Adolesc Med 15 (2004) 235 – 251 Vaginitis in adolescents Tahniat S. Syed, MD, MPHa,*, Paula K. Braverman, MDb a Section, Adolescent Medicine, St. Christopher’s Hospital for Children, Drexel University College of Medicine, Erie at Front Street, Philadelphia, PA 19134, USA b Division of Adolescent Medicine, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Mail location 4000, 3333 Burnet Avenue, Cincinnati, OH 45229, USA Vaginitis is a condition that involves inflammation or infection of the vulva and vaginal wall. It is a common medical complaint for adolescent girls in the outpatient setting. Advances in understanding the pathophysiology of certain causes of vaginitis have allowed improved diagnosis and treatment of these patients. Etiologies of vaginitis can be divided into nonspecific and specific causes. Nonspecific vaginitis represents noninfectious processes such as a foreign body, chemical irritants, or dermatoses. Specific vaginitis is infection-related, which may be sexually acquired. This article focuses on the three most common causes of a specific vaginitis: yeast, trichomoniasis, and bacterial vaginosis (BV). Historical clues It can be difficult to evaluate an adolescent girl with vaginal symptoms thoroughly. Some adolescents may feel uncomfortable talking about their symptoms for fear of the examination or that sexual activity will be reported to, or suspected by, their parents. This discomfort, compounded with potential embarrassment or unease with a changing body, may make it more difficult to obtain an adequate history and perform an examination than with an adult patient. Many clinicians also may feel uncomfortable evaluating these symptoms. Patient confidentiality should be ensured, allowing for a chance to meet alone with the adolescent, as well as paying special attention to patient comfort during the examination. Obtaining a history related to vaginitis can be uncomfortable for the adolescent and clinician, but a thorough history can narrow the differential diagnosis and thus the extent of physical examination needed to confirm the diagnosis. The examiner should start with questions related to the present symptoms, such as duration, * Corresponding author. E-mail address: tss28@drexel.edu (T. Syed). 1547-3368/04/$ – see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.admecli.2004.02.003 236 T.S. Syed, P.K. Braverman / Adolesc Med 15 (2004) 235–251 location, and history of similar symptoms and treatment. Systemic symptoms, such as fever and abdominal pain, usually are not seen with vaginitis alone, and may suggest another disease process. If there is discharge, its color, consistency, odor, and amount should be ascertained. Because of the availability of over-thecounter (OTC) vaginal medications, a history of self-medication should be taken. Because vulvar symptoms can occur with patients presenting with a complaint of ‘‘vaginitis,’’ questions regarding irritation, itching, burning, redness, and dyspareunia also should be asked. Vaginitis also can present with lower – urinary tract signs and symptoms such as a urethritis or dysuria. It is important to make this distinction between urine and gynecologic studies to prevent the overdiagnosis of urinary tract infections and underdiagnosis of vaginal infections. The sexual history is important and obtained most accurately with the patient alone, and includes frequency and number of sexual partners, history of sexually transmitted diseases (STDs) or pelvic inflammatory disease (PID), and the use of barriers such as condoms. The use of douches is associated with BV [1]. Nonspecific causes of vaginitis can include the use of perfumed soap, laundry detergent, panty-liners, and fabric softener as well as the use of washcloths, which can facilitate the movement of fecal bacteria to the perineal area. Other causes of nonspecific vaginal irritation can occur from taking bubble baths, poor bathroom hygiene, wearing tightly fitting clothes, and long-term exposure to wet undergarments, as in the case of enuresis or wet swimwear. Predisposing factors for yeast vaginitis may include a history of recent antibiotic use, pregnancy, diabetes mellitus, and lowered immune states, such as infection with HIV. A thorough history can help determine a specific versus a nonspecific etiology as well as what type of physical examination and laboratory testing are needed [2]. Physical examination The genital examination for a patient with suspected vaginitis is best done with the patient in the lithotomy position on a gynecology examination table. A bright light is needed to aid in proper visualization; if such a light