This chapter deals primarily with APGO Educational Topic Area:
TOPIC 36 SEXUALLY TRANSMITTED INFECTIONS AND URINARY TRACT INFECTIONS
Students should be able to describe preventive measures and screening protocols for sexually transmitted infections. They should be able to outline a basic approach to evaluation and management for common sexually transmitted infections. Further, they should be able to discuss pathophysiology of pelvic inflammatory disease, describe initial evaluation and management, and identify long-term consequences.
Clinical Case
A 24-year-old patient complains of a vaginal discharge and burning with urination for 2 weeks. The symptoms persist despite having taken a course of over-the-counter yeast medication and drinking cranberry juice to treat what she suspects is a bladder infection. She was contacted yesterday by her new boyfriend because he had been told by his doctor that he tested positive for chlamydia. She uses oral contraceptives and does not use condoms. Her urinalysis and wet prep of vaginal secretions in the office are normal. There is a moderate amount of gray discharge at the cervical os and in the vagina.
Sexually transmitted diseases (STDs) are one of the most common gynecologic problems in sexually active women. STDs can be transmitted by oral, vaginal, or anal sex. The transmission of an STD may have varied consequences, including infertility, cancer, and even death. STDs are the most common cause of preventable infertility and are strongly associated with ectopic pregnancy. The risk of acquiring human immunodeficiency virus (HIV) may be associated with some STDs making effective STD prevention, screening, and treatment an even greater public health priority. STDs can also take an individual toll, resulting in pain, discomfort, and strain on personal relationships.
Most STDs require skin-to-skin contact or exchange of body fluids for transmission. Anal sex poses a particularly high risk, because tissues in the rectum break easily, and organisms can be transmitted through these breaks. Several STDs can be transmitted through oral–genital contact. Some patients have the misconceptions that this type of sexual contact is not at-risk behavior, or that they are not sexually active when engaging in this behavior.
Assessment for STDs should be a routine part of women’s
GENERAL DIAGNOSTIC PRINCIPLES
Many STDs are asymptomatic in women or are asymptomatic during the initial stages. As a result, a thorough sexual history and physical examination are both essential in detecting the presence of an STD. About 20% to 50% of patients with one STD have a coexisting infection; as a result, when one infection is confirmed, other infections must be suspected.
On physical examination, the inguinal region should be evaluated for rashes, lesions, and adenopathy. The vulva, perineum, and perianal areas should be inspected for lesions or ulcerations, and palpated for thickening or swelling. The Bartholin glands, Skene ducts, and urethra should be evaluated because these are frequent sites of gonorrheal infection. In patients with urinary symptoms, the urethra should be gently milked to express any discharge. The vagina and cervix should be inspected for lesions and abnormal discharge. The signs of many STDs may be characterized by genital ulcers or infection of the cervix (cervicitis), urethra (urethritis), or both (Table 29.1). If a patient engages in anal intercourse, the rectum should be considered a potential site for infection. For completeness, the oral cavity as well as the cervical and other lymph nodes should be evaluated, if appropriate, based upon the patient’s modes of sexual expression.
SCREENING
STD screening for nonpregnant women depends on the age of the patient and assessment of risk factors (Box 29.1). When a patient is diagnosed with cervicitis, she should also be screened for pelvic inflammatory disease (PID), chlamydial infection, gonorrhea, bacterial vaginosis, and trichomoniasis and treated, if necessary. A woman diagnosed with PID should be tested for chlamydial infection, gonorrhea, and HIV.
BOX 29.1 Sexually Transmitted Disease Screening Recommendations from the American College of Obstetricians and Gynecologists
Routine Screening
• Sexually active women ages 25 years and younger should be routinely screened for chlamydial and gonorrheal infection.
• Women with developmental disabilities should be screened for sexually transmitted diseases (STDs).
• Human immunodeficiency virus (HIV) screening is recommended for all women who are or ever have been sexually active. (Physicians should be aware of and follow their states’ HIV screening requirements.)
Screening Based on Risk Factors
• Women with a history of multiple sexual partners or a sexual partner with multiple contacts, sexual contact with culture-proved STDs, a history of repeated episodes of STDs, or attendance at clinics for STDs should be regularly screened for STDs.
• Asymptomatic women age 26 years and older who are at high risk for infection should be routinely screened for chlamydial infection and gonorrhea.
American College of Obstetricians and Gynecologists. www.acog.org/wellwoman.
PREVENTION
Prevention of STDs includes educating patients about delaying sexual activity, limiting the number of sexual partners, and using condoms. For some STDs, including human papillomavirus (HPV) and hepatitis B, immunizations are available to reduce or prevent transmission.
