- Email: [email protected]
Gynecologic infections
Emerg Med Clin N Am 21 (2003) 631–648
Gynecologic infections Wesley Zeger, DOa,b,*, Kurtis Holt, MDa a
Department of Emergency Medicine, Madigan Army Medical Center, Tacoma, WA 98431, USA b University of Washington, Department of Medicine, Division of Emergency Medicine, Box 356123, 1959 NE Pacific Street, Seattle, WA 98195-6123, USA
Gynecologic infections are a common reason for women to present to the mergency department. This article reviews the more common vulvo-vaginal infections, cervicitis, pelvic inflammatory disease, tubo-ovarian abscess, and the Fitz-Hugh–Curtis syndrome. Emphasis is placed on epidemiology, diagnosis, and management, as well as on comparing the pregnant and nonpregnant patient when appropriate.
Vulvo-vaginal infections Candida vulvovaginitis Candidal vaginal infections are primarily caused by Candida albicans, with other Candida spp. causing a minority of infections [1,2]. The risk of candidal vaginitis may be increased in women who are immunosuppressed or who recently used corticosteroids, antibiotics, or higher-dose estrogen oral contraceptives. In addition, women who use intrauterine devices and vaginal sponges also may be at increased risk [2,3]. Diagnosis is made by clinical symptoms and microscopy. Patients typically present with vulvovaginal pruritis, dyspareunia, dysuria, or white, curdlike discharge. On examination, the mucosa is typically erythematous and edematous. In addition, satellite lesions may be seen in the genital area. On microscopic evaluation, a normal pH (4–4.5) with hyphae, pseudohyphae, or budding yeast on the saline wet preparation or 10% potassium hydroxide preparation confirm fungal presence (Fig. 1). The role of culture in patients with signs and symptoms of candidal vaginitis but negative microscopy is * Corresponding author. Department of Emergency Medicine, Madigan Army Medical Center, Tacoma, WA 98431. E-mail address: [email protected] (W. Zeger). 0733-8627/03/$ - see front matter Ó 2003 Elsevier Inc. All rights reserved. doi:10.1016/S0733-8627(03)00039-7
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Fig. 1. Polarizing microscopy of multiple singlets and budding yeast (small arrows) belonging to the species Candida glabrata in a patient with a mixed infection and clue cells (large arrow) in vaginal secretions associated with bacterial vaginitis. (Copyright Ó 1997 Massachusetts Medical Society. All rights reserved. Reproduced with permission from Sobel JD. Vaginitis. N Engl J Med 1997;337:1896–1907.)
not clear [1–3]. Treatment with the azole class of drugs is the initial therapeutic recommendation [1–3]. Treatment with an intravaginal or oral antifungal medication is a matter of patient preference, because both are typically azole derivatives [2]. Recommended duration of intravaginal therapy is 3 to 7 days; fluconazole by mouth is a single dose [1]. Fluconazole should not be used during pregnancy. During pregnancy, current recommendations are for a 7-day course of topical therapy [1]. Bacterial vaginosis Although bacterial vaginosis is thought to be the most common cause of infectious vaginitis, its cause and pathogenesis are poorly understood. No single bacterial organism has been consistently identified, and it is thought to be a polymicrobial anaerobic infection [4–8]. Incidence rates range from 10% to 40%, depending on the population studied [2,4,5], with the epidemiologic data limited by sampling bias [5,6]. Nonetheless, infection with bacterial vaginosis is associated with significant morbidity. It can lead to upper genital tract infections including cervicitis and pelvic inflammatory disease [5,6,8] and has been associated with an increased risk of HIV infection [4,6,9]. In pregnant patients, there is a causal relationship between bacterial vaginosis and preterm delivery [4,10]. Other obstetric
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complications of bacterial vaginosis include intrapartum and postpartum infections as well as first trimester miscarriage [5,6,11]. Bacterial vaginosis can cause a thin, homogeneous, milklike vaginal discharge. Because up to 50% of infected women may be asymptomatic, however, diagnosis is primarily made by microscopy [5,6]. Classically, the diagnosis is made by the presence of three of the four Amsel criteria: 1. Homogeneous, thin vaginal fluid that adheres to vaginal walls 2. Vaginal fluid pH higher than 4.5 3. Release of amine odor with alkalinization of vaginal fluid (the so-called ‘‘whiff test’’) 4. Presence of vaginal epithelial cells with borders obscured with adherent, small bacteria (so-called ‘‘clue’’ cells) (see Fig. 1). Other diagnostic tests include Gram staining of vaginal fluid or secretions, DNA probes, and Femexam Amines Testcards (Cascade Health Care Products, Inc., Portland, OR) [2,5,7,8]. Currently, treatment should be provided for symptomatic nonpregnant women as well as for symptomatic and asymptomatic pregnant women. During pregnancy, treatment of asymptomatic patients reduces the incidence of preterm delivery and postdelivery infectious complications [1,3–6,12]. Prevention of preterm delivery is most apparent in high-risk patients (ie, those who have had a prior preterm delivery) [1,4–6]. Sexual partners do not need to be treated [1]. Primary treatment options for the nonpregnant patient are oral metronidazole (500 mg two times/day for 7 days), metronidazole (0.75% vaginal gel, 5 g once daily for 5 days), or 2% clindamycin vaginal cream (5 g once daily for 7 days) [1,5,13]. During pregnancy, the recommended primary treatment is oral metronidazole (250 mg three times/day for 7 days) or oral clindamycin (300 mg two times/day for 7 days) [1,5]. Intravaginal clindamycin cream should not be used during pregnancy because its use has been associated with an increase risk of preterm delivery [1]. Trichomonas vaginalis Trichomonas vaginalis, a parasite that is transmitted primarily through sexual activity [2,3,9], infects 2 to 3 million Americans annually [12]. In addition to the vaginal discomfort, trichomoniasis facilitates the transmission of HIV [2,3,9]. During pregnancy, infection has been associated with delivery of low birth weight infants and preterm deliveries [2,3,9,14]. Treatment of asymptomatic pregnant patients does not seem to decrease the incidence of preterm deliveries, however [14]. Trichomonas infection can cause vulvar irritation, dyspareunia, dysuria, urinary frequency, and a malodorous purulent vaginal discharge. Up to 50% of infections may be asymptomatic [9]. Physical examination may show an erythematous vaginal mucosa or punctate hemorrhages on the cervix.
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Diagnosis is typically made by identification of motile trichomonads on a saline wet preparation. Trichomonads, however, are seen in only 50% to 80% of confirmed cases using cultures as the criterion standard for diagnosis [2,3]. Cultures from a specialized parasite media have a sensitivity of 85% to 95%, but results are delayed [15]. Newer diagnostic methods such as DNA probes, monoclonal antibody kits, and polymerase chain reaction (PCR) techniques provide rapid and more accurate results [2,9,15]. DNA probes and monoclonal antibody kits are about 90% sensitive and more than 99% specific. PCR techniques can use either vaginal swabs or urine and are more sensitive than culture techniques [15]. Current recommended therapy is oral metronidazole, 2 g as a single dose, or, alternatively, oral metronidazole, 500 mg two times/day for 7 days [1]. Patients allergic to metronidazole should be referred for desensitization according to recommendations from the 2002 Centers for Disease Control and Prevention (CDC) guidelines [1]. Sanford [16] recommends the following as an alternate therapy: intravaginal paromomycin cream (250 mg daily for 2 weeks), zinc sulfate douches, or oral tinidazole (500 mg four times/day) plus intravaginal tinidazole (500 mg two times/day) for 14 days. Pregnant patients should be treated with oral metronidazole, 2 g as a single dose [1]. This therapeutic option is controversial in the first trimester, and these patients should be referred to their obstetrician [1,2]. Sexual partners should be treated [1]. Herpes vulvo-vaginitis Herpes simplex virus-1 (HSV-1) and Herpes simplex virus-2 (HSV-2) are the most common herpes viruses causing genital infections. Additionally, herpes virus is the most common cause of genital ulcers [1]. It was long thought that only HSV-2 could cause a genital infection, but now it is well known that HSV-1 is implicated in causing up to 15% to 30% of genital infections [17]. Both HSV-1 and HSV-2 are spread following contact with infectious secretions. Thus oral-to-oral, oral-to-genital, and genital-togenital contacts are all associated with the development of herpes virus infection. Herpes virus infection rates are on the rise. The national prevalence of infection with HSV-2 rose 30% between 1978 and 1991, with 22% of the population older than 12 years of age infected by the early 1990s [18]. White teenagers and young adults had the largest increase. It seems as though, aside from HIV, genital herpes will be the most concerning sexually transmitted disease by 2010 [19]. A primary episode is defined as genital herpes with the absence of antibodies to HSV-1 and HSV-2. It is classically associated with systemic symptoms including headache, fever, malaise, and other flulike symptoms. Recurrent infections are more typical with HSV-2: as many as 95% of persons infected with HSV-2 have recurrences within 1 year of primary infection, whereas only 50% of HSV-1 infections recur [20]. This difference
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presumably results from the difficulty HSV-1 has in establishing latency in the sacral ganglia. Most recent estimates indicate that approximately 10% of patients with history and physical examination suggesting first-episode genital herpes have serologic evidence of previous infection [21]. Furthermore, as many as 70% of people infected with HSV lack symptoms [22], but HSV can be isolated and transmitted from the genital tract during these socalled symptomatic periods. Transmission is highly variable; some persons contract the virus after only one exposure, whereas others do not contract the virus despite years of unprotected sexual activity [23]. Transmission from a mother to her baby during vaginal delivery is relatively rare (<3%). Vertical transmission, however, increases to around 30% in women who develop genital HSV in the third trimester because protective antibodies are unable to develop before delivery [24]. Diagnosis Patients with primary genital herpes can be systemically ill with fever, headache, malaise, abdominal pain, and myalgias; however, one third of patients with a primary outbreak are not systemically ill [25]. The lesions are painful and often described as burning [1]. With primary outbreaks, the genital lesions are typically longer lasting, more numerous, and more painful. The symptoms usually begin 1 to 4 weeks after exposure. The lesions begin as vesicles and then rupture, exposing the ulcerated base. Ulcerated lesions persist for 1 to 2 weeks, crust, and heal without scars. Cervical lesions are present up to 90% of the time, along with extravaginal lesions. The average time from onset of lesions to complete healing is usually around 3 weeks. Genital herpes may be the most frequent cause of previously undiagnosed genitourinary complaints, because dysuria can be present in up to 80% of cases [25,26]. The clinical picture of HSV-1 and HSV-2 genital infections is indistinguishable. Recurrent attacks tend to be subtler in presentation and are the most frequently seen outbreaks in the emergency department. The patient presents to the emergency department thinking this is the primary outbreak, when actually the patient contracted the virus months to years previously. The patient may or may not complain of the classic prodromal symptoms of burning, pain, and itching. Immunodeficiency, trauma, fever, or sexual intercourse can precipitate a recurrence [27]. Persistent stressors tend to be more likely to trigger an outbreak rather than transient mood states or short-term stressors or life changes [28]. The type-specific herpes culture has replaced the Tzanck smear as the criterion for diagnosing herpes infection. Some recommend that a virus culture and also type-specific HSV serology be done on the initial visit, because the serology is important to predict the risk for the number and possibility of recurrent outbreaks. Realistically, if the patient has good follow-up, virus cultures may be done in the emergency department, and serology done at follow-up. Because the herpes virus is the most common