is not available, an otoscope light can be used for visualization and magnification, if needed. First, the examiner should palpate for the presence, size, and tenderness of inguinal lymphadenopathy. Next, the pubic hair should be inspected for sexual maturity rating and signs of inflammation or infection. The clinician can then inspect the perineum for areas of erythema or excoriation. Lastly, the rectum can be inspected for disease involvement. It is important to explain the examination step by step, as this may be the first gynecologic examination for the adolescent. If the patient is sexually active, or if the clinician suspects sexual activity, a speculum should be inserted to visualize the cervix and to obtain testing for chlamydia and gonorrhea. The speculum also aids in the visualization of the vaginal walls, which normally appear pink and rugated. Normal vaginal discharge characteristically appears clear to white in color, accumulates in the posterior fornix, and does not adhere to the lateral vaginal walls. The acidity can T.S. Syed, P.K. Braverman / Adolesc Med 15 (2004) 235–251 237 be determined by placing pH paper against the lateral wall of the lower one third of the vagina. A wet preparation also can be obtained at this time by using a cotton-tipped swab to obtain a sample of discharge from the posterior fornix of the vagina. The sample can then be placed into a tube filled with 1 mL of nonbacteriostatic normal saline. If the examiner does not believe it is necessary to insert a speculum, either because STD testing is not needed or because the cervix does not need to be visualized, then the examiner can obtain a vaginal swab only for wet preparation. In this case, a premoistened cotton-tipped swab can be inserted to obtain the sample. A bimanual examination also may not be necessary unless the patient is sexually active and PID needs to be excluded. The laboratory evaluation consists of obtaining the vaginal pH, the wet preparation evaluation, and testing for gonorrhea and chlamydia when there is a concern for sexually transmitted infection. The wet preparation has the advantage of being completed with the patient still in the office. A view on low power (10 magnification) can be done to scan the entire slide quickly for areas that need further inspection. Next, the slide can be viewed and interpreted based on high-power magnification (40). The sample should be examined for clue cells (normally less than 20% per high-power field), white blood cells (normally fewer than 7– 10 per high-power field) and the presence or absence of trichomoniasis and yeast. The amine or ‘‘whiff’’ test also should be performed by adding a drop of 10% potassium hydroxide to the sample. A positive whiff is a detection of a ‘‘fishy’’ odor when amines (putracine and cadavaracine) are volatized in certain disease processes, such as BV and trichomoniasis. Normal physiologic discharge The vaginal examination of a female who has undergone puberty is different from one who has not. The prepubertal vagina appears reddened because of blood vessels apparent under the thin hypoestrogenic mucosa. The pH is elevated, usually above 4.7, and skin or fecal flora may be present normally. With rising estrogen levels and the onset of puberty, the mucosa thickens, giving a lighter pink appearance, and the vagina becomes colonized with lactobacillus species that produce lactic acid, lowering the pH to 4.5 or less. Certain strains of lactobacilli can produce hydrogen peroxide, which is paramount in inhibiting the overgrowth of normal facultative anaerobes [2]. The adolescent girl who has initiated puberty will have normal vaginal secretions from several different glands, including the vulva, sebaceous, sweat, Bartholin’s, and Skene’s. Other substances, such as exfoliated cells, cervical mucus, and secretions from the endometrial cavity and fallopian tubes, can be present. This results in a clear-to-white discharge that characteristically does not adhere to the vaginal walls, pools in the posterior fornix, and has an acidic pH of less than 4.5. Normal variations in the menstrual cycle and different stressors can alter the consistency and amount of the normal discharge, which must be considered when evaluating the patient [3,4]. 