Coxsackieviruses Clinical Presentation

More than 90% 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 3 months have been noted to have the highest incidence of clinically recognized aseptic meningitis, partly because lumbar punctures are often performed for the evaluation of fever in this age group. 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 occur early in the course of disease and have been reported in 5-10% of patients with enteroviral meningitis. No long-term neurologic deficits appear to exist in infants with aseptic meningitis. Adults may experience a more prolonged period of fever and headache compared with infants and children.

Encephalitis

Encephalitis is an unusual manifestation of CNS infection, although it is sometimes observed in association with aseptic meningitis. Enteroviruses accounts for approximately 5% of all cases of encephalitis. Coxsackievirus types A9, B2, and B5 have been linked with encephalitis. In rare cases, it mimics encephalitis secondary to herpes simplex virus.

Neurologic diseases

Rarely, coxsackieviruses have been implicated in additional neurologic diseases such as sporadic cases of flaccid motor paralysis that closely mimic poliovirus infection. Additionally, cases of Guillain-Barré syndrome have been described with coxsackievirus serotypes A2, A5, and A9.

Myopericarditis

Myopericarditis can occur at any age although has a predilection for adolescents and young adults. Enteroviruses account for half of all cases of acute viral myopericarditis.

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. Myocardial enzyme levels in the serum are frequently elevated.

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.

Diabetes

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 young children than in adolescents and adults. Prompt recovery is typical, with almost all patients recovering completely. Group A coxsackieviruses are the most common viruses isolated from herpangina patients.

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.

• 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.

• 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.