Sarah S. Long
Herpangina is a common, specific, acute febrile viral illness that usually occurs in epidemic form in young children in the summer and fall in temperate climates. Although the clinical symptoms and signs were mentioned in 1906, Zahorsky introduced the name herpangina in 1924, to distinguish the clinical entity.
At least 24 enteroviral agents have been isolated in epidemic or sporadic cases of herpangina. Group A coxsackieviruses were associated definitively in the early 1950s with summer epidemics of herpangina, when suckling mice were inoculated for virus isolation; nine different group A coxsackieviruses have been documented to cause epidemic herpangina. With use of serology, tissue-culture, and molecular diagnostic techniques, multiple echoviruses, group B coxsackieviruses, and enterovirus 71 also have been associated with epidemic or sporadic cases of herpangina. Other viruses, such as herpes simplex virus (HSV) and polioviruses, are occasional causes of nonepidemic herpangina. Group A coxsackieviruses probably continue to be the most common cause of herpangina, although confirmation is lacking because some group A viruses are recovered only after the inoculation of suckling mice.
Coxsackieviruses are 30-nm particles composed of a single strand of RNA with a protein coat of icosahedral symmetry. Morphologically, they are indistinguishable from each other and from other enteroviruses, are stable at a pH of 3, and are resistant to inactivation by ether. Assignment of a virus to group A or group B is based on its chemical properties, ability to grow in tissue cultures, pathogenicity for laboratory animals, and serologic reactivity.
Enteroviruses have a worldwide distribution, and they produce disease in both sporadic and epidemic forms, particularly during summer in temperate climates. Sporadic cases occur throughout the year. Humans are the only known natural host. The majority of enteroviral infections cause either no symptoms or mild nonspecific febrile illnesses. Illness is reported most commonly in children of 1 to 4 years of age. In a family study of enterovirus 71, the transmission rate to household contacts was 52%, with 53% of infected adults but only 6% of children remaining asymptomatic. In epidemic enteroviral disease, all age groups can be symptomatic.
In experimental infection with coxsackievirus A4 in rhesus monkeys, oropharyngeal lesions typical of herpangina developed 2 to 7 days after inoculation. The data suggest that, regardless of the site of inoculation, oropharyngeal lesions occur and represent the secondary site of infection after viremia, rather than the primary site of viral replication.
In humans, the transmission of the viruses that cause herpangina is predominantly fecal-oral or oral-oral. Airborne transmission probably occurs, but is less common. Viruses can be isolated from throat and fecal specimens in the acute phase of illness and from fecal specimens for several weeks after recovery. Infection elicits the production of type-specific humoral and secretory antibody. The role of cellular immune responses is not well-defined. Infection appears to elicit life-long protection from clinical illness caused by the same agent. Local reinfection with a brief period of viral replication occurs.
CLINICAL MANIFESTATIONS AND COMPLICATIONS
The diagnosis of herpangina is suggested by the presence and character of lesions in the oropharynx. With no prodrome, or only a few hours of anorexia or listlessness, herpangina begins suddenly with the onset of fever. Temperature varies from normal to 41°C, and onset can be accompanied by a seizure. High fever, listlessness, and vomiting are more common in children younger than 5 years. Headache, backache, sore throat, and dysphagia are noted by older patients. Usually, the oropharyngeal lesions are present at the onset of fever or occur in the subsequent 24 hours. The characteristic lesion evolves from a small papule to a 1- to 2-mm vesicle with surrounding erythema and then to an ulcer. Lesions enlarge to only 3 to 4 mm over the cause of 3 days and remain discrete (i.e., do not coalesce, as do ulcers of HSV infection, mucositis, and Stevens-Johnson syndrome). The average number of lesions is five, with more than 20 being distinctly unusual. Characteristically, lesions involve the anterior tonsillar pillars, tonsils, soft palate, uvula, and pharyngeal wall. Occasionally, posterior buccal surfaces and the tip of the tongue are involved. The diagnosis of herpangina should be made only when the enanthem on the posterior oral cavity is obvious. Usually, other diseases associated with enanthems can be distinguished by careful attention to the number, size, and nature of the lesions involved. Features differentiating herpangina from other diseases with enanthems are shown in Table 257.1. Depending on the enterovirus circulating, epidemic aseptic meningitis can accompany herpangina. Enterovirus 71 is unduly complicated by poliomyelitis-like syndrome, encephalomyelitis, and cardiopulmonary failure.