Clinical Expert Series

Management of Persistent Vaginitis
Paul Nyirjesy,

MD

With vaginitis remaining a common condition that leads women to seek care, it is not surprising
that some women develop chronic vulvovaginal problems that are difficult to diagnose and
treat. With a differential diagnosis that encompasses vulvar disorders and infectious and
noninfectious causes of vaginitis, accurate diagnosis is the cornerstone of choosing effective
therapy. Evaluation should include a symptom-specific history, careful vulvar and vaginal
examination, and office-based tests (vaginal pH, amine test, saline and 10% potassium hydroxide
microscopy). Ancillary tests, especially yeast culture with speciation, are frequently crucial to
obtaining a correct diagnosis. A heavy but normal physiologic discharge can be determined by
excluding other causes. With vulvovaginal candidiasis, differentiating between Candida albicans
and non-albicans Candida infection has important treatment ramifications. Most patients with C
albicans infections can be successfully treated with maintenance antifungal therapy, usually with
fluconazole. Although many non-albicans Candida, particularly Candida glabrata, may at times
be innocent bystanders, vaginal boric acid therapy is an effective first choice for many true nonalbicans Candida infections. Recurrent bacterial vaginosis, a difficult therapeutic challenge, can
often be controlled with maintenance therapy. Multiple options, especially high-dose tinidazole,
have been used for metronidazole-resistant trichomoniasis. With the aging of the U.S. population, atrophic vaginitis and desquamative inflammatory vaginitis, both associated with hypoestrogenism, are encountered frequently in women with persistent vaginitis.
(Obstet Gynecol 2014;0:1–12)
DOI: 10.1097/AOG.0000000000000551

V

aginal complaints are considered one of the most
common reasons that women seek the care of
a health care provider.1 Although the word “vaginitis”
is used as a diagnostic term by patients and health care
providers alike, it is a nonspecific term encompassing
a broad range of conditions that cause vulvovaginal
symptoms and affect women in virtually every age
group. After a standard evaluation, it is estimated that
70% of episodes of vaginitis in premenopausal women
are caused by bacterial vaginosis, vulvovaginal candi-

From the Department of Obstetrics and Gynecology, Drexel University School of
Medicine, Philadelphia, Pennsylvania.
Continuing medical education for this article is available at http://links.lww.
com/AOG/A573.
Corresponding author: Paul Nyirjesy, MD, 245 North 15th Street, New
College Building, 16th Floor, Philadelphia, PA 19102; e-mail: pnyirjes@
drexelmed.edu.
Financial Disclosure
Dr. Nyirjesy has been a consultant for Novadigm, Viamet Pharmaceuticals,
Symbiomix, Cepheid, and Hologics. He has received research grants from
Novadigm, Viamet Pharmaceuticals, Symbiomix, and Becton–Dickinson.
© 2014 by The American College of Obstetricians and Gynecologists. Published
by Lippincott Williams & Wilkins.
ISSN: 0029-7844/14

VOL. 0, NO. 0, MONTH 2014

diasis, and trichomoniasis.2 Furthermore, as the population in the United States ages, an increasing
number of women may develop symptomatic atrophic vaginitis. For most women, episodes of vaginitis
will resolve without any difficulty or long-term
sequelae.
On the other hand, many women with vulvovaginal symptoms remain undiagnosed or either fail to
improve or recur after treatment. Although persistent
vaginitis is seldom life-threatening, it leads to morbidities of discomfort and pain, days lost from school or
work, and impaired sexual functioning and self-image.
Because women with chronic or recurrent symptoms
are a therapeutic challenge for health care providers,
their problems may be ignored or trivialized and may
last for months or years. As a result, they often selfmedicate with various over-the-counter and alternative medicines; sometimes these treatments in turn
exacerbate symptoms and make the overall problem
worse.3 This article describes a systematic approach to
diagnosis and management, which can lead to complete cure or at least significant symptom resolution
for the vast majority of affected women.

