Introduction
Background
Coxsackieviruses belong to the family Picornaviridae and the genus Enterovirus, which also includes poliovirus and echovirus. Enteroviruses are among the most common and important human pathogens. Coxsackieviruses share many characteristics with poliovirus. With control of poliovirus infections in much of the world, more attention has been focused on understanding the nonpolio enteroviruses such as coxsackievirus.
Coxsackieviruses are nonenveloped viruses with linear single-stranded RNA. Coxsackieviruses are divided into group A and group B viruses based on early observations of their pathogenicity in mice. Group A coxsackieviruses were noted to cause a flaccid paralysis, which was caused by generalized myositis, while group B coxsackieviruses were noted to cause a spastic paralysis due to focal muscle injury and degeneration of neuronal tissue. At least 23 serotypes (1-22, 24) of group A and 6 serotypes (1-6) of group B are recognized.
In general, group A coxsackieviruses tend to infect the skin and mucous membranes, causing herpangina, acute hemorrhagic conjunctivitis (AHC), and hand-foot-and-mouth (HFM) disease. Group B coxsackieviruses tend to infect the heart, pleura, pancreas, and liver, causing pleurodynia, myocarditis, pericarditis, and hepatitis. Both group A and group B coxsackieviruses can cause nonspecific febrile illnesses, rashes, upper respiratory tract disease, and aseptic meningitis.
The development of insulin-dependent diabetes (IDDM) has recently been associated with recent enteroviral infection, particularly coxsackievirus B infection. This relationship is currently being studied further.
Pathophysiology
Coxsackieviruses are transmitted primarily via the fecal-oral route and respiratory aerosols, although transmission via fomites is possible. The viruses initially replicate in the upper respiratory tract and the distal small bowel. They have been found in the respiratory tract up to 3 weeks after initial infection and in feces up to 8 weeks after initial infection. The viruses have been found to replicate in the submucosal lymph tissue and disseminate to the reticuloendothelial system. Further dissemination to target organs occurs following a secondary viremia.
Frequency
United States
Approximately 10 million symptomatic enteroviral infections are estimated to occur annually in the United States. From 2002-2004, an estimated 16.4-24.3% of these illnesses were attributed to coxsackievirus serotypes. For 2 of the 3 years, coxsackievirus B1 was the predominant serotype. The Centers for Disease Control and Prevention (CDC) found that coxsackievirus infections accounted for approximately 25% of all neonatal enterovirus infections (26,737) from 1983 to 2003.1 Those due to coxsackievirus B4 were associated with a higher mortality rate than any other serotype.
International
Coxsackievirus infections have worldwide distribution. They can be isolated year-round in tropical climates, with a decreasing incidence of disease and seasonality in areas of higher latitude.
Mortality/Morbidity
Mortality due to coxsackievirus infection is uncommon. Neonates and immunocompromised individuals are at most risk for complications secondary to all enteroviral infections.
Sex
During the first decade, enteroviral infections are more common in males, with a male-to-female ratio of 2:1. The reason for this increased incidence is not well known.
Age
Coxsackievirus infection occurs in all age groups but is more common in young children and infants. Children are at higher risk of infection during the first year of life. The rate of illness decreases greatly following the first decade of life.
Clinical
History
Ninety percent of coxsackieviruses infections are asymptomatic or cause nonspecific febrile illnesses. In neonates, they are the most common cause of febrile illnesses during the summer and fall months. Thirteen percent of newborns with fever in the first month of life were noted to have an enteroviral infection. In addition to nonspecific illnesses, various well-described illnesses have been associated with coxsackievirus infections.- Aseptic meningitis
- Patients with aseptic meningitis may have rapid or gradual onset of fever and chills, nausea and vomiting, malaise, headaches, neck pain, light sensitivity, and upper respiratory symptoms. Infants younger than 12 months have been noted to have the greatest incidence of meningitis. These infants often present with only a febrile illness characterized by irritability and anorexia. Meningismus occurs in only approximately 50% of infants with enteroviral meningitis.
- Coxsackievirus B infection is more likely than coxsackievirus A to be associated with meningitis.
- Seizures, lethargy, and movement disorders have been reported in 5-10% of patients with enteroviral meningitis. No long-term neurologic deficits appear to exist in infants with aseptic meningitis.
- Encephalitis is an unusual manifestation of CNS infection, although it is sometimes observed in association with aseptic meningitis. Coxsackievirus infection accounts for approximately 5% of all cases of encephalitis. In rare cases, it mimics encephalitis secondary to herpes simplex virus.
- Rarely, coxsackieviruses have been implicated in additional neurologic diseases. Coxsackievirus A7 has been noted to cause sporadic motor neuron paralysis that closely mimics poliovirus infection. Additionally, cases of Guillain-Barré syndrome have been described.
- Myopericarditis may present in patients of any age.
- Manifestations of myopericarditis range from an asymptomatic presentation to heart failure and death. Between the two extremes, most patients report dyspnea, chest pain, fever, and malaise.
- Symptoms may be preceded by an upper respiratory infection within the preceding 7-14 days.
- Presenting signs include pericardial friction rub, gallop rhythm, and cardiomegaly and/or pericardial effusion on chest radiography.
