eMedicine Specialties > Infectious Diseases > Viral Infections

Coxsackieviruses: Differential Diagnoses & Workup

Author: Michael Rajnik, MD, Assistant Professor, Department of Pediatrics, Acting Program Director, Pediatric Infectious Disease Fellowship Program, Uniformed Services University of the Health Sciences
Coauthor(s): Nhat M Doan, MD, Fellow, Department of Internal Medicine, Division of Infectious Diseases, Washington Hospital Center
Contributor Information and Disclosures

Updated: Jun 30, 2008

Differential Diagnoses

Ependymoma

Other Problems to Be Considered

Aseptic meningitis

Encephalitis
  • Arboviruses
  • Herpes simplex virus (HSV)
  • Lymphocytic choriomeningitis virus
Myopericarditis
Exanthems
  • HFM disease
    • Herpes simplex: Patients are more ill, have higher fever and cervical adenopathy, and have no lesions on extremities.
    • VZV: Patients are also more ill, rarely have oral lesions, and the palms of the hands and soles of the feet are rarely affected.
  • Herpangina
    • Other viral causes of pharyngitis and bacterial tonsillitis: These do not produce vesicular lesions.
    • Primary herpetic gingivostomatitis: Gingivitis is prominent, and systemic toxicity and cervical lymphadenitis are present; scrapings of lesions do not reveal giant cells or intranuclear inclusions.
    • HFM disease: These lesions also occur on extremities.
    • Aphthous stomatitis: Lesions tend to be larger and occur in older children and adults.
Epidemic pleurodynia
Acute hemorrhagic conjunctivitis
  • Adenovirus causing keratoconjunctivitis: The incubation period is 1-3 weeks, whereas the incubation period is 1 day with acute hemorrhagic conjunctivitis (AHC). In addition, subconjunctival hemorrhage is usually not observed with keratoconjunctivitis.
  • Bacterial or chlamydial conjunctivitis must be considered, but these conditions usually do not cause an extensive outbreak.

Workup

Laboratory Studies

Definitive diagnosis can be made based on isolation of the virus in cell culture. Cytopathic effect can usually be seen within 2-6 days. Samples are normally taken from the stool or rectal swabs but may be isolated from the oropharynx early in the disease course. False-positive culture results are possible, as excretion can occur for up to 8 weeks after initial infection. Serology can be difficult to interpret. Traditionally, enteroviral infections have been noted after a rise in neutralizing antibodies titer (at least a 4-fold rise in titer between acute and convalescent phase). PCR is also available, with a sensitivity of 66-90%.

  • Aseptic meningitis: The workup needs to rule out bacterial meningitis, and appropriate antibiotics should be administered until the workup is complete. Diagnosis requires cerebrospinal fluid (CSF) evaluation, which tends to show a lymphocytic predominance, normal-to-decreased glucose levels, and normal-to-slightly elevated protein levels. The virus can be isolated via cell culture (sensitivity, 30-35%) or PCR (sensitivity, 66-90%). A recent study in infants reported that routine CSF PCR for enteroviruses resulted in shorter hospital stays (by 1.54 days) and a decreased duration of antibiotic use (by 33%).2
  • Encephalitis: Diagnostic workup requires CSF evaluation, which yields findings similar to those of aseptic meningitis.
  • Myopericarditis: Diagnosis is generally circumstantial, with evidence of infection from the oropharynx, feces, or on serology.
  • Acute hemorrhagic conjunctivitis (AHC): Diagnosis requires conjunctival swabs or scrapings, which are 90% successful. A rising antibody titer can be demonstrated.

Imaging Studies

  • Head CT scanning without contrast may be obtained upon initial presentation of meningitis and/or encephalitis to rule out hemorrhage, increased intracranial pressure, or mass lesions.
  • Echocardiography can be used to evaluate overall cardiac function and valvular disease in patients with myopericarditis and heart failure.

