Herpes Simplex Workup

  • Author: Michelle R Salvaggio, MD, FACP; Chief Editor: Burke A Cunha, MD   more...
 
Updated: Jan 5, 2012
 

Laboratory Studies

  • Herpes simplex virus (HSV) infection is best confirmed by isolation of the virus in tissue culture (the criterion standard for diagnosis). Tissue culture success is operator-dependent, but this modality can yield positive results within 48 hours of inoculation.
    • Characteristic cytopathic effect with ballooning of cells and cell death are observed, and death of the entire monolayer of cells may be rapid.
    • Immunofluorescent staining of the tissue culture cells can be used to quickly identify HSV and can distinguish between types 1 and 2.
  • The characteristic cytologic changes induced by HSV can be demonstrated in Tzank smears (see Procedures); however, this procedure does not distinguish between HSV-1 and HSV-2.
    • Rapid diagnosis (usually within an hour) is possible based on the histological appearance of the lesion.
    • Multinucleated giant cells and epithelial cells containing eosinophilic intranuclear inclusion bodies distinguish the lesions of herpesviruses.
    • Punch biopsy provides more reliable material for histological examination, particularly when lesions are infected with bacteria and fungi.
  • Detection of HSV DNA in clinical specimens is possible with polymerase chain reaction (PCR) techniques.
    • In HSV encephalitis, PCR using CSF provides a rapid, noninvasive diagnostic technique that is as sensitive as brain biopsy.[11]
    • PCR has been used to detect HSV-2 as the cause of recurrent meningitis (Mollaret) and has shown a strong association between HSV-1 and Bell's palsy.
    • PCR can be used to detect asymptomatic viral shedding.
  • Direct fluorescent antigen (DFA): Cells scraped from ulcer bases can be stained with a direct fluorescent antibody, used to distinguish HSV-1 from HSV-2. Additionally, tissue culture cells can also be stained (see above). This procedure can usually be performed within 2-3 hours.
  • Antibody testing can demonstrate a primary seroconversion, particularly with HSV-1 in childhood.[1]
    • Because of sero–cross-reactivity, HSV-1 and HSV-2 are not generally distinguishable unless a glycoprotein G antibody assay is available. Testing for HSV-specific immunoglobulin M (IgM) antibodies is not available.
    • Antibody titer increases generally do not occur during recurrences of HSV infection. Therefore, the test is generally not used for the diagnosis of mucocutaneous HSV relapse.
    • Antibody testing has been the mainstay of large-scale epidemiologic studies.
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Imaging Studies

Brain imaging studies in HSV encephalitis generally demonstrate focal localization in the temporal area that is associated with edema and contrast enhancement.

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Procedures

Tzanck preparation is a time-honored procedure for assisting in the diagnosis of cutaneous herpesvirus infections. However, it does not easily distinguish HSV-1, HSV-2, and varicella-zoster virus.

  • Typically, an intact vesicle is used from which the vesicular fluid is aspirated by puncture with a sterile tuberculin syringe. This fluid can be used for viral culture or PCR.
  • Aspiration should facilitate complete collapse of the vesicle because it is not multiloculated as cutaneous poxvirus infections can be.
  • After aspiration, the vesicle should be unroofed aseptically.
  • Using a sterile instrument, the floor of the newly produced ulcer can then be scraped. The obtained material can be spread on a glass microscope slide and then dried and fixed for staining.
  • Staining can be performed with a Papanicolaou smear stain or, alternatively, whatever is available will suffice (eg, Gram, Giemsa, or Wright stain).
  • A positive result is the finding of multinucleate giant cells.

DFA: Using appropriate immunofluorescent antibody reagents, the smear can be used to distinguish different herpesviruses and nonherpesviruses that may be present (eg, vaccinia, smallpox).

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Contributor Information and Disclosures
Author

Michelle R Salvaggio, MD, FACP  Assistant Professor, Department of Internal Medicine, Section of Infectious Diseases, University of Oklahoma College of Medicine; Medical Director of Infectious Diseases Institute, Director, Clinical Trials Unit, Director, Ryan White Programs, Department of Medicine, University of Oklahoma Health Sciences Center; Attending Physician, Infectious Diseases Consultation Service, Infectious Diseases Institute, OU Medical Center

Michelle R Salvaggio, MD, FACP is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America

Disclosure: Merck Honoraria Speaking and teaching

Coauthor(s)

Larry I Lutwick, MD  Professor of Medicine, State University of New York Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus

Larry I Lutwick, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Meena Seenivasan, MD  Fellow, Department of Infectious Disease, State University of New York Health Science Center at Brooklyn

Disclosure: Nothing to disclose.

Swati Kumar, MD  Assistant Professor of Pediatrics, Division of Infectious Diseases, Medical College of Wisconsin, Consulting Staff, Children's Specialty Group, Children's Hospital of Wisconsin

Swati Kumar, MD is a member of the following medical societies: American Academy of Pediatrics, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Thomas J Marrie, MD  Dean of Faculty of Medicine, Dalhousie University Faculty of Medicine, Canada

Thomas J Marrie, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society for Microbiology, Canadian Infectious Disease Society, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Charles V Sanders, MD  Edgar Hull Professor and Chairman, Department of Internal Medicine, Professor of Microbiology, Immunology and Parasitology, Louisiana State University School of Medicine at New Orleans; Medical Director, Medicine Hospital Center, Charity Hospital and Medical Center of Louisiana at New Orleans; Consulting Staff, Ochsner Medical Center

Charles V Sanders, MD is a member of the following medical societies: Alliance for the Prudent Use of Antibiotics, Alpha Omega Alpha, American Association for the Advancement of Science, American Association of University Professors, American Clinical and Climatological Association, American College of Physician Executives, American College of Physicians, American Federation for Medical Research, American Foundation for AIDS Research, American Geriatrics Society, American Lung Association, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Association for Professionals in Infection Control and Epidemiology, Association of American Medical Colleges, Association of American Physicians, Association of Professors of Medicine, Infectious Disease Society for Obstetrics and Gynecology, Infectious Diseases Society of America, Louisiana State Medical Society, Orleans Parish Medical Society, Royal Society of Medicine, Sigma Xi, Society of General Internal Medicine, Southeastern Clinical Club, Southern Medical Association, Southern Society for Clinical Investigation, and Southwestern Association of Clinical Microbiology

Disclosure: Nothing to disclose.

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.

References

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This neonate displayed a maculopapular outbreak on his feet due to congenitally acquired herpes simplex virus infection. Courtesy of the CDC/Judith Faulk.
 
 
 
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