John W. Wilson MD
Nancy K. Henry PhD, MD
URETHRITIS
Essentials of Diagnosis
General Considerations
Urethritis is the most common sexually transmitted disease (STD) syndrome recognized in men and is frequently seen in women with coinciding cervicitis. Cases can be of two types, gonococcal urethritis and nongonococcal urethritis (NGU), based on the presence or absence of Neiserria gonorrhoeae. The two forms are not mutually exclusive. Coinfection with N gonorrhoeae and Chlamydia trachomatis or Ureaplasma urealyticum occurs in 15–25% of heterosexual men with urethritis. NGU that occurs soon after curative therapy for gonorrhea is called postgonococcal urethritis (PGU).
The Centers for Disease Control and Prevention estimates that NGU is 2.5-fold more prevalent than gonococcal urethritis in the United States and much of the developed world. However, gonococcal urethritis accounts for up to 80% of acute urethritis cases in certain underdeveloped regions of the world. Among people of higher socioeconomic status and college students, NGU is more common. In urban STD clinics, gonococcal urethritis is more common.
Etiology
Box 15-1 lists causative organisms associated with various forms of urethritis. Noninfectious causes exist but should be considered only after infectious pathogens are excluded.
C trachomatis is an obligate intracellular parasite. It causes >4 million infections each year. However, a recent multicenter study reported a declining percentage of NGU cases caused by C trachomatis, < 25% in some centers. This may reflect the increasing use of faster diagnostic tests, enabling an earlier diagnosis and treatment. The result is a decrease in the reinfection rate and spread of disease.
The role of U urealyticum is less clear in NGU. U urealyticum may be found in the urethra of many asymptomatic sexually active men and is a common commensal organism in the genital tract of sexually active women. Nevertheless, U urealyticum is believed to have a pathogenic role. There is an increased prevalence and concentration of the organism in the urethra of men with NGU compared with those without NGU. Men with NGU and U urealyticum isolated from the urethra respond better to antimicrobial agents with antiureaplasma activity than to those without antiureaplasma activity.
The importance of T vaginalis as a cause of urethritis has been controversial. A recent study showed the organism to be present in 17% of patients with nonchlamydial NGU in one U.S. series, indicating a more epidemiological association between T vaginalis and NGU than previously thought. Furthermore, a favorable symptomatic response of men with trichomonad-positive NGU to metronidazole has been demonstrated.
There has been compelling evidence that M genitalium is another cause for urethritis. It is more prevalent in homosexual men and in individuals with persistent and recurrent NGU. Detection is more for epidemiological interest because recurrent urethritis is usually treated with agents that are active against M genitalium.
HSV is an uncommon cause of urethritis. When it occurs, it is usually in the setting of primary genital herpes infection. Urethral involvement is less common in recurrent disease.
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BOX 15-1 Cause of Urethritis |
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Clinical Findings
The incubation of C trachomatis urethritis is longer, between 7 and 21 days. Symptoms of NGU tend to arise less abruptly, and the urethral discharge is less profuse and more mucoid in appearance. Dysuria may be present without urethral discharge. Urinary frequency, hematuria, and urgency are infrequent with either infection.
Trichomonas urethritis in men is often asymptomatic, making detection difficult. Acute symptomatic trichomoniasis in men usually presents with signs and symptoms similar to chlamydial urethritis. Purulent urethritis and prostatitis are unusual.
In HSV urethritis, dysuria is usually more severe, and the urethral discharge may be diffuse and mucoid. There may be regional lymphadenopathy and constitutional symptoms present with primary HSV urethritis. Genital lesions are not always present.
Examination of the Urethral Discharge. The diagnosis of urethritis can be made microscopically based on the presence of five or more leukocytes per high-power field in a sample of urethral exudate. The leukocyte esterase test is an alternative screening test for urethritis that can be used on first voided urine samples. It is nonspecific and has a sensitivity of 80%.
The diagnosis of gonococcal urethritis can be made on a stained slide of male urethral exudate if gram-negative diplococci are seen. This finding is present in >95% of symptomatic men with gonococcal urethritis. The presence of gram-negative diplococci, however, does not rule out the possibility of coinfection with NGU organisms.
Detection of N gonorrhoeae. If the urethral Gram stain is negative for gonococci, a culture should be done. N gonorrhoeae is a fastidious organism requiring a selective growth medium in a CO2-rich environment. Selective growth media include Thayer-Martin, Martin-Lewis, and New York City media.
Nonculture or rapid diagnostic tests for gonococcal infection include Gonozyme, the Gen-Probe Pace 2 and the ligase chain reaction (LCR). Gonozyme is an enzyme immunoassay that can detect gonococcal antigens within the urethra, cervix, and urine. The Gen-Probe Pace 2 uses nonisotopic probes to detect ribosomal RNA. LCR utilizes a DNA amplification technique to detect trace amounts of organism-specific nucleic acid sequences from urethral and endocervical swab specimens and urine samples.
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Table 15-1. Clinical comparison between gonococcal and nongonococcal urethritis. |
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Detection of C trachomatis. Cell culture is considered the gold standard for chlamydial testing. It has a sensitivity of 75–80% and a specificity approaching 100%. The addition of an enzyme immunoassay to culture increases the sensitivity to 95%. Cultures are expensive and may require 3–7 days for results.
