Phòng khám chuyên khoa da li�u - Thạc s� bác s� Hu�nh Văn Quang

Sexually Transmitted Diseases: Overview and Clinical Approach

Sexually Transmitted Diseases: Overview and Clinical Approach

King K. Holmes

CLASSIFICATION AND EPIDEMIOLOGY

Certain sexually transmitted diseases (STDs), such as syphilis, gonorrhea, HIV infection, hepatitis B, and chancroid, are most concentrated within “core populations” having high rates of partner change, concurrent partners, or “dense” sexual networks—for example, prostitutes and their clients, some homosexual men, and persons involved in the use of illicit drugs, particularly crack cocaine and methamphetamine. Other STDs are distributed more evenly throughout society. For example, chlamydial infections, genital infections with human papillomavirus (HPV), and genital herpes can spread efficiently in relatively low-risk populations.

In general, the product of three factors determines the initial rate of spread of any sexually transmitted infection (STI) within a population: rate of exposure of susceptible to infectious people, efficiency of transmission per exposure, and duration of infectivity of those in-fected. Efforts to prevent and control STIs attempt to decrease the duration of infectivity (through early diagnosis and curative or suppressive treatment), to decrease the efficiency of transmission (e.g., through promotion of condom use and safer sexual practices), and to decrease the rate of exposure of susceptibles to infected persons (e.g., through individual counseling and efforts to change the norms of sexual behavior).

In all societies, STDs rank among the most common of all infectious diseases, with >30 infections now classified as predominantly sexually transmitted or as frequently sexually transmissible Table 1). In developing countries, with three-quarters of the world's population and 90% of the world's STDs, such factors as population growth (especially in adolescent and young-adult age groups), rural-to-urban migration, wars, and poverty create exceptional vulnerability to disease resulting from risky sexual behaviors. During the 1990s, in China, Russia, the other states of the former Soviet Union, and South Africa, internal social structures changed rapidly as borders opened to the West, unleashing enormous new epidemics of HIV infection and other STDs. HIV has become the leading cause of death in some developing countries, and HPV and hepatitis B virus (HBV) remain important causes of cervical and hepatocellular carcinoma, respectively—two of the most common malignancies in the developing world. Sexually transmitted herpes simplex virus (HSV) infections now cause most genital ulcer disease throughout the world and an increasing proportion of cases of genital herpes in developing countries with generalized HIV epidemics, where the positive feedback loop between HSV and HIV transmission is a growing, intractable problem. Globally, five curable STDs—gonorrhea, chlamydial infections, syphilis, chancroid, and trichomoniasis—caused ~350 million new infections annually in the mid-1990s. Up to 50% of women of reproductive age in developing countries have bacterial vaginosis (arguably acquired sexually). All six of these curable infections have been associated with increased risk of HIV transmission or acquisition.

In the industrialized countries, fear of HIV infection since the mid-1980s, coupled with widespread behavioral interventions and better-organized systems of care for the curable STDs, have helped curb the transmission of the latter diseases. Nonetheless, foci of hyperendemic transmission persist in the southeastern United States and in most large U.S. cities. Rates of gonorrhea and syphilis remain higher in the United States than in any other Western industrialized country. The remarkable resurgence of gonorrhea and syphilis among homosexual and bisexual men in many parts of the United States and Europe since the 1990s reflects increased risk-taking since the advent of potent antiretroviral therapy and has been accompanied by increasing HIV transmission in this group. The prevalence of antibody to HSV-2 has begun to fall only recently (since the mid-1990s), and genital HPV remains the most common sexually transmitted pathogen, infecting one-third of a cohort of U.S. college women within 2 years in a study conducted during the 1990s.

MANAGEMENT OF COMMON STD SYNDROMES

Although other chapters discuss management of specific STIs, delineating treatment based on diagnosis of a specific infection, most patients are actually managed (at least initially) on the basis of presenting symptoms and signs and associated risk factors, even in industrialized countries. Table 2 lists some of the most common clinical STD syndromes and their microbial etiologies. Strategies for their management are outlined below.

STD care and management begin with risk assessment and proceed to clinical assessment, diagnostic testing or screening, treatment, and prevention. Indeed, the routine care of any patient begins with risk assessment (e.g., for risk of heart disease, cancer). STD/HIV risk assessment is important in primary care, urgent care, and emergency care settings as well as in specialty clinics providing adolescent, prenatal, and family planning services. STD/HIV risk assessment guides interpretation of symptoms that could reflect an STD; decisions on screening or prophylactic/preventive treatment; risk reduction counseling and intervention (e.g., hepatitis B vaccination); and notification of partners of patients with known infections. Consideration of routine demographic data (e.g., gender, age, marital status, area of residence) is a simple first step in STD/HIV risk assessment. For example, national guidelines now recommend routine screening of sexually active females ≤25 years of age for Chlamydia trachomatis infection. Table 3 provides a set of 10 STD/HIV risk-assessment questions that clinicians can pose verbally or that health care systems can adapt (with yes/no responses) into a routine self-administered questionnaire for use in clinics. The initial framing statement gives permission to discuss taboo topics.

Risk assessment is followed by clinical assessment (elicitation of information on specific current symptoms and signs of STDs). Confirmatory diagnostic tests (for persons with symptoms or signs) or screening tests (for those without symptoms or signs) may involve microscopic examination, culture, antigen detection tests, genetic probe or amplification tests, or serology. Initial syndrome-based treatment should cover the most likely causes. For certain syndromes, results of rapid tests can narrow the spectrum of this initial therapy (e.g., wet mount of vaginal fluid for women with vaginal discharge, Gram's stain of urethral discharge for men with urethral discharge, rapid plasma reagin test for genital ulcer). After the institution of treatment, STD management proceeds to the “4 C's” of prevention and control: contact tracing, ensuring compliance with therapy, and counseling on risk reduction, including condom promotion and provision.

URETHRITIS IN MEN

During the 1990s, the incidence of reported gonorrhea among men in the United States fell to 126 cases per 100,000 population; the incidence figures then leveled off through 2002. The incidence of reported C. trachomatis infections among men has been increasing steadily (with increased testing), reaching 130 cases per 100,000 in 2002. Until recently, C. trachomatis caused ~30 to 40% of cases of nongonococcal urethritis (NGU); however, the proportion of cases due to this organism may have declined in some populations served by effective chlamydial-control programs. HSV and Trichomonas vaginalis each cause a small proportion of NGU cases in the United States. Recently, multiple studies have consistently implicated Mycoplasma genitalium as a probable cause of many Chlamydia-negative cases, while fewer studies than in the past have implicated Ureaplasma urealyticum. Coliform bacteria can cause urethritis in men who practice insertive anal intercourse. The initial diagnosis of urethritis in men currently includes specific tests only for Neisseria gonorrhoeae and C. trachomatis. The following summarizes the approach to the patient with suspected urethritis:

• Establish the presence of urethritis. If proximal-to-distal “milking” of the urethra does not express a purulent or mucopurulent discharge, even after the patient has not voided for several hours or preferably overnight, a Gram's-stained smear of overt discharge or of an anterior urethral specimen obtained by passage of a small urethrogenital swab 2 to 3 cm into the urethra usually reveals ≥5 neutrophils per 1000× field in areas containing cells; in gonococcal infection, such a smear usually reveals gram-negative intracellular diplococci as well. Alternatively, the centrifuged sediment of the first 20 to 30 mL of voided urine can be examined for inflammatory cells, either by microscopy showing ≥10 leukocytes per high-power field or by the leukocyte esterase test. Patients with symptoms who lack objective evidence of urethritis may have functional rather than organic problems and generally do not benefit from repeated courses of antibiotics.
• Evaulate for complications or alternative diagnoses. A brief history and examination will exclude epididymitis and systemic complications, such as disseminated gonococcal infection (DGI) and Reiter's syndrome. Although digital examination of the prostate gland seldom contributes to the evaluation of sexually active young men with urethritis, men with dysuria who lack evidence of urethritis as well as sexually inactive men with urethritis should undergo prostate palpation, urinalysis, and urine culture to exclude bacterial prostatitis and cystitis.