OBSTETRICS & GYNECOLOGY

Copyright ª American College of Obstetricians and Gynecologists

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the mode of administration (oral. itching. erosions. Finally. they serve to underscore the broad differential diagnosis. or alterations in the vulvar architecture such as periclitoral scarring or resorption of the labia minora. color. topical. antibiotics. knowing the timing of the last dose of any treatment is important. 18% had two or more concurrent diagnoses. ulcers. finding erosive lichen planus in the mouth or hidradenitis suppurativa in the axillae makes it easier to recognize it on the vulva. but health care providers should note that many women with persistent “vaginitis” have chronic vulvar diseases. they should be avoided wherever possible. atrophy. including separating all the skin folds to look for abnormalities such as redness. When doing so. which complicate management and prevent overall improvement. It may seem daunting to evaluate a woman who has seen multiple health care providers and tried many therapies over the years without improvement. For example. irritation.3 the differential diagnosis encompasses a broad array of vulvar and vaginal conditions. chronic discomfort. it is helpful to review patient symptoms in detail with a structured interview. or combinations thereof. we review what types of treatments have been administered (antifungals. if a woman reliably improves after each course of antifungal therapy only to recur later. and acute exacerbations of chronic discomfort. asking about chronic dyspareunia and whether it is with intromission as opposed to thrusting is quite important. corticosteroids. Asking patients whether symptoms are located mainly in 2 Nyirjesy Management of Persistent Vaginitis the vulva. erosions. because cervicitis can cause an abnormal irritating discharge. recurrent vulvovaginal candidiasis (21%). Thus. the length of therapy for each course (episodic or maintenance). fissures. accurate diagnosis is the cornerstone of effective therapy. questions about soaps. and even synechiae before obtaining samples. the cervix itself should be examined to assess for any mucopurulent discharge or areas of contact bleeding. and use of over-the-counter antifungal and numbing agents containing sensitizers such as benzocaine are important for identifying and removing possible irritants. viscosity.5 Conversely. Although these results may be different in other practice populations. Although this type of review may seem time-consuming. Similarly. Finally. Nyirjesy and colleagues4 found that the most common diagnoses were contact dermatitis (21%). douching. but being aware of possible causes creates a framework for evaluation and management. even women with obvious vulvar diseases such as lichen sclerosus can also have vaginal processes such as candidiasis or atrophic vaginitis. and physiologic discharge (9%). burning. For example. With symptoms such as itching. and the response to each type of therapy (complete. Patients who report an abnormal discharge are asked about quantity. and relationship to the menstrual cycle. a sign of possible vestibulodynia. A general physical examination may yield a diagnosis before doing a pelvic examination. it only takes a few minutes and provides a concise picture of what symptoms are bothering the patient. With contact dermatitis commonly found in this population. atrophic vaginitis (15%). nonexistent). This review focuses on the etiology and treatment of those entities that cause primarily vaginal symptoms. masses. dermatologic. a sexual history may lead to testing for sexually transmitted infections. vestibule. she is much more likely to have vulvovaginal candidiasis than someone who describes no improvement. burning or irritation. Examination of the vestibule should also include palpation with a swab to look for tenderness. or vagina can be helpful. Those reporting an abnormal odor are asked to describe it in more detail. 62% of whom had had symptoms for more than 1 year. including infectious. and neuropathic pain conditions. particularly in women with chronic symptoms. feminine hygiene products. inflammatory. Furthermore. In this population in which selftreatment is common. Pelvic examination should begin with inspection of the vulva. estrogen). we try to distinguish among acute episodes.EVALUATION OF PATIENTS WITH PERSISTENT VAGINITIS Although most women with chronic vaginitis believe that they have recurrent yeast infections. recently discussed by the American College of Obstetricians and Gynecologists.6 Obtaining an appropriate history is the first step to proper diagnosis. even short term. odor. partial. Because selfdiagnosis and telephone diagnosis are frequently inaccurate. localized provoked vestibulodynia (13%). Because patients have frequently received many different forms of treatment. In one prospective survey of 200 patients evaluated at a tertiary care vaginitis center. both). Patient symptoms can be broadly grouped into those of discharge. which we routinely administer in our tertiary care vaginitis center. because women with localized provoked vestibulodynia have pain with penetration but few daily symptoms. vaginal evaluation should start with inspection to look for evidence of inflammation. because any recent medication hampers the clinician’s ability to do a thorough evaluation. Practice guidelines by both the American College of Obstetricians and Gynecologists6 and the Centers OBSTETRICS & GYNECOLOGY Copyright ª American College of Obstetricians and Gynecologists .

estrogen plays a key role in maintaining the normal vaginal environment. they are more costly than current modalities. Obstet Gynecol 2014. should be considered for focal abnormalities. particularly if the etiology is unclear. During a woman’s reproductive years. Figure 2. Reprinted with kind permission from Springer Science+Business Media: Nyirjesy P. Although these latter two organisms may be commensals. yeast cultures with speciation of the organism play an integral part in diagnosing. Finally. the gold standard test remains either culture or the more easily available polymerase chain reaction (PCR) with the U.4 understanding the normal vaginal environment is important. and group B streptococci are frequently found. Lactobacilli become the dominant flora. Polymerase chain reaction testing for Neisseria gonorrhoeae and Chlamydia trachomatis and bacterial cultures looking specifically for group A strep- tococci or Staphylococcus aureus should be considered in women with many white blood cells on saline microscopy.7:458–62.7. Gardnerella vaginalis. We perform this latter test in all of our patients at risk for a sexually transmitted infection. culture of the vagina demonstrates a variety of organisms. NORMAL VAGINAL PHYSIOLOGY AND DISCHARGE With physiologic discharge occurring as the final diagnosis in 9% of the patients referred to our tertiary care program. Frequently underused.S. Before puberty. fissures.8 Saline microscopy can aid in diagnosing bacterial vaginosis and trichomoniasis. In addition. As shown in Table 1. including skin and fecal flora and lactobacilli. those with many white blood cells on microscopy. VOL. Routine bacterial cultures are otherwise unhelpful and can be misleading. Sobel JD. the vaginal epithelium thickens. vulvar biopsies. which lowers the pH of the vagina to less than 4. PCR testing for yeast and bacterial vaginosis). Food and Drug Administration–cleared APTIMA T vaginalis assay.for Disease Control and Prevention7 stress the importance of in-office testing for vaginal pH. MONTH 2014 Nyirjesy Management of Persistent Vaginitis Copyright ª American College of Obstetricians and Gynecologists 3 . 0. vaginal pH testing in particular can be used to drive the entire diagnostic process.9 For other tests for vaginal infections (ie. Advances in diagnosing vaginitis: development of a new algorithm. the vagina is thinned and has a high pH. these easily available tests can frequently diagnose common forms of vaginitis. and in the case of PCR testing for yeast and bacterial vaginosis. there is currently little evidence that they are superior to current gold standards. The findings of vesicles. If Trichomonas vaginalis infection is suspected but not proven. Vaginal Fig. because normal vaginal flora such as Escherichia coli. A pH-based framework for diagnosing the most common causes of vaginitis. amines. and. Curr Infect Dis Rep 2005. and both saline and 10% potassium hydroxide microscopy. and ancillary tests are frequently indicated. 1. point-of-care enzymatic. Under the influence of estrogen. enterococci. antigen and DNA tests for candida. and trichomoniasis. NO. However. and those in whom evaluation is consistent with recurrent bacterial vaginosis. office testing has poor performance characteristics. Gardnerella. and ruling out vulvovaginal candidiasis. less commonly. or ulcers should routinely lead to PCR tests for herpes simplex virus and possibly type-specific immune globulin G antibody testing. they are also occasional causes of purulent vaginitis. Management of Persistent Vaginitis. vaginal biopsies. Nyirjesy. by assessing for increased white blood cells and abnormal cytology such as parabasal cells. Figure 1 describes the pH-based algorithm that we use in practice. treating. Of those. 0. saline microscopy tests for atrophic vaginitis and desquamative inflammatory vaginitis.

