INTRODUCTION TO CHAPTER
Despite all the advances in antiviral therapy and the body’s efficient immune system, the viruses that cause common skin infections continue to evade complete destruction. The herpes simplex and herpes zoster virus can persist in a dormant state in the ganglia. The viruses that cause verrucae vulgaris (common warts) and molluscum contagiosum can persist for months to several years in the epidermis.
Herpes simplex and herpes zoster infections can cause significant illness and death, especially in immunocompromised patients if the infection spreads to other organs. Common nongenital warts and molluscum contagiosum rarely cause significant problems in immunocompetent patients, but for various reasons most patients want treatment for these conditions. Genital warts are often asymptomatic and may be clinically undetectable; however, patients with oncogenic wart virus infections are at increased risk for anogenital and oropharyngeal cancers.
Herpes simplex viruses (HSV) cause primary, latent, and recurrent infections. Human herpes virus-1 (HSV-1) primarily infects the oral cavity, lips, and perioral skin. Human herpes virus-2 (HSV-2) primarily infects the genital area. However, HSV-1 is becoming a common cause of genital herpes infections in young women. HSV has a worldwide distribution and is more common in less developed countries. Antibodies to HSV-1 are present in up to 85% of adults, and antibodies to HSV-2 are present in 20% to 25% of adults.1 However, many patients who have antibodies to HSV do not recall having an infection.
HSV-1 and HSV-2 are human herpesviruses (HHV) that have double-stranded DNA and replicate within the nuclei of infected cells. HSV infects mucocutaneous tissue after direct contact or by way of secretions, mainly saliva in the case of HSV-1. The virus is transmitted via sensory nerves to the ganglia, where it may reside in a latent stage. Recurrent infections are caused by reactivation of the virus which travels back to the skin or mucous membranes resulting in an active infection. Immune mechanisms suppress the virus with clearing of the lesions in 1 to 2 weeks, but latency in the ganglia persists. Recurrent mucocutaneous infection may occur every few weeks to months to years. Viral shedding may continue after the infection has clinically resolved.
Patients with orolabial HSV may complain of “fever blisters” or “cold sores” on the lips or perioral area or sores within the oral cavity. Patients with genital herpes may complain of pain or tingling in the genital area in the prodromal and active phase of the infection. Primary infection occurs 3 to 7 days following exposure. Localized pain, tenderness, and burning may be accompanied by fever, malaise, and tender lymphadenopathy. Vesicles develop, progressing to pustules and/or erosions. The eruption resolves in 1 to 2 weeks. Recurrent infection tends to be milder, with fewer vesicles and absent, or minimal systemic symptoms. Fever, sun exposure, and possibly stress may trigger recurrence of infection. Many individuals harboring HSV are asymptomatic.
HSV infections present with vesicles that tend to be grouped in clusters with underlying and surrounding erythema.
There are several presentations of HSV infections:
HSV-1 most frequently affects the lip area (Figure 11-1), but may involve the buccal mucosa, gingiva, and oropharyngeal membranes. Primary infection may present as a gingivostomatitis in children, with fever, sore throat, and painful vesicles and ulcerative erosions on the tongue, palate, gingiva, buccal mucosa, and lips. Patients may develop lymphadenopathy and an inability to eat. Recurrent eruptions are less severe, mostly affecting the vermilion border of the lip, and, less frequently, the perioral skin, nose, and cheeks. Patients may develop concomitant impetigo.
HSV-2 usually affects the genital area and is the most common cause of genital ulcerations. The primary infection may be extremely painful with erosive vulvitis or vaginitis. The cervix, perineum, and buttocks may be involved with accompanying inguinal lymphadenopathy and dysuria. Affected men may develop an erosive balanitis. Recurrent genital infections can be subclinical or mild with few vesicles (Figure 11-2), clearing in 1 to 2 weeks. Most individuals found to be seropositive for HSV-2 have no reported history of genital herpes symptoms, yet shed the virus and can transmit the virus to a partner.
