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Therapeutic Strategies

Herpes Simplex Virus Infections, Cutaneous

Timothy Berger Bruce Wintroub

Saturday, January 01, 2011

Herpes simplex virus (HSV) occurs in 2 common locations: orofacial (usually due to HSV-1) and genital (usually due to HSV-2). For therapeutic purposes, infections are classified as: (1) initial or first-episode (the first time the patient reports having herpes simplex - this may not be the primary infection); initial orofacial herpes simplex may clinically present as herpetic gingivostomatitis; (2) recurrent; (3) in the setting of immunosuppression; or (4) extensive or disseminated cutaneous infection as a complication of a skin disease, which impairs cutaneous immunity. This disseminated cutaneous form usually occurs in the setting of atopic dermatitis and is termed eczema herpeticum (Table 1). It may also be seen in Darier's disease, autoimmune bullous disorders, and some congenital disorders of cornification. In the immunosuppressed host and in the disseminated cutaneous form, orofacial and genital and initial and recurrent disease are all treated similarly, therefore no distinction is made when discussing therapy. Herpatic whitlow is managed similarly to genital HSV. Acyclovir or one of its better-absorbed relatives (valacyclovir or famciclovir) is clearly the treatment of choice, when indicated, for all forms of HSV infections. Acyclovir resistance may rarely appear in immunosuppressed, especially HIV-infected, persons. Systemic and neonatal HSV infections are not discussed.

Table 1. Herpes Simplex Therapy

Pattern Orofacial Genital
Initial (first episode) Topicals
Recurrent Topicals Topicals
ACV suppression
Immunosuppressed Topical ACV
ACV (oral, IV)
ACV suppression
Topical ACV
ACV (oral, IV)
ACV suppression
Eczema herpeticum ACV (oral, IV) ACV (oral, IV)

ACV=acyclovir, valacyclovir, or famciclovir; IV=intravenous.

First-episode herpes simplex

First steps

  1. For initial (or first-episode) orofacial HSV and primary genital HSV patients, all immunocompromised patients, and eczema herpeticum patients: Oral acyclovir 200 mg 5 times a day while awake (about every 4 hours). In hospitalized patients with intravenous lines, or for those with HSV infection requiring hospitalization, intravenous acyclovir 5 mg per kg 3 times daily (adjusted for renal function) can be considered. Therapy is continued for 7-10 days.
  2. In atopic and HIV-infected patients, and in others when clinically indicated, culture for coexistent bacterial superinfection (usually S. aureus) and treat appropriately.
  3. For eczema herpeticum: Treat the atopic dermatitis.
  4. For genital HSV: Evaluate for other sexually transmitted diseases (STDs).
  5. For the immunosuppressed: Topical acyclovir ointment 4-5 times a day may accelerate healing.
  6. If the initial episode is mild, or the diagnosis is made when the lesions are in the eroded stage: Topical antibiotics may be applied to reduce secondary infection and accelerate wound healing.

Alternative steps (first episode)

  1. For initial (first-episode) herpes simplex, eczema herpeticum, and infections in the immunosuppressed: Valacyclovir 1000 mg orally twice daily, or famciclovir 250 mg orally 3 times daily, is as effective as oral acyclovir and allows for a more convenient dosing schedule. They are more expensive.

Recurrent herpes simplex

First steps

Recurrent herpes simplex can be treated episodically (at the time of each symptomatic outbreak), or suppressively (constant oral antiviral therapy to prevent clinical recurrences). Episodic treatment on average in the immunocompetent host reduces the signs and symptoms of recurrent HSV by about 1 day. Most cases of orofacial herpes simplex are treated episodically, and except in those cases of orofacial HSV complicated by erythema multiforme minor (see below), no form of suppressive therapy of orofacial herpes simplex can be recommended based on scientific evidence. When very rarely required, the guidelines for suppressive therapy for genital herpes should be followed. For genital herpes, suppressive therapy should be discussed with the patient. Suppressive therapy prevents recurrences, improves quality of life, and reduces the risk of transmission to sexual partners. Where therapy in HIV-infected patients is different, it is listed separately.

