What Causes Shingles to Flare Up?

Shingles flares up when the varicella-zoster virus, dormant in your nerve cells since a childhood bout of chickenpox, reactivates because the immune surveillance keeping it in check has weakened. The most common reason for that weakening is simply getting older, but a surprising range of other factors can tip the balance: disease, medications, stress, sun exposure, even physical injury to the body. Understanding these triggers matters because some are avoidable and others signal that vaccination deserves serious consideration.

Why the Virus Is Already There

If you had chickenpox at any point in your life, the varicella-zoster virus (VZV) never actually left. After your childhood infection cleared, the virus retreated into clusters of nerve cells called ganglia that run along your spinal cord and up into your skull. It sits there silently, held in check by a branch of your immune system called cell-mediated immunity, specifically by T cells that recognize VZV and keep it from multiplying. As long as those T cells stay active and numerous enough, the virus stays dormant. A shingles flare-up is what happens when that immune patrol falters and the virus travels back down a nerve to the skin, producing the characteristic painful, blistering rash in the area that nerve supplies.¹

Aging Is the Single Biggest Trigger

The risk of shingles rises steeply after age 50, and roughly a third of people who live into their eighties will experience an episode. The reason is straightforward: the T cells responsible for controlling VZV deteriorate with age. Research comparing immune responses in younger and older adults vaccinated against VZV found that CD8+ T cells in older people undergo pronounced changes, including shifts in the types of memory cells present, reduced diversity of their virus-recognizing receptors, and a loss of the “stem-like” qualities that allow long-lasting immune memory.² In plain terms, older immune systems have fewer and less versatile soldiers available to keep VZV in line. This age-driven decline is why shingles is overwhelmingly a disease of later life, even though the virus has been dormant in the body for decades.

Conditions That Compromise Immune Control

Any disease that weakens cell-mediated immunity can open the door for VZV reactivation. A large meta-analysis of risk factors found that people living with HIV/AIDS faced roughly triple the risk of shingles compared with controls, while blood cancers like lymphoma and leukemia more than doubled the risk.³ A separate population-based study that looked at 21 specific cancer types found that blood cancers were especially dangerous, with myeloma linked to roughly four times the odds of developing shingles.⁴ Solid-organ transplant recipients and people who have undergone stem-cell transplants are also at sharply elevated risk, with shingles rates in these groups sometimes reaching many times the rate in the general population.⁵

Diabetes, particularly type 2 diabetes, also raises the likelihood of a flare-up. The chronic low-grade inflammation and impaired immune function that accompany poorly controlled blood sugar appear to make it easier for VZV to reactivate, and people with type 2 diabetes face elevated risk not only of shingles itself but also of its most dreaded complication, postherpetic neuralgia.⁶

COVID-19 has added another layer. A systematic review of shingles cases in COVID-19 patients found that VZV-related rashes appeared at a median of about seven days after the start of respiratory symptoms, suggesting that the acute immune disruption caused by SARS-CoV-2 infection can trigger reactivation surprisingly quickly.⁷

Medications That Can Set Off Reactivation

Because many modern drugs are designed to suppress immune activity, they can inadvertently give VZV the opening it needs. A pharmacovigilance analysis of two decades of FDA adverse-event reports identified the drugs most frequently linked to shingles. By sheer volume of reports, TNF-inhibitors used for autoimmune conditions (adalimumab and etanercept) and the JAK inhibitor tofacitinib were at the top. But the drugs with the strongest statistical signal relative to all other reported side effects were newer and more targeted immune suppressors: anifrolumab, a lupus drug, showed the highest disproportionality signal, followed by ocrelizumab and alemtuzumab, both used in multiple sclerosis, and tofacitinib and baricitinib, JAK inhibitors widely prescribed for rheumatoid arthritis.⁸

If you take any immunosuppressive medication, this does not mean shingles is inevitable, but it does mean the topic is worth raising with your prescribing doctor. Many rheumatologists and neurologists now recommend the recombinant zoster vaccine before starting certain biologic therapies, precisely because the risk is well recognized.

Stress, Physical Trauma, and Sun Exposure

People often suspect that stress triggered their shingles episode, and there is real evidence behind the intuition. A case-control study of older adults found that patients who developed shingles were more than twice as likely to have experienced stressful negative life events in the two to six months before the rash appeared, compared with matched controls.⁹ The mechanism is not entirely mysterious: psychological stress triggers hormonal changes (mainly elevated cortisol) that dampen the T-cell activity responsible for keeping VZV locked down.

Physical trauma to the body can also provoke reactivation, though this is rarer. Case reports document shingles erupting along the nerve that supplies a recently injured area. One such report described VZV reactivation along the trigeminal nerve after facial trauma, producing severe pain at the injury site.¹⁰ The thinking is that local tissue damage and the inflammatory response it triggers may disrupt the nerve environment enough to rouse the dormant virus.

Ultraviolet radiation from the sun is another trigger that gets less public attention than it deserves. Research following large groups of people over time has linked higher UV exposure to increased shingles risk. UV light suppresses T-cell function both locally in the skin and throughout the body by releasing immune-dampening signaling molecules, essentially weakening the very arm of immunity that keeps VZV dormant.¹¹ Seasonal variation in shingles cases, with more episodes during sunnier months, further supports this connection, and melanin’s photoprotective effects may partially explain lower reactivation rates in people with darker skin.¹²

Genetics and Family History

Not everyone with declining immunity develops shingles, which has led researchers to look for genetic explanations. Genome-wide analyses have identified a region in the HLA complex, the part of our DNA that governs immune recognition of foreign invaders, that reaches statistical significance for its association with when people develop shingles. The gene involved, HCP5, is actually an endogenous retrovirus fragment that likely influences VZV activity through regulatory functions.¹³

Variations in the gene that produces interleukin-10, an immune-regulating molecule, have also been found at higher rates in shingles patients. Certain versions of this gene may impair the immune system’s ability to respond effectively to VZV, making carriers more susceptible to reactivation. Other genetic variations in HLA Class I genes have been linked to the risk of postherpetic neuralgia specifically.¹⁴ The practical takeaway is that if close family members have had shingles, your own risk may be somewhat higher, independent of age or immune status.

