Dormant chickenpox virus is an under-recognised cause of serious disease

Varicella zoster virus, the cause of chickenpox and shingles, can trigger stroke, vision loss and other serious neurological complications often without a rash

A recent review has set out the surprisingly wide range of neurological and systemic diseases that can be caused varicella zoster virus (VZV), the virus responsible for chickenpox and shingles.

More than 90 per cent of people worldwide carry dormant VZV. Yet researchers at the University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA, have said that the virus remains an under-recognised cause of serious neurological and systemic disease, particularly in patients who do not develop the characteristic shingles rash when it reactivates.

Once a person has recovered from chickenpox – or primary VZV infection – the virus remains dormant in nerve cells for life. As the immune system changes with age, or becomes suppressed through illness or medical treatment, VZV can reactivate, most commonly causing a case of shingles. At least one in three people who carry the virus will experience reactivation during their lifetime.

But shingles is only one manifestation of VZV reactivation with the reactivated virus being to also mimic several other common diseases. It can affect sensory nerves, blood vessels and multiple organs producing a wide spectrum of disease. The most common manifestation remains shingles, which presents as fluid-filled blisters on one side of the face or body. Shingles can be complicated by persistent, debilitating pain known as postherpetic neuralgia, one of the most common causes of suicide among older adults who live with chronic pain.

VZV can also cause Ramsay Hunt syndrome, in which shingles develops in the ear alongside facial paralysis on one side of the head, and has been linked to stroke, vision loss, paralysis and abdominal pain with or without an accompanying rash. Shingles can even recur, particularly in those with undiagnosed immune system problems.

Even when VZV produces classic shingles, individuals face an increased risk of stroke, cardiovascular events and dementia. Many of these complications can also occur in children who have had chickenpox, indeed, up to a third of arterial ischaemic strokes in children have been attributed to VZV.

VZV reactivation does not always produce a rash. When the virus reactivates in nerve clusters, it can travel along nerves to the skin, causing shingles, or travel more deeply into the body to affect blood vessels and organs, sometimes in both directions at once. When the virus spreads internally without a visible skin rash, the resulting infection can be considerably harder to recognise, 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 Dr Maria Nagel, professor of neurology and ophthalmology at the CU Anschutz School of Medicine and the review’s 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,” she said.

Diagnosing chickenpox and shingles is generally straightforward given that chickenpox typically presents with widespread fluid-filled blisters, and shingles with a one-sided rash confined to a specific region. Diagnosing VZV-related disease more broadly, however, can be considerably more 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,” she continued.

In such cases, doctors may need to use specialised 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.

Vaccination can reduce the risk of VZV infection and reactivation, including through the chickenpox vaccine and the recombinant shingles vaccine, although clinicians need to evaluate patients for contraindications, such as active shingles and other medical conditions, before either vaccine is given.

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 specialise in the neurological and systemic manifestations of VZV,” said Nagel.

“Recognising these infections requires an awareness that VZV can behave very differently from the classic picture of shingles,” she added.

The review’s authors have said that important questions remain about how VZV contributes to vascular and neurodegenerative disease, how best to diagnose infections that occur without a rash, and how to develop more effective treatments for severe or atypical disease.

For further reading please visit: 10.1038/s41572-026-00735-5