travel costs.7 Parabasal cells. Vaginal colonization occurs through multiple routes. or excoriations. up to 30% at any single time and 70% if followed longitudinally for 1 year.8 billion. the annual market has been estimated at $275 million. usually with Candida albicans. with women noting a clear mucus midcycle to a thick white discharge at other times. a woman’s perception of her discharge correlates quite poorly with vulvovaginal candidiasis. which typically causes itching. depending on the health care provider.12 Although findings may be minimal. or sexual transmission.11 Although most people believe that a thick white discharge is the hallmark symptom of yeast infections. is present in normal healthy women.7 Clue cells. when a discharge is physiologic. an abnormal discharge may sometimes be the result of occult urinary incontinence. when suspected. including local transport from the perineum and perianal areas. some patients require multiple visits with normal evaluations to be fully reassured. the first line in diagnosis.7 Negative Clinical diagnosis Vulvovaginal candidiasis .4.11 Approximately 75% of women will develop symptomatic vulvovaginal candidiasis at least once in their lives. In our experience. polymerase chain reaction.10 The associated annual costs of vulvovaginal candidiasis in the United States in 1995.Table 1. and perhaps 8–10% will suffer from four or more episodes every year. were estimated to be $1. Candida colonization. soreness.7 Unremarkable. mixed flora Negative Negative Yeast culture with speciation Gram stain (Nugent score) Trichomonas vaginalis PCR Maturation index Clinical diagnosis Condition Amines Current Gold Standard PCR. Even more uncommonly.14 Thus. the current definition of recurrent disease. Testing for Causes of Vaginitis Vaginal pH Saline or 10% Potassium Hydroxide Microscopy Normal . a heavy discharge coming from the upper genital tract may be the result of an endometrial polyp or fallopian tube malignancy.7 $4. digital introduction. including medical and treatment expenses.12 Office microscopy (Table 1). only has a sensitivity of approximately 50%13 and.15 To develop a symptomatic infection. or dyspareunia. increased white blood cells. the prerequisite is colonization with Candida species. certainly in women with recurrent infection and possibly in those in whom candidiasis is suspected but not proven. fissures.2 complaints of a thick white discharge often lead to repeated use of unnecessary antifungal therapy and raise fears of recurrent infection. and time missed from work. yeast cultures with speciation should be obtained to confirm the diagnosis. OBSTETRICS & GYNECOLOGY Copyright ª American College of Obstetricians and Gynecologists . Furthermore. Hormonal influences will change a discharge. blastospores Negative Bacterial vaginosis $4. and despite evidence that the symptom of discharge is nonspecific. external dysuria. burning.4. a common event for almost every woman. 4 Nyirjesy Management of Persistent Vaginitis 50% of women will experience sporadic recurrences. Because many women and health care providers are taught that a thick white discharge is most frequently caused by vulvovaginal candidiasis. coccobacillary flora Positive Trichomoniasis Varies Trichomonads Variable Atrophic vaginitis Desquamative inflammatory vaginitis $4. in a study at a Dutch dermatology clinic. VULVOVAGINAL CANDIDIASIS With the proliferation of over-the-counter antifungal drugs. pelvic ultrasonography or sonohysterography should be considered. may have high false-positive rates. Diagnosing a discharge as physiologic can only be done by excluding potential causes. which can be diagnosed by having a patient take phenazopyridine for 1–2 days and looking for a change in the color of the discharge. almost doubling the rate of diagnosis. discharge usually becomes heavier. Repeated sampling through patient vaginal self-culture for yeast may further aid in diagnosis.4. irritation. decreased mixed flora Parabasal cells. swelling. 6white blood cells. vaginal signs are usually limited to erythema or occasionally thrush. examination may reveal vulvar redness. four weekly self-obtained cultures for yeast increased the number of positives from 59 at baseline to 111 in 441 women with suspected recurrent candidiasis. bacillary flora Hyphae. and these medications number in the top 10 of all over-the-counter medications sold in the United States. which will be discussed later.

