The patient presenting with an STI usually has one or more of the signs or symptoms described in this section. Management considerations for STIs include assessing the patient’s adherence to therapy and ensuring follow-up, treating STIs in partners, and determining pregnancy risk. Treatment of each STI is detailed in Table 44–1.
In most cases of cervicitis no organism is isolated. The most common causes include C trachomatis or N gonorrhoeae. HSV, T vaginalis, and Mycoplasma genitalium are less common causes. Bacterial vaginosis is now recognized as a cause of cervicitis. Cervicitis can also be present without an STI.
Two major diagnostic signs characterize cervicitis: (1) purulent or mucopurulent endocervical exudate visible in the endocervical canal or on an endocervical swab and (2) easily induced bleeding with the passage of a cotton swab through the cervical os. Cervicitis is often asymptomatic, but many patients with cervicitis have an abnormal vaginal discharge or postcoital bleeding.
Although endocervical Gram stain may show an increased number of polymorphonuclear leukocytes, this finding has a low positive predictive value and is not recommended for diagnosis. Patients with cervicitis should be tested for C trachomatis, N gonorrhoeae, and trichomoniasis by using the most sensitive and specific tests available at the site.
Persistent cervicitis is difficult to manage and requires reassessment of the initial diagnosis and reevaluation for possible re-exposure to an STI. Cervicitis can persist despite repeated courses of antimicrobial therapy. Presence of a large ectropion can contribute to persistent cervicitis.
Empiric treatment for both gonorrhea and chlamydial infection is recommended because coinfection is common. If the patient is asymptomatic except for cervicitis, then treatment may wait until diagnostic test results are available (see Table 44–1). Follow-up is recommended if symptoms persist. Patients should be instructed to abstain from sexual intercourse until they and their sex partners are cured and treatment is completed.
PELVIC INFLAMMATORY DISEASE
PID is defined as inflammation of the upper female genital tract and may include endometritis, salpingitis, tubo-ovarian abscess, and pelvic peritonitis. It is the most common gynecologic disorder necessitating hospitalization for female patients of reproductive age in the United States. The incidence is highest in teenage girls. Those who are sexually active have a high risk (1 in 8) of developing PID, whereas women in their 20s have one-tenth the risk. Predisposing risk factors include multiple sexual partners, younger age of initiating sexual intercourse, prior history of PID, and lack of condom use. Lack of protective antibody from previous exposure to sexually transmitted organisms and cervical ectopy contribute to the development of PID. Many adolescents with subacute or asymptomatic PID are never identified.
PID is a polymicrobial infection. Causative agents include N gonorrhoeae, Chlamydia trachomatis, anaerobic bacteria that reside in the vagina, and genital mycoplasmas. Vaginal douching and other mechanical factors such as retained for multiple years intrauterine devices or prior gynecologic surgery increase the risk of PID by providing access of lower genital tract organisms to pelvic organs. Recent menses and bacterial vaginosis have been associated with the development of PID.
PID may be challenging to diagnose because of the wide variation in the symptoms and signs. No single historical, clinical, or laboratory finding has both high sensitivity and specificity for the diagnosis. Diagnosis of PID is usually made clinically (Table 44–2). Typical patients have lower abdominal pain, pelvic pain, or dysuria. Systemic symptoms such fever, nausea or vomiting may be present. Vaginal discharge is variable. Cervical motion tenderness, uterine or adnexal tenderness, or signs of peritonitis are often present. Mucopurulent cervicitis is present in 50% of patients. Tubo-ovarian abscesses can often be detected by careful physical examination (feeling a mass or fullness in the adnexa).
Table 44–2.Diagnostic criteria for pelvic inflammatory disease. ||Download (.pdf) Table 44–2. Diagnostic criteria for pelvic inflammatory disease.
Empiric treatment of PID should be initiated in sexually active young women and others at risk for sexually transmitted infections if one or more of the following minimum criteria are present:
Additional supportive criteria
Oral temperature > 38.3°C (101°F)
Abnormal cervical or vaginal mucopurulent discharge or cervical friability
Presence of abundant white blood cells on microscopic evaluation of vaginal secretions diluted in saline
Elevated erythrocyte sedimentation rate or elevated C-reactive protein
Laboratory documentation of infection with Neisseria gonorrhoeae or Chlamydia trachomatis
Definitive criteria (selected cases)
Histopathologic evidence of endometritis on endometrial biopsy
Tubo-ovarian abscess on sonography or other radiologic tests
Laparoscopic abnormalities consistent with PID
Laboratory findings may include elevated WBCs with a left shift and elevated acute phase reactants (erythrocyte sedimentation rate or C-reactive protein). A positive test for N gonorrhoeae or C trachomatis is supportive, although 25% of the time neither of these bacteria is detected. Pregnancy needs to be ruled out, because patients with an ectopic pregnancy can present with abdominal pain and concomitant pregnancy will affect management.
Laparoscopy is the gold standard for detecting salpingitis. It is used if the diagnosis is in question or to help differentiate PID from an ectopic pregnancy, ovarian cysts, or adnexal torsion. Endometrial biopsy should be performed in women undergoing laparoscopy who do not have visual evidence of salpingitis because some women may have isolated endometritis. The clinical diagnosis of PID has a positive predictive value for salpingitis of 65%–90% in comparison with laparoscopy. Pelvic ultrasonography also is helpful in detecting tubo-ovarian abscesses, which are found in almost 20% of teens with PID. Transvaginal ultrasound is more sensitive than abdominal ultrasound. All women who have acute PID should be tested for N gonorrhoeae and C trachomatis and should be screened for HIV infection.
