History
Fifty to eighty percent of patients with echoviral infections are asymptomatic. The most common presentation is a nonfocal, asymptomatic febrile illness. Illnesses may be caused by virtually any enteroviral serotype and are indistinguishable clinically from infection with many other viral agents. Disease syndromes characteristic of enteroviral infections (eg, aseptic meningitis, pericarditis) are, in fact, unusual manifestations of infection. Severe hepatitis, hepatic failure, and disseminated enteroviral infections have been reported in neonates, hematolymphoid malignancies, and hematopoietic transplant recipients. [19, 20]
Acute aseptic meningitis
Acute aseptic meningitis manifests as signs and symptoms of meningeal irritation and cerebrospinal fluid (CSF) pleocytosis in the absence of bacteria or fungi. CSF cell counts are typically 10-500/µL and may show neutrophil predominance early but invariably shift to a lymphocyte predominance. [9]
The onset may be gradual or abrupt. Echoviral meningitis may have a biphasic pattern. Fever and myalgias with clinical defervescence followed by reappearance of fever and headache herald the onset of meningitis, similar to what is observed in poliomyelitis.
Meningismus, when present, varies from mild to severe. Only about one third of patients demonstrate Kernig and Brudzinski signs. Pharyngitis and other symptoms of upper respiratory tract infection are often present. [9]
Complications such as febrile seizures, lethargy, coma, and movement disorders are reported in 5% to 10% of cases and may overlap with an encephalitis-type illness. Adults may experience a longer period of fever and illness than younger patients, and those with severe cases may be incapacitated for 1-2 weeks.
Encephalitis
Encephalitis is a well-described, but rare, manifestation of coxsackievirus and echovirus CNS infection.
Symptoms include lethargy, drowsiness, personality changes, seizures, paresis, and coma.
Although quite rare, enteroviral CNS infections have been reported to cause an encephalitis lethargica–type picture with oculogyric crisis, cranial nerve palsies, and a parkinsonism-like picture.
Rash
Skin rashes are more common with echoviral infections than with other enteroviral infections. Exanthems may be maculopapular, morbilliform, macular, petechial, or papulopustular.
Respiratory illness
Echovirus, similar to many enteroviruses, may be associated with pyrexial illness (the so-called summer grippe), with sore throat, cough, or coryza.
Echovirus 11 can be associated with croup.
Herpangina
Herpangina is a well-characterized, vesicular, oral mucosal process involving the tonsillar fossa and soft palate. Symptoms include elevated temperature, pharyngitis, and dysphagia.
It is commonly observed in summer outbreaks involving younger children, often younger than 10 years, and less common in adolescents and young adults.
Herpangina begins abruptly with fevers as high as 104°F and is associated with nonpersistent vomiting, myalgia, and headache. Sore throat and dysphagia are the prominent symptoms and precede the appearance of the oral lesions.
Epidemic pleurodynia (Bornholm disease)
First described by William Cooper, MD, in 1888, the term "devil's grip" was used to describe cases from an outbreak of fever and chest pain. The illness is characterized by an abrupt onset of fever and sharp spasms of pain involving the intercostal muscles. Pain also may involve abdominal muscles and mimic acute abdomen.
Major epidemics have occurred at infrequent 10- to 20-year intervals. It typically affects older adults, with children having a milder course.
The illness usually is self-limited, with resolution in most individuals within 1 week. The first episode of pain usually is the most symptomatic. Subsequent episodes tend to be shorter in duration and accompanied by lower temperature elevation. Dull aching of involved muscles may be reported between episodes, but the patient usually appears well between the paroxysms.
Most patients recover within a week, but about 25% may experience relapses up to a month after the first attack.
Paralysis and other neurologic complications of echovirus infection
Paralytic disease caused by nonpolio enteroviruses usually is less prominent than poliovirus-associated paralysis. Muscle weakness is more common than flaccid paralysis and usually is not permanent. Cranial nerve involvement has been reported and usually manifests as oculomotor palsy. Cases of fatal bulbar involvement have been reported.
Guillain-Barré syndrome has been reported rarely in patients infected with echovirus serotypes 6, 7, [21] and 22.
Transverse myelitis has been reported with echovirus 2, 5, 11, [22] 18, [23] 19, 25, and 30. [24]
Myocardial/pericardial disease
Enteroviral myocarditis often is associated with an upper respiratory tract illness and may occur at any age, but seems to be particularly prominent in adolescents and young adults. Males are affected twice as often as females. In many cases, an upper respiratory tract illness is reported within 2 weeks prior to the onset of cardiac manifestations.