NO. the approach that is commonly used is maintenance Nyirjesy Management of Persistent Vaginitis Copyright ª American College of Obstetricians and Gynecologists 5 . behavioral.7 In general. an intrauterine device.25 Finally. they all have similar efficacy for C albicans infections with an expected cure rate of 80– 90% in uncomplicated patients.7 In at least half of women with recurrent vulvovaginal candidiasis.19 With antibiotic use. antibiotic and estrogen use. 0. VOL. and behavioral factors are familiar to most health care providers. C albicans remains by far the most common cause of infection. Although each has its own advantages and disadvantages.11 The transition from asymptomatic colonization to symptomatic infection may be the result of intrinsic host. Women with recurrent infections have increased vaginal Candida species colonization rates. with C glabrata and Candida parapsilosis being the most common. immunosuppression. candida may be a commensal organism. For infections resulting from C albicans. as many 5%. actual transmission is thought to be uncommon. and mycotoxins. With C albicans infections.27 However.29 Most experts agree that management begins by obtaining a positive yeast culture with speciation of the organism to confirm the diagnosis and identify the pathogen and then using that information to aggressively treat the infection. diabetes.23 As reviewed by Sobel. this is a transient asymptomatic event. and treatment of the male partner to prevent vulvovaginal candidiasis is not recommended.23 Although up to 20% of male partners of women with recurrent infections may harbor candida strains on their penises. which result in increased susceptibility to infection.21 In our experience.16 After colonization. glycosuria may be one mechanism contributing to both colonization and symptomatic infection.25 most affected women seem to exhibit altered local immunoregulatory mechanisms. 0. is associated with a relief of symptoms. Diabetics may be more prone to developing infections caused by Candida glabrata18. which in turn causes symptoms. perhaps 54% of women have no improvement of symptoms after successful eradication.24 As reviewed by Fidel. may inhibit phagocytic activity and suppress the local immune system. other women. 40% have a similar result. perhaps with sporadic recurrence. these regimens are clearly inadequate in women with complicated disease with failure rates of 35% within just 1 month of treatment. most women with recurrent disease develop a pattern in which the infection clears with antifungal therapy only to recur within a few weeks to months. but some women develop a symptomatic infection that goes away easily with standard antifungal therapy. may be at play. including genetic factors.for most. should be considered complicated and are more likely to fail standard antifungal therapy.20 In menopausal women. it has been suggested that symptomatic candidiasis is the result of an increased sensitivity to yeast.6. In the past. determined by a negative follow-up culture. it can be difficult to distinguish between one who truly has vulvovaginal candidiasis as opposed to one who is asymptomatically colonized with yeast and has a separate cause for the symptoms. although topical and systemic corticosteroid use may be more common. prescription to over-the-counter. including secreted aspartate proteinases. its eradication results in a relief of symptoms in up to 90% of cases. it was felt that these women had a decreased immune response. phospholipases. Of these. Sexual activity. with many women asymptomatically colonized with yeast. and with C parapsilosis. women with uncomplicated infections are otherwise healthy women with mild-to-moderate symptoms resulting from sporadic episodes of infections caused by C albicans. more recently.28 For uncomplicated disease.26 In tertiary care vaginitis programs.23 Whatever the cause. symptomatic episodes seem to occur mainly in women with preexisting colonization. systemic immunosuppression is rare in women with vulvovaginal candidiasis.22 and using contraception with oral contraceptives. exogenous estrogen use increases the risk of both candidal colonization and infection.27 Most treatment guidelines distinguish between uncomplicated and complicated vulvovaginal candidiasis. An effective approach to resolve the question is to treat her and see if successful treatment. leading to an inflammatory response to yeast colonization. and subsequent germination promotes subsequent vaginitis. or a diaphragm with spermicide have all been associated with increased infection. In an even smaller group. Virulence factors produced by Candida species. or organism-related factors. environmental. proteases. including those with recurrent vulvovaginal candidiasis and those with nonalbicans Candida infections. approximately 30% of women will be infected by other species of yeast. ranging from oral to topical. there is a more complicated course with either failure to respond to treatment and the development of chronic infection17 or relatively rapid relapse after successful antifungal therapy and eventual recurrent disease. other host factors. when a woman with persistent vaginitis has a positive yeast culture. and 1-day to 7-day regimens.7 However.26 adherence of yeast cells to vaginal epithelium causes colonization. there are no clear risk factors. usually with the same strain of yeast. there are many available treatments. Furthermore. particularly orogenital sex. with C glabrata. but. MONTH 2014 In most women with vulvovaginal candidiasis.

