Can Shingles Cause a False Positive for HSV-2?

It is common for individuals to wonder whether a shingles infection, caused by the varicella-zoster virus (VZV), could lead to a false positive result when testing for Herpes Simplex Virus type 2 (HSV-2). The diagnostic relationship between these viruses and the nuances of their testing can be complex. This article explores the connections between these distinct yet related viruses and their diagnostic evaluations.

Understanding Herpesviruses: VZV and HSV-2

Both Varicella-Zoster Virus (VZV), which causes shingles, and Herpes Simplex Virus type 2 (HSV-2), the primary cause of genital herpes, belong to the Herpesviridae family. These viruses are characterized by their ability to establish lifelong infections, often remaining dormant within nerve cells after initial exposure. VZV is initially acquired as chickenpox, a widespread childhood illness, and can later reactivate to cause shingles.

While VZV primarily causes chickenpox and shingles, HSV-2 is most commonly associated with genital herpes, a sexually transmitted infection. Despite their shared viral family and similar latency mechanisms, VZV and HSV-2 are distinct viruses that typically cause different clinical conditions. Their familial ties help explain why cross-reactions might occur in certain diagnostic tests, as they share some genetic and protein similarities.

How HSV-2 is Diagnosed

Diagnosing HSV-2 often involves looking for specific antibodies the body produces in response to the virus. Serological, or blood antibody, tests are a common method for this purpose. These tests detect two main types of antibodies: Immunoglobulin M (IgM) and Immunoglobulin G (IgG). IgM antibodies are generally the first to appear after an initial infection, usually becoming detectable within about 10 days, but their levels typically decrease over time.

IgG antibodies, on the other hand, develop several weeks after infection, usually around two weeks, and persist in the bloodstream indefinitely, indicating a past or current infection. While antibody tests can reveal exposure, they have limitations, including a “window period” during which antibodies may not yet be detectable, even if an infection is present. It can take up to 12 to 16 weeks after exposure for IgG antibodies to reach detectable levels, potentially leading to false negative results if tested too early.

The Role of Shingles in HSV-2 Test Results

A shingles infection can influence HSV-2 test results, particularly those relying on antibody detection. This occurs due to “cross-reactivity,” where antibodies produced against VZV are mistakenly recognized as HSV-2 antibodies by less specific tests. The genetic and structural similarities between VZV and HSV-2, both herpesviruses, contribute to this cross-reaction. This can result in a “false positive” for HSV-2, meaning the test indicates HSV-2 infection when VZV antibodies are the actual cause.

Older or less specific antibody tests, such as some IgM assays or less sensitive IgG tests, are more prone to this cross-reactivity. The FDA has issued reminders about potential false reactive results in HSV-2 serological tests. Such false positives are particularly noted when test results fall into a low positive range, often between 1.1 and 3.0 on some enzyme immunoassay (EIA) tests.

Steps to Confirm or Clarify a Diagnosis

Receiving an HSV-2 positive result, especially after a shingles infection, warrants further investigation to confirm or clarify the diagnosis. Consulting a healthcare provider is an important step for a comprehensive evaluation of the test results and clinical history. The healthcare provider can assess symptoms, medical history, and risk factors to determine the most appropriate next steps.

Confirmatory testing options are available to provide a more definitive diagnosis. Highly specific HSV-2 antibody tests, such as glycoprotein G (gG)-based IgG assays or the Western Blot, are often recommended. These tests are designed to differentiate between HSV-1 and HSV-2 antibodies with greater accuracy, reducing the chance of false positives caused by cross-reactivity with VZV. If active lesions are present, direct viral detection methods like Polymerase Chain Reaction (PCR) can be utilized, as PCR is highly sensitive in detecting the virus’s genetic material directly from a lesion sample. A thorough clinical assessment, combined with these advanced diagnostic tools, is essential for an accurate diagnosis and appropriate management.