Eight types of herpesviruses infect humans, two of which are herpes simplex viruses (HSV). Both types of herpes simplex virus, 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 results from close contact with a person who is actively shedding virus. Viral shedding 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
Physical or emotional stress
Generally, recurrent eruptions are less severe and occur less frequently over time.
(See Overview of Herpesvirus Infections Overview of Herpesvirus Infections Eight types of herpesviruses infect humans (see Table: Herpesviruses That Infect Humans). After initial infection, all herpesviruses remain latent within specific host cells and may subsequently... read more .)
Diseases Caused by Herpes Simplex Virus
Central nervous system (CNS) infection
HSV rarely causes fulminant hepatitis in the absence of cutaneous lesions.
In patients with HIV infection Human Immunodeficiency Virus (HIV) Infection Human immunodeficiency virus (HIV) infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ lymphocytes and impair cell-mediated immunity, increasing risk of certain... read more , 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 Erythema Multiforme Erythema multiforme is an inflammatory reaction, characterized by target or iris skin lesions. Oral mucosa may be involved. Diagnosis is clinical. Lesions spontaneously resolve but frequently... read more , possibly caused by an immune reaction to the virus.
Mucocutaneous herpes simplex infection
Lesions may appear anywhere on the skin or mucosa but are most frequent in the following locations:
Mouth or lips (perioral infection)
Conjunctiva and cornea
Generally, after a prodromal period (typically < 6 hours 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 rupture and dry, forming a thin, yellowish crust.
Healing generally occurs within 10 to 19 days after onset in primary infection or within 5 to 10 days in recurrent infection. 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 due to HIV infection or other conditions, 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. Herpetic pharyngitis can occur in adults as well as 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 eating and drinking may lead to dehydration. After resolution, the virus resides dormant in the semilunar ganglion.
Herpes labialis is usually a recurrence 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.
Genital herpes Genital Herpes Genital herpes is a sexually transmitted infection caused by human herpesvirus 1 or 2. It causes ulcerative genital lesions. Diagnosis is clinical with laboratory confirmation by culture, polymerase... read more is the most common ulcerative sexually transmitted infection in developed countries. Genital HSV can be caused by HSV-1 or HSV-2.
Herpes simplex keratitis
Herpes simplex keratitis Herpes Simplex Keratitis Herpes simplex keratitis is corneal infection with herpes simplex virus. It may involve the iris. Symptoms and signs include foreign body sensation, lacrimation, photophobia, and conjunctival... read more (HSV infection of the corneal epithelium) causes pain, tearing, photophobia, and corneal ulcers that often have a branching pattern.
Herpetic whitlow Herpetic Whitlow Herpetic whitlow is a cutaneous infection of the distal aspect of the finger caused by herpes simplex virus. (See also Overview and Evaluation of Hand Disorders.) Herpetic whitlow may cause... read more , a swollen, painful, erythematous lesion of the finger, results from inoculation of HSV through the skin and is most common among health care practitioners.
Neonatal herpes simplex
Neonatal HSV infection Neonatal Herpes Simplex Virus (HSV) Infection Neonatal herpes simplex virus infection is usually transmitted during delivery. A typical sign is vesicular eruption, which may be accompanied by or progress to disseminated disease. Diagnosis... read more develops in neonates, including those whose mothers have no suggestion of current or past herpes infection. It is most commonly transmitted during birth through contact with vaginal secretions containing HSV and usually involves HSV-2.
Neonatal HSV infection usually develops between the 1st and 4th week of life, often causing mucocutaneous vesicles or central nervous system involvement. It causes major morbidity and mortality.
Herpes simplex CNS infection
Herpes encephalitis Encephalitis Encephalitis is inflammation of the parenchyma of the brain, resulting from direct viral invasion or occurring as a postinfectious immunologic complication caused by a hypersensitivity reaction... read more occurs sporadically and may be severe. Multiple early seizures are characteristic.
Viral meningitis Viral Meningitis Viral meningitis tends to be less severe than acute bacterial meningitis. Findings include headache, fever, and nuchal rigidity. Diagnosis is by cerebrospinal fluid (CSF) analysis. Treatment... read more may result from HSV-2. It is usually self-limited.