Episodic therapy (orofacial herpes simplex)

  1. For orofacial herpes simplex, acyclovir 200 mg 5 times daily or 800 mg twice daily for 5 days, or
  2. Valacyclovir 2000 mg (2 grams) twice daily for 1 day.
  3. In nonimmunosuppressed hosts, the application of a potent topical steroid will reduce the duration and symptoms associated with recurrent orofacial herpes simplex, when used in conjunction with an oral antiviral agent. Apply fluocinolone acetonide ointment twice daily in addition to the oral antiviral agents above.
  4. For HIV-infected patients: Acyclovir 200 mg 5 times daily or 400 mg 3 times daily; valacylcovir 1000 mg twice daily; or famciclovir 500 mg twice daily; all for 5-10 days (until lesions are healed).
  5. Topical antibiotic ointments may be applied to eroded or crusted lesions to prevent secondary infection and accelerate wound healing.

Episodic treatment (genital herpes)

  1. Acyclovir 200 mg 5 times daily or 800 mg twice daily for 5 days, or
  2. Valacyclovir 500 mg twice daily for 3 days, or
  3. Famciclovir 125 mg twice daily for 5 days
  4. For HIV-infected patients: Acyclovir 200 mg 5 times daily or 400 mg 3 times daily, valacylcovir 1000 mg twice daily; or famciclovir 500 mg twice daily; all for 5-10 days (until lesions are healed).
  5. Topical antibiotics ointments may be applied to eroded or crusted lesions to prevent secondary infection and accelerate wound healing.

Suppressive therapy (genital herpes)

  1. Acyclovir 400 mg twice daily; or
  2. Valacyclovir 500 mg once daily (1000 mg for those with 10 or more recurrences per year), or
  3. Famciclovir 250 mg twice daily.
  4. For HIV-infected persons: Acyclovir 400-800 mg 2 to 3 times per day, or valacyclovir 500 mg twice daily, or famciclovir 500 mg twice daily.

Adjunctive therapy

  • For primary and recurrent orofacial HSV in nonimmunosuppressed patients:
    • Lesions are likely to recur and patients need to be so advised
    • Patients should avoid triggers (especially intense sun exposure), and should use a sunscreen on the face and a lip balm containing a sunscreen
    • Sun-exposure-triggered recurrent orofacial HSV may be suppressed by acyclovir 400 mg twice daily for 3 days prior to exposure and continued through the time of exposure. This is good for trips to the tropics and before skiing
    • Orofacial HSV followed by erythema multiforme is an indication for suppressive therapy (see above). About 50% of patients with erythema multiforme minor will have a significant reduction in their episodes
    • Patients with recurrent orofacial HSV undergoing surgical procedures like lip peels, dermabrasion, or extensive dental work, which may trigger their HSV, should be given antiviral therapy: acyclovir orally (400 mg 3 times daily) for two days prior to the surgical procedure and until the wound is healed
  • For primary and recurrent genital HSV in nonimmunosuppressed patients:
    • Recurrence is common and patients should be so advised
    • Patient education/counseling is essential. When active lesions are present, patients should abstain from sexual relations involving contact of the lesion(s) with their sexual partner. Condom use for all sexual relations should be strongly encouraged. Men and women with genital herpes at any site may shed virus from the urethra cervix and genital skin and should be considered infectious. HSV may be transmitted by asymptomatic persons with no visible lesions, and they may infect their sexual partners. This counseling should be documented in the medical record
  • For eczema herpeticum patients:
    • Recurrences are unusual, therefore, chronic suppression is unnecessary. Patient education, a high index of suspicion, and rapid diagnosis and institution of treatment are the keys to preventing subsequent episodes
    • Chronic therapy for the associated atopic dermatitis is essential.


  1. Failure to adjust the acyclovir dose for decreased renal function can lead to side effects, especially when high-dose intravenous acyclovir is given. (Monitor renal function during intravenous acyclovir therapy and ensure adequate hydration to prevent renal impairment.)
  2. Genital ulcers are difficult to diagnose. HSV-2 is the most common cause of genital ulcer disease in the United States, and accurate, confirmed diagnosis is essential. Do not tell the patient they have herpes unless it is confirmed by culture or fluorescent antibody.
  3. Serologic testing can identify infected persons and those at risk for infection. It cannot be used, however, to diagnose an ulcer as due to HSV.
  4. Be alert for the genital ulcer containing multiple pathogens, and evaluate patients with genital HSV for other sexually transmitted diseases.
  5. Rarely, acyclovir-resistant mutants of HSV may cause chronic genital or oral ulcers in immunosuppressed (virtually always HIV-infected) patients. Viral culture with sensitivity testing will identify these situations.

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