Varicella zoster virus can reactivate years after chickenpox and affect every organ without the telltale shingles rash, making this treatable infection difficult to recognize
New research published today in Nature Reviews Disease Primers is shedding light on the surprisingly broad range of neurological and systemic diseases that can be caused by varicella zoster virus (VZV), the virus that causes chickenpox and shingles.
More than 90% of people worldwide carry dormant VZV. Yet despite its prevalence, VZV remains an underrecognized cause of serious neurological and systemic disease, particularly when patients do not develop the characteristic shingles rash when the virus flares up, according to researchers at the University of Colorado Anschutz.
How does varicella zoster virus reactivate?
After a person recovers from chickenpox, or primary VZV infection, VZV remains dormant in nerve cells for life. As the immune system changes with age or becomes suppressed by illness or medical treatment, the virus can reactivate, most commonly causing shingles. At least 1 in 3 people who carry VZV will experience reactivation during their lifetime.
Shingles is one manifestation of VZV reactivation, but reactivated VZV can also mimic other common diseases.
What diseases and complications can VZV cause?
VZV reactivation can affect sensory nerves, blood vessels and multiple organs, causing a wide spectrum of disease. The most common manifestation of reactivation is shingles with fluid-filled blisters on one side of the face or body. Shingles can be complicated by persistent, debilitating pain (postherpetic neuralgia), one of the most common causes of suicide in older adults with chronic pain. VZV can cause Ramsay Hunt syndrome with shingles in the ear and facial paralysis on one side of the head. VZV can also cause stroke, vision loss, paralysis, and abdominal pain with or without rash. Shingles can even recur, particularly in those with undiagnosed problems of their immune system.
Even when VZV produces classic shingles, individuals have an increased risk of stroke, cardiovascular events and dementia.
Additionally, many of these complications can occur in children with chickenpox. In fact, up to one-third of arterial ischemic strokes in children are due to VZV.
Can VZV cause disease without a shingles rash?
VZV reactivation does not always cause a rash. When the virus reactivates in nerve clusters, it can travel along nerves to the skin, causing shingles, or travel deeper into the body to affect blood vessels and organs. Sometimes it travels in both directions. When the virus spreads internally without causing a skin rash, the infection can be harder to recognize, diagnose and treat.
"VZV is an extraordinarily stealthy virus because it can cause disease in places throughout the body without necessarily announcing its presence with a rash," said Maria Nagel, MD, professor of neurology and ophthalmology at the CU Anschutz School of Medicine and corresponding author. "In my practice, one of the most under-recognized manifestations of VZV disease without rash is zoster sine herpete ("internal shingles") where the patient presents with severe, one-sided burning pain with normal imaging studies. Until the diagnosis of VZV infection is made, the underlying cause of the patient's pain goes untreated."
How are VZV infections diagnosed and treated?
Diagnosing chickenpox and shingles is generally straightforward. Chickenpox typically presents with widespread fluid-filled blisters, while shingles typically presents with a one-sided rash in a specific region. However, diagnosing VZV-related disease can be particularly challenging.
"Doctors need to recognize that VZV neurological and systemic disease can occur without a rash or months after a rash," said Nagel. "When someone presents with a puzzling neurological or systemic condition that affects one side of the body, VZV should be considered as a potential cause, even when there is no obvious evidence of shingles."
In those cases, doctors may need to use specialized blood or spinal fluid tests to look for signs of the virus.
Antiviral medications are used to treat VZV infections, while severe or disseminated infections may require intravenous antiviral treatment.
Can vaccination help prevent VZV disease?
Vaccination can reduce the risk of VZV infection and reactivation, including through the chickenpox vaccine and recombinant shingles vaccine. However, it is important to evaluate for any contraindications, such as active shingles and other medical conditions.
Despite the virus's enormous global reach, significant gaps remain in understanding and treating its diverse manifestations.
"There is a critical shortage of clinicians and researchers who specialize in the neurological and systemic manifestations of VZV," said Nagel. "Recognizing these infections requires an awareness that VZV can behave very differently from the classic picture of shingles."
Researchers say important questions remain about how VZV contributes to vascular and neurodegenerative disease, how best to diagnose infections without a rash and how to develop more effective treatments for severe or atypical disease.