Fingers (herpetic whitlow) may be affected in children who suck their fingers or in healthcare workers from exposure to secretions.
Herpes simplex keratitis is the second most common cause of corneal blindness in the United States. It presents with pain, redness, blurred vision, and photophobia.
Primary neonatal infection usually develops after exposure to HSV in a mother’s vaginal secretions during delivery, less commonly the virus is transmitted in utero. This is much more likely to occur when the mother has a primary infection. Infected healthcare workers can also transmit the virus to the neonate. Vesicles, if present, appear 4 to 7 days after birth and may be localized or widespread. The central nervous system and visceral organs can be affected, sometimes in the absence of skin lesions. Infected neonates may have significant morbidity and mortality.
Patients with atopic dermatitis are at risk of developing eczema herpeticum, which is disseminated cutaneous HSV infection (Figure 8-10). This may begin as an orolabial HSV infection, which rapidly spreads, or may develop after exposure to an individual with HSV infection.
Tzanck smears can be done by scraping the base of a lesion with a number 15 scalpel blade and spreading the contents on a glass slide (Table 4-2). Microscopic examination after staining with the Wright or Giemsa stain reveals multinucleated epithelial giant cells (Figure 4-4). A skin biopsy will show changes in the nuclei of keratinocytes characteristic of a viral infection. Viral cultures and polymerase chain reaction (PCR) are sensitive and specific tests and can differentiate HSV-1 from HSV-2. The Western blot is a 99% sensitive and specific test for serologic status.
The key diagnostic clinical features of herpes simplex are painful, grouped vesicles, or erosions on the face or genital area.
For orolabial herpes
✓ Impetigo: Presents with flaccid vesicles with a honey-colored crust, usually not recurrent in the same area.
✓ Aphthous stomatitis: Presents with painful 4 to 8 mm oral ulcers with white centers and sharp red borders.
✓ Other: Behcet’s disease, diphtheria, herpangina (coxsackie virus infection), Epstein–Barr Virus (EBV) infection, oral candidiasis, and drug-induced mucositis.
For genital herpes
✓ Syphilitic chancre: Presents most commonly with a single, nontender, indurated ulcer.
✓ Other: Trauma, aphthae, chancroid, and granuloma inguinale.
Mild and limited orolabial HSV in immunocompetent patients does not require therapy; however, moderate to severe disease can be treated with topical or oral medications as listed in Tables 11-1 and 11-2. Treatment should be initiated quickly after onset of symptoms, as these medications may not be helpful if started 72 hours after onset of symptoms.
Oral medications for primary genital herpes and recurrent orolabial and genital herpes infections in immunocompetent adults.
|Generic & Brand Names||Selected Dosing Options||Duration (days)|
Primary: 400 mg 3 times a day
Recurrent genital: 400 mg 3 times a day or 800 mg twice a day
Primary: 250 mg 3 times a day
Recurrent orolabial: 1500 mg one dose
Recurrent genital: 125 mg twice a day
Recurrent genital: 1000 mg twice a day
Primary: 1 g twice a day
Recurrent genital: 500 mg twice a day
Recurrent orolabial: 2 g every 12 h
The Centers for Disease Control and Prevention (CDC) has updated information for clinicians on the treatment of immunocompromised patients and for chronic suppressive treatment for genital herpes.2 Immunocompromised individuals require higher doses of oral antiviral medications or may require intravenous therapy. Recurrent episodes of HSV-1 are less common after age 35. Recurrent episodes of genital herpes can have a major psychosocial impact on an affected individual. The American Social Health Association (www.ashastd.org) and the CDC have patient-oriented information on these issues.
Patients with ocular or systemic involvement and immunocompromised patients with widespread disease should be referred to the appropriate specialist.
Centers for Disease Control and Prevention: www.cdc.gov/std/Herpes/STDFact-Herpes.htm
American Academy of Dermatology: www.aad.org/skin-conditions/dermatology-a-to-z/herpes-simplex