Evaluate for gonococcal and chlamydial infection. An absence of typical gram-negative diplococci on Gram's-stained smear of urethral exudate containing inflammatory cells warrants a preliminary diagnosis of NGU and should lead to testing of the urethral specimen for C. trachomatis. Culture or DNA detection tests for N. gonorrhoeae may be positive when Gram's staining is negative; certain strains of N. gonorrhoeae can result in negative urethral Gram's stains in up to 30% of cases of urethritis. Results of tests for gonococcal and chlamydial infection predict the patient's prognosis (with greater risk for recurrent NGU if neither chlamydiae nor gonococci are found than if either is detected) and can guide both the counseling given to the patient and the management of the patient's sexual partner(s).

• Treat urethritis.

Table 4 summarizes the steps in management of sexually active men with symptoms of urethral discharge and/or dysuria.

TREATMENT

In practice, if Gram's stain does not reveal gonococci, urethritis is treated with a regimen effective for NGU, such as azithromycin (1.0 g orally in a single dose) or doxycycline (100 mg orally bid for 7 days). If gonococci are demonstrated by Gram's stain or if no diagnostic tests are performed to definitively exclude gonorrhea, treatment should include a single-dose regimen for gonorrhea plus azithromycin or doxycycline treatment for C. trachomatis. Sexual partners should be tested for gonorrhea and chlamydial infection and should receive the same regimen given to the male index case. Patients with confirmed persistence or recurrence of urethritis after treatment should be re-treated with the initial regimen if they did not comply with the original treatment or were reexposed to an untreated partner. Otherwise, an intraurethral swab specimen and a first-voided urine sample should be cultured for T. vaginalis. If compliance with initial treatment is confirmed and reexposure excluded, treatment with metronidazole (2 g orally in a single dose) plus erythromycin base (500 mg orally qid for 7 days) is recommended.

EPIDIDYMITIS

Acute epididymitis, almost always unilateral, must be differentiated from testicular torsion, tumor, and trauma. Torsion, a surgical emergency, usually occurs in the second or third decade of life and produces a sudden onset of pain, elevation of the testicle within the scrotal sac, rotation of the epididymis from a posterior to an anterior position, and absence of blood flow on Doppler examination or ^99mTc scan. Persistence of symptoms after a course of therapy for epididymitis suggests the possibility of testicular tumor. In sexually active men under age 35, acute epididymitis is caused most frequently by C. trachomatis and less commonly by N. gonorrhoeae and is usually associated with overt or subclinical urethritis. Acute epididymitis occurring in older men or following urinary tract instrumentation is usually caused by urinary pathogens. Similarly, epididymitis in men who have practiced insertive rectal intercourse is often caused by Enterobacteriaceae. These men usually have no urethritis but do have bacteriuria.

TREATMENT

Ceftriaxone (250 mg as a single dose IM) followed by doxycycline (100 mg orally bid for 10 days) is effective for epididymitis caused by N. gonorrhoeae or C. trachomatis. Alternatively, ofloxacin (300 mg orally bid for 10 days) or levofloxacin (500 mg orally once daily for 10 days) is also effective for syndrome-based treatment of epididymitis because of effectiveness against Enterobacteriaceae as well as N. gonorrhoeae and C. trachomatis; however, emerging gonococcal resistance to fluoroquinolones now limits the use of these drugs in some areas.

URETHRITIS AND THE URETHRAL SYNDROME IN WOMEN

C. trachomatis, N. gonorrhoeae, and occasionally HSV cause symptomatic urethritis—known as the urethral syndrome in women—characterized by “internal” dysuria (usually without urinary urgency or frequency) and pyuria, with Escherichia coli or other uropathogens not present in urine at counts of ≥10²/mL. In contrast, the dysuria associated with vulvar herpes or vulvovaginal candidiasis (and perhaps with trichomoniasis) is often described as “external,” being caused by painful contact of urine with the inflamed or ulcerated labia or introitus. Acute onset, association with urinary urgency or frequency, hematuria, or suprapubic bladder tenderness suggests bacterial cystitis. Among women with symptoms of acute bacterial cystitis, costovertebral pain and tenderness or fever suggests acute pyelonephritis.

Signs of vulvovaginitis, coupled with symptoms of external dysuria, suggest vulvar infection (e.g., with HSV or Candida albicans). Among dysuric women without signs of vulvovaginitis, bacterial UTI must be differentiated from the urethral syndrome by assessment of risk, evaluation of the pattern of symptoms and signs, and specific microbiologic testing. An STD etiology of the urethral syndrome is suggested by young age, more than one current sexual partner, a new partner within the past month, a partner with urethritis, or coexisting mucopurulent cervicitis (see below). The finding of a single urinary pathogen, such as E. coli or Staphylococcus saprophyticus, at a concentration of ≥10²/mL in a properly collected specimen of midstream urine from a dysuric woman with pyuria indicates probable bacterial UTI, whereas pyuria with <10² conventional uropathogens per milliliter of urine (“sterile” pyuria) suggests acute urethral syndrome due to C. trachomatis or N. gonorrhoeae. Gonorrhea and chlamydial infection should be sought by specific tests (e.g., nucleic acid amplification tests on the first 10 mL of voided urine). Among dysuric women with sterile pyuria caused by infection with N. gonorrhoeae or C. trachomatis, appropriate treatment alleviates dysuria.

VULVOVAGINAL INFECTIONS

Abnormal Vaginal Discharge

If directly questioned about vaginal discharge during routine health checkups, many women acknowledge having nonspecific symptoms of vaginal discharge that do not correlate with objective signs of inflammation or with actual infection. However, unsolicited reporting of abnormal vaginal discharge does suggest bacterial vaginosis or trichomoniasis. Specifically, an abnormally increased amount or an abnormal odor of the discharge is associated with one or both of these conditions. Cervical infection with N. gonorrhoeae or C. trachomatis does not appear to cause an increased amount or abnormal odor of discharge, but cervicitis, like trichomoniasis, can include the production of an increased number of neutrophils in vaginal fluid, resulting in a yellow color. Vulvar conditions such as genital herpes or vulvovaginal candidiasis can cause vulvar pruritus, burning, irritation, or lesions as well as external dysuria (as urine passes over the inflamed vulva) or vulvar dyspareunia.

Certain vulvovaginal infections may have serious sequelae. Trichomoniasis, bacterial vaginosis, and vulvovaginal candidiasis have all been associated with increased risk of acquisition of HIV infection. Vaginal trichomoniasis and bacterial vaginosis early in pregnancy independently predict premature onset of labor. Bacterial vaginosis can also lead to anaerobic bacterial infection of the endometrium and salpinges. Vaginitis may be an early and prominent feature of toxic shock syndrome, and recurrent or chronic vulvovaginal candidiasis develops with increased frequency among women with systemic illnesses, such as diabetes mellitus or HIV-related immunosuppression (although only a very small proportion of women with recurrent vulvovaginal candidiasis in the United States actually have a serious predisposing illness).

