Neonatal

In newborn infants, herpes simplex virus (HSV) infection can manifest as the following: (1) disseminated disease involving multiple organs, most prominently liver and lungs, but in 60% to 75% of cases also involving the central nervous system; (2) localized central nervous system (CNS) disease, with or without skin involvement (CNS disease); or (3) disease localized to the skin, eyes, and mouth (SEM disease). Approximately 20% of cases of neonatal HSV manifest as disseminated disease, one third manifest as CNS disease, and 40% to 45% manifest as SEM disease. Approximately 60% of neonates with disseminated disease or CNS disease have skin lesions, and approximately 80% to 85% of neonates with SEM disease will have skin involvement. In the absence of skin lesions, the diagnosis of neonatal HSV infection is difficult. Disseminated infection should be considered in neonates with sepsis syndrome, negative bacteriologic culture results, and severe liver dysfunction. HSV also should be considered as a causative agent in neonates with fever, irritability, and abnormal cerebrospinal fluid (CSF) findings, especially in the presence of seizures or during a time of year when enteroviruses are not circulating in the community. Although asymptomatic HSV infection is common in older children, it rarely, if ever, occurs in neonates.

Neonatal herpetic infections often are severe, with attendant high mortality and morbidity rates, even when antiviral therapy is administered. Recurrent skin lesions are common in surviving infants and may be associated with CNS sequelae if skin lesions occur frequently during the first 6 months of life.

Initial signs of HSV infection can occur anytime between birth and approximately 6 weeks of age, although most infected infants develop clinical disease within the first month of life. Infants with disseminated disease and SEM disease have an earlier age of onset, typically presenting between the first and second weeks of life; infants with CNS disease usually present with illness between the second and third weeks of life.

Children Beyond the Neonatal Period and Adolescents

Most primary HSV infections during the period of childhood beyond the neonatal period are asymptomatic. Gingivostomatitis, which is the most common clinical manifestation of HSV during childhood, is caused by HSV type 1 (HSV-1) and is characterized by fever, irritability, tender submandibular adenopathy, and an ulcerative enanthem involving the gingiva and mucous membranes of the mouth, often with perioral vesicular lesions.

Genital herpes, which is the most common manifestation of primary HSV infection in adolescents and adults, is characterized by vesicular or ulcerative lesions of the male or female genital organs, perineum, or both. Genital herpes usually is caused by HSV type 2 (HSV-2), but at least 20% of genital herpes is caused by HSV-1. Most cases of primary genital herpes infection are not recognized as such by the infected person or diagnosed by a health care professional.

Eczema herpeticum with vesicular lesions concentrated in the areas of eczematous involvement can develop in patients with dermatitis who are infected with HSV.

In immunocompromised patients, severe local lesions and, less commonly, disseminated HSV infection with generalized vesicular skin lesions and visceral involvement can occur.

After primary infection, HSV persists for life in a latent form. The site of latency for virus causing herpes labialis is the trigeminal ganglion, and the usual site of latency for genital herpes is the sacral dorsal root ganglia, although any of the sensory ganglia can be involved, depending on the site of primary infection. Reactivation of latent virus most commonly is asymptomatic. When symptomatic, recurrent herpes labialis HSV-1 manifests as single or grouped vesicles in the perioral region, usually on the vermilion border of the lips (typically called "cold sores" or "fever blisters"). Symptomatic recurrent genital herpes manifests as vesicular lesions on the penis, scrotum, vulva, cervix, buttocks, perianal areas, thighs, or back. Recurrences may be heralded by a prodrome of burning or itching at the site of an incipient recurrence, identification of which can be useful in instituting antiviral therapy early.

Conjunctivitis and keratitis can result from primary or recurrent HSV infection. Herpetic whitlow consists of single or multiple vesicular lesions on the distal parts of fingers. HSV infection also can be a precipitating factor in erythema multiforme.

HSV encephalitis (HSE) occurs in children beyond the neonatal period or in adolescents and adults and can result from primary or recurrent HSV-1 infection. Symptoms and signs usually include fever, alterations in the state of consciousness, personality changes, seizures, and focal neurologic findings. Encephalitis commonly has an acute onset with a fulminant course, leading to coma and death in untreated patients. HSE usually involves the temporal lobe; thus, temporal lobe abnormalities on imaging studies or encephalography in the context of a consistent clinical picture should increase the suspicion for HSE. Cerebrospinal fluid pleocytosis with a predominance of lymphocytes and some erythrocytes is usual. HSV infection also can cause meningitis with nonspecific Clinical Manifestations that usually are mild and self-limited. Such episodes of meningitis usually are associated with genital HSV-2 infection. A number of unusual CNS manifestations of HSV have been described, including Bell palsy, atypical pain syndromes, trigeminal neuralgia, ascending myelitis, postinfectious encephalomyelitis, and Mollaret meningitis.