Differential diagnosis includes other gynecologic illnesses (ectopic pregnancy, threatened or septic abortion, adnexal torsion, ruptured and hemorrhagic ovarian cysts, dysmenorrhea, endometriosis, or mittelschmerz), gastrointestinal illnesses (appendicitis, cholecystitis, hepatitis, gastroenteritis, or inflammatory bowel disease), and urinary tract illnesses (cystitis, pyelonephritis, or urinary calculi).
Scarring of the fallopian tubes is one of the major sequelae of PID. After one episode of PID, 17% of patients become infertile, 17% develop chronic pelvic pain, and 10% will have an ectopic pregnancy. Infertility rates increase with each episode of PID; three episodes of PID result in a 73% infertility rate. Duration of symptoms appears to be the largest determinant of infertility. Hematogenous or lymphatic spread of organisms from the fallopian tubes rarely causes inflammation of the liver capsule (perihepatitis) resulting in symptoms of pleuritic right upper quadrant pain and elevation of liver function tests.
The objectives of treatment are both to achieve a clinical cure and to prevent long-term sequelae. There are no differences in short- and long-term clinical and microbiologic response rates resulting from parenteral or oral therapy. PID is frequently managed at the outpatient level, although some clinicians argue that all adolescents with PID should be hospitalized because of the frequency of complications. Severe systemic symptoms and toxicity, signs of peritonitis, inability to take fluids, pregnancy, nonresponse or intolerance of oral antimicrobial therapy, and tubo-ovarian abscess favor hospitalization. In addition, if the health care provider believes that the patient will not adhere to treatment, hospitalization is warranted. Pregnant women with PID should be admitted to hospital and treated with parental antibiotics to reduce the increased risk of morbidity. Surgical drainage may be required for adequate treatment of tubo-ovarian abscesses.
The broad-spectrum antibiotic regimens described in Table 44–1 cover the numerous microorganisms associated with PID. All treatment regimens should be effective against N gonorrhoeae and C trachomatis because negative endocervical screening tests do not rule out upper reproductive tract infection with these organisms. Outpatient treatment should be reserved for compliant patients who have classic signs of PID without systemic symptoms. Patients with PID who receive outpatient treatment should be reexamined within 24–48 hours, with phone contact in the interim, to assess persistent disease or treatment failure. Patients should have substantial improvement within 48–72 hours. An adolescent should be reexamined 7–10 days after the completion of therapy to ensure the resolution of symptoms.
J: Pelvic inflammatory disease. N Engl J Med 2015;372():2039–2048
The most common bacterial causes of urethritis in males are N gonorrhoeae and C trachomatis. Additionally, T vaginalis, HSV, Ureaplasma urealyticum, and M genitalium cause urethritis. Approximately 15%–25% of nongonococcal, nonchlamydial urethritis can be attributed to either M genitalium or U urealyticum. Coliforms may cause urethritis in males practicing insertive anal intercourse. Mechanical manipulation or contact with irritants can also cause transient urethritis. It is important to recognize that urethritis in both males and females are frequently asymptomatic.
Females often present with symptoms of a urinary tract infection and “sterile pyuria” (no enteric bacterial pathogens isolated), which reflects urethritis caused by the organisms described above.
If symptomatic, males present most commonly with a clear or purulent discharge from the urethra, dysuria, or urethral pruritus. Hematuria and inguinal adenopathy can occur. Most infections caused by C trachomatis and T vaginalis are asymptomatic, while 70% of males with M genitalium and 23%–90% with gonococcal urethritis are symptomatic.
In a symptomatic male a positive leukocyte esterase test on first-void urine, or microscopic examination of first-void urine demonstrating more than 10 WBCs per high-power field, is suggestive of urethritis. Gram stain of urethral secretions demonstrating more than 5 WBCs per high-power field is also suggestive. Gonococcal urethritis is established by documenting the presence of WBCs containing intracellular gram-negative diplococci. Urethral swab or first-void urine for NAAT should be sent to the laboratory to detect N gonorrhoeae and C trachomatis. Evaluation for T vaginalis should be considered as newer technologies increase the sensitivity and specificity of detecting T vaginalis over wet mount. Microscopic examination of urethral discharge is not a sensitive test. Specific NAAT testing of urine is available for Mycoplasma and Ureaplasma, though it is not often clinically utilized.
Complications include recurrent or persistent urethritis, epididymitis, prostatitis, or Reiter syndrome.
Patients with objective evidence of urethritis should receive empiric treatment for gonorrhea and chlamydial infection, ideally directly observed in the office (see Table 44–1). Some data suggest better outcomes for treatment of M genitalium with azithromycin. If the infection is unresponsive to initial treatment and the infection is NAAT-negative, trichomoniasis should be ruled out and nongonococcal, nonchlamydial urethritis should be suspected and treated appropriately. Patients should be instructed to return for evaluation if symptoms persist or recur after completion of initial empiric therapy. Symptoms alone, without documentation of signs or laboratory evidence of urethral inflammation, are not a sufficient basis for retreatment. Sexual partners should either be evaluated or treated for gonorrhea and chlamydial infection.
Epididymitis in a male who is sexually active is most often caused by C trachomatis or N gonorrhoeae. Epididymitis caused by Escherichia coli occurs among males who are the insertive partners during anal intercourse and in males who have urinary tract abnormalities.
Epididymitis presents as a constellation of pain, swelling, and inflammation of the epididymis. In many cases, the testis is also involved.
B. Laboratory and Diagnostic Studies
Diagnosis is generally made clinically. Color Doppler ultrasound can help make the diagnosis. Although often not available, radionuclide scanning of the scrotum is the most accurate method of diagnosis. Laboratory evaluation is identical to evaluation for suspected urethritis.
Acute epididymitis must be distinguished from orchitis due to infarct, testicular torsion, viral infection, testicular cancer, tuberculosis, or fungal infection.
Infertility is rare, and chronic local pain is uncommon.
