Genital herpes

Genital herpes is a recurrent viral infection that is incurable and highly contagious, with 75% of sexual partners of infected individuals contracting the disease. Although among the most prevalent STIs, 80% of infected individuals are unaware that they are infected. Asymptomatic shedding that leads to transmission may occur as frequently as once in 5 days . Excellent online patient education and support can be found www.ashastd.org .

There are two distinct types of herpes simplex virus (HSV), type 1 (HSV-1) and type 2 (HSV-2). Genital HSV-1 transmitted from orolabial lesions to the vulva during oral-genital contact or from genital to genital to contact with a partner with genital HSV-1, is the most commonly acquired genital herpes in women younger than 25 years.

Although subclinical primary herpes infection is common, when the primary infection is symptomatic, both local and systemic disease manifestations occur. Local effects include vulvar skin paresthesia preceding eruption of multiple painful vesicles, which progress to shallow, superficial ulcers over a large area of the vulva. Patients may experience multiple ulcer crops for 2 to 6 weeks, which heal without scarring ( Fig. 23.7 ). Viral shedding may occur for 2 to 3 weeks, and during primary infections, positive cultures for herpesvirus may be obtained from lesions in 80% of women. Severe vulvar pain, tenderness, and inguinal adenopathy and simultaneous involvement of the vagina and cervix are common ( Fig. 23.8 ).

Herpes genitalis. Superficial ulcers are noted following rupture of vesicles.

Primary herpes involving the cervix. A necrotic exophytic mass is seen on posterior lip. This was clinically thought to be invasive carcinoma. Herpes simplex virus culture was positive. The lesion spontaneously disappeared.

(From Kaufman RH, Faro S. Herpes genitalis: clinical features and treatment. Clin Obstet Gynecol. 1985;28:152-163.)

Systemic symptoms, including general malaise and fever, are experienced by 70% of women during the primary infection. Primary infections of the urethra and bladder may result in acute urinary retention, necessitating catheterization. The symptoms of vulvar pain, pruritus, and discharge peak between days 7 and 11 of the primary infection. The typical woman experiences severe symptoms for approximately 14 days.

Recurrent genital herpes is a local disease with less severe symptoms typically with unilateral involvement lasting an average of 7 days. In the first year of HSV-2 infection, 80% of women experience a recurrence, and if the primary HSV-2 infection was severe, the recurrences will occur approximately twice as often. With an initial HSV-1 pelvic infection, there is a 55% chance of a recurrence within 1 year, with the average rate of recurrence slightly less than one episode per year.

A common feature of recurrence is a prodromal phase of sacroneuralgia, vulvar burning, tenderness, and pruritus for a few hours to 5 days before vesicle formation. Extragenital sites of recurrent infection are common. The herpesvirus resides in a latent phase in the dorsal root ganglia of S2, S3, and S4.

The diagnosis of genital herpes is often made clinically by simple inspection. Viral cultures are useful in primary episodes, when culture sensitivity is 80%, but less useful in recurrent episodes. The most accurate and sensitive technique for identifying herpesvirus is the polymerase chain reaction (PCR) assay. Serologic tests determine whether a woman was infected with herpesvirus in the past. The Western blot assay for antibodies to herpes is the most specific method but is not widely available and is difficult to perform. HSV serologic testing should be considered for persons presenting for an STI evaluation, especially for those with multiple sex partners or HIV infection and at increased risk for HIV acquisition. Screening for HSV-1 or HSV-2 in the general population is not indicated .

Enzyme-linked immunoassay (ELISA) and immunoblot tests are available for HSV-1 and HSV-2. Rapid serologic point-of-care tests are available for HSV-2 antibodies. Appropriate screening tests for other STIs should be obtained because they may coexist with herpes.

Treatment of HSV-1 or HSV-2 may be used for three different clinical scenarios summarized in Table 23.2 : primary episode, recurrent episode and daily suppression. Daily suppressive therapy is recommended when the woman has six or more episodes annually or for psychological distress. It is important for patients to be aware that asymptomatic viral shedding can occur even when on daily suppressive therapy.

