Definitions

In medical contexts, "labia" is a general term for "lip"; "herpes labialis" does not refer to the labia of
the genitals, though the etymology is the same. When the viral infection affects both face and mouth,
the broader term "orofacial herpes" is used to describe the condition, whereas the term "herpetic
stomatitis" is used to specifically describe infection of the mouth; "stomatitis" is derived from the
Greek word stoma that means "mouth".

Signs and symptoms

Herpes infections usually show no symptoms;[5] when symptoms do appear they typically resolve
within two weeks.[6] The main symptom of oral infection is inflammation of the mucosa of the cheek
and gumsknown as acute herpetic gingivostomatitiswhich occurs within 510 days of infection.
Other symptoms may also develop, including headache, nausea, dizziness and painful ulcers
sometimes confused with canker soresfever, and sore throat.[6]
Primary HSV infection in adolescents frequently manifests as
severe pharyngitis with lesions developing on the cheek and gums. Some individuals develop
difficulty in swallowing (dysphagia) and swollen lymph nodes(lymphadenopathy).[6] Primary HSV
infections in adults often results in pharyngitis similar to that observed in glandular fever (infectious
mononucleosis), but gingivostomatitis is less likely.
Recurrent oral infection is more common with HSV-1 infections than with HSV-2. Symptoms typically
progress in a series of eight stages:
1. Latent (weeks to months incident-free): The remission period; After initial infection, the
viruses move to sensory nerve ganglia (trigeminal ganglion),[7] where they reside as
lifelong, latent viruses. Asymptomatic shedding of contagious virus particles can occur
during this stage.
2. Prodromal (day 01): Symptoms often precede a recurrence. Symptoms typically begin with
tingling (itching) and reddening of the skin around the infected site. This stage can last from
a few days to a few hours preceding the physical manifestation of an infection and is the
best time to start treatment.
3. Inflammation (day 1): Virus begins reproducing and infecting cells at the end of the nerve.
The healthy cells react to the invasion with swelling and redness displayed as symptoms of
infection.
4. Pre-sore (day 23): This stage is defined by the appearance of tiny, hard, inflamed papules
and vesicles that may itch and are painfully sensitive to touch. In time, these fluidfilled blisters form a cluster on the lip (labial) tissue, the area between the lip and skin
(vermilion border), and can occur on the nose, chin, and cheeks.
5. Open lesion (day 4): This is the most painful and contagious of the stages. All the tiny
vesicles break open and merge to create one big, open, weeping ulcer. Fluids are slowly
discharged from blood vessels and inflamed tissue. This watery discharge is teeming with

active viral particles and is highly contagious. Depending on the severity, one may develop a
fever and swollen lymph glands under the jaw.[8]
6. Crusting (day 58): A honey/golden crust starts to form from the syrupy exudate. This
yellowish or brown crust or scab is not made of active virus but from blood serum containing
useful proteins such asimmunoglobulins. This appears as the healing process begins. The
sore is still painful at this stage, but, more painful, however, is the constant cracking of the
scab as one moves or stretches their lips, as in smiling or eating. Virus-filled fluid will still
ooze out of the sore through any cracks.
7. Healing (day 914): New skin begins to form underneath the scab as the virus retreats into
latency. A series of scabs will form over the sore (called Meier Complex), each one smaller
than the last. During this phase irritation, itching, and some pain are common.
8. Post-scab (1214 days): A reddish area may linger at the site of viral infection as the
destroyed cells are regenerated. Virus shedding can still occur during this stage.
The recurrent infection is thus often called herpes simplex labialis. Rare reinfections occur inside the
mouth (intraoral HSV stomatitis) affecting the gums, alveolar ridge, hard palate, and the back of the
tongue, possibly accompanied by herpes labialis.[6]
A lesion caused by herpes simplex can occur in the corner of the mouth and be mistaken for angular
cheilitis of another cause. Sometimes termed "angular herpes simplex". [9] A cold sore at the corner of
the mouth behaves similarly to elsewhere on the lips. Rather than utilizing antifungal creams,
angular herpes simplex is treated in the same way as a cold sore, with topical antiviral drugs.