238 T.S. Syed, P.K. Braverman / Adolesc Med 15 (2004) 235–251 Abnormal vaginal discharge An abnormal discharge often is associated with other symptoms, such as complaints of itching or redness. This discharge can vary in color and consistency, such as thin, thick, frothy, yellow, green, gray, or white. Usually, abnormal discharge is from an infectious cause, but noninfectious etiologies are common as well. Douching, perfumed soaps, laundry detergent, toilet paper, fabric softeners, and other feminine hygiene products can act as local irritants producing an abnormal discharge. Another cause of abnormal discharge is a foreign body, such as a retained tampon, condom, or toilet paper, which tends to result in a malodorous, bloody discharge. Depending on the type of foreign body and duration, however, the discharge may have other characteristics. Infectious causes are usually sexually transmitted, such as chlamydia, gonorrhea, trichomoniasis, mycoplasma, ureaplasma, and, less commonly, herpes. Nonsexually transmitted infectious causes include BV and yeast. Yeast vaginitis Epidemiology Because it is not a reportable disease, the prevalence of yeast vaginitis is unknown. Prevalence of self-reported history of yeast vaginitis varies highly. In a population of university students, 54.7% reported a diagnosis of yeast vaginitis by age 25 [5]. In another student population, the prevalence of yeast was reported to be 20% [6] and in a family practice clinic the prevalence was approximately 72% [7]. Overall estimates are that approximately 75% of women will have at least one episode of yeast vaginitis in their lifetime. Recurrent episodes are also common. In a study of 2000 women over 18 years of age, 8% reported four or more episodes in a 1-year period [8]. The incidence may be higher because many women never seek medical attention because of self-diagnosis and subsequent treatment with OTC preparations. In 1995, OTC antifungal vaginal medication sales were reportedly approximately $269 million [9]. Although yeast usually causes characteristic signs and symptoms, asymptomatic colonization is present in 25% to 50% of immunocompetent females [10]. Approximately 80% to 92% of yeast infections are caused by Candida albicans. Saccharomyces cerevisiae and other candidal species such as C glabrata can be found in immunocompetent women with recurrent disease [11]. Pathogenesis Multiple factors contribute to a patient developing yeast vaginitis. Not only are vaginal epithelial cells more prone to infection with C albicans [12], but the vaginal environment seems to be inherently susceptible. Estrogen, for example, has been shown to enhance the adherence of Candida to vaginal epithelium, which may explain why increased infection is seen during pregnancy and with T.S. Syed, P.K. Braverman / Adolesc Med 15 (2004) 235–251 239 high-dose oral contraception (75 –150 mg) [6]. A woman also is predisposed to yeast vaginitis when she has taken broad-spectrum antibiotics, which eradicate the normal vaginal flora, allowing for overgrowth of yeast. The association of antibiotics was shown in a recent study to have an odds ratio of 1.75 in relation to yeast vaginitis [13]. Other associations with yeast growth include diabetes mellitus and other immunodeficiency states, such as HIV infection. In women with recurrent yeast vaginitis, presence of an immunocompromised state, particularly HIV, should be considered. Recurrent yeast infections also occur in women with an acquired, reduced T-cell reactivity to Candida antigen [14]. Although yeast vaginitis is not considered an STD, asymptomatic penile carriage as well as yeast balinitis can be responsible for yeast transmission to women. Treatment of male sexual partners has not been shown to prevent infections in women [15]. Links also have been made to orogenital sexual transmission [16]. Other risk factors include tightly fitting clothing, enuresis, and stress. Links related to recurrent yeast infections include the use of feminine hygiene products and sexual activity [17]. Yeast infections can occur in any age group, but occur most commonly in reproductive-aged women, whether sexually active or not. Clinical presentation Women with yeast vaginitis typically present with a complaint of vulvar itching, burning, redness, irritation, or discharge. Dysuria, particularly external dysuria, and urinary frequency are symptoms that often mislead clinicians to a diagnosis of cystitis but may indicate presence of yeast vaginitis instead. The patient usually describes the discharge as white, thick, and odorless. Typical ‘‘yeast symptoms’’ do not predict disease consistently. In a study of 545 women with symptoms characteristic for yeast vaginitis, only 28% had positive cultures for C albicans [18]. Thus, a thorough history and a consideration of STD testing are needed. Diagnosis A diagnosis of yeast vaginitis is made by the combination of clinical presentation, physical examination findings, and observation of yeast on the wet