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cause of urogenital complaints in the emergency department, women presenting with unexplained urogenital complaints should have an extensive genito-urinary examination. First-time outbreaks (either primary or nonprimary) of HSV ulcers yield virus in 80% of cases, whereas ulcers from recurrent infections are positive 40% of the time [29]. Equally as important, however, is the need for screening for treponemal antibodies (syphilis) in the emergency department evaluation. A significant number of patients who present with a typical herpes infection are later found to have syphilis [30]. Treatment Other than prevention and patient education, antiviral medications are the mainstay of treatment. These medications can be used for Symptomatic management only, to improve lesion healing and to reduce symptoms Episodic antiviral therapy for recurrence Continuous antiviral therapy to prevent recurrent attacks. Of the three antiviral agents, acyclovir has the most comprehensive longterm safety data. The advantage of the other antiviral agents is their simpler dosing schedule [31]. They are generally effective only if given within 48 hours of symptom onset. Episodic treatment is generally not as effective as continuous therapy to reduce recurrent attacks and shedding. Only patients who have six or more recurrences per year are considered as candidates for continuous antiviral therapy [32]. The treatment regimen for initial episodes of initial genital HSV infection is oral acyclovir, 200 mg five times daily for 10 days, or 400 mg three times daily for 10 days. Oral famciclovir, 250 mg three times daily, or oral valacyclovir HCL, 1 g twice daily, offer a more convenient dosing schedule but at a higher cost and unproven safety data. Resiquimod, a new topical agent that acts as an immunity-enhancing agent, seems promising in phase I and II trials. These studies indicate that, if applied within 24 hours of prodromal symptom onset, resiquimod can significantly shorten the duration of symptoms and lengthen the time between recurrences [33]. There has long been hope that an effective and safe herpes vaccine would be developed, but currently, none exists. Special patient populations Pregnant patients. Genital herpes is acquired for the first time during pregnancy in 2% to 3% of the general obstetric population [34]. If acquired during pregnancy, the herpes virus poses little threat to the fetus as long as HSV seroconversion has been completed by the time of labor [35]. The most important points for the emergency physician are [35] A patient with a new diagnosis of genital herpes should be referred as soon as possible to her obstetrician. A patient presenting with evidence of genital herpes and rupture of membranes should be referred immediately for delivery.
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Not every pregnant patient with genital herpes needs a cesarean section. Pregnant patients often have a subtle presentation. The antiviral medications are generally thought to be safe in pregnancy but should only be used if within 48 hours of onset of symptoms and for the most symptomatic of patients. Postpartum mothers with active genital herpes are able to handle their newborns and do not require isolation, but they must wash their hands frequently and before handling their newborns. HIV-positive patients. As with most other sexually transmitted diseases, herpes is a well-known and important cofactor in the transmission of HIV. Many believe that people infected with the herpes virus should also be screened for HIV. There is evidence to suggest that HSV infection increases HIV transcription and plasma viral load, which may adversely affect the clinical course of HIV disease [36]. Also, the immunosuppression associated with HIV can increase the rate of subclinical HSV shedding in both men and women. HIV-positive patients should be treated with intravenous acyclovir (5 mg/kg) if their CD4 count is below 200 and severe or disseminated disease is present. Other conditions possibly necessitating intravenous therapy include urinary retention or inability to tolerate oral therapy for any reason. Bartholin’s gland cyst and abscess Bartholin’s glands are bilateral vulvo-vaginal bodies located in the labia minora at approximately the 4 o’clock and 8 o’clock positions on the posterolateral aspect of the vestibule. Normally pea-sized and draining through a 2.5-cm duct into a fold between the hymeneal ring and the labium, they can become cystic and subsequently form abscesses. Growing rapidly, the cysts can be a source of extreme pain and discomfort. Patients are usually 20 to 30 years old, and by the time they have decided to come to the emergency department, they are indeed in a great deal of pain. The predominant organisms associated with these abscesses are anaerobic and most commonly include Bacteroides fragilis and Peptostreptococcus. About 10% to 15% of the time Neisseria gonorrhoeae is the causative agent. Chlamydia trachomatis is involved less frequently [37]. Patients who are in enough discomfort to necessitate a visit to the emergency department will most likely present with an abscess. The management is as follows [38]: local anesthesia and sterile preparation is followed by a scalpel stab incision, approximately 1.0 to 1.5 cm long, deep into the abscess from inside the labium because an outside incision can cause a permanent fistula. Following the incision and drainage, a hemostat is used to break up all the loculations. A Word catheter is then placed. The balloon tip is inserted into the abscess and inflated with water or lubricating gel. The free end is then tucked into the vagina [39]. Simple incision and drainage without Word catheter placement may be inadequate and lead to
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a considerable number of recurrences of abscesses. Gynecologic followup should be arranged in 5 to 7 days for definitive management. Use of prophylactic antibiotics is not recommended unless there is significant surrounding cellulites or signs of systemic illness. Syphilis Syphilis is caused by the spirochete Treponema pallidum. The incidence of syphilis has declined from 20.1 cases per 100,000 in the late 1970s to 3.2 cases per 100,000 in 1997 [40]. This diagnosis should be considered in any patient who presents with an ulcerative lesion in the genital area. Primary syphilis manifests as a single, painless, clean-based ulcer, usually within 3 weeks but sometimes 2 to 3 months after infection. The labia and vaginal wall are most often affected, but lesions can occur on the cervix. Secondary syphilis is associated with the characteristic maculopapular generalized rash including the palms and soles. Arthralgias, pharyngitis, and lymphadenopathy are also seen. Secondary syphilis is typically seen 2 to 8 weeks after exposure. Tertiary syphilis develops in approximately 30% of untreated patients and presents with numerous neurologic, cardiovascular, and other systemic effects [41]. The diagnosis of syphilis should be entertained for patients with unexplained rashes, arthralgias, and neurologic or systemic complaints. Syphilis is initially screened for with a rapid plasma regain (RPR) or a Venereal Disease Research Laboratory (VDRL) test. Confirmatory testing is required for definitive diagnosis. Physicians should have a low threshold of suspicion to screen for this disease, because significant long-term morbidity can occur if not treated. Treatment for syphilis has changed little. Penicillin remains the mainstay of treatment. For primary or secondary syphilis, a single dose of penicillin G benzathine, 2.4 million units intramuscularly, is sufficient. Penicillin is the only acceptable therapy for patients who have neurosyphilis or are who are pregnant. Consequently, skin testing and desensitization are recommended for pregnant patients who have a true allergy to penicillin [1]. Acceptable second-line antibiotics for primary and secondary syphilis in the nonpregnant patient are doxycycline (100 mg two times/day for 10 days), erythromycin (500 mg four times/day for 14 days), or ceftriaxone (1 g/day intramuscularly for 8-10 days). For neurosyphilis, intravenous penicillin, 4 million units every 4 hours for 10 to 14 days, is recommended, along with admission [1,42].
Cervical infections The most common causes of cervicitis are C trachomatis and N gonorrhoeae, with C trachomatis being the most common [9]. Other implicated organisms include actinomycetes (classically, in patients using intrauterine devices), Mycomplasma hominis, Ureaplasma urealyticum,
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cytomegalovirus, tuberculosis, and other bacteria associated with bacterial vaginosis. Females between the ages 15 and 25 years are most commonly infected with these sexually transmitted bacteria [9], and infection rates in women with chlamydia are increasing, whereas those with gonorrhea are decreasing [43]. A recent epidemiologic study in Washington found adults between ages 40 and 80 years accounted for 9% of the cases of chlamydia and gonorrhea [44]. Complications of cervical infection include further spread to the upper genital tract and increased susceptibility to HIV infection [9]. Chlamydia and gonorrhea can cause dysuria, urinary frequency and urgency, pelvic pain, vaginal bleeding, and vaginal discharge. A recent prospective emergency department-based study found that up to 17% of women with a chief complaint of vaginal bleeding had cultures positive for C trachomatis, N gonorrhoeae, or both [45]. Mucopurulent cervicitis is often asymptomatic. Although it can be caused by C trachomatis or N gonorrhoeae, neither organism is isolated in most cases [1]. Thus, mucopurulent cervicitis is not a sensitive predictor of infection, because most patients with C trachomatis or N gonorrhoeae do not have mucopurulent cervicitis [1]. Pelvic examination may reveal a tender, friable cervix but can be completely normal. Therefore, a clinical diagnosis based on the probability of disease may be inaccurate and could result in a significant number of untreated women [46]. Diagnosis is based on laboratory confirmation. Historically, culture was the only way to confirm a diagnosis, but C trachomatis can be difficult to culture. Polymerase chain reaction and ligase chain reaction (LCR) methods have been shown to have a greater than 99% specificity for detection of C trachomatis and N gonorrhoeae in cervical, urethral, and urine specimens [9]. Health care providers should have an extremely low threshold of suspicion to seek confirmatory testing in any potential genital-urinary complaint. Treatment should be based on laboratory confirmation, with two exceptions. Empiric treatment for both gonorrhea and chlamydia should be given to patients with a high likelihood of disease and those likely to be lost to follow-up [1]. Sexual partners should be identified and treated. Patients should abstain from intercourse for 7 days after a single dose of antibiotics or after completion of a 7-day regimen [1]. Pregnant patients should have repeat testing 3 weeks after treatment to demonstrate efficacy [1]. Treatment regimens shown in Table 1 are based on the 2002 CDC guidelines [1].