Nonculture rapid diagnostic tests, including the direct fluorescence antibody (DFA) test, enzyme-linked immunoassay (EIA) test, and DNA probe tests, provide a more prompt diagnosis than culture with roughly an equivalent specificity. The sensitivity is 70–90%. The Gen-Probe Pace 2 and LCR assays detect rRNA and DNA sequences, respectively, of both N gonorrhoeae and C trachomatis. The sensitivity is higher than that of cell cultures without compromise in specificity.
Detection of Other Pathogens. Identification of U urealyticum requires culture. Because U urealyticum can be isolated in men without urethritis, a positive culture for U urealyticum does not necessarily identify the cause of the urethritis.
The gold standard for diagnosing trichomoniasis is isolating the protozoa in culture. A more rapid and less expensive method is the direct microscopic wet mount examination of urethral discharge. The accuracy of the exam is based on identifying motile protozoa with characteristic morphology. The wet mount exam is routinely used to evaluate women for vaginal trichomoniasis (50–70% sensitive) but is less sensitive with urethral discharge from infected men.
Differential Diagnosis
Noninfectious causes of urethritis should be considered only after infectious pathogens are excluded. Urethritis caused by Wegener's granulomatosis may be suggested by the findings of upper- or lower-respiratory-tract disease, mucosal ulcerations, cartilaginous destruction, and glomerulonephritis. Stevens-Johnson's syndrome may produce a urethritis associated with characteristic skin and mucosal lesions with systemic toxicity. Prior exposure to certain drugs (eg, sulfonamides, nonsteroidal anti-inflammatory drugs, and phenytoin) is typical. Urethral trauma from instrumentation and indwelling urinary catheters is a frequent cause of urethritis in hospitalized patients. Urethral irritation from renal stones, spermicides, and alcohol can also occur.
Complications
Disseminated gonorrhea, which occurs in 0.5% of untreated cases of gonococcal infection, presents with fever, arthritis or tenosynovitis, and a skin rash. The rash may be scattered pustular lesions or hemorrhagic necrotic blisters on extensor surfaces of the extremities. Reiter's syndrome is a human leukocyte antigen B27-associated spondyloarthropathy that can follow a genitourinary infection with C trachomatis. It is characterized by urethritis, asymmetric oligoarthritis, conjunctivitis, and skin and mucous membrane lesions. Reiter's syndrome can also follow bacterial gastroenteritis caused by Salmonella, Shigella, Yersinia, and Campylobacter spp. Epididymitis and urethral strictures secondary to urethritis are rare with treatment. A small proportion of patients may develop conjunctivitis caused by either N gonorrhoeae or C trachomatis. This is most likely a result of autoinoculation with these organisms from a genital source.
Treatment
Gonococcal urethritis can be successfully treated with a number of single-dose regimens (Box 15-2). Intramuscular ceftriaxone cures nearly 100% of genital infections and is effective for the treatment of gonococcal infection at all sites. Ceftriaxone is also active against incubating syphilis. Oral cefixime is nearly as active against N gonorrhoeae and is less expensive.
For the beta-lactam–allergic patient, oral ciprofloxacin or ofloxacin is highly effective. Both are less expensive and better tolerated than ceftriaxone but are contraindicated in pregnancy and for patients under age 18. Patients with disseminated gonococcal infection should be hospitalized for intravenous therapy.
Many patients who experience symptomatic relief after a single-dose treatment for gonococcal urethritis develop a prompt recurrence or persistence of milder symptoms. This syndrome is called postgonococcal urethritis (PGU) and is the result of dual infection of the urethra with N gonorrhoeae and organisms of NGU. N gonorrhoeae is eradicated by a single dose of the aforementioned cephalosporins and quinolones, but the organisms responsible for NGU are often spared. PGU should be suspected if signs, symptoms, or laboratory evidence of urethritis is found 4–7 days after a single-dose treatment for gonococcal urethritis. Unless chlamydial infection has been specifically ruled out through testing, all patients treated for gonococcal infections should also be treated for chlamydial infection.
Patients with recurrent or persistent symptoms should be retreated with the initial regimen if noncompliance is suspected; otherwise a wet mount and culture for T vaginalis can be done. Treatment of Trichomonas-caused urethritis with a single oral dose of metronidazole is usually sufficient.
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BOX 15-2 Treatment of Infectious Urethritis and/or Cervicitis |
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Prognosis
In early gonococcal infections, a single course of the appropriate antimicrobial agent is almost always curative. Recurrent disease is more common in NGU; however, patients failing therapy need to be questioned about drug compliance and the possibility of re-exposure to an infected partner. Complications are rare when infectious urethritis is treated early. To prevent reinfection and the spread of disease, patients should avoid sexual contact for 7 days after a single-dose treatment or during a 7-day treatment regimen. Sexual contact should also be avoided until infected partners have been adequately treated.
