Pathogenesis

During puberty, increasing levels of estrogen cause the vaginal epithelium to thicken and cornify and the cellular glycogen content to rise, the latter causing the vaginal pH to fall. These changes increase the resistance of the vaginal epithelium to penetration by certain organisms (including Neisseria gonorrhoeae) and increase the susceptibility to others (Candida albicans and Trichomonas, Chapter 276). The transformation of the vaginal cells leaves columnar cells on the ectocervix, forming a border of the 2 cell types on the ectocervix, known as the squamocolumnar junction. The appearance is referred to as ectopy (Fig. 114-4). With maturation, this tissue involutes. Prior to involution, it represents a unique vulnerability to infection for adolescent females. A 15 yr old sexually active girl with endocervical colonization has a 1:8 chance of developing PID compared to the 1:80 chance for a 24 yr old. As a result of these physiologic changes, gonococcal infection becomes primarily cervical and susceptibility to ascending infection is greatest during menses, when the pH is 6.8-7.0. The association of early sexual debut and younger gynecologic age with increased risk of sexually transmitted infections supports this explanation of the pathogenesis of infection in young adolescents.

Figure 114-4 Cervical ectopy.

(From the Seattle STD/HIV Prevention Training Center at the University of Washington: Claire E. Stevens.)

STI Screening

Early detection and treatment are the primary STI control strategies. Some of the most common STIs in adolescents, including HPV, HSV, chlamydia, and gonorrhea, are usually asymptomatic and if undetected can be spread inadvertently by the infected host. Screening initiatives for chlamydial infections have demonstrated reductions in PID cases by up to 40%. Although federal and professional medical organizations recommend annual chlamydia screening for sexually active females 24 yr and younger, in 2007, less than half (42%) of the sexually active females enrolled in commercial and Medicaid health plans were screened. The lack of a dialogue about STIs or the provision of STI services at annual preventive service visits to adolescents who are sexually experienced are missed opportunities for screening and education. Comprehensive, confidential, reproductive health services including STI screening should be offered to all sexually experienced adolescents (Table 114-2).

Definitions, Etiology, and Clinical Manifestations

STI syndromes are generally characterized by the location of the manifestation (vaginitis) or the type of lesion (genital ulcer). Certain constellations of presenting symptoms suggest the inclusion of a possible STI in the differential diagnosis.

Urethritis

Urethritis is an STI syndrome characterized by inflammation of the urethra, usually due to an infectious etiology. Urethritis may present with urethral discharge, urethral itching, dysuria, or urinary frequency. Urgency, frequency of urination, erythema of the urethral meatus, and scrotal pain are less common clinical presentations. Many patients are completely asymptomatic at the time of diagnosis. On examination, the classic finding is mucoid or purulent discharge from the urethral meatus (Fig. 114-5). If no discharge is evident on exam, providers may attempt to express discharge by applying gentle pressure to the urethra from the base distally to the meatus 3-4 times. Chlamydia trachomatis and N. gonorrhoeae are the most commonly identified pathogens. Mycoplasma genitalium and Ureaplasma urealyticum are considered potential pathogens in nongonococcal urethritis (NGU) when chlamydia is not confirmed. NGU caused by these pathogens may be less responsive to usual NGU therapy. Trichomonas vaginalis and HSV should also be considered in the NGU differential diagnosis. Sensitive diagnostic tests for these NGU pathogens are not available but should be considered when NGU is not responsive to treatment. Noninfectious causes of urethritis include urethral trauma or foreign body. Unlike in females, urinary tract infections are fairly rare in males who have no past genitourinary medical history. In the typical sexually active adolescent male, dysuria and urethral discharge suggest the presence of an STI unless proven otherwise. Laboratory evaluation is essential to identify the involved pathogens to determine treatment, partner notification, and disease control.

Figure 114-5 Gonococcal urethral discharge.

(From the Seattle STD/HIV Prevention Training Center at the University of Washington: Connie Celum and Walter Stamm.)

Cervicitis

The inflammatory process in cervicitis involves the deeper structures in the mucous membrane of the cervix uteri. Vaginal discharge can be a manifestation of cervicitis, if the cervical discharge is profuse. Less subtle clinical manifestations of cervicitis are irregular or postcoital bleeding, mucopurulent discharge from the os, and a friable cervix. The cervical changes associated with cervicitis must be distinguished from cervical ectopy in the younger adolescent to avoid the over diagnosis of inflammation (Fig. 114-6; see Fig. 114-4). The pathogens identified most commonly with cervicitis are C. trachomatis and N. gonorrhoeae, although no pathogen is identified in the majority of cases. HSV is a less common pathogen associated with ulcerative and necrotic lesions on the cervix.