Common symptoms include shortness of breath, chest pain, fever, and weakness.
Orchitis
Orchitis has been rarely reported with echovirus 6 [25] and 30, [26] in both cases in association with aseptic meningitis.
Physical
Acute aseptic meningitis
The highest rates of clinically recognized aseptic meningitis are reported in infants younger than 3 months. This observation may, in part, be related to the practice of performing lumbar punctures for pyrexia in this age group.
Only a small number of the infants have clinical evidence of neurologic disease.
Adults with acute aseptic meningitis demonstrate signs and symptoms of meningeal irritation and typically have a brief prodrome of fever and chills. Headache usually is a predominant complaint and may be accompanied by neck stiffness, pharyngitis, and symptoms of upper respiratory tract infections. [9]
Encephalitis
This primarily affects children and young adults.
Encephalitis can complicate aseptic meningitis or may occur in the absence of meningitis.
Focal encephalitis can manifest as a spectrum of signs, including partial motor seizures, hemichorea, and/or acute cerebellar ataxia.
Paralysis (and other neurologic complications) of echoviral infections
Paralysis caused by nonpolio enteroviruses is usually less severe than that caused by polioviruses.
Muscle weakness is more common than flaccid paralysis.
Cranial nerve involvement occasionally has been associated with unilateral oculomotor palsy.
Guillain-Barré syndrome and transverse myelitis are extremely rare complications of enteroviral infection. [9]
Vesicular rashes
Vesicular rashes are similar to lesions of hand-foot-and-mouth disease but occur in crops on the head, trunk, and extremities.
Unlike chickenpox, these vesicles do not progress to pustules and scabs. Herpetiform rash caused by echovirus 11 has been reported in immunocompromised adult patients.
Petechial and purpuric rashes have been reported with echovirus 9 and coxsackievirus A9 infections. When these rashes have a hemorrhagic component, the illness can be confused with meningococcal disease, particularly when aseptic meningitis occurs.
Acute respiratory disease
Enteroviral upper respiratory tract illness is clinically similar to diseases caused by other agents, including rhinovirus, adenovirus, respiratory syncytial virus, and mycoplasma.
Herpangina
This is characterized by pharyngeal erythema and mild tonsillar exudate.
Painful lesions originate as small macules and evolve over a day to erythematous centrally ulcerated papules that are 2-4 mm in diameter. Palatal lesions number no more than 10-12. Pyrexia resolves over 2-4 days, but the enanthem may persist for as long as a week.
Pleurodynia
Despite its name, pleurodynia is a disease of muscle, not of the pleura or peritoneum. It likely results from direct viral invasion of muscles. In many cases, the pain can be reproduced by pressure on the affected muscles. Palpable, sometimes visible, muscle swelling can be found.
It begins abruptly with spasmodic pain, usually involving the lower part of the rib cage or adjacent abdominal area. Pyrexia as high as 39.5°C occurs within 1 hour after the onset of the spasm, subsiding with the pain. Sore throat and headache can occur, but cough and rhinitis are absent.
The pain often is poorly localized, and its severity varies substantially. It is described as sticking, lancinating, stabbing, constricting, or viselike. Most commonly, the pain occurs at the costovertebral angle and can be unilateral or bilateral. Adults tend to have more thoracic pain involving the intercostal muscles. Pain may occur in the upper abdomen or the epigastrium. Periumbilical pain and pain in the lower abdomen is more common in children.
Spasmodic pain is characteristic. Chest pain may produce thoracic splinting with shallow rapid respiration.
Chronic meningoencephalitis
This may develop in hosts who are agammaglobulinemic or otherwise immunocompromised.
Enteroviral infections can be associated with considerable morbidity and mortality in immunocompromised hosts. Persistent and sometimes fatal CNS infections have been associated with defective B-lymphocyte function. Most cases occur in children with X-linked agammaglobulinemia. [27, 28]
Nervous system manifestations may be totally absent or may present as meningismus, headache, lethargy, papilledema, seizure disorders, motor weakness, tremors, or ataxia. These abnormalities may fluctuate in severity, disappear, or progress steadily.
Myopericarditis
Enteroviral infections can produce myopericarditis, with severity ranging from asymptomatic disease to intractable heart failure. Sudden death may occur in apparently healthy adults who are later found to have evidence of viral myocarditis at autopsy.
