Cold sore (fever blister) outbreak triggers. -

Known local and systemic triggering factors. | How frequently do outbreaks occur? | The process that follows herpesvirus reactivation. | Why cold sores tend to recur in the same location.

Images of herpes simplex virions.

The herpes simplex virus.

What causes cold sore breakouts?

The underlying process.
Following a person's initial oral herpes infection (an event that doesn't involve cold sore formation) Details, some virus particles (virions) will remain in their body. (And will do so forever.)

As this page explains, most of the time these virions will lie dormant and cause no apparent effects.

However at times, in response to some type of triggering event (discussed below), they can become activated.

Once reactivation has begun, a cascade of events will occur that ultimately results in the formation of a cold sore breakout.


What types of events can trigger cold sore/fever blister outbreaks?

There are a number of factors and events that have been identified, however the level of importance that any one plays for an individual will vary.

Triggers are generally categorized as either being systemic (factors involving multiple aspects of the person's body) or local (regional events that affect the area of lesion formation).

Systemic initiators -
  • Emotional upset or stress.
  • Physical stress and fatigue, including just being "run down."
  • Illness, fever. This can include conditions like a cold, the flu, an upper respiratory infection or other viral infection (potentially HIV infection).
  • Menstruation or pregnancy. For some women, cold sores are more frequent around the time of their monthly periods.
  • Sideropenia (iron deficiency).
  • Immune system weakness or deficiency. Also, treatments associated with immunosuppression (such as after an organ transplant) or chemotherapy (like that associated with treating cancer).


Local triggers -
  • Injury (physical trauma) to the lips or surrounding skin, such as a bite, scrape, cut or dermabrasion.
  • Exposure of the lips to bright sunlight, sunburn or an ultraviolet light source. Or extreme dryness, wind or cold exposure that results in chapping.
  • Dental treatment can act as a trigger for breakouts. This includes dental injections, periodontal procedures (gum work) and tooth extractions. Also, non-dental surgical procedures performed in the orofacial area.

Section references - El Hayderi, Arduino

Locations where cold sores (fever blisters) form.

Animation showing the locations where cold sores form.

How often do cold sore breakouts occur?

  • 5 to 10% of the general population experiences 6 or more outbreaks per year (Rooney), with some people having as many as 12 or more (McCarthy).
  • Most people probably have somewhere between "less than 2" (Rooney) and 4 (McCarthy) per year.
  • All told, somewhere between 16 to 38% of the general population suffers from these lesions.

    However, the number of cold sores that a person gets typically diminishes after the age of 35 years (Opstelten). To the point whereby their senior years, only 20% of people continue to experience them. (El Hayderi)

Section references - McCarthy, Rooney, Opstelten, El Hayderi

Additional factors that influence a person's cold sore breakouts.

a) The cold-sore gene.

It's suggested that some individuals may have a genetic susceptibility to getting cold sores.

A paper by Kriesel reported that their team identified a specific gene on chromosome 21 (gene C21orf91) as the likely source for this trait, although the mechanism by which it has its effect is not fully understood. They have given it the name "Cold Sore Susceptibility Gene 1" (CSSG1).

Section references - Kriesel

b) Seasonality.

We decided to look for evidence of a possible seasonal trend in cold sore/fever blister outbreaks.

Our method, and what our graph below shows, was to investigate how often people searched the Google index each month for the keywords "cold sores." (We're making the assumption that few people have an interest in this topic unless they're looking for solutions for their own current/active lesions.)

As you can see, search activity for this topic seems to peak during the winter months. And that would make sense considering that it's a time of year when people are often stressed (such as from a hectic holiday season or common cold) or exposed to harsh environmental conditions (cold, wind, dryness) that can result in lip chapping. (These events are known triggers for cold sore formation.)

Admittedly, our research method shouldn't be interpreted as a rigorous scientific investigation.

Graph showing monthly Google web searches for the term 'cold sores'.

Internet search data suggests that cold sore occurrence likely peaks during the winter months.

What happens after viral reactivation?

a) Background.

Following a person's primary oral herpes infection What to look for., some of the virus particles that were associated with that event travel along sensory nerve fibers running from the affected area to that region's corresponding nerve ganglion.

(A ganglion serves as a hub or relay station along a nerve fiber trunk. The one usually involved with cold sores is the trigeminal ganglion.)

Once they arrive, the virions take up permanent residence. And for most of their time in the ganglion, they exist in a dormant state.


b) Viral reactivation.

The herpes virus lives in association with facial nerve fibers.

Animation showing the association of herpes virus particles and the face's nerve fibers.