Figure 114-6 Inflamed cervix due to gonococcal cervicitis.

(From Centers for Disease Control and Prevention: STD clinical slides (website). www.cdc.gov/std/training/clinicalslides/slides-dl.htm. Accessed June 12, 2009.

Genital Ulcer Syndromes

An ulcerative lesion in a mucosal area exposed to sexual contact is the unifying characteristic of infections associated with these syndromes. These lesions are most frequently seen on the penis and vulva, but also occur on oral and rectal mucosa depending on the adolescent’s sexual practices. HSV, Treponema pallidum (syphilis), and Haemophilus ducreyi (chancroid) are the most common organisms associated with genital ulcer syndromes.

Genital herpes, the most common ulcerative STI among adolescents, is a chronic, life-long viral infection. Two sexually transmitted HSV types have been identified, HSV-1 and HSV-2. The majority of cases of recurrent genital herpes are caused by HSV-2. Most HSV-2–infected persons are unaware of their diagnosis because they experience mild or unrecognized infections but continue to shed virus intermittently in the genital tract. Therefore, the majority of genital herpes infections are transmitted by asymptomatic persons who are unaware of their infection.

Although the initial herpetic lesion is a vesicle, by the time the patient presents clinically, the vesicle most often has ruptured spontaneously, leaving a shallow, painful ulcer. Up to 50% of first genital herpes episodes are caused by HSV-1, but recurrences and subclinical shedding are much more frequent for genital HSV-2 infection.

Syphilis and chancroid are less common causes of genital ulcers in adolescents than in adults. Lymphogranuloma venereum due to C. trachomatis serovars L1-L3, and donovanosis are rare infections in the USA and other industrialized countries, although outbreaks of lymphogranuloma venereum do occur in MSM. In these circumstances, genital ulcerations with inflamed inguinal lymph nodes (buboes) are unusual; proctitis or proctocolitis is the usual manifestation. HIV is present in affected men.

Clinical characteristics differentiating the lesions of the most common infections associated with genital ulcers are presented in Table 114-3, along with the required laboratory diagnosis to identify the causative agent accurately. The differential diagnosis includes Behçet disease (Chapter 155), Crohn disease (Chapter 328), and acute genital ulcers (AGU) due to Epstein-Barr virus (Chapter 246). AGU often follows a flu or mononucleosis-like illness in an immunocompetent female and is unrelated to sexual activity. The lesions are 0.5-2.5 cm in size, bilateral, symmetric, multiple, painful and necrotic, and are associated with inguinal lymphadenopathy. This primary infection is also associated with fever and malaise. The diagnosis may require EBV titers, or PCR testing. Treatment is supportive care including pain management.

Table 114-3 SIGNS, SYMPTOMS, AND PRESUMPTIVE AND DEFINITIVE DIAGNOSES OF GENITAL ULCERS

Diagnosis

Most adolescents infected with viral and bacterial STI pathogens usually do not report symptoms suggestive of infection. With the increased use of very sensitive, noninvasive, nucleic acid amplification tests (NAAT), providers are finding that most genital infections in females as well as many males are asymptomatic. Therefore, a good sexual history is key to identifying adolescents who should be screened for STIs and for identifying those who require a laboratory diagnostic evaluation for an STD syndrome.

When eliciting a sexual health history, discussions should be appropriate for the patient’s developmental level. In addition to questions regarding vaginal or urethral discharge, genital lesions, and lower abdominal pain among females, one should ask about prior treatment of any STI symptoms, including self-treatment using over-the-counter medications. Dyspareunia is a consistent symptom in adolescents with PID. Providers must ask about oral or anal sexual activity to determine sites for specimen collection.

Urethritis should be objectively documented by either (1) mucoid or purulent urethral discharge, (2) ≥5 WBC per high-power field on microscopic examination of a urethral secretions Gram stain, (3) ≥10 WBC per high-power field on microscopic examination of first-void urine (FVU) specimen, or (4) positive FVU leukocyte esterase test. The presence of gram-negative intracellular diplococci on microscopy confirms the diagnosis of gonococcal urethritis. Patient complaint without objective clinical or laboratory evidence does not fulfill diagnostic criteria. All patients with complaints, whether or not diagnostic criteria are fulfilled, should be tested for gonorrhea and chlamydia.

An essential component of the diagnostic evaluation of vaginal, cervical or urethral discharge is a chlamydia and gonorrhea NAAT. NAATs are the most sensitive chlamydia tests available and allow for noninvasive STI testing via urine and self-collected vaginal swabs in addition to testing endocervical and urethral specimens (Table 114-4). Gonorrhea and chlamydia NAATs perform well on rectal and oropharyngeal specimens and can be performed by most commercial laboratories.

