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Author: Hon A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand, 1997. Updated October 2015.
Herpes simplex is a common viral infection that presents with localised blistering. It affects most people on one or more occasions during their lives.
Herpes simplex is commonly referred to as cold sores or fever blisters, as recurrences are often triggered by a febrile illness, such as a cold.
Herpes simplex is caused by one of two types of herpes simplex virus (HSV), members of the Herpesvirales family of double-stranded DNA viruses.
However, either virus can affect almost any area of skin or mucous membrane.
After the primary episode of infection, HSV resides in a latent state in spinal dorsal root nerves that supply sensation to the skin. During a recurrence, the virus follows the nerves onto the skin or mucous membranes, where it multiplies, causing the clinical lesion. After each attack and lifelong, it enters the resting state.
During an attack, the virus can be inoculated into new sites of skin, which can then develop blisters as well as the original site of infection.
Primary attacks of Type 1 HSV infections occur mainly in infants and young children. In crowded, underdeveloped areas of the world, nearly all children have been infected by the age of 5. In less crowded places, the incidence is lower; for example, less than half of university entrants in Britain have been infected. Type 2 HSV infections occur mainly after puberty and are often transmitted sexually.
HSV is transmitted by direct or indirect contact with someone with active herpes simplex, which is infectious for 7–12 days. Asymptomatic shedding of the virus in saliva or genital secretions can also lead to transmission of HSV, but this is infrequent, as the amount shed from inactive lesions is 100 to 1000 times less than when it is active. The incubation period is 2–12 days.
Minor injury helps inoculate HSV into the skin. For example:
Primary infection with HSV can be mild or subclinical, but symptomatic infection tends to be more severe than recurrences. Type 2 HSV is more often symptomatic than Type 1 HSV.
Primary Type 1 HSV most often presents as gingivostomatitis, in children between 1 and 5 years of age. Symptoms include fever, which may be high, restlessness and excessive dribbling. Drinking and eating are painful, and the breath is foul. The gums are swollen and red and bleed easily. Whitish vesicles evolve to yellowish ulcers on the tongue, throat, palate and inside the cheeks. Local lymph glands are enlarged and tender.
The fever subsides after 3–5 days and recovery is usually complete within 2 weeks.
Primary Type 2 HSV usually presents as genital herpes after the onset of sexual activity. Painful vesicles, ulcers, redness and swelling last for 2 to 3 weeks, if untreated, and are often accompanied by fever and tender inguinal lymphadenopathy.
In males, herpes most often affects the glans, foreskin and shaft of the penis. Anal herpes is more common in males who have sex with men than with heterosexual partners.
In females, herpes most often arises on the vulva and in the vagina. It is often painful or difficult to pass urine. Infection of the cervix may progress to severe ulceration.
After the initial infection, whether symptomatic or not, there may be no further clinical manifestations throughout life. Where viral immunity is insufficient, recurrent infections are common, particularly with Type 2 genital herpes.
Recurrences can be triggered by:
In many cases, no reason for the eruption is evident.
The vesicles tend to be smaller and more closely grouped in recurrent herpes, compared to primary herpes. They usually return to roughly the same site as the primary infection.
Itching or burning is followed an hour or two later by an irregular cluster of small, closely grouped, often umbilicated vesicles on a red base. They normally heal in 7–10 days without scarring. The affected person may feel well or suffer from fever, pain and have enlarged local lymph nodes.
Herpetic vesicles are sometimes arranged in a line rather like shingles and are said to have a zosteriform distribution, particularly when affecting the lower chest or lumbar region.
White patches or scars may occur at the site of recurrent HSV attacks and are more evident in those with the skin of colour.
If there is clinical doubt, HSV can be confirmed by culture or PCR of a viral swab taken from fresh vesicles. HSV serology is not very informative, as it’s positive in most individuals and thus not specific for the lesion with which they present.
Herpes simplex may cause swollen eyelids and conjunctivitis with opacity and superficial ulceration of the cornea (dendritic ulcer, best seen after fluorescein staining of the cornea).
Throat infections may be very painful and interfere with swallowing.
In patients with a history of atopic dermatitis or Darier disease, HSV may result in severe and widespread infection, known as eczema herpeticum. The skin disease can be active or historical. Numerous blisters erupt on the face or elsewhere, associated with swollen lymph glands and fever.
A single episode or recurrent erythema multiforme is an uncommon reaction to herpes simplex. The rash of erythema multiforme appears as symmetrical plaques on hands, forearms, feet and lower legs. It is characterised by target lesions, which sometimes have central blisters. Mucosal lesions may be observed.
Cranial/facial nerves may be infected by HSV, producing temporary paralysis of the affected muscles. Rarely, neuralgic pain may precede each recurrence of herpes by 1 or 2 days (Maurice syndrome). Meningitis is rare.
Disseminated infection and/or persistent ulceration due to HSV can be serious in debilitated or immune deficient patients, for example in people with human immunodeficiency virus (HIV) infection.
Complications of herpes simplex infection
Mild, uncomplicated eruptions of herpes simplex require no treatment. Blisters may be covered if desired, for example with a hydrocolloid patch. Severe infection may require treatment with an antiviral agent.
Antiviral drugs used for herpes simplex and their usual doses are:
In New Zealand, famciclovir is not currently funded by PHARMAC (April 2019).
Higher doses and/or longer courses of antiviral drugs may be used for immunocompromised patients, eczema herpeticum, or for disseminated herpes simplex.
Topical aciclovir or penciclovir may shorten attacks of recurrent herpes simplex, provided the cream is started early enough.
Antiviral drugs will stop HSV multiplying once it reaches the skin or mucous membranes but cannot eradicate the virus from its resting stage within the nerve cells. They can, therefore, shorten and prevent attacks but a single course cannot prevent future attacks. Repeated courses may be prescribed, or the medication may be taken continuously to prevent frequent attacks.
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