Approach Considerations
Enteroviruses can be excreted in human feces for up to 3 months after infection. However, a clinically identifiable syndrome correlates with the acute phase of infection, during which time virus can be found in the throat, blood, and various organs.
There are no confirmatory laboratory tests, procedures, or imaging that are used in routine clinical practice for HFMD or herpangina. Diagnosis for these conditions mainly is based on clinical presentation and assessment.
Laboratory Studies
Definitive diagnosis of coxsackievirus infection can be made based on isolation of the virus in cell culture. Cytopathic effect usually can be seen within 2 to 6 days. Samples normally are taken from the stool or rectal swabs; the virus also can be isolated from the oropharynx early in the disease course. However, given improved sensitivity and faster turn-around time, polymerase chain reaction (PCR) has emerged as the most prominent diagnostic tool used for enteroviral detection. Serology is available as a diagnostic modality but can be difficult to interpret. Traditionally, enteroviral infections are diagnosed after a rise in neutralizing antibody titer (at least a 4-fold rise in titer between acute and convalescent phase).
Aseptic meningitis
Before a diagnosis of aseptic meningitis can be made, bacterial meningitis should be considered and excluded. Empiric antibiotics typically are required during this time period. Diagnosis requires cerebrospinal fluid (CSF) evaluation, which tends to show a lymphocytic predominance, normal-to-decreased glucose levels, and normal-to-slightly elevated protein levels. The virus can be isolated via PCR (sensitivity, 66-90%) and, much less commonly, cell culture (sensitivity, 30-35%). A recent study in infants reported that routine CSF PCR for enteroviruses resulted in shorter hospital stays (by 1.54 days) and a decreased duration of antibiotic use (by 33%).
Encephalitis
Diagnostic workup requires a lumbar puncture (LP) with CSF evaluation, which yields findings similar to those of aseptic meningitis.
Electroencephalography (EEG) can be considered in some patients, particularly for the evaluation of nonconvulsive or subclinical seizures. Enteroviral and other causes of viral encephalitis typically appear as diffuse background slowing on EEG, but epileptiform activity may be present as well. [20]
Please see section on Imaging Studies below for further recommendations
Myopericarditis
Laboratory tests generally are circumstantial, with evidence of infection based upon positive PCR tests from the oropharynx or feces, or upon serological testing.
Acute hemorrhagic conjunctivitis (AHC)
Diagnosis requires conjunctival swabs or scrapings, which are 90% successful. A rising antibody titer also can theoretically be used to confirm a diagnosis.
Imaging Studies
Computed tomographic (CT) scanning of the brain can be obtained upon initial presentation of patients with suspected meningitis and/or encephalitis to evaluate for hemorrhage, increased intracranial pressure, or mass lesions.
Magnetic Resonance Imaging (MRI) of the brain can show hyperintense signal uptake in the posterior brain stem, substantia nigra, dentate nucleus, and anterior horns of the spinal cord. [21]
Echocardiography should be used to evaluate cardiac function and valvular disease in patients with myopericarditis and/or heart failure.
Cardiovascular Magnetic Resonance (CMR) can be used to identify imaging features characteristic of myocarditis such as necrosis, scarring, and myocardial hyperemia and edema. [22]
Other Tests
Depending upon the clinical presentation, a throat culture can be obtained to evaluate for possible streptococcal pharyngitis and/or tonsillitis.
HIV testing can be considered in patients who present with nonspecific febrile illness or rashes, depending on the epidemiologic history.
ECG changes in myopericarditis include ST-segment elevations or nonspecific ST segment and/or T-wave abnormalities, arrhythmia, and heart block.
In select instances in which viral myocarditis is being considered as the etiological cause for new-onset heart failure, endomyocardial biopsy might be indicated.
Procedures
Lumbar puncture is crucial in the evaluation of suspected meningitis and/or encephalitis.
Skin biopsy rarely may be helpful in the evaluation of nonspecific exanthems.
Histologic Findings
Intracytoplasmic viral particles may be observed, especially with skin lesions and/or rashes of HFMD.