Causes
Herpes labialis infection occurs when the herpes simplex virus comes into contact with oral
mucosal tissue or abraded skin of the mouth. Infection by the type 1 strain of herpes simplex virus
(HSV-1) is most common; however, cases of oral infection by the type 2 strain are increasing.
[6]
Specifically, type 2 has been implicated as causing 1015% of oral infections.
Cold sores are the result of the virus reactivating in the body. Once HSV-1 has entered the body, it
never leaves. The virus moves from the mouth to remain latent in the central nervous system. In
approximately one-third of people, the virus can "wake up" or reactivate to cause disease. When
reactivation occurs, the virus travels down the nerves to the skin where it may cause blisters (cold
sores) around the lips, in the mouth or, in about 10% of cases, on the nose, chin, or cheeks.
Cold sore outbreaks may be influenced by stress, menstruation, sunlight, sunburn, fever,
dehydration, or local skin trauma. Surgical procedures such as dental or neural surgery, lip tattooing,
or dermabrasion are also common triggers. HSV-1 can in rare cases be transmitted to newborn
babies by family members or hospital staff who have cold sores; this can cause a severe disease
called neonatal herpes simplex.
The colloquial term for this condition, "cold sore" comes from the fact that herpes labialis is often
triggered by fever, for example, as may occur during an upper respiratory tract infections (i.e. a cold).
[10]

People can transfer the virus from their cold sores to other areas of the body, such as the eye, skin,
or fingers; this is called autoinoculation. Eye infection, in the form of conjunctivitis or keratitis, can
happen when the eyes are rubbed after touching the lesion. Finger infection (herpetic whitlow) can
occur when a child with cold sores or primary HSV-1 infection sucks his fingers.
Blood tests for herpes may differentiate between type 1 and type 2. When a person is not
experiencing any symptoms, a blood test alone does not reveal the site of infection. Genital herpes
infections occurred with almost equal frequency as type 1 or 2 in younger adults when samples were
taken from genital lesions. Herpes in the mouth is more likely to be caused by type 1, but (see
above) also can be type 2. The only way to know for certain if a positive blood test for herpes is due
to infection of the mouth, genitals, or elsewhere, is to sample from lesions. This is not possible if the
afflicted individual is asymptomatic.

Prevention
The likelihood of the infection being spread can be reduced through behaviors such as avoiding
touching an active outbreak site, washing hands frequently while the outbreak is occurring, not
sharing items that come in contact with the mouth, and not coming into close contact with others (by
avoiding kissing, oral sex, or contact sports).
Because the onset of an infection is difficult to predict, lasts a short period of time and heals rapidly,
it is difficult to conduct research on cold sores. Though famciclovir improves lesion healing time, it is
not effective in preventing lesions; valaciclovir and a mixture of acyclovir and hydrocortisone are
similarly useful in treating outbreaks but may also help prevent them. [11]
Oral acyclovir and valacyclovir are effective in preventing recurrent herpes labialis if taken prior to
the onset of any symptoms or exposure to any triggers.[3]

Treatment
Docosanol, a saturated fatty alcohol, is a safe and effective topical application that has been
approved by the United States Food and Drug Administration for herpes labialis in adults with
properly functioning immune systems. It is comparable in effectiveness to prescription topical
antiviral agents. Due to its mechanism of action, there is little risk of drug resistance.[12] The duration
of symptoms can be reduced by a small amount if an antiviral, anesthetic or non-treatment cream
(such as zinc oxide or zinc sulfate) is applied promptly.[7]
Effective antiviral medications include acyclovir and penciclovir, which can speed healing by as
much as 10%.[11] Famciclovir or valacyclovir, taken in pill form, can be effective using a single day,
high-dose application and is more cost effective and convenient than the traditional treatment of
lower doses for 57 days.[13]