CERVICITIS
Essentials of Diagnosis
General Considerations
Cervicitis is the most common STD syndrome in women and is caused primarily by N gonorrhoeae, C trachomatis, HSV, and human papillomavirus (HPV). It represents an inflammation of the columnar and subepithelium of the endocervix and can involve any contiguous columnar epithelium that lies exposed on the ectocervix. In adolescent girls, the transition zone is frequently everted over part of the ectocervix, thereby increasing the amount of susceptible columnar tissue exposed to a pathogen. This biological circumstance, combined with an increased number of sexual partners without barrier methods of contraception, places adolescent girls at highest risk for cervicitis from an STD pathogen. Interestingly, oral contraceptives cause cervical eversion (ectropion) and may increase the risk of chlamydial infection but have not been shown to increase gonococcal infection.
Even though most of these organisms also cause male urethritis, there is a strong gender bias for infection in women. Male-to-female transmission of infection is more common than female to male.
Clinical Findings
Infectious cervicitis has often been referred to as the “silent partner” of male urethritis. The lack of well-recognized symptoms and signs of cervical inflammation has largely impeded clinical recognition of sexually transmitted cervical infections.
C trachomatis typically causes a mucopurulent cervicitis, but nonspecific abdominal pain and spotting with intercourse may occur. Cervical abnormalities are often subtle, and only one-third of women note a vaginal discharge that originates from the inflamed cervix. On examination, 20–70% of infected women will have a completely normal appearing cervix.
HSV cervicitis usually presents with a more mucoid, less commonly mucopurulent cervical discharge. Affected patients may complain of lower abdominal pain. The cervix usually appears friable with occasional frank ulcers or necrosis. External genital lesions are usually absent. Inguinal adenopathy is unusual unless accompanied by external genital lesions.
The diagnosis of HSV cervicitis can be made cytologically by observing multinucleated giant cells, often with intranuclear inclusions. The diagnosis can be confirmed by isolating the virus in culture or by immunofluorescent staining. Viral isolation will permit the differentiation of HSV-1 from HSV-2. This has prognostic significance because HSV-1 is less likely than HSV-2 to cause recurrent genital herpes.
Differential Diagnosis
Symptoms of dysuria, vaginal discharge, and abdominal pain are not specific for cervicitis. Vulvovaginitis, pelvic inflammatory disease (PID), urethritis, and cystitis may produce a similar clinical picture. A speculum exam and urinalysis are indicated to rule out vaginitis, urethritis, and cystitis. Erythema around the cervical os can indicate infection or merely represent cervical ectropion.
Complications
There are four categories of complications from cervical infections: (a) ascending intraluminal spread of infection producing endometritis, salpingitis, PID, ectopic pregnancies, and infertility; (b) ascending infection during pregnancy, producing premature rupture of the membranes, premature birth, low birth weight, spontaneous abortion, and intrauterine death; (c) initiation or promotion of cervical neoplasia; and (d) perinatal infections acquired during delivery through an infected birth canal, including ophthalmia neonatorum/inclusion conjunctivitis and neonatal herpes.
Gonococcal and chlamydial infections are the most common causes of PID, ectopic pregnancy, and impaired fertility in women. If not adequately treated, 20–40% of women infected with C trachomatis and 10–40% of women infected with N gonorrhoeae develop PID. At least 25% of women with PID during their reproductive years develop a related complication, including infertility, ectopic pregnancy, and chronic pelvic pain.
Treatment
The treatment options for gonococcal and chlamydial cervicitis are the same as those described for infectious urethritis (Box 15-2). The treatment program should always include activity against both C trachomatis and N gonorrhoeae. The tetracyclines, including doxycycline, and the quinolones are contraindicated during pregnancy. For pregnant patients, erythromycin (base or ethylsuccinate) or amoxicillin is recommended for anti-Chlamydia therapy. Treatments for HSV and HPV are described later.
Prognosis
Early treatment of cervicitis is quite effective, usually with prompt resolution of symptoms. As with their male counterparts, women with recurrent disease need to be questioned regarding treatment compliance and reexposure. Asymptomatic disease remains a significant problem. Therefore, screening women is a major element in Chlamydia prevention. The recommendations for Chlamydia screening in women are listed in Table 15-2. To prevent reinfection and the spread of disease, the same measures should be taken as described for urethritis.
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Table 15-2. Recommendations for chlamydia screening in women. |
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VULVOVAGINITIS
Essentials of Diagnosis
General Considerations
The three most common types of vaginal infections in adult women are vulvovaginal candidiasis (20–25%), BV (30–45%), and trichomoniasis (15–20%). Other less common pathogen-related causes include ulcerative vaginitis attributed to Staphylococcus aureus toxins in women with toxic shock syndrome, clindamycin-responsive desquamative inflammatory vaginitis, group A streptococcal vaginitis, and idiopathic vulvovaginal ulceration associated with HIV infection.
Clinical Findings
Table 15-3 summarizes the clinical and microscopic findings associated with vaginitis.
A normal vaginal pH (4–4.5) and the microscopic finding of budding yeasts or pseudohyphae on a slide of vaginal discharge with 10% KOH can make the diagnosis. If the KOH is negative and clinical suspicion for candidiasis is high, a culture for Candida spp. can be performed.