Pelvic inflammatory disease Pelvic inflammatory disease (PID) afflicts about 11% of women in the United States [47,48]; adolescents are at a higher risk than adults [49]. Cohort data (with laparoscopically proven PID) have shown that women
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Table 1 CDC treatment guidelines for cervicitis Chlamydia trachomatis
Neisseria gonorrheoae
Primary
Aztyhromycin 1 g orally as a single does or Doxycycline 100 mg orally BID for 7 days
Cefixime 400 mg as a single dose or Ceftriaxone 125 mg IM as a single dose or Ciprofloxacin 500 mg as a single dose or Ofloxacin 400 mg as a single dose or Levofloxacin 250 mg orally as a single dose
Alternate
Erythromycin base 500 mg orally QID for 7 days or Ofloxacin 300 mg orally BID for 7 days or Levofloxacin 500 mg orally once daily for 7 days
Spectinomycin 2 g IM as a single dose
Pregnancy (primary)
Erythromycin base 500 mg orally QID for 7 days or Amoxicillin 500 mg orally TID for 7 days
Cefixime 400 mg orally as a single dose or Ceftriaxone 125 mg IM as a single dose
Pregnancy (alternate)
Azythromycin 1 g orally as single dose
Spectinomycin 2 g IM as a single dose
diagnosed with PID have an increased risk of infertility. About 40% of women are infertile after an initial infection, and 75% are infertile after a subsequent infection [47,50]. Additionally, 25% will develop chronic abdominal pain, and almost 10% will have an ectopic location with their first pregnancy [47,50]. In addition, C trachomatis commonly causes asymptomatic PID, and these patients are more likely to develop complications [49]. Patients using an intrauterine device may be a greater risk of developing PID than those who do not use any contraception [51]. Data on this topic are mixed, however, and a cause-effect relationship has not been established [51,52]. Although uncommon, PID can occur during pregnancy [53,54]. Retrospective data indicate that in pregnancy PID occurs most commonly in the first trimester, although it can occur later in pregnancy [53,54]. Overall, good epidemiologic and management data in the United States are sparse because of the difficulty in accurately identifying
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patients with PID and the high lost-to-follow-up rates in evaluating the sequelae of pelvic infections [47,55]. Diagnosis The clinical diagnosis of PID is often difficult [47,48]. Symptoms suggestive of PID include abdominal pain, dyspareunia, vaginal discharge, and abnormal vaginal bleeding. The presence of mucopurulent cervical discharge, or leukorrhea (more white blood cells than epithelial cells in four high-powered fields) in the vaginal vault has good sensitivity for PID but very poor specificity [48]. Although a complete blood cell count, erythrocyte sedimentation rate, or C-reactive protein test are often ordered as part the laboratory evaluation for diagnosing PID, their wide variability makes them unreliable, especially in the HIV-positive patient [56,57]. The criterion standard continues to be laparoscopy, but endometrial biopsy consistent with endometritis may also be reliable [47,48]. Ultrasonography is most useful in differentiating PID from a tubo-ovarian abscess [58,59]; however, free fluid in the pelvis, endometrial thickening, or distension of the endometrial cavity can be seen in PID [58]. In the emergency department setting, PID should be diagnosed in women with lower abdominal tenderness, cervical motion tenderness, and adenexal tenderness for which another cause is not likely [1,60], because laboratory results (ie, cultures, PCR, or LGR) are typically not available. Management The decision to admit patients with PID is controversial, and there are not any good studies on which to base decisions. The CDC guidelines, based on consensus opinion and observational studies, suggest hospitalization when [1]
Surgical emergencies such as appendicitis cannot be excluded The patient is pregnant The patient does not respond clinically to oral antimicrobial therapy The patient is unable to follow or tolerate an outpatient oral regimen The patient has severe illness, nausea and vomiting, or high fever The patient has a tubo-ovarian abscess.
The International Disease Society for Obstetrics and Gynecology-USA grades PID into four stages [61]. 1. Stage 1: lower abdominal pain, cervical motion tenderness, and adnexal tenderness and more than 1 minor criteria defined by the CDC Oral temperature greater than 101 F (greater than 38.3 C), Abnormal cervical or vaginal discharge Elevated erythrocyte sedimentation rate Elevated C-reactive protein
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Laboratory documentation of cervical infection with N gonorrhoeae or C trachomatis Stage 2: Stage 1 plus peritonitis Stage 3: Tubo-ovarian complex or abscess on physical examination or by ultrasonography Stage 4: Ruptured tubo-ovarian abscess. The Society recommends outpatient management for women with stage 1 disease with the exception of
Pregnant patients Adolescents Nulligravidae who desire future pregnancy Patients unable to take oral medication or be seen in follow-up.
Antibiotic therapy is also somewhat controversial, because PID can be polymicrobial [62]. Chlamydia trachomatis and N gonorrhoeae are isolated most frequently, but pathogens associated with bacterial vaginosis are also frequently isolated [8,49]. Bacterial vaginosis and plasma cell endometritis are more common in HIV-positive women, suggesting that adequate anaerobic coverage should be given in this population [56]. Furthermore, bacteria cultured from the cervix do not necessarily correlate to those isolated form the endometrium or fallopian tubes [49], and vice versa [63]. Current recommended antibiotic therapies (Table 2) are from the CDC 2002 guidelines. If outpatient therapy is chosen, patients should have follow-up reexamination in 48 to 72 hours [1].
Tubo-ovarian abscess Tubo-ovarian abscess (TOA) is a serious complication of pelvic inflammatory disease, and up to 15% will rupture, causing a surgical emergency [49]. It is the most common cause of an intra-abdominal abscess in premenopausal women [64]. Although up to one third of women hospitalized with PID develop a TOA, up to 50% of TOAs are not associated with PID [64]. Most TOAs consist of polymicrobic anaerobic bacteria [54,59,64,65]. HIV-positive women develop TOAs more frequently than HIV-negative women, and these abscesses also tend to be polymicrobic [56]. Although TOAs are uncommon in pregnancy, when they do occur, they are most common in the first trimester. Regarding second and third trimester abscesses, ‘‘it is with great hesitancy and often with great embarrassment, that the diagnosis pelvic inflammatory disease [referring to TOA] is made’’ [66]. It is not clear if patients using intrauterine devices are at increased risk for TOA [65]. In general, the pathogenesis of TOA has not been well elucidated, and TOA should remain in the differential even without a recent history of PID.
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Table 2 CDC guidelines for the treatment of PID
Primary
Outpatient
Inpatient
Regimen A Ofloxacin 400 mg PO bid for 14 days or Levofloxacin 500 mg PO once daily for 14 days with or without metronidazole 500 mg PO bid for 14 days Regimen B Ceftriaxone 250 mg IM once or Cefoxitin 2 g IM once and probenicid 1 g once orally, concurrently
Regimen A Cefotetan 2 g IV q 12 hrs or Cefoxitin 2 g IVq 6 hours plus Doxycycline 100 mg q 12 hours IV or PO Regimen B Clindamycin 900 mg IV q 8 hours plus Gentamicin IV/IM 2 mg/kg loading dose followed by 1.5 mg/kg IV q 8 hours (once daily dosing may be substituted)
plus doxycycline 100 mg PO BID for 14 days with or without metronidazole 500 mg PO bid for 14 days Alternate
Ofloxacin 400 mg IV q 12 hours or Levofloxacin 500 mg q 24 hours plus Doxycycline 100 mg q 12 hours IV or PO with or without Metronidazole 500 mg IV every 8 hours or Unasyn 3 g IV every 6 hours
Patients with a TOA typically have abdominal pain with severe tenderness, often with peritoneal signs on palpation [64]. Palpation on bimanual examination may be difficult because of pain. Thus, differentiation from stage 2 PID based on clinical examination is not reliable [64]. Fever may be absent. In addition, the white blood cell count, erythrocyte sedimentation rate, and C-reactive protein test can be normal, although they are usually elevated [59,64]. Definitive diagnosis is made by direct visualization or an imaging study. Pelvic ultrasound is the initial modality of choice with a reported sensitivity of 93% and specificity of 98% [64]. Computed tomography may be used to define the abscess better or may be appropriate if the ultrasound evaluation is inconclusive. Leukocyte scintigraphy may have a future role, but it has not been well studied [67].
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All patients with a TOA should be admitted. The choice of operative versus nonoperative management is left up to the consultant. Initial antibiotics should cover anaerobic and sexually transmitted bacteria. Recommended therapies include intravenous ofloxacin (400 mg every 12 hours) and metronidazole (500 mg every 8 hours) or intravenous ampicillin/sulbactam (3 g every 8 hours) and oral or intravenous doxycycline (100 mg every 12 hours) [16].