Patient notification is an important part of prevention. When an STD is diagnosed, the patient’s sexual partner(s) should also be evaluated. In the United States, cases of gonorrhea, chlamydial infection, and syphilis must be reported to local health departments. Treatment of male sexual partners is important in the prevention of reinfection. In expedited partner therapy, a patient’s sexual partner receives drug therapy for an STD without undergoing physical evaluation or testing. The American College of Obstetricians and Gynecologists supports the use of expedited partner therapy in accordance with the Centers for Disease Control and Prevention guidelines as a method for preventing reinfection of patients with gonorrhea and chlamydia when their partners are unable or unwilling to otherwise seek medical care. Although this approach to therapy typically does not result in adverse reactions, potential risk does exist. Sexual partners should always be encouraged to seek medical evaluation on their own. In some states, expedited partner therapy is prohibited or restricted; therefore, it is important for providers to be familiar with local laws and regulations.
SPECIFIC INFECTIONS
Tables 29.1 and 29.2 summarize the prevalence, signs and symptoms, evaluation, and special considerations of the most common STDs according to whether they present as cervicitis or genital ulcers. Treatment protocols change frequently, and the most current guidelines can be found on the Centers for Disease Control and Prevention (CDC) Web site (www.cdc.gov).
Chlamydia trachomatis (Chlamydia)
C. trachomatis is a Gram-negative obligate intracellular bacterium that lacks the metabolic and biochemical ability to produce adenosine triphosphate and preferentially infects columnar epithelial cells. Chlamydial infection is the most frequently reported infectious disease in the United States. In 2006, over 1 million cases were reported to the CDC. Despite the high number of reported cases, most cases of chlamydial infection are unreported. It is estimated that over 1.7 million cases of chlamydial infections remain undiagnosed each year. If untreated, up to 40% of women with chlamydia will develop PID, which can result in significant complications, including ectopic pregnancy, chronic pelvic pain, and infertility. Chlamydial infections are also responsible for nongonococcal urethritis and inclusion conjunctivitis. Because of the serious consequences of untreated infection, it is recommended that all sexually active women age 25 years or younger should be screened annually. Older women with risk factors, such as multiple sexual partners or a new partner, should also receive annual screening.
Diagnosis
Chlamydial infection may be asymptomatic, or the clinical presentation can be subtle and nonspecific. Symptoms may include abnormal vaginal discharge and vaginal bleeding. Cervicitis, characterized by a mucopurulent discharge from the cervix and eversion or ectropion of the cervix that results in intermittent cervical bleeding, may also suggest the diagnosis (Fig. 29.1). Ascending infection causes mild salpingitis (infection of the fallopian tubes) with insidious symptoms. Once salpingitis is established, it may remain active for many months, with increasing risk of tubal damage. Because chlamydia is frequently found in conjunction with Neisseria gonorrhoeae infection, any patient with known or suspected gonorrhea infection should also be evaluated for chlamydia.
Laboratory testing for chlamydial infection is accomplished by culture, direct immunofluorescence, enzyme immunoassay, nucleic acid hybridization tests, and nucleic acid amplification tests (NAATs) of endocervical swab specimens. NAATs are the most sensitive tests for endocervical swab specimens and are Food and Drug Administration (FDA) approved for use with vaginal swab specimens. Adolescents who are reluctant to undergo a pelvic examination or who receive care where pelvic examination is not possible can be tested with urine screening.
FIGURE 29.1. Cervicitis. Mucopurulent discharge from the cervix and eversion or ectropion of the cervix resulting in intermittent cervical bleeding are suggestive of cervicitis, which may be caused by chlamydia or gonorrheal infection. (Centers for Disease Control, Atlanta, GA; 1970.)
Treatment
Chlamydia is usually treated with azithromycin or doxycycline. Alternative antibiotic therapies include erythromycin base, erythromycin ethylsuccinate, ofloxacin, and levofloxacin. Clinicians should inform patients that gastrointestinal side effects with erythromycin may be significant. Those patients with persistent symptoms, who are suspected to be noncompliant with treatment, or who may have become reinfected should have a test of cureperformed (repeated testing) 3 to 4 weeks after initial treatment is completed.
Because of the risk of reinfection, any woman with chlamydial infection should be retested 3 months after treatment. Patients undergoing treatment for chlamydia should be instructed to abstain from sexual intercourse until treatment is completed and all sexual partners are treated.