The pH of the vaginal fluid is elevated above 4.5 (usually in the range of 4.7–5.5). A characteristic “fishy” odor is produced when the vaginal fluid is mixed with 10% KOH. This is called a positive “whiff test” and is the result of volatilization of aromatic amines at an alkaline pH. A wet mount or a Gram stain of the vaginal fluid shows vaginal epithelial cells covered with coccobacilli. These characteristic epithelial cells are called “clue cells.” Established diagnostic criteria for BV require three of the following four signs: (1) presence of clue cells, (2) homogenous noninflammatory discharge adherent to vaginal walls, (3) vaginal fluid pH >4.5, and (4) positive whiff test.
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Table 15-3. Clinical features of vaginitis.1 |
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On examination, the vaginal and exocervical epithelium may have an edematous and erythematous appearance with increased vascularity and petechiae formation. This is often referred to as the “strawberry cervix” of trichomoniasis. The vaginal pH is usually >5.0. The vaginal discharge contains many leukocytes and may elicit an odor when 10% KOH is added (positive whiff test). Confirmation of trichomoniasis is made when motile, pear-shaped trichomonads are seen on the wet mount; however, this occurs in only 50–70% of cases. In patients with an elevated vaginal pH, increased number of leukocytes, and an absence of motile trichomonads or clue cells on the wet mount, a culture for T vaginalis can be done to confirm the diagnosis.
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BOX 15-3 Treatment of Infectious Vaginitis |
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Differential Diagnosis
Toxic shock syndrome with S aureus can produce vaginitis along with characteristic symptoms of fever, rash, hypotension, multiorgan abnormalities, and often a polymucositis. Desquamative inflammatory vaginitis may produce prominent cell exfoliation and purulent vaginal discharge with an elevated pH. Patients may respond to clindamycin or corticosteroids.
Noninfectious causes of vaginitis must be distinguished from infectious ones. Atrophic vaginitis commonly affects postmenopausal women and is the result of decreased estrogen levels. There is thinning of the vaginal epithelium, reduced lubrication, an increase in vaginal pH, and an overgrowth of nonacidophilic coliforms. Symptoms include vaginal soreness, dyspareunia, postcoital burning, and occasional vaginal spotting. Treatment consists of topical vaginal estrogen. Other noninfectious causes include chemicals or irritants (eg, spermicides, topical antimycotic drugs, minipads, or topical fluorouracil), contact dermatitis, and collagen vascular disease.
Complications
PID, plasma cell endometriosis, and posthysterectomy vaginal-cuff cellulitis are the major complications of BV (see Chapter 22). In pregnant women, BV is associated with preterm labor, premature rupture of the membranes, chorioamnionitis, and postcesarean and postpartum endometritis. Asymptomatic high-risk pregnant women (eg, prior preterm delivery) should be screened for BV early in the second trimester. Trichomoniasis also may be associated with premature rupture of the membranes and preterm delivery.
Treatment
The optimal treatment for recurrent vulvovaginal candidiasis is not yet established. The initial treatment of recurrent vulvovaginal candidiasis is usually the same as for an acute episode. The duration, however, may be extended to 10–14 days, followed by a lower-dose maintenance regimen for 6 months. It is unclear whether the pathogenesis of recurrent infections involves the persistence of risk factors, repeated sexual transmission, an immunologic deficit, or a treatment failure. Treatment failure is not uncommon with C glabrata.
If BV is discovered during screening of asymptomatic pregnant women, treatment should be given at the beginning of the second trimester with metronidazole or clindamycin. If treatment must be given during the first trimester, clindamycin is recommended. Although there is concern for the effects of metronidazole to the unborn fetus, evidence of definitive teratogenicity remains unclear and is considered minimal after the first trimester. The treatment of high-risk pregnant women may reduce preterm delivery.
Prognosis
Although not usually considered as a life-threatening disease, the symptoms of vaginitis can be severe and recurrent disease problematic. Screening during pregnancy can help lower BV and Trichomonas-associated maternal and neonatal complications.
GENITAL ULCER DISEASE
Essentials of Diagnosis
General Considerations
Genital ulcer disease involves a disruption of the skin and mucous membranes of the genitalia and often is the presenting complaint of a sexually acquired infection. Treponema pallidum is the spirochete responsible for all stages of syphilis. It is the second most common cause of genital ulcer disease in both underdeveloped and developed countries, although it is more common in the latter. Haemophilus ducreyi, a gram-negative bacillus, is the organism responsible for chancroid. The disease is most prevalent in Africa and developing countries; however, a number of outbreaks have occurred in New Orleans and other large cities along the Gulf Coast. Genital herpes is the most common cause of genital ulcer disease in North America and Europe. It is an incurable and recurrent disease affecting an estimated 5 million–20 million Americans. Of all first-episode genital herpes lesions, 85% are produced by HSV-2 and the remaining 15% by HSV-1 (see Chapter 33). Recurrent infections are much more common with HSV-2. Sexual transmission of HSV can occur during asymptomatic periods. LGV is a chlamydial infection caused by the highly invasive L1, L2, and L3 serovars of C trachomatis. LGV is endemic in Africa, India, Southeast Asia, South America, and the Caribbean. Donovanosis is an ulcerative disease caused by the gram-negative bacillus Calymmatobacterium granulomatosis. Other names for this disorder include granuloma inguinale, granuloma venereum, granuloma donovani, chronic venereal sore, and granuloma inguinale tropicum. Although rare in the United States, donovanosis is a common cause of genital ulceration in southeastern India, New Guinea, the Caribbean, and parts of South America.