Table 114-4 AMPLIFIED GONORRHEA AND CHLAMYDIA TESTS AND APPROVED SPECIMENS FOR TESTING*

* Specimens approved for testing as of June 22, 2010.

Evaluation of adolescent females with vaginitis includes laboratory data. The cause of vaginal symptoms usually can be determined by pH and microscopic examination of the discharge. Using pH paper, an elevated pH (i.e., >4.5) is common with BV or trichomoniasis. For microscopic exam, a slide can be made with the discharge diluted in 1-2 drops of 0.9% normal saline solution and another slide with discharge diluted in 10% potassium hydroxide (KOH) solution. Examining the saline specimen slide under a microscope may reveal motile or dead T. vaginalis or clue cells (epithelial cells with borders obscured by small bacteria), which are characteristic of bacterial vaginosis. WBCs without evidence of trichomonads or yeast are usually suggestive of cervicitis. The yeast or pseudohyphae of Candida species are more easily identified in the KOH specimen (Fig. 114-7). The sensitivity of microscopy is approximately 60-70% and requires immediate evaluation of the slide for optimal results. Therefore, lack of findings does not eliminate the possibility of infection. T. vaginalis culture is more sensitive than microscopy. Objective signs of vulvar inflammation in the absence of vaginal pathogens, along with a minimal amount of discharge, suggest the possibility of mechanical, chemical, allergic, or other noninfectious irritation of the vulva (Table 114-5).

Figure 114-7 Common normal and abnormal microscopic findings during examination of vaginal fluid. KOH, potassium hydroxide solution; PMN, polymorphonuclear leukocyte; RBC, red blood cell.

(From Adolescent medicine: state of the art reviews, vol 14, no 2, Philadelphia, 2003, Hanley & Belfus, pp 350–351.)

Table 114-5 PATHOLOGIC VAGINAL DISCHARGE

From Mitchell H: Vaginal discharge—causes, diagnosis, and treatment, Br Med J 328:1306–1308, 2004.

In settings where microscopy is not available, alternative tests may be used to diagnose vaginitis. The OSOM Trichomonas Rapid Test (Genzyme Diagnostics, Cambridge, MA), an immunochromatographic capillary flow dipstick technology, is Clinical Laboratory Improvement Amendments (CLIA)-waived and results are available in 10 min. The Affirm VPIII (Becton Dickenson, San Jose, CA), a nucleic acid probe test that evaluates for T. vaginalis, G. vaginalis, and C. albicans, is a moderate complexity laboratory test and results are available within 45 min. Both tests have a sensitivity >83% and a specificity >97% and are point-of-care diagnostics.

The definitive diagnosis of PID is difficult based on clinical findings alone. Clinical diagnosis is imprecise and no single historical, physical, or laboratory finding is both sensitive and specific for the diagnosis of acute PID. Clinical criteria have a positive predictive value of only 65-90% compared with laparoscopy. Although health care providers should maintain a low threshold for the diagnosis of PID, additional criteria to enhance specificity of diagnosis, such as transvaginal ultrasonography, can be considered (Table 114-6).

Isolation of HSV in cell culture is the preferred virologic test for genital ulcers, but culture sensitivity is low and false negatives do occur due to intermittent viral shedding. HSV PCR assays are more sensitive and can be used instead of viral culture. The Tzanck test is insensitive and nonspecific and should not be relied on.

Accurate type-specific HSV serologic assays are based on the HSV-specific glycoprotein G2 (HSV-2) and glycoprotein G1 (HSV-1). Both laboratory-based and point-of-care tests are available. Because nearly all HSV-2 infections are sexually acquired, the presence of type-specific HSV-2 antibody implies anogenital infection. The presence of HSV-1 antibody alone is more difficult to interpret because of the frequency of oral HSV infection acquired during childhood. Type-specific HSV serologic assays might be useful in the following scenarios: (1) recurrent genital symptoms or atypical symptoms with negative HSV cultures; (2) a clinical diagnosis of genital herpes without laboratory confirmation; and (3) a partner with genital herpes, especially if considering suppressive antiviral therapy to prevent transmission.

For syphilis screening more laboratories are now using treponemal enzyme immunoassay (EIA) tests. A positive treponemal EIA test identifies both previously treated and untreated or incompletely treated syphilis. False-positive results can occur, particularly among populations with low syphilis prevalence. Persons with a positive treponemal screening test should have a standard nontreponemal test with titer, such as an RPR or VDRL to guide patient management decisions.