In serodiscordant couples a prospective placebo-controlled randomized trial has demonstrated that daily use of valacyclovir for suppression in the seropositive partner results in significantly fewer cases of HSV acquisition in the seronegative partner. Regular use of condoms in serodiscordant couples also decreases transmission but is not 100% protective. Women who are HSV seronegative are three times as likely to acquire HSV infection from seropositive male partners compared with seronegative males acquiring HSV from infected female partners.

The CDC recommends that acyclovir or other suppressive drugs be discontinued after 12 months to determine the subsequent rate of recurrence for each individual woman. Acyclovir is a drug with minimal toxicity, and reports have documented its safety in patients receiving daily therapy for as long as 6 years and with valacyclovir or famciclovir for 1 year; however, even without HSV suppressive treatment, clinical recurrences tend to dramatically decrease in number.

A vaccine would be the logical approach for optimum prevention of herpes. Research is ongoing.

Granuloma inguinale (donovanosis)

Granuloma inguinale, also known as donovanosis, is a chronic, ulcerative, bacterial infection of the skin and subcutaneous tissue of the vulva. Granuloma inguinale is common in tropical climates such as New Guinea and the Caribbean Islands, but fewer than 20 cases are reported each year in the United States. Spread through both sexual and close nonsexual contact, it is not highly contagious, and chronic exposure is usually necessary with a variable incubation period from 1 to 12 weeks. It is caused by an intracellular, gram-negative, nonmotile, encapsulated rod, Klebsiella granulomatis, which is difficult to culture on standard media. There are no U.S. Food and Drug Administration (FDA)–approved molecular tests for the detection of K. granulomatis DNA. Serologic tests are nonspecific.

The disease course is as follows:

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  The initial nodule progresses into a painless, slowly progressing ulcer surrounded by granulation tissue.

  
  
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  The ulcer has a beefy red appearance, bleeds easily when touched, and is painless and without regional adenopathy.

  
  
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  Multiple nodules are typically present, resulting in ulcers that grow and coalesce.

  
  
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  Chronic disease eventually destroys the normal vulvar architecture with scarring and lymphatic obstruction, producing marked enlargement of the vulva.

The disease is usually clinically diagnosed in endemic areas but may also be established by identifying Donovan bodies in smears and specimens taken from the ulcers ( Fig. 23.9 ). Donovan bodies appear as clusters of dark-staining bacteria with a bipolar (safety pin) appearance found in the cytoplasm of large mononuclear cells. The differential diagnosis includes lymphogranuloma venereum, vulvar carcinoma, syphilis, chancroid, genital herpes, amebiasis, and other granulomatous diseases.

Donovanosis. Biopsy specimen shows intracytoplasmic Donovan bodies (hematoxylin-eosin stain).

(From Hart G. Donovanosis. In: Holmes KK, Mårdh PA, Sparling PF, et al, eds. Sexually Transmitted Diseases. New York: McGraw-Hill; 1984.)

A wide range of oral broad-spectrum antibiotics may be used to manage granuloma inguinale. The CDC recommends azithromycin 1 g orally once a week or 500 mg daily for 3 weeks and until all lesions have healed. See guidelines for alternative antibiotic regimens. Rarely, medical therapy fails and surgical excision is required. Coinfection with another sexually transmitted pathogen is a distinct possibility. Sex partners of women who have granuloma inguinale should be examined if they have had sexual contact during the 60 days preceding the onset of symptoms.

Lymphogranuloma venereum

Lymphogranuloma venereum (LGV) is a chronic infection of lymphatic tissue produced by Chlamydia trachomatis found most commonly in the tropics with fewer than 150 new cases reported each year in the United States, most of which occur in men . In women the vulva is the most common site of infection, but the urethra, rectum, and cervix may also be involved. This STI is caused by serotypes L1, L2, and L3 of C. trachomatis. Serologic studies in high-risk populations have found that subclinical infection is common. The incubation period is between 3 and 30 days.

There are three distinct phases of vulvar and perirectal LGV.

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  Primary infection: A shallow, painless ulcer is present that heals rapidly without therapy typically located on the vestibule or labia but occasionally in the periurethral or perirectal region.