Empiric therapy (see Table 44–1) is indicated before culture results are available. As an adjunct to therapy, bed rest, scrotal elevation, and analgesics are recommended until fever and local inflammation subside. Lack of improvement of swelling and tenderness within 3 days requires reevaluation of both the diagnosis and therapy. Sex partners should be evaluated and treated for gonorrhea and chlamydial infections.
PROCTITIS, PROCTOCOLITIS, & ENTERITIS
Proctitis occurs predominantly among persons who participate in anal intercourse. Enteritis occurs among those whose sexual practices include oral-fecal contact. Proctocolitis can be acquired by either route depending on the pathogen. Common sexually transmitted pathogens causing proctitis or proctocolitis include C trachomatis (including lymphogranuloma venereum [LGV] serovars), Treponema pallidum, HSV, N gonorrhoeae, Giardia lamblia, and enteric organisms. As many as 85% of rectal infections with N gonorrhoeae and C trachomatis are asymptomatic. The presence of symptomatic or asymptomatic proctitis may facilitate the transmission of HIV infection.
Proctitis, defined as inflammation limited to the distal 10–12 cm of the rectum, is associated with anorectal pain, tenesmus, and rectal discharge. Acute proctitis among persons who have recently practiced receptive anal intercourse is most often sexually transmitted. The symptoms of proctocolitis combine those of proctitis, plus diarrhea or abdominal cramps (or both), because of inflamed colonic mucosa more than 12 cm from the anus. Enteritis usually results in diarrhea and abdominal cramping without signs of proctitis or proctocolitis.
B. Laboratory and Diagnostic Studies
Evaluation may include anoscopy or sigmoidoscopy, stool examination, culture or NAAT for appropriate organisms, and serology for syphilis.
Management will be determined by the etiologic agent (see Table 44–1 and Chapter 42). Reinfection may be difficult to distinguish from treatment failure.
Adolescent girls may have a normal physiologic leukorrhea, secondary to turnover of vaginal epithelium. Infectious causes of discharge include T vaginalis, C trachomatis, N gonorrhoeae, and bacterial vaginosis pathogens. Candidiasis is a yeast infection that produces vaginal discharge, but is not usually sexually transmitted. Vaginitis in general may have produced vaginal discharge, vulvar itching, and irritation. Discharge may be white, gray, or yellow. Physiologic leukorrhea is usually white, homogeneous, and not associated with itching, irritation, or foul odor. Mechanical, chemical, allergic, or other noninfectious irritants of the vagina may cause vaginal discharge.
Bacterial vaginosis is a polymicrobial infection of the vagina caused by an imbalance of the normal bacterial vaginal flora. The altered flora has a paucity of hydrogen peroxide–producing lactobacilli and increased concentrations of anaerobic bacteria (Prevotella spp and Mobiluncus spp), Gardnerella vaginalis, Ureaplasma, and Mycoplasma. It is unclear whether bacterial vaginosis is sexually transmitted, but it is associated with having multiple sex partners and women with bacterial vaginosis are at increased risk for other STIs.
The most common symptom is a copious, malodorous, homogeneous thin gray-white vaginal discharge. Patients may report vaginal itching or dysuria. A fishy odor may be most noticeable after intercourse or during menses, when the high pH of blood or semen volatilizes the amines.
Bacterial vaginosis is most often diagnosed by the use of clinical criteria, which include (1) presence of thin, white discharge that smoothly coats the vaginal walls, (2) fishy (amine) odor before or after the addition of 10% KOH (whiff test), (3) pH of vaginal fluid greater than 4.5 determined with narrow-range pH paper, and (4) presence of “clue cells” on microscopic examination. Clue cells are squamous epithelial cells that have multiple bacteria adhering to them, making their borders irregular and giving them a speckled appearance. Diagnosis requires three out of four criteria, although many female patients who fulfill these criteria have no discharge or other symptoms.
Bacterial vaginosis during pregnancy is associated with adverse outcomes such as premature labor, preterm delivery, intra-amniotic infection, and postpartum endometritis. In the nonpregnant individual, it may be associated with PID and urinary tract infections.
All female patients who have symptomatic disease should receive treatment to relieve vaginal symptoms and signs of infection (see Table 44–1). Pregnant patients should receive treatment to prevent adverse outcomes of pregnancy. Treatment for patients who do not complain of vaginal discharge or itching, but who demonstrate bacterial vaginosis on routine pelvic examination, is unclear. Because some studies associate bacterial vaginosis and PID, the recommendation is to have a low threshold for treating asymptomatic bacterial vaginosis. Follow-up visits are unnecessary if symptoms resolve. Recurrence of bacterial vaginosis is not unusual. Follow-up examination 1 month after treatment for high-risk pregnant patients is recommended.
Males do not develop infection equivalent to bacterial vaginosis and are often asymptomatic. Treatment of male partners has no effect on the course of infection in females but treatment is recommended for women who have sex with women.
G: Diagnosis and management of bacterial vaginosis and other types of abnormal vaginal bacterial flora: a review. Obstet Gynecol Surv 2010;65:462
Trichomoniasis is caused by T vaginalis, a flagellated protozoan that infects 3.7 million people annually in the United States.
Fifty percent of females with trichomoniasis develop a symptomatic vaginitis with vaginal itching, a green-gray malodorous frothy discharge, and dysuria. Occasionally postcoital bleeding and dyspareunia may be present. The vulva may be erythematous and the cervix friable.
Mixing the discharge with normal saline facilitates detection of the flagellated protozoan on microscopic examination (wet preparation). This has a sensitivity of only 60%–70% even with immediate evaluation of the slide to achieve optimal results. Culture and NAAT testing are available when the diagnosis is unclear. NAAT tests are sensitive, but expensive, and not readily available. Two FDA-approved, point-of-care antigen-based detection assays for T vaginalis are available, but false positive results are problematic in low disease prevalence populations. Both antigen assays are performed on vaginal secretions and have a sensitivity greater than 83% and a specificity greater than 97%. Trichomonal urethritis frequently causes a positive urine leukocyte esterase test and WBCs on urethral smear.