Fitz-Hugh–Curtis syndrome The Fitz-Hugh-Curtis syndrome was initially described in 1848 by a Danish surgeon Martinus Hassig. Thomas Fitz-Hugh and Arthur Curtis reported it in the English literature in the 1930s [68]. Data on Fitz-Hugh– Curtis syndrome are limited to reviews of case reports; thus epidemiologic, diagnostic, and management data are inherently flawed. Despite these limitations, Fitz-Hugh–Curtis syndrome is thought to be composed of two components. In the acute phase, patients have sharp right upper quadrant pleuritic pain that can radiate to the shoulder [68]. In the chronic phase, peritoneal adhesions form causing chronic abdominal pain (typically right upper quadrant) [68]. Tubal infection may or may not be concurrently present [68]. Although Fitz-Hugh-Curtis syndrome initially was thought to be caused exclusively by N gonorrhoeae pelvic infection, C trachomatis has emerged recently as the most reported causative bacteria [68,69,72,73]. Classically, it has mimicked acute cholecystitis, pneumonia, and pulmonary embolism but has also presented with unilateral or bilateral flank pain mimicking renal colic, colonic ileus, left upper quadrant pain (perisplenitis), and epigastric pain mimicking a perforated peptic ulcer [68,69,72,73]. Complications are uncommon, but subdiaphragmatic abscess, small bowel obstruction, and unnecessary surgery have been described [68]. Diagnosis is difficult because the index of suspicion needs to be high, and because there is no standard for diagnosis. In general, the diagnosis should be considered in patients with upper abdominal pain and normal routine investigations, specifically of the gallbladder and liver function tests [68]. Although one case series describes a sample of patients with elevated liver function tests, this patient population included a significant number of patients with a history of hepatitis or intravenous drug abuse [68]. Furthermore, this case series (small overall compared with the whole case series) is the only one to describe abnormal liver function tests as common in the presentation of Fitz-Hugh–Curtis syndrome [68]. Fever has been invariably present in case series, as has an elevated white blood cell count [68,69,72,73]. Abdominal pain, cervicitis, or PID may be present on pelvic examination, but the examination can be unremarkable [68,69,72,73]. Cervical cultures are typically positive but have been negative in a variable portion of patients in which N gonorrhoeae or C trachomatis grew out from
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intraperitoneal cultures [68]. Adhesions and perihepatic ascites may be visualized by ultrasonography or computed tomographic scan, but these imaging modalities have not been studied in Fitz-Hugh–Curtis syndrome and thus should not be relied on for definitive diagnosis [70,72]. Fitz-Hugh– Curtis syndrome is diagnosed clinically in patients with upper abdominal pain without another cause, a genital infection (symptomatic or asymptomatic), and cultures positive for N gonorrhoeae or C trachomatis. Although the incidence of adhesions varies between 25% and 100% [71,72], the current standard for diagnosis is the presence of laparoscopically visualized adhesions and positive cervical or abdominal cultures [68,72]. The goal of treatment is to prevent chronic abdominal pain. Current treatment involves bacterial eradication with antibiotics and surgical lysis of adhesions. Based on case reports, patients should be treated with antibiotics if they have symptomatic genital infections and upper abdominal pain or asymptomatic genital infections, upper abdominal pain, and positive cultures. There are no formal antibiotic recommendations. Doxycycline and penicillin (320,000 units given as a single dose intramuscularly) are most commonly reported; however, penicillin was used before resistance to penicillin became common [68,69,72–74]. Duration of therapy for doxycycline has ranged from 10 days to 4 weeks. Thus, a reasonable antibiotic regimen is oral doxycycline for 14 days plus ceftriaxone (250 mg given in a single dose intramuscularly) or oral ofloxacin (400 mg two times/day) plus oral metronidazole (500 mg two times/day) for 14 days. Patients should be referred for evaluation and management of adhesions. Summary The scope of gynecologic infections presenting to the emergency department is quite diverse. This article presents an update on the current literature for vaginitis, cervicitis, pelvic inflammatory disease, tubo-ovarian abscesses, the Fitz-Hugh-Curtis syndrome, herpes, and syphilis. Inadequate identification or treatment of these diseases can result is significant morbidity or mortality for the patient and for the fetus. References [1] American College of Obstetricians and Gynecologists practice bulletin. Management of herpes in pregnancy. Number 8, October 1999. Clinical management guidelines for obstetrician-gynecologists. Int J Gynaecol Obstet 2000;68:165–73. [2] Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2002. MMWR Morb Mortal Wkly Rep 2002;51:1–78. [3] Summary of notifiable diseases, United States, 1997. MMWR Morb Mortal Wkly Rep 1002;46: ii–vii, 3–87. [4] Ashley RL, Corey L. HSV type specific antibody tests: patients are ready, are clinicians? Genitourin Med 1997;73:235–6. [5] Barton SE. Herpes management and prophylaxis. Dermatol Clin 1998;16:799–803.
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[6] Benedetti J, Corey L, Ashley R. Recurrence rates in genital herpes after symptomatic firstepisode infection. Ann Intern Med 1994;121:847–54. [7] Blanchard AC, Pastorek II JG, Weeks T. Pelvic inflammatory disease during pregnancy. South Med J 1987;80:1363–5. [8] Blumstein H. Incision and drainage. In: Roberts J, Hedges JR, editors. Clinical procedures in emergency medicine. 3rd edition. Philadelphia: WB Saunders; 1998. p. 646–7. [9] Brown ZA. Genital herpes complicating pregnancy. Dermatol Clin 1998;16:xiv, 805–10. [10] Brown ZA, Selke S, Zeh J, et al. The acquisition of herpes simplex virus during pregnancy. N Engl J Med 1997;337:509–15. [11] Carey JC, Klebanoff MA, Hauth JC, et al. Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. N Engl J Med 2000;342:534–40. [12] Centers for Disease Control and Prevention. 1998 guidelines for treatment of sexually transmitted diseases. MMWR Morb Mortal Wkly Rep 1998;47:1–111. [13] Centers for Disease Control and Prevention. Sexually transmitted diseases surveillance, 1997. Atlanta: US Department of Health and Human Services; 1998. p. 143. [14] Cohen F, Kemeny ME, Kearney KA, et al. Persistent stress as a predictor of genital herpes recurrence. Arch Intern Med 1999;159:2430–6. [15] Corey L. Raising the consciousness for identifying and controlling viral STDs: fears and frustrations–Thomas Parran Award Lecture. Sex Transm Dis 1998;25:58–69. [16] Counselman FL. An unusual presentation of Fitz-Hugh-Curtis syndrome. J Emerg Med 1994;12:167–70. [17] Sutton MY. Lower genital tract infections and HIV in women. Curr Infect Dis Rep 2000;2:539–45. [18] Diamond C, Selke S, Ashley R, et al. Clinical course of patients with serologic evidence of recurrent genital herpes presenting with signs and symptoms of first episode disease. Sex Transm Dis 1999;26:221–5. [19] Drake S, Taylor S, Brown D, et al. Improving the care of patients with genital herpes. BMJ 2000;321:619–23. [20] Emmert DH, Kirchner JT. Sexually transmitted diseases in women. Gonorrhea and syphilis. Postgrad Med 2000;107:181–4, 189–90, 193–7. [21] Ferris DG, Litaker MS, Woodward L, et al. Treatment of bacterial vaginosis: a comparison of oral metronidazole, metronidazole vaginal gel, and clindamycin vaginal cream. J Fam Pract 1995;41:443–9. [22] Fiorino AS. Intrauterine contraceptive device-associated actinomycotic abscess and Actinomyces detection on cervical smear. Obstet Gynecol 1996;87:142–9. [23] Fleming DT, McQuillan GM, Johnson RE, et al. Herpes simplex virus type 2 in the United States, 1976 to 1994. N Engl J Med 1997;337:1105–11. [24] Frenkel LM, Garratty EM, Shen JP, et al. Clinical reactivation of herpes simplex virus type 2 infection in seropositive pregnant women with no history of genital herpes. Ann Intern Med 1993;118:414–8. [25] Gareen IF, Greenland S, Morgenstern H. Intrauterine devices and pelvic inflammatory disease: meta-analyses of published studies, 1974–1990. Epidemiology 2000;11:589–97. [26] Gatt D, Heafield T, Jantet G. Curtis-Fitz-Hugh syndrome: the new mimicking disease? Ann R Coll Surg Engl 1986;68:271–4. [27] Gatt D, Jantet G. Perisplenitis and perinephritis in the Curtis-Fitz-Hugh syndrome. Br J Surg 1987;74:110–2. [28] Grimes DA. Intrauterine device and upper-genital-tract infection. Lancet 2000;356: 1013–9. [29] Hemsel DL, Ledger WJ, Martens M, et al. Concerns regarding the Centers for Disease Control’s published guidelines for pelvic inflammatory disease. Clin Infect Dis 2001; 32:103–7.