Clinical Findings
Table 15-4 summarizes the clinical findings associated with genital ulcer disease.
Primary Syphilis. After an incubation period of ~21 days (range 3–90 days), a painless ulcer appears at the site of inoculation. This ulcer is called a chancre and is the hallmark of primary syphilis. Typically a solitary chancre exists, but multiple chancres may be present in HIV patients. The base of the chancre is usually clean and the borders smooth. The most common locations include the glans penis, frenulum, and penile shaft in men and the labia, vagina, and cervix in women. Extragenital locations for chancres include the perianal region (especially in homosexual men), oral mucosa, and pharynx. Unilateral or bilateral adenopathy usually develops after the chancre. The adenopathy is firm, nontender, and never fluctuant.
Chancroid. After a short incubation period of 2–7 days, one to three (or more) painful ulcers appear in the genital region. The ulcer base is typically necrotic and purulent with ragged undermined borders. The lesion is not indurated and has historically been called the “soft chancre.” Painful inguinal lymphadenopathy is much more common in men (>50%) than in women. It is usually unilateral but occasionally can be bilateral. The lymph nodes can enlarge and become fluctuant. Although the findings of a painful ulcer and tender inguinal adenopathy are suggestive of chancroid, the addition of suppurative adenopathy is almost pathognomonic.
Genital Herpes. Genital herpes also has a short incubation period of ~2–7 days. The characteristic lesions are multiple vesicles on an erythematous base. In women, these lesions frequently involve the labia minora and majora, cervix, and occasionally the vagina. In men, the glans and shaft of the penis are common sites. Homosexual men may manifest herpetic lesions over the perianal area. Several days after the appearance of the vesicles, they rupture, creating shallow, intensely painful ulcers that subsequently become crusted. Urethritis may occasionally develop.
Primary genital herpes is the initial infection by HSV in a patient without anti-HSV antibodies. It may be preceded by constitutional symptoms of low-grade fever, chills, headache, malaise, and myalgia. These symptoms are likely related to a transient viremia and usually subside after 1 week. More localized symptoms then develop, including genital pain, itching, dysuria, and tender adenopathy. Localized paresthesia may develop in the outbreak site 24–48 h before the appearance of the vesicles. The skin lesions of primary genital herpes generally last 2–3 weeks. Nonprimary, first-episode genital herpes refers to patients previously infected with HSV, who have developed antibodies to HSV. The symptoms are usually milder, and the disease course shorter than in primary genital herpes. Systemic symptoms are generally absent. Recurrent genital herpes is a local disease without systemic symptoms and has a significantly milder presentation and shorter course than primary or nonprimary, first-episode genital herpes. These lesions generally resolve in 1 week.
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Table 15-4. Clinical features of genital ulcer disease. |
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Lymphogranuloma Venereum. Clinically, there are distinct stages of LGV. The first stage is marked by the formation of a primary genital skin or mucosal lesion in the form of a papule or herpetiform ulcer. It usually develops between 3 days and 3 weeks (up to 6 months) after exposure. It is painless and transient, and it heals rapidly without scarring. It is often unnoticed. The second stage is characterized by enlarged painful lymphadenopathy, which is unilateral in two-thirds of cases. This often is the presenting complaint of LGV and usually develops 2–6 weeks after exposure. Enlargement of nodes above and below the inguinal ligament produces the characteristic “groove sign.” It is pathognomonic for LGV and occurs in approximately one-third of cases. Lymph nodes may become fluctuant (buboes) and can spontaneously rupture, forming loculated abscesses, fistulas, or sinus tracts. Approximately one-third of inguinal buboes become fluctuant and rupture, whereas the other two-thirds involute over time to form a hard inguinal mass without suppuration. Systemic symptoms may include fever, chills, myalgia, and arthralgia.
Donovanosis. After a variable incubation period of 3–180 days, a small painless papule or nodule forms. It later erodes to form a beefy red, granulomatous ulcer. There are clinical variants of donovanosis classified by the appearance of the primary lesion: (1) ulcerative and ulcerogranulomatous, (2) hypertrophic or verrucous, (3) necrotic, and (4) sclerotic or cicatricial. Multiple lesions may coalesce to form large painless ulcers. Eventual healing occurs with scar formation. Classic buboes are absent in donovanosis.
Primary Syphilis. An immediate diagnosis of primary syphilis can be made by identifying the corkscrew appearance of T pallidum on dark-field microscopy. A negative result on dark-field microscopy does not rule out primary syphilis. Nontreponemal serologic tests such as VDRL (Venereal Disease Research Laboratory) and RPR (Rapid Plasma Reagin) have a sensitivity in primary syphilis of 59–87% and can be falsely nonreactive. Nontreponemal titers usually correlate with disease activity and should become nonreactive after treatment. Specific treponemal tests such the FTA-ABS (Fluorescent Treponemal Antibody Absorption Test) and the MHA-TP (Microhemagglutination—Treponema pallidum) are more specific serologic tests and usually remain positive indefinitely. Nontreponemal and treponemal tests should be interpreted together.