Neisseria gonorrhoeae (Gonorrhea)
Infections with N. gonorrhoeae, a Gram-negative intracellular diplococcus, are the second most common STD in the United States. It is estimated that 600,000 new cases of gonorrhea occur each year in the United States, and less than half of them are reported to the CDC. The emergence of antimicrobialresistant strains, an increased frequency of asymptomatic infections, and changing patterns of sexual behavior have all contributed to a rise in its incidence. The highest rates of infection are seen in adolescents and young adults. N. gonorrhoeae infection can lead to PID with resultant risks of infertility caused by adhesion formation, tubal damage, and hydrosalpinx formation. Studies also suggest that infection with N. gonorrhoeae may facilitate transmission of HIV. Infections with N. gonorrhoeae are easily acquired by women and can involve the genital tract, rectum, and pharynx. Gonorrhea is considered a reportable disease in all states, and sexual partners of infected individuals must be tested and treated.
Diagnosis
Signs and symptoms appear within 3 to 5 days of infection, but asymptomatic infections are common in both men and women. In men, infection is characterized by urethritis, a mucopurulent or purulent discharge from the urethra. In women, signs and symptoms are often mild enough to be overlooked and can include purulent discharge from the urethra, Skene duct, cervix,vagina, or anus. Anal intercourse is not always a prerequisite to anal infection. A greenish or yellow discharge from the cervix A greenish or yellow discharge from the cervix indicative of cervicitis should alert the physician to the possibility of either N. gonorrhoeae or C. trachomatis infection. Infection of the Bartholin glands can lead to secondary infections, abscesses, or cyst formation. When the gland becomes swollen and painful, incision and drainage are appropriate.
The laboratory diagnosis of N. gonorrhoeae infection in women is made by testing endocervical, vaginal, or urine specimens. Specimens can be tested by culture, nucleic hybridization, or NAAT. Culture is the most widely used testing modality for specimens obtained from the pharynx or rectum, insofar as there are no nonculture tests that are FDA approved for the testing of these specimens. Male urethral specimens may be tested by Gram stain in symptomatic men but are not recommended as definitive testing for women or asymptomatic men. All patients who are tested for gonorrhea should also be tested for other STDs, including chlamydia, HIV, and syphilis.
Treatment
Aggressive therapy for patients with either suspected or confirmed N. gonorrhoeae should be undertaken to prevent the serious sequelae of untreated disease. Because of the emergence of quinolone-resistant strains of N. gonorrhoeae, these antimicrobials are no longer used for the treatment of these infections. The recommended treatment regimen is intramuscular ceftriaxone plus oral dose(s) of either azithromycin or doxycycline. Due to the high likelihood of concurrent chlamydial infection, patients should be treated for chlamydia as well, if chlamydial infection is not ruled out by NAAT.
Pelvic Inflammatory Disease
PID involves infection of the upper genital tract (endometrium, fallopian tubes, ovaries, and pelvic peritoneum) as a result of direct spread of pathogenic organisms along mucosal surfaces after initial infection of the cervix. The predominant organisms responsible for PID are C. trachomatis and N.gonorrhoeae. Other organisms that have been isolated from the fallopian tubes of patients with PID include Mycoplasma, Streptococcus, Staphylococcus , Haemophilus , Escherichia coli , Bacteroides, Peptostreptococcus , Clostridium , and Actinomyces.
Timing of cervical infection in relation to the menstrual cycle is important; the endocervical mucus resists upward spread,especially during the progesterone-dominant part of the cycle. Oral contraceptives mimic this effect, which explains, in part, their action in limiting PID. The presence of motile sperm or strings from an intrauterine contraceptive device can facilitate penetration of organisms through this protective barrier. Tubal ligation usually provides a barrier to spread, although, in some cases, small microchannels facilitate continued spread. The relative mobility of the fallopian tube probably contributes to the rapid and widespread extension of infection.
Risk Factors
The greatest risk factor for PID is prior PID. Other risk factors include adolescence, having multiple sexual partners, not using condoms, and infection with any of the causative organisms. Between 10% and 40% of women with untreated chlamydial or gonorrheal infections of the cervix will develop acute PID. Early diagnosis and treatment of PID helps to prevent infertility and ectopic pregnancy. Infertility, which is due to scarring of damaged fallopian tubes and intraperitoneal adhesions, occurs in approximately 15% of patients after a single episode of salpingitis, increasing to 75% after three or more episodes. The risk of ectopic pregnancy is increased 7 to 10 times in women with a history of salpingitis.
Diagnosis
Symptoms of PID may be as nonspecific as vaginal discharge or abnormal vaginal bleeding. Patients suspected of having PID should be differentiated from those with ectopic pregnancy, septic incomplete abortions, acute appendicitis, diverticular disease, and adnexal torsion. More pronounced signs include muscular guarding, cervical motion tenderness, or rebound tenderness. A purulent cervical discharge is often seen, and the adnexa are usually moderately to exquisitely tender with a mass or fullness potentially palpable. Fever or chills may also be present, and the white blood cell count is usually elevated (Box 29.2). Peritoneal involvement can include perihepatitis(Fitz-Hugh-Curtis syndrome), which is a result of infection ascending via the right paracolic gutter leading to localized fibrosis and scarring of the anterior surface of the liver and adjacent peritoneum. It is probably caused by chlamydial infection more often than by gonorrheal infection, with which it was originally described (Fig. 29.2). In severe cases or in patients with one or more prior episodes of PID, tuboovarian abscesses (TOAs) may form. Patients with TOA are acutely ill, often presenting with high fever, tachycardia, severe pelvic and abdominal pain, and nausea and vomiting.
