Respiratory disease – Upper respiratory tract symptoms, eg, sore throat and coryza, are common with enterovirus infections. Lower respiratory tract involvement may include pneumonia and bronchiolitis. Pleurodynia is associated with paroxysmal thoracic pain. EV-D68 has been associated with lower respiratory tract disease, both in children with and without asthma.
Acute hemorrhagic conjunctivitis – Epidemic; associated with severe eye pain, photophobia, conjunctival erythema, and congestion. (See also hemorrhagic viral conjunctivitis.)
Myocarditis / pericarditis – Upper respiratory symptoms typically precede onset of fatigue, chest pain, and shortness of breath.
Encephalitis / meningoencephalitis – Acute onset of altered mental status, abnormal neurologic examination, and/or seizures. Brainstem encephalitis (EV-A71) can lead to noncardiogenic pulmonary edema and nonmyocarditic cardiopulmonary collapse.
Polio-like acute flaccid paralysis – Prodromal febrile illness followed by acute, typically asymmetric, flaccid weakness of the limbs with decreased reflexes and intact sensation; cranial nerve dysfunction may also be present. Several nonpolio enteroviruses are associated with acute flaccid paralysis in children similar to that caused by polioviruses. Most notably, clusters of acute flaccid paralysis in children have been associated with EV-A71 outbreaks, some of which have been widespread in parts of Asia. Geographic and temporal association of acute flaccid paralysis and cranial nerve dysfunction in children during outbreaks of EV-D68 respiratory disease in 2014 in the United States was noted. Acute flaccid paralysis temporally associated with the EV-D68 outbreak is referred to as acute flaccid myelitis. Per the Centers for Disease Control and Prevention (CDC), on September 9, 2022, the CDC Health Alert Network urged health care providers to consider EV-D68 as a possible cause of acute, severe respiratory illness (with or without fever) in children and the potential for an increase in acute flaccid myelitis cases in the upcoming weeks.
Enterovirus infections can occur throughout the year but most commonly cause outbreaks of disease in the late summer and early fall in temperate regions.
Most enterovirus infections are self-limited and not immediately life-threatening. However, some presentations can represent life-threatening emergencies, including brainstem encephalitis, myocarditis, severe respiratory distress, and neonatal enterovirus sepsis. Neonates, children with immunoglobulin deficiencies, and transplant recipients are predisposed to more severe and persistent disease. Long-term morbidity may occur, including chronic dilated cardiomyopathy, persistent neurologic deficits, and polio-like acute flaccid paralytic disease.
Note: In 2022 and 2023, pediatric invasive group A streptococcal (iGAS) infections and noninvasive group A streptococcal infection cases have been associated with respiratory infections due to enterovirus among other viruses. Concurrent or preceding viral infections, including varicella (chickenpox), may increase risk for iGAS infection. Severe outcomes of iGAS infections include necrotizing fasciitis, streptococcal toxic shock syndrome, and death.
Bacterial pericarditis (Staphylococcus aureus, H influenzae, M pneumoniae) – Typically high fever, purulent pericardial effusion, elevated inflammatory markers. Positive blood or pericardial bacterial cultures.
Other viruses (adenovirus, influenza, etc) – Can present similarly and be difficult to differentiate. Viral PCR of nasopharynx, bronchoalveolar lavage, blood, pericardial fluid, or myocardial biopsy can assist in identification.
Central nervous system disease – Viral meningitis, encephalitis, and polio-like acute flaccid paralysis:
Bacterial meningitis (S pneumoniae, H influenzae, Neisseria meningitidis) – Ill-appearing children with high fever and meningeal signs. Typically high cerebrospinal fluid (CSF) white blood count (>500/mm3), low CSF glucose, high CSF protein. Positive CSF gram stain and culture.