Epidemiology
Herpes labialis is endemic throughout the world. A large survey of young adults on six continents
reported that 33.2% of males and 28% of females had herpes labialis on two or more occasions
during the year before study. The lifetime prevalence in the United States of America is estimated at
20-45% of the adult population. Lifetime prevalence in France was reported by one study as 32.4%
in males and 42.1% in females. In Germany, the prevalence was reported at 31.7% in people aged

between 35 and 44 years, and 20% in those aged 6574. In Jordan, another study reported a
lifetime prevalence of 26.4%.[1]

References
1.

^ Jump up to:a b c Lee C, Chi CC, Hsieh SC, Chang CJ, Delamere FM, Peters MC, Kanjirath
PP, Anderson PF (2011). "Interventions for treatment of herpes simplex labialis (cold sores on the lips)
(Protocol)". Cochrane Database of Systematic Reviews (10). doi:10.1002/14651858.CD009375.

2.

Jump up^ "Cold sores, sometimes called fever blisters, are groups of small blisters on the lip
and around the mouth." WebMD, Cold sores - topic overview: http://www.webmd.com/skin-problemsand-treatments/tc/cold-sores-topic-overview

3.

^ Jump up to:a b Rahimi H, Mara T, Costella J, Speechley M, Bohay R (May 2012).

"Effectiveness of antiviral agents for the prevention of recurrent herpes labialis: a systematic review
and meta-analysis.". Oral surgery, oral medicine, oral pathology and oral radiology 113 (5): 618
27. doi:10.1016/j.oooo.2011.10.010. PMID 22668620.

4.

Jump up^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the
Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.

5.

Jump up^ Opstelten W, Neven AK, Eekhof J (December 2008). "Treatment and prevention of
herpes labialis". Can Fam Physician 54 (12): 16831687. PMC 2602638. PMID 19074705.

6.

^ Jump up to:a b c d e Bruce AJ, Rogers RS (2004). "Oral manifestations of sexually transmitted
diseases". Clin. Dermatol.22 (6): 520527. doi:10.1016/j.clindermatol.2004.07.005. PMID 15596324.

7.

^ Jump up to:a b Opstelten W, Neven AK, Eekhof J (December 2008). "Treatment and
prevention of herpes labialis.".Canadian family physician Medecin de famille canadien 54 (12): 1683
7. PMC 2602638. PMID 19074705.

8.

Jump up^ Emmert DH (Mar 15, 2000). "Treatment of common cutaneous herpes simplex
virus infections.". American family physician 61 (6): 1697706, 1708. PMID 10750877.

9.

Jump up^ Park KK, Brodell RT, Helms SE (June 2011). "Angular cheilitis, part 1: local
etiologies.". Cutis; cutaneous medicine for the practitioner 87 (6): 28995. PMID 21838086.

10.

Jump up^ Scully C (2013). Oral and maxillofacial medicine : the basis of diagnosis and
treatment (3rd ed.). Edinburgh: Churchill Livingstone. pp. 277281. ISBN 9780702049484.

11.

^ Jump up to:a b Harmenberg J, Oberg B, Spruance S (2010). "Prevention of ulcerative lesions

by episodic treatment of recurrent herpes labialis: A literature review". Acta Derm. Venereol. 90 (2):
12230. doi:10.2340/00015555-0806. PMID 20169294.

12.

Jump up^ Treister NS, Woo SB (2010). "Topical n-docosanol for management of recurrent
herpes labialis". Expert Opin Pharmacother 11 (5): 853
60. doi:10.1517/14656561003691847. PMID 20210688.

13.

Jump up^ Gilbert SC (2007). "Management and prevention of recurrent herpes labialis in
immunocompetent patients".Herpes 14 (3): 5661. PMID 18371287.