Herpes Simplex (Nongenital)

Herpes simplex virus (HSV) infections are caused by two virus types: HSV-1 and HSV-2. HSV-1 causes most nongenital skin infections.
Nongenital HSV infection is extremely common. In fact, herpes-specific antibody (for type 1 and, less commonly, type 2) can be found in the serum of many adults who have never had clinical evidence of HSV. Asymptomatic shedding probably accounts for the widespread transmission of this ubiquitous virus.
Patients who have HIV/AIDS or those who are under treatment with immunosuppressants for organ transplantation or cancer chemotherapy are at greatest risk for contracting severe recalcitrant HSV infections.
Most primary HSV infections occur in childhood and are asymptomatic or subclinical. The clinical presentations and management of HSV infections in children are presented in Chapter 6: Superficial Viral Infections.

These highly contagious viruses are spread by direct contact with the skin or mucous membranes of an individual who is actively shedding the virus during an active outbreak or with body fluids containing the virus.
After initial acute infection, HSV, a double-stranded DNA virus, establishes latent infection in the local nerve ganglia.
The virus remains latent until precipitating factors or triggers, such as sunlight exposure, menses, fever, common colds, immunosuppression, or stress reactivate it.

Symptomatic primary HSV infections tend to be more severe than those of recurrent disease; findings may include gingivostomatitis, fever, sore throat, as well as submandibular or cervical lymphadenopathy.
Encephalitis and aseptic meningitis are rare complications of primary infections.
Distinguishing primary HSV infection from severe cases of recurrent HSV can be difficult.
The following sequence of events describes the easily recognizable evolution of HSV infection:
1. A single vesicle or a group of vesicles overlies an erythematous base (Fig. 17.23). Vesicles may sag in the center (umbilicate).
2. Vesicles may become pustules, or they may dry and become crusts or erosions (Figs. 17.24 and 17.25).
3. Lesions generally heal without scarring.

Primary orolabial herpes simplex (discussed in Chapter 6: Superficial Viral Infections)

Primary HSV-1 infection most commonly affects the lips (herpes labialis), oral mucosa, or pharynx (Fig. 17.26).
Painful vesicles on an erythematous base may develop on the lips, gingiva, buccal mucosa, palate, or tongue and are often associated with erythema and edema. Lesions tend to ulcerate and heal within 2 to 3 weeks.

Recurrent orolabial herpes simplex

Symptoms are generally milder and the number of lesions fewer than those associated with primary HSV infection.
Patients commonly experience a prodrome of itching, pain, or numbness.
The recurrent vesicular lesions eventually erode and form crusts.
Infrequently, regional lymphadenopathy occurs.
Over time, recurrences decrease in frequency and often stop altogether.
Persistent ulcerative or verrucous vegetative lesions may be seen in immunocompromised patients.
Most cases of recurrent erythema multiforme appear to be triggered by recurrent (both clinical and subclinical) HSV episodes (discussed in Chapter 27: Diseases of Cutaneous Vasculature).
Lesions tend to recur at, or near, the same location within the distribution of a sensory nerve.
Such recurrences are most often seen on or near the vermilion border of the lip (herpes labialis) (Fig. 17.27).

Herpetic Whitlow

Painful herpetic whitlow results from the direct inoculation of the virus onto the skin of the fingertip (Fig. 17.28).
Before the current stringent infection control measures and the widespread use of gloves by health care providers, herpetic whitlow was an occupational hazard among dental and medical health care personnel whose fingertips came in contact with infected oral or respiratory excretions.

Eczema Herpeticum

Also known as Kaposi varicelliform eruption, eczema herpeticum (Fig. 17.29) is an uncommon disseminated form of HSV infection caused by HSV-1. It occurs mainly in children who have severe atopic dermatitis, burns, or other inflammatory skin conditions (discussed in Chapter 6: Superficial Viral Infections).

Herpes Gladiatorum

Herpes gladiatorum is caused by HSV-1 and is seen as a papular or vesicular eruption on the torsos of athletes in sports involving close physical contact (e.g., wrestling).