Trichomonas infection in females has been associated with adverse pregnancy outcomes. Male partners of females diagnosed with trichomoniasis have a 22% chance of having trichomoniasis. Half of males with trichomoniasis will have urethritis. Male partners should receive empiric therapy for trichomoniasis. Rescreening for T vaginalis at 3 months following initial infection is recommended for women due to the high rate of reinfection.
See Table 44–1 for treatment recommendations.
et al: Trichomonas vaginalis
vaginitis in obstetrics and gynecology practice: new concepts and controversies. Obstet Gynecol Surv 2013;68:43
: Modern diagnosis of Trichomonas vaginalis
infection. Sex Transmitted Infect 2013;89(6):424–428
3. Vulvovaginal Candidiasis
Vulvovaginal candidiasis is caused by Candida albicans in 85%–90% of cases. Most females will have at least one episode of vulvovaginal candidiasis in their lifetime, and almost half will have two or more episodes. The highest incidence is between ages 16 and 30 years. Predisposing factors include recent use of antibiotics, diabetes, pregnancy, and HIV. Risk factors include vaginal intercourse, especially with a new sexual partner, use of oral contraceptives, and use of spermicide. This disease is usually caused by unrestrained growth of Candida that normally colonizes the vagina asymptomatically or is infected secondarily from Candida present in the GI tract. Recurrences reflect reactivation of colonization.
Typical symptoms include pruritus and a white, cottage cheese-like vaginal discharge without odor. The itching is more common midcycle and shortly after menses. Other symptoms include vaginal soreness, vulvar burning, vulvar edema and redness, dyspareunia, and dysuria (especially after intercourse).
The diagnosis is usually made by visualizing yeast or pseudohyphae with 10% KOH (90% sensitive) or Gram stain (77% sensitive) in the vaginal discharge. Fungal culture can be used if symptoms and microscopy are not definitive or if disease is unresponsive or recurrent. However, culture is not very specific as colonization is common in asymptomatic females. Vaginal pH is normal with yeast infections.
The only complication of vulvovaginal candidiasis is recurrent infections. Most females with recurrent infection have no apparent predisposing or underlying conditions.
Short-course topical formulations effectively treat uncomplicated vaginal yeast infections (see Table 44–1). The topically applied azole drugs are more effective than nystatin. Treatment with azoles results in relief of symptoms and negative cultures in 80%–90% of patients who complete therapy. Oral fluconazole as a one-time dose is an effective oral treatment. Patients should be instructed to return for follow-up visits only if symptoms persist or recur. Six-month prophylaxis regimens have been effective in many female patients with persistent or recurrent yeast infection. Recurrent disease is usually due to C albicans that remains susceptible to azoles, and should be treated for 14 days with oral azoles. Some nonalbicans Candida will respond to itraconazole or boric acid gelatin capsules (600 mg daily for 14 days) intravaginally. Treatment of sex partners is not recommended, but may be considered for females who have recurrent infection.
In the United States, young, sexually active patients who have genital ulcers have genital herpes or syphilis. The relative frequency of each disease differs by geographic area and patient population; however, in most areas, genital herpes is the most prevalent of these diseases. More than one of these diseases could be present in a patient with genital ulcers. All ulcerative diseases are associated with an increased risk for HIV infection. Oral and genital lesions may be presenting symptoms during primary HIV infection (acute retroviral syndrome). Less common causes of genital ulceration include chancroid and donovanosis.
Location of the ulcers is dependent on the specific type of sexual behavior. Ulcers may be vaginal, vulvar, cervical, penile, or rectal. Oral lesions may occur concomitantly with genital ulcerations or as stand-alone lesions in HSV infection and syphilis. Each etiologic agent has specific characteristics that are described in the following sections. Lesion pain, inguinal lymphadenopathy, and urethritis may be found in association with the ulcers.
1. Herpes Simplex Virus Infection
HSV is the most common cause of visible genital ulcers (See Also Chapter 40). HSV-1 is commonly associated with infections of the face, including the eyes, pharynx, and mouth. However, each serotype is capable of infecting either region. HSV-1 infections are frequently established in children by age 5 through oral acquisition; lower socioeconomic groups have higher infection rates. Both HSV-1 and HSV-2 cause STIs. The prevalence of both infections in the United States increases during teen years. In this age group and young adults, HSV-1 has become the predominant cause of genital infection. Rates of HSV-2 seroprevalence reach 20%–40% in 40-year-olds. HSV infections are lifelong as a result of latent infection of sensory ganglia, although many individuals infected with either type of HSV infection have not been diagnosed because of mild or unrecognized symptoms. Nevertheless, these individuals can still asymptomatically shed virus and thereby unknowingly transmit the infection, and they can reactivate the virus to cause clinical infection in themselves.
Symptomatic initial genital HSV infection causes vesicles of the vulva, vagina, cervix, penis, rectum, or urethra, which are quickly followed by shallow, painful ulcerations. Atypical presentation of HSV infection includes vulvar erythema and fissures. Urethritis may occur. Initial infection can be severe, lasting up to 3 weeks, and be associated with fever and malaise, as well as localized tender adenopathy. The pain and dysuria can be extremely uncomfortable, requiring sitz baths, topical anesthetics, and occasionally catheterization for urinary retention.
