Figure 240-5).
  • IDUs are at risk for contracting systemic infections, including HIV and hepatitis B or hepatitis C.
    • Injecting drug users are at risk of endocarditis, osteomyelitis (Figures 240-6and 240-7), and an abscess of the epidural region. These infections can lead to long hospitalizations for intravenous antibiotics. The endocarditis that occurs in IDUs involves the right-sided heart valves (see Chapter 50, Bacterial Endocarditis).2 They are also at risk of septic emboli to the lungs, group A β-hemolytic streptococcal septicemia, septic arthritis, and candidal and other fungal infections.


Content 3

Content 13

Content 11


Which of the following cell types are specific to a latent genital infection with HSV-2?

Next Question
You will be able to view all answers at the end of your quiz.

The correct answer is B.

 Latent infection by HSV-2 has been shown to occur primarily in the sacral ganglia, whereas HSV-1 latency has been demonstrated in trigeminal, superior cervical, and vagal nerve ganglia. Varicella-zoster virus remains latent in neural sensory ganglia.


USMLE Reviewer (Subscription Required)