Vaginitis in adolescents *, Paula K. Braverman, MD a,

Transcription

Vaginitis in adolescents *, Paula K. Braverman, MD a,
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: [email protected] (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. Follow-up usually is
not necessary for BV, although if it is, one should allow at least 1 month to
diagnosis treatment failure or reoccurrence. Long-term maintenance with any
regimen is not recommended.
Summary
Vaginitis is a common complaint of adolescent females. It can cause extreme
distress for some patients, especially those with recurrent symptoms. Thus, it is
important to take care when evaluating these patients and to acknowledge their
frustration when appropriate. A thoughtful and thorough history will determine
most causes, with the most common being yeast, trichomoniasis, and BV.
References
[1] Merchant J, Oh K, Klerman L. Douching: a problem for adolescents girls and young women.
Arch Pediatr Adolesc Med 1999;153:834 – 7.
[2] Nyirjesy P. Vaginitis in the adolescent patient. Pediatr Clin North Am 1999;46:733 – 45.
[3] Mardh PA. The vaginal ecosystem. Am J Obstet Gynecol 1991;165:1163 – 8.
[4] Carr P, Felsenstein D, Friedman R. Evaluation and management of vaginitis. J Gen Intern Med
1998;13:335 – 46.
[5] Geiger A, Foxman B, Gillespie B. The epidemiology of vulvovaginal candidiasis among university students. Am J Pub Health 1995;85:1146 – 8.
[6] Foxman B. The epidemiology of vulvovaginal candidiasis: risk factors. Am J Public Health
1990;80:329 – 31.
[7] Berg AO, Heidrich FE, Fihn SD, Bergman JJ, Wood RW, Stamm WE. Establishing the cause
of genitourinary symptoms in women in a family practice. Comparison of clinical examination
and comprehensive microbiology. JAMA 1984;251:620 – 5.
[8] Foxman B, Barlow R, D’Arcy H, Gillespie B, Sobel JD. Candida vaginitis: self-reported incidence and associated costs. Sex Transm Dis 2000;27:230 – 5.
[9] DP Hamacher & Associates (Hamacher Resource Group). Stock Check. Feminine health care:
a changing market share. Drug Topics 1996;42 – 7.
[10] Holland J, Young M, Lee O, Chen S. Vulvovaginal carriage of yeasts other than Candida
albicans. Sex Transm Infect 2003;79:249 – 50.
[11] Nyirjesy P, Seeney S, Terry Grody M, Jordan C, Buckely H. Chronic fungal vaginitis: the value
of cultures. Am J Obstet Gynecol 1995;173:820 – 3.
[12] King RD, Lee J, Morris A. Adherence of Candida albicans and other Candida species to mucosal
epithelial cells. Infect Immun 1980;27:667 – 74.
[13] Spinillo A, Capuzzo E, Acciano S, De Santolo A, Zara F. Effect of antibiotic use on the prevalence of symptomatic vulvovaginal candidiasis. Am J Obstet Gynecol 1999;180(1 Pt 1):14 – 7.
[14] Sobel J. Pathogenesis and treatment of recurrent vulvovaginal candidiasis. Clin Infect Dis 1992;
14:S148 – 53.
[15] Sobel J. Pathophysiology of vulvovaginal candidiasis. J Reprod Med 1989;34:S572 – 80.
[16] Geiger A, Foxman B. Risk factors for vulvovaginal candidiasis: a case-control study among
university students. Epidemiology 1996;7:182 – 7.
[17] Spinillo A, Pizzoli G, Colonna L, Nicola S, De Seta F, Guaschino S. Epidemiologic character-
T.S. Syed, P.K. Braverman / Adolesc Med 15 (2004) 235–251
[18]
[19]
[20]
[21]
[22]
[23]
[24]
[25]
[26]
[27]
[28]
[29]
[30]
[31]
[32]
[33]
[34]
[35]
[36]
[37]
[38]
[39]
249
istics of women with idiopathic recurrent vulvovaginal candidiasis. Obstet Gynecol 1993;81:
721 – 7.
Eckert LO, Hawes SE, Stevens CE, Koutsky LA, Eschenbach DA, Holmes KK. Vulvovaginal
candidiasis: clinical manifestations, risk factors, management algorithm. Obstet Gynecol 1998;
92:757 – 65.
Metzger G. Laboratory diagnosis of vaginal infections. Clin Lab Sci 1998;11:47 – 52.
Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines
2002. MMWR Recomm Rep 2002;51(RR-6):1 – 80.
Mathema B, Cross E, Dun E, Park S, Bedell J, Slade B, et al. Prevalence of vaginal colonization
by drug-resistant Candida species in college-age women with previous exposure to over-thecounter azole antifungals. Clin Infect Dis 2001;33:e23 – 7.