Because PID may not be associated with specific signs and symptoms, empiric treatment for PID is recommended for sexually active young women who appear to have no other cause of illness and who are found to have uterine tenderness, adnexal tenderness, or cervical motion tenderness on pelvic examination. Women who are diagnosed with PID should also undergo testing for chlamydial, HIV, and gonorrheal infection.
Treatment
The 2012 CDC recommendation for uncomplicated gonorrhea includes combination therapy with ceftriaxone 250 mg intramuscularly and either azithromycin 1 g orally as a single dose or doxycycline 100 mg orally twice daily for 7 days. However, many patients require hospitalization for adequate care. The decision for hospitalization may be based on specific criteria (Box 29.3). The focus of inpatient management is high-dose intravenous (IV) antibiotic therapy with an antimicrobial spectrum that covers aerobic and anaerobic organisms. In the case of a TOA that does not respond to antibiotics, surgical drainage or even hysterectomy, depending on the reproductive status and desires of the patient, may be warranted. Interventional radiology provides a potential alternative technique of abscess drainage. Rupture of a TOA with septic shock is a life-threatening complication with mortality approaching 10%. These patients must be treated surgically.
BOX 29.2 Clinical Criteria for Diagnosis of Acute Salpingitis
Presence of one or more of the following:
1. Cervical motion tenderness
2. Uterine tenderness
3. Adnexal tenderness
PLUS
One or more of the following:
1. Temperature >101° F (>38.3° C)
2. Cervical or vaginal mucopurulent discharge
3. Abundant white blood cells on microscopy of vaginal fluid
4. Elevated erythrocyte sedimentation rate
5. Elevated C-reactive protein
6. Laboratory documentation of cervical infection with
Neisseria gonorrhoeae or Chlamydia trachomatis
Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines, 2010. http://www.cdc.gov/std/treatment/2010/default.htm. Accesed October 16, 2012.
FIGURE 29.2. Perihepatitis (Fitz-Hugh-Curtis syndrome). Adhesions between the liver and diaphragm are evidence of perihepatitis caused by chlamydial infection. (From Overton C, Davis C, McMillan L, Shaw RW. An Atlas of Endometriosis. 3rd ed. London: Informa UK; 2007:9.4.)
BOX 29.3 Suggested Criteria for Hospitalization for Pelvic Inflammatory Disease
• Surgical emergencies (e.g., appendicitis) cannot be excluded.
• The patient is pregnant.
• The patient has not responded clinically to oral antimicrobial therapy.
• The patient is unable to follow or tolerate an outpatient oral regimen.
• The patient has a severe illness, nausea and vomiting, or high fever.
• The patient has a tuboovarian abscess.
Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines, 2010. http://www.cdc.gov/std/treatment/2010/default.htm. Accesed October 16, 2012.
Genital Herpes
Genital herpes is caused by infection with HSV, a DNA virus. This highly contagious condition affects more than 50 million persons in the United States. There are two types of HSV. HSV-1 is associated with cold sore lesions of the mouth but is increasingly the cause of genital lesions, particularly among adolescent and young women. HSV-2 is still the most common cause of genital infections, although an increasing proportion of new genital herpes infections among women may be due to HSV-1. Women infected with HSV-1 remain at risk for acquiring HSV-2 infection. If left untreated, lesions spontaneously heal in 2 to 3 weeks.
Diagnosis
Up to 75% of primary infections (occurring in patients with no evidence of HSV-1 or HSV-2 antibodies) go unrecognized by either the patient or provider. First-episode infections are typically the most severe, with recurrent episodes being milder. Symptoms of an initial infection often include a flu-like syndrome and frequent neurologic involvement, occurring 2 to 3 days following infection. Painful vesicles appear on the vulva, vagina, cervix, perineum, and perianal skin, often extending onto the buttocks, 3 to 7 days after exposure. These vesicles lyse and progress to shallow, painful ulcers with a red border. The lesions of herpes simplex infections are distinguishable from the ulcers found in chancroid, syphilis, or granuloma inguinale by their appearance and extreme tenderness. They typically resolve in approximately 1 week (Fig. 29.3). Dysuria caused by vulvar lesions or urethral and bladder involvement may lead to urinary retention. Patients with primary lesions may require hospitalization for pain control or management of urinary complications. Aseptic meningitis with fever, headache, and meningismus occurs in some patients 5 to 7 days after the appearance of the genital lesions.