preparation. C albicans is the organism responsible for most uncomplicated cases. Upon physical examination, the labia and vaginal walls may appear erythematous and edematous. Because of the itching, involved perineal skin may be excoriated. The intertriginous groin area also may be erythematous with ‘‘satellite’’ lesions present. A thick, white discharge adhering to the vaginal walls may be observed. The diagnosis is supported by the observation on a wet preparation (saline and 10% potassium hydroxide) or Gram stain of vaginal discharge, which reveals the buds or pseudohyphae most commonly seen with C albicans. Other, less common species, such as C glabrata and S cerevisiae, produce only blastospores, which may be more difficult to detect with saline microscopy [11]. The use of 240 T.S. Syed, P.K. Braverman / Adolesc Med 15 (2004) 235–251 10% potassium hydroxide in wet preparations improves the visualization of yeast by disrupting cellular material that might obscure the yeast. Also associated are a normal vaginal pH of less than 4.5 and a lack of amine odor when potassium hydroxide is added [19]. Because the sensitivity of saline or potassium hydroxide microscopy is about 50%, often the diagnosis must be made based on history and physical examination. A culture is usually unnecessary to confirm a diagnosis, and a trial of antifungal treatment can be initiated. A culture may be indicated in cases of recurrent yeast vaginitis or for concerns of less common varieties of yeast that may be more resistant to standard therapy [11]. Treatment Because asymptomatic colonization occurs in over 20% of women, treatment should be initiated for symptomatic women. Three- to seven-day intravaginal topical formulations effectively treat uncomplicated yeast vaginitis (Box 1) [20]. Patients should be advised to apply the medication before going to sleep rather than upon waking to avoid leakage while upright. Topical azole drugs are more effective than nystatin, resulting in relief of symptoms and negative cultures in 80% to 90% of patients who complete therapy. Because the creams and suppositories are oil-based, the patient should be advised that it could weaken latex condoms. Unnecessary or inappropriate use of OTC preparations is common and can lead to the delay of treatment of other etiologies. Use of OTC preparations does not induce or increase significantly resistance of yeast to prescription azole therapy, however, although it may be a future concern [21]. Fluconazole, 150 mg, administered as a single dose is the only oral treatment approved by the US Food and Drug Administration (FDA) for the treatment of vaginal yeast infection. This single dose is as safe and effective as traditional, 7-day, intravaginal azole therapies [22], and this alternative oral treatment may be considered for adolescents who are uncomfortable with an intravaginal applicator, such as those who have never had sexual intercourse, or are averse to that method, such as those with a history of sexual assault. For patients with recurrent yeast vaginitis, an evaluation for underlying immunosuppressive disorders, such as diabetes mellitus and HIV, should be considered. Environmental changes, such as eliminating nylon and tightly fitting undergarments, could have an effect [23]. Because only high-dose oral contraceptives have been associated with yeast vaginitis, discontinuing the low-dose formulations should be considered only in extreme cases. Empiric treatment of sexual partners is usually not indicated, but for patients with recurrent infection, it may be helpful to examine the male partner for signs of yeast balinitis and treat him accordingly. In women with recurrent yeast infections, defined as four or more symptomatic episodes per year [20], cultures should be obtained to look for species that are not as sensitive to conventional antifungal treatment [11]. These patients may require longer treatment for up to 2 weeks with intravaginal antifungal medication or with oral fluconazole. In general, patients diagnosed T.S. Syed, P.K. Braverman / Adolesc Med 15 (2004) 235–251 241 Box 1. Centers for Disease Control and Prevention recommendations for treatment of yeast vaginitis [20] Intravaginal agents Butoconazole 2% cream, 5 g, intravaginally for 3 days (OTC) Butoconazole 2% cream, 5 g, single intravaginal application Clotrimazole 1% cream, 5 g, intravaginally for 7 to 14 days (OTC) Clotrimazole, 100 mg, vaginal tablet for 7 days Clotrimazole, 100 mg, vaginal tablet, two tablets for 3 days Clotrimazole, 500 mg, vaginal tablet, one tablet in a single application Miconazole 2% cream, 5 g, intravaginally for 7 