7. This approach gives almost all women a prolonged period of symptom relief. 73. and 22%.33 Finally. a recent report by Marchaim31 of clinically fluconazole-resistant C albicans vulvovaginal candidiasis.001).7 because they may be more easily accepted by prescription plans. administered daily in a gelatin capsule for 14 days. have been used successfully in our practice (unpublished observation). Limited experience with topical amphotericin B as a 50-mg suppository offers another option for C glabrata infections.antifungal therapy. For women who recur after maintenance therapy (approximately 50%).32 Vaginal boric acid at 600 mg. given 5 g daily for 14 days. but it is no longer recommended because of the risk of liver toxicity. Centers for Disease Control and Prevention. In a study of maintenance fluconazole for recurrent vulvovaginal candidiasis.5% vaginal cream. possibly induced by long-term use of fluconazole. and 42. used daily for 14 days. in the placebo group (P. and then followed for an additional 6 months (observation phase). 5 g/d34 wk Hydrocortisone 10% vaginal cream.5 g twice/wk Estradiol (0. but the approaches used for C glabrata or Table 2. 3 g/d34 wk Sobel30 Sobel32 Sobel43 CDC7 NAMS51 Sobel58 CDC. 9.01% vaginal cream 2–4 g/d daily for 1–2 wk.010 mg) tablet/d32 wk. Although unstudied. The second line of therapy. respectively. The initial regimen used was 100 mg ketoconazole daily for 6 months. then once/wk36 mo Boric acid 600-mg capsules vaginally per d32 wk Metronidazole 0. Of the 343 patients who were studied for efficacy. then 1 g 1–3 times/wk Conjugated estrogen (0. the proportions of women who remained disease-free at 6.6.32 Apart from occasionally causing local irritation and an abnormal discharge. Initial Treatment Options for Women With Chronic Vaginitis Condition Treatments Normal Vulvovaginal candidiasis Candida albicans Non-albicans Candida Bacterial vaginosis Trichomoniasis Atrophic vaginitis (vaginal treatments) Desquamative inflammatory vaginitis Source None indicated Fluconazole 150 mg orally every 3 d33.6 The advent of fluconazole in the early 1990s led to the replacement of ketoconazole by fluconazole as maintenance. it is inexpensive and well-tolerated. which prevent the use of fluconazole. and 12 months in the fluconazole group were 91. evidence is limited to case reports or small case series. 3 days apart. gastrointestinal discomfort. many health care providers restart maintenance if the pathogen remains C albicans.75% vaginal gel 5 g/d310 d. with C parapsilosis.. has been shown to be effective32 but has become prohibitively expensive.625 mg/g) cream 0.34 For other non-albicans Candida infections. Although clinical and in vitro resistance to C albicans is rare. and only one had a mild elevation in aminotransferase levels. allergy. then twice a week for 6 months.9% compared with 36. the same cannot be said for non-albicans Candida species. There are some situations such as pregnancy. or cost. is recommended as initial therapy and cures up to 70% of C glabrata infections (Table 2). in which patients are treated with a prolonged (usually 6-month) regimen. 6 Nyirjesy Management of Persistent Vaginitis OBSTETRICS & GYNECOLOGY Copyright ª American College of Obstetricians and Gynecologists . NAMS. North American Menopause Society. flucytosine compounded into a 15. Current guidelines7 suggest using topical regimens intermittently.30 women were initially given three doses of 150 mg fluconazole. those specific formulations are no longer commercially available. Only one patient discontinued treatment because of an adverse event (headache) attributable to fluconazole. one case series described successful mycologic cure in 17 of 19 patients receiving 200 mg fluconazole twice a week for a month and six of six patients receiving 600-mg daily boric acid vaginal capsules twice daily for 2 weeks. raises new concerns and underscores the need to bring the patients on maintenance therapy back to make sure that they have a negative culture and are responding to treatment appropriately. alternate doses of fluconazole (100 or 200 mg) are also recommended. They were then randomized to weekly 150 mg fluconazole or placebo for 6 months (treatment phase). Thus. headaches. maintenance fluconazole therapy is a well-tolerated and effective approach to treating recurrent C albicans infections (Table 2). Regimens of miconazole 2% cream or clotrimazole 1% cream. then twice/wk Estradiol (2 mg) ring every 3 mo Clindamycin 2% vaginal cream. 28. to induce a negative culture. Although alternate topical maintenance regimens with clotrimazole have been described and shown to be effective. then twice/wk34 mo Tinidazole 2 g/d daily for 5 d Estradiol 0. Although resistance to fluconazole seems to be fortunately rare.

