Dermatologic Manifestations of Enteroviral Infections 

The human enterovirus genus is a member of the Picornaviridae family of small, icosahedral, single-stranded, positive-sense RNA viruses. A total of 92 serotypes are currently recognized by the International Committee on Taxonomy of Viruses classification^[1] :

• Human enterovirus type A (17 serotypes): These include coxsackie A virus types 2-10, 12, 14, and 16 and echovirus type 71. New enterovirus serotypes were described in 2005 (types 76, 89, 90, and 91), and it is believed that they are a subgroup of human enterovirus type A.^[2]
• Human enterovirus type B (56 serotypes): These include coxsackie A virus type 9; coxsackie B virus types 1-6; echovirus types 1-7, 9, 11-21, 24-27, and 29-33; and enterovirus type 69. The 13 new serotypes reported in 2007 (enterovirus types 79-88, 97, 100, and 101) are probably members of human enterovirus type B.^[2]
• Human enterovirus type C (16 serotypes) - The most well known are coxsackie A virus types 1, 11, 13, 15, 17-22, and 24. Poliovirus types 1-3 have been included in this group.
• Human enterovirus type D - Enterovirus types 68 and 70, including several newly identified serotypes, such as enterovirus 73-75^{[3, 4]} and enterovirus types 77-78^[5]

Human enteroviruses are distributed worldwide, with 2 major patterns of infections, endemic and epidemic, within a given geographical area.^[1]

Enteroviruses usually cause transient, often subclinical, infections. Enteroviruses are also responsible for a wide variety of syndromes, including exanthematic fever, enteritis, encephalitis, aseptic meningitis, myocarditis, and respiratory tract infections. Coxsackieviruses, echoviruses, and enterovirus type 71 are also significant causes of cutaneous disease. A relationship between enterovirus RNA and chronic fatigue syndrome has been described,^[6] and these viruses could initiate and perpetuate the immunological response seen in chronic fatigue syndrome.

Coxsackieviruses are separated into 2 groups, A and B. Coxsackie A viruses are the primary etiologic agents of herpangina and hand-foot-and-mouth disease (HFMD). Coxsackie B viruses are associated with epidemic pleurodynia (ie, Bornholm disease), epidemic myalgia, myocarditis, and pericarditis. Bowles et al suggest that coxsackie B virus may be an etiologic agent of juvenile dermatomyositis.^[7]

Zahorsky first described the clinical spectrum of herpangina in 1920. Later, coxsackie A virus was isolated from pharyngeal washings and stool samples of patients with herpangina. Subsequently, many reports have confirmed this association. Robinson et al first isolated the coxsackie A virus type 16 serotype in 1957 during a Canadian epidemic of exanthema and stomatitis.^[8] Two years later, Alsop et al used the term hand-foot-and-mouth disease to describe a similar eruption in England.^[9]

Echoviruses include 34 distinct serotypes, and at least half can cause a rash. The 2 skin diseases specifically associated with echoviruses are Boston exanthem disease (BED), caused by echovirus type 16, and eruptive pseudoangiomatosis, (EP) caused by echovirus types 25 and 32.

Enteroviruses are spread from person to person by oral-oral and fecal-oral routes and, because the virus can be isolated from cutaneous and ocular lesions, presumably, may also be transmitted through direct contact with fluid from these cutaneous and ocular lesions.

Another source of infection could be swimming pools because enteroviruses are easily detectable in natural and treated water sources.

It has been suggested that enteroviruses can be transmitted antenatally, either transplacentally or potentially via ascending infection. When maternal enterovirus infection is acquired during late pregnancy, vertical transmission has been shown to be relatively common.^[2]

The viral incubation period is usually 2-5 days. The viruses are highly contagious, and they are a common cause of widespread outbreaks. After the ingestion of infectious material, enteroviruses are implanted and replicated in the alimentary tract (nasopharynx and ileum). If local replication is limited, the disease remains asymptomatic. If the virus passes into the regional lymphatic nodes and the reticuloendothelial system organs, minor or nonspecific disease may develop. Virus may also spread by the hematologic route, which results in a more severe and characteristically systemic illness.

Immune activation by the enterovirus leads to the production of immunoglobulin M (IgM) type-specific antibodies, which may be detected in the serum 1 week after infection. They are responsible for neutralization and rapid elimination of the virus from the blood and other sites of implantation. Serum IgM antibodies can be detected for 6 months after the patient's recovery, and convalescent immunoglobulin G can be detected for 1-2 years. Most enteroviral infections confer lifelong immunity to the serotype-specific agent. In addition, antibodies to these related viruses are known to cross-react, and they do so in different patterns, based on the country, serotype, and specific population, making comparisons of disease-based studies amongst these groups difficult.

Frequency

United States

Although enteroviruses are responsible for an estimated 50 million infections and 30,000-50,000 hospitalizations each year, note that less than 1% of infections result in significant symptomatic illness and the vast majority of hospitalizations are for aseptic meningitis.^[10]

International

The frequency is not known, but some estimates put the number at 1 billion or more annually worldwide. Persons in lower socioeconomic groups are more frequently affected than persons in other groups.

Mortality/Morbidity

Occasionally, cardiac and neurological complications occur. Deaths in neonates infected with enteroviruses have been reported. They are usually the result of fulminant myocarditis.

When viral transmission is antenatal, neonatal enterovirus infection is very severe and has a poor outcome.^[2]

Sex

Some authors suggest a slight male predominance, but this has not been confirmed.

Age

Enteroviral infections mainly affect children younger than 10 years, probably because they lack cross-reacting immunity resulting from repeated exposures, but they are not uncommon in adults.