Adolescents with STIs should be offered HIV testing. Rapid HIV testing with the availability of results in 10-20 min can be useful in settings in which the likelihood of adolescents returning for their results is low. Point-of-care, CLIA-waived tests for whole blood finger-stick and oral fluid specimen testing are available. Clinical studies have demonstrated that the rapid HIV test performance is comparable to those of EIAs. Because some reactive test results may be false-positive, every reactive rapid test must be confirmed by a more specific test, such as a Western blot.

Treatment

See Part XVI for chapters on the treatment of specific microorganisms and Tables 114-7 to 114-9. Treatment regimens using over-the-counter products for candida vaginitis and pediculosis reduce financial and access barriers to rapid treatment for adolescents, but there are potential risks for inappropriate self-treatment and complications from untreated more serious infections that must be considered before using this approach. Minimizing noncompliance with treatment, finding and treating the sexual partners, addressing prevention and contraceptive issues, offering available vaccines to prevent STIs and making every effort to preserve fertility are additional physician responsibilities. Repeat testing in 3-4 mo is recommended for patients with chlamydial and gonorrheal infections. Some experts also recommend repeat testing for trichomonas infection. Once an infection is diagnosed, partner evaluation, testing, and treatment are recommended for sexual contacts within 60 days of symptoms or diagnosis or the most recent partner if sexual contact was >60 days, even if the partner is asymptomatic. Abstinence is recommended for at least 7 days after both patient and partner are treated. A test for pregnancy should be performed for all females with suspected PID, since the test outcome will affect management.

Table 114-7 MANAGEMENT GUIDELINES FOR UNCOMPLICATED BACTERIAL STIS IN ADOLESCENTS AND ADULTS

IM, intramuscular; IV, intravenous; NAAT, nucleic acid amplification test.

Adapted for Centers for Disease Control and Prevention: 2010 Sexually transmitted diseases treatment guidelines, 2010 MMWR 59(No. RR-12):1-110, 2010.

Table 114-8 MANAGEMENT GUIDELINES FOR UNCOMPLICATED MISCELLANEOUS SEXUALLY TRANSMITTED INFECTIONS IN ADOLESCENTS AND ADULTS

Adapted for Centers for Disease Control and Prevention: 2010 Sexually transmitted diseases treatment guidelines, 2010 MMWR 59(No. RR-12):1-110, 2010.

Table 114-9 MANAGEMENT GUIDELINES FOR UNCOMPLICATED GENITAL WARTS AND GENITAL HERPES IN ADOLESCENTS AND ADULTS

Adapted from Centers for Disease Control and Prevention: STD Treatment Guidelines 2010, MMWR 59(No. RR-12):1-110, 2010.

Diagnosis and therapy are often necessarily carried out within the context of a confidential relationship between the physician and the patient. Therefore, the need to report certain STIs to health department authorities should be clarified at the outset. Health departments are HIPAA-exempt and will not violate confidentiality. Health department role is to assure that treatment and case finding have been accomplished and that sexual partners have been notified of their STI exposure. Expedited partner therapy (EPT), where the patient delivers the medication or a prescription for the medication to the partner for treatment without a clinical assessment, is a strategy to reduce further transmission of infection, particularly for male partners of women with gonorrhea and/or chlamydia who are otherwise unlikely to seek care for STI exposure. In randomized trials, EPT has reduced the rates of persistent or recurrent gonorrhea and chlamydia infection. Serious adverse reactions are rare with recommended chlamydia and gonorrhea treatment regimens, such as doxycycline, azithromycin, and cefixime. Transient gastrointestinal side effects are more common but rarely result in severe morbidity. Many states expressly permit EPT or may potentially allow its practice. Resources for information regarding EPT and state laws are available at the Centers for Disease Control and Prevention website (www.cdc.gov/std/ept/).

Prevention

Health care providers should integrate sexuality education into clinical practice with children from early childhood through adolescence. Providers should counsel adolescents regarding sexual behaviors associated with risk of STI acquisition and should educate using evidence-based prevention strategies, which include a discussion of abstinence and other risk reduction strategies, such as consistent and correct condom use. The U.S. Preventative Task Force recommends high-intensity behavioral counseling to prevent STIs for all sexually active adolescents. The HPV vaccine series with either the bivalent (HPV types 16 and 18) or quadrivalent (HPV types 16, 18, 11, and 6) vaccine is routinely recommended for 11 and 12 yr old females, although it can be given at 9 yr of age. Catch-up vaccination is recommended for 13 through 26 yr old females who have not yet received or completed the vaccine series. The quadrivalent HPV may also be given to males aged 9 through 26 to reduce their likelihood of acquiring genital warts.