days (OTC) Miconazole, 100 mg, vaginal suppository, one suppository for 7 days (OTC) Miconazole, 200 mg, vaginal suppository, one suppository for 3 days (OTC) Nystatin, 100,000 IU, vaginal tablet, one tablet for 14 days Tioconazole 6.5% ointment, 5 g, intravaginally in a single application (OTC) Terconazole 0.4% cream, 5 g, intravaginally for 7 days Terconazole 0.8% cream, 5 g, intravaginally for 3 days Terconazole, 80 mg, vaginal suppository, one suppository for 3 days Oral agent Fluconazole, 150 mg, oral tablet, one tablet in single dose and treated for uncomplicated yeast vaginitis do not require follow-up unless symptoms persist [20]. Trichomonas vaginitis Trichomonas vaginalis is one of the most ancient eukaryotic organisms. First described by Donne in 1836, this parasite continues to be one of the most common sexually transmitted infections, with an estimated 5 million new cases occurring annually in the United States [24]. Although most individuals are asymptomatic carriers, many infected persons suffer from chronic symptoms as well as serious complications. Its pathophysiology remains only partly understood, making it difficult to eradicate. 242 T.S. Syed, P.K. Braverman / Adolesc Med 15 (2004) 235–251 General morphology T vaginalis is seen upon direct microscopy as a one-celled motile trophozoite that is oval and about the size of a white blood cell (7 –15 mm). The morphology can vary, however, to at least twice that size and rounder shape. It has four anterior flagella and a fifth flagellum that is incorporated into its undulating membrane. An axostyle protrudes posteriorly, resulting in a pointed shape that is hypothesized to aid in attachment as well as contribute to cytotoxic damage of the vaginal environment. T vaginalis can be detected in vaginal and urine specimens (contaminated with vaginal or urethral secretions), as well as secretions from the male urethra, prostate, and epididymis [19,25]. Epidemiology True prevalence is unknown because trichomoniasis is not a reportable disease. Estimates from North America are more than 8 million new cases per year. With no geographic predilection, there are an estimated 170 million new cases annually of T vaginalis worldwide [26]. Reports from prenatal, family planning, and college health clinics show between 3% and 48% of sexually active females as being diagnosed with trichomoniasis [27]. Risk factors for trichomoniasis include a low socioeconomic status, African-American race, multiple sexual partners, and marijuana use [28]. Pathogenesis T vaginalis is considered a sexually transmitted infection because it is transmitted primarily through contact with genitourinary secretions. Theoretically, nonsexual transmission could occur, as live trichomonads can survive for a limited time outside of the human body in certain moist environments. In general, nonsexual transmission is extremely rare, so that when trichomoniasis is diagnosed, sexual transmission is presumed. Multiple mechanisms are involved in the virulence of T vaginalis, such as cellto-cell adhesion, hemolysis, the excretion of proteinases, and its ability to evade the host immune system [25,29,30]. T vaginalis produces changes in the vaginal environment that may facilitate growth of vaginal anaerobic bacteria, which may explain why trichomoniasis frequently co-occurs with BV [4,25]. Trichomoniasis also frequently is found concurrently with other STDs, such as gonorrhea, HIV, and chlamydia. The vigorous mechanical motion of the trichomonads is thought to harm normal cells, causing a variable amount of vaginal mucosal erythema. Colpitis macularis, also known as strawberry cervix, describes punctate intraepithelial hemorrhages on the cervix that can occur with trichomoniasis in approximately 2% of infected patients [25]. Diagnosis Female patients with trichomoniasis usually present with a complaint of profuse, frothy green, malodorous, watery discharge. Another common complaint T.S. Syed, P.K. Braverman / Adolesc Med 15 (2004) 235–251 243 is that of pruritis. The examination may show only mild vaginal inflammation and rarely, colpitis macularis [31]. As with all STDs, however, frequently there are no symptoms, especially in males. The diagnosis in a male patient is made clinically either by a persistent urethritis where other diagnoses have been ruled out, or by partner exposure. Less commonly, men with trichomoniasis complain of urethral discharge and have inflammatory cells present in urethral secretions [32]. Upon physical examination of the female patient, the diagnosis is suggested by observation of the characteristic copious, green, frothy