Thus vulvovaginal symptoms or signs warrant careful evaluation, including pelvic examination, simple rapid diagnostic tests, and appropriate therapy specific for the anatomical site and type of infection. Unfortunately, a recent survey in the United States indicated that clinicians seldom perform the tests required to establish the cause of such symptoms. Further, comparison of telephone and office management of vulvovaginal complaints has documented the inaccuracy of the former, and comparison of evaluations by nurse-midwives with those by physician-practitioners showed that the practitioners' clinical evaluations correlated poorly both with the nurses' evaluations and with diagnostic tests. The diagnosis and treatment of the three most common types of vaginal infection are summarized in Table 5.

Inspection of the vulva and perineum may reveal tender genital ulcerations (typically due to HSV infection, occasionally due to chancroid) or fissures (typically due to vulvovaginal candidiasis) or discharge visible at the introitus before insertion of a speculum (suggestive of bacterial vaginosis or trichomoniasis). Speculum examination permits the clinician to discern whether the discharge in fact looks abnormal and whether any abnormal discharge in the vagina emanates from the cervical os (mucoid and, if abnormal, yellow) or from the vagina (not mucoid, since the vaginal epithelium does not produce mucus). Symptoms or signs of abnormal vaginal discharge should prompt testing of vaginal fluid for pH, fishy odor when mixed with 10% KOH, and microscopic features when mixed with saline and with 10% KOH. Additional objective laboratory tests useful for establishing the cause of abnormal vaginal discharge include Gram's staining detect alterations in the vaginal flora; card tests for bacterial vaginosis, as described below; and a new DNA probe test (the Affirm test) to detect T. vaginalis and C. albicans as well as the increased concentrations of Gardnerella vaginalis associated with bacterial vaginosis.

TREATMENT

Patterns of treatment for vaginal discharge vary widely. In developing countries, where clinics or pharmacies often dispense treatment based on symptoms alone without examination or testing, oral treatment with metronidazole—either as a 2-g single dose or as a 7-day regimen—provides reasonable coverage against both trichomoniasis and bacterial vaginosis, the usual causes of symptoms of vaginal discharge; metronidazole treatment of sex partners prevents reinfection of women with trichomoniasis, even though it does not help prevent the recurrence of bacterial vaginosis. Guidelines promulgated during the 1990s by the World Health Organization suggested treatment for cervical infection and for vulvovaginal candidiasis in women with symptoms of abnormal vaginal discharge; in retrospect, these recommendations were faulty, since these conditions seldom produce such symptoms.

In industrialized countries, clinicians treating symptoms and signs of abnormal vaginal discharge should at least differentiate between bacterial vaginosis and trichomoniasis, because optimal management of patients and partners differs for these two conditions (as discussed briefly below).

Vaginal Trichomoniasis

Symptomatic trichomoniasis characteristically produces a profuse, yellow, purulent, homogeneous vaginal discharge and vulvar irritation, often with visible inflammation of the vaginal and vulvar epithelium and petechial lesions on the cervix (the so-called strawberry cervix, usually evident only by colposcopy). The pH of vaginal fluid usually rises to ≥5.0. In women with typical symptoms and signs of trichomoniasis, microscopic examination of vaginal discharge mixed with saline reveals motile trichomonads in most culture-positive cases. However, in the absence of symptoms or signs, culture is often required for detection of the organism. Polymerase chain reaction (PCR) tests for T. vaginalis compare favorably with culture, and PCR testing of urine is now disclosing surprisingly high prevalences of this pathogen among men at several STD clinics in the United States. Treatment of asymptomatic as well as symptomatic cases reduces rates of transmission and prevents later development of symptoms.

TREATMENT

Only nitroimidazoles consistently cure trichomoniasis. Tinidazole and ornidazole have longer half-lives than metronidazole but do not give better results than a single 2-g oral dose of metronidazole, which is much less expensive. Treatment of male sexual partners—often facilitated by dispensing metronidazole to the female patient to give to her partner(s), with a warning about avoiding the concurrent use of alcohol—significantly reduces both the risk of reinfection and the reservoir of infection. Treatment with 0.75% metronidazole gel intravaginally, although moderately effective for bacterial vaginosis, is not reliable for vaginal trichomoniasis. Systemic use of metronidazole is not recommended during the first trimester of pregnancy but is considered safe thereafter. In a large randomized trial, metronidazole treatment of trichomoniasis during pregnancy did not reduce the frequency of perinatal morbidity.

Bacterial Vaginosis

This syndrome (formerly termed nonspecific vaginitis, Haemophilus vaginitis, anaerobic vaginitis, or Gardnerella-associated vaginal discharge) is characterized by symptoms of vaginal malodor and a slightly to moderately increased white discharge, which appears homogeneous, is low in viscosity, and smoothly coats the vaginal mucosa. An interesting observation is that new genital HPV infection in young women is associated with increased subsequent risk of developing bacterial vaginosis. Other risk factors include multiple sexual partners and recent intercourse with a new partner, but metronidazole treatment of male partners has not reduced the rate of recurrence among affected women.

The vaginal fluid of women with bacterial vaginosis is characterized by markedly increased prevalences and concentrations of G. vaginalis, Mycoplasma hominis, and several anaerobic bacteria [e.g., Mobiluncus spp., Prevotella spp. (formerly Bacteroides spp.), and some Peptostreptococcus spp.]. The vaginal fluid usually lacks hydrogen peroxide–producing Lactobacillus spp., which constitute most of the normal vaginal flora and perhaps help protect against certain cervical and vaginal infections. Vaginal douching, use of intravaginal nonoxynol-9 spermicide, and new sexual partners can all result in loss of vaginal colonization by hydrogen peroxide–producing lactobacilli.

Bacterial vaginosis is conventionally diagnosed clinically with the Amsel criteria, which include any three of the following four clinical abnormalities: (1) objective signs of increased white homogeneous vaginal discharge; (2) a vaginal discharge pH of >4.5; (3) liberation of a distinct fishy odor (attributable to volatile amines such as trimethylamine) immediately after vaginal secretions are mixed with a 10% solution of KOH; and (4) microscopic demonstration of “clue cells” on a wet mount prepared by mixing vaginal secretions with normal saline in a ratio of ~1:1. A diagnostic card test facilitates screening of vaginal fluid for pH > 4.5 and amines, and a dipstick test detects proline aminopeptidase, an enzyme associated with this syndrome.

TREATMENT

The standard dosage of metronidazole for the treatment of bacterial vaginosis is 500 mg orally bid for 7 days. The single 2-g oral dose of metronidazole recommended for trichomoniasis produces somewhat lower short-term cure rates. Intravaginal treatment with 2% clindamycin cream [one full applicator (5 g containing 100 mg of clindamycin phosphate) each night for 7 nights] or with 0.75% metronidazole gel [one full applicator (5 g containing 37.5 mg of metronidazole) twice daily for 5 days] is also approved for use in the United States and does not elicit systemic adverse reactions. Oral clindamycin (300 mg bid for 7 days) and clindamycin ovules (100 g intravaginally once at bedtime for 3 days) have also been approved. Unfortunately, long-term recurrence (i.e., several months later) is distressingly common after either oral or intravaginal treatment. Treatment of male partners with metronidazole does not prevent recurrence of bacterial vaginosis.