Other Tests

  • Obtain a throat culture to rule out streptococcal pharyngitis and/or tonsillitis.
  • HIV testing is always appropriate in patients who present with nonspecific febrile illness or rashes.
  • An EEG can be used to detect the presence of and localize seizure activity.
  • ECG changes in myopericarditis include ST-segment elevations or nonspecific ST segment, T-wave abnormalities, arrhythmia, and heart block.

Procedures

  • Lumbar puncture is crucial in the evaluation of meningitis and/or encephalitis.
  • Skin biopsy may be helpful in the evaluation of nonspecific exanthems.
  • Obtain a Tzank smear to rule out herpes virus infection.

Histologic Findings

Intracytoplasmic viral particles may be observed, especially with skin lesions and/or rashes of HFM.

More on Coxsackieviruses

Overview: Coxsackieviruses
Differential Diagnoses & Workup: Coxsackieviruses
Treatment & Medication: Coxsackieviruses
Follow-up: Coxsackieviruses
References

References

  1. Khetsuriani N, Lamonte A, Oberste MS, et al. Neonatal enterovirus infections reported to the national enterovirus surveillance system in the United States, 1983-2003. Pediatr Infect Dis J. Oct 2006;25(10):889-93. [Medline].

  2. King RL, Lorch SA, Cohen DM, et al. Routine cerebrospinal fluid enterovirus polymerase chain reaction testing reduces hospitalization and antibiotic use for infants 90 days of age or younger. Pediatrics. Sep 2007;120(3):489-96. [Medline].

  3. Schiff GM, Sherwood JR. Clinical activity of pleconaril in an experimentally induced coxsackievirus A21 respiratory infection. J Infect Dis. Jan 2000;181(1):20-6. [Medline].

  4. Brunetti L, DeSantis ER. Treatment of viral myocarditis caused by coxsackievirus B. Am J Health Syst Pharm. Jan 15 2008;65(2):132-7. [Medline].

  5. Yue-Chun L, LiSha G, Jiang-Hua R, Peng-Lin Y, Jia-Feng L, Ji-Fei T, et al. Protective effects of carvedilol in murine model with the coxsackievirus B3-induced viral myocarditis. J Cardiovas Pharmacol. Jan/2008;51:92-98. [Medline].

  6. Shi L, Xiong H, He J, et al. Antiviral activity of arbidol against influenza A virus, respiratory syncytial virus, rhinovirus, coxsackie virus and adenovirus in vitro and in vivo. Arch Virol. 2007;152(8):1447-55. [Medline].

  7. Bergman I, Painter MJ, Wald ER, et al. Outcome in children with enteroviral meningitis during the first year of life. J Pediatr. May 1987;110(5):705-9. [Medline].

  8. Berlin LE, Rorabaugh ML, Heldrich F, et al. Aseptic meningitis in infants < 2 years of age: diagnosis and etiology. J Infect Dis. Oct 1993;168(4):888-92. [Medline].

  9. Cheung CT, Deisher TA, Luo H, et al. Neutralizing anti-4-1BBL treatment improves cardiac function in viral myocarditis. Lab Invest. Jul 2007;87(7):651-61. [Medline].

  10. Dagan R, Jenista JA, Menegus MA. Association of clinical presentation, laboratory findings, and virus serotypes with the presence of meningitis in hospitalized infants with enterovirus infection. J Pediatr. Dec 1988;113(6):975-8. [Medline].

  11. Dagan R, Menegus MA. A combination of four cell types for rapid detection of enteroviruses in clinical specimens. J Med Virol. Jul 1986;19(3):219-28. [Medline].

  12. Dulbecco R, Ginsberg H. Virology. 2nd ed. 1988:207-209.

  13. Enterovirus surveillance--United States, 2002-2004. MMWR Morb Mortal Wkly Rep. Feb 17 2006;55(6):153-6. [Medline].

  14. Jenista JA, Powell KR, Menegus MA. Epidemiology of neonatal enterovirus infection. J Pediatr. May 1984;104(5):685-90. [Medline].

  15. Levinson W, Jawetz E. Medical Microbiology & Immunology: Examination & Board Review. 6th ed. New York, NY: McGraw Hill Text; 2000:238-239.

