Global prevalence of HSV increases with age affecting almost half of the population by the age of 15 years and 60% to 90% by adulthood. Clinical disease in humans is caused by two members of the Herpesviridae family, HSV1 and HSV2. The Herpes virus enters the host through epithelial cells and may undergo replication at the site of invasion. After the primary infection has occurred, HSV travels through the periaxonal sheath of sensory nerves to ganglia of the host nervous system. The cervical and lumbosacral sensory ganglia are particularly vulnerable. The virus replicates in ganglia and may persist for life. An asymptomatic person can shed virus, but during primary infection and reactivation, virus shedding is increased. Reactivation of virus can occur as a result of a variety of external and internal triggers including fever, immunosuppression, local trauma, menstruation, stress, fatigue, temperature changes, and exposure to sunlight.17
Clinical manifestations are highly variable and include primary and secondary presentations. Viral manifestation can result in encephalitis and serious systemic symptoms, self-limited simple mucocutaneous signs, or asymptomatic infection. HSV1 is mainly associated with infections involving the mouth, pharynx, and eyes, while HSV2 primarily shows genital mucosal symptoms. Overlap between types occurs, and both viruses enter the central nervous system and cause systemic disease by the same mechanism.
The most common manifestation of HSV1 is primary herpetic gingivostomatitis. This is seen in young children older than 6 months of age and may be subclinical. A prodrome of fever, irritability, malaise, and loss of appetite lasting 1 to 2 days is followed by vesicles on the oral mucosa and tongue that rapidly rupture and become superficial and painful ulcers. Perioral extension of the ulcers is common. An intense gingivitis is almost always present and helps to distinguish HSV from coxsackievirus enanthems. Tender submandibular adenopathy is usually present. Symptoms may last up to 2 weeks (see Chapter 97 for the review of genital HSV) (Fig. 91-6A).
Herpes simplex. (Used with permission from Melissa Peters, MD)
Another common presentation of HSV is recurrent orofacial herpes, commonly referred to as “fever blisters.” This secondary phenomenon occurs in 15% to 40% of patients who have had symptomatic or asymptomatic primary herpetic oral infections. Reactivation of virus decreases with age. There may be a prodrome of pain or pruritis before emergence of the labial ulcer. Less frequently, intraoral vesicles may recur.
A number of distinct secondary manifestations of HSV occur. Patches of cutaneous HSV occur commonly from contact of abraded skin with active oral or other herpes lesions actively shedding virus. Outbreaks among athletes have been termed “herpes gladiatorum.” Herpetic whitlow is caused by secondary inoculation of virus from mouth to fingers. This is common in children with primary herpetic gingivostomatitis who suck their thumbs or fingers (Fig. 91-6B). To the untrained eye, a whitlow can be confused with paronychia, and attempts at drainage can cause damaging cosmetic results. This is a self-limited problem with complete resolution in 2 to 3 weeks.
Eczema herpeticum (Kaposi varicelliform eruption) is an uncommon but serious primary manifestation of HSV in children with atopic dermatitis and breaks in skin integrity. The virus is usually transmitted from a labial lesion on the caregiver to the eczematous eruption (Fig. 91-6C). Erythema multiforme (EM) has been associated with HSV reactivation and possibly with primary infections. In some series, presence of HSV with EM has been as high as 75%.18 Recurrent EM with recrudescence of HSV can occur repeatedly with attacks lasting up to 2 weeks. The characteristic acral EM rash (erythematous and of multiforme) occurs within 10 days of reactivation and may last 2 weeks (see Chapter 86).
In the US, neonatal herpes occurs in up to 0.15% of births.19 Most infections arise from intrapartum transfer of virus, but can be contracted postnatally from oral, genital, or hand contact from a caregiver or from contaminated fomites. Three distinct clinical entities can result. Disseminated herpes presents in the first 1 to 4 weeks of life with a clinical presentation similar to bacterial sepsis and a mortality rate of 25% with antiviral treatment. Symptoms may occur as late as 6 weeks of life. Herpes encephalitis may present with seizures in the neonatal period and, if untreated, will progress to systemic disease. Neonatal herpes with involvement limited to the skin, eye, and mouth can result in minimal morbidity if treated early with antiviral agents. Congenital HSV infection is rare, but presents as a small for gestational-age infant, usually premature, and with microcephaly, retinitis, and vesicular rash.
Uncomplicated HSV infection can be diagnosed clinically. When necessary, DFA of skin lesions provides quick and reliable results. PCR of the cerebrospinal fluid is particularly useful in diagnosing neonatal HSV and herpes encephalitis. Use of the Tzanck smear for diagnosis should be discouraged. There is a high incidence of false-negatives, and the Tzanck test cannot distinguish HSV from varicella-zoster virus. Culture from lesions or body fluids will grow in vitro in 1 to 15 days.
Serious complications are mainly limited to the immunocompromised host, the neonate, and those with involvement of the eye or central nervous system. Ocular herpes or herpes keratoconjunctivitis remains a major cause of blindness worldwide. Conjunctivitis can be unilateral or bilateral and result in corneal ulcerations. Herpes meningoencephalitis may occur at any age and have no skin manifestations at presentation. Neonatal herpes in the first 6 weeks of life, as described above has significant mortality and morbidity even with adequate treatment. Scarring is uncommon, but can occur, especially with eczema herpeticum in children with chronic cutaneous conditions.
Antiviral agents can suppress virus replication and modify the clinical course but cannot eradicate the virus. Acyclovir is the mainstay for systemic disease in neonates, infants, and young children. However, its poor bioavailability and short plasma half-life make newer but more expensive options attractive for treatment of adolescents and immunosuppressed hosts. These include drugs with greater bioavailability such as valacyclovir and famciclovir. (Table 91-1)
Topical antiviral agents such as docosanol 10%, penciclovir 1%, and acyclovir 5% creams have been shown to reduce the symptoms of recurrent labial herpes when started early during the prodrome. Careful monitoring for bacterial super infection is important as well, and should be addressed as it occurs.