No controlled data support the use of currently available vaginal or oral preparations of lactobacilli for the treatment or prevention of recurrence of bacterial vaginosis. In a randomized trial, repeated intravaginal inoculation of a vaginal peroxide-producing Lactobacillus species following treatment of bacterial vaginosis with metronidazole did not reduce the frequency of recurrence. A meta-analysis of 18 studies concluded that bacterial vaginosis during pregnancy substantially increased the risk of preterm delivery and of spontaneous abortion. Although intravaginal treatment of bacterial vaginosis during pregnancy has not reduced perinatal morbidity, oral clindamycin treatment of this syndrome early in pregnancy significantly reduced the risk of late miscarriage and of preterm delivery. Oral antimicrobial treatment of bacterial vaginosis for ≥7 days early in pregnancy may reduce the risk of preterm delivery for women with a history of this pregnancy outcome.

Vulvovaginal Pruritus, Burning, or Irritation

Vulvovaginal candidiasis produces vulvar pruritus, burning, or irritation, generally without symptoms of increased vaginal discharge or malodor. Genital herpes can produce similar symptoms, with lesions sometimes difficult to distinguish from the fissures caused by candidiasis. Signs of vulvovaginal candidiasis include vulvar erythema, edema, fissures, and tenderness. With candidiasis, a white scanty vaginal discharge sometimes takes the form of white thrush-like plaques or cottage cheese–like curds adhering loosely to the vaginal mucosa. C. albicans accounts for nearly all cases of symptomatic vulvovaginal candidiasis, which probably arise from endogenous strains of C. albicans that have colonized the vagina or the intestinal tract. Complicated vulvovaginal candidiasis includes cases that recur four or more times per year; are unusually severe; are caused by non-albicans Candida spp.; or occur in women with uncontrolled diabetes, debilitation, immunosuppression, or pregnancy.

The diagnosis of vulvovaginal candidiasis usually involves the demonstration of pseudohyphae or hyphae by microscopic examination of vaginal fluid mixed with saline or 10% KOH or subjected to Gram's staining. Microscopic examination is less sensitive than culture but correlates better with symptoms.

TREATMENT

Symptoms and signs of vulvovaginal candidiasis warrant treatment, usually intravaginal administration of any of several imidazole antibiotics (e.g., miconazole or clotrimazole) for 3 to 7 days. Over-the-counter marketing of such preparations has reduced the cost of care and made treatment more convenient for many women with recurrent yeast vulvovaginitis. However, most women who purchase these preparations do not have vulvovaginal candidiasis, while many do have other vaginal infections that require different treatment. Therefore, only women with classic symptoms of vulvar pruritus and a history of previous episodes of yeast vulvovaginitis documented by an experienced clinician should self-treat. Single-dose oral treatment with fluconazole (150 mg) is also effective and is preferred by many patients. Management of complicated cases (see above) and those that do not respond to the usual intravaginal or single-dose oral therapy often involves prolonged or periodic oral therapy; this situation is discussed extensively in the 2002 STD Treatment Guidelines published by the Centers for Disease Control and Prevention (CDC). Treatment of sexual partners is not routinely indicated.

Other Causes of Vaginal Discharge or Vaginitis

In the ulcerative vaginitis associated with staphylococcal toxic shock syndrome, Staphylococcus aureus should be promptly identified in vaginal fluid by Gram's stain and by culture. In desquamative inflammatory vaginitis, smears of vaginal fluid reveal neutrophils, massive vaginal epithelial-cell exfoliation with increased numbers of parabasal cells, and gram-positive cocci; this syndrome may respond to treatment with 2% clindamycin cream. Additional causes of vaginitis and vulvovaginal symptoms include retained foreign bodies (e.g., tampons), cervical caps, vaginal spermicides, vaginal antiseptic preparations or douches, vaginal epithelial atrophy (in postmenopausal women or during prolonged breast-feeding in the postpartum period), allergic reactions to latex condoms, vaginal aphthae associated with HIV infection or Behçet's syndrome, and vestibulitis (a poorly understood syndrome).

MUCOPURULENT CERVICITIS

Mucopurulent cervicitis (MPC) refers to inflammation of the columnar epithelium and subepithelium of the endocervix and of any contiguous columnar epithelium that lies exposed in an ectopic position on the exocervix. MPC in women represents the “silent partner” of urethritis in men, being equally common and often caused by the same agents (N. gonorrhoeae, C. trachomatis, or—in a significant association shown by two recent case-control studies—M. genitalium); however, MPC is more difficult to recognize. As the most common manifestation of these serious bacterial infections in women, MPC can be a harbinger or sign of upper genital tract infection, also known as pelvic inflammatory disease (PID; see below). In pregnant women, MPC can lead to obstetric complications. More than half of all cases of MPC in the United States today remain idiopathic.

The diagnosis of MPC rests on the detection of yellow mucopurulent discharge from the cervical os or of increased numbers of polymorphonuclear leukocytes (PMNs) in Gram's-stained or Papanicolaou-stained smears of endocervical mucus. MPC due to C. trachomatis can also produce edematous cervical ectopy (see below) and endocervical bleeding upon gentle swabbing. Unlike the endocervicitis produced by gonococcal or chlamydial infection, cervicitis caused by HSV produces ulcerative lesions on the stratified squamous epithelium of the exocervix as well as on the columnar epithelium. Yellow cervical mucus on a white swab removed from the endocervix indicates the presence of PMNs. The mucus should be rolled thinly on a slide for Gram's staining. The presence of ≥20 polymorphonuclear cells per 1000× microscopic field within strands of cervical mucus not contaminated by vaginal squamous epithelial cells or vaginal bacteria indicates endocervicitis . Detection of intracellular gram-negative diplococci in carefully collected endocervical mucus is quite specific but ≤50% sensitive for gonorrhea. Therefore, specific and sensitive tests for N. gonorrhoeae as well as C. trachomatis are also indicated in the evaluation of MPC.

TREATMENT

Although the above criteria for MPC are neither highly specific nor highly predictive of gonococcal or chlamydial infection in many settings, current CDC guidelines call for consideration of empirical treatment for MPC, pending test results, “for a patient who has suspected gonorrhea or chlamydial infection, if (a) the prevalences of these infections are high in the patient population, and (b) the patient might be difficult to locate after treatment.” In this situation, therapy should include a single-dose regimen effective for gonorrhea plus treatment for chlamydial infection, as outlined in Table 4 for the treatment of urethritis. In settings where gonorrhea is much less common than chlamydial infection, initial therapy for chlamydial infection alone suffices, pending test results for gonorrhea. The etiology and potential benefit of treatment of endocervicitis not associated with gonorrhea or chlamydial infection remain undefined. Although the antimicrobial susceptibility of M. genitalium is not yet well defined, it currently seems reasonable to use azithromycin to treat possible M. genitalium infection in such cases. Sexual partner(s) of a woman with MPC should be examined and given a regimen similar to that chosen for the woman unless results of tests for gonorrhea or chlamydial infection in either partner warrant different therapy or no therapy.

CERVICAL ECTOPY

Cervical ectopy, often mislabeled “cervical erosion,” is easily confused with infectious endocervicitis. Ectopy represents the presence of the one-cell-thick columnar epithelium extending from the endocervix out onto the visible ectocervix. In ectopy, the cervical os may contain clear or slightly cloudy mucus but usually not yellow mucopus. Colposcopy shows intact epithelium. Normally found during adolescence and early adulthood, ectopy gradually recedes through the second and third decades of life, as squamous metaplasia replaces the ectopic columnar epithelium. Oral contraceptive use favors the persistence or reappearance of ectopy, while smoking apparently accelerates squamous metaplasia. Cauterization of ectopy is not warranted. Ectopy may render the cervix more susceptible to infection with N. gonorrhoeae, C. trachomatis, or HIV.

