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 immunocompromised patients, 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.
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
Physical or emotional stress
Generally, recurrent eruptions are less severe and occur less frequently over time.
HSV rarely causes fulminant hepatitis in the absence of cutaneous lesions.
Lesions may appear anywhere on the skin or mucosa but are most frequent in the following locations:
Mouth or lips (perioral infection)
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.
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.
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.
Clusters of vesicles or ulcers on an erythematous base are unusual in genital ulcers other than those due to HSV infection.
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.
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.
Acyclovir 20 mg/kg IV every 8 hours for 14 to 21 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.
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.
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Treatment of mucocutaneous presentations of herpes simplex virus infections
Infections by herpes simplex virus (HSV) types I and II are diverse and quite frequent. After primary infection, the virus establishes a life-long latency in the sensory ganglia and recrudescences may occur at an unpredictable rate. Recurrent labial and genital herpes infections represent the majority of clinical manifestations of HSV infections. Their management is currently well established using evidence-based medicine data. Primary labial herpes is generally not treated with antivirals in otherwise healthy children, although intravenous aciclovir may be offered in severe primary infections, particularly in the immunocompromised patient. The decision whether or not to treat recurrent labial herpes should be evaluated individually and depends on the frequency and severity of relapses, the impairment of the quality of life, and the cost of therapy. Patients with mild disease may benefit from topical therapy, and those with severe and frequent recurrences may be considered for intermittent or long-term oral antiviral therapy. Primary genital herpes is treated with oral or intravenous antivirals, depending on the severity of the infection and associated symptoms. Recurrent genital herpes can be managed with episodic short courses of oral antivirals in patients whose recurrences are moderate to severe and rare, and have a clear prodrome. Patients with >5 episodes/year, severe recurrences or unrecognisable prodromes may be best managed with long-term suppressive antiviral prophylaxis. HSV is also responsible for a variety of other clinical manifestations, including herpetic whitlow, neonatal infection, disseminated and atypical cutaneous infections, traumatic herpes, eczema herpeticum, and HSV-associated erythema multiforme. HSV infection may also represent a complication following cosmetic procedures of the oro-facial region, surgical and dental interventions, sun exposure and burns. Precise treatment guidelines for these HSV infections are not firmly established.
Management of mucocutaneous herpes simplex virus infections
Herpes simplex virus type 1 and 2 are causes of common inflammatory conditions of the mucous membranes and skin. The proper management of these infections begins with an accurate diagnosis. Viral cultures should be performed whenever possible. Patients should be counselled regarding the proper care of lesions, the risk of complications, the likelihood of experiencing recurrent infection, and should be urged to avoid intimate contact while lesions are active. Antiviral therapy is now available to ameliorate the symptoms and shorten the duration of infection in selected patients, but does not prevent recurrences. Topical, oral and intravenous preparations of acyclovir are effective in treatment of primary herpes simplex infections. Immunosuppressed patients with herpes simplex infections also benefit from acyclovir therapy. Oral activity has some activity in ameliorating recurrent genital herpes and should be considered for patients who are particularly troubled by their infections.
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Simplex mucocutaneous herpes
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