Sobel J, Brooker D, Stein G. Single oral dose fluconazole compared with conventional clotrimazole tropical therapy of Candida vaginitis. Am J Obstet Gynecol 1995;172:1263 – 8.
Sobel J, Faro S, Force R, Foxman B, Ledger WJ, Nyirjesy PR, et al. Vulvovaginal candidiasis:
epidemiologic, diagnostic, and therapeutic considerations. Am J Obstet Gynecol 1998;178:
203 – 11.
Cates Jr W. Estimates of the incidence and prevalence of sexually transmitted diseases in the
United States. American Social Health Association Panel. Sex Transm Dis 1999;26:52 – 7.
Petrin D, Delgaty K, Bhatt R, Garber G. Clinical and microbiological aspects of Trichomonas
vaginalis. Clin Microbiol Rev 1998;11:300 – 17.
World Health Organization. An overview of selected curable sexually transmitted diseases. In:
Global program on AIDS. Geneva (Switzerland): World Health Organization; 1995.
Cotch M, Pastorek J, Nugent R, Hillier SL, Gibbs RS, Martin DH, et al. Trichomonas vaginalis
associated with low birth weight and preterm delivery. The Vaginial Infections and Prematurity
Study Group. Sex Transm Dis 1997;24:353 – 60.
Crosby R, DiCliemente R, Wingood G, Harrington K, Davies SL, Hook EW, et al. Predictors of
infection with Trichomonas vaginalis: a prospective study of low income African-American
adolescent females. Sex Transm Dis 2002;78:360 – 4.
Alderete J, Provenzano D. The vagina has reducing environment sufficient for activation of
Trichomonas vaginalis cysteine proteinases. Genitourin Med 1997;73:291 – 6.
Lehker M, Sweeney D. Trichomonad invasion of the mucous layer requires adhesins, mucinases,
and motility. Sex Transm Infect 1999;75:231 – 8.
Wolner-Hanssen P, Krieger J, Stevens C, Kiviat NB, Koutsky L, Critchlow C, et al. Clinical
manifestations of vaginal trichomoniasis. JAMA 1989;261:571 – 6.
Krieger J, Jenny C, Verdon M, Siegel N, Springwater R, Critchlow C, et al. Clinical manifestations of Trichomoniasis in men. Ann Intern Med 1993;118:844 – 9.
Wiese W, Patel SR, Patel SC, Ohl C, Estrada C. A meta-analysis of the Papanicolaou smear
and wet mount for the diagnosis of vaginal trichomoniasis. Am J Med 2000;108:301 – 8.
Kingston MA, Bansal D, Carlin EM. ‘Shelf life’ of Trichomonas vaginalis. Int J STD AIDS 2003;
14:28 – 9.
Ohlemeyer C, Hornberger L, Lynch D, Swierkosz E. Diagnosis of Trichomonas vaginalis in
adolescent females: InPouch TV culture versus wet-mount microscopy. J Adolesc Health 1998;
22:205 – 8.
Borchardt K, Zhang M, Shing H, Flink K. A comparison of the sensitivity of the InPouch TV,
Diamond’s, and Trichosel media for detection of Trichomonas vaginalis. Genitourin Med 1997;
73:297 – 8.
Lossick J, Kent H. Trichomonas: trends in diagnosis and management. Am J Obstet Gynecol
1991;165:1219 – 22.
Paterson B, Tabrizi S, Garland S, Fairley C, Bowden F. The tampon test for trichomoniasis:
a comparison between conventional methods and a polymerase chain reaction for Trichomonas
vaginalis in women. Sex Transm Infect 1998;74:136 – 9.
Witkin S, Inglis S, Polaneczky M. Detection of Chlamydia trachomatis and Trichomonas vaginalis by polymerase chain reaction in introital specimens from pregnant women. Am J Obstet
Gynecol 1996;175:165 – 7.
250
T.S. Syed, P.K. Braverman / Adolesc Med 15 (2004) 235–251
[40] duBouchet L, McGregor J, Ismail M, McCormack W. A pilot study of metronidazole vaginal gel
versus oral metronidazole for the treatment of Trichomonas vaginalis vaginitis. Sex Transm Dis
1998;25:176 – 9.
[41] Pattman R. Recalcitrant vaginal trichomoniasis. Sex Transm Infect 1999;75:127 – 8.
[42] Antonelli N, Diehl S, Wright J. A randomized trial of intravaginal nonoxynol 9 versus oral
metronidazole in the treatment of vaginal trichomoniasis. Am J Obstet Gynecol 2000;182:
1008 – 10.
[43] Sobel J, Nagappan V, Nyirjesy P. Metronidazole-resistant vaginal trichomoniasis-an emerging
problem [correspondence]. N Engl J Med 1999;341:292 – 3.