After primary infection, the HSV migrates via nerve fibers to remain dormant in the dorsal root ganglia. Recurrences are triggered by unknown stimuli, resulting in the virus traveling down the nerve fiber to the affected area. Recurrent lesions are usually less painful than those of a primary infection and persist for 2 to 5 days. Recurrent lesions may occur in women who already have antibodies to the same serotype. They can be unilateral rather than bilateral and present as fissures or vulvar irritation, as opposed to being vesicular in appearance. Infections with HSV-1 are less likely to cause recurrences than HSV-2, a characteristic that may be a consideration when suppressive therapy is being contemplated.
FIGURE 29.3. Genital herpes. The linear appearance of these painful herpetic erosions on the labia is a result of coalescence of several closely grouped vesicles. (Courtesy of Barbara Romanowski, MD. In Morse SA, Ballard RC, Homes KK, Moreland AA. Atlas of Sexually Transmitted Diseases and AIDS. Philadelphia, PA: Mosby/Elsevier; 2003:13.12.)
Most HSV-1 and HSV-2 infections in women are asymptomatic. The classic presentation of a painful cluster of vesicles and ulcers occurs in only a small proportion of women. When symptomatic, most patients have atypical presentations such as abrasions, fissures, and itching without obvious lesions. Viral shedding can occur for up to 3 weeks after lesions appear. Definitive diagnosis must be confirmed with reliable laboratory testing.
Tests
The laboratory tests used most often are viral culture and polymerase chain reaction (PCR). Culture is highly specific; however, it is not very sensitive, with a false-negative rate of 25% with primary infection and as high as 50% in a recurrent infection. PCR testing, though expensive, has a higher sensitivity and is increasingly used in many settings as the definitive test for HSV infection. In addition to these viral detection methods, the detection of type-specific antibodies to HSV-1 and HSV-2 in the blood also can help to establish the diagnosis. These tests may yield false-negative test results when administered in the early stages of infection, as the median time from infection to seroconversion is 22 days. Approximately 20% of patients may remain seronegative after 3 months, particularly if they have received antiviral therapy. Type-specific testing may be useful in the following scenarios: 1) recurrent genital or atypical symptoms with negative HSV cultures, 2) clinical diagnosis of genital herpes in the absence of laboratory diagnosis, and 3) a partner with genital herpes.
Treatment
Antiviral drugs are the mainstay of treatment. Oral medication can reduce the duration of viral shedding and shorten the initial symptomatic disease course, but it does not affect the long-term course of the disease. There is nothing available that eradicates the latent virus from the dorsal root ganglion. Treatments for first-episode genital herpes include acyclovir, famciclovir, and valacyclovir. Treatment is usually prescribed for 7 to 10 days but can be given longer if new lesions persist. These therapies do not decrease the likelihood of recurrence. Lesions should be kept clean and dry, and analgesics (e.g., acetaminophen or ibuprofen) should be provided as needed. Warm-water baths can provide symptomatic relief during the first few days. Topical lidocaine may also prove beneficial but can result in local allergic reactions. Severe episodes may require hospitalization for parenteral analgesia and IV antiviral therapy. Such therapy is generally recommended for immunosuppressed or otherwise compromised patients.
Recurrences may also be treated with oral antiviral therapy. Episodic therapy decreases the duration of the episode (lesion, pain, and viral shedding) and is most effective when the patient initiates the therapy at prodrome, or at the beginning of the episode. Treatment regimens for recurrences are usually of a shorter duration than those administered for first episodes (i.e., 3–5 days). Episodic therapy is recommended for patients with infrequent symptomatic recurrences. Patients with frequent occurrences may be offered daily suppressive therapy, which prevents 80% of recurrences and results in a 48% reduction in viral transmission between sexual partners. It should also be recommended for women with HSV-2 whose sexual partners do not have HSV or who have HSV-1 infection. Such discordant couples should also be advised that consistent use of condoms decreases but does not eliminate the risk of transmission. Patient request for suppressive therapy for herpes is also a consideration for outbreak prevention.
Pregnant women with a history of genital herpes should be carefully screened throughout the prenatal course for evidence of outbreaks. Cesarean delivery to prevent neonatal transmission is indicated for women with active lesions or a typical herpetic prodrome at the time of delivery.