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[30] Hill DA, Lense JJ. Office management of Bartholin gland cysts and abscesses. Am Fam Physician 1998;57:1611–6, 1619–20. [31] Hillier SL, Nugent RP, Eschenbach DA, et al. Association between bacterial vaginosis and preterm delivery of a low- birth-weight infant. The Vaginal Infections and Prematurity Study Group. N Engl J Med 1995;333:1737–42. [32] Hoffman L, Ma OJ, Gaddis G, et al. Cervical infections in emergency department patients with vaginal bleeding. Acad Emerg Med 2002;9:781–5. [33] Hunt SM, Kincheloe BW, Schreier PC. Tubo-ovarian abscess in pregnancy. Obstet Gynecol 1974;43:57–60. [34] Kirchner JT, Emmert DH. Sexually transmitted diseases in women. Chlamydia trachomatis and herpes simplex infections. Postgrad Med 2000;107:55–8, 61–5. [35] Klebanoff MA, Carey JC, Hauth JC, et al. Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic Trichomonas vaginalis infection. N Engl J Med 2001;345:487–93. [36] Korn AP. Gynecologic care of women infected with HIV. Clin Obstet Gynecol 2001; 44:226–42. [37] Koumans EH, Kendrick JS. Preventing adverse sequelae of bacterial vaginosis: public health program and research agenda. CDC Bacterial Vaginosis Working Group. Sex Transm Dis 2001;28:292–7. [38] Larkin JA, Lit L, Toney J, et al. Recognizing and treating syphilis in pregnancy. Medscape Womens Health 1998;3:5. [39] Lepine LA, Hillis SD, Marchbanks PA, et al. Severity of pelvic inflammatory disease as a predictor of the probability of live birth. Am J Obstet Gynecol 1998;178:977–81. [40] Lopez-Zeno JA, Keith LG, Berger GS. The Fitz-Hugh-Curtis syndrome revisited. Changing perspectives after half a century. J Reprod Med 1985;30:567–82. [41] McCormick M, DelCastillo J, Berk RS. An atypical presentation of the Fitz-Hugh-Curtis syndrome. J Emerg Med 1990;8:55–8. [42] McGee D. Miscellaneous urologic conditions. In: Harwood-Nuss A, Wolfson A, Linden C, et al, editors. The clinical practice of emergency medicine. 3rd edition. Philadelphia: Lippincott Williams & Wilkins; 2001. p. 312. [43] McGregor JA, French JI. Bacterial vaginosis in pregnancy. Obstet Gynecol Surv 2000; 55:S1–19. [44] Mertz GJ, Schmidt O, Jourden JL, et al. Frequency of acquisition of first-episode genital infection with herpes simplex virus from symptomatic and asymptomatic source contacts. Sex Transm Dis 1985;12:33–9. [45] Mole L, Ripich S, Margolis D, et al. The impact of active herpes simplex virus infection on human immunodeficiency virus load. J Infect Dis 1997;176:766–70. [46] Morris M, Nicoll A, Simms I, et al. Bacterial vaginosis: a public health review. BJOG 2001;108:439–50. [47] Murthy JH, Hiremagalur SR. Differentiation of tubo-ovarian abscess from pelvic inflammatory disease, and recent trends in the management of tubo-ovarian abscess. J Tenn Med Assoc 1995;88:136–8. [48] Ness RB, Soper DE, Peipert J, et al. Design of the PID Evaluation and Clinical Health (PEACH) Study. Control Clin Trials 1998;19:499–514. [49] Oleszczuk LJ, Keith LG. Vaginal infection: prophylaxis and perinatal outcome–a review of the literature. Int J Fertil Womens Med 2000;45:358–67. [50] Oxman MN. Genital herpes. In: Gorbach SL, BJBN editor. Infectious diseases. 2nd edition. Philadelphia: WB Saunders; 1998. p. 986–1007. [51] Pavletic AJ, Wolner-Hanssen P, Paavonen J, et al. Infertility following pelvic inflammatory disease. Infect Dis Obstet Gynecol 1999;7:145–52. [52] Peipert JF, Ness RB, Soper DE, et al. Association of lower genital tract inflammation with objective evidence of endometritis. Infect Dis Obstet Gynecol 2000;8:83–7. [53] Prober CG. Herpetic vaginitis in 1993. Clin Obstet Gynecol 1993;36:177–87.
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[54] Rachinsky I, Boguslavsky L, Goldstein D, et al. Diagnosis of pyogenic pelvic inflammatory diseases by 99mTc-HMPAO leukocyte scintigraphy. Eur J Nucl Med 2000;27:1774–7. [55] Ralph SG, Rutherford AJ, Wilson JD. Influence of bacterial vaginosis on conception and miscarriage in the first trimester: cohort study. BMJ 1999;319:220–3. [56] Reljic M, Gorisek B. C-reactive protein and the treatment of pelvic inflammatory disease. Int J Gynaecol Obstet 1998;60:143–50. [57] Rodgers CA, O’Mahony C. High prevalence of herpes simplex virus type 1 in female anogenital herpes simplex. Int J STD AIDS 1995;6:144. [58] Rome ES. Pelvic inflammatory disease: the importance of aggressive treatment in adolescents. Cleve Clin J Med 1998;65:369–76. [59] Ross J. Pelvic inflammatory disease. BMJ 2001;322:658–9. [60] Sanford J. Sanford guide to antimicrobial therapy. 32nd edition. Hyde Park (VT): Antimicrobial Therapy Inc; 2002. [61] Schwebke JR. Bacterial vaginosis. Curr Infect Dis Rep 2000;2:14–7. [62] Shanahan D, Lord PH, Grogono J, et al. Clinical acute cholecystitis and the Curtis-FitzHugh syndrome. Ann R Coll Surg Engl 1988;70:44–6. [63] Sherer DM, Schwartz BM, Abulafia O. Management of pelvic abscess during pregnancy: a case and review of the literature. Obstet Gynecol Surv 1999;54:655–62. [64] Slap GB, Forke CM, Cnaan A, et al. Recognition of tubo-ovarian abscess in adolescents with pelvic inflammatory disease. J Adolesc Health 1996;18:397–403. [65] Sobel JD. Vaginitis. N Engl J Med 1997;337:1896–903. [66] Stephenson J. New therapy promising for genital herpes. JAMA 2001;285:2182–3. [67] Sweet RL. Gynecologic conditions and bacterial vaginosis: implications for the nonpregnant patient. Infect Dis Obstet Gynecol 2000;8:184–90. [68] Derchi LE, Serafini G, Gandolfo N, et al. Ultrasound in gynecology. Eur Radiol 2001;11:2137–55. [69] van Der Schee C, van Belkum A, Zwijgers L, et al. Improved diagnosis of Trichomonas vaginalis infection by PCR using vaginal swabs and urine specimens compared to diagnosis by wet mount microscopy, culture, and fluorescent staining. J Clin Microbiol 1999; 37:4127–30. [70] van Dongen PW. Diagnosis of Fitz-Hugh-Curtis syndrome by ultrasound. Eur J Obstet Gynecol Reprod Biol 1993;50:159–62. [71] Wald A. Herpes. Transmission and viral shedding. Dermatol Clin 1998;16(xiv):795–7. [72] Walker CK, Workowski KA, Washington AE, et al. Anaerobes in pelvic inflammatory disease: implications for the Centers for Disease Control and Prevention’s guidelines for treatment of sexually transmitted diseases. Clin Infect Dis 1999;28(Suppl 1):S29–36. [73] Xu F, Schillinger JA, Aubin MR, et al. Sexually transmitted diseases of older persons in Washington State. Sex Transm Dis 2001;28:287–91. [74] Yealy DM, Greene TJ, Hobbs GD. Underrecognition of cervical Neisseria gonorrhoeae and Chlamydia trachomatis infections in the emergency department. Acad Emerg Med 1997;4:962–7.
Gynecologic infections Wesley Zeger, DOa,b,*, Kurtis Holt, MDa a
Department of Emergency Medicine, Madigan Army Medical Center, Tacoma, WA 98431, USA b University of Washington, Department of Medicine, Division of Emergency Medicine, Box 356123, 1959 NE Pacific Street, Seattle, WA 98195-6123, USA
Gynecologic infections are a common reason for women to present to the mergency department. This article reviews the more common vulvo-vaginal infections, cervicitis, pelvic inflammatory disease, tubo-ovarian abscess, and the Fitz-Hugh–Curtis syndrome. Emphasis is placed on epidemiology, diagnosis, and management, as well as on comparing the pregnant and nonpregnant patient when appropriate.
Vulvo-vaginal infections Candida vulvovaginitis Candidal vaginal infections are primarily caused by Candida albicans, with other Candida spp. causing a minority of infections [1,2]. The risk of candidal vaginitis may be increased in women who are immunosuppressed or who recently used corticosteroids, antibiotics, or higher-dose estrogen oral contraceptives. In addition, women who use intrauterine devices and vaginal sponges also may be at increased risk [2,3]. Diagnosis is made by clinical symptoms and microscopy. Patients typically present with vulvovaginal pruritis, dyspareunia, dysuria, or white, curdlike discharge. On examination, the mucosa is typically erythematous and edematous. In addition, satellite lesions may be seen in the genital area. On microscopic evaluation, a normal pH (4–4.5) with hyphae, pseudohyphae, or budding yeast on the saline wet preparation or 10% potassium hydroxide preparation confirm fungal presence (Fig. 1). The role of culture in patients with signs and symptoms of candidal vaginitis but negative microscopy is * Corresponding author. Department of Emergency Medicine, Madigan Army Medical Center, Tacoma, WA 98431. E-mail address: [email protected] (W. Zeger). 0733-8627/03/$ - see front matter Ó 2003 Elsevier Inc. All rights reserved. doi:10.1016/S0733-8627(03)00039-7
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Fig. 1. Polarizing microscopy of multiple singlets and budding yeast (small arrows) belonging to the species Candida glabrata in a patient with a mixed infection and clue cells (large arrow) in vaginal secretions associated with bacterial vaginitis. (Copyright Ó 1997 Massachusetts Medical Society. All rights reserved. Reproduced with permission from Sobel JD. Vaginitis. N Engl J Med 1997;337:1896–1907.)
