Vaginitis and Sexually Transmitted Diseases Part 3

Treatment

Because the diagnosis of PID can be challenging, the sequelae of PID can be severe, and treatment is safe and inexpensive, all patients suspected of having PID should undergo treatment for PID. The CDC recommends initiating treatment of PID in all sexually active young women with adenexal tenderness or cervical motion tenderness.8 These criteria are likely to be sensitive, but they are also quite nonspecific.

Table 4 Treatment Regimens for Pelvic Inflammatory Disease

Route

Regimen

Cefotetan, 2 g I.V. q. 12 hr

or

Cefoxitin, 2 g I.V. q. 6 hr

plus

Doxycycline, 100 mg p.o. or I.V. q. 12 hr

Clindamycin, 900 mg I.V. q. 8 hr

plus

Gentamicin, 2 mg/kg I.V. or I.M. once, then 1.5 mg/kg I.V. q. 8 hr (single daily dose may be used)

Parenteral

Ofloxacin, 400 mg I.V. q. 12 hr

or

Levofloxacin, 500 mg I.V. q.d.

plus

Doxycycline, 100 mg p.o. or I.V. q. 12 hr

with or without

Metronidazole, 500 mg I.V. q. 8 hr

or

Ampicillin-sulbactam, 3 g I.V. q. 6 hr


Oral

Ofloxacin, 400 mg p.o., b.i.d.

or

Levofloxacin, 500 mg I.V. q.d. for 14 days

with or without

Metronidazole, 500 mg p.o., b.i.d., for 14 days

Ceftriaxone, 250 mg I.M. once

or

Cefoxitin, 2 g I.M. once with probenecid, 1 g p.o.

plus

Doxycycline, 100 mg b.i.d. for 14 days

with or without

Metronidazole, 500 mg p.o., b.i.d., for 14 days

*Parenteral therapy can be discontinued after the patient improves clinically, but doxycycline should be continued for 14 days.

Treatment for PID is directed against C. trachomatis, N. gonor-rhoeae, gram-negative facultative anaerobes, vaginal anaerobes, and streptococci. Numerous regimens have been found acceptable [see Table 4].Patients should show significant improvement within 3 days after starting therapy. Those receiving oral therapy should be reevaluated within 72 hours. Treatment should include efforts to ensure that sexual partners also receive therapy. In addition, patients with Chlamydia or N. gonorrhoeae infections should be rescreened for those infections 10 to 18 weeks after treatment.

Complications

Although the vast majority of women with PID in developed nations recover fully, long-term sequelae are common; these sequelae include tubal infertility, ectopic pregnancy, and chronic pelvic pain. In the largest study of PID sequelae performed to date, Swedish investigators performed laparoscopy on 1,730 women with suspected PID and then followed them for a mean of 6.9 years. After a single episode of PID, 8% of patients suffered tubal infertility, compared with 1% of control subjects in whom there was no laparoscopic evidence of PID. Of PID patients who subsequently became pregnant, 10% had an ectopic pregnancy, compared with 1% of women without PID. Similarly, pelvic pain lasting longer than 6 months occurred in 17% of women with PID but in only 2% of control subjects.107 Recurrent episodes of PID multiplied the risk of sequelae [see Figure 2], as did more severe PID and longer duration of symptoms before treatment.

Genital Ulcer Disease

Genital ulcers are a frequent presentation of STDs. Epidemio-logic studies, as well as studies measuring HIV shedding, suggest that genital ulcer disease (GUD) increases the risk of both HIV acquisition and HIV transmission.3,108 As a result, the prevention and treatment of GUD is a high public health priority.

Etiology

Herpes, syphilis, and chancroid are the major causes of genital ulcer disease. Less common causes of GUD include lym-phogranuloma venereum (infection with L-serotypes of C. tra-chomatis), donovanosis (infection with Calymmatobacterium gran-ulomatis), superinfection of ectoparasitic infections, trauma, neoplasm, Behcet syndrome, Reiter syndrome, and fixed drug eruptions (e.g., from doxycycline or sulfonamides).

Herpes is the most common cause of GUD in developed nations. In the United States in 2000, over two million people sought care for genital herpes. In contrast, a total of 5,979 cases of primary and secondary syphilis and 82 cases of chancroid were reported to the CDC.28 A 1996 study of 516 STD clinic patients with genital ulcers found that 62% had HSV, 10% had syphilis, 3% had both syphilis and herpes, 3% had chancroid, and 22% had no identified pathogen.

Proportion of women experiencing an ectopic pregnancy or tubal infertility by number of episodes of pelvic inflammatory disease (PID) among 1,282 patients with PID and 448 control subjects.