Human Papillomavirus
HPV occurs in up to 80% of sexually active women by the age of 50 years. Transmission occurs through contact with infected genital skin, mucous membranes, or body fluids from a partner with either overt or subclinical HPV infections. HPV is species specific and only infects humans. Most infections are transient, but the proportion of women whose infections resolve decreases with age. HPV infections are typically asymptomatic and are identified only when DNA hybridization testing is done on Pap smears. Unlike other STDs, sequelae of HPV infection may take years to develop. More than 100 HPV subtypes have been identified, with at least 40 identified in genital infections. HPV viral types are routinely classified into low-risk and high-risk categories. “Low-risk” subtypes, such as 6 and 11, are associated with genital condyloma. Subtypes such as 16, 18, 31, 33, and 45 are called “high risk” because of their association with cervical dysplasia and cervical cancer. Of the high-risk subtypes, HPV 16 and 18 together account for approximately two thirds of cervical cancer cases, whereas low-risk HPV subtypes rarely lead to cancer.
Condyloma Acuminata
Condyloma acuminata (genital or venereal warts) are soft, fleshy growths caused by HPV infection that may arise from the vulva, vagina, cervix, urethral meatus, perineum, and anus (Fig. 29.4). They may occasionally also be found on the tongue or oral cavity. These distinctive lesions may be single or multiple and generally cause few symptoms. They are often accompanied by other STDs. Because HPV is spread by direct skin-to-skin contact, symmetrical lesions across the midline are common.
FIGURE 29.4. Condyloma acuminata. (From Wilkinson EJ, Stone IK. Atlas of Vulvar Disease. Baltimore, MD: Williams & Wilkins; 2003:9.3.)
FIGURE 29.5. Syphilis chancres. Note the punched-out appearance and rolled edges. (From Wilkinson EJ, Stone IK. Atlas of Vulvar Disease. Baltimore, MD: Williams & Wilkins; 2003:8.46.)
Diagnosis
The diagnosis of condyloma acuminata is based on physical examination, but it may be confirmed through biopsy of the warts. Thorough inspection of the external genitalia and anogenital region should be performed during the routine gynecologic examination, especially in patients with known cervical or vaginal lesions. Because the condyloma lata of syphilis may be confused with genital warts, the clinician must be able to distinguish the two types of lesions in patients at high risk for both infections (see Fig. 29.5).
Treatment
Management options include chemical treatments, cautery, and immunologic treatments. Patient-applied products include podofilox and imiquimod; these treatments should not be used during pregnancy. Treatments that are administered by a health care provider include application of trichloroacetic acid, application of podophyllin resin in tincture of benzoin, cryosurgery, surgical excision, laser surgery, or intralesional interferon injections. Lesions exceeding 2 cm respond best to cryotherapy, cautery, or laser treatment.
Lesions are more resistant to therapy in patients who are pregnant, have diabetes, smoke, or are immunosuppressed. In patients with extensive vaginal or vulvar lesions, cesarean delivery is sometimes recommended to avoid vaginal lacerations and/or problems with suturing tissues with extensive warts. Cesarean delivery also decreases the slight risk of transmission to the infant, which can cause subsequent development of laryngeal papillomata.
Cervical Dysplasia
The relationship between infection with high-risk subtypes of HPV and cervical dysplasia and cancer is now well established. The diagnosis and management of these conditions is covered in Chapter 47. A quadrivalent HPV vaccine ( Gardasil) protects against HPV genotypes 6, 11, 16, and 18 (the strains of HPV that cause 90% of genital warts and 70% of cervical cancers). Another bivalent vaccine (Cervarix) is used to protect against types 16 and 18.
The American College of Obstetricians and Gynecologists (College) currently recommends that all girls and women ages 9 to 26 years be immunized against HPV. The vaccine is a protective tool and is not a substitute for cancer screening; women should be advised to follow current cervical cytologic screening guidelines regardless of their vaccination status.
Syphilis
In the United States, the incidence of syphilis declined 89.7% in the 1990s and reached its lowest rate in 2000. Beginning in 2001, the rate of syphilis began to increase, especially among men who have sex with men. Rates in women also increased, although not as steeply. In addition, after a 14-year decline, the rate of congenital syphilis increased to 3.7% between 2005 and 2006. In 2004, the incidence of primary and secondary syphilis among women was 0.8 cases per 100,000 population. This rose to 1.5 in 2008. Most recently, the reported incidence was 1.1 per 100,000 in 2010. One reason suggested for the rise in syphilis rates overall is the increasing use of nonpenicillin antibiotics to treat penicillin-resistant gonorrhea; in the past, penicillin treatment of gonorrhea provided treatment for coexisting syphilis.
Treponema pallidum, the causative organism of syphilis, is one of a small group of spirochetes that are virulent in humans. Because this motile anaerobic spirochete can rapidly invade intact moist mucosa, the most common sites of entry for women are the vulva, vagina, and cervix. Transplacental spread may occur at any time during pregnancy and can result in congenital syphilis (see Chapter 24).