not clear [1–3]. Treatment with the azole class of drugs is the initial therapeutic recommendation [1–3]. Treatment with an intravaginal or oral antifungal medication is a matter of patient preference, because both are typically azole derivatives [2]. Recommended duration of intravaginal therapy is 3 to 7 days; fluconazole by mouth is a single dose [1]. Fluconazole should not be used during pregnancy. During pregnancy, current recommendations are for a 7-day course of topical therapy [1]. Bacterial vaginosis Although bacterial vaginosis is thought to be the most common cause of infectious vaginitis, its cause and pathogenesis are poorly understood. No single bacterial organism has been consistently identified, and it is thought to be a polymicrobial anaerobic infection [4–8]. Incidence rates range from 10% to 40%, depending on the population studied [2,4,5], with the epidemiologic data limited by sampling bias [5,6]. Nonetheless, infection with bacterial vaginosis is associated with significant morbidity. It can lead to upper genital tract infections including cervicitis and pelvic inflammatory disease [5,6,8] and has been associated with an increased risk of HIV infection [4,6,9]. In pregnant patients, there is a causal relationship between bacterial vaginosis and preterm delivery [4,10]. Other obstetric
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complications of bacterial vaginosis include intrapartum and postpartum infections as well as first trimester miscarriage [5,6,11]. Bacterial vaginosis can cause a thin, homogeneous, milklike vaginal discharge. Because up to 50% of infected women may be asymptomatic, however, diagnosis is primarily made by microscopy [5,6]. Classically, the diagnosis is made by the presence of three of the four Amsel criteria: 1. Homogeneous, thin vaginal fluid that adheres to vaginal walls 2. Vaginal fluid pH higher than 4.5 3. Release of amine odor with alkalinization of vaginal fluid (the so-called ‘‘whiff test’’) 4. Presence of vaginal epithelial cells with borders obscured with adherent, small bacteria (so-called ‘‘clue’’ cells) (see Fig. 1). Other diagnostic tests include Gram staining of vaginal fluid or secretions, DNA probes, and Femexam Amines Testcards (Cascade Health Care Products, Inc., Portland, OR) [2,5,7,8]. Currently, treatment should be provided for symptomatic nonpregnant women as well as for symptomatic and asymptomatic pregnant women. During pregnancy, treatment of asymptomatic patients reduces the incidence of preterm delivery and postdelivery infectious complications [1,3–6,12]. Prevention of preterm delivery is most apparent in high-risk patients (ie, those who have had a prior preterm delivery) [1,4–6]. Sexual partners do not need to be treated [1]. Primary treatment options for the nonpregnant patient are oral metronidazole (500 mg two times/day for 7 days), metronidazole (0.75% vaginal gel, 5 g once daily for 5 days), or 2% clindamycin vaginal cream (5 g once daily for 7 days) [1,5,13]. During pregnancy, the recommended primary treatment is oral metronidazole (250 mg three times/day for 7 days) or oral clindamycin (300 mg two times/day for 7 days) [1,5]. Intravaginal clindamycin cream should not be used during pregnancy because its use has been associated with an increase risk of preterm delivery [1]. Trichomonas vaginalis Trichomonas vaginalis, a parasite that is transmitted primarily through sexual activity [2,3,9], infects 2 to 3 million Americans annually [12]. In addition to the vaginal discomfort, trichomoniasis facilitates the transmission of HIV [2,3,9]. During pregnancy, infection has been associated with delivery of low birth weight infants and preterm deliveries [2,3,9,14]. Treatment of asymptomatic pregnant patients does not seem to decrease the incidence of preterm deliveries, however [14]. Trichomonas infection can cause vulvar irritation, dyspareunia, dysuria, urinary frequency, and a malodorous purulent vaginal discharge. Up to 50% of infections may be asymptomatic [9]. Physical examination may show an erythematous vaginal mucosa or punctate hemorrhages on the cervix.
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Diagnosis is typically made by identification of motile trichomonads on a saline wet preparation. Trichomonads, however, are seen in only 50% to 80% of confirmed cases using cultures as the criterion standard for diagnosis [2,3]. Cultures from a specialized parasite media have a sensitivity of 85% to 95%, but results are delayed [15]. Newer diagnostic methods such as DNA probes, monoclonal antibody kits, and polymerase chain reaction (PCR) techniques provide rapid and more accurate results [2,9,15]. DNA probes and monoclonal antibody kits are about 90% sensitive and more than 99% specific. PCR techniques can use either vaginal swabs or urine and are more sensitive than culture techniques [15]. Current recommended therapy is oral metronidazole, 2 g as a single dose, or, alternatively, oral metronidazole, 500 mg two times/day for 7 days [1]. Patients allergic to metronidazole should be referred for desensitization according to recommendations from the 2002 Centers for Disease Control and Prevention (CDC) guidelines [1]. Sanford [16] recommends the following as an alternate therapy: intravaginal paromomycin cream (250 mg daily for 2 weeks), zinc sulfate douches, or oral tinidazole (500 mg four times/day) plus intravaginal tinidazole (500 mg two times/day) for 14 days. Pregnant patients should be treated with oral metronidazole, 2 g as a single dose [1]. This therapeutic option is controversial in the first trimester, and these patients should be referred to their obstetrician [1,2]. Sexual partners should be treated [1]. Herpes vulvo-vaginitis Herpes simplex virus-1 (HSV-1) and Herpes simplex virus-2 (HSV-2) are the most common herpes viruses causing genital infections. Additionally, herpes virus is the most common cause of genital ulcers [1]. It was long thought that only HSV-2 could cause a genital infection, but now it is well known that HSV-1 is implicated in causing up to 15% to 30% of genital infections [17]. Both HSV-1 and HSV-2 are spread following contact with infectious secretions. Thus oral-to-oral, oral-to-genital, and genital-togenital contacts are all associated with the development of herpes virus infection. Herpes virus infection rates are on the rise. The national prevalence of infection with HSV-2 rose 30% between 1978 and 1991, with 22% of the population older than 12 years of age infected by the early 1990s [18]. White teenagers and young adults had the largest increase. It seems as though, aside from HIV, genital herpes will be the most concerning sexually transmitted disease by 2010 [19]. A primary episode is defined as genital herpes with the absence of antibodies to HSV-1 and HSV-2. It is classically associated with systemic symptoms including headache, fever, malaise, and other flulike symptoms. Recurrent infections are more typical with HSV-2: as many as 95% of persons infected with HSV-2 have recurrences within 1 year of primary infection, whereas only 50% of HSV-1 infections recur [20]. This difference
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presumably results from the difficulty HSV-1 has in establishing latency in the sacral ganglia. Most recent estimates indicate that approximately 10% of patients with history and physical examination suggesting first-episode genital herpes have serologic evidence of previous infection [21]. Furthermore, as many as 70% of people infected with HSV lack symptoms [22], but HSV can be isolated and transmitted from the genital tract during these socalled symptomatic periods. Transmission is highly variable; some persons contract the virus after only one exposure, whereas others do not contract the virus despite years of unprotected sexual activity [23]. Transmission from a mother to her baby during vaginal delivery is relatively rare (<3%). Vertical transmission, however, increases to around 30% in women who develop genital HSV in the third trimester because protective antibodies are unable to develop before delivery [24]. Diagnosis Patients with primary genital herpes can be systemically ill with fever, headache, malaise, abdominal pain, and myalgias; however, one third of patients with a primary outbreak are not systemically ill [25]. The lesions are painful and often described as burning [1]. With primary outbreaks, the genital lesions are typically longer lasting, more numerous, and more painful. The symptoms usually begin 1 to 4 weeks after exposure. The lesions begin as vesicles and then rupture, exposing the ulcerated base. Ulcerated lesions persist for 1 to 2 weeks, crust, and heal without scars. Cervical lesions are present up to 90% of the time, along with extravaginal lesions. The average time from onset of lesions to complete healing is usually around 3 weeks. Genital herpes may be the most frequent cause of previously undiagnosed genitourinary complaints, because dysuria can be present in up to 80% of cases [25,26]. The clinical picture of HSV-1 and HSV-2 genital infections is indistinguishable. Recurrent attacks tend to be subtler in presentation and are the most frequently seen outbreaks in the emergency department. The patient presents to the emergency department thinking this is the primary outbreak, when actually the patient contracted the virus months to years previously. The patient may or may not complain of the classic prodromal symptoms of burning, pain, and itching. Immunodeficiency, trauma, fever, or sexual intercourse can precipitate a recurrence [27]. Persistent stressors tend to be more likely to trigger an outbreak rather than transient mood states or short-term stressors or life changes [28]. The type-specific herpes culture has replaced the Tzanck smear as the criterion for diagnosing herpes infection. Some recommend that a virus culture and also type-specific HSV serology be done on the initial visit, because the serology is important to predict the risk for the number and possibility of recurrent outbreaks. Realistically, if the patient has good follow-up, virus cultures may be done in the emergency department, and serology done at follow-up. Because the herpes virus is the most common
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cause of urogenital complaints in the emergency department, women presenting with unexplained urogenital complaints should have an extensive genito-urinary examination. First-time outbreaks (either primary or nonprimary) of HSV ulcers yield virus in 80% of cases, whereas ulcers from recurrent infections are positive 40% of the time [29]. Equally as important, however, is the need for screening for treponemal antibodies (syphilis) in the emergency department evaluation. A significant number of patients who present with a typical herpes infection are later found to have syphilis [30]. Treatment Other than prevention and patient education, antiviral medications are the mainstay of treatment. These medications can be used for Symptomatic management only, to improve lesion healing and to reduce symptoms Episodic antiviral therapy for recurrence Continuous antiviral therapy to prevent recurrent attacks. Of the three antiviral agents, acyclovir has the most comprehensive longterm safety data. The advantage of the other antiviral agents is their simpler dosing schedule [31]. They are generally effective only if given within 48 hours of symptom onset. Episodic treatment is generally not as effective as continuous therapy to reduce recurrent attacks and shedding. Only patients who have six or more recurrences per year are considered as candidates for continuous antiviral therapy [32]. The treatment regimen for initial episodes of initial genital HSV infection is oral acyclovir, 200 mg five times daily for 10 days, or 400 mg three times daily for 10 days. Oral famciclovir, 250 mg three times daily, or oral valacyclovir HCL, 1 g twice daily, offer a more convenient dosing schedule but at a higher cost and unproven safety data. Resiquimod, a new topical agent that acts as an immunity-enhancing agent, seems promising in phase I and II trials. These studies indicate that, if applied within 24 hours of prodromal symptom onset, resiquimod can significantly shorten the duration of symptoms and lengthen the time between recurrences [33]. There has long been hope that an effective and safe herpes vaccine would be developed, but currently, none exists. Special patient populations Pregnant patients. Genital herpes is acquired for the first time during pregnancy in 2% to 3% of the general obstetric population [34]. If acquired during pregnancy, the herpes virus poses little threat to the fetus as long as HSV seroconversion has been completed by the time of labor [35]. The most important points for the emergency physician are [35] A patient with a new diagnosis of genital herpes should be referred as soon as possible to her obstetrician. A patient presenting with evidence of genital herpes and rupture of membranes should be referred immediately for delivery.