Symptoms tend to be more severe in females. Recurrence in the genital area with HSV-2 is likely (65%–90%). Approximately 40% of individuals infected with HSV-2 will experience at least six recurrences per year in the early years after initial infection. Prodromal pain in the genital, buttock, or pelvic region is common prior to recurrences. Recurrent genital herpes is of shorter duration (5–7 days), with fewer lesions and usually no systemic symptoms. Commonly, there is a decrease in the frequency of recurrences over time, although approximately one-third of individuals fail to demonstrate this improvement. First-episode genital herpes infection caused by HSV-1 is usually the consequence of oral-genital sex. Primary HSV-1 infection generally is as severe as HSV-2 infection, and treatment is the same. Recurrence of genital HSV-1 is less frequent than genital HSV-2. Genital HSV-1 occurs in less than 50% of patients.
Diagnosis of genital HSV infection is often made presumptively, but in one large series this diagnosis was incorrect for 20% of cases. Cell culture and PCR testing are the CDC’s preferred methods of testing. NAAT is more sensitive. Direct immunofluorence assays are available, but lack sensitivity.
Genital HSV infections must be distinguished from other ulcerative STI lesions, including syphilis, chancroid, and lymphogranuloma venereum (LGV). Non-STIs might include herpes zoster, Behçet syndrome, or lichen sclerosis. (See next two sections Syphilis and Chancroid.)
Complications, almost always only with the first episode of genital HSV infection, include viral meningitis, urinary retention, transmission to newborns at birth, and pharyngitis. Infection with genital HSV, whether active or not, greatly increases the likelihood of transmitting or acquiring HIV infection within couples discordant for HIV.
All patients with active lesions should be counseled to abstain from sexual contact. Almost all patients have very frequent periodic asymptomatic shedding of HSV, and most cases of genital HSV infection are transmitted by persons who are unaware that they have the infection or are asymptomatic when transmission occurs. Reactivation with asymptomatic shedding occurs even in individuals who were asymptomatically infected. Individuals with prior HSV infection should be encouraged to use condoms to protect susceptible partners. Antiviral prophylaxis of infected individuals reduces shedding and significantly reduces the chance of transmission to their sexual partners.
Antiviral drugs administered within the first 5 days of primary infection decrease the duration and severity of HSV infection (see Table 44–1). The effect of antivirals on the severity or duration of recurrent disease is limited. For best results, therapy should be started with the prodrome or during the first day of the attack. Patients should have a prescription at home to initiate treatment. If recurrences are frequent and cause significant physical or emotional discomfort, patients may elect to take antiviral prophylaxis on a daily basis to reduce the frequency (70% decrease) and duration of recurrences. Treatment of first or subsequent attacks will not prevent future attacks, but recurrence frequency and severity decrease in many individuals over time.
CDC: Sexually transmitted diseases treatment guideline, 2015. MMWR 6(3): 2015.
Syphilis is an acute and chronic STI caused by infection with Treponema pallidum. The national rate of syphilis has increased annually since reaching an all-time low in 2000. Increases have been observed in both genders, but predominantly in males who have sex with men, who now account for 82% of primary and secondary cases reported to the CDC. In 2015, the CDC reported an increase of 19% in new cases of primary and secondary syphilis, and the rate among men aged 15–19 years was the highest reported since 1995. Men between the ages of 20 and 24 years have the highest rates of syphilis. Nearly 50% of the cases of syphilis in MSM in 2015 were also living with HIV.
Skin and mucous membrane lesions characterize the acute phase of primary and secondary syphilis. Lesions of the bone, viscera, aorta, and central nervous system predominate in the chronic phase (tertiary syphilis) (see Chapter 42). Prevention of syphilis is also important because syphilitic mucosal lesions facilitate transmission of HIV.
Primary syphilis usually presents as a solitary chancre at the point of inoculation. Characteristically, the chancre presents as a painless, indurated, nonpurulent ulcer with a clean base and associated nontender, firm adenopathy. The chancre appears on average 21 days (range: 3–90 days) after exposure and resolves spontaneously 4–8 weeks later. Because it is painless, it may go undetected, especially if the lesion is within the vagina, oropharynx, urethra, or rectum. Chancres may occur on the genitalia, anus, or oropharynx. Secondary syphilis occurs 4–10 weeks after the chancre appears, with generalized malaise, adenopathy, and a nonpruritic maculopapular rash that often includes the palms and soles. Secondary syphilis resolves in 1–3 months, but can recur. Verrucous lesions known as condylomata lata may develop on the genitalia. These must be distinguished from genital warts.
If the patient has a suspect primary lesion, is at high risk, is a contact, or may have secondary syphilis, a nontreponemal serum screen—either RPR or VDRL—should be performed. If the nontreponemal test is positive, then a specific treponemal test—a fluorescent treponemal antibody-absorbed (FTA-ABS) or microhemagglutination–T pallidum (MHA-TP) test—is done to confirm the diagnosis.
If a patient is engaging in high-risk sexual behavior or is living in an area in which syphilis is endemic, RPRs should be drawn yearly to screen for asymptomatic infection. Annual RPR testing among high-risk groups is essential to distinguish between early latent syphilis (1 year or less postinfection), late latent syphilis (> 1 year postinfection), or syphilis of unknown duration, as treatment recommendations vary. Syphilis is reportable to state health departments, and all sexual contacts need to be evaluated. Patients also need to be evaluated for other STIs, especially HIV. People with HIV have increased rates of failure with some treatment regimens and treatment of the HIV infection should occur as soon as indicated after diagnosis.
Untreated syphilis can lead to tertiary complications with serious multiorgan involvement, including aortitis and neurosyphilis. Transmission to the fetus can occur from an untreated pregnant individual (see Chapters 2 and 42).
See Table 44–1 for treatment recommendations. Patients should be reexamined and serologically evaluated with nontreponemal tests at 6 and 12 months after treatment. If signs or symptoms persist or recur, or patients do not have a fourfold decrease in their nontreponemal test titer, they should be considered to have failed treatment or be reinfected and need retreatment.
