Herpes labialis
Encyclopedia
Herpes labialis or "orolabial herpes" is an infection of the lip
Lip
Lips are a visible body part at the mouth of humans and many animals. Lips are soft, movable, and serve as the opening for food intake and in the articulation of sound and speech...

 by herpes simplex virus
Herpes simplex virus
Herpes simplex virus 1 and 2 , also known as Human herpes virus 1 and 2 , are two members of the herpes virus family, Herpesviridae, that infect humans. Both HSV-1 and HSV-2 are ubiquitous and contagious...

 (HSV-1). An outbreak typically causes small blisters or sores on or around the mouth commonly known as cold sores or fever blisters. The sores typically heal within 2–3 weeks, but the herpes virus remains dormant
Dormancy
Dormancy is a period in an organism's life cycle when growth, development, and physical activity are temporarily stopped. This minimizes metabolic activity and therefore helps an organism to conserve energy. Dormancy tends to be closely associated with environmental conditions...

 in the facial nerve
Nerve
A peripheral nerve, or simply nerve, is an enclosed, cable-like bundle of peripheral axons . A nerve provides a common pathway for the electrochemical nerve impulses that are transmitted along each of the axons. Nerves are found only in the peripheral nervous system...

s, following orofacial infection, periodically reactivating (in symptomatic people) to create sores in the same area of the mouth or face at the site of the original infection.

HSV-1 affected 57.7% of Americans tested in a 1999-2004 study. By age 50, 80%–90% of adults have the virus. More than 50 million adults in the U.S. develop symptomatic episodes every year. Cold sore has a rate of frequency that varies from rare episodes to 12 or more recurrences per year. Most sufferers experience one to three attacks annually. The frequency and severity of outbreaks generally decreases over time.

The virus is transmitted from cold sores and also when there are no symptoms, as it can make copies of itself on the skin in the absence of a blister.

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
Etymology
Etymology is the study of the history of words, their origins, and how their form and meaning have changed over time.For languages with a long written history, etymologists make use of texts in these languages and texts about the languages to gather knowledge about how words were used during...

 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
Stoma
In botany, a stoma is a pore, found in the leaf and stem epidermis that is used forgas exchange. The pore is bordered by a pair of specialized parenchyma cells known as guard cells that are responsible for regulating the size of the opening...

 that means "mouth".

Signs and symptoms

Herpes infections often show no symptoms; when symptoms do appear they typically resolve within two weeks. The main symptom of oral infection is inflammation of the mucosa of the cheek and gums—known as acute herpetic gingivostomatitis
Gingivostomatitis
Gingivostomatitis is a combination of gingivitis and stomatitis, or an inflammation of the oral mucosa and gingiva. Herpetic gingivostomatitis is often the initial presentation during the first herpes simplex infection. It is of greater severity than herpes labialis which is often the subsequent...

—which occurs within 5–10 days of infection. Other symptoms may also develop, including headache, nausea, dizziness and painful ulcers—sometimes confused with canker sores—fever, and sore throat. Primary HSV infection in adolescents frequently manifests as severe pharyngitis
Pharyngitis
Pharyngitis is an inflammation of the throat or pharynx. In most cases it is quite painful, and is the most common cause of a sore throat.Like many types of inflammation, pharyngitis can be acute – characterized by a rapid onset and typically a relatively short course – or chronic....

 with lesion
Lesion
A lesion is any abnormality in the tissue of an organism , usually caused by disease or trauma. Lesion is derived from the Latin word laesio which means injury.- Types :...

s developing on the cheek and gums. Some individuals develop difficulty in swallowing (dysphagia
Dysphagia
Dysphagia is the medical term for the symptom of difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, the term is sometimes used as a condition in its own right. Sufferers are sometimes unaware of their dysphagia....

) and swollen lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...

s (lymphadenopathy
Lymphadenopathy
Lymphadenopathy is a term meaning "disease of the lymph nodes." It is, however, almost synonymously used with "swollen/enlarged lymph nodes". It could be due to infection, auto-immune disease, or malignancy....

). Primary HSV infections in adults often results in pharyngitis similar to that observed in glandular fever (infectious mononucleosis
Infectious mononucleosis
Infectious mononucleosis is an infectious, widespread viral...

), 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 (see viral life cycle
Viral life cycle
Viruses are similar to living organisms, however there are differences. One of the ways a virus can be seen as living is that a virus needs to replicate and create progeny. However, unlike other organisms, a virus cannot survive on its own. It is only active when replicating within a host, using a...

):
  1. Latent (weeks to months incident-free): The remission period; After initial infection, the viruses move to sensory nerve ganglia (Trigeminal ganglion
    Trigeminal ganglion
    The trigeminal ganglion is a sensory ganglion of the trigeminal nerve that occupies a cavity in the dura mater, covering the trigeminal impression near the apex of the petrous part of the temporal bone.-Relations:It is somewhat crescentic in shape, with its convexity...

    ), where they reside as life-long, latent viruses
    Virus latency
    Virus latency is the ability of a pathogenic virus to lie dormant within a cell, denoted as the lysogenic part of the viral life cycle. A latent viral infection is a type of persistent viral infection which is distinguished from a chronic viral infection...