Chancroid. Because of the technical difficulty and specialized media required by H ducreyi for growth in the laboratory, the diagnosis of chancroid is made more frequently on clinical grounds. Culture media containing supplemented agar and vancomycin in a CO2-enriched atmosphere can successfully be used to grow H ducreyi. If confirmation by culture is not possible, then a clinical diagnosis of chancroid should be made and treatment begun only after genital herpes and primary syphilis have been excluded.
Genital Herpes. A Tzank smear of tissue scraped from a herpetic lesion can reveal the characteristic multinucleated giant cells of HSV infection. Viral culture has been the standard and most specific test for genital herpes, but requires 1–3 days for a result. Rapid nonculture techniques such as immunofluorescent staining and the enzyme-linked immunosorbent assay have become more widely used but are more expensive.
Lymphogranuloma Venereum. The isolation of C trachomatis from an inguinal lymph node aspirate is the most definitive test for the diagnosis of LGV. However, the recovery of Chlamydia spp. by this method is < 30%. Serologic testing is an alternative diagnostic method.
Donovanosis. The diagnosis of donovanosis is usually made clinically based on the history and exam findings on a patient with recent sexual contact in an endemic part of the world. The diagnosis can be confirmed by demonstration of the typical intracellular “Donovan Bodies” in a Giemsa or Wright's stain of crushed tissue smears or biopsy specimens. Routine culturing and serologic tests are not widely available.
Differential Diagnosis
Any genital ulcer pathogen can produce a “textbook picture” of another pathogen. A complete patient history (including travel), examination for other lesions or adenopathy, and laboratory testing are essential for an accurate diagnosis. Acute ulcers restricted to the genital area in sexually active patients strongly suggest a sexually transmitted pathogen or possibly trauma secondary to coitus. Ulcers involving both the genital and nongenital areas suggest a noninfectious process such as Behèet's disease, dermatitis herpetiformis, erythema multiforme or Stevens-Johnson syndrome, pemphigus, pemphigoid, fixed drug eruption, contact dermatitis, or squamous cell carcinoma. Fellatio can result in the simultaneous presentation of oral and genital lesions, such as HSV and syphilis. In tropical endemic regions, additional considerations include filariasis, cutaneous leishmaniasis, amebiasis, and schistosomiasis.
Complications
All genital ulcers are prone to secondary bacterial infections with a variety of genital bacteria. Additionally, edema of the foreskin in uncircumcised men may produce phimosis. Without treatment, chancres of primary syphilis and lesions of genital herpes heal spontaneously. Patients with syphilis progress into the secondary stage, whereas those with genital herpes may later experience recurrence of their lesions. The ulcers of chancroid and LGV continue to grow slowly by local extension and can produce further tissue and organ damage. LGV may further lead to perianal abscesses and rectovaginal, rectovesical, and anal fistulas and strictures. Lymphatic obstruction and edema may occur. Rectal LGV is associated with an increased incidence of rectal cancer. Complications of donovanosis scarring include urethral, vaginal, and anal strictures and lymphedema of the external genitalia.
Treatment
Primary Syphilis. Penicillin remains the treatment of choice for any stage of syphilis (Box 15-4). For early syphilis (primary, secondary, and latent syphilis of < 1 year's duration), a single intramuscular dose of benzathine penicillin G is recommended. Some authorities, however, recommend giving two or three doses 1 week apart, especially in the immunocompromised patient. For the penicillin-allergic patient, doxycycline or tetracycline may be used. Patients intolerant to the tetracyclines can use erythromycin or intramuscular ceftriaxone, although treatment failures and lack of clinical experience, respectively, have limited their use. Because T pallidum has been isolated in the cerebrospinal fluid in patients with only a chancre, a lumbar puncture with cerebral spinal fluid exam should be performed in primary or secondary syphilis if there are signs or symptoms of neurologic involvement (ophthalmic and/or auditory symptoms or cranial nerve palsies) or treatment failures.
Chancroid. A single dose of intramuscular ceftriaxone or oral azithromycin or 7 days of erythromycin are recommended first-line treatments. Some HIV-positive patients require a more prolonged therapy than the single-dose formats. For these patients, the 7-day erythromycin regimen is preferred. Alternative therapies include amoxicillin/clavulanic acid or ciprofloxacin. Fluctuant adenopathy may require needle aspiration or drainage. Symptomatic improvement should occur within days, but complete healing of ulcers may require up to 1 month.
Genital Herpes. Uncomplicated genital herpes will heal spontaneously. Treatment is available to decrease viral shedding and shorten the duration of disease. For first-episode genital herpes, oral acyclovir, valacyclovir, or famciclovir is recommended for 10 days. For recurrent disease, any one of these regimens can be given for an additional 5 days. For immunocompromised patients, including HIV-positive patients, acyclovir should be given until clinical resolution. Suppressive therapy is recommended for patients with severe and frequent recurrent episodes of genital herpes. Acyclovir can be given for up to a year, after which a 1- or 2-month “drug-free” interval is recommended to assess recurrence rate. Valacyclovir or famciclovir can be used as an alternative agent for suppressive therapy.
