Herpesviruses 1 & 2, Oral & Genital

Essentials of Diagnosis

• Recurrent small grouped painful vesicles, especially in the orolabial and genital areas, on an erythematous base

• May follow minor infections, trauma, stress, or sun exposure

• Regional tender lymphadenopathy may occur

• Direct fluorescent antibody tests are positive

General Considerations

• The patient may have recurrent self-limited attacks, provoked by sun exposure, orofacial surgery, fever, or a viral infection

• Herpes simplex type 2 (HSV-2) causes lesions whose morphology and natural history are similar to those caused by herpes simplex type 1 (HSV-1) but are typically located on the genitalia; the infection is acquired by sexual contact

• Genital herpes may also be due to HSV-1

• Risk factors for HSV transmission include

  • Black race

  • Female gender

  • History of sexually transmitted infections

  • An increased number of partners

  • Contact with commercial sex workers

  • Lower socioeconomic status

  • Young age at onset of sexual activity

  • Total duration of sexual activity

• Asymptomatic shedding of either virus is common and may be responsible for transmission

• Asymptomatic HSV-2–infected individuals shed the virus less frequently than those with symptomatic infection

• HSV-2 seropositivity increases the risk of HIV acquisition (it is threefold higher among persons who are HSV-seropositive than among those who are HSV-2 seronegative)

• Conversely, HSV-2 reactivates more frequently in advanced HIV infection

Demographics

• Up to 85% of adults have serologic evidence of HSV-1 infections, most often acquired asymptomatically in childhood

• About 25% of the US population has serologic evidence of infection with HSV-2

• In monogamous heterosexual couples where one partner has HSV-2 infection, seroconversion of the noninfected partner occurs in 10% over a 1-year period

  • Up to 70% of such infections appeared to be transmitted during periods of asymptomatic shedding; uninfected female partners are at greater risk than males

Symptoms and Signs

• HSV-1 and HSV-2 disease

  • Burning and stinging are principal symptoms

  • Neuralgia may precede or accompany attacks

  • Lesions consist of small, grouped vesicles on an erythematous base that can occur anywhere but that most often occur on the vermillion border of the lips, the penile shaft, the labia, the perianal skin, and the buttocks

  • Any erosion in anogenital region can be due to herpes simplex

  • Regional lymph nodes may be swollen and tender

  • The lesions usually crust and heal in 1 week

• HSV-1 disease

  • Largely involves the mouth and oral cavity

  • Occasionally, primary infections may be manifested as severe gingivostomatitis

  • Digital lesions (whitlows) are an occupational hazard in medicine and dentistry

  • Contact sports (eg, wrestling) are associated with outbreaks of skin infections

  • Primary infection is usually more severe than recurrences but may be asymptomatic

  • Recurrences often

    • Tend to be labial

    • Involve fewer lesions

    • Heal faster

  • HSV-2 lesions

    • Largely involve the genital tract, with the virus remaining latent in the presacral ganglia

    • Lesions arising on the external genitalia are multiple, painful, small, grouped, and vesicular

    • Occasionally, lesions arise in the perianal region or on the buttocks and upper thighs

    • Dysuria, cervicitis, and urinary retention may occur in women

Differential Diagnosis

• Impetigo

• Varicella zoster infection

  • Chickenpox

  • Herpes zoster (shingles)

• Scabies

• Trauma

• Other genital lesions

  • Syphilis

  • Chancroid

  • Lymphogranuloma venereum

  • Behçet syndrome

  • Fixed drug eruption

• Other oral lesions

  • Aphthous ulcers

  • Herpangina (coxsackievirus)

  • Erythema multiforme

  • Pemphigus

  • Primary HIV infection

  • Candidiasis

  • Reactive arthritis

  • Systemic lupus erythematosus

  • Behçet syndrome

  • Bullous pemphigoid

Laboratory Tests

• Viral cultures of vesicular fluid or direct fluorescent antibody staining of scraped lesions remain the standard of diagnosis

• Intranuclear inclusion bodies and multinucleated giant cells on a Tzanck preparation or Calcofluor stain are indicative of herpetic infection

• Polymerase chain reaction (PCR) is a more sensitive diagnostic assay

• A DNA microarray test for simultaneous detection of HSV-1, HSV-2, varicella zoster virus, cytomegalovirus, Epstein Barr virus, HHV-6, and adenovirus in immunocompromised patients is sensitive, specific, cost-effective, and time saving

• Treatment is often not necessary in immunocompetent patients, but it can ameliorate and shorten the duration of symptoms if initiated early

• For first clinical episode

  • Acyclovir is 400 mg orally five times daily (or 800 mg three times daily)

  • Valacyclovir, 1000 mg orally twice daily

  • Famciclovir, 250 mg orally three times daily

  • Duration of treatment: 7–10 days, depending on the severity of the outbreak

• For mild recurrences

  • Most cases do not require therapy

  • If treatment is desired, recurrent genital herpes outbreaks may be treated with

    • Valacyclovir, 500 mg orally twice daily for 3 days

    • Acyclovir, 200 mg orally five times a day for 5 days

    • Famciclovir, 125 mg orally twice daily for 5 days

    • Valacyclovir, 2 g twice daily for 1 day, or famciclovir, 1 g once or twice in 1 day, are equally effective short-course alternatives and can abort impending recurrences of both orolabial and genital herpes

    • The addition of a potent topical corticosteroid three times daily reduces the duration, size, and pain of orolabial herpes treated with an oral antiviral agent

• For frequent or severe recurrences

  • Acyclovir, 400 mg orally twice daily

  • Valacyclovir, 500 mg orally once daily

  • Famciclovir, 125–250 mg orally twice daily

  • Pritelivir, 100 mg orally once daily, may have superior reduction of viral shedding in HSV-2 compared to valacyclovir 500 mg daily oral dose

  • Long-term suppression appears very safe, and after 5–7 years a substantial proportion of patients can discontinue treatment

Complications

• Pyoderma

• Eczema herpeticum

• Herpetic whitlow

• Herpes gladiatorum (epidemic herpes transmitted by contact)

• Esophagitis

• Neonatal infection

• Keratitis

• Encephalitis

• Recurrent attacks lasting several days

Prognosis

• Recurrent attacks last several days and patients generally recover without sequelae

• For frequent or severe recurrences, suppressive treatment reduces outbreaks by 85% and reduces viral shedding by more than 90%; this results in about a 50% reduced risk of transmission

Prevention

• Sunscreens are very useful adjuncts in preventing sun-induced recurrences

• Any preventive antiviral medication should be started 24 hours prior to ultraviolet light exposure, dental surgery, or orolabial cosmetic surgery

• Although some studies have shown the use of latex condoms and patient education to be effective in reducing genital herpes transmission, others have not shown benefit

• No single or combination intervention absolutely prevents transmission

When to Refer

• Refractory cases not responding to oral antiviral therapy