discharge, performing a vaginal pH, which is typically above 5, and detecting a positive whiff when potassium hyrdoxide is added to the wet mount. The diagnosis is confirmed by observing motile trichomonads by way of direct saline microscopy. This is the most efficient and cost-effective way to diagnose trichomoniasis. Recent metaanalysis of studies using the wet preparation to diagnose trichomoniasis revealed a pooled sensitivity rate of 58% and specificity of 65% [33]. The sensitivity depends on the clinician’s microscopy skills as well as the timing of observation. The diagnostician must be careful to view a fresh specimen, as trichomonads die in as few as 10 minutes [34]. To aid in specimen preservation, after the sample is taken with a cotton-tipped swab and placed into a test tube of 1 mL of nonbacteriostatic saline, the patient can be asked to hold the test tube, which keeps the specimen warm and may increase the longevity of the trichomonads, if present. It is important to scan the entire slide with a careful eye to detect trichomonads that are slow-moving or atypical in appearance. Trichomoniasis also is reported occasionally on routine Papanicolaou smears. Although a pooled sensitivity was reported to be 57%, Papanicolaou smears have the advantage of being fixed and read at a later time, which may account for the higher pooled specificity of 97% found on meta-analysis [33]. Several commercial laboratory tests for trichomoniasis are available. The most common is the In PouchTV (Biomed Diagnostics, San Jose, California), which is a special liquid medium that allows growth of the organism so that it can be visualized subsequently upon direct microscopy for up to 5 days. The medium is inoculated by placing female or male urogenital specimens directly into the pouch containing the growth medium. The reagents in the medium contain trypticase, protease peptone, yeast extract, maltose and other sugars, amino acids, salts, and antifungal and antimicrobial agents in a normal saline phosphate buffer. Using the In PouchTV can increase trichomoniasis detection rates by twofold compared with the wet preparation [35,36]. It is a good alternative to other culture media that are costly and difficult to obtain. Several culture media for trichomoniasis exist, such as the Diamond’s trypticase –yeast extract – maltose (TYM), which traditionally has been the most sensitive (92% – 95%) and is thus regarded as the criterion standard [37]. Other testing methods, such as direct immunoflourescence assay, direct enzyme immunoassay, and latex agglutination, for trichomoniasis also have been developed. Although all three are more sensitive than wet preparation and give fairly rapid results, they are not readily available. Newer rapid diagnostic tests using DNA probes and monoclonal 244 T.S. Syed, P.K. Braverman / Adolesc Med 15 (2004) 235–251 antibodies are showing improved sensitivities of up to 99% [38,39]. No FDAapproved polymerase chain reaction test for trichomoniasis is available in the United States, but some are available from some commercial laboratories [20]. Treatment The only class of medications useful for treating trichomoniasis is the nitroimidazoles. Metronidazole is the only type available in the United States and approved by the FDA for the treatment of trichomoniasis. The current recommendation for treatment is metronidazole, 2 g, orally in a single dose, which results in cure rates as high as 90% to 95% [20]. Increased cure rates are seen with partner treatment and should be advised routinely. Patients should be warned about the side effects of metronidazole, such as gastrointestinal effects and the disulfiram-like effect when alcohol is consumed. No treatment is as efficacious as the oral form; thus, metronidazole intravaginal gel is not recommended to treat trichomoniasis, as it does not achieve therapeutic levels in the urethra or perivaginal glands [40,41]. Other topical preparations, such as nonoxynol-9, are much less efficacious than oral metronidazole [42]. In teenagers, follow-up in 1 month should be considered to ensure that the medicine was taken, that the partner was notified to obtain treatment, and that reinfection did not occur. A vaginal swab taken during the follow-up visit could help to confirm treatment success. If trichomoniasis is still detected, reinfection should be suspected. Although fairly rare, metronidazole-resistant trichomoniasis has been reported [43]. For refractory or suspected resistant cases, the patient should be treated with metronidazole, 500 mg, twice a day orally for 7 days. If treatment failure occurs again, the patient should be