eMedicine Specialties > Infectious Diseases > Viral Infections

Enteroviruses: Differential Diagnoses & Workup

Author: Alexander Velazquez, MD, Fellow, Department of Infectious Diseases, Orlando Regional Medical Center
Coauthor(s): Mark R Wallace, MD, FACP, FIDSA, Clinical Professor of Medicine, Florida State University College of Medicine; Infectious Disease Fellowship Director, Orlando Regional Medical Center; Smeeta Sinha, MD, Staff Physician, Department of Dermatology, UMDNJ-New Jersey Medical School; Rajendra Kapila, MD, MBBS, Professor of Medicine, Department of Medicine, UMDNJ, New Jersey Medical School; Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School; Pratibha Dua, MD, MBBS, Staff Physician, Department of Internal Medicine, The Brooklyn Hospital Center
Contributor Information and Disclosures

Updated: Nov 10, 2009

Differential Diagnoses

Adenoviruses
Myocardial Infarction
Botulism
Pharyngitis, Bacterial
Ehrlichiosis
Pharyngitis, Viral
Hand-Foot-and-Mouth Disease
Pleurodynia
Herpangina
Rocky Mountain Spotted Fever
Herpes Simplex
Varicella-Zoster Virus
Lyme Disease

Other Problems to Be Considered

Acute hemorrhagic conjunctivitis

Adenovirus keratoconjunctivitis
Gonococcal conjunctivitis

Myopericarditis

Acute myocardial infarction
Angina
Ischemic and nonischemic cardiomyopathy
Other viral pericarditis

Aseptic meningitis

Arbovirus infection
Lyme disease
Rocky Mountain spotted fever
Ehrlichiosis
Incompletely treated bacterial meningitis
Syphilis
Tuberculosis meningitis
Sarcoidosis

Hand-foot-and-mouth disease

Herpes simplex
Aphthous stomatitis
Erythema multiforme
Atypical varicella

Abortive polio

Aseptic meningitis

Paralytic polio

Guillain-Barré syndrome
Botulism
Arthropod-borne viral encephalitis

Herpangina

Bacterial tonsillitis
Aphthous stomatitis
Other viral tonsillitis
Oral herpes simplex infections

Pleurodynia

Pneumonia
Pulmonary infarction
Rib fracture
Costochondritis
Herniated intervertebral disc
Renal colic
Myocardial infarction
Prodromal phase of zoster
Acute abdomen
Empyema

Guillain-Barré syndrome is an acute demyelinating polyneuropathy and, in the postpolio era, is the most common cause of generalized paralysis. The major symptom is rapidly progressive paralysis, which, unlike in polio, is symmetrical. Paralysis of the lower extremities is followed by paralysis of the upper extremities, and both proximal and distal muscle groups are involved. Deep tendon reflexes are initially reduced and are later absent. A mild sensory disturbance or paresthesia occurs. The cerebrospinal fluid (CSF) typically has an elevated protein level and a normal cell count (albuminocytologic dissociation).

Workup

Laboratory Studies

  • Diagnosis of enterovirus infections is often clinical. Laboratory diagnosis can be achieved with serological tests, viral isolation by cell culture, and polymerase chain reaction (PCR).
    • Serology: The microneutralization test is the most widely used method for detecting antibodies to enteroviruses. Serological examination reveals a 4-fold increase in antibodies to enteroviruses between the acute and convalescent phases of illness.46 This diagnostic modality is infrequently used since it is serotype-specific, relatively insensitive, poorly standardized, labor intensive, and too slow for clinical purposes.
    • Viral isolation: The virus can be isolated from CSF, blood, or feces, depending on the site affected, and the yield is increased if multiple sites are sampled. Enterovirus produces a characteristic cytopathic effect in cultured cells. Poliovirus is easily cultured from stool and nasopharyngeal secretions, but isolation from the CSF is more difficult. The cytopathic effect is confirmed by indirect immunofluorescence using a broadly specific monoclonal antibody. The sensitivity of viral culture ranges from 60%-75%.47
    • PCR: This rapid test is highly sensitive and specific for detecting enteroviral RNA in CSF specimens, with a sensitivity of 100% and specificity of 97%.48,49 PCR provides rapid results and is the best diagnostic test for use in CSF but is limited by availability in some areas and cost in underdeveloped regions.50
    • Cardiac enzyme levels may be elevated in persons with myopericarditis, indicating myocardial damage.
    • CSF analysis: The CSF profile in patients with aseptic meningitis usually reveals a mildly elevated white blood cell count, and the differential invariably shifts to a predominance of lymphocytes during the initial 1-2 days of illness. Glucose levels are normal or mildly decreased,51 while the protein level is normal or slightly increased.
    • In 2008, a multiplex real-time PCR (RT-PCR) assay was developed for simultaneous detection, identification, and quantification of enterovirus 70 and a coxsackievirus A24 variant. The novel technique is used as a rapid diagnostic method to evaluate for enterovirus-related AHC.52

Imaging Studies

  • Chest radiography: In patients with myopericarditis, chest radiography may reveal cardiomegaly secondary to pericardial effusion or cardiac dilation. In pleurodynia, chest radiographic findings are normal.
  • Echocardiography: Transient wall motion abnormalities may be detectable in mild cases. Severe cases may demonstrate acute ventricular dilation and reduced ejection fraction.