  16. Modlin JF. Coxsackieviruses, echoviruses, and newer enteroviruses. In: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 5th ed. Philadelphia, Pa: Churchill-Livingstone; 2000:1904-1919.

  17. Moore M. Centers for Disease Control. Enteroviral disease in the United States, 1970-1979. J Infect Dis. Jul 1982;146(1):103-8. [Medline].

  18. Morens DM, Pallansch MA. Epidemiology. Human Enterovirus Infections. 1995;1.

  19. Pallansch MA, Anderson LJ. Coxsackievirus, echovirus, and other enteroviruses. In: Gorbach SL, ed. Infectious Diseases. 2nd ed. Philadelphia, Pa: WB Saunders Co; 1998:2164-2170.

  20. Rantala H, Uhari M. Occurrence of childhood encephalitis: a population-based study. Pediatr Infect Dis J. Jul 1989;8(7):426-30. [Medline].

  21. Rorabaugh ML, Berlin LE, Heldrich F, et al. Aseptic meningitis in infants younger than 2 years of age: acute illness and neurologic complications. Pediatrics. Aug 1993;92(2):206-11. [Medline].

  22. Rotbart HA. Pleconaril therapy of potentially life-threatening enterovirus infections. 36th Annual Meeting of the Infectious Disease Society of America. 1998.

  23. Rotbart HA. Pleconaril treatment of enterovirus and rhinovirus infections. Infect Med. 2000;17:488.

  24. Rotbart HA. Treatment of picornavirus infections. Antiviral Res. Feb 2002;53(2):83-98. [Medline].

  25. Rotbart HA, Ahmed A, Hickey S, et al. Diagnosis of enterovirus infection by polymerase chain reaction of multiple specimen types. Pediatr Infect Dis J. Apr 1997;16(4):409-11. [Medline].

  26. Rotbart HA, McCracken GH Jr, Whitley RJ, et al. Clinical significance of enteroviruses in serious summer febrile illnesses of children. Pediatr Infect Dis J. Oct 1999;18(10):869-74. [Medline].

  27. Rotbart HA, Webster AD. Treatment of potentially life-threatening enterovirus infections with pleconaril. Clin Infect Dis. Jan 15 2001;32(2):228-35. [Medline].

  28. Sawyer MH, Holland D, Aintablian N, et al. Diagnosis of enteroviral central nervous system infection by polymerase chain reaction during a large community outbreak. Pediatr Infect Dis J. Mar 1994;13(3):177-82. [Medline].

  29. Voroshilova MK, Chumakov MP. Poliomyelitis-like properties of AB-IV Coxsackie A7 group of viruses. Prog Med Virol. 1959;2:106.

  30. Weller TH, Enders JF, Buckingham M, et al. The etiology of epidemic pleurodynia: a study of two viruses isolated from a typical outbreak. J Immunol. Sep 1950;65(3):337-46. [Medline].

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,

Contributor Information and Disclosures

Author

Michael Rajnik, MD, Assistant Professor, Department of Pediatrics, Acting Program Director, Pediatric Infectious Disease Fellowship Program, Uniformed Services University of the Health Sciences
Michael Rajnik, MD is a member of the following medical societies: American Academy of Pediatrics, Armed Forces Infectious Diseases Society, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.

Coauthor(s)

Nhat M Doan, MD, Fellow, Department of Internal Medicine, Division of Infectious Diseases, Washington Hospital Center
Nhat M Doan, MD is a member of the following medical societies: American Medical Association and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Medical Editor

Maria D Mileno, MD, Assistant Professor, Department of Internal Medicine, Division of Infectious Diseases, Brown University
Maria D Mileno, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, International Society of Travel Medicine, and Sigma Xi
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

John W King, MD, Professor of Medicine, Section of Infectious Diseases, Louisiana State University Health Sciences Center; Director, Viral Therapeutics Clinics for Hepatitis; Consulting Staff, Department of Infectious Diseases, Overton Brook Veterans Affairs Medical Center
John W King, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Association of Subspecialty Professors, Infectious Diseases Society of America, and Sigma Xi
Disclosure: emedicine $50.00 author of chapter

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.