treated with metronidazole orally, 2 g, once a day for 3 to 5 days. Trichomoniasis that does not resolve with this regimen may warrant culture and susceptibility testing. Partner treatment should be ensured and abstinence should be recommended until partner treatment is accomplished. For patients with an allergy or severe adverse reactions to metronidazole, desensitization is recommended [20,44]. Complications Trichomoniasis has been linked with adverse pregnancy outcomes—mainly premature rupture of membranes, preterm delivery, and low birthweight [27,45]. These links are not strong because of confounding factors, such as smoking, that make data difficult to interpret. Also, treating asymptomatic infections does not appear to lessen the associations [46]. Pregnant women, as well as those who are infected with HIV, can be treated with metronidazole, 2 g, orally in a single dose. Multiple studies have not demonstrated a consistent association between metronidazole and teratogenic or mutagenic effects in infants [20]. There have been an increasing number of reports of HIV acquisition associated with trichomoniasis [47,48]. This relationship is most likely caused by the local cytotoxic damage done by the trophozoite, with resulting inflammation and physical breakdown of the mucosal barrier. Patients with HIV and trichomoniasis T.S. Syed, P.K. Braverman / Adolesc Med 15 (2004) 235–251 245 also have been reported to have higher incidence of PID [49]. The relationship of trichomoniasis and PID may be caused by the motility of the trichomonads, which may facilitate the movement of other organisms from the vagina to the upper reproductive organs. Bacterial vaginosis Definition Bacterial vaginosis is a clinical syndrome that is represented by complex and poorly understood changes in the normal vaginal flora that result in discharge with a fishy odor. Although frequently included as a cause of vaginitis, BV is truly a vaginosis because it does not cause inflammation typical of a vaginitis. Despite the difference in terminology, symptomatic BV is the most common cause of abnormal discharge and odor. The overall prevalence is underestimated, however, because of the large number of asymptomatic patients. Pathogenesis The pathophysiology of BV involves the replacement or reduction of the normal hydrogen peroxide – producing lactobacillus species in the vagina. This environmental change allows growth of higher-than-normal concentrations of mixed anaerobic bacteria, including Gardnerella vaginalis, Peptostreptococcus spp, Prevotella spp, Mycoplasma hominis, Ureaplasma urealyticum, and Mobiluncus spp [3,50,51]. The cause of BV is not well understood, but significant associations and predisposing factors have been hypothesized. For example, BV usually is diagnosed more frequently in sexually active reproductive-aged patients. Despite this association, partner treatment is not effective, but the use of condoms during intercourse tends to reduce the symptoms. Because BV also is diagnosed occasionally in virgins, it is not considered to be a sexually transmitted infection. Women may be more predisposed to developing BV if they lack normal lactobacilli. Douching and use of other chemical ‘‘hygiene’’ products also can alter the vaginal ecosystem and result in BV [1]. Clinical presentation A patient with BV typically presents with a complaint of vaginal discharge with a fishy odor. There are otherwise no complaints of systemic symptoms, such as pain or rashes. Although not required for the diagnosis, there is typically a history of sexual activity. Diagnosis A combination of clinical and laboratory findings can be used to diagnose BV. Upon speculum examination, a characteristic thin, gray or white, homogenous 246 T.S. Syed, P.K. Braverman / Adolesc Med 15 (2004) 235–251 discharge can be seen coating the vaginal walls. Because of the lack of lactic acid and hydrogen peroxide production, the vaginal pH is elevated above 4.5. There is no pain associated; therefore, the bimanual examination is normal with this condition. The saline wet preparation reveals a lack of lactobacilli and presence of clue cells, which are vaginal epithelial cells that have a stippled or foamy appearance from being studded with bacteria. To classify as a true clue cell, the bacteria should cover the surface of the epithelial cell and spread past the cell boundary, giving a ‘‘shaggy’’ appearance [19]. Because BV produces a noninflammatory discharge, a normal amount of white blood cells (fewer than 7– 10 per high-power field) is observed. The amines putracine and cadaveracine, volatized from the wet mount sample when