When activated, the virus forms a cold sore in the area the nerve services.

In response to some type of triggering event (like those listed above), the dormant virus particles become activated. (The actual mechanism by which this transformation takes place is not completely understood).
Once reactivated, the following cascade of events occurs:
  • Virus particles exit the ganglion. - The virions travel down nerve fibers that run from the ganglion to the skin tissue of the person's perioral area (the area around the mouth).

    The nerve fibers involved are those that actually service this region.

  • The virions exit the nerve fibers and enter into some of the region's skin cells Details | Pictures. Once inside, they begin to replicate (multiply in numbers).
  • As the number of virions increases, the infected skin cells eventually die. This triggers an inflammation response in the surrounding tissues, and culminates in ulcer formation.

    With the progression of these events and the healing process that follows, the cold sore passes through its 5 stages of formation. Details | Pictures

Section references - Hull

c) Factors influencing herpes reactivation.

The conundrum.

It's known that most of us do harbor the herpes simplex virus Statistics, yet not all people experience cold sores. Equally perplexing, of those that do, why do some people have breakouts more frequently than others?

While there's no firm answer to these questions, herpesvirus reactivation is thought to be significantly influenced by the following component factors, each of which varies with each individual.

  1. The virus - This includes both the specific herpes strain as well as the number of virions residing in the ganglion.
  2. The triggering conditions - Factors include the relative severity of the event and the health status of the host at the time.
  3. Host genetics - As mentioned above, recent research suggests that a person's genetic makeup can influence their susceptibility to the reactivation process.

Section references - Kriesel

Cold sore breakouts generally correlate with periods of immune system stress.

The basic idea associated with this statement is that when normal or optimal health conditions exist, a person's immune system is able to keep the herpes virus relatively in check. But when it's compromised (like during sickness), the virus has an easier time in overcoming body defenses, replicating and causing lesions.

  • As you read through the known outbreak triggers listed above, it's easy enough to envision how many of them correlate with periods when a person's immune system would be under stress.
  • Whereas cold sores/fever blisters are typically just a nuisance for those who are healthy, they can be a serious matter (longer-lasting, more severe) for immunocompromised individuals (people who have a chronically debilitated or compromised immune system).


The herpes virus lives in association with specific facial nerve fibers.

Animation showing the association of herpes virus particles and the face's nerve fibers.

Once activated, the virus forms a cold sore in the area the particular nerve services.

Why cold sores tend to recur in the same place.

While you may not have noticed, the details above that outline the cascade of events that take place when the herpes virus becomes reactivated also explain why cold sores tend to reoccur in the same general location each time. Here's a recap:
  • The herpes virus lives in association with specific nerves, and a specific nerve ganglion (the trigeminal).
  • Because of that, when virus reactivation is triggered and virions begin to travel back down nerve fibers, they're deposited in the same general skin location as with other outbreaks (see illustration).
  • Since a nerve ganglion (the location where the dormant virus resides) is a type of nerve "hub," it's possible that on some occasions the nerve fibers traveled are different than before. If so, the cold sore that forms that time will be in a slightly different location.


Why you need to know about cold sore triggers.

Knowing when to expect a cold sore/fever blister is a very important part of managing them. That's because for best results it's imperative that any treatment is begun at the earliest sign of lesion formation.

[This goes for all types of treatments, not just prescription antivirals but also OTC products and home remedies too.]

By observing which factors typically trigger their cold sores, a person can learn when to anticipate an outbreak. And this may give them an opportunity to begin the use of medication early enough (preferably during the Tingle stage Description) that it can affect the course of their lesion and its symptoms, possibly significantly.


 Page references sources: 

Arduino PG, et al. Herpes Simplex Virus Type 1 infection: Overview on relevant clinico-pathological features.

El Hayderi L, et al. Severe herpes simplex virus type-I infections after dental procedures.

Hull CM, et al. Novel Composite Efficacy Measure To Demonstrate the Rationale and Efficacy of Combination Antiviral–Anti-Inflammatory Treatment for Recurrent Herpes Simplex Labialis.

Kriesel JD, et al. Cold sore susceptibility gene-1 genotypes affect the expression of herpes labialis in unrelated human subjects.

McCarthy JP, et al. Treatment of Herpes Labialis: Comparison of Two OTC Drugs and Untreated Controls.

Opstelten W, et al. Treatment and prevention of herpes labialis.

Rooney JF, et al. Oral acyclovir to suppress frequently recurrent herpes labialis. A double-blind, placebo-controlled trial.

All reference sources for topic Dental Crowns.