Nutrition and Vitamin D

Your immune system requires adequate nutrition to function, and specific deficiencies have been tied to shingles risk. Micronutrient shortfalls can impair the T-cell responses that keep VZV contained, and supplementation has shown some benefit in reducing herpetic pain in patients already dealing with an outbreak or postherpetic neuralgia.¹⁵

Vitamin D has drawn particular attention. It supports immune function by stimulating T-cell maturation and increasing the proportion of regulatory T cells that help manage inflammation. Low vitamin D levels have been associated with shingles reactivation, and the connection may be partly indirect: vitamin D deficiency correlates with higher mental stress, and stress itself promotes VZV reactivation through hormonal effects on the nerve cells where the virus hides.¹⁶ None of this means taking vitamin D supplements will prevent shingles outright, but maintaining adequate levels is one modifiable factor in a landscape where many triggers are not within your control.

Subclinical Reactivation Without Symptoms

One of the more striking findings in VZV research is that the virus reactivates far more often than people realize, usually without producing any symptoms at all. Studies of astronauts aboard the Space Shuttle and International Space Station provided a vivid demonstration. Before spaceflight, VZV DNA was almost never detected in astronauts’ saliva. During and after missions, about 30% of saliva samples came back positive for VZV DNA across all eight astronauts tested in one study.¹⁷ Follow-up work confirmed that this was not just harmless viral fragments: infectious VZV was recovered from the saliva of two out of three astronauts in a subsequent study, the first proof that the virus can shed in an infectious form without producing any disease in the person shedding it.¹⁸

Spaceflight is an extreme environment that combines physical stress, disrupted sleep, radiation exposure, and immune suppression. But the finding is relevant on the ground too: it suggests the virus likely stirs from time to time in all of us, only crossing the threshold into a full-blown shingles episode when the immune system is sufficiently compromised. The occasional minor stirring may actually help maintain immunity by reminding T cells what VZV looks like, a phenomenon called “exogenous boosting” that some researchers believe has protected younger cohorts historically exposed to children with chickenpox.

Can Shingles Happen More Than Once

Many people assume shingles is a one-time event, but recurrence is possible. Estimates of how many people experience a second episode vary widely depending on the population studied and the follow-up period, ranging from roughly 1% to nearly 10% of those who have had a first episode.¹⁹ In the Shingles Prevention Study, recurrences were confirmed by PCR and always involved wild-type VZV (not vaccine virus). Each recurrence occurred in a different nerve territory than the original episode, sometimes on the opposite side of the body, and appeared 12 to 28 months after the first bout.²⁰ The same risk factors that cause a first episode, particularly immunosuppression, older age, and female sex, tend to predict recurrence as well.

When Shingles Arrives Without a Rash

Doctors sometimes struggle to diagnose a condition called zoster sine herpete, in which VZV reactivates and causes nerve pain but never produces the telltale blistering rash. Cases are considered rare, though the true frequency is unknown precisely because the absence of visible blisters makes diagnosis difficult. Beyond pain without rash, VZV can also reactivate to cause neurological problems such as facial palsy without any skin eruption at all.²¹ One study comparing outcomes of facial palsy caused by zoster sine herpete to outcomes in Bell’s palsy (which has a different cause) found that recovery rates were significantly worse in the zoster group.²² If you develop unexplained nerve pain along one side of your body or sudden facial weakness, VZV reactivation is worth considering even if no rash appears.

What Happens to the Nerves During a Flare

The pain of shingles is not just skin-deep. During an active episode, the reactivating virus damages nerve fibers as it travels from the ganglion to the skin, producing a combination of inflammatory tissue injury and direct nerve damage.²³ In most people the nerves heal over weeks or months. In those who develop postherpetic neuralgia, the damage persists. Skin biopsies of affected areas show dramatic loss of small nerve fibers in the outer skin layers. One study found that people with postherpetic neuralgia had roughly a fifth of the normal nerve-fiber density in their affected skin, compared with shingles patients who recovered without lasting pain. Unexpectedly, the nerve damage extended to the opposite side of the body as well, suggesting a bilateral mechanism that researchers are still working to understand.²⁴

How the Recombinant Vaccine Changes the Equation

The most effective way to prevent flare-ups is the recombinant zoster vaccine (Shingrix), which was designed specifically to restore the VZV-specific cellular and antibody immunity that declines with age.²⁵ Unlike the older live vaccine, which used a weakened form of the whole virus, Shingrix targets a single viral protein and includes an adjuvant that provokes a stronger immune response even in older adults.

Long-term data show that immune responses to Shingrix remain well above pre-vaccination levels for at least a decade, with both T-cell and antibody markers holding at several times their baseline levels through year ten. However, there is a meaningful decline in the first few years after vaccination, and at least a quarter of people in the oldest age groups showed waning cellular immunity within a few years, raising the question of whether a booster dose may eventually be needed.²⁶ For now, no booster is officially recommended, but it is an area of active study.

Shingles in children is uncommon but not unheard of. It occurs most often in kids who were exposed to VZV in utero or during the first year of life, when their immune systems were still immature. Healthy children with no particular risk factors only rarely develop shingles, a reminder that the combination of viral latency and immune decline is what typically drives reactivation.²⁷