C parapsilosis are likely to be effective. and adverse events. tinidazole (oral). increased risk of infection after gynecologic surgery.6. Bacteroides species.7 Although commercial laboratories now offer VOL.2 Associated sociodemographic factors include a younger age. Bradshaw and colleagues found that the risk factors for recurrence were a history of bacterial vaginosis. they can often be cured with a second course of the same therapy. a single recurrence or more may occur in up to 58% of women within 12 months. or having a female sex partner. Leptotrichia species and many others. Peptostreptococcus species. and greater than 20% clue cells on saline microscopy). Nyirjesy Management of Persistent Vaginitis Copyright ª American College of Obstetricians and Gynecologists 7 . After the early report by Gardner and Dukes40 describing G vaginalis as a possible cause of bacterial vaginosis. 0.38 In a cohort of 130 Australian women treated with a 7-day course of oral metronidazole. and douching. In a molecular analysis of uncultivated organisms. mode of administration. Usually.39 Recent controversies about the role of the sexual partner and the possible development of vaginal biofilms as a result of G vaginalis infection have fueled new discussion of why women get bacterial vaginosis and why some women recur. there may be less of a need to treat non-albicans Candida infections. preterm birth. With standard antibiotic regimens. having a regular sex partner throughout the study. 0. Initially thought to be caused by G vaginalis. P. cervicitis. having less than a high school education. A vaginal Gram stain. and an increased susceptibility to human immunodeficiency virus. the bacterial load may be decreased but the biofilm may not be eliminated. which coats certain surfaces and within which bacteria hide from and are protected from the effects of antibiotics. Amsel’s criteria have a sensitivity of 92%.6. NO.6 Compared with the Nugent score and much easier to perform in an office setting. there is no evidence of clear clinical superiority of these expensive tests over Amsel’s and Nugent criteria nor have they been shown to help in guiding therapy. and postpartum endometritis in pregnant women. the best known example is the biofilm that occurs on infected foreign bodies such as central venous catheters. and clindamycin (oral or topical) are all recommended as initial treatments. the most common complaints are of an abnormal vaginal discharge and a fishy odor. MONTH 2014 PCR-based modalities to diagnose bacterial vaginosis using various criteria. and that hormonal contraception had a protective effect. Metronidazole (oral or topical). In women with disease. bacterial vaginosis is considered the most common form of vaginitis. positive amine test. more recent studies using standard culture and DNA-based technologies have shown that a broad range of bacteria. is considered the gold standard. where the presence or absence of different bacterial morphotypes is scored.7 They offer equivalent efficacy and can be distinguished from each other on the basis of cost.7 After treatment.6 Although at least 50% of infected women have no symptoms. living at or near the federal poverty level. including urinary tract infections. Eggerthella species. trichomonal..36 This disturbed vaginal flora is a risk factor for many infectious morbidities. including Atopobium vaginae. the biofilm consists primarily of G vaginalis and sometimes with A vaginae. Biofilms are a type of slime produced by bacteria. known as the Nugent score. and genital herpes infections in nonpregnant women as well as spontaneous abortion. the vulvovaginal examination will be normal apart from a discharge described as watery and gray. later research suggested that it was instead caused by complex changes in vaginal flora and G vaginalis was ignored until recently. which can be demonstrated on electron microscopy of vaginal biopsies. but rather biofilm-associated G vaginalis. These data suggest that it is not the mere presence of G vaginalis that causes bacterial vaginosis.001). bacterial vaginosisassociated bacteria. bacterial vaginosis-associated bacteria-3. As noted earlier. Diagnosis relies on finding three of four Amsel’s criteria (abnormal gray discharge. high vaginal pH. chlamydial.28 BACTERIAL VAGINOSIS Affecting approximately 30% of women. Megasphaera type 1. thus setting the stage for recurrence after treatment. because the yeast may be an innocent bystander in at least 50% of cases.35 Bacterial vaginosis is marked by a disturbance in the vaginal microflora with a lack of the normal hydrogen peroxide-producing lactobacilli and an overgrowth of primarily anaerobic organisms. As reviewed by Verstraelen and Swidsinski.41 recent studies have found that 90% of women with and 10% without bacterial vaginosis have a complex polymicrobial biofilm. gonococcal. being non-Hispanic black or Mexican American. Mobiluncus species. Megasphaera species. they also found that women with both A vaginae and G vaginalis present initially had a much higher rate of recurrence at 1 year than those in whom G vaginalis alone was present (83% compared with 38%. If patients fail an initial course of treatment. bacterial vaginosis-associated bacteria-2. are found in vaginal samples of infected women. particularly those resulting from C glabrata. pelvic inflammatory disease. Fusobacterium species. Prevotella species.37 Culture for G vaginalis is not recommended because of a lack of specificity.

Food and Drug Administration–cleared OSOM Trichomonas Rapid Antigen Test may provide a rapid (less than 10 minutes) result in the office. if T vaginalis infection is suspected but not proven.7 In an attempt to prevent reinfection. Although these results represent the most promising ones to date. failure to reestablish normal lactobacillus-dominant flora. Centers for Disease Control and Prevention guidelines recommend obtaining cultures OBSTETRICS & GYNECOLOGY Copyright ª American College of Obstetricians and Gynecologists .48 Thus.43 In this study of 127 evaluable women. and 28 weeks from the initial visit was 87. Based on these various theories. more recently. culture or PCR is recommended. a patient with this uncommon clinical scenario should be managed in conjunction with an allergist. With a resistant infection. Physical findings include vulvovaginal erythema.47 Thus. In women who have sex with women. Most uncomplicated cases will be cured with treatment with either oral metronidazole or tinidazole along with treatment of the sexual partner.44 Cumulative cure at 12. bacterial vaginosis and its recurrence could be the result of one or several mechanisms: reinfection through sexual activity. patients who are allergic to nitroimidazoles represent a therapeutic challenge. and 65%. respectively. not all patients with trichomoniasis are straightforward. health care providers may also encounter women with allergic reactions to nitroimidazoles. it remains difficult to truly cure women with recurrent bacterial vaginosis. the cleaning of shared sex toys between uses is encouraged. and occasionally punctate hemorrhages of the vaginal mucosa and cervix. treatment of partner studies. the best approach seems to be maintenance therapy. Thus. or persistence of a vaginal biofilm. dyspareunia.7 and 10. vulvovaginal soreness and itching. such as the U. despite serious limitations. oral or parenteral desensitization to metronidazole followed by treatment has been shown to be highly effective in a study of 15 patients treated and cured with such an approach. Fortunately. infection recurred in 26% of metronidazole gel and 59% of placebo patients (P5. To date. and metronidazole resistance.46 Occasionally. although data supporting this recommendation are lacking. The finding of polymicrobial G vaginalis–dominant biofilm in men has added further fuel to the debate. With resistance. have shown no benefit and are not recommended. 16. a 51% recurrence rate within 3 months and 59% rate of vulvovaginal candidiasis because of prolonged antibiotic therapy demonstrate the need for more effective therapy.S. However. TRICHOMONIASIS Considered the third most common cause of infectious vaginitis.42 data in favor of sexual transmission include evidence that bacterial vaginosis can be transmitted between female sexual partners. Because in vitro resistance correlates poorly with clinical outcome.42 and recolonization with lactobacillus supplements.2 trichomoniasis is a surprisingly uncommon diagnosis at our tertiary care vaginitis 8 Nyirjesy Management of Persistent Vaginitis center and is found in fewer than 1% of the women referred to us (unpublished observation). reinfection.6. the most common issues pertaining to trichomoniasis in women with persistent vaginitis are missed diagnosis (31%) and metronidazoleresistant infection (33%). the latter estimated at anywhere between 1. the only controlled study consisted of metronidazole gel twice weekly for 4 months after an initial 10-day course of therapy (Table 2). an alternate regimen of 500 mg metronidazole or tinidazole twice a day for 7 days followed by 21 days of 600 mg boric acid daily followed by an additional twice weekly metronidazole gel regimen for 16 weeks was studied in 77 episodes of recurrent bacterial vaginosis. but routine screening or treatment of the female partner is not. Although hypersensitivity reactions have been rare. As noted in a review of 45 cases seen in a specialty vaginitis clinic. if a patient returns with ongoing trichomoniasis after treatment. 78.Gardner and Dukes40 had also hypothesized that bacterial vaginosis was sexually transmitted.41 Thus.001). discharge.1%. the in vitro mechanisms are the result of both aerobic and anaerobic pathways. Although up to 50% of infected women may be asymptomatic. tinidazole. The mainstay of therapy has been metronidazole and.45 symptomatic women will complain of an abnormal discharge (clear to yellow–green and frothy).7 For now. However.7 However. the data implicating the male partner from the Bradshaw study and the finding of similar flora in the male partners of women with bacterial vaginosis. With a sensitivity of 60–70%. we routinely recommend consistent condom use for 3–6 months.7 However. other cases were incident cases occurring in women being treated for other conditions. as summarized by Muzny and Schwebke.6. but this theory was later discounted. metronidazole-resistant trichomoniasis is primarily a clinical diagnosis. and pain on urination. Treatment failure can be related to noncompliance. saline microscopy alone is simply not a good enough test to reliably diagnose trichomoniasis. To date. health care providers should check to make sure that the treatment was taken and that reinfection did not occur. a variety of potential treatment interventions make sense. Other tests. with a failure rate of 50% by 36 weeks of follow-up.

