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Herpes simplex
viruses (human herpesviruses 1 and 2) commonly cause recurrent infection affecting
the skin, mouth, lips, eyes, and genitals. Common severe infections
include encephalitis, meningitis, neonatal herpes, and, in immunocompromised
patients, disseminated infection. Mucocutaneous infections cause
clusters of small painful vesicles on an erythematous base. Diagnosis
is clinical; laboratory confirmation by culture, PCR, direct immunofluorescence,
or serology can be performed. Treatment is symptomatic; antiviral therapy
with acyclovir, valacyclovir, or famciclovir is helpful for severe
infections and, if begun early, in recurrent or primary infections.
Both types of herpes simplex virus (HSV), HSV-1 and HSV-2, can cause oral or genital infection. Most often, HSV-1 causes gingivostomatitis, herpes labialis, and herpes keratitis. HSV-2 usually causes genital lesions. Transmission of HSV occurs from close contact with an individual who is actively shedding virus. Viral shedding generally occurs from lesions but can occur even when lesions are not apparent.
After the initial infection, HSV remains dormant in nerve ganglia from which it can periodically emerge, causing symptoms. Recurrent herpetic eruptions are precipitated by overexposure to sunlight, febrile illnesses, physical or emotional stress, immunosuppression, or unknown stimuli. Recurrent eruptions are generally less severe, and generally occur less frequently over time.
Diseases Caused
by Herpes Simplex
Mucocutaneous infection is most common. Ocular infection (herpes keratitis), CNS infection, and neonatal herpes are unusual but more serious manifestations. HSV rarely causes fulminant hepatitis in the absence of cutaneous lesions. In patients with HIV infection, herpetic infections can be particularly severe. Progressive and persistent esophagitis, colitis, perianal ulcers, pneumonia, encephalitis, and meningitis may occur.
HSV outbreaks may be followed by erythema multiforme (see Hypersensitivity and Inflammatory Disorders: Erythema Multiforme) possibly from an immune reaction to the virus. Eczema herpeticum is a complication of HSV infection in which patients have severe disease in skin regions with eczema.
Mucocutaneous
infection:
Lesions may appear anywhere on the skin or mucosa but are most frequent around or in the mouth or on the lips, conjunctiva and cornea, and genitals. Generally, after a prodromal period (typically < 6 h in recurrent HSV-1) of tingling discomfort or itching, clusters of small, tense vesicles appear on an erythematous base. Clusters vary in size from 0.5 to 1.5 cm but may coalesce. Lesions on the nose, ears, eyes, fingers, or genitals may be particularly painful. Vesicles typically persist for a few days, then dry, forming a thin, yellowish crust. Healing generally occurs 8 to 12 days after onset. Lesions usually heal completely, but recurrent lesions at the same site may cause atrophy and scarring. Skin lesions can develop secondary bacterial infection. In patients with depressed cell-mediated immunity from HIV infection or other causes, prolonged or progressive lesions may persist for weeks or longer. Localized infections can disseminate, particularly—and often dramatically—in immunocompromised patients.
Acute
herpetic gingivostomatitis usually results from primary infection with HSV-1, typically in children. Occasionally, through oral-genital contact, the cause is HSV-2. Intraoral and gingival vesicles rupture, usually within several hours to 1 or 2 days, to form ulcers. Fever and pain often occur. Difficulty in eating and drinking may lead to dehydration. After resolution, the virus resides dormant in the semilunar ganglion.
Herpes
labialis is usually a secondary outbreak of HSV. It develops as ulcers (cold sores) on the vermilion border of the lip or, much less commonly, as ulcerations of the mucosa of the hard palate.
Herpetic
whitlow, a swollen, painful, erythematous lesion of the distal phalanx, results from inoculation of HSV through the skin and is most common in health care practitioners (see Hand Disorders: Herpetic Whitlow).
Genital
herpes is the most common ulcerative sexually transmitted disease in developed countries. It is usually caused by HSV-2, although 10 to 30% involve HSV-1. Primary lesions develop 4 to 7 days after contact. The vesicles usually erode to form ulcers that may coalesce. Lesions may occur on the prepuce, glans penis, and penile shaft in men and on the labia, clitoris, perineum, vagina, and cervix in women. They may occur around the anus and in the rectum in men or women who engage in receptive rectal intercourse. Genital HSV infection may cause urinary hesitancy, dysuria, urinary retention, or constipation. Severe sacral neuralgia may occur. Scarring may follow healing, and recurrences occur in 80% with HSV-2 and 50% with HSV-1. Primary genital lesions are usually more painful, prolonged, and widespread and are more likely to be bilateral and involve regional adenopathy and constitutional symptoms than recurrent genital lesions. Recurrent lesions may have severe prodromal symptoms and may involve the buttock, groin, or thigh.
Herpes
simplex keratitis:
HSV infection of the corneal epithelium produces pain, tearing, photophobia, and corneal ulcers that often have a branching pattern (see Corneal Disorders: Herpes Simplex Keratitis).