    . Asymptomatic shedding of contagious virus cells can occur during this stage.
  2. Prodromal (day 0–1): 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 2–3): 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 fluid-filled blister
    Blister
    A blister is a small pocket of fluid within the upper layers of the skin, typically caused by forceful rubbing , burning, freezing, chemical exposure or infection. Most blisters are filled with a clear fluid called serum or plasma...

    s 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.
  6. Crusting (day 5–8): 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
    Blood serum
    In blood, the serum is the component that is neither a blood cell nor a clotting factor; it is the blood plasma with the fibrinogens removed...

     containing useful proteins such as albumin
    Albumin
    Albumin refers generally to any protein that is water soluble, which is moderately soluble in concentrated salt solutions, and experiences heat denaturation. They are commonly found in blood plasma, and are unique to other blood proteins in that they are not glycosylated...

     and globulins. This appears as the healing process begins and should not be scraped or picked at. 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 9–14): 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 (12–14 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
Alveolar ridge
An alveolar ridge is one of the two jaw ridges either on the roof of the mouth between the upper teeth and the hard palate or on the bottom of the mouth behind the lower teeth. The alveolar ridges contain the sockets of the teeth....

, hard palate
Hard palate
The hard palate is a thin horizontal bony plate of the skull, located in the roof of the mouth. It spans the arch formed by the upper teeth.It is formed by the palatine process of the maxilla and horizontal plate of palatine bone....

, and the back of the tongue, possibly accompanied by herpes labialis.

Causes

Herpes labialis infection occurs when the herpes simplex virus comes into contact with oral mucosa
Oral mucosa
The oral mucosa is the mucous membrane epithelium of the mouth. It can be divided into three categories.*Masticatory mucosa, para-keratinized stratified squamous epithelium, found on the dorsum of the tongue, hard palate and attached gingiva....

l 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.

Cold sores are the result of the virus's reactivating in the body. Once HSV-1 has entered the body, it never leaves. The virus moves from the mouth to quietly reside (“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, 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
Neonatal herpes simplex
Neonatal herpes simplex is a rare but serious condition, usually caused by vertical transmission of herpes simplex virus from mother to newborn.-Transmission:...

.

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
Herpetic whitlow
A herpetic whitlow is a lesion on a finger or thumb caused by the herpes simplex virus. It is a painful infection that typically affects the fingers or thumbs. Occasionally infection occurs on the toes or on the nail cuticle. Herpes whitlow can be caused by infection by HSV-1 or HSV-2...

) can occur when a child with cold sores or primary HSV-1 infection sucks his/her fingers.

Treatment

Docosanol
Docosanol
Docosanol, also known as behenyl alcohol, is a saturated fatty alcohol used traditionally as an emollient, emulsifier, and thickener in cosmetics, nutritional supplement , and more recently, in a Food and Drug Administration approved pharmaceutical, Abreva, approved as an antiviral agent for...

, a saturated
Saturated fat
Saturated fat is fat that consists of triglycerides containing only saturated fatty acids. Saturated fatty acids have no double bonds between the individual carbon atoms of the fatty acid chain. That is, the chain of carbon atoms is fully "saturated" with hydrogen atoms...

 fatty alcohol
Fatty alcohol
Fatty alcohols are aliphatic alcohols consisting of a chain of 8 to 22 carbon atoms. Fatty alcohols usually have even number of carbon atoms and a single alcohol group attached to the terminal carbon. Some are unsaturated and some are branched...

, is a safe and effective topical
Topical
In medicine, a topical medication is applied to body surfaces such as the skin or mucous membranes such as the vagina, anus, throat, eyes and ears.Many topical medications are epicutaneous, meaning that they are applied directly to the skin...

 application that has been approved by the United States Food and Drug Administration for herpes labialis in adults with properly functioning immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

s. It is comparable in effectiveness to prescription topical antiviral agents. Due to its mechanism of action, there is little risk of drug resistance
Drug resistance
Drug resistance is the reduction in effectiveness of a drug such as an antimicrobial or an antineoplastic in curing a disease or condition. When the drug is not intended to kill or inhibit a pathogen, then the term is equivalent to dosage failure or drug tolerance. More commonly, the term is used...

. The duration of symptoms can be reduced by a small amount if an antiviral
Antiviral drug
Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...

, anaesthetic or non-treatment cream (such as zinc oxide
Zinc oxide
Zinc oxide is an inorganic compound with the formula ZnO. It is a white powder that is insoluble in water. The powder is widely used as an additive into numerous materials and products including plastics, ceramics, glass, cement, rubber , lubricants, paints, ointments, adhesives, sealants,...

 or zinc sulfate
Zinc sulfate
Zinc sulfate is the inorganic compound with the formula ZnSO4 as well as any of three hydrates. It was historically known as "white vitriol". It is a colorless solid that is a common source of soluble zinc ions.-Production and reactivity:...

) is applied promptly. Effective antiviral medications include acyclovir and penciclovir, which can speed healing by as much as 10%. Famciclovir
Famciclovir
Famciclovir is a guanine analogue antiviral drug used for the treatment of various herpesvirus infections, most commonly for herpes zoster . It is a prodrug form of penciclovir with improved oral bioavailability...

 or valaciclovir, 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 5–7 days.

Lysine
Lysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....

 has been suggested as a treatment for herpes labialis based on in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...

studies, but the evidence is inconclusive in humans.

Prevention

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 contact with others (by avoiding kissing, oral sex, or contact sports) can reduce the likelihood of the infection being spread to others.

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.
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