• Coxsackievirus A causes herpangina and hand, foot and mouth disease.¹
• Coxsackievirus B causes Bornholm disease as well as myocarditis and pericarditis.

It is named after the town of Coxsackie in New York state.

Epidemiology¹

Infection is common - in temperate climates, most frequent in summer and autumn and, in the tropics, all year round. It tends to affect those under 16 but adults are also affected.

Spread is usually from the faeco-oral route or oral-oral route, with an incubation period of 2 to 6 days.

Presentation¹

• Herpangina has an incubation period of about 4 days.¹
  • Mild pyrexia, headache, sore throat, dysphagia, loss of appetite and sometimes vomiting and abdominal pain occur.
  • Tiny grey-white papulovesicles, about 1 mm or 2 mm in diameter, appear on the uvula, soft palate and tonsils.
  • There is an erythematous halo, which progresses to a shallow ulcer.
  • It is caused mainly by Coxsackie A (serotypes 2-6, 8 and 10) and occasionally Coxsackie B (serotypes 1-4 ). It resolves uneventfully in 5 to 10 days.
• Hand, foot and mouth disease is caused by Coxsackievirus A.
  
  
  
  
  
  
• Bornholm disease affects the intercostal muscles:
  • Pain on inspiration is similar to pleuritic pain and pulmonary embolism may be suspected.
  • The muscles are locally tender.
  • There will be no haemoptysis.
  • There may be a slight sensation of dyspnoea or pain on breathing.
• Myocarditis is usually asymptomatic but it is a reason not to do strenuous exercise when pyrexial, as under these circumstances myocarditis may cause ventricular fibrillation and death. Intrauterine infection can result in death from myocarditis.
• Pericarditis is discussed elsewhere.
• Coxsackievirus B5 causes pustular stomatitis with erythema multiforme.
• Coxsackievirus A4 causes a widespread vesicular eruption.
• Coxsackievirus B1 has been reported as causing severe infection and death in neonates in America in 2007-2008.²

Differential diagnosis¹

• Aphthous ulcers.
• Drug eruptions.
• Herpes simplex.
• Rubella.
• Erythema multiforme.
• Other causes of chest pain - e.g. pulmonary embolism, other cardiac causes of chest pain, costochondritis, etc.

Investigations

Usually diagnosis is clinical but some laboratory tests are available. The most specific findings are found in samples from the blood and vesicles. Faecal specimens are less useful.

• IgM with enzyme-linked immunosorbent assay (ELISA) can aid diagnosis. Blood samples are required in the acute phase because IgM disappears rapidly.
• Cell culture of the virus is possible.
• Polymerase chain reaction (PCR) has made enteroviral subtyping possible but it is difficult and expensive and not routinely performed.

Associated diseases¹

• If acquired in the first trimester of pregnancy Coxsackieviruses can cause spontaneous abortion.
• Maternal Coxsackievirus infections have also been associated with type 1 diabetes in the offspring.
• Maternal Coxsackievirus B infection has been associated to an increase in fetal cardiac abnormalities.
• Coxsackieviruses A and B can cross the placenta and cause stillbirth by villous necrosis and a variety of other means.³
• Coxsackievirus infection has also been linked with chronic fatigue syndrome (CFS), also referred to as myalgic encephalitis (ME).

Management¹

• Mouth rinses with topical anaesthetics can ease the pain.
• Antipyretic analgesics such as paracetamol and ibuprofen are the main treatment.
• Allopurinol mouthwash has proved effective in speeding up the resolution of oral lesions.
• Antiviral agents are not currently indicated, although one research study found that interferon-1β may be useful in the management of Coxsackie B myocarditis.⁴

Prognosis

These diseases tend to be self-limiting, although there are (very) occasional case reports of adult fatalities.⁵

They are very common in pregnancy, especially at times of the year when prevalence is high but the outcome is usually benign if the mother was asymptomatic. As many as 65% of women who give birth to infants with proven enteroviral infection have symptomatic disease during the perinatal period. Maternal Coxsackievirus B may cause an increase in early spontaneous abortions and rarely, fetal myocarditis.⁶ It is also associated with an increased risk of stillbirth. Maternal echoviruses do not affect the fetus but their ability to cause severe maternal illness may result in stillbirth.³

Coxsackievirus infection tends to be seen as a trivial and self-limiting infection but perhaps we should consider it as more like rubella (that is, also trivial and self-limiting except in pregnancy). Whereas rubella is a problem in early pregnancy, Coxsackievirus appears to be a danger in both the early and late stages.

Prevention

Hand washing reduces spread within the family. There is no vaccine against Coxsackieviruses.

Document references

1. Nogués-Siuraneta S et al, Dermatologic Manifestations of Enteroviral Infections, Medscape, Jul 2010
2. Wikswo ME, Khetsuriani N, Fowlkes AL, et al; Increased activity of Coxsackievirus B1 strains associated with severe disease Clin Infect Dis. 2009 Sep 1;49(5):e44-51. [abstract]
3. Silver RM, Varner MW, Reddy U, et al; Work-up of stillbirth: a review of the evidence. Am J Obstet Gynecol. 2007 May;196(5):433-44. [abstract]
4. Scassa ME, de Giusti CJ, Questa M, et al; Human embryonic stem cells and derived contractile embryoid bodies are Stem Cell Res. 2011 Jan;6(1):13-22. Epub 2010 Sep 18. [abstract]
5. Legay F, Leveque N, Gacouin A, et al; Fatal coxsackievirus A-16 pneumonitis in adult. Emerg Infect Dis. 2007 Jul;13(7):1084-6. [abstract]
6. Ornoy A, Tenenbaum A; Pregnancy outcome following infections by coxsackie, echo, measles, mumps, hepatitis, polio and encephalitis viruses. Reprod Toxicol. 2006 May;21(4):446-57. Epub 2006 Feb 9. [abstract]

Internet and further reading

• Knowlton KU; CVB infection and mechanisms of viral cardiomyopathy. Curr Top Microbiol Immunol. 2008;323:315-35. [abstract]
• Romero JR; Pediatric group B coxsackievirus infections. Curr Top Microbiol Immunol. 2008;323:223-39. [abstract]
• Kemball CC, Alirezaei M, Whitton JL; Type B coxsackieviruses and their interactions with the innate and adaptive Future Microbiol. 2010 Sep;5(9):1329-47. [abstract]

Acknowledgements