Stages
Syphilis can be a long-term disease with several stages.
Primary Stage
Primary syphilis, the first stage of the disease, is characterized by the appearance of a chancre at the site of entry approximately 10 to 60 days after infection with T. pallidum. The chancre has a firm, punched-out appearance and has rolled edges (Fig. 29.5). Because it is small and painless, the chancre may be missed during routine physical examination. Adenopathy or other mild systemic symptoms may also be present. The chancre heals spontaneously within 3 to 6 weeks. Serologic testing results at this stage of syphilis are generally negative.
Secondary Stage
Between 4 and 8 weeks after the primary chancre appears, manifestations of secondary syphilis develop. These include skin rash that often appears as rough, red or brown lesions on the palms of the hands and soles of the feet.Other symptoms include lymphadenopathy, fever, headache, weight loss, fatigue, muscle aches, and patchy hair loss. Highly infective secondary eruptions, called mucocutaneous mucous patches, occur in 30% of patients during this stage. In moist areas of the body, flat-topped papules may coalesce, forming condyloma lata (Fig. 29.6). These may be distinguished from venereal warts by their broad base and flatter appearance.
FIGURE 29.6. Condyloma lata in a patient with syphilis. (From Wilkinson EJ, Stone IK. Atlas of Vulvar Disease. Baltimore, MD: Williams & Wilkins; 2003:8.47.)
In untreated individuals, this stage resolves spontaneously in 2 to 6 weeks, and the disease enters the latent stage.
Latent Stage
During the early latent stage (<1 year after secondary syphilis), the patient has no signs or symptoms of the disease, although serologic tests are positive. Relapse of symptoms is possible. Late latent syphilis (1 year after secondary syphilis) is less contagious than early latent cases.
Tertiary Stage
One third of untreated cases can progress to the tertiary stage of the disease in which transmission of the infection is highly unlikely; however, severe damage to the central nervous and cardiovascular systems develops, along with ophthalmic and auditory abnormalities. Destructive, necrotic, granulomatous lesions, called gummas, may develop 1 to 10 years after infection.
Diagnosis
Syphilis is diagnosed by identifying motile spirochetes on dark-field microscopic examination and direct fluorescent antibody tests of material from primary or secondary lesions or lymph node aspirates. Presumptive diagnosis is possible with nontreponemal tests (the Venereal Disease Research Laboratory [VDRL] and rapid plasma reagin) and treponemal tests (e.g., fluorescent treponemal antibody absorption and T. pallidum particle agglutination [Box 29.4]). The use of only one serologic test is insufficient; false-positive non-treponemal test results are sometimes associated with medi-cal conditions unrelated to syphilis. A woman with a positive treponemal test will usually have this positive result for life, irrespective of treatment or activity of the disease. When neurosyphilis is suspected, a lumbar puncture, with a VDRL performed on the spinal fluid, is required.
BOX 29.4 Types of Serologic Tests for Syphilis
Nontreponemal
Venereal Disease Research Laboratory (VDRL)
Rapid plasma reagin (RPR) card test
Automated reagin test
Treponemal
Fluorescent treponemal antibody absorption (FTA-ABS)
Treponema pallidum particle agglutination (TP-PA)
Microhemagglutination assay for antibodies to Treponema pallidum (MHA-TP)
Treatment
Syphilis is treated with benzathine penicillin G. The patient should be monitored using quantitative VDRL titers and examinations at 3, 6, and 12 months. She should abstain from sexual intercourse until lesions are completely healed.
Human Immunodeficiency Virus and Acquired Immune Deficiency Syndrome
Acquired immune deficiency syndrome (AIDS) is the advanced manifestation of infection by HIV, an RNA retrovirus. The virus targets “helper” T cells (those with the CD4 marker) and monocytes. Depletion of these CD4 cells is an important manifestation of HIV infection. Two types of HIV have been identified. HIV-1 is the most common type in the United States, whereas HIV-2 is more common in West African countries. The progression of HIV-1 infection varies from individual to individual. In addition to depletion in the number of CD4 cells, HIV-1 may weaken the immune function of these cells. Both lead to immune system compromise that leaves the body vulnerable to serious, often life-threatening infections from other bacteria, viruses, and parasites.
Etiology
It is estimated that 1.2 million individuals in the United States are living with HIV or AIDS. AIDS is now one of the top five causes of death in reproductive-age women. The proporwomen in the United States has more than tripled, from 7% in 1985 to 27% in 2008. AIDS is the third leading cause of death in African American women ages 24 to 44 years and the fourth leading cause of death in Hispanic women in the same age group. The three primary methods of contracting the virus are 1) intimate sexual contact, 2) use of contaminated needles or blood products, and 3) perinatal transmission from mother to child. HIV transmission in pregnancy has been greatly reduced as a result of routine screening in the first trimester as well as aggressive therapy at the time of delivery. Viral loads are calculated at the time of labor, and most infants born to HIV-infected mothers are delivered via cesarean birth.
