Studies show that myocarditis is a relatively uncommon occurrence in children (Box 282.1). Myocarditis generally is a sporadic disease, although epidemics have been reported. In a significant number of cases, manifestations may be subclinical and recognized either through other findings (e.g., electrocardiographic changes) or, perhaps, not at all.

Myocarditis also may be only one component of a generalized disease and, if the cardiac dysfunction is mild, may be completely overlooked, which could explain the discrepancy between the clinical and the autopsy series. Myocarditis may be secondary to many of the common infectious illnesses that affect children and infants. Various causes are listed in Box 281.2. Alternatively, myocarditis may occur as a manifestation of hypersensitivity or as a toxic reaction to drug administration.

Until the early 1990s, coxsackievirus B was the most frequently reported cause of epidemics in children. This organism was found to be associated with myocarditis during a nursery epidemic in southern Rhodesia. Reports from Holland, the United States, Singapore, and South Africa have followed. Infections secondary to coxsackieviruses occur commonly throughout the general population. Target organs include the upper respiratory tract, gastrointestinal tract, liver (hepatitis), lung (pneumonia), central nervous system (meningoencephalitis), lymph nodes (infectious mononucleosis-like syndrome), kidney (hemolytic uremic syndrome), and heart (carditis). Significant titers of type-specific protective antibodies are present in most adults in the United States. After birth, spread occurs by the fecal-oral or airborne route. The coxsackievirus B organisms use receptors that are not shared with other enteroviruses to attach to their target cells. These receptors are thought to be an element essential for viral replication and may help determine tissue tropism. Infections caused by coxsackievirus B or enteroviruses are subclinical in 50% of cases. During an outbreak of coxsackievirus B in Europe, in 1965, cardiac manifestations were noted in 5% of patients. A much higher percentage (12%) of patients in similar outbreaks of the disease that same year in Scotland, Finland, and Austria developed some evidence of myocardial dysfunction. Whereas myocarditis is associated with coxsackievirus B serotypes 1 to 6, the most serious disease is attributed to types 3 and 4. Coxsackievirus B antigens have been demonstrated with the use of an immunofluorescent technique in 41% of 29 infants and children who were found at routine autopsy to have had interstitial myocarditis. Another study found 1,299 cases of unexpected death in an autopsy series of 2,427 patients; 20 cases of viral myocarditis were identified. Of the 20, nearly one-half had positive serologic evidence for coxsackievirus B infection. One investigator found a 9% incidence of myocarditis in 67 verified cases of influenza infection during a 1978 epidemic in Sweden. Although much less common, coxsackievirus A and echoviruses also are suspected etiologies.

Rubella virus, a teratogen present during the first trimester of pregnancy, also is implicated in myocarditis. Persistence of the virus in the fetus has been shown to produce severe cases of myocarditis. One study found 10 of 47 infants with congenital rubella to have evidence of myocarditis. Seven of these infants had active disease, and four died with severe myocardial failure. Morbidity secondary to chronic cardiac dysfunction was thought to be severe in the survivors. A significant reduction in the number of cases of congenital rubella has occurred because of aggressive immunization programs, and only 28 cases were recorded in 1975.

More recently, adenovirus has emerged as a major cause of this disease in children. The identification of this agent has been aided greatly by use of modern molecular biologic techniques, including in situ hybridization and polymerase chain reaction (PCR). PCR has been used to examine autopsy specimens of patients with myocarditis and a previously unidentified etiology. In those cases, adenovirus emerged as the major organism, placing it second in importance to the enteroviruses as the etiologic agent responsible for myocarditis.

Herpes simplex virus results in infections of newborns at a rate of 1 in 7,500 deliveries. Type 2 virus is found most commonly and usually is acquired from the genital tract.
Herpesvirus has been found in the myocardium of autopsy specimens, documenting its association with myocarditis.

During a 1-year period, investigators found a 5.8% incidence of myocarditis in 312 cases of varicella. In that study, patients who complained of skeletal myalgia seemed to have a significantly higher risk of developing cardiac involvement.

With the appearance of recent bioterrorism threats, the U.S. Department of Defense initiated a Smallpox Vaccination Program in December of 2002. In little more than 2 years, they had immunized 615,000 personnel, representing the largest smallpox vaccination program in 25 years. Within a cohort of 540,824 people vaccinated, 67 developed a myopericarditis as evidenced by symptoms of chest pain and enzymatic (troponin) as well as echocardiographic and electrocardiographic evidence of disease. These cases all developed within 30 days of receiving vaccination and fortunately, all recovered. This information may be important should any further initiatives be needed in the future.