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Herpes Simplex Virus (HSV) Infections

(Herpes Labialis; Herpetic Gingivostomatitis)

By

Kenneth M. Kaye

, MD, Harvard Medical School

Reviewed/Revised Dec 2023
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Herpes simplex viruses (human herpesviruses types 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 patients who are immunocompromised, disseminated infection. Mucocutaneous infections cause clusters of small painful vesicles on an erythematous base. Diagnosis is clinical; laboratory confirmation by culture, polymerase chain reaction, direct immunofluorescence, or serologic testing can be done. Treatment is symptomatic; antiviral therapy with acyclovir, valacyclovir, or famciclovir is helpful for severe infections and, if begun early, for recurrent or primary infections.

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. (See Overview of Herpesvirus Infections Overview of Herpesvirus Infections Eight types of herpesviruses infect humans (see table ). After initial infection, all herpesviruses remain latent within specific host cells and may subsequently reactivate. Clinical syndromes... read more .)

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 reactivate, causing symptoms. Recurrent herpetic eruptions are precipitated by

  • Overexposure to sunlight

  • Febrile illnesses

  • Physical or emotional stress

  • Immunosuppression

  • Unknown stimuli

Generally, recurrent eruptions are less severe and occur less frequently over time.

Diseases Caused by Herpes Simplex Virus

Diseases include

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 Human Immunodeficiency Virus (HIV) Infection , herpetic infections can be particularly severe. Progressive and persistent esophagitis, colitis, perianal ulcers, pneumonia, encephalitis, and meningitis may occur.

Eczema herpeticum Complications of atopic dermatitis Complications of atopic dermatitis is a complication of HSV infection in which severe herpetic disease develops in skin regions with eczema.

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)

  • Genitals

  • 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 patients who are immunocompromised.

Acute herpetic gingivostomatitis usually results from primary infection with HSV-1, typically in children. Herpetic pharyngitis can occur in adults as well as children. Through oral-genital contact, the cause can be either HSV-1 or 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.

Herpes simplex keratitis

Herpetic whitlow

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 Herpetic Whitlow , a swollen, painful, erythematous lesion of the finger, results from inoculation of HSV through the skin and is most common among health care professionals.

Herpes simplex CNS infection

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.

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 Neonatal Herpes Simplex Virus (HSV) Infection 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.

Diagnosis of Herpes Simplex Virus

  • History and physical examination

  • 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 Herpes Zoster , 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.

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 medications, 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 patients who are immunocompromised. 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

  • Treating primary herpes infection with medications, even if done early, does not prevent recurrence.

Herpes simplex keratitis

Neonatal herpes simplex

IV acyclovir should be used for therapy.

Herpes simplex CNS infection

Encephalitis is treated with IV acyclovir. Treatment for 14 to 21 days is preferred to prevent potential relapse.

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; usually in the setting of renal insufficiency).

Key Points

  • 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 reactivate, 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.

Drugs Mentioned In This Article

Drug Name Select Trade
Sitavig, Zovirax, Zovirax Cream, Zovirax Ointment, Zovirax Powder, Zovirax Suspension
Valtrex
Famvir
Viroptic
Foscavir
Bactroban, Centany, Centany AT
Neo-Fradin
AK-Tracin, Baciguent, BaciiM, Baci-Rx, Bacitracin Zinc, Ocu-Tracin
Advocate Pain Relief Stick, Americaine, Anbesol, Anbesol Baby , Anbesol Jr , Banadyne-3, Benzodent, Benz-O-Sthetic, Boil-Ease, Cepacol Sensations, Chloraseptic, Comfort Caine , Dry Socket Remedy, Freez Eez, HURRICAINE, HURRICAINE ONE, Little Remedies for Teethers, Monistat Care, Orabase, OraCoat CankerMelts, Orajel, Orajel Baby, Orajel Denture Plus, Orajel Maximum Strength, Orajel P.M., Orajel Protective, Orajel Severe Pain, Orajel Swabs, Orajel Ultra, Oral Pain Relief , Oticaine , Otocain, Outgro, Pinnacaine, Pro-Caine, RE Benzotic, Topex, Topicale Xtra, Zilactin-B
7T Lido, Akten , ALOCANE, ANASTIA, AneCream, Anestacon, Aspercreme with Lidocaine, AsperFlex, Astero , BenGay, Blue Tube, Blue-Emu, CidalEaze, DermacinRx Lidocan III, DermacinRx Lidogel, DermacinRx Lidorex, DERMALID, Dologesic, Ela-Max, GEN7T, Glydo, Gold Bond, LidaFlex, LidaMantle, Lido King Maximum Strength, Lidocan, Lidocare, Lidoderm, LidoDose, LidoDose Pediatric, Lidofore, LidoHeal-90, LIDO-K , LidoLite, Lidomar , Lidomark, LidoPure, LidoReal-30, LidoRx, Lidosense 4 , Lidosense 5, Lidosol, Lidosol-50, LIDO-SORB, Lidotral, Lidovix L, LIDOZION, Lidozo, Lidtopic, Lidtopic Max, LMX 4, LMX 4 with Tegaderm, LMX 5, LTA, Lubricaine, Lubricaine For Her, Lydexa, MENTHO-CAINE , Moxicaine, Numbonex, Professional DNA Collection Kit, Proxivol, ReadySharp Lidocaine, RectaSmoothe, RectiCare, Regenecare HA, Salonpas Lidocaine, Senatec, Solarcaine, SOLUPAK, SUN BURNT PLUS, Topicaine, Tranzarel, VacuStim Silver, Xyliderm, Xylocaine, Xylocaine Dental, Xylocaine in Dextrose, Xylocaine MPF, Xylocaine Topical, Xylocaine Topical Jelly, Xylocaine Topical Solution, Xylocaine Viscous, Zilactin-L, ZiloVal, Zingo, Zionodi, ZTlido
Denavir
Abreva
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