Figure 2 Proportion of women experiencing an ectopic pregnancy or tubal infertility by number of episodes of pelvic inflammatory disease (PID) among 1,282 patients with PID and 448 control subjects.

Table 5 Clinical Features and Laboratory Diagnosis of Genital Ulcers

Disease

Etiology

Incubation Period

Number of Lesions

Primary Lesion Type

Ulcer Diameter

Ulcer Characteristics

Pain or Tenderness

Lymphadenopathy

Laboratory Diagnosis

Syphilis

Treponema pallidum

9-90 days

Usually one

Papule

5-15 mm

Superficial or deep; sharply demarcated; indurated; nonvascular, purulent base

Uncommon

Firm, nontender, bilateral

Darkfield microscopy, RPR/VDRL and FTA, MHA-TP

Herpes

HSV-1 or -2

2-7 days

Multiple, may coalesce

Vesicle

1-2 mm

Superficial; erythematous edges, no induration

Frequently tender

Firm, tender, small; often bilateral with first episode

DFA, culture, serology

Chancroid

Haemophilus ducreyi

1-14 days

Multiple, may coalesce

Pustule

Variable

Deep; irregular, undermined edges; purulent base bleeds easily

Usually tender

Tender, may be fluctuant, loculated; usually unilateral

Culture of ulcer base,* NAAT (e.g., PCR, LCR, TMA, SDA)

LGV

L-serotypes of Chlamydia trachomatis

3 days to 6 wk

Usually one

Papule, pustule, or vesicle

2-10 cm

Very rarely seen, because of rapid healing; can be superficial, deep, elevated, round, or oval

Variable

Tender, may suppurate or form sinus tracts; loculated, usually unilateral; more common in men than women

Culture, PCR, microimmuno-fluorescent antibody

Donovanosis

Calymmato-bacterium granulomatis

1-4 wk (up to 6 mo)

Variable

Papule

Variable

Extensive, indolent ulcer with granulation tissue; elevated, rolled irregular edges on raised ulcer; beefy-red vascular base bleeds easily+

Uncommon

None; pseudobuboes

Giemsa or Wright stain of tissue smear

*Culture of material from bubo seldom positive.

+Less common variants can be hypertrophic, necrotic, or sclerotic.

DFA—direct fluorescent antibody

HSV—herpes simplex virus

LGV—lymphogranuloma venereum

LCR—ligase chain reaction

MHA-TP—microhemagglutination as-say-T. pallidum

NAAT—nucleic acid amplification test

PCR—polymerase chain reaction

RPR—rapid plasma reagin

SDA—strand displacement amplification

TMA—transcription-mediated amplification

VDRL—Venereal Disease Research Laboratory

Traditionally, chancroid and syphilis have been the most common cause of genital ulcers in most developing nations. However, recent studies undertaken in sub-Saharan Africa have documented the increasing importance of herpes as a cause of GUD, particularly in areas where HIV is highly prevalent.

Diagnosis

Clinical Manifestations

When examining patients with genital ulcers, clinicians should note the number and depth of lesions; the presence of vesicles, induration, necrotic material on the ulcer bed, or an undermined ulcer border (i.e., the ulcer invades beneath the superficial edges); the presence or absence of pain; and any associated adenopathy [see Table 5]. Although physical findings can be helpful, different GUD etiologies cannot be reliably distinguished by physical examination alone.111

Laboratory Tests

Because physical findings are unreliable, clinical assessment should be supported by laboratory evaluation. The laboratory evaluation of GUD typically concentrates on herpes and syphilis. Chancroid, donovanosis, or LGV should be considered if the patient lives in or has traveled to an area where one of those infections is common or if the physical findings are highly suggestive of one of those infections.

When possible, laboratory evaluation should include dark-field microscopy, serologic testing for syphilis (e.g., rapid plasma reagin [RPR] or venereal disease research laboratory (VDRL); and fluorescent treponemal antibody [FTA] or microhemagglutina-tion assay for antibody to T. pallidum), and culture for herpes. If available, RPR should be performed. Dark-field microscopy is 70% to 95% sensitive in detecting treponemes, but sensitivity is highly dependent on the expertise of the technician. Culture should seek to distinguish between HSV-1 and HSV-2, because the former typically produces a less severe infection with fewer recurrences. This is particularly important in light of recent data that suggest that HSV-1 is an increasingly common cause of genital herpes.112 If initial evaluation does not establish a cause of genital ulcers and the clinician’s suspicion for chancroid, LGV, or donovanosis remains low, further diagnostic efforts should focus on ruling out genital herpes. Several type-specific serologic tests that target the HSV glycoprotein G-2 (gG-2) are now available.113 Patients who have no serologic evidence of HSV-2 may have primary infections. Only limited data are available on how soon se-roconversion can be detected by commercially available type-specific tests, but the median time from exposure to seroconver-sion appears to be 2 to 3 weeks. Patients with a clinical syndrome consistent with genital herpes who test negative for HSV-2 should be retested after 6 to 12 weeks if an intervening recurrence of genital ulcers does not establish the diagnosis of HSV infection and the clinical suspicion for genital herpes is high. Older HSV serologic tests are neither sensitive nor specific and should not be used. Clinicians should be aware that type-specific serologic tests have not been studied extensively for HSV-2 screening. Given the imperfect specificity of these tests, it is likely that widespread testing in populations in which the prevalence of HSV-2 is low will result in large numbers of false positive test results. Because of poor specificity, a positive HSV-2 serologic test result in a patient without signs or symptoms of genital herpes or definite exposure to HSV-2 should be interpreted with caution.