[44] Pearlman M, Yashar C, Ernst S, Solomon W. An incremental dosing protocol for women with
severe vaginal trichomoniasis and adverse reactions to metronidazole. Am J Obstet Gynecol
1996;174:934 – 6.
[45] Minkoff H, Grunebaum A, Schwarz R, Feldman J, Cummings M, Cromblehome W, et al. Risk
factors for prematurity and premature rupture of membranes: a prospective study of the vaginal
flora in pregnancy. Am J Obstet Gynecol 1984;150:965 – 72.
[46] Klebanoff M, Carey C, Hauth J, Hillier SL, Nugent RP, Thom EA, 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.
[47] Buve A, Weiss H, Laga M, Van Dyck E, Musonda R, Zekeng L, et al. The epidemiology of
trichomonas in women in four African cities. AIDS 2001;15(Suppl 4):S89 – 96.
[48] Sorvillo F, Kerndt P. Trichomonas vaginalis and amplification of HIV-1 transmission. Lancet
1998;351:213 – 4.
[49] Moodley P, Wilkinson D, Connolly C, Moodley J, Sturm A. Trichomonas vaginalis is associated with pelvic inflammatory disease in women infected with human immunodeficiency virus.
Clin Infect Dis 2002;34:519 – 22.
[50] Hill G. The microbiology of bacterial vaginosis. Am J Obstet Gynecol 1993;169:450 – 4.
[51] Schwebke J, Lawing L. Prevalence of Mobiluncus spp among women with and without bacterial
vaginosis as detected by polmerase chain reation. Sex Transm Dis 2001;28:195 – 9.
[52] Amsel R, Totten P, Spiegel C, Chen K, Eschenbach D, Holmes K. Nonspecific vaginitis.
Diagnostic criteria and microbial and epidemiologic associations. Am J Med 1983;74:14 – 22.
[53] Speigel C, Amsel R, Holmes K. Diagnosis of bacterial vaginosis by direct gram stain of vaginal
fluid. J Clin Microbiol 1983;18:170 – 7.
[54] Nugent R, Krohn M, Hillier S. Reliability of diagnosing bacterial vaginosis is improved by a
standardized method of gram stain interpretation. J Clin Microbiol 1991;29:297 – 301.
[55] Taylor-Robinson D, Morgan D, Sheehan M, Rosenstein I, Lamont R. Relation between gramstain and clinical criteria for diagnosing bacterial vaginosis with special reference to gram grade
II evaluation. Int J STD AIDS 2003;14:6 – 10.
[56] Lamont R, Hudson E, Hay P, et al. A comparison of the use of Papanicolaou-stained cervical
cytological smears with gram-stained vaginal smears for the diagnosis of bacterial vaginosis in
early pregnancy. Int J STD AIDS 1999;10:93 – 7.
[57] Davis J, Connor E, Clark P, Wilkinson E, Duff P. Correlation between cervical cytologic results
and gram stain as diagnostic tests for bacterial vaginosis. Am J Obstet Gynecol 1997;177:532 – 5.
[58] Eschenbach D. Bacterial vaginosis: emphasis on upper genital tract complications. Obstet Gynecol Clin North Am 1989;16:593 – 610.
[59] McGregor J, French J, Seo K. Premature rupture of membranes and bacterial vaginosis. Am J
Obstet Gynecol 1993;169:463 – 6.
[60] Leitich H, Bodner-Adler B, Brunbauer M, Kaider A, Egarter C, Husslein P. Bacterial vaginosis
as a risk factor for preterm delivery: a meta-analysis. Am J Obstet Gynecol 2003;189:139 – 47.
[61] Peipert J, Montagno A, Cooper A, Sung JC. Bacterial vaginosis as a risk factor for upper genital
tract infection. Am J Obstet Gynecol 1997;177:1184 – 7.
[62] Sweet R. Role of bacterial vaginosis in pelvic inflammatory disease. Clin Infect Dis 1995;20:
S271 – 5.
[63] Cook R, Redondo-Lopez V, Schmitt C, Meriwether C, Sobel J. Clinical, microbiological, and
biochemical factors in recurrent bacterial vaginosis. J Clin Microbiol 1992;30:870 – 7.
T.S. Syed, P.K. Braverman / Adolesc Med 15 (2004) 235–251
251
[64] Briselden A, Hillier S. Longitudinal study of the biotypes of Gardnerella vaginalis. J Clin Microbiol 1990;28:2761 – 4.
[65] Van Kessel K, Assefi N, Marrazzo J, Eckert L. Common complimentary and alternative therapies for yeast vaginitis and bacterial vaginosis: a systematic review. Obstet Gynecol Surv 2003;
58:351 – 8.