Lumbosacral myeloradiculitis, typically caused by HSV-2, can occur during primary infection or reactivation of HSV-2 infection and can result in urinary retention or obstipation.
Diagnosis of Herpes Simplex Virus
Sometimes laboratory confirmation
Polymerase chain reaction (PCR) of cerebrospinal fluid (CSF) and MRI for HSV encephalitis
Diagnosis of HSV infection 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-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), PCR, and antigen detection. Fluid and material for culture should be obtained from the base of a vesicle or 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 Herpes Zoster Herpes zoster is infection that results when varicella-zoster virus reactivates from its latent state in a posterior dorsal root ganglion. Symptoms usually begin with pain along the affected... read more , which rarely recurs and usually causes more severe pain and larger groups of lesions that are distributed along a dermatome and typically do not cross the midline.
Clusters of vesicles or ulcers on an erythematous base are unusual in genital ulcers other than those due to HSV infection.
If herpes infections recur frequently, do not resolve, or do not respond to antiviral drugs as expected, immunocompromise, possibly due to HIV infection Human Immunodeficiency Virus (HIV) Infection Human immunodeficiency virus (HIV) infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ lymphocytes and impair cell-mediated immunity, increasing risk of certain... read more , should be suspected.
Treatment of Herpes Simplex Virus
Usually acyclovir, valacyclovir, or famciclovir
For keratitis, topical trifluridine (typically in consultation with an ophthalmologist)
Treating primary HSV infection with drugs, even if done early, does not prevent the possibility of recurrence.
Mucocutaneous herpes simplex infection
Isolated infections often go untreated without consequence.
Acyclovir, valacyclovir, or famciclovir can be used to treat 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 beta-lactams). Systemic analgesics may help.
Gingivostomatitis and pharyngitis may require symptom relief with topical anesthetics (eg, dyclonine, benzocaine, viscous lidocaine). (NOTE: Lidocaine must not be swallowed because it anesthetizes the oropharynx, the 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 every 2 hours while awake for 4 days, beginning during the prodrome or when the first lesion appears. Toxicity appears to be minimal. Famciclovir 1500 mg as one dose or valacyclovir 2 g orally every 12 hours for 1 day can be used to treat recurrent herpes labialis. Acyclovir-resistant strains are resistant to penciclovir, famciclovir, and valacyclovir. Docosanol 10% cream may be effective when used 5 times a day.
Herpetic whitlow heals in 2 to 3 weeks without treatment. Topical acyclovir has not been shown to be effective. Oral or IV acyclovir can be used in immunosuppressed patients and those with severe infection.
Pearls & Pitfalls
Herpes simplex keratitis
Treatment of herpes simplex keratitis Treatment Herpes simplex keratitis is corneal infection with herpes simplex virus. It may involve the iris. Symptoms and signs include foreign body sensation, lacrimation, photophobia, and conjunctival... read more involves topical antivirals, such as trifluridine, and should be supervised by an ophthalmologist.
Neonatal herpes simplex
Acyclovir 20 mg/kg IV every 8 hours for 14 days should be used if renal function is normal. A dose of 20 mg/kg IV every 8 hours for at least 21 days is indicated for CNS and disseminated HSV disease.
Herpes simplex CNS infection
Encephalitis is treated with acyclovir 10 mg/kg IV every 8 hours for 14 to 21 days if renal function is normal. Treatment for 14 to 21 days is preferred to prevent potential relapse. Higher doses up to 20 mg/kg IV every 8 hours are used in children.
Viral meningitis is usually treated with IV acyclovir. Acyclovir is generally very well-tolerated. However, adverse effects can include phlebitis, renal dysfunction, and, rarely, neurotoxicity (lethargy, confusion, seizures, coma).
HSV usually causes mucocutaneous infection but sometimes causes keratitis, and serious CNS infection can occur in neonates and in adults.
After initial infection, HSV remains dormant in nerve ganglia, from which it can periodically emerge, causing symptoms.
Diagnose mucocutaneous infections clinically, but do viral culture, PCR, or antigen detection if patients are neonates, immunocompromised, or pregnant or have a CNS infection or severe disease.
Give IV acyclovir to patients with serious infections.
For mucocutaneous infections, consider oral acyclovir, valacyclovir, or famciclovir; for herpes labialis, an alternative is topical penciclovir or docosanol.