Dermatologic Manifestations of Herpes Simplex Workup

Updated: Mar 17, 2020
  • Author: Sean P McGregor, DO, PharmD; Chief Editor: William D James, MD  more...
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Approach Considerations

The approach to the patient presenting with cutaneous features of herpes simplex virus (HSV) infection can sometimes be difficult, and laboratory testing can aid in the diagnosis. Additionally, age, immune status, and pregnancy should be considered in all patients presenting with features of HSV infection.


Laboratory Studies

Multiple modalities are available that can aid in the diagnosis of herpes simplex virus (HSV) infection. A survey of 81 public health laboratories in 2016 found that 37,101 HSV tests were performed. [44] The criterion standard for the diagnosis of HSV infection is viral culture. Detection and typing of HSV can be completed by obtaining a viral culture from unroofed skin vesicles. Early in the course of recurrent infection, 80-90% of viral cultures of untreated lesions are positive, but the false-negative rate increases after 48 hours of lesion onset.

Polymerase chain reaction (PCR) assays have become more widely available for the detection of HSV DNA. Detection and differentiation between HSV-1 and HSV-2 can be accomplished rapidly with high sensitivity and specificity, ranging from 95-99%. [45, 46] In a study comparing viral culture and PCR, HSV was detected in 31% of viral culture specimens and 53% of PCR specimens. [47] The average time for viral culture was 3 days, in comparison to 4 hours with PCR. [47] This is especially important in cases of suspected CNS infection, and PCR has replaced viral culture as the diagnostic test of choice in such cases. [48]

In the office, a Tzanck smear can be performed as a rapid test for the diagnosis of HSV infection. A Tzanck smear is prepared by scraping the floor of the herpetic vesicle. The sample may be stained with a Giemsa stain, Wright stain, or a Papanicolaou stain and then evaluated under a microscope. The presence of multinucleated giant cells is indicative of HSV infection, although the findings are not specific for the type of herpes virus. Approximately 50% of the results are positive.

Direct fluorescent antibody (DFA) testing may be used on air-dried smears, and approximately 75% of the results are positive.

Serologic assays use HSV-specific glycoproteins for detection and typing. Point-of-care and laboratory-based studies are available for HSV-2, and detection rates range from 80-98%. [48] In the early stages of infection, false-negative results may occur. [48] Serologic assays to detect antibodies against HSV-1 and HSV-2 may be useful in identifying organ transplant recipients or pregnant women who may be at risk for HSV reactivation. Their use is also becoming more common for confirming infection and for testing partners or those with asymptomatic infection. Western blot assays are highly sensitive and specific, and they can be considered in patients with suspected false-positive test results. [48]

Depending on the clinical scenario, the virus may be isolated from cerebrospinal fluid (CSF), stool, urine, the throat, anogenital mucosa, the nasopharynx, and conjunctivae. HSV-1 DNA has also been detected in tears and saliva. [49]


Histologic Findings

Cells infected with herpes simplex virus (HSV) demonstrate ballooning and reticular epidermal degeneration, epidermal acantholysis, and intraepidermal vesicles. Intranuclear inclusion bodies, steel-gray nuclei, multinucleate giant keratinocytes, and multilocular vesicles may also be present. Epidermal necrosis and an inflammatory infiltrate of lymphocytes and neutrophils may be observed. Additionally, up to one third of biopsy specimens may contain eosinophils. [50]  Histologic examination alone is unable to differentiate between subtypes of HSV. Immunoperoxidase techniques may be used to distinguish HSV-1 and HSV-2 antigens in formalin-fixed tissue samples.