Disseminated Herpes Simplex

Widespread and extensive herpes simplex infection can occur in individuals who are immunocompromised (i.e., hematologic malignancy, bone marrow or organ transplant recipients, or HIV infection).
HSV infection in immunocompromised patients, may present with atypical signs and symptoms of HSV infection such as larger lesions in atypical locations and a more widespread distribution. Ulcers may be pustular, necrotic, or verrucous and tend to be more persistent.

Herpetic Sycosis

Herpetic sycosis presents as a vesiculopustular eruption, in a perifollicular distribution in the beard area of men.
Often results from autoinoculation after shaving.

Ocular Herpes Simplex

Herpes conjunctivitis, keratitis, uveitis, optic neuritis, and retinitis are possible sequelae of HSV infection of the eye.

Outline
Primary orolabial herpes simplex (discussed in Chapter 6: Superficial Viral Infections)
Recurrent orolabial herpes simplex
Herpetic Whitlow
Eczema Herpeticum
Herpes Gladiatorum
Disseminated Herpes Simplex
Herpetic Sycosis
Ocular Herpes Simplex

The diagnosis of HSV is usually based on clinical appearance and history.
The following tests performed on “fresh” lesions, may help to confirm the diagnosis:
- A Tzanck preparation is a bedside test that can rapidly determine the presence of HSV or VZV by showing multinucleated giant cells (Fig. 17.30). (See the description of the Tzanck procedure in the sidebar.)
- Viral culture can detect and type HSV but can take 2 to 5 days. Specimen should be obtained from the base of an intact vesicle; ideally early in the course of the infection. The false-negative rate increases after 48 hours of lesion onset.
- Direct fluorescent antibody (DFA) testing can be performed on cells obtained from the base of an intact vesicle smeared on a slide (similar to the specimen obtained for a Tzanck preparation). When available, it is the preferred diagnostic test because of its high sensitivity, rapid turnaround time (<24 hours), and its ability to distinguish between HSV and VZV.
- Polymerase chain reaction (PCR) is now increasingly being used as a quick, sensitive, and specific method to detect HSV DNA in specimens from the skin.
- Serologic tests for HSV are generally not very useful because the majority of the general adult population has antibodies to herpes simplex; however, primary HSV infection can be documented by demonstration of seroconversion, high titers, or rising titers.

Tzanck Preparation

Positive Tzanck Preparation. This test does not distinguish between herpes simplex and herpes zoster.

A Tzanck preparation is used to aid in the diagnosis of HSV, herpes zoster, and VZV. This technique furnishes an inexpensive, efficient provisional diagnosis, but it does not enable one to distinguish HSV from VZV.

For best results, a fresh, intact vesicle or bulla usually present for less than 24 hours is preferred.
After the lesion is swabbed with an alcohol preparation, the blister is unroofed by piercing it with a no. 11 blade or a large bore needle, followed by blotting with gauze.
The underlying moist base of the lesion is then scraped with a no. 15 scalpel blade, and a thin layer of material is spread onto a glass slide.
The specimen is then air-dried and stained with a supravital stain such as Giemsa, Wright, or methylene blue, which is left on for 1 minute.
The specimen is then gently flooded with tap water for 15 seconds to remove any remaining stain.
Examination, initially under 40-power magnification and then 100-power oil immersion, helps identify the characteristic multinucleated giant cells.

Differential Diagnosis

Aphthous Stomatitis

Lesions of aphthous stomatitis are small, punched-out erosions that occur on the tongue and on the buccal, labial, and gingival mucosa (seeChapter 21: Disorders of the Oral Cavity, Lips, and Tongue).
Typically consist of painful, shallow, gray or yellow 2- to 3-mm erosions.

Hand-Foot-and-Mouth Disease (HFMD)

Lesions are generally asymptomatic in adults.
Oval erythematous erosions are most often seen on the soft palate and uvula (seeChapter 7: Viral and Bacterial Exanthems). May also appear on the hands and feet.
HFMD often presents with a mild prodrome of fever and malaise prior to mucosal and skin eruption.
The enterovirus, coxsackievirus A type 16 is the etiologic agent involved in most cases of HFMD, but the illness is also associated with other enteroviruses, such as enterovirus 71 (EV-71).

Extraorolabial Herpes Simplex

Herpes Zoster

Lesions of herpes zoster are unilateral, dermatomal in distribution, and often painful (see the discussion of herpes zoster below).
Lesions are also grouped but tend to vary in size.
May be clinically indistinguishable from HSV when lesions are located in a single focus.