PELVIC INFLAMMATORY DISEASE

The term pelvic inflammatory disease usually refers to infection that ascends from the cervix or vagina to involve the endometrium and/or fallopian tubes. Infection can extend beyond the reproductive tract to cause pelvic peritonitis, generalized peritonitis, perihepatitis, or pelvic abscess. In rare instances, infection extends secondarily to the pelvic organs from adjacent foci of inflammation (e.g., appendicitis, regional ileitis, or diverticulitis), as a result of hematogenous dissemination (e.g., of tuberculosis), or as a rare complication of certain tropical diseases (e.g., schistosomiasis). Intrauterine infection can be primary (spontaneously occurring and usually sexually transmitted) or secondary to invasive intrauterine surgical procedures [e.g., dilatation and curettage, termination of pregnancy, insertion of an intrauterine device (IUD), or hysterosalpingography] or to parturition.

Etiology

The agents most often implicated in acute PID include those that are primary causes of endocervicitis (N. gonorrhoeae and C. trachomatis) and those that can be regarded as components of an altered vaginal flora. In general, PID is most often associated with gonorrhea where there is a high incidence of gonorrhea—e.g., in developing countries and in indigent, inner-city populations in the United States. In recent case-control studies, detection of M. genitalium by PCR in endometrial specimens has also been significantly associated with histopathologic diagnoses of endometritis.

Anaerobic and facultative organisms (especially Prevotella species, peptostreptococci, E. coli, Haemophilus influenzae, and group B streptococci) as well as genital mycoplasmas have been isolated from specimens obtained at laparoscopy from the peritoneal fluid or fallopian tubes in a varying proportion (typically one-fourth to one-third) of women with PID studied in the United States. The difficulty of determining the exact microbial etiology of an individual case of PID has implications for the approach to empirical antimicrobial treatment of this infection.

Epidemiology

In the United States in 2002, women 15 to 44 years of age made ~200,000 initial visits to physician's offices for PID, and an estimated 66,000 women were hospitalized for acute PID. Important risk factors for acute PID include the presence of endocervical infection or bacterial vaginosis, a history of salpingitis or of recent vaginal douching, and the use of an IUD (especially among nulliparous women, during the first few months after IUD insertion, and among women with multiple sex partners). Certain other iatrogenic factors, such as dilatation and curettage or cesarean section, can increase the risk of PID, especially among women with endocervical gonococcal or chlamydial infection or bacterial vaginosis. The onset of symptoms of N. gonorrhoeae–associated and C. trachomatis–associated PID often occurs during or soon after the menstrual period; this timing suggests that menstruation is a risk factor in women with endocervical infection. Experimental inoculation of the fallopian tubes of lower primates has shown that repeated exposure to C. trachomatis leads to the greatest degree of tissue inflammation and damage; thus, immunopathology probably contributes to the pathogenesis of chlamydial salpingitis. Women using oral contraceptives appear to be at decreased risk of symptomatic PID, and tubal sterilization reduces the risk of salpingitis by preventing intraluminal spread of infection into the tubes.

Clinical Manifestations

ENDOMETRITIS: A CLINICAL PATHOLOGIC SYNDROME

A study of women with clinically suspected PID who were undergoing both endometrial biopsy and laparoscopy showed that those with endometritis alone differed from those who also had salpingitis in that they significantly less often had lower quadrant, adnexal, or cervical motion or abdominal rebound tenderness; fever; or elevated C-reactive protein levels. In addition, women with endometritis alone differed from those with neither endometritis nor salpingitis in that they more often had gonorrhea, chlamydial infection, and risk factors such as douching or IUD use. Thus, women with endometritis alone were intermediate between those with neither endometritis nor salpingitis and those with salpingitis with respect to risk factors, clinical manifestations, cervical infection prevalence, and elevated C-reactive protein.

SALPINGITIS

Symptoms of nontuberculous salpingitis classically evolve from a yellow or malodorous vaginal discharge caused by MPC and/or bacterial vaginosis to midline abdominal pain and abnormal vaginal bleeding caused by endometritis and then to bilateral lower abdominal and pelvic pain caused by salpingitis, with nausea, vomiting, and increased abdominal tenderness caused by peritonitis.

The abdominal pain in nontuberculous salpingitis is usually described as dull or aching. In some cases, pain is lacking or is atypical, but active inflammatory changes are found in the course of an unrelated evaluation or procedure, such as a laparoscopic evaluation for infertility. Abnormal uterine bleeding precedes or coincides with the onset of pain in ~40% of women with PID, symptoms of urethritis (dysuria) occur in 20%, and symptoms of proctitis (anorectal pain, tenesmus, and rectal discharge or bleeding) are occasionally seen in women with gonococcal or chlamydial infection.

Speculum examination shows evidence of MPC (yellow endocervical discharge, easily induced endocervical bleeding) in the majority of women with gonococcal or chlamydial PID. Cervical motion tenderness is produced by stretching of the adnexal attachments on the side toward which the cervix is pushed. Bimanual examination reveals uterine fundal tenderness due to endometritis and abnormal adnexal tenderness due to salpingitis that is usually, but not necessarily, bilateral. Adnexal swelling is palpable in about one-half of women with acute salpingitis, but evaluation of the adnexae in a patient with marked tenderness is not reliable. The initial temperature is >38°C in only about one-third of patients with acute salpingitis. Laboratory findings include elevation of the erythrocyte sedimentation rate (ESR) in 75% of patients with acute salpingitis and elevation of the peripheral white blood cell count in up to 60%.

Unlike nontuberculous salpingitis, genital tuberculosis often occurs in older women, many of whom are postmenopausal. Presenting symptoms include abnormal vaginal bleeding, pain (including dysmenorrhea), and infertility. About one-quarter of these women have had adnexal masses. Endometrial biopsy shows tuberculous granulomas and provides optimal specimens for culture.

PERIHEPATITIS AND PERIAPPENDICITIS

Pleuritic upper abdominal pain and tenderness (usually localized to the right upper quadrant) develop in 3 to 10% of women with acute PID. Symptoms of perihepatitis arise during or after the onset of symptoms of PID and may overshadow lower abdominal symptoms, thereby leading to a mistaken diagnosis of cholecystitis. In perhaps 5% of cases of acute salpingitis, early laparoscopy reveals perihepatic inflammation ranging from edema and erythema of the liver capsule to exudate with fibrinous adhesions between the visceral and parietal peritoneum. When treatment is delayed and laparoscopy is performed late, dense “violin-string” adhesions can be seen over the liver; chronic exertional or positional right upper quadrant pain ensues when traction is placed on the adhesions. Although perihepatitis, also known as the Fitz-Hugh–Curtis syndrome, was for many years specifically attributed to gonococcal salpingitis, most cases are now attributed to chlamydial salpingitis. In patients with chlamydial salpingitis, serum titers of microimmunofluorescent antibody to C. trachomatis are typically much higher when perihepatitis is present than when it is absent.

Physical findings include right upper quadrant tenderness and usually include adnexal tenderness and cervicitis, even in patients whose symptoms do not suggest salpingitis. Results of liver function tests and right upper quadrant ultrasonography are nearly always normal. The presence of MPC and pelvic tenderness in a young woman with subacute pleuritic right upper quadrant pain and normal ultrasonography of the gallbladder points to a diagnosis of perihepatitis.

Periappendicitis (appendiceal serositis without involvement of the intestinal mucosa) has been found in ~5% of patients undergoing appendectomy for suspected appendicitis and can occur as a complication of gonococcal or chlamydial salpingitis.