Diagnosis and Management
The screening test for AIDS is an enzyme-linked immunosorbent assay that tests for antibodies against HIV. Although rare, false-positive tests are possible and are more common in multiparous women and women taking oral contraceptives. Confirmation is achieved with the more specific Western blot technique.
Management of HIV focuses on prevention and chemotherapy. Prevention emphasizes the use of latex condoms and safe sex practices. Drug therapy for HIV infection includes four classes of anti-HIV drugs, including the nucleoside/ nucleotide reverse transcriptase inhibitors such as zidovudine, nonnucleoside reverse transcriptase inhibitors, protease inhibitors, and fusion inhibitors.
In nonpregnant women, therapy is recommended for all symptomatic patients. Initiation of therapy for the asymptomatic patient with HIV is controversial. Factors involved in the decision making include the viral load and the CD4 cell count. Results are monitored with plasma HIV RNA levels. Instead of monotherapy, combination therapies of at least three agents have been recommended. In nonpregnant women, selection of medications should take into account any possibility of a planned or unplanned pregnancy.
Other Sexually Transmitted Diseases
C. trachomatis serotypes L1, L2, and L3 cause lymphogranuloma venereum (LGV), a disease that has increased in prevalence in the Netherlands and other European countries. When transmitted via vaginal intercourse, LGV presents with inguinal or femoral lymphadenopathy in women. When transmitted anally, symptoms of anal bleeding, purulent anal discharge, constipation, and anal spasms may occur. A self-limiting genital or rectal vesicle or papule sometimes forms at the site of entry of the bacterium. LGV is a systemic infection that, if untreated, can cause secondary infection of rectal or anal lesions, which may lead to abscesses or fistulas.
Donovanosis, previously called granuloma inguinale, is caused by sexual transmission of the bacterium Calymmatobacterium granulomatis. Although fewer than 100 new cases are reported each year in the United States, it is endemic in Papua New Guinea, central Australia, India, and western Africa. The ulcerative lesions are vascular and bleed easily on contact. The disease is diagnosed clinically and can be confirmed by special stains of specimens taken from the lesions or from biopsy.
Chancroid, another STD characterized by genital ulcers, usually occurs in discrete outbreaks. Ten percent of individuals diagnosed with chancroid are also infected with HSV or T. pallidum. It is also a cofactor for HIV transmission. The causative bacterium, Haemophilus ducreyi, is difficult to culture. PCR is often used to confirm the diagnosis, which is made by clinical criteria and ruling out syphilis and HSV through testing of the ulcer secretion. Although rare in the United States, it is endemic in many developing countries. As a result, high-risk patients with painful ulcers should have this diagnosis considered.
Molluscum contagiosum is caused by the DNA poxvirus molluscum contagiosum virus. It is a highly contagious viral skin infection that can be transmitted through sexual contact. It is characterized by small, painless papules that appear on the genital region, inner thighs, and buttocks. The papules usually resolve spontaneously within 6 months to 1 year. Cryotherapy or topical preparations, such as trichloroacetic acid and benzoyl peroxide, are used to treat the disease and prevent transmission.
Parasitic infections include pediculosis pubis (pubic lice) and scabies. Pubic lice are usually transmitted by sexual contact; some cases in which the lice have been transmitted through contact with infested clothing or bedding have been reported. The etiologic agent is the crab louse, Phthirus pubis. Scabies, caused by skin infestation of the human itch mite, can be transmitted via these same routes. The predominant symptom of both conditions is itching of the pubic area. Pubic lice or nits can sometimes be detected on pubic hair. Itching due to scabies infection may be delayed several weeks as the individual becomes sensitized to the antigens released by the parasites; however, itching may occur within 24 hours following reinfection. Pubic lice and scabies are treated with topical medications. The insecticide permethrin is first-line therapy for both pubic lice and scabies. Lindane is approved by the FDA but is not recommended as a first-line treatment due to its potential toxicity.
Clinical Follow-Up
The patient needs testing for the presence of a sexually transmitted disease because of both her symptoms and her boyfriend’s documented infection. She agrees to testing for not just chlamydia, but also gonorrhea, syphilis, human immunodeficiency virus, and trichomoniasis. Testing for both herpes and hepatitis is also offered, but the patient declines these tests. Her test results are all negative except for chlamydia. She is treated with doxycycline, and her symptoms resolve. She is instructed to use condoms to prevent sexually transmitted infections. She is retested in 3 months, and her culture is negative. She remains asymptomatic.
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