Management

Topical Therapy

Skin symptoms may be eased by soaking in Burow solution (aluminum acetate) two to three times daily. Alternatively, soaks with water or saline may help dry the eruption and may prevent secondary infection.
Patients can lessen the discomfort of oral HSV lesions by applying viscous lidocaine applications or OTC “caine” products, taking oral analgesics, or sucking on ice cubes for intraoral lesions.
Patients in whom sun exposure incites recurrent HSV of the lips may apply an opaque sun-blocking agent before sun exposure.
Topical acyclovir 5% ointment (Zovirax), penciclovir 1% cream (Denavir), and docosanol 10% cream (Abreva) are not very effective treatments, but they may help reduce healing time.

Systemic Therapy

Pharmacologic agents used for the treatment of HSV include acyclovir, valacyclovir, and famciclovir. Valacyclovir is rapidly converted to acyclovir, and its bioavailability is greater than that of acyclovir. Similarly, famciclovir is converted to the more bioavailable penciclovir.
Dose reduction is recommended for patients who have renal impairment.
The use of valacyclovir should be given cautiously in renal and bone marrow transplant recipients and in those infected with HIV because of reports of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.

Primary Herpes Simplex

Valacyclovir (Valtrex), 1 g twice daily for 7 to 10 days.
Famciclovir (Famvir), 250 mg three times daily for 7 to 10 days.
Acyclovir, 200 mg five times daily, or 400 mg three times daily for 10 days.

Recurrent Herpes Simplex

Treatment should be initiated at the first sign of prodrome, because it can often abort the lesions. The following are treatment options:

Valacyclovir (Valtrex), 2 g twice daily for 1 day taken about 12 hours apart. This is a shorter, more economical course.
Famciclovir (Famvir), single-day therapy: 1,000 mg in the morning and 1,000 mg in the evening, or 125 mg twice daily for 5 days. In HIV-positive patients, 500 mg twice a day is given for 7 days.
Acyclovir, 200 mg 5 times/day; or 400 mg three times daily; or 800 mg twice daily for 5 days.
For frequent recurrences (more than six recurrences per year), persistent HSV, severe disease, or recurrent erythema multiforme, long-term suppressive oral therapy may be used.
Treatment options for long-term suppressive therapy include the following:
1. Valacyclovir, 1 g daily for 6 to 12 months; attempt to taper dose to 500 mg or to discontinue after 6 to 12 months.
2. Famciclovir, 250 mg twice daily for 12 months.
3. Acyclovir, 400 mg twice daily for 12 months.
After 1 year of treatment with these agents, the need for daily suppressive therapy should be reassessed.
Immunocompromised hosts with severe infection, patients with Kaposi varicelliform eruption, or with HSV encephalitis often require intravenous acyclovir therapy.
SEE PATIENT HANDOUT“Herpes Simplex” IN THE COMPANION eBOOK EDITION.

SEE PATIENT HANDOUT “Herpes Zoster” IN THE COMPANION eBOOK EDITION.

Helpful Hints

Recurrent aphthous stomatitis (canker sores) has no known viral association but has a clinical appearance and course similar to recurrent herpes labialis, and is often misdiagnosed as such. Recurrent HSV lesions however, infrequently occur inside the mouth.
HSV lesions can be seen inside the mouth in a primary infection, or in immunocompromised patients.
Although HSV infections may occur anywhere on the body, 70% to 90% of HSV-1 infections occur above the umbilicus.
In contrast, 70% to 90% of HSV-2 infections occur below the umbilicus (discussed in Chapter 28: Sexually Transmitted Diseases).
Pregnant women with active genital HSV may need a cesarean section to prevent neonatal HSV, a potentially fatal disease.

Points to Remember

Intraoral ulcers in immunocompetent patients are most likely canker sores (aphthous stomatitis).
Recurrent HSV attacks can be aborted by short-term treatment with oral antivirals administered during the prodromal stage.
Frequent recurrences can be suppressed with daily oral antivirals.

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Basics ⬇

Pathogenesis ⬆ ⬇

Clinical Manifestations ⬆ ⬇

Clinical Variant ⬆ ⬇

Diagnosis ⬆