Neonatal
herpes simplex:
Infection develops in newborns, including in those whose mothers have no suggestion of current or past herpes infection. It is often transmitted during birth and usually involves HSV-2. It usually develops between the 1st and 4th wk of life, often causing mucocutaneous vesicles or CNS involvement. It causes major morbidity and mortality (see Infections in Neonates: Neonatal Herpes Simplex Virus (HSV) Infection).
CNS
infection:
Herpes encephalitis (see also Brain Infections: Encephalitis) occurs sporadically and may be severe. Multiple early seizures are characteristic. Aseptic meningitis (see Meningitis: Aseptic Meningitis) may result from HSV-2. It is usually self-limited and may involve lumbosacral myeloradiculitis, which may produce urinary retention or obstipation.
Diagnosis
Diagnosis is often clinical based on characteristic lesions. Laboratory confirmation can be helpful, especially if infection is severe, the patient is immunocompromised or pregnant, or lesions are atypical. A Tzanck test (a superficial scraping from the base of a freshly ruptured vesicle stained with Wright's-Giemsa stain) often reveals multinucleate giant cells in HSV or varicella-zoster virus infection. Definitive diagnosis is with culture, seroconversion involving the appropriate serotype (in primary infections), and biopsy. Material for culture should be obtained from a vesicle or the base of a freshly ulcerated lesion. HSV can sometimes be identified using direct immunofluorescence assay of scrapings of lesions. PCR of CSF and MRI are used to diagnose HSV encephalitis.
HSV should be distinguished from herpes zoster, which rarely recurs and usually causes more severe pain and larger groups of lesions that are distributed along a dermatome. Clusters of vesicles or ulcers on an erythematous base are unusual in genital ulcers other than herpes.
Patients with herpes infections that recur frequently, fail to heal, or fail to respond to antiviral drugs as expected should be suspected of being immunocompromised, possibly from HIV infection.
Treatment
Mucocutaneous
infection:
Isolated infections often go untreated without consequence. Acyclovir , valacyclovir , or famciclovir can be used for treatment of infection, especially when it is primary. Infection with acyclovir -resistant HSV is rare and occurs almost exclusively in immunocompromised patients. Foscarnet may be effective for acyclovir -resistant infections. Secondary bacterial infections are treated with topical antibiotics (eg, mupirocin or neomycin - bacitracin ) or, if severe, with systemic antibiotics (eg, penicillinase-resistant β-lactams). All mucocutaneous herpes infections are treated symptomatically. Systemic analgesics may help.
Gingivostomatitis typically requires only symptom relief with topical anesthetics applied directly with a swab (eg, dyclonine 0.5% liquid or benzocaine 2 to 20% ointment q 2 h as needed). When many large areas are affected, 5% lidocaine viscous may be used as a mouth rinse 5 min before mealtime. (Note: Lidocaine
must not be swallowed because it anesthetizes the oropharynx, hypopharynx,
and possibly the epiglottis. Children must be watched for signs
of aspiration.) Severe cases can be treated with acyclovir , valacyclovir , or famciclovir .
Herpes
labialis responds to oral and topical acyclovir . The duration of a recurrent eruption may be decreased by about a day by applying penciclovir 1% cream q 2 h while awake for 4 days, beginning during the prodrome or when the 1st lesion appears. Toxicity appears to be minimal. Acyclovir -resistant strains are resistant to penciclovir . Docosanol 10% cream may be effective when used 5 times/day.
Genital
herpes is treated with antiviral drugs. Acyclovir 200 mg po 5 times/day for 10 days, valacyclovir 1 g po bid for 10 days, or famciclovir 250 mg po tid for 7 to 10 days can be used for primary eruptions. These drugs reduce viral shedding and symptoms in severe primary infections. However, even early treatment of primary infections does not prevent recurrences.
In recurrent eruptions, symptom duration and severity can be reduced marginally by antiviral treatment, particularly during the prodromal phase. Acyclovir 200 mg po q 4 h for 5 days, valacyclovir 500 mg po bid for 3 days, or famciclovir 125 mg po bid for 5 days can be used. Beginning at the 1st symptom or sign of recurrence, patients with frequent eruptions (eg, > 6 eruptions/yr) may receive suppressive antiviral therapy with acyclovir 400 mg po bid, valacyclovir 500 to 1000 mg po once/day, or famciclovir 250 mg po bid. Doses should be adjusted for renal insufficiency. Adverse effects are infrequent with oral administration but may include nausea, vomiting, diarrhea, headache, and rash.
Herpes
simplex keratitis:
Treatment involves topical antivirals, such as idoxuridine or trifluridine , and should be supervised by an ophthalmologist (see Corneal Disorders: Herpes Simplex Keratitis).
Neonatal
herpes simplex:
Acyclovir 20 mg/kg IV q 8 h for 14 to 21 days should be used. A dose of 20 mg/kg IV q 8 h for 21 days is indicated for CNS and disseminated HSV disease.
CNS
infection:
Encephalitis is treated with acyclovir 10 mg/kg IV q 8 h for 14 to 21 days. Aseptic meningitis is usually treated with IV acyclovir . Adverse effects include phlebitis, rash, and neurotoxicity (lethargy, confusion, seizures, coma).
Last full review/revision November 2005
Content last modified November 2005
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