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Not every pregnant patient with genital herpes needs a cesarean section. Pregnant patients often have a subtle presentation. The antiviral medications are generally thought to be safe in pregnancy but should only be used if within 48 hours of onset of symptoms and for the most symptomatic of patients. Postpartum mothers with active genital herpes are able to handle their newborns and do not require isolation, but they must wash their hands frequently and before handling their newborns. HIV-positive patients. As with most other sexually transmitted diseases, herpes is a well-known and important cofactor in the transmission of HIV. Many believe that people infected with the herpes virus should also be screened for HIV. There is evidence to suggest that HSV infection increases HIV transcription and plasma viral load, which may adversely affect the clinical course of HIV disease [36]. Also, the immunosuppression associated with HIV can increase the rate of subclinical HSV shedding in both men and women. HIV-positive patients should be treated with intravenous acyclovir (5 mg/kg) if their CD4 count is below 200 and severe or disseminated disease is present. Other conditions possibly necessitating intravenous therapy include urinary retention or inability to tolerate oral therapy for any reason. Bartholin’s gland cyst and abscess Bartholin’s glands are bilateral vulvo-vaginal bodies located in the labia minora at approximately the 4 o’clock and 8 o’clock positions on the posterolateral aspect of the vestibule. Normally pea-sized and draining through a 2.5-cm duct into a fold between the hymeneal ring and the labium, they can become cystic and subsequently form abscesses. Growing rapidly, the cysts can be a source of extreme pain and discomfort. Patients are usually 20 to 30 years old, and by the time they have decided to come to the emergency department, they are indeed in a great deal of pain. The predominant organisms associated with these abscesses are anaerobic and most commonly include Bacteroides fragilis and Peptostreptococcus. About 10% to 15% of the time Neisseria gonorrhoeae is the causative agent. Chlamydia trachomatis is involved less frequently [37]. Patients who are in enough discomfort to necessitate a visit to the emergency department will most likely present with an abscess. The management is as follows [38]: local anesthesia and sterile preparation is followed by a scalpel stab incision, approximately 1.0 to 1.5 cm long, deep into the abscess from inside the labium because an outside incision can cause a permanent fistula. Following the incision and drainage, a hemostat is used to break up all the loculations. A Word catheter is then placed. The balloon tip is inserted into the abscess and inflated with water or lubricating gel. The free end is then tucked into the vagina [39]. Simple incision and drainage without Word catheter placement may be inadequate and lead to
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a considerable number of recurrences of abscesses. Gynecologic followup should be arranged in 5 to 7 days for definitive management. Use of prophylactic antibiotics is not recommended unless there is significant surrounding cellulites or signs of systemic illness. Syphilis Syphilis is caused by the spirochete Treponema pallidum. The incidence of syphilis has declined from 20.1 cases per 100,000 in the late 1970s to 3.2 cases per 100,000 in 1997 [40]. This diagnosis should be considered in any patient who presents with an ulcerative lesion in the genital area. Primary syphilis manifests as a single, painless, clean-based ulcer, usually within 3 weeks but sometimes 2 to 3 months after infection. The labia and vaginal wall are most often affected, but lesions can occur on the cervix. Secondary syphilis is associated with the characteristic maculopapular generalized rash including the palms and soles. Arthralgias, pharyngitis, and lymphadenopathy are also seen. Secondary syphilis is typically seen 2 to 8 weeks after exposure. Tertiary syphilis develops in approximately 30% of untreated patients and presents with numerous neurologic, cardiovascular, and other systemic effects [41]. The diagnosis of syphilis should be entertained for patients with unexplained rashes, arthralgias, and neurologic or systemic complaints. Syphilis is initially screened for with a rapid plasma regain (RPR) or a Venereal Disease Research Laboratory (VDRL) test. Confirmatory testing is required for definitive diagnosis. Physicians should have a low threshold of suspicion to screen for this disease, because significant long-term morbidity can occur if not treated. Treatment for syphilis has changed little. Penicillin remains the mainstay of treatment. For primary or secondary syphilis, a single dose of penicillin G benzathine, 2.4 million units intramuscularly, is sufficient. Penicillin is the only acceptable therapy for patients who have neurosyphilis or are who are pregnant. Consequently, skin testing and desensitization are recommended for pregnant patients who have a true allergy to penicillin [1]. Acceptable second-line antibiotics for primary and secondary syphilis in the nonpregnant patient are doxycycline (100 mg two times/day for 10 days), erythromycin (500 mg four times/day for 14 days), or ceftriaxone (1 g/day intramuscularly for 8-10 days). For neurosyphilis, intravenous penicillin, 4 million units every 4 hours for 10 to 14 days, is recommended, along with admission [1,42].
Cervical infections The most common causes of cervicitis are C trachomatis and N gonorrhoeae, with C trachomatis being the most common [9]. Other implicated organisms include actinomycetes (classically, in patients using intrauterine devices), Mycomplasma hominis, Ureaplasma urealyticum,
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cytomegalovirus, tuberculosis, and other bacteria associated with bacterial vaginosis. Females between the ages 15 and 25 years are most commonly infected with these sexually transmitted bacteria [9], and infection rates in women with chlamydia are increasing, whereas those with gonorrhea are decreasing [43]. A recent epidemiologic study in Washington found adults between ages 40 and 80 years accounted for 9% of the cases of chlamydia and gonorrhea [44]. Complications of cervical infection include further spread to the upper genital tract and increased susceptibility to HIV infection [9]. Chlamydia and gonorrhea can cause dysuria, urinary frequency and urgency, pelvic pain, vaginal bleeding, and vaginal discharge. A recent prospective emergency department-based study found that up to 17% of women with a chief complaint of vaginal bleeding had cultures positive for C trachomatis, N gonorrhoeae, or both [45]. Mucopurulent cervicitis is often asymptomatic. Although it can be caused by C trachomatis or N gonorrhoeae, neither organism is isolated in most cases [1]. Thus, mucopurulent cervicitis is not a sensitive predictor of infection, because most patients with C trachomatis or N gonorrhoeae do not have mucopurulent cervicitis [1]. Pelvic examination may reveal a tender, friable cervix but can be completely normal. Therefore, a clinical diagnosis based on the probability of disease may be inaccurate and could result in a significant number of untreated women [46]. Diagnosis is based on laboratory confirmation. Historically, culture was the only way to confirm a diagnosis, but C trachomatis can be difficult to culture. Polymerase chain reaction and ligase chain reaction (LCR) methods have been shown to have a greater than 99% specificity for detection of C trachomatis and N gonorrhoeae in cervical, urethral, and urine specimens [9]. Health care providers should have an extremely low threshold of suspicion to seek confirmatory testing in any potential genital-urinary complaint. Treatment should be based on laboratory confirmation, with two exceptions. Empiric treatment for both gonorrhea and chlamydia should be given to patients with a high likelihood of disease and those likely to be lost to follow-up [1]. Sexual partners should be identified and treated. Patients should abstain from intercourse for 7 days after a single dose of antibiotics or after completion of a 7-day regimen [1]. Pregnant patients should have repeat testing 3 weeks after treatment to demonstrate efficacy [1]. Treatment regimens shown in Table 1 are based on the 2002 CDC guidelines [1].
Pelvic inflammatory disease Pelvic inflammatory disease (PID) afflicts about 11% of women in the United States [47,48]; adolescents are at a higher risk than adults [49]. Cohort data (with laparoscopically proven PID) have shown that women
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Table 1 CDC treatment guidelines for cervicitis Chlamydia trachomatis
Neisseria gonorrheoae
Primary
Aztyhromycin 1 g orally as a single does or Doxycycline 100 mg orally BID for 7 days
Cefixime 400 mg as a single dose or Ceftriaxone 125 mg IM as a single dose or Ciprofloxacin 500 mg as a single dose or Ofloxacin 400 mg as a single dose or Levofloxacin 250 mg orally as a single dose
Alternate
Erythromycin base 500 mg orally QID for 7 days or Ofloxacin 300 mg orally BID for 7 days or Levofloxacin 500 mg orally once daily for 7 days
Spectinomycin 2 g IM as a single dose
Pregnancy (primary)
Erythromycin base 500 mg orally QID for 7 days or Amoxicillin 500 mg orally TID for 7 days
Cefixime 400 mg orally as a single dose or Ceftriaxone 125 mg IM as a single dose
Pregnancy (alternate)
Azythromycin 1 g orally as single dose
Spectinomycin 2 g IM as a single dose
diagnosed with PID have an increased risk of infertility. About 40% of women are infertile after an initial infection, and 75% are infertile after a subsequent infection [47,50]. Additionally, 25% will develop chronic abdominal pain, and almost 10% will have an ectopic location with their first pregnancy [47,50]. In addition, C trachomatis commonly causes asymptomatic PID, and these patients are more likely to develop complications [49]. Patients using an intrauterine device may be a greater risk of developing PID than those who do not use any contraception [51]. Data on this topic are mixed, however, and a cause-effect relationship has not been established [51,52]. Although uncommon, PID can occur during pregnancy [53,54]. Retrospective data indicate that in pregnancy PID occurs most commonly in the first trimester, although it can occur later in pregnancy [53,54]. Overall, good epidemiologic and management data in the United States are sparse because of the difficulty in accurately identifying
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patients with PID and the high lost-to-follow-up rates in evaluating the sequelae of pelvic infections [47,55]. Diagnosis The clinical diagnosis of PID is often difficult [47,48]. Symptoms suggestive of PID include abdominal pain, dyspareunia, vaginal discharge, and abnormal vaginal bleeding. The presence of mucopurulent cervical discharge, or leukorrhea (more white blood cells than epithelial cells in four high-powered fields) in the vaginal vault has good sensitivity for PID but very poor specificity [48]. Although a complete blood cell count, erythrocyte sedimentation rate, or C-reactive protein test are often ordered as part the laboratory evaluation for diagnosing PID, their wide variability makes them unreliable, especially in the HIV-positive patient [56,57]. The criterion standard continues to be laparoscopy, but endometrial biopsy consistent with endometritis may also be reliable [47,48]. Ultrasonography is most useful in differentiating PID from a tubo-ovarian abscess [58,59]; however, free fluid in the pelvis, endometrial thickening, or distension of the endometrial cavity can be seen in PID [58]. In the emergency department setting, PID should be diagnosed in women with lower abdominal tenderness, cervical motion tenderness, and adenexal tenderness for which another cause is not likely [1,60], because laboratory results (ie, cultures, PCR, or LGR) are typically not available. Management The decision to admit patients with PID is controversial, and there are not any good studies on which to base decisions. The CDC guidelines, based on consensus opinion and observational studies, suggest hospitalization when [1]
Surgical emergencies such as appendicitis cannot be excluded The patient is pregnant The patient does not respond clinically to oral antimicrobial therapy The patient is unable to follow or tolerate an outpatient oral regimen The patient has severe illness, nausea and vomiting, or high fever The patient has a tubo-ovarian abscess.