Chancroid is caused by Haemophilus ducreyi. It is relatively rare outside of the tropics and subtropics, but is endemic in some urban areas in the United States, and has been associated with HIV infection, drug use, and prostitution. Coinfection with syphilis or HSV occurs in as many as 17% of patients. A detailed history, including travel, may prove to be important in identifying this infection.
The typical lesion begins as a papule that erodes after 24–48 hours into an ulcer. The ulcer is painful and has ragged, sharply demarcated edges and a purulent base (unlike syphilis). The ulcer is typically solitary and somewhat deeper than HSV infection. The lesions may occur anywhere on the genitals and are more common in men than in women. Tender, fluctuant (unlike syphilis and HSV) inguinal adenopathy is present in 50% of patients. A painful ulcer in combination with suppurative inguinal adenopathy is very often chancroid.
Gram stain shows gram-positive cocci arranged in a boxcar formation. Culture, which has a sensitivity of less than 80%, can be performed on a special medium that is available in academic centers. NAAT testing may improve laboratory diagnosis in areas where such testing is available.
Chancroid is distinguished from syphilis by the painful nature of the ulcer and the associated tender suppurative adenopathy. HSV vesicles often produce painful ulcers, but these are multiple, smaller, and shallower than chancroid ulcers. Adenopathy associated with initial HSV infection does not suppurate. A presumptive diagnosis of chancroid should be considered in a patient with typical painful genital ulcers and regional adenopathy when the test results for syphilis and HSV are negative.
Symptoms improve within 3 days after therapy (see Table 44–1). Most ulcers resolve in 7 days, although large ulcers may take 2 weeks to heal. All sexual contacts need to be examined and given treatment, even if asymptomatic. Individuals with HIV coinfection may have slower rates of healing or treatment failures.
4. Lymphogranuloma Venereum
Lymphogranuloma venereum (LGV), caused by C trachomatis serovars L1, L2, or L3, is generally rare in the United States. The disease is endemic in Southeast Asia, the Caribbean, Latin America, and areas of Africa. Since 2003, an increased number of cases in the United States, Western Europe, and Canada have occurred primarily among men who have sex with men and have been associated with HIV coinfection.
Patients with LGV present with a painless vesicle or ulcer that heals spontaneously, followed by the development of tender adenopathy that is typically unilateral. A classic finding is the groove sign—an inguinal crease created by concomitant involvement of inguinal and femoral nodes. These nodes become matted and fluctuant and may rupture. LGV can cause proctocolitis with rectal ulceration, purulent anal discharge, fever, tenesmus, and lower abdominal pain, primarily in men who have sex with men.
Diagnosis of LGV can be difficult. It generally requires a clinical suspicion based on physical examination findings. Lesion swabs and lymph node aspirates can be tested for Chlamydia by culture, DFA, or NAAT. NAAT is not FDA cleared for rectal specimens. Additional genotyping is necessary to differentiate LGV from non-LGV serovars of Chlamydia. In the absence of laboratory testing to confirm the diagnosis, one should treat for LGV if clinical suspicion is high.
Differential diagnosis during the adenopathy phase includes bacterial adenitis, lymphoma, and cat-scratch disease. Differential diagnosis during the ulcerative phase encompasses all causes of genital ulcers.
See Table 44–1 for treatment recommendations. Despite the effectiveness of azithromycin for non-LGV chlamydial infections, there have been no controlled treatment trials to recommend its use in LGV. HIV-infected individuals are treated the same as non-HIV infected individuals, but should be monitored closely to assess response to treatment.
JA: Manifestations and management of lymphogranuloma venereum. Curr Opin Infect Dis 2009;22:57
Granuloma inguinale, or donovanosis, is caused by Klebsiella granulomatis, a gram-negative bacillus that is rare in the United States, but is endemic in India, the Caribbean, and southern Africa. An indurated subcutaneous nodule erodes to form a painless, friable ulcer with granulation tissue. Diagnosis is based on clinical suspicion and supported by a Wright or Giemsa stain of the granulation tissue that reveals intracytoplasmic rods (Donovan bodies) in mononuclear cells. See Table 44–1 for treatment recommendations. Relapse may occur 6–18 months after apparently effective treatment with a 3-week course of doxycycline.
GENITAL WARTS & HUMAN PAPILLOMAVIRUS
Condylomata acuminata, or genital warts, are caused by HPV, which can also cause cervical dysplasia and cervical cancer, and oropharyngeal and anal cancers. HPV is transmitted sexually. An estimated 20 million people in the United States are infected annually with HPV, including approximately more than 9 million sexually active adolescents and young adults 15–24 years of age. The majority (74%) of new HPV infections occurs among those 15–24 years of age; in females younger than age 25 years, the prevalence ranges between 28% and 46%. It is estimated that 32%–50% of adolescent females having sexual intercourse in the United States have HPV infections, though only 1% may have visible lesions. Thirty to 60% of males whose partners have HPV have evidence of condylomata on examination. An estimated 1 million new cases of genital warts occur every year in the United States.
Although there are almost 100 serotypes of HPV, types 6 and 11 cause approximately 90% of genital warts, and HPV types 16 and 18 cause more than 70% of cervical dysplasia and cervical cancer. The infection is more common in persons with multiple partners and in those who initiate sexual intercourse at an early age.
Pap smears should be obtained starting at age 21 and then every 3 years. More frequent and earlier evaluations are recommended if there are additional risk factors such as coinfection with HIV.
For males, verrucous lesions are found on the shaft or corona of the penis. Lesions also may develop in the urethra or rectum. Lesions do not produce discomfort. They may be single or found in clusters. Females develop verrucous lesions on any genital mucosal surface, either internally or externally, and often develop perianal lesions.