Laboratory findings are summarized in Table 1. the medical literature is peppered with other medications used in resistant trichomonas cases.cdc. The main complaints are those of dryness. Importantly. affected women may sometimes note a heavier discharge. mostly to no avail. However.51. yellow or watery. paromomycin had a 58% cure rate.50 To minimize the risk of ulceration.7 Beyond that.51 Finally. When we suspect desquamative inflammatory vaginitis. we routinely perform vaginal bacterial cultures. is believed to be the most common cause of vulvovaginal symptoms in menopausal women.49 Apart from nitroimidazoles. contact bleeding. an aminoglycoside agent active against protozoa including T vaginalis. 92% were cured with highdose tinidazole. and a yellow watery discharge. low-dose vaginal estrogen.53 For those women preferring systemic therapy. However. dyspareunia. experience with paromomycin. then. Used as a 5% cream. in 469 women with chronic vaginitis. ie. symptomatic vulvovaginal atrophy. but vestibular and vulvar ulceration is a side effect that limits its use. VULVOVAGINAL ATROPHY As one might expect. and external dysuria.gov/std). examination reveals severe introital and vaginal erythema and a copious vaginal discharge. suggests that it may be one option in problematic women. For most women. various treatment regimens have been proposed. The nuances and controversies surrounding treatment of vulvovaginal atrophy have recently been reviewed.4 Initially thought of as a possible bacterial overgrowth of an atrophic vagina55 or even a variant of lichen planus. Intravaginal dihydroepiandrosterone or hyaluronic acid may be considered as possible alternatives to estrogen. 2 g metronidazole or tinidazole orally daily for 5 days is recommended as initial therapy (Table 2). In a series of 33 patients who failed courses of high-dose metronidazole. itching. looking for group A streptococci or S aureus. patients are instructed to apply a barrier such as petrolatum to the vestibule. it was diagnosed not only in women older than 50 years (48%) but also in younger women (5%).51 As summarized by the North American Menopause Society. along with burning and severe dyspareunia. or perimenopausal or postmenopausal) and notices the onset of an abnormal discharge. 500 mg orally twice daily for 7 days. most women with vulvovaginal atrophy may not relate their symptoms to menopausal changes. a lack of response to topical estrogen may also serve to distinguish between the two conditions. the most extensive experience is with high-dose tinidazole. NO. Because some patients with severe atrophic vaginitis may have white blood cells on microscopy. usually described as yellow or brown. MONTH 2014 continued sexual activity as initial therapy for women with vulvovaginal atrophy. 0. 1 g two or three times a day orally along with 500 mg a day vaginally for 14 days. very few controlled studies have been done to assess their effect. where they studied 98 women Nyirjesy Management of Persistent Vaginitis Copyright ª American College of Obstetricians and Gynecologists 9 .56 the cause remains unknown. vestibular and vaginal pallor. burning.49 Recently. A longer course of metronidazole. Furthermore. recognition and treatment of atrophy are part of any discussion of chronic vaginitis. postpartum and breastfeeding.51 Expert consensus opinion51 recommends nonhormonal vaginal lubricants and moisturizers as well as VOL. Unlike vulvovaginal atrophy. and even blood-tinged. if necessary. The most extensive published experience was from Wayne State University. it may be the result of a local toxin-induced inflammatory reaction to S aureus infection57 or even group A streptococcal infection. used commonly in our practice. The typical patient with desquamative inflammatory vaginitis is hypoestrogenic (on continuous lowdose birth control pills. In a minority of women. atrophic vaginitis. 0.52 DESQUAMATIVE INFLAMMATORY VAGINITIS First described by Gray and Barnes in 1965. The presence of white blood cells on saline microscopy can distinguish it from atrophy. can provide adequate symptom relief (Table 2).52 Thus. web site: http:// www.54 desquamative inflammatory vaginitis is a condition that is unfamiliar to most health care providers yet is found in up to 8% of women with persistent vaginitis. Because the cause remains unknown. it should be noted that more than 50% of women older than 50 years with chronic vaginitis may have causes that are separate from atrophic vaginitis with desquamative inflammatory vaginitis (15%) and lichen sclerosus (14%) being the most common.for resistance testing and can offer management recommendations (telephone: 404-718-4141. 5 g vaginally nightly. although published experience is very limited. Despite the sensation of dryness. Findings include atrophy of the labia majora or minora. systemic estrogen (with or without progesterone) or ospemifene may be considered. and PCR for T vaginalis. vaginal erythema or even petechiae. a loss of rugal folds. the combination of high-dose (1 g three times a day) tinidazole and paromomycin cream nightly for 14 days was used successfully in two women with clinical resistance to high-dose tinidazole. the degree of atrophic changes as measured by findings and maturation index does not correlate with symptoms.