The International Disease Society for Obstetrics and Gynecology-USA grades PID into four stages [61]. 1. Stage 1: lower abdominal pain, cervical motion tenderness, and adnexal tenderness and more than 1 minor criteria defined by the CDC Oral temperature greater than 101 F (greater than 38.3 C), Abnormal cervical or vaginal discharge Elevated erythrocyte sedimentation rate Elevated C-reactive protein
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Laboratory documentation of cervical infection with N gonorrhoeae or C trachomatis Stage 2: Stage 1 plus peritonitis Stage 3: Tubo-ovarian complex or abscess on physical examination or by ultrasonography Stage 4: Ruptured tubo-ovarian abscess. The Society recommends outpatient management for women with stage 1 disease with the exception of
Pregnant patients Adolescents Nulligravidae who desire future pregnancy Patients unable to take oral medication or be seen in follow-up.
Antibiotic therapy is also somewhat controversial, because PID can be polymicrobial [62]. Chlamydia trachomatis and N gonorrhoeae are isolated most frequently, but pathogens associated with bacterial vaginosis are also frequently isolated [8,49]. Bacterial vaginosis and plasma cell endometritis are more common in HIV-positive women, suggesting that adequate anaerobic coverage should be given in this population [56]. Furthermore, bacteria cultured from the cervix do not necessarily correlate to those isolated form the endometrium or fallopian tubes [49], and vice versa [63]. Current recommended antibiotic therapies (Table 2) are from the CDC 2002 guidelines. If outpatient therapy is chosen, patients should have follow-up reexamination in 48 to 72 hours [1].
Tubo-ovarian abscess Tubo-ovarian abscess (TOA) is a serious complication of pelvic inflammatory disease, and up to 15% will rupture, causing a surgical emergency [49]. It is the most common cause of an intra-abdominal abscess in premenopausal women [64]. Although up to one third of women hospitalized with PID develop a TOA, up to 50% of TOAs are not associated with PID [64]. Most TOAs consist of polymicrobic anaerobic bacteria [54,59,64,65]. HIV-positive women develop TOAs more frequently than HIV-negative women, and these abscesses also tend to be polymicrobic [56]. Although TOAs are uncommon in pregnancy, when they do occur, they are most common in the first trimester. Regarding second and third trimester abscesses, ‘‘it is with great hesitancy and often with great embarrassment, that the diagnosis pelvic inflammatory disease [referring to TOA] is made’’ [66]. It is not clear if patients using intrauterine devices are at increased risk for TOA [65]. In general, the pathogenesis of TOA has not been well elucidated, and TOA should remain in the differential even without a recent history of PID.
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Table 2 CDC guidelines for the treatment of PID
Primary
Outpatient
Inpatient
Regimen A Ofloxacin 400 mg PO bid for 14 days or Levofloxacin 500 mg PO once daily for 14 days with or without metronidazole 500 mg PO bid for 14 days Regimen B Ceftriaxone 250 mg IM once or Cefoxitin 2 g IM once and probenicid 1 g once orally, concurrently
Regimen A Cefotetan 2 g IV q 12 hrs or Cefoxitin 2 g IVq 6 hours plus Doxycycline 100 mg q 12 hours IV or PO Regimen B Clindamycin 900 mg IV q 8 hours plus Gentamicin IV/IM 2 mg/kg loading dose followed by 1.5 mg/kg IV q 8 hours (once daily dosing may be substituted)
plus doxycycline 100 mg PO BID for 14 days with or without metronidazole 500 mg PO bid for 14 days Alternate
Ofloxacin 400 mg IV q 12 hours or Levofloxacin 500 mg q 24 hours plus Doxycycline 100 mg q 12 hours IV or PO with or without Metronidazole 500 mg IV every 8 hours or Unasyn 3 g IV every 6 hours
Patients with a TOA typically have abdominal pain with severe tenderness, often with peritoneal signs on palpation [64]. Palpation on bimanual examination may be difficult because of pain. Thus, differentiation from stage 2 PID based on clinical examination is not reliable [64]. Fever may be absent. In addition, the white blood cell count, erythrocyte sedimentation rate, and C-reactive protein test can be normal, although they are usually elevated [59,64]. Definitive diagnosis is made by direct visualization or an imaging study. Pelvic ultrasound is the initial modality of choice with a reported sensitivity of 93% and specificity of 98% [64]. Computed tomography may be used to define the abscess better or may be appropriate if the ultrasound evaluation is inconclusive. Leukocyte scintigraphy may have a future role, but it has not been well studied [67].
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All patients with a TOA should be admitted. The choice of operative versus nonoperative management is left up to the consultant. Initial antibiotics should cover anaerobic and sexually transmitted bacteria. Recommended therapies include intravenous ofloxacin (400 mg every 12 hours) and metronidazole (500 mg every 8 hours) or intravenous ampicillin/sulbactam (3 g every 8 hours) and oral or intravenous doxycycline (100 mg every 12 hours) [16].
Fitz-Hugh–Curtis syndrome The Fitz-Hugh-Curtis syndrome was initially described in 1848 by a Danish surgeon Martinus Hassig. Thomas Fitz-Hugh and Arthur Curtis reported it in the English literature in the 1930s [68]. Data on Fitz-Hugh– Curtis syndrome are limited to reviews of case reports; thus epidemiologic, diagnostic, and management data are inherently flawed. Despite these limitations, Fitz-Hugh–Curtis syndrome is thought to be composed of two components. In the acute phase, patients have sharp right upper quadrant pleuritic pain that can radiate to the shoulder [68]. In the chronic phase, peritoneal adhesions form causing chronic abdominal pain (typically right upper quadrant) [68]. Tubal infection may or may not be concurrently present [68]. Although Fitz-Hugh-Curtis syndrome initially was thought to be caused exclusively by N gonorrhoeae pelvic infection, C trachomatis has emerged recently as the most reported causative bacteria [68,69,72,73]. Classically, it has mimicked acute cholecystitis, pneumonia, and pulmonary embolism but has also presented with unilateral or bilateral flank pain mimicking renal colic, colonic ileus, left upper quadrant pain (perisplenitis), and epigastric pain mimicking a perforated peptic ulcer [68,69,72,73]. Complications are uncommon, but subdiaphragmatic abscess, small bowel obstruction, and unnecessary surgery have been described [68]. Diagnosis is difficult because the index of suspicion needs to be high, and because there is no standard for diagnosis. In general, the diagnosis should be considered in patients with upper abdominal pain and normal routine investigations, specifically of the gallbladder and liver function tests [68]. Although one case series describes a sample of patients with elevated liver function tests, this patient population included a significant number of patients with a history of hepatitis or intravenous drug abuse [68]. Furthermore, this case series (small overall compared with the whole case series) is the only one to describe abnormal liver function tests as common in the presentation of Fitz-Hugh–Curtis syndrome [68]. Fever has been invariably present in case series, as has an elevated white blood cell count [68,69,72,73]. Abdominal pain, cervicitis, or PID may be present on pelvic examination, but the examination can be unremarkable [68,69,72,73]. Cervical cultures are typically positive but have been negative in a variable portion of patients in which N gonorrhoeae or C trachomatis grew out from
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intraperitoneal cultures [68]. Adhesions and perihepatic ascites may be visualized by ultrasonography or computed tomographic scan, but these imaging modalities have not been studied in Fitz-Hugh–Curtis syndrome and thus should not be relied on for definitive diagnosis [70,72]. Fitz-Hugh– Curtis syndrome is diagnosed clinically in patients with upper abdominal pain without another cause, a genital infection (symptomatic or asymptomatic), and cultures positive for N gonorrhoeae or C trachomatis. Although the incidence of adhesions varies between 25% and 100% [71,72], the current standard for diagnosis is the presence of laparoscopically visualized adhesions and positive cervical or abdominal cultures [68,72]. The goal of treatment is to prevent chronic abdominal pain. Current treatment involves bacterial eradication with antibiotics and surgical lysis of adhesions. Based on case reports, patients should be treated with antibiotics if they have symptomatic genital infections and upper abdominal pain or asymptomatic genital infections, upper abdominal pain, and positive cultures. There are no formal antibiotic recommendations. Doxycycline and penicillin (320,000 units given as a single dose intramuscularly) are most commonly reported; however, penicillin was used before resistance to penicillin became common [68,69,72–74]. Duration of therapy for doxycycline has ranged from 10 days to 4 weeks. Thus, a reasonable antibiotic regimen is oral doxycycline for 14 days plus ceftriaxone (250 mg given in a single dose intramuscularly) or oral ofloxacin (400 mg two times/day) plus oral metronidazole (500 mg two times/day) for 14 days. Patients should be referred for evaluation and management of adhesions. Summary The scope of gynecologic infections presenting to the emergency department is quite diverse. This article presents an update on the current literature for vaginitis, cervicitis, pelvic inflammatory disease, tubo-ovarian abscesses, the Fitz-Hugh-Curtis syndrome, herpes, and syphilis. Inadequate identification or treatment of these diseases can result is significant morbidity or mortality for the patient and for the fetus. References [1] American College of Obstetricians and Gynecologists practice bulletin. Management of herpes in pregnancy. Number 8, October 1999. Clinical management guidelines for obstetrician-gynecologists. Int J Gynaecol Obstet 2000;68:165–73. [2] Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2002. MMWR Morb Mortal Wkly Rep 2002;51:1–78. [3] Summary of notifiable diseases, United States, 1997. MMWR Morb Mortal Wkly Rep 1002;46: ii–vii, 3–87. [4] Ashley RL, Corey L. HSV type specific antibody tests: patients are ready, are clinicians? Genitourin Med 1997;73:235–6. [5] Barton SE. Herpes management and prophylaxis. Dermatol Clin 1998;16:799–803.
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