Among women with salpingitis, HIV infection is associated with increased severity of salpingitis and with tuboovarian abscess requiring hospitalization and surgical drainage. Nonetheless, among women with HIV infection and salpingitis, the clinical reponse to conventional antimicrobial therapy (coupled with drainage of tuboovarian abscess, when found) has been satisfactory.

Diagnosis

Treatment appropriate for PID must not be withheld from patients who have an equivocal diagnosis; it is better to err on the side of overdiagnosis and overtreatment. On the other hand, it is essential to differentiate between salpingitis and other pelvic pathology, particularly surgical emergencies such as appendicitis and ectopic pregnancy.

Nothing short of laparoscopy definitively identifies salpingitis, but routine laparoscopy to confirm suspected salpingitis is generally impractical. Most patients with acute PID have lower abdominal pain of <3 weeks' duration, pelvic tenderness on bimanual pelvic examination, and evidence of lower genital tract infection (e.g., MPC). Approximately 60% of such patients have salpingitis at laparoscopy, and perhaps 10 to 20% have endometritis alone. Among the patients with these findings, a rectal temperature >38°C, a palpable adnexal mass, and elevation of the ESR to >15 mm/h also raise the probability of salpingitis, which has been found at laparoscopy in 68% of patients with one of these additional findings, 90% of patients with two, and 96% of patients with three. However, only 17% of all patients with laparoscopy-confirmed salpingitis have had all three additional findings.

In a woman with pelvic pain and tenderness, increased numbers of PMNs (30 per 1000× microscopic field in strands of cervical mucus) increase the predictive value of a clinical diagnosis of acute PID, as do onset with menses, history of recent abnormal menstrual bleeding, presence of an IUD, history of salpingitis, and sexual exposure to a male with urethritis. Appendicitis or another disorder of the gut is favored by the early onset of anorexia, nausea, or vomiting; the onset of pain later than day 14 of the menstrual cycle; or unilateral pain limited to the right or left lower quadrant. Whenever the diagnosis of PID is being considered, serum assays for human β-chorionic gonadotropin should be performed; these tests are usually positive with ectopic pregnancy. Ultrasonography and magnetic resonance imaging (MRI) can be useful for the identification of tuboovarian or pelvic abscess. MRI of the tubes can also show increased tubal diameter, intratubal fluid, or tubal wall thickening in cases of salpingitis.

The primary and uncontested value of laparoscopy in women with lower abdominal pain is for the exclusion of other surgical problems. Some of the most common or serious problems that may be confused with salpingitis (e.g., acute appendicitis, ectopic pregnancy, corpus luteum bleeding, ovarian tumor) are unilateral. Unilateral pain or pelvic mass, although not incompatible with PID, is a strong indication for laparoscopy unless the clinical picture warrants laparotomy instead. Atypical clinical findings, such as the absence of lower genital tract infection, a missed menstrual period, a positive pregnancy test, or failure to respond to appropriate therapy, are other common indications for laparoscopy. Endometrial biopsy is relatively sensitive and specific for the diagnosis of endometritis, which correlates well with the presence of salpingitis.

Endocervical swab specimens should be examined by Gram's staining for PMNs and gram-negative diplococci and by nucleic acid amplification tests for N. gonorrhoeae and C. trachomatis. The clinical diagnosis of PID made by expert gynecologists is confirmed by laparoscopy or endometrial biopsy in ~90% of women who also have cultures positive for N. gonorrhoeae or C. trachomatis. Even among women with no symptoms suggestive of acute PID who were attending an STD clinic or gynecology clinic in Pittsburgh, endometritis was significantly associated with endocervical gonorrhea or chlamydial infection or bacterial vaginosis, being detected in 26, 27, and 15% of women with these conditions, respectively.

TREATMENT

Women with PID can be treated as either outpatients or inpatients. In the multicenter Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) trial, 831 women with mild to moderately severe symptoms and signs of PID were randomized to receive either inpatient treatment with intravenous (IV) cefoxitin and doxycycline or outpatient treatment with a single intramuscular (IM) dose of cefoxitin plus oral doxycycline. Short-term clinical and microbiologic outcomes and long-term outcomes were equivalent in the two groups. Nonetheless, hospitalization should be considered when (1) the diagnosis is uncertain and surgical emergencies such as appendicitis and ectopic pregnancy cannot be excluded, (2) pelvic abscess is suspected, (3) severe illness or nausea and vomiting preclude outpatient management, (4) the patient has HIV infection, (5) the patient is assessed as unable to follow or tolerate an outpatient regimen, or (6) the patient has failed to respond to outpatient therapy. Some experts also prefer to hospitalize adolescents with PID for initial therapy.

Recommended combination regimens for ambulatory or parenteral management of PID are presented in Table 6. Women managed as outpatients should receive a combined regimen with broad activity, such as ceftriaxone followed by doxycycline. Metronidazole can be added, if tolerated, to enhance activity against anaerobes. Alternatively, oral ofloxacin or levofloxacin, each continued for 14 days and given with or without metronidazole, provides good coverage of the major pathogens. Although few methodologically sound clinical trials (especially with prolonged follow-up) have been conducted, one meta-analysis suggested a benefit of providing good coverage against anaerobes.

The following two parenteral regimens have given nearly identical results in a multicenter randomized trial:

• Doxycycline (100 mg bid, given IV or by mouth) plus cefotetan (2.0 g IV every 12 h) or cefoxitin (2.0 g IV every 6 h). Administration of these drugs should be continued by the IV route for at least 48 h after the patient's condition improves and then followed with doxycycline (100 mg bid by mouth) to complete 14 days of therapy.
• Clindamycin (900 mg IV every 8 h) plus gentamicin (2.0 mg/kg IV or IM, followed by 1.5 mg/kg every 8 h) in patients with normal renal function. Once-daily dosing of gentamicin (with combination of the total daily dose into a single daily dose) has not been evaluated in PID but has been efficacious in other serious infections and could be substituted.

Treatment with these drugs should be continued for at least 48 h after the patient's condition improves and then followed with oral doxycycline (100 mg bid by mouth) or clindamycin (450 mg qid by mouth) to complete 14 days of therapy. In cases with tuboovarian abscess, clindamycin rather than doxycycline for continued therapy may provide better coverage for anaerobic infection.

Follow-Up

Hospitalized patients should show substantial clinical improvement within 3 to 5 days. Women treated as outpatients should be clinically reevaluated within 72 h. A follow-up telephone survey of women seen in an emergency room and given a prescription for 10 days of oral doxycycline for PID found that 28% never filled the prescription and 41% stopped taking medication early (after an average of 4.1 days), often because of persistent symptoms, lack of symptoms, or side effects. Women not responding favorably to ambulatory therapy should be hospitalized. After completion of treatment, tests for persistent or recurrent infection with N. gonorrhoeae or C. trachomatis should be performed if symptoms persist or recur or if the patient has not complied with therapy or has been reexposed to an untreated sex partner.

Surgery

Surgery is necessary for the treatment of salpingitis only in the face of life-threatening infection (such as rupture or threatened rupture of a tuboovarian abscess) or for drainage of an abscess. Conservative surgical procedures are usually sufficient. Pelvic abscesses can often be drained by posterior colpotomy, and peritoneal lavage can be used if there is generalized peritonitis.

Prognosis

Among 900 women in Sweden who underwent long-term follow-up for a mean period of 8 years after successful treatment of an acute episode of PID with various regimens (that today would often not be considered to provide optimal broad antimicrobial activity), late sequelae included infertility due to bilateral tubal occlusion, ectopic pregnancy due to tubal scarring without occlusion, chronic pelvic pain, and recurrent salpingitis. The postsalpingitis risk of infertility due to tubal occlusion among sexually active women not using contraceptives was 14% at 15 to 24 years of age and 26% at 25 to 34 years of age; the risk for women of all ages combined was 11% after one episode of salpingitis, 23% after two episodes, and 54% after three or more episodes. A study at the University of Washington found a sevenfold increase in the risk of ectopic pregnancy and an eightfold increase in the rate of hysterectomy after PID.