potassium hydroxide is added, give a characteristic fishy odor (a positive whiff). BV can be diagnosed by the use of clinical or Gram stain criteria. Clinical criteria first described by Amsel and colleagues [52]and recommended by the Centers for Disease Control and Prevention [20] require three of the four following symptoms or signs: positive whiff greater than 20% per high-power field of clue cells a thin, gray or white, noninflammatory, homogenous vaginal discharge that coats the walls vaginal pH above 4.5 Gram-stained vaginal smears as a way of diagnosing BV also have been described [53]. Because the sensitivity is low, a modification of grading Gram stains based on lactobacillus and other bacterial morphotypes into three grades was developed by Nugent [54]. Grade I is considered normal, grade II is intermediate, and grade III is equated with BV. Grade II and III show strong correlation with the clinical criteria, with sensitivities of 37% and 92%, respectively [55]. The use of Papanicolaou-stained smears to diagnose BV also has been described, but is less reliable, is inconvenient because of a minimum 2- to 3-weeks’ reporting time, and requires a confirmatory test if positive [56,57]. Newer, commercially available tests, such as the FemExam test card (Cooper Surgical, Shelton, Connecticut) and Pip Activity TestCard (Litmus Concepts, Inc., Santa Clara, California), detect increased pH and amines and may be helpful for the diagnosis of BV [20]. Complications BV has been associated with pregnancy-related complications, such as preterm labor and birth, premature rupture of membranes, low birth weight, clinical and microscopic evidence of chorioamnionitis, postpartum endometritis, and postoperative infections [58 – 60]. The associations of pregnancy-related complications are strengthened by the results of several studies that indicate that treatment of pregnant women who have BV and are at high risk for preterm delivery T.S. Syed, P.K. Braverman / Adolesc Med 15 (2004) 235–251 247 may reduce the risk for prematurity. BV is also a risk factor for PID [61,62]. For example, bacteria associated with BV have been recovered from the endometrium and fallopian tubes of women who have PID. BV has also been linked to postabortion PID. Postabortion infectious complications also were reduced in those treated for BV in other trials. Thus, screening and treatment for BV before a procedure that involves instrumentation of the cervix, such as a surgical abortion, should be considered [20]. Treatment BV can be difficult to treat, with recurrences as high as 30% to 40% [63,64]. The purpose of the current therapy is to decrease the amount of anaerobic bacteria so that the normal lactobacillus has a chance to regrow and stabilize the vaginal environment. The most successful therapy to date for nonpregnant females is metronidazole. This drug can be given orally in a dosage of 500 mg twice a day for 7 days (Box 2) [20]. Metronidazole also is available as an intravaginal preparation. Unlike trichomoniasis, for BV metronidazole gel is equally efficacious as the oral form. Patients should be advised to avoid alcohol consumption during treatment and 24 hours thereafter to avoid the disulfiram-like reaction. Clindamycin cream and ovules also are used to treat BV, but are less efficacious compared with the metronidazole regimens and should not be used as first-line treatment. Again, clinicians should warn patients that the use of oil-based medications may weaken latex condoms. The recommendation for pregnant women with BV is metronidazole, 250 mg, three times a day for 7 days [20]. Environmental changes, such as avoidance of douching or other feminine hygiene Box 2. Centers for Disease Control and Prevention recommendations for the treatment of bacterial vaginosis [20] Recommended treatments Metronidazole, 500 mg, twice a day for 7 days Metronidazole gel 0.75% one full applicator (5 g) intravaginally, once a day for 5 days Clindamycin cream 2%, one full applicator (5 g) intravaginally at bedtime for 7 days Alternative treatments Metronidazole, 2 g, orally in a single dose Clindamycin, 300 mg, orally twice a day for 7 days Clindamycin ovules, 100 g, intravaginally once at bedtime for 3 days 248 T.S. Syed, P.K. Braverman / Adolesc Med 15 (2004) 235–251 products and use of barrier contraception, are helpful. Other therapies, such as oral and intravaginal lactobacillus as a way of recolonizing the vagina, have shown varying success [65]. Partner treatment does not appear to affect the disease process in women, and thus is not recommended. 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