Bullous Viral Eruptions

1

What do herpes simplex virus (HSV) and varicella-zoster virus (VZV) have in common?

HSV-1, HSV-2, and VZV are all members of the human herpesvirus family. Other members of this family include cytomegalovirus, Epstein-Barr virus, human herpesvirus-6, human herpesvirus-7, and human herpesvirus-8. The human herpesviruses all contain double-stranded DNA, share certain structural features and mechanisms for infection and replication, and have the capacity to establish latent infection in the human host.

2

What happens during primary HSV infection?

Primary infection refers to an individual's first infection with HSV, either type 1 or 2, at any site. These patients are seronegative initially but subsequently develop HSV-specific antibodies. During primary infection, HSV gains access to the host through the epithelial surface. Following active replication within the skin or mucosa, HSV infects the associated cutaneous neurons and migrates to the sensory root ganglia, where a latent infection is established. Primary HSV infection may be associated with extensive cutaneous lesions, severe pain, and systemic symptoms; however, in many cases, the primary infection is asymptomatic (or unrecognized).

3

What about recurrent HSV infection?

Recurrent HSV infection represents reactivation of the latent virus in the sensory ganglia. “Reactivated” virus particles migrate along the nerves to the site in the skin where the primary infection occurred, with subsequent viral replication and the development of clinical lesions ( Fig. 25.1 A ). The most common sites for recurrent herpes simplex infection are the lips (herpes labialis, “cold sores”), genitalia (herpes genitalis), and sacral area ( Fig. 25.1 B). Often, individuals experience a prodrome of tingling or burning in the skin prior to the development of visible lesions. Certain factors, such as fever, stress, menses, and sun exposure, may precipitate recurrent infection. The frequency of recurrent infection varies greatly between individuals. In most individuals, clinically evident recurrence becomes less frequent over time.

4

What is the difference between a primary and an initial HSV infection?

When an individual without preexisting antibodies to either HSV-1 or HSV-2 develops an infection with HSV (either type 1 or 2), it is referred to as the primary infection. When an individual with preexisting antibodies to one type of HSV then experiences an infection with the other HSV type, it is referred to as the initial (or initial, nonprimary) infection.

5

How is HSV transmitted?

HSV is transmitted by direct contact of the infected mucocutaneous surface(s) of one individual with the mucosa or skin of another individual. HSV does not survive long outside its normal habitat, and so transmission by contact with fomites is extremely uncommon. It is assumed that HSV-1 is generally transmitted inadvertently during childhood from infected family members, whereas infection with HSV-2 may develop later when individuals become sexually active.

6

How long is the incubation period for HSV (i.e., the time from initial infection to appearance of vesicles)?

The time interval between exposure and development of primary disease is estimated to be 3 to 14 days. However, not all cases of primary disease are symptomatic, and so the first evidence of infection may be a recurrent episode, well after the actual exposure. This is important to note, especially in the case of genital infection, where the sudden development of “herpes” in one partner in a monogamous couple could create concerns regarding infidelity.

7

Define asymptomatic shedding.

In individuals previously infected with HSV, virus may periodically be present at the site of infection in the absence of clinically evident lesions. This is referred to as asymptomatic shedding. During asymptomatic shedding, the presence of virus may be documented by viral culture or polymerase chain reaction (PCR). Although the viral titer is lower than during clinically active disease, transmission of the virus can nevertheless occur. In fact, contact during periods of asymptomatic shedding is thought to be responsible for many cases of disease transmission.

8

Can you be infected with HSV and not know it?

Yes. Many individuals who give no history of HSV infection are seropositive for HSV-specific antibodies. Using viral culture or PCR, HSV can periodically be recovered from the mouth and/or anogenital region of such individuals (see “asymptomatic shedding” earlier). Based on the seroprevalence of herpes-specific antibody, 70% to 80% of the population is infected with HSV-1, and 25% to 30% with HSV-2. It is estimated that out of every four individuals with genital herpes, three do not know they are infected, and that more than half the population in the United States will become seropositive for HSV by adulthood.

9

How do HSV-1 and HSV-2 differ?

HSV types 1 and 2 are very closely related, sharing approximately 50% homology in their genetic composition. As expected, many of their viral proteins are also similar (known as type-common), although each type also produces unique proteins (type-specific). Immunohistologic techniques can be used to distinguish these type-specific proteins and differentiate HSV-1 from HSV-2 in clinical situations. Serologic testing that can accurately identify and differentiate antibodies to HSV-1 versus antibodies to HSV-2 is now also available (glycoprotein G type-specific assays). HSV-1 is usually associated with oral herpes and HSV-2 with genital herpes, although each virus can affect both sites. HSV-1 cannot be differentiated from HSV-2 based on the appearance of the skin lesions alone.

Nasrallah GK, Dargham SR, Abu-Raddad LJ. Negative epidemiological association between HSV-1 and HSV-2 infections. Heliyon . 2019;5(10):e02549.

10

How do you diagnose HSV infection?

The clinical history of recurrent blisters or erosions in the same site (especially in an oral or genital distribution) is highly suspicious for HSV infection. A prodrome of tingling or burning is also consistent with this diagnosis. On physical examination, the classic lesion is grouped vesicles on an erythematous base (see Fig. 25.1 A), but more often, only nonspecific crusted erosions are seen. To confirm the diagnosis, laboratory assessment may be needed. The gold standard remains viral culture. However, use of many other rapid and sensitive techniques for detection of viral-specific proteins or nucleic acids is often available. For any method of detection, the age of the lesion sampled is critical. Vesicles are optimal but ulcers and erosions, if they are not dry and crusted, may also yield positive results.

11

How is a Tzanck smear performed?

In a Tzanck smear, the base of the suspected herpetic lesion is gently scraped, and the skin or mucosal cells removed are placed on a glass slide. The cells are stained and then examined by light microscopy for evidence of viral-induced cytologic change, including the characteristic multinucleated giant cells (see Chapter 3, Fig. 3.5 ). Tzanck smears provide an efficient and inexpensive method of diagnosis, although the results are not always definitive. This technique cannot distinguish HSV-1 from HSV-2 or HSV from VZV.