External, visible lesions have unique characteristics that make the diagnosis straightforward. Condylomata acuminata can be distinguished from condylomata lata (syphilis), skin tags, and molluscum contagiosum by application of 5% acetic acid solution. Acetowhitening is used to indicate the extent of cervical infection.
Pap smears detect cervical abnormalities. HPV infection is the most frequent cause of an abnormal smear. Pap smear findings are graded by the atypical nature of the cervical cells. These changes range from atypical squamous cells of undetermined significance (ASCUS) to low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL). LSIL encompasses cellular changes associated with HPV and mild dysplasia. HSIL includes moderate dysplasia, severe dysplasia, and carcinoma in situ.
Follow-up for ASCUS is controversial, as only 25% progress to dysplasia, and the remainder is stable or regress. Updated recommendations prefer repeat cytology in 12 months with no HPV DNA testing. If a test for HPV DNA is performed and is positive, then repeat cytology in 12 months is recommended. If the grade of the atypical squamous cells remains uncertain or if there is HSIL, colposcopy is recommended. If LSIL is detected, colposcopy is not needed, but a repeat Pap smear should be done in 1 year, and if LSIL or HSIL are subsequently detected, the patient should be referred for colposcopy for direct visualization or biopsy of the cervix (or both). If a Pap smear shows signs of inflammation only, and concomitant infection such as vaginitis or cervicitis is present, the smear should be repeated after the inflammation has cleared.
The differential diagnosis includes normal anatomic structures (pearly penile papules, vestibular papillae, and sebaceous glands), molluscum contagiosum, seborrheic keratosis, and syphilis.
Because genital warts can proliferate and become friable during pregnancy, many experts advocate their removal during pregnancy. HPV types 6 and 11 can cause laryngeal papillomatosis in infants and children. Complications of appropriate treatment include scarring with changes in skin pigmentation or pain at the treatment site. Pap smears with persistent or high-grade dysplasia require biopsy and/or resection, which may result in cervical abnormalities that complicate pregnancy. Cervical cancer is the most common and important sequelae of HPV and persistent cervical dysplasia.
The use of condoms significantly reduces, but does not eliminate, the risk for transmission to uninfected partners. The quadrivalent HPV vaccine is 96%–100% effective in preventing HPV-6 and 11–related genital warts and HPV-16 and 18–related cervical dysplasia. It is recommended for females aged 9–26 years and males aged 9–21 years. Males are protected against genital warts and anal cancer, which has a significantly increased incidence in males who practice anal sex. A 9-valent vaccine which contains an additional five valent serotypes has now replaced the quadrivalent vaccine (see Chapter 10).
Penile and external vaginal or vulvar lesions can be treated topically. Treatment may need to occur weekly for 4–6 weeks. An experienced practitioner should treat internal and cervical lesions (see Table 44–1). Treatment may clear the visible lesions, but not reduce the presence of virus, nor is it clear whether transmission of HPV is reduced by treatment.
Warts may resolve or remain unchanged if left untreated or they may increase in size or number. Treatment can induce wart-free periods in most patients. Most recurrences occur within the 3 months following completion of a treatment regimen. Appropriate follow-up of abnormal Pap smears is essential to detect any progression to malignancy.
ASCCP Consensus Guidelines for Management of Abnormal Cervical Cytology. Available at: http://www.asccp.org
Accessed June 6, 2017.
WK: Human papillomavirus: what every provider should know. Am J Obstet Gyn 2013;208:169
et al: Risk factors and other epidemiologic considerations for cervical cancer screening: a narrative review for the U.S. Preventive Services Task Force. Ann Intern Med 2011;155:698
In the United States, viral hepatitis is linked primarily to three viruses: hepatitis A (HAV), hepatitis B (HBV), and hepatitis C (HCV) (See also Chapter 22). Each virus has the potential to be spread through sexual activity. HAV is spread via fecal-oral transmission and oral-anal contact. Both HBV and HCV are spread through contact with blood or body fluids. Sexual transmission of HBV is believed to be much more efficient than that of HCV although recent data has suggested increased transmission of HCV in MSM.
Universal immunization recommendations for HAV and HBV have contributed to the decline in the prevalence of these diseases. However, individuals born before implementation of routine vaccination, especially those in high-risk groups (multiple sexual partners or men who have sex with men), should receive vaccination.
2. Human Immunodeficiency Virus
In 2015, 22% of new HIV infections in the United States occurred in youth and young adults aged 13–24 years (See also Chapter 41). Data suggest that adolescents and young adults are less likely to be aware of their HIV infection than older individuals with HIV. Because of the long latency period between infection with HIV and progression to AIDS, it is felt that many HIV-positive young adults contracted HIV during adolescence. CDC incidence data indicate that young men who have sex with men continue to be the highest-risk group, particularly young men of color. Young women account for approximately one-third of the infections in this age group with black and Hispanic women bearing a disproportionate burden of the disease. Risk factors for contracting HIV include a prior STI, infrequent condom use, practicing insertive or receptive anal sex (both males and females), prior genital HSV infection, practicing survival sex (ie, trading sex for money or drugs), intravenous drug or crack cocaine or crystal methamphetamine use, homelessness, and being the victim of sexual abuse (males).
HIV infection should be considered in all sexually active youth, whether they have sex with males, females, or both. The CDC and the United States Preventative Services Task Force recommend adolescents be offered HIV testing at least once. Individual risk factors should then be used to determine the frequency of repeat testing. Opportunities for HIV screening in adolescents should include STI screening or treatment, pregnancy testing, or routine health evaluations. Most states allow adolescents to consent to HIV testing and treatment, but providers should be aware of their particular State’s laws.
Adolescents may be asymptomatic with recent HIV infection or may present with the acute retroviral syndrome, which is evident 2–6 weeks after exposure. The acute clinical syndrome, which occurs in about 50% of patients, is generally indistinguishable from other viral illnesses with respect to fever, malaise, and upper respiratory symptoms. Distinguishing features include generalized lymphadenopathy, rash, oral and genital ulcerations, aseptic meningitis, and thrush. After the acute illness, signs and symptoms may be absent for many years.
