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

Routine bacterial cultures are otherwise unhelpful and can be misleading. Nyirjesy. including skin and fecal flora and lactobacilli. Gardnerella. During a woman’s reproductive years. Food and Drug Administration–cleared APTIMA T vaginalis assay. and ancillary tests are frequently indicated. Under the influence of estrogen. by assessing for increased white blood cells and abnormal cytology such as parabasal cells