Prevention

A randomized controlled trial designed to determine whether selective screening for chlamydial infection reduced the risk of subsequent PID showed that women randomized to undergo screening had a 56% lower rate of PID over the following year than did women receiving the usual care without screening. This report helped to prompt the establishment of U.S. national guidelines for risk-based chlamydial screening of young women as a highly effective way to reduce the incidence of PID and the prevalence of post-PID sequelae, while also reducing sexual transmission of C. trachomatis.

ULCERATIVE GENITAL LESIONS

Genital ulceration reflects a set of important STIs, most of which sharply increase the risk of sexual acquisition and shedding of HIV. In a 1996 study of genital ulcers in 10 of the U.S. cities with the highest rates of primary syphilis, PCR testing of ulcer specimens demonstrated HSV in 62% of patients, Treponema pallidum in 13%, and Haemophilus ducreyi in 12 to 20%.

In Asia and Africa, chancroid was once considered the most common type of genital ulcer, followed in frequency by primary

syphilis and then genital herpes. With increased efforts to control chancroid and syphilis, together with more frequent recurrences or persistence of genital herpes attributable to HIV infection, PCR testing of genital ulcers now clearly implicates genital herpes as the most common cause of genital ulceration in many developing countries. Lymphogranuloma venereum  and donovanosis (granuloma inguinale; continue to cause genital ulceration in developing countries but rarely occur today in North America or Europe. Other causes of genital ulcer include (1) candidiasis and traumatized genital warts—both readily recognized; (2) lesions due to genital involvement of more widespread dermatoses; and (3) cutaneous manifestations of systemic diseases, such as genital mucosal ulceration in Stevens-Johnson syndrome or Behçet's disease.

Diagnosis

Although most genital ulcerations cannot be diagnosed confidently on clinical grounds alone, clinical findings plus epidemiologic considerations (Table 7) can usually guide initial management (Table 8) pending results of further tests. Clinicians should order a rapid serologic test for syphilis in all cases of genital ulcer and a dark-field or direct immunofluorescence test (or PCR test, where available) for T. pallidum in all lesions except those highly characteristic of infection with HSV (i.e., those with herpetic vesicles). All patients presenting with genital ulceration should be asked to undergo serologic testing for HIV infection.

Typical vesicles or pustules or a cluster of painful ulcers preceded by vesiculopustular lesions suggests genital herpes. These typical clinical presentations make detection of the virus optional; however, many patients want confirmation of the diagnosis, and differentiation of HSV-1 from HSV-2 has prognostic implications, since the latter causes more frequent genital recurrences.

Painless, nontender, indurated ulcers with firm, nontender inguinal adenopathy suggest primary syphilis. If dark-field examination and a rapid serologic test for syphilis are initially negative and the patient will comply with follow-up and sexual abstinence, the performance of two more dark-field examinations on successive days before treatment is begun will improve the sensitivity of the diagnosis of syphilis. Repeated serologic testing for syphilis 1 or 2 weeks after treatment of seronegative primary syphilis usually demonstrates seroconversion.“Atypical” or clinically trivial ulcers may be more common manifestations of genital herpes than classic vesiculopustular lesions. Specific tests for HSV in such lesions are therefore indicated. Type-specific serologic tests for serum antibody to HSV-2, now commercially available, may give negative results, especially when patients present early with the initial episode of genital herpes or when HSV-1 is the cause of genital herpes (as is often the case today). Furthermore, a positive test for HSV-2 antibody does not prove that the current lesions are herpetic, since nearly one-fourth of the general population of the United States becomes seropositive for HSV-2 during early adulthood. Nonetheless, a positive HSV-2 serology does enable the clinician to tell the patient that he or she has had genital herpes, should learn to recognize symptoms, should avoid sex during recurrences, and should consider use of condoms or suppressive antiviral therapy, both of which can reduce transmission to a sexual partner.

Demonstration of H. ducreyi by culture (or by PCR test, when available) is most useful when ulcers are painful and purulent, especially if inguinal lymphadenopathy with fluctuance or overlying erythema is noted; if chancroid is prevalent in the community; or if the patient has recently had a sexual exposure elsewhere in a chancroid-endemic area (e.g., a developing country). Enlarged, fluctuant lymph nodes should be aspirated for culture or PCR tests to detect H. ducreyi as well as for Gram's staining and culture to rule out the presence of other pyogenic bacteria.

When genital ulcers persist beyond the natural history of initial episodes of herpes (2 to 3 weeks) or of chancroid or syphilis (up to 6 weeks) and do not resolve with syndrome-based antimicrobial therapy, then—in addition to the usual tests for herpes, syphilis, and chancroid—biopsy is indicated to exclude donovanosis, carcinoma, and other nonvenereal dermatoses. HIV serology should also be undertaken, since chronic, persistent genital herpes is common in AIDS.

TREATMENT

Immediate syndrome-based treatment for acute genital ulcerations (after collection of all necessary diagnostic specimens) is often appropriate before all test results become available, because patients with typical initial or recurrent episodes of genital or anorectal herpes can benefit from prompt oral antiviral therapy; because early treatment of sexually transmitted causes of genital ulcers decreases further transmission; and because some patients do not return for test results and treatment. The patient with nonvesicular ulcerative lesions who may not return for follow-up or may continue sexual activity should receive initial treatment for syphilis, together with empirical therapy for chancroid if there has been an exposure in an area where chancroid occurs or if regional lymph node suppuration is evident. In resource-poor settings lacking ready access to diagnostic tests, this approach to syndromic treatment for syphilis and chancroid has helped bring these two diseases under control. Finally, empirical antimicrobial therapy may be indicated if ulcers persist and the diagnosis remains unclear after a week of observation despite attempts to diagnose herpes, syphilis, and chancroid.

PROCTITIS, PROCTOCOLITIS, ENTEROCOLITIS, AND ENTERITIS

Sexually acquired proctitis, with inflammation limited to the rectal mucosa (the distal 10 to 12 cm), results from direct rectal inoculation of typical STD pathogens. In contrast, inflammation extending from the rectum to the colon (proctocolitis), involving both the small and the large bowel (enterocolitis), or involving the small bowel alone (enteritis) can result from ingestion of typical intestinal pathogens through oral-anal exposure during sexual contact. Anorectal pain and mucopurulent, bloody rectal discharge suggest proctitis or protocolitis. Proctitis commonly produces tenesmus (causing frequent attempts to defecate, but not true diarrhea) and constipation, whereas proctocolitis and enterocolitis more often cause true diarrhea. In all three conditions, anoscopy usually shows mucosal exudate and easily induced mucosal bleeding (i.e., a positive “wipe test”), sometimes with petechiae or mucosal ulcers. Exudate should be sampled for Gram's staining and other microbiologic studies. Sigmoidoscopy or colonoscopy shows inflammation limited to the rectum in proctitis or disease extending at least up into the sigmoid colon in proctocolitis.

The AIDS era brought an extraordinary shift in the clinical and etiologic spectrum of intestinal infections among homosexual men. The number of cases of the acute intestinal STIs described above fell as high-risk sexual behaviors became less common in this group. At the same time, the number of AIDS-related opportunistic intestinal infections increased rapidly, many associated with chronic or recurrent symptoms. The incidence of these infections has since fallen with increasingly effective antiretroviral therapy.