Epidemic enteroviral myopericarditis appears to be rare. Most cases have been sporadic, even during enteroviral epidemics.
Chest pain occurs in as many as 90% of cases and often is dull in nature. A transient friction rub has been observed in 35% to 80% of cases.
Causes
Acute aseptic meningitis
More than 90% of community-acquired cases of viral meningitis are caused by group B coxsackieviruses or echoviruses. The most common serotypes are group B coxsackievirus serotypes 2-5 and echovirus serotypes 4, 6, 9, 11, 16, and 30.
Aseptic meningitis is most commonly associated with echovirus 30. [1]
Encephalitis
Enteroviruses, including poliovirus, account for 10% to 20% of proven cases of viral encephalitis. This ranks behind arboviruses, herpes simplex virus, and lymphocytic choriomeningitis viruses.
Many serotypes have been implicated as causes of encephalitis; coxsackievirus types A9, B2, and B5 and echovirus types 6 and 9 are the serotypes reported most often. The evidence linking each of these serotypes to encephalitis is quite variable.
Paralysis and other neurologic complications of echovirus infections
Sporadic cases of flaccid motor paralysis are associated with echoviruses 6 and 9.
Less frequently implicated serotypes include echoviruses 1-4, 7, 11, 14, 16-18, and 30. [29]
Rash
The virus can be isolated from the vesicular lesions of patients with hand-foot-and-mouth disease; therefore, these lesions appear to be a direct result of viral invasion of the skin after viremia.
Serotypes associated with rubellalike rash include coxsackievirus A9 and echoviruses 2, 4, 11, 19, and 25.
Vesicular herpetiform eruptions have been linked to coxsackievirus A9 and echovirus 11.
Respiratory tract infection
Among the echoviruses, serotype 11 is the most firmly established cause of respiratory disease, although serotypes 4, 8, 9, 20, 22, and 25 also may be causal agents.
In volunteers infected experimentally and, occasionally, in patients with naturally acquired disease, some coxsackieviruses and echoviruses may be linked with pneumonia. The role of enteroviruses in lower respiratory illness is not clearly defined; at present, they should be thought of as rare causes of pneumonia.
Herpangina
Group A coxsackieviruses (serotypes 1-10, 16, and 22) most commonly are recovered from patients with herpangina. Other less commonly isolated serotypes from herpangina include group B coxsackieviruses 1-5 and echoviruses 3, 6, 9, 16, 17, 25, and 30.
Epidemic pleurodynia
Group B coxsackievirus is the most important cause of epidemic pleurodynia. Less common agents implicated as a cause of pleurodynia include some group A coxsackieviruses and echoviruses 1, 6, 9, 16, and 19. [30]
Chronic meningoencephalitis
This is seen in agammaglobulinemic and immunocompromised hosts.
Echoviruses (and polioviruses) can cause persistent and even fatal CNS infections in immunocompromised patients. Picornaviruses require an extracellular phase for cell-to-cell transfer, providing an opportunity for the virus to be inactivated by antibody-mediated mechanisms.
Most cases have been caused by echoviruses, including types 5, 6, 7, 11, and 27.
Myopericarditis
Enteroviruses appear to be the most common viral etiology of acute myopericarditis. In older children and adults, the disease can range from asymptomatic cardiac involvement to intractable heart failure and death.
Experimental studies in murine models strongly suggest that viral replication occurs in myocytes and results in myocyte necrosis and focal infiltration by inflammatory cells.
A chronic inflammatory process can persist, with variable degrees of fibrosis and loss of myocytes. [9]
Hepatitis
Fulminant hepatitis has been reported with echovirus 9, 18, and 25 in persons receiving anti-CD 20 antibody. [31]
Complications
Acute aseptic meningitis
Complications (eg, febrile seizures, complex seizures, lethargy, coma, movement disorders) occur early in the course of aseptic meningitis in 5% to 10% of patients.
Adults may experience a more prolonged period of fever and headache than infants and children; some adult patients may require weeks to return to normal activity.
Paralysis and other neurologic complications
Paralytic disease caused by nonpolio enteroviruses characteristically is less severe than poliovirus-associated paralysis. In fact, muscle weakness is more common than flaccid paralysis, and the paresis usually is not permanent.
Cranial nerve involvement occasionally has resulted in complete unilateral oculomotor palsy. Cases of fatal bulbar involvement are rare.
Guillain-Barré syndrome and transverse myelitis have been reported in a small number of patients in association with echovirus.