  
  
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  Secondary phase: 1 to 4 weeks later, painful inguinal and perirectal adenopathy is present, with 50% of patients developing systemic symptoms, including general malaise and fever. Without treatment, the infected nodes become increasingly tender, enlarged, matted together, and adherent to overlying skin, forming a bubo ( Fig. 23.10 ) (tender lymph nodes), which is a double genitocrural fold, or groove sign.

  
  

  
  

  
  

  

  
  

  
  

  Lymphogranuloma venereum bubo.

  
  
  
  
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  Tertiary phase: Extensive tissue destruction of the external genitalia and anorectal region may occur during the tertiary phase. This tissue destruction and secondary extensive scarring and fibrosis may result in elephantiasis, multiple fistulas, and stricture formation of the anal canal and rectum.

Diagnosis is established by detecting C. trachomatis by culture, direct immunofluorescence, or nucleic acid detection from the pus or aspirate from a tender lymph node. Chlamydia serologic testing (complement fixation titers >1:64) can support the diagnosis in the appropriate clinical context. In the absence of specific LGV diagnostic testing, patients should be treated based on the clinical presentation, including proctocolitis or genital ulcer disease with lymphadenopathy. The differential diagnosis of LGV includes syphilis, chancroid, granuloma inguinale, bacterial lymphadenitis, vulvar carcinoma, genital herpes, and Hodgkin disease.

The CDC recommends doxycycline, 100 mg twice daily for at least 21 days, as the preferred treatment, with alternative treatments listed on CDC website. Antibiotic therapy cures the bacterial infection and prevents further tissue destruction, but fluctuant nodes should be aspirated to prevent sinus formation. Rarely, incision and drainage of infected nodes are necessary to alleviate inguinal pain. The late sequelae of the destructive tertiary phase of LGV often require extensive surgical reconstruction. It is important to administer antibiotics during the perioperative period.

Chancroid

Chancroid is a sexually transmitted, acute, ulcerative disease of the vulva, common in developing countries but infrequent in the United States , caused by Haemophilus ducreyi, a highly contagious, small, nonmotile, gram-negative rod. Epidemiologic studies have suggested that chancroid tends to occur in clusters and may account for a substantial portion of genital ulcer cases when present; however, difficulty in making the diagnosis may cause underreporting. The clinical importance of chancroid has been enhanced by reports that the genital ulcers of chancroid facilitate the transmission of HIV infection . The incubation period is short, usually 3 to 6 days. Tissue trauma and excoriation of the skin must precede initial infection because H. ducreyi is unable to penetrate and invade normal skin.

Syphilis

Syphilis is a chronic, complex systemic disease that is commonly underreported. It remains one of the most important STIs in the United States. Early syphilis is a cofactor in the transmission and acquisition of HIV, and 25% of new syphilis cases occur in persons coinfected with HIV. Even with mandatory screening, congenital syphilis continues to be a public health problem. Syphilis should be included in the differential diagnosis of all genital ulcers and cutaneous rashes of unknown origin, and all women diagnosed with syphilis should be screened for HIV.

Syphilis facts include the following:

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  Etiologic agent: the spirochete Treponema pallidum, which penetrates skin or mucous membranes

  
  
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  Detection: noncultivable. Can be diagnosed via dark-field microscopy, direct fluorescent antibody tests ( Fig. 23.11 ), or serologic testing.

  
  

  
  

  
  

  

  
  

  
  

  Dark-field microscopic appearance of Treponema pallidum.

  
  
  
  
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  Incubation period: 10 to 90 days, with an average of 3 weeks.

  
  
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  Moderately contagious: 3% to 10% of patients contract the disease from a single sexual encounter with an infected partner; 30% of individuals become infected during a 1-month exposure to a sexual partner with primary or secondary syphilis. Patients are contagious during primary and secondary stages and probably for the first year of latent syphilis.

  
  
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  Transmission: via kissing or touching a person who has an active lesion on the lips, oral cavity, breast, or genitals. Case transmission can occur with oral-genital contact.

