Can a patient still have shingles with a negative varicella zoster (VZV) polymerase chain reaction (PCR) result?

From the Guidelines

Yes, a patient can still have shingles despite a negative varicella zoster virus (VZV) PCR test result. The presence of virus-specific IgM in CSF is usually indicative of CNS disease, and CSF varicella zoster virus IgM antibodies may also be present in patients with a negative CSF varicella zoster virus PCR result 1. This suggests that a negative PCR result does not exclude the diagnosis of varicella encephalitis or shingles.

Key Considerations

• VZV PCR is highly sensitive and specific, but false negatives can occur, particularly if the sample is collected late in the course of the rash or if sampling technique is inadequate 1.
• Clinical diagnosis remains paramount when evaluating potential shingles cases, and treatment should be considered even with negative PCR results if a patient presents with the characteristic unilateral, dermatomal, vesicular rash accompanied by pain or tingling.
• Standard treatment includes antiviral medications such as acyclovir, valacyclovir, or famciclovir, ideally started within 72 hours of rash onset to reduce severity and complications.

Diagnostic Approach

• A negative PCR result cannot be used as definitive evidence against the diagnosis of shingles or varicella encephalitis 1.
• The diagnosis of shingles should be based on a combination of clinical presentation, epidemiology, and results of other diagnostic studies.
• If a patient presents with a characteristic rash and symptoms, treatment should be initiated promptly, regardless of the PCR result.

Treatment

• Antiviral medications such as acyclovir (800 mg five times daily for 7-10 days), valacyclovir (1000 mg three times daily for 7 days), or famciclovir (500 mg three times daily for 7 days) are effective in reducing the severity and complications of shingles.
• Treatment should be started within 72 hours of rash onset to maximize efficacy.

From the Research

Varicella Zoster PCR Negative and Shingles Diagnosis

• A negative varicella zoster (VZV) polymerase chain reaction (PCR) result does not necessarily rule out the possibility of shingles, as the diagnosis of shingles is typically made clinically based on symptoms such as unilateral dermatomal pain and rash 2, 3, 4.
• The PCR test may not always detect the presence of VZV, especially if the sample is taken from a lesion that is no longer actively shedding virus or if the test is performed too early or too late in the course of the disease 5.
• Other diagnostic methods, such as virus isolation and serological tests, may be used to confirm the diagnosis of shingles, especially in cases where the clinical presentation is atypical or the PCR result is negative 3, 5.
• It is also possible for patients to have a condition called "zoster sine herpete," where the virus reactivates without causing a rash, making diagnosis based on PCR results alone even more challenging 6.

Clinical Presentation and Diagnosis

• The clinical presentation of shingles typically includes prodromal symptoms such as pain, itching, and malaise, followed by the appearance of a maculopapular and vesicular rash in a dermatomal distribution 2, 3, 4.
• The diagnosis of shingles is often made based on the patient's history and physical examination, and laboratory tests such as PCR and serology may be used to support the diagnosis 2, 3, 5.
• In some cases, the diagnosis of shingles may be made based on the presence of postherpetic neuralgia (PHN), which is a common complication of shingles characterized by persistent pain in the affected dermatome 2, 4.