Treatment

Treatment of patients with genital ulcers is usually empirical [see Table 6]. If patients have physical findings suggestive of syphilis, are residents of or recent travelers to areas where syphilis remains common, or are members of groups at high risk for syphilis (e.g., men who have sex with men, as well as commercial sex workers or their clients), treatment should include benzathine penicillin G, 2.4 million units intramuscularly, and a regimen for genital herpes [see Table 7]. If the suspicion for syphilis is low and follow-up can be ensured, initial empirical treatment can focus on genital herpes alone. The treatment and follow-up of patients with genital herpes and syphilis are discussed in other subsections.

Patients with genital herpes should be counseled about the recurrent nature of the infection and advised that subclinical viral shedding is common. The median recurrence rate in the first year after HSV-2 acquisition is 0.33 recurrences monthly.114 During the first 6 months after HSV-2 acquisition, virus can be isolated by culture on 6% of days and by PCR on 20% to 35% of days.115 It is not known to what extent HSV can be transmitted by patients whose cultures are negative and whose PCR results are positive. The American Social Health Association Web site (http://www.ashastd.org) is an excellent source of information on STD in general and genital herpes in particular, and it has information on support services for persons with genital herpes.

STDs in Men Who Have Sex with Men and Anorectal STDs in Women

Although surveillance data on STDs in men who have sex with men (MSM) are limited, cases of gonorrhea and syphilis in MSM in selected cities in the United States declined by more than 10-fold in the decade following the first recognition of AIDS.116 More recently, numerous cities in the United States and Europe have reported rising rates of STDs in MSM.30,117 Limited data suggest that HIV transmission may also be increasing.118 Because STDs can enhance HIV transmission, the control of STDs in MSM is a public health priority. Moreover, an STD can be a sentinel event, alerting the clinician to a patient’s risk of acquiring HIV infection or transmitting it to others.

General considerations in msm

Several aspects of the care of MSM merit consideration. First, it is imperative that clinicians adopt a nonjudgmental, direct approach when discussing sexual behavior. In addition to the questions typically included in a sexual history, clinicians should ask patients about the HIV status of their sexual partners and about their anal sexual exposure. The latter can be determined by asking, "Are you a top, a bottom, or both a top and a bottom?" The term top refers to a man who practices insertive anal sex; a bottom practices receptive anal sex.

Second, the spectrum of STD is wider in MSM than in heterosexuals. Several pathogens that are rarely sexually transmitted among heterosexuals are relatively common causes of STD in MSM. These include hepatitis A virus, Shigella species, Salmonella species, Campylobacter species, Giardia lamblia, and Entamoeba histolytica. Strongyloides stercoralis and Enterobius vermicularis are occasionally transmitted sexually in MSM.

Table 6 Treatment of Genital Ulcers

Disease

Regimen

Syphilis

Benzathine penicillin G, 2.4 million U I.M.*

Chancroid

Azithromycin, 1 g p.o. once

or

Ceftriaxone, 250 mg I.M. once

or

Ciprofloxacin, 500 mg p.o., b.i.d., for 3 days

or

Erythromycin, 500 mg p.o., t.i.d., for 7 days

Lymphogranuloma venereum

Doxycycline, 100 mg p.o., b.i.d., for 21 days

Doxycycline, 100 mg p.o. for at least 3 wk or until lesion is healed

Donovanosis

or

Trimethoprim-sulfamethoxazole, double strength (800 mg/160 mg), one tablet p.o., b.i.d., for at least 3 wk or until lesion is healed

Herpes

See Table 7

Note: treatment should always include evaluation and treatment of sexual partners.

*For primary or secondary syphilis.