In 2014, the CDC updated its recommendations for HIV screening. The new recommendations are based on the availability of technologies that allow for earlier detection of HIV infection than offered by ELISA followed by Western Blot confirmation. The new testing algorithm for serum or plasma recommends the use of an HIV 1/2 antigen/antibody combination immunoassay for initial testing. This test detects antibodies to both HIV-1 and HIV-2 and the HIV-1 p24 antigen. This detects both established infections and more recent infections.
If acute HIV infection is suspected, HIV testing should be done by HIV RNA PCR testing or HIV DNA PCR testing. Routine serological testing may not be positive for 2-3 weeks or longer. Viral load values of less than 10,000 copies/mL by RNA PCR may indicate a false positive in this setting and repeat testing would be indicated.
The most important aspect of identifying adolescents and young adults with HIV infection is linking them to care. Data support the treatment of youth with HIV infection in care settings that provide comprehensive, multidisciplinary care. These settings will be best equipped to provide emotional support, preventative care, risk reduction for contacts, access to research, and guidance on the appropriate timing of antiretroviral therapies.
Centers for Disease Control and Prevention; Association of Public Health Laboratories: Laboratory Testing for the Diagnosis of HIV Infection: Updated Recommendations. Available at: http://dx.doi.org/10.15620/cdc.23447
. Published June 27, 2014. Accessed May 26, 2017.
: Screening for HIV: U.S. Preventative services task force recommendation statement. Ann Intern Med 2013;159(3):161–168
3. HIV Postsexual Exposure Prophylaxis
Adolescents may present to health care providers seeking nonoccupational HIV postexposure prophylaxis (nPEP) following an assault or a high-risk sexual encounter. The risk of acquiring HIV infection through sexual assault or abuse is low but present. The risk for HIV transmission from a positive contact per episode of receptive penile-anal sexual exposure is estimated at 0.5%–3%; the risk per episode of receptive vaginal exposure is estimated at less than 0.1%–0.2%. HIV transmission also occurs from receptive oral exposure, but the risk is unknown. The risk of HIV transmission may be increased in certain conditions: traumatic vaginal, anal, or oral penetration; site of exposure to ejaculate; HIV viral load in ejaculate; duration of HIV infection in the assailant or partner; and presence of an STI, prior genital HSV infection, or genital lesions in either partner. The risk is greatly reduced if the contact is successfully receiving antiretroviral therapy.
Health care providers that consider offering nPEP should take into account the likelihood that exposure to HIV occurred, the potential benefits and risks of such therapy, and the interval between the exposure and initiation of therapy. It will be helpful to know the HIV status of the sexual contact. The CDC provides an algorithm for consideration of nPEP. In general, nPEP is not recommended when more than 72 hours have passed since exposure. If the patient decides to take nPEP, clinical management should be implemented according to published CDC guidelines. Providers should be aware that structural barriers exist to obtaining nPEP, and that adolescent assault victims have a high discontinuation rate due to adverse effects from the medication.
Centers for Disease Control and Prevention: Antiretroviral postexposure prophylaxis after sexual, injection-drug use, or other nonoccupational exposure to HIV in the United States: recommendations from the U.S. Department of Health and Human Services. MMWR Recomm Rep 2005;54(RR–2):1–20
KH: Practical guidance for nonoccupational postexposure prophylaxis to prevent HIV infection: an editorial review. AIDS 2014;28(11):1545–1554
4. HIV Preexposure Prophylaxis (PrEP)
In 2014, the US Public Health Service released guidance on the use of PrEP in the United States. The guidance followed the Food and Drug Administration’s approval of a coformulated HIV antiretroviral (tenofovir and emtricitabine) for use as preexposure prophylaxis based on data from two large international trials. The approval for use does not include individuals under age 18 years. Initial studies to determine safety and acceptability in younger individuals at high risk for HIV acquisition revealed high rates of acceptability but adherence dropped as intervals between study visits lengthened suggesting that increased adherence support may be needed. Providers considering the use of PrEP in a minor at risk of infection should consult with an experienced prescriber and know the laws of their particular state with respect to providing preventive HIV medication without parental consent.
et al: An HIV preexposure prophylaxis demonstration project and safety study for young MSM. J Acquir Immune Defic Syndr 2017;74(1):21–29
Pthirus pubis, the pubic louse, lives in pubic hair. The louse or the nits can be transmitted by close contact from person to person. Patients complain of itching and may report having seen the insect. Examination of the pubic hair may reveal the louse crawling around or attached to the hair. Closer inspection may reveal the nit or sac of eggs, which is a gelatinous material (1–2 mm) stuck to the hair shaft. See Table 44–1 for treatment recommendations.
Sarcoptes scabiei, the causative organism in scabies, is smaller than the louse. It can be identified by the classic burrow, which is created by the organism laying eggs and traveling just below the skin surface. Scabies can be sexually transmitted by close skin-to-skin contact and can be found in the pubic region, groin, lower abdomen, or upper thighs. The rash is intensely pruritic, especially at night, erythematous, and scaly. See Table 44–1 for treatment options. Ivermectin is an oral therapeutic option for scabies that may hold particular promise in the treatment of severe infestations or in epidemic situations. When treating with lotion or shampoo, the entire area needs to be covered for the time specified by the manufacturer. One treatment usually clears the infestation, although a second treatment may be necessary. Bed sheets and clothes must be washed in hot water. Both sexual and close personal or household contacts within the preceding month should be examined and treated.
PA: Scabies and pediculosis pubis: an update of treatment regimens and general review. Clin Infect Dis 2007;44:S153