Other Tests

  • ECG: Nonspecific ST-T changes may be observed in persons with myopericarditis. Severe disease may cause Q waves, ventricular tachyarrhythmias, and heart block. ECG findings may demonstrate evolution through several stages of myopericarditis, as follows:
    • Stage I - Diffuse ST elevation with PR depression
    • Stage II - Normalization of ST and PR segments
    • Stage III - Deep symmetric inversion of T waves
    • Stage IV - May revert to normal or permanent T-wave inversions
  • Electroencephalography: This test may be useful for evaluating the extent and severity of illness in patients with encephalitis.
  • Ophthalmic slit-lamp examination: In persons with AHC, corneal erosions may be visualized using a fluorescein stain. Enterovirus 70 and coxsackievirus A24 can often be recovered from conjunctival swabs during the first 3 days of infection.

Histologic Findings

  • Histopathologic findings in most enterovirus infections are usually nonspecific, consisting primarily of lymphocytic infiltrates and cellular destruction.
  • Histologic findings in patients with polio have been well studied. Evidence of infection is pronounced in the spinal cord, medulla, pons, and mid brain. Neuronal destruction is observed, along with an inflammatory infiltrate composed of lymphocytes, macrophages, and polymorphonuclear leukocytes.

More on Enteroviruses

Overview: Enteroviruses
Differential Diagnoses & Workup: Enteroviruses
Treatment & Medication: Enteroviruses
Follow-up: Enteroviruses
References
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Further Reading

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Keywords

Enterovirus, enteroviral infections, Bornholm disease, Bornholm's disease, epidemic myalgia, Sylvest's disease, Sylvest disease, devil's grip, polio, poliovirus, coxsackievirus group A, coxsackievirus group B, echovirus, aseptic meningitis, poliomyelitis, viral heart disease, hand foot and mouth disease, hand-foot-and-mouth disease, HFM disease, hemorrhagic conjunctivitis, herpangina, pleurodynia, myocarditis, pericarditis, meningoencephalitis, common cold, aseptic meningitis, acute hemorrhagic conjunctivitis, AHC, viremia, myopericarditis, abortive polio, nonparalytic polio, paralytic polio

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Contributor Information and Disclosures

Author

Alexander Velazquez, MD, Fellow, Department of Infectious Diseases, Orlando Regional Medical Center
Alexander Velazquez, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Coauthor(s)

Mark R Wallace, MD, FACP, FIDSA, Clinical Professor of Medicine, Florida State University College of Medicine; Infectious Disease Fellowship Director, Orlando Regional Medical Center
Mark R Wallace, MD, FACP, FIDSA is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Tropical Medicine and Hygiene, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Smeeta Sinha, MD, Staff Physician, Department of Dermatology, UMDNJ-New Jersey Medical School
Smeeta Sinha, MD is a member of the following medical societies: Alpha Omega Alpha, Phi Beta Kappa, and Sigma Xi
Disclosure: Nothing to disclose.

Rajendra Kapila, MD, MBBS, Professor of Medicine, Department of Medicine, UMDNJ, New Jersey Medical School
Rajendra Kapila, MD, MBBS is a member of the following medical societies: American College of Physicians, American Medical Association, Infectious Diseases Society of America, and Infectious Diseases Society of New Jersey
Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

Pratibha Dua, MD, MBBS, Staff Physician, Department of Internal Medicine, The Brooklyn Hospital Center
Pratibha Dua, MD, MBBS is a member of the following medical societies: American Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Mary Nettleman, MD, MS, Chair, Department of Medicine, Michigan State University
Mary Nettleman, MD, MS is a member of the following medical societies: American College of Physicians, Association of Professors of Medicine, Central Society for Clinical Research, Infectious Diseases Society of America, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Ronald A Greenfield, MD, Professor, Department of Internal Medicine, Section of Infectious Diseases, University of Oklahoma College of Medicine
Ronald A Greenfield, MD is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Central Society for Clinical Research, Infectious Diseases Society of America, Medical Mycology Society of the Americas, Phi Beta Kappa, Southern Society for Clinical Investigation, and Southwestern Association of Clinical Microbiology
Disclosure: Pfizer Honoraria Speaking and teaching; Gilead Honoraria Speaking and teaching; Ortho McNeil Honoraria Speaking and teaching; Wyeth Honoraria Speaking and teaching; Abbott Honoraria Speaking and teaching; Astellas Honoraria Speaking and teaching; Cubist  Speaking and teaching

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.

 
 
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