Third, the anus is a more common sexual organ for MSM than it is for heterosexuals. Consequently, STD should figure prominently in the differential diagnosis of MSM who present with anorectal symptoms, and rectal screening should be part of standard STD screening in MSM.24 Finally, although there are no guidelines for regular STD screening of heterosexual men, the CDC currently recommends annual STD screening for MSM [see Table 1].8

Proctitis, proctocolitis, and enteritis

Although anorectal STD occurs in both men and heterosexual women, anal STD syndromes are more common in MSM. The symptoms of anorectal infection vary, depending on the level and extent of anatomic involvement and on the microbiologic etiology.119 Proctitis is limited to the rectum. It results from direct inoculation of pathogens through anal sex and presents as some combination of rectal pain, constipation, hematochezia, tenes-mus, and mucopurulent rectal discharge. Sexually transmitted proctitis is caused by gonorrhea, chlamydial infection (non-LGV), syphilis, or HSV. In proctocolitis, the inflammatory process extends to the colon. As a result, in addition to the symptoms of proctitis, patients may complain of diarrhea, abdominal pain, and bloating or nausea. Most cases of proctocolitis result from oral-genital or oral-anal sex (anilingus, or so-called rimming) and are caused by Shigella, Salmonella, or Campylobacter species; E. histolytica; or LGV serovars of C. trachomatis. G. lamblia infection involves the small bowel alone (enteritis) and typically presents as diarrhea, abdominal pain, and bloating or nausea in the absence of rectal symptoms. The differential diagnosis in patients presenting with symptoms of colitis or proctocolitis should include Clostridium difficile infection and inflammatory bowel disease. In persons with HIV infection and CD4+ T cell counts less than 50/mm3, cytomegalovirus infection is also a possibility. Depending on their level of immunosuppression, HIV-infected patients presenting with enteritis should also be evaluated for Mycobacterium avium complex, cryptosporidium, Isospora belli, Cyclospora cayetanensis, and Microsporidia organisms.

Table 7 Treatment of Genital Herpes in Immunocompetent Patients

Primary herpes

Acyclovir, 400 mg p.o., t.i.d., for 7-10 days

or

Valacyclovir, 1 g p.o., b.i.d., for 7-10 days

or

Famciclovir, 250 mg p.o., t.i.d., for 7-10 days

Recurrent herpes

Acyclovir, 800 mg p.o., b.i.d., for 5 days

or

Acyclovir, 800 mg p.o., t.i.d., for 2 days

or

Valacyclovir, 1g p.o., q.d., for 5 days

or

Valacyclovir, 500 mg p.o., b.i.d., for 3-5 days

or

Famciclovir, 125 mg p.o., t.i.d., for 5 days

Diagnosis

History and Physical Examination

Evaluation of a patient with anorectal symptoms should include questions about anal, oral-genital, and oral-anal sex and condom use. In the evaluation, an attempt should be made to differentiate symptoms of proctitis, proctocolitis, and enteritis. Physical examination should include a careful anal examination, digital rectal examination, and anoscopy directed toward finding ulcers consistent with HSV or syphilis, condylomata lata, or rectal discharge or bleeding.

Laboratory Tests

If a rectal exudate is present, a Gram stain should be performed to look for gonorrhea. The reported sensitivity of Gram stain is highly variable (30% to 79%).120 In one study, rectal Gram stain specimens obtained by anoscopy were more sensitive in detecting gonorrhea than were those obtained blindly (53% versus 79%).120 In men without rectal symptoms, however, anoscop-ically obtained rectal cultures do not appear to be more sensitive in detecting gonorrhea than those obtained by blindly inserting a swab 2 to 3 cm into the rectum.121

Laboratory evaluation in patients with suspected proctitis or proctocolitis should include cultures for gonorrhea and chlamy-dial infection, a serologic test for syphilis, and a rapid syphilis test. Rectal ulcers or lesions should be cultured for HSV; when possible, a specimen should be obtained for dark-field evaluation. If symptoms suggest proctocolitis, stool specimens should be obtained for enteric pathogens and E. histolytica. Patients with recent antibiotic exposures should also be tested for C. difficile. Stool Giardia antigen testing should be performed if enteritis is suspected.

Treatment

In general, treatment should be directed by laboratory findings. If patients with proctitis have severe symptoms or if follow-up cannot be ensured, empirical therapy should be directed against gonorrhea and chlamydial infection. The CDC recommends treatment with ceftriaxone, 250 mg intramuscularly, and doxycycline, 100 mg a day orally for 7 days. Alternative therapies for gonorrhea (cefixime, 400 mg orally or ciprofloxacin, 500 mg orally once) and chlamydial infection (azithromycin, 1 g orally once) are probably effective but have not been studied. Clinicians should have a low threshold for adding empirical therapy for herpes to this regimen.

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