Cold sores

Herpes labialis

Herpes labialis
Classification and external resources
Herpes labialis of the lower lip. Note the blisters in a group marked by an arrow.

Herpes labialis, (also called cold sores,^[1] fever blisters,^[2] herpes simplex labialis,^[1] recurrent herpes labialis,^[3] ororolabial herpes),^[4]:368 is a type of herpes simplex occurring on the lip, i.e. an infection caused by herpes simplex virus (HSV). An outbreak typically causes small blisters or sores on or around the mouth. The sores typically heal within 2–3 weeks, but the herpes virus remains dormant in the facial nerves, 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.

Cold sore has a rate of frequency that varies from rare episodes to 12 or more recurrences per year. People with the condition typically experience one to three attacks annually. The frequency and severity of outbreaks generally decreases over time.

Definitions

In medical contexts, "labia" is a general term for "lip"; "herpes labialis" does not refer to the labia of the genitals, though the etymologyis 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 themucosa of the cheek and gums—known as acute herpetic gingivostomatitis—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.^[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 (see viral life cycle):

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 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 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 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 serumcontaining useful proteins such as immunoglobulins. 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 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, 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 10–15% of oral infections.

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 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.

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.^[11] The duration of symptoms can be reduced by a small amount if an antiviral, anaesthetic 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%.^[12] Famciclovir 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.^[13]

Lysine has been suggested as a treatment for herpes labialis based on in vitro 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.^[12]

Oral acyclovir (800-1,600 mg daily) and valacyclovir (500 mg daily for 4 months) are effective in preventing recurrent herpes labialis if taken prior to the onset of any symptoms or exposure to any triggers.^[3]

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 65–74. In Jordan, another study reported a lifetime prevalence of 26.4%.^[1]