Presumptive diagnosis and screening of syphilis rely on two types of serologic tests: the nonspecific nontreponemal and the specific antitreponemal antibody tests . The nontreponemal tests, such as the Venereal Disease Research Laboratory (VDRL) slide test and the rapid plasma reagin (RPR) card test, are inexpensive and easy to perform and are used as screening tests for the disease. They become positive 4 to 6 weeks after exposure and also are a useful index of treatment response because quantitative nontreponemal antibody titers usually correlate with the activity of the disease. Approximately 1% of patients have technical or biologic false-positive results, usually associated with extremely low titers (<1:8). A false-negative result also is a possibility, occurring in approximately 1% to 2% of tests. This negative reaction occurs in women in whom there is an excess of anticardiolipin antibody in the serum, termed the prozone phenomenon. Because serologic testing relies on a humoral immune response to infection, women with immunocompromise also may have false-negative tests.

A nonspecific positive test result is confirmed by a specific antitreponemal test, which is more sensitive but may produce false-positive results, especially in women with lupus erythematosus ( Table 23.3 ). The standard for antitreponemal tests are the fluorescent-labeled Treponema antibody absorption (FTA-ABS) test and the microhemagglutination assay for antibodies to T. pallidum (MHA-TP). A woman with a positive reactive treponemal test usually will have this positive reaction for her lifetime, regardless of treatment or activity of the disease.

Clinically, syphilis is divided into primary, secondary, latent, and tertiary stages.

Primary syphilis

Approximately 2 to 3 weeks after exposure painless papule appears at inoculation site and soon ulcerates to produce the classic chancre—a painless ulcer, 1 to 2 cm, with a raised indurated margin and a nonexudative base ( Fig. 23.12 ). The chancre is typically solitary, painless, and found on the vulva, vagina, or cervix, with nontender and firm regional adenopathy during the first week of clinical disease. Within 2 to 6 weeks, the painless ulcer heals spontaneously; hence, many women do not seek treatment, a feature that enhances the likelihood of transmission. Syphilis is not often diagnosed in the primary stage in women.

Primary chancre of syphilis.

Secondary syphilis

Hematogenous dissemination of the spirochetes leads to systemic disease that develops in approximately 25% of patients between 6 weeks and 6 months (average, 9 weeks) after the primary chancre if primary syphilis is untreated. An untreated attack of secondary syphilis lasts 2 to 6 weeks and produces a multitude of systemic symptoms, such as rash, fever, headache, malaise, lymphadenopathy, and anorexia. The classic rash of secondary syphilis is red macules and papules over the palms of the hands and the soles of the feet ( Fig. 23.13 ). Vulvar lesions of condyloma latum are large, raised, flattened, grayish white areas ( Fig. 23.14 ). On wet surfaces of the vulva, soft papules often coalesce to form ulcers that are larger than herpetic ulcers and are not tender unless secondarily infected. A woman with syphilis is most infectious during the first 1 to 2 years of disease, with decreasing infectivity thereafter.

Secondary syphilis: maculopapular rash. Characteristic maculopapular rash of secondary syphilis affecting the trunk (A), palms (B), and soles (C). (D) Angular mouth ulcer in the same patient.

(From Wickremasinghe S, et al. Syphilitic punctate inner retinitis in immunocompetent gay men. Ophthalmology. 2009;116(6): 1195-200.)

Multiple lesions of condylomata lata on vulva and perineum. Dark-field microscopic findings were positive.

(From Faro S. Sexually transmitted diseases. In: Kaufman RH, Faro S, eds. Benign Diseases of the Vulva and Vagina. 4th ed. St. Louis: Mosby–Year Book; 1994.)

Tertiary syphilis

Tertiary syphilis develops in approximately 33% of patients who are not appropriately treated during the primary, secondary, or latent phases of the disease ( Fig. 23.15 ) and is devastating in its potentially destructive effects on the central nervous, cardiovascular, and musculoskeletal systems. The manifestations of late syphilis include optic atrophy, tabes dorsalis, generalized paresis, aortic aneurysm, and gummas of the skin and bones. A gumma is similar to a cold abscess, with a necrotic center and the obliteration of small vessels by endarteritis.

Approximate time course of the clinical manifestations of early syphilis and neurosyphilis. Shaded areas corresponding to each syndrome represent the approximate proportion of patients with the syndrome specified and do not indicate the proportion of all patients with syphilis who have that syndrome.

(From Hook EW 3rd, Marra CM. Acquired syphilis in adults. N Engl J Med. 1992;326(16):1060-1069.)