Herpes Simplex Reactivation

Once herpes simplex virus enters the body, it remains there for life, mostly dormant in nerve cells. Periodically, the virus can “wake up” and travel back to the skin, causing recurring outbreaks of blisters and sores.

Table of contents

• What is herpes simplex reactivation?
• How reactivation happens in the body
• What triggers the virus to reactivate
• Symptoms during reactivation
• Reactivation without symptoms
• Treatment and management

What is herpes simplex reactivation?

Herpes simplex reactivation is when the herpes virus, which has been dormant in your body, becomes active again. After the first infection with herpes simplex virus (HSV), the virus does not leave your body. Instead, it travels along nerve pathways and hides in clusters of nerve cells called ganglia, located near the spinal cord.^[1] There, the virus remains inactive, sometimes for long periods.^[2]

When the virus reactivates, it begins multiplying again and travels back through the nerve fibers to the skin surface.^[4] This can cause another outbreak of symptoms, though reactivation does not always lead to visible sores or noticeable illness.^[7]

Most people with herpes simplex experience reactivation at some point in their lives. For oral herpes, the virus typically reactivates one to six times per year, though this varies greatly among individuals.^[13] The likelihood and frequency of reactivation differs between HSV-1 and HSV-2, with HSV-2 genital herpes showing more frequent recurrences than HSV-1 genital herpes.^[8]

How reactivation happens in the body

Understanding how reactivation works requires knowing what happens after the initial infection. Once HSV gains entry to the body through the skin or mucous membranes, the virus begins making copies of itself and spreading.^[5] Your immune system responds by mobilizing to limit the virus’s spread.

To avoid the immune system, HSV retreats along nerve pathways. In cases of genital herpes, HSV hides in the sacral ganglion, located at the base of the spine. In oral or facial herpes, the virus finds its way to the trigeminal ganglion, at the top of the spine.^[5] In these nerve root clusters, the virus remains latent, similar to being in a sleep cycle.^[1]

The phenomenon of latency means the virus creates a small but permanent colony inside your body that can be completely inactive but stays for a lifetime.^[5] Periodically, various biological events can cause the dormant virus to wake up and begin traveling the nerve pathways back to the skin.^[5] When it reaches the skin surface, it may cause signs and symptoms again, though this does not always happen.^[4]

What triggers the virus to reactivate

Many different factors can trigger herpes simplex virus to reactivate from its dormant state. Reactivation can be triggered by a variety of stimuli that activate different cellular processes.^[1] Understanding these triggers may help you reduce the frequency of outbreaks.

Common triggers include:^[4][13]

• Fever or illness
• Emotional stress or anxiety
• Physical trauma, such as dental procedures
• Overexposure of the lips to sunlight or ultraviolet radiation
• Extremes in temperature
• Suppression of the immune system (for example, by medications taken to prevent organ transplant rejection, or in people with weakened immune systems)

In many cases, the trigger is unknown.^[4] Research has shown that interactions between different viruses can also trigger dormant viruses to reactivate.^[6] For instance, when the immune system responds to one type of infection, this response can inadvertently cause herpes virus to reactivate.^[6]

The virus can be transmitted to others during reactivation, both when symptoms are present and sometimes when no symptoms are visible. There are several days throughout the year when the virus may be on the surface of the skin without any symptoms, a process called asymptomatic shedding.^[5]

Symptoms during reactivation

When the herpes virus reactivates, symptoms are usually less severe and shorter in duration compared to the first infection.^[4] Many people notice warning signs before visible symptoms appear. Before a cold sore or genital herpes outbreak occurs, people often feel a tingling, itching, or burning sensation at the site, lasting from minutes to a few hours, followed by redness and swelling.^[3][4]

Common symptoms during reactivation include:^[2][3]

• Painful, recurring blisters or ulcers
• Fluid-filled blisters that break open and crust over
• Sores on the lips or around the mouth (oral herpes)
• Bumps, blisters, or open sores around the genitals or anus (genital herpes)

For oral herpes, recurrences usually produce a cluster of sores on the rim of the lip, commonly called cold sores or fever blisters.^[4] The sores quickly form a scab, and after about five to ten days, the scab falls off and the episode ends.^[4] Less often, tingling and redness occur without blister formation.^[4]

During a study of herpes labialis (cold sores), the median duration of HSV-1 shedding was 60 hours when measured by laboratory testing, with peak viral load occurring at 48 hours and no virus detected beyond 96 hours after symptom onset.^[13]

Reactivation without symptoms

It is important to understand that reactivation does not necessarily mean you will have visible symptoms. Most people with herpes have no symptoms or only mild symptoms, and many are not aware they have the infection.^[3] The majority of persons infected with HSV-2 have not had the condition diagnosed, many of whom have mild or unrecognized infections but shed virus intermittently.^[8]

Reactivation does not necessarily imply clinical symptoms, as reflected in the asymptomatic shedding of virus from mucous membranes.^[7] During these periods of asymptomatic reactivation, the virus may be on the surface of the skin even when no blisters can be seen.^[4] This means the virus can be transmitted to others during sexual contact even when there are no visible sores.^[5]

Consequently, most genital herpes infections are transmitted by persons unaware that they have the infection or who are asymptomatic when transmission occurs.^[8] This is one reason why herpes is such a common infection worldwide.^[3]

Treatment and management

There is no cure for herpes simplex virus, meaning the virus cannot be eliminated from your body once you are infected.^[2] However, antiviral medications can help manage outbreaks and reduce the frequency of reactivation.

The primary treatment options include oral antiviral medications such as acyclovir, valacyclovir, and famciclovir.^[10] These medications work by interfering with the virus’s ability to replicate itself.^[10] Antivirals are most effective when taken within 72 hours of the appearance of lesions.^[10]

For people with recurrent infections, there are different treatment approaches:^[14]

• Episodic treatment: Taking medication only during outbreaks to reduce severity and duration
• Suppressive therapy: Taking daily medication to prevent or reduce the frequency of outbreaks

The primary role of chronic suppressive therapy is to decrease the frequency, severity, and duration of outbreaks, and to reduce the risk of transmitting the virus to others.^[14] Long-term suppressive therapy can be continued for up to one year, with reassessment at the end of therapy.^[10] Studies have shown that recurrences of herpes can be suppressed with daily oral acyclovir or valacyclovir.^[13]

Topical treatments such as acyclovir cream, penciclovir, and docosanol are available but are generally less effective than oral medications.^[13] Many people find that identifying and avoiding their personal triggers can help reduce the frequency of reactivation episodes.^[4]

The best approach to managing herpes reactivation depends on the frequency and severity of recurrent infections and your personal preferences.^[10] It is important to discuss treatment options with your healthcare provider to determine what is most appropriate for your situation.