Porth's Essentials of Pathophysiology, 4e

1052

Genitourinary and Reproductive Function

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primary infections include fever, headache, malaise, muscle ache, and lymphadenopathy. Primary infections may be debilitating enough to require hospitalization, particularly in women. First episodes of nonprimary infections (acquisition of HSV-2 in persons with preex- isting antibodies to HSV-1 or, more rarely, acquisition of HSV-1 in persons with preexisting HSV-2 antibodies) are associated with fewer lesions, a shorter duration of disease, and a lower rate of complications than primary infections. Recurrent HSV episodes are usually milder than the initial episode—there typically are fewer lesions, and viral shedding occurs at a lower concentration and for a shorter duration (about 3 days). However, the prodro- mal symptoms of itching, burning, and tingling at the lesion site are similar. Except for the greater tendency of HSV-2 to recur, the clinical manifestations of genital HSV-2 and HSV-1 infections are similar. The frequency and severity of recurrence vary from person to person. Numerous factors, including emotional stress, lack of sleep, overexertion, other infections, vigorous or pro- longed coitus, and premenstrual or menstrual distress, have been identified as triggering mechanisms. Diagnosis andTreatment Diagnosis of genital herpes is based on symptoms, appearance of the lesions, and identification of the virus taken from the lesions. Viral culture can gener- ally isolate the virus in 5 days, is relatively inexpensive, and is highly specific. However, it is not very sensitive, with false-negative results of 25% with primary infec- tions and as high as 50% with recurrent infections. Polymerase chain reaction (PCR), which can detect sin- gle copies of viral DNA by amplifying the DNA many millions of times, has a higher sensitivity and has become the preferred method to confirm a diagnosis of genital HSV infection. 4,11 In addition to identifying the virus from a sample taken from the herpes lesion, detection of type-specific antibodies to HSV-1 and HSV-2 from a blood sample also can help to establish the diagnosis. These tests yield false-negative results when used in the early stages of infection, since it takes approximately 22 days for the body to produce antibodies to the virus. 2 Approximately 20% of patients may remain seronega- tive for 3 months, particularly if they have received anti- viral medications. 2 This type of testing may prove useful in confirming infection in persons with recurrent genital symptoms and negative HSV testing, or in establishing a clinical diagnosis of genital herpes in a partner of a person with genital herpes. 4 There is no known cure for genital herpes, and the methods of treatment are largely symptomatic. The oral antiviral drugs acyclovir, valacyclovir, and famciclovir have become the cornerstone for management of geni- tal herpes. 2,11 By interfering with viral DNA replication, these drugs decrease the frequency of recurrences, shorten the duration of active lesions, reduce the number of new lesions formed, and decrease viral shedding. Valacyclovir, the active component of acyclovir, and famciclovir have greater bioavailability, which enables improved dosing

1. Penetration of virus into skin. Local replication and entry of virus into cutaneous neurons

2. Centripetal migration in the axon of uncoated nucleocapsids

3. Synthesis of infectious virions

4. Centrifugal migration of infectious virions to epidermis

FIGURE 41-2. Pathogenesis of primary mucocutaneous herpes simplex virus infection. (From Corey L, Spear PG. Infections with herpes simplex viruses: Part 1. N Engl J Med. 1986;314:686.)

infection, development and maintenance of latency, and frequency of HSV recurrences. Herpes simplex virus is transmitted by contact with infectious lesions, but may also be transmitted when no symptoms or lesions are present. Although most HSV genital infections were once caused by HSV-2, it is now increasingly common for infections to be caused by both HSV-1 and HSV-2, particularly among adolescents and young women. 12 Persons infected with HSV-1 remain at risk for acquiring HSV-2. Most cases of HSV-2 infec- tion are subclinical, manifesting as asymptomatic or symptomatic but unrecognized infections. These sub- clinical infections can occur in people who have never had a symptomatic outbreak or they can occur between recognized clinical recurrences. Up to 70% of genital herpes is spread through asymptomatic shedding by people who do not realize they have the infection. 11,12 This “unknown” transmission of the virus to sex part- ners explains why this infection has reached epidemic proportions throughout the world. 12 The incubation period for HSV is 2 to 12 days. 11 Genital HSV infection may manifest as a first-episode or recurrent infection. The initial symptoms of primary genital herpes infections include tingling, itching, and pain in the genital area, followed by eruption of small pustules and vesicles. These lesions rupture on approxi- mately the 5th day to form wet ulcers that are excru- ciatingly painful to touch and can be associated with dysuria, dyspareunia, and urine retention. This period is followed by a 10- to 12-day interval during which the lesions crust over and gradually heal. Involvement of the cervix, vagina, urethra, and inguinal lymph nodes is common in women with primary infections. In men, the infection can cause urethritis and lesions of the penis and scrotum. Rectal and perianal infections are possible with anal contact. Systemic symptoms associated with