Lymphogranuloma Venereum. The treatment of choice for LGV has been doxycycline or tetracycline. Alternative agents include erythromycin and sulfisoxazole. Fluctuant lymph nodes should be drained by needle aspiration to prevent rupture and sinus tract formation.
Donovanosis. There has been no general consensus regarding the optimal treatment of donovanosis because of the lack of controlled studies. Recommended oral treatments include doxycycline, tetracycline, or trimethoprim-sulfamethoxazole for at least 3 weeks or until visible healing has occurred. Alternative oral agents include ciprofloxacin and erythromycin base. The addition of an aminoglycoside should be considered if the lesions do not respond within the first few days of therapy.
Prognosis The individual and societal impact of genital-ulcer disease depends on timely recognition and treatment of disease. Acknowledging the frequency of coinfecting pathogens and the increased risk of HIV transmission maximizes the potential for individual cure and regional containment.
OTHER SEXUALLY TRANSMITTED DISEASES
SKIN & MUCOUS MEMBRANE DISEASES
There are >70 different HPV genotypes based on differences within the DNA structure. HPV types 6 and 11 cause condyloma acuminatum (anogenital warts), the most common viral STD in the United States, which is rarely associated with cervical dysplasia. HPV types 16, 18, 31, 33, and 35 cause cervical infection, which is present in ~20% of reproductive-age women in the United States. Cervical infection is the most common source of squamous cell abnormalities on Pap smears and has a direct oncogenic association with cervical cancer.
Diagnosis is usually based on visual identification of genital warts, cytologic examination of scraped cervical cells, or cervical biopsy. Treatment options for genital warts include podofilox 0.5% solution, cryotherapy, podophyllin resin 10–25%, trichloroacetic acid or bichloracetic acid 80–90%, intralesional interferon, laser surgery, and surgical removal. Treatment of cervical HPV infection should be conducted through an expert to exclude high-grade squamous intraepithelial lesions.
Molluscum contagiosum is a benign disease caused by a virus of the Poxviridae family. It is spread by close human contact, including sexual contact. There are classically 2- to 10-mm domed-shaped papules, often with a central depression (umbilication). They may occur anywhere on the body except the palms and are often grouped. In HIV infected patients, the infection is often generalized with skin lesions appearing on the face and upper body. The diagnosis is usually made clinically but can be confirmed with histopathologic examination. Local treatment includes curettage or cryotherapy. There is no systemic therapy available.
PELVIC INFLAMMATORY DISEASE
PID includes endometriosis, salpingitis, tubo-ovarian abscess, and pelvic peritonitis. When PID develops as a complication of cervicitis, N gonorrhoeae and C trachomatis are the pathogens primarily responsible. Symptoms of PID include abnormal cervical or vaginal discharge, abdominal pain, and fever. On exam there may be cervical motion and adnexal and lower abdominal tenderness. It is important to diagnose and treat PID as early as possible. For patients requiring hospitalization, intravenous cefoxitin or cefotetan plus doxycycline (IV or oral) can be given (Box 15-5). Alternatively, intravenous clindamycin plus gentamicin can be given, followed by oral doxycycline. Outpatient treatments include oral ofloxacin plus metronidazole or ceftriaxone (or cefoxitin and oral probenecid) plus oral doxycycline. Duration of intravenous treatment is dependent on the severity of the clinical presentation.
EPIDIDYMITIS
In men under age 35, the most common pathogens are N gonorrhoeae and C trachomatis. Homosexual men may have enteric pathogens from rectal intercourse. Unilateral testicular pain and tenderness are common. There is usually palpable swelling of the epididymis. The evaluation and diagnostic tests are the same as those for urethritis. Treatment regimens include ceftriaxone plus doxycycline or ofloxacin (Box 15-5).
PROCTITIS
Proctitis acquired through receptive anal intercourse can be caused by N gonorrhoeae, C trachomatis (including LGV serovars), T pallidum (syphilis), and HSV. Treatment includes ceftriaxone plus doxycycline (Box 15-5).
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BOX 15-4 Treatment of Genital Ulcer Disease |
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BOX 15-5 Treatment of other Sexually Transmitted Diseases |
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Prevention
STDs collectively rank as one of the most common groups of diseases throughout the world. There are ~150 million–300 million curable cases of STDs per year with 5 million–12 million cases in North America alone. The most significant global problem in STD management today is not one of treatment, but one of prevention. No single STD can be regarded as an isolated problem. The presence of an STD identifies high-risk behavior through which multiple infections, including HIV, can occur. The primary-care physician has a significant opportunity to not only rapidly diagnose and treat STDs, but also to reduce the risks of reinfection to the patient and spread of disease within a community.
STD prevention begins with the identification of high-risk patients by taking a sexual history. A risk factor assessment includes the patient's age during the first sexual encounter and first STD, number of previous STDs, number of partners, risk assessment of those partners, type of contraception used (if any), and future plans for sexual activity. Once the risk factors are identified, the educational process can begin.
Patient education is the most significant preventative measure against STDs. The goal is to educate patients about methods and behaviors that can reduce the potential for STD transmission. Male condoms, when used correctly, are the most effective method in preventing infections transmitted between mucosal surfaces and transmission of HIV disease. Condoms do not cover all exposed skin areas and may be less effective in preventing infections transmitted through skin-to-skin contact. Female condoms also serve as an effective mechanical barrier to prevent the transmission of infection. Diaphragms do offer protection against gonococcal and chlamydial cervicitis and trichomoniasis; however, they should not be assumed to protect against HIV infection. Vaginal spermicides may reduce the risk of gonococcal and chlamydial infections, but they offer minimal to no protection against HIV infection. Although nonbarrier contraceptive measures such as hormonal supplements, surgical sterilization, and hysterectomy prevent pregnancy, they offer no protection against HIV or other STDs.
Sexual contacts of infected patients must be evaluated. Partner identification enables the treatment of persons who may be infected but are asymptomatic.
Not only will early diagnosis and treatment prevent the serious, long-term complications of STDs, but it will also help reduce the spread of disease within a community.
As stated earlier, all patients with an STD should be evaluated for other STDs. The presence of one pathogen doesn't eliminate the possibility of other coinfecting pathogens or an earlier untreated infection with a different pathogen. The physician must balance a high index of suspicion with screening programs to diagnose STDs as early as possible and to break the chain of STD transmission.
REFERENCES
Urethritis
Heath CB, Heath JM: Chlamydia trachomatis infection update. Am Fam Physician 1995;52:1455.
Kreiger JN: Trichomoniasis in men: old issues and new data. Sex Transmit Dis 1995;22:83.
Lind I: Antimicrobial resistance in Neisseria gonorrhoeae. Clin Infect Dis 1997;24(Suppl 1):S93.
Schmid GP, Fontanarosa PB: Evolving strategies for management of the nongonococcal urethritis syndromes. J Am Med Assoc 1995;274:577.
Stamm WE et al: Azithromycin for empirical treatment of the nongonococcal urethritis syndrome in men. J Am Med Assoc 1995;274:545.
Weber JT, Johnson RE: New treatments for Chlamydia trachomatis genital infection. Clin Infect Dis 1995; 20(Suppl 1):S66.
Cervicitis
Centers for Disease Control and Prevention: 1998 guidelines for treatment of sexually transmitted diseases. Morbid Mortal Wkly Rep 1997;47:49.
Majeroni BA: Chlamydial cervicitis: complications and new treatment options. Am Fam Physician 1994;49: 1825.
Miller KE: Women's health: sexually transmitted diseases. Prim Care Clin Off Pract 1997;24:179. (Women's health. Sexually transmitted diseases.)
Zenilman JM: Gonorrhea: clinical and public health issues. Hosp Pract 1993:29.(Review.)
Vulvovaginitis
Centers for Disease Control and Prevention: 1998 Guidelines for treatment of sexually transmitted diseases. Morbid Mortal Wkly Rep 1997;47:70.
Holmes KK: Lower genital tract infections in women. In Holmes KK et al: Sexually Transmitted Diseases, 3rd ed. McGraw-Hill, 1999.
Joesoef MR, Schmed GP: Bacterial vaginosis: review of treatment options and potential clinical indications for therapy. Clin Infect Dis 1995;20(Suppl 1):S72.
Reef SE et al: Treatment options for vulvovaginal candidiasis, 1993. Clin Infect Dis 1995;20(Suppl 1):S80.
Sobel JD: Vaginitis. N Engl J Med 1997;337:1899. (Review article.)
Genital Ulcer Disease
Centers for Disease Control and Prevention: 1998 Guidelines for treatment of sexually transmitted diseases. Morbid Mortal Wkly Rep 1997;47:18.
Mroczkowski TF, Martin DH: Genital ulcer disease. Dermatol Clin. 1994;12:753.
Ballard RC: Genital ulcer adenopathy syndrome. In Holmes KK et al: Sexually Transmitted Diseases, 3rd ed. McGraw-Hill, 1999.
Schulte JM, Schmid GP: Recommendations for treatment of chancroid, 1993. Clin Infect Dis 1995;20 (Suppl 1):S39.
Other Sexually Transmitted Diseases
Centers for Disease Control and Prevention: 1998 Guidelines for treatment of sexually transmitted diseases. Morbid Mortal Wkly Rep 1997;47.
Morrison EA: Natural history of cervical infection with human papillomavirus. Clin Infect Dis 1994;18:172.
Stone KM: Human papillomavirus infection and genital warts: update on epidemiology and treatment. Clin Infect Dis 1995;20(Suppl 1):S91.
Prevention
Borgatta L: Sexually transmitted diseases. Ann NY Acad Sci 1994;736:102.
Centers for Disease Control and Prevention: 1998 Guidelines for treatment of sexually transmitted diseases. Morbid Mortal Wkly Rep 1997;47:79.
Miller KE: Sexually transmitted diseases. Women's Health 1997;24:179.
Sciarra JJ: Sexually transmitted diseases: global importance. Int J Gynecol Obstet 1997;58:107.