ECG abnormalities may range from ST-segment elevations to heart block. Echocardiography may show diminished ejection fractions and left ventricular wall abnormalities. - The male-to-female ratio is 2:1. The mortality rate is low, and the prognosis in children is believed to be better than that in adults. Complications include pericardial effusion, arrhythmia, heart block, valvular dysfunction, and dilated cardiomyopathy.
- Data suggest that type-1 insulin-dependent diabetes may result from group B coxsackievirus infections. Epidemiologic data note that clustering of newly onset diabetes mellitus occurs 1-3 months following infection with the virus. Similarly, animal models noted infection of pancreatic islet cells.
- Exanthems: Two of the more distinctive exanthems caused by coxsackievirus are as follows:
- Hand-foot-and-mouth (HFM) disease often affects children and spreads easily to other family members. Patients present with a sore throat and mouth. Vesicles that coalesce, form bullae, and then ulcerate form on the buccal mucosa and tongue. Seventy-five percent of patients have peripheral cutaneous lesions at approximately the same time. Biopsy reveals intracytoplasmic viral particles. The most common virus isolated is coxsackievirus A16.
- Herpangina is a vesicular enanthem of the posterior oropharynx with fever, sore throat, occasional throat exudate, odynophagia, and dysphagia, which is observed more often in children than in adults. Prompt recovery is typical, with almost all patients recovering completely.
- Epidemic pleurodynia
- This is a muscular disease, and viral invasion of muscles, causing inflammation, is suspected; however, direct histologic evidence is lacking. Epidemic pleurodynia is usually associated with outbreaks of group B coxsackievirus infection.
- Patients present with fever and sharp, paroxysmal, spasmodic pain in the chest and upper abdomen.
- All patients recover completely within 1 week.
- Acute hemorrhagic conjunctivitis
- Pain and edema of the eyelids and subconjunctival hemorrhage are present.
- Patients may also report photophobia, foreign body sensation, fever, malaise, and headache. These symptoms usually resolve spontaneously within one week.
- Rare complications include keratitis and motor paralysis.
- This condition is highly contagious and has resulted in epidemics and pandemics.
Physical
- Aseptic meningitis: On examination, patients may have signs of nuchal rigidity and other evidence of meningeal irritation, photophobia, pharyngitis, and rash.
- Encephalitis: In contrast to patients with aseptic meningitis, whose brain function is normal, patients with encephalitis may present with cerebral dysfunction that manifests as altered mental status, personality changes, and neurologic deficits (eg, motor, sensory, speech impairment). An EEG may be helpful in localizing and characterizing the seizure focus.
- Myopericarditis
- The presentation in patients with myopericarditis ranges from asymptomatic to critical illness secondary to severe heart failure. Most patients report fever, malaise, upper respiratory tract symptoms, dyspnea, and chest pain. Chest pain increases when the patient is lying down and improves when the patient sits up and leans forward.
- On examination, the point of maximal pulse (PMI) may be displaced, pericardial friction rub may be heard, and signs of heart failure (eg, S3 gallop, pulmonary edema) may be present.
- HFM: Physical examination findings include vesicular lesions that may appear on the tongue or buccal mucosa, as well as the hands and feet, including the palms and soles. Uncommonly, the buttocks and genitalia are involved. The vesicles are tender and may ulcerate. However, the vesicles are usually not pruritic, which helps to distinguish them from chickenpox lesions.
- Epidemic pleurodynia: On physical examination, edema of the involved muscles and tenderness to palpation may occur.
- Acute hemorrhagic conjunctivitis (AHC): Physical examination findings include subconjunctival hemorrhage. Eye pain, edema of the eyelids, photophobia, and a serous discharge may be present. Slit lamp examination may reveal keratitis.
Causes
- Aseptic meningitis: Coxsackievirus B (serotypes 2-5) and echoviruses account for more than 90% of viral causes of aseptic meningitis.
- Exanthems: Coxsackieviruses cause many different types of rashes. Whether the viruses directly cause the rashes or immunologic mechanisms are responsible for the rashes is not known. An exception is HFM, in which viruses are isolated directly from the lesions. HFM is predominantly caused by coxsackievirus A16. In most other instances, rashes can be attributed to coxsackieviruses only if findings on concurrent polymerase chain reaction (PCR) or serology are positive.
- AHC: Coxsackievirus serotype A24 generally causes AHC. Transmission usually occurs via contact of contaminated fingers or fomites with the eyes. To prevent further transmission, strict handwashing should be encouraged and sharing of towels should be avoided.
More on Coxsackieviruses |
 Overview: Coxsackieviruses |
| Differential Diagnoses & Workup: Coxsackieviruses |
| Treatment & Medication: Coxsackieviruses |
| Follow-up: Coxsackieviruses |
| References |
| Next Page » |
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Further Reading
Keywords
coxsackieviruses, coxsackie viruses, coxsackie virus A, coxsackievirus A, hand-foot-and-mouth disease, hand-foot-mouth disease, HFM disease, vesicular stomatitis with exanthem, coxsackievirus B, coxsackie virus B, Bamle disease, Bornholm disease, Daae disease, Sylvest disease, benign dry pleurisy, epidemic pleurodynia, devil's grip, devil's grippe, diaphragmatic pleurisy, epidemic benign dry pleurisy, epidemic diaphragmatic pleurisy, epidemic myalgia, epidemic myositis, myositis epidemica acuta, epidemic transient diaphragmatic spasm, aseptic meningitis, acute hemorrhagic conjunctivitis, AHC, enteroviral infection,