Acquisition of N. gonorrhoeae, HSV, or C. trachomatis during receptive anorectal intercourse causes most cases of infectious proctitis in women or homosexual men. Primary and secondary syphilis can also produce anal or anorectal lesions, with or without symptoms. Gonococcal or chlamydial proctitis typically involves the most distal rectal mucosa and the anal crypts and is clinically mild, without systemic manifestations. In contrast, primary proctitis due to HSV and proctocolitis due to the strains of C. trachomatis that cause LGV usually produce severe anorectal pain and often cause fever. Perianal ulcers and inguinal lymphadenopathy, most commonly due to HSV, can also occur in LGV or syphilis. Sacral nerve root radiculopathies, usually presenting as urinary retention, laxity of the anal sphincter, or constipation, may complicate primary herpetic proctitis. In LGV, rectal biopsy typically shows crypt abscesses, granulomas, and giant cells—findings resembling those in Crohn's disease; such findings should always prompt rectal culture and serology for LGV, which is a curable infection. Syphilis can also produce rectal granulomas, usually in association with infiltration by plasma cells or other mononuclear cells. Syphilis, LGV, and HSV infection involving the rectum can produce perirectal adenopathy that is sometimes mistaken for malignancy; syphilis, LGV, HSV infection, and chancroid involving the anus can produce inguinal adenopathy, because anal lymphatics drain to inguinal lymph nodes.

Diarrhea and abdominal bloating or cramping pain without anorectal symptoms and with normal findings on anoscopy and sigmoidoscopy occur with inflammation of the small intestine (enteritis) or with proximal colitis. In homosexual men without HIV infection, enteritis is often attributable to Giardia lamblia. Sexually acquired proctocolitis is most often due to Campylobacter or Shigella spp.

TREATMENT

Acute proctitis in persons who have practiced receptive intercourse is usually sexually acquired. Such patients should undergo anoscopy to detect rectal ulcers or vesicles and petechiae after swabbing of the rectal mucosa; to examine rectal exudates for PMNs and gram-negative diplococci; and to obtain rectal swab specimens for testing for rectal gonorrhea, chlamydial infection, herpes, and syphilis. Pending test results, patients with proctitis should receive empirical syndromic treatment—e.g., with ceftriaxone (a single IM dose of 125 mg for gonorrhea) plus doxycycline (100 mg bid by mouth for 7 days for possible chlamydial infection) plus treatment for herpes or syphilis if indicated.

PREVENTION AND CONTROL OF STDS

Prevention and control of STDs require (1) reduction of the average rate of sexual exposure through alteration of behaviors and behavioral norms among both susceptible and infected persons in all population groups; (2) reduction of the efficiency of transmission through the promotion of safer sexual practices, the use of condoms during casual or commercial sex, hepatitis B immunization, and many other approaches (e.g., early detection and treatment of other STIs to reduce the efficiency of sexual transmission of HIV); and (3) shortening of the duration of infectivity of STDs through early detection and curative or suppressive treatment of patients and their sexual partners.

Financial and time constraints imposed by managed-care practice patterns often curtail screening and prevention services. As outlined, the success of clinicians' efforts to detect and treat STDs depends in part on societal efforts to teach young people how to recognize symptoms of STDs; to motivate those with symptoms to seek care promptly; and to make such care accessible, affordable, and acceptable, especially to the young indigent patients most likely to acquire an STD.

Since many infected individuals develop no symptoms or fail to recognize and report symptoms, clinicians should routinely perform an STI risk assessment for teenagers and young adults as a guide to selective screening. U.S. Preventive Services Task Force Guidelines recommend screening sexually active female patients ≤25 years of age for C. trachomatis whenever they present for health care (at least once a year); older women should be tested if they have more than one sexual partner, have begun a new sexual relationship since the previous test, or have another STD diagnosed. In the United States, widespread selective screening of young women for cervical C. trachomatis infection in some regions has been associated with a 50 to 60% drop in prevalence, and such screening also protects the individual woman from PID. Sensitive urine-based genetic amplification tests permit expansion of screening to men, teenage boys, and girls in settings where examination is not planned or is impractical (e.g., during pre-participation sports examinations).

Although gonorrhea is now substantially less common than chlamydial infection in industrialized countries, screening tests for N. gonorrhoeae are still appropriate for women and teenage girls attending STD clinics and for sexually active teens and young women from areas of high gonorrhea prevalence. However, multiplex nucleic acid amplification tests that combine screening for N. gonorrhoeae and C. trachomatis in a single low-cost assay may facilitate the prevention and control of both infections in populations at high risk.

All patients with newly detected STIs or at high risk for STIs according to routine risk assessment as well as all pregnant women should be encouraged to undergo serologic testing for syphilis and HIV infection, with appropriate HIV counseling before and after testing. Randomized trials have shown that risk-reduction counseling of patients with STDs significantly lowers subsequent risk of acquiring an STD; such counseling should now be considered a standard component of STD management. Preimmunization serologic testing for antibody to HBV is indicated for unvaccinated persons who are known to be at high risk, such as homosexually active men and injection drug users. In most young persons, however, it is more cost-effective to vaccinate against HBV without serologic screening.

Partner notification is the process of identifying and informing partners of infected patients of possible exposure to an STI and of examining, testing, and treating partners as appropriate. In a series of 22 reports concerning partner notification during the 1990s, index patients with gonorrhea or chlamydial infection named a mean of 0.75 to 1.6 partners, of whom one-fourth to one-third were infected; those with syphilis named 1.8 to 6.3 partners, with one-third to one-half infected; and those with HIV infection named 0.76 to 5.31 partners, with up to one-fourth infected. Persons who transmit infection or who have recently been infected and are still in the incubation period usually have no symptoms or only mild symptoms and seek medical attention only when notified of their exposure. Therefore, the clinician must encourage patients to participate in partner notification, must ensure that exposed persons are notified, and must guarantee confidentiality to all involved. In the United States, local health departments often offer assistance in partner notification, treatment, and/or counseling. It seems both feasible and most useful to notify those partners exposed within the patient's likely period of infectiousness, which is often considered the preceding 1 month for gonorrhea, 1 to 2 months for chlamydial infection, and up to 3 months for early syphilis.

Persons with a new-onset STD always have a source contact who gave them the infection; in addition, they may have a secondary (spread or exposed) contact with whom they had sex after becoming infected. The identification and treatment of these two types of contacts have different objectives. Treatment of the source contact (often a casual contact) benefits the community by preventing further transmission; treatment of the recently exposed secondary contact (typically a spouse or another steady sexual partner) prevents both the development of serious complications (such as PID) in the partner and reinfection of the index patient. A recent survey of a random sample of U.S. physicians found that most instructed patients to abstain from sex during treatment, to use condoms, and to inform their sex partners after being diagnosed with gonorrhea, chlamydial infection, or syphilis; physicians sometimes gave the patients drugs for their partners. However, follow-up of the partners by physicians was infrequent. A recent randomized trial compared patients' delivery of therapy to partners exposed to gonorrhea or chlamydial infection with conventional notification and advice to partners to seek evaluation for STD; patients' delivery of therapy to their partners significantly reduced rates of reinfection of the index patient. State-by-state variations in regulations on this approach have not been well defined.

In summary, clinicians and public health agencies share responsibility for the prevention and control of STDs. In the managed-care era, the role of primary care clinicians has become increasingly important in prevention as well as in diagnosis and treatment.

• < Trước
• Tiếp tục >