vulvar or vaginal biopsies. American College of Obstetricians and Gynecologists. 191–203. Sobel JD. Sobel JD.59:1–110. editors. Heidrich FE.treated in a nonrandomized fashion with either 2% clindamycin vaginal cream (5 g) or 10% hydrocortisone compounded vaginal cream (3–5 g) daily for 4–6 weeks.58 After initial treatment. MMWR Recomm Rep 2010. when appropriate. 8. Yih MC. Culhane JF. Normal genital flora. Bergman JJ. 7. Obstet Gynecol 2006. 11. Barlow R. and saline and potassium hydroxide microscopy  obtain yeast culture with speciation. Vulvovaginal candidiasis. Klink K.reported incidence and associated costs. REFERENCES 1. and 16% were only partially controlled with ongoing treatment. management algorithm. vagina. ACOG Practice Bulletin No. Gardnerella vaginalis. and cervix  perform vaginal pH. p. 10 Nyirjesy Management of Persistent Vaginitis FINAL CONCERNS Because women with chronic vaginitis are often desperate to try some sort of treatment to help their symptoms. 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Savan K. The comparison of hyaluronic acid vaginal tablets with estradiol vaginal tablets in the treatment of atrophic vaginitis: a randomized controlled trial. Prognosis and treatment of desquamative inflammatory vaginitis. Reichman O. Desquamative inflammatory vaginitis: a new subgroup of purulent vaginitis responsive to topical 2% 57. Edlind TD. Edwards L. clindamycin therapy. Obstet Gynecol 1988. Obstetrics & Gynecology and Public Access A number of research-funding agencies now require or request authors to submit the postprint (the article after peer review and acceptance but not the final published article) to a repository that is accessible online by all without charge. Temur M. Uhri M. J Low Genit Tract Dis 2012. 7ELLCOME4RUST/PENACCESSPOLICY!VAILABLEATHTTPWWWWELLCOMEACUK!BOUT US 0OLICY0OLICY AND POSITION STATEMENTS74$HTM2ETRIEVED/CTOBER.IBRARYOF-EDICINE. Within medical research. three funding agencies in particular have announced such policies: s4HE.- ARTICLES THATREQUIREDEPOSIT4HEJOURNALSAUTHORAGREEMENTFORMAVAILABLEAT http://edmgr. Am J Obstet Gynecol 1965. Vaginitis in women. Vaginal toxic shock reaction triggering desquamative inflammatory vaginitis. (OWARD(UGHES-EDICAL)NSTITUTE0UBLICACCESS!VAILABLEATHTTPWWWHHMIORG about/research/journals/main?action=search. diagnosis and treatment. Nyirjesy P. Obstet Gynecol 2011. Schlievert PM. 2014. 58. Yoo W.92:125–36. Misra D.nih.77 WILLIDENTIFYTOTHE.pdf) provides the mechanism for identifying such articles.gov/.)( 1 s4HE(OWARD(UGHES-EDICAL)NSTITUTE((-) 2 s4HE7ELLCOME4RUST3 As a service to our authors.283:539–43. Gray LA. Sobel JD. Gencer I. the journal’s publisher (Lippincott Williams & 7ILKINS. Desquamative vaginitis: lichen planus in disguise. Retrieved October 7. LWW will transmit the postprint of an article based on research funded in whole or in part by one or more of these THREEAGENCIESTO0UB-ED#ENTRAL References 53$EPARTMENTOF(EALTHAND(UMAN3ERVICES. 53. Am J Obstet Gynecol 1994. 56. 54.ATIONAL.71:832–6. Friedrich EG Jr.17:88–91.171: 1215–20. Sobel JD.ATIONAL)NSTITUTESOF(EALTHPUBLIC access. Ekin M.. J Low Genit Tract Dis 2013. Retrieved October 7.117:850–5. 2014. Barnes ML. Available at http://publicaccess.analysis of a prospective database.com/ong/accounts/agreementform. 55. Yas¸ar L. 16:24–9. et al. Pereira N. Arch Gynecol Obstet 2011.ATIONAL)NSTITUTESOF(EALTH.ovid.

 Questions? #ONTACTTHE%DITORIALOFlCEATOBGYN GREENJOURNALORGOR   rev 12/2014 12 Nyirjesy Management of Persistent Vaginitis OBSTETRICS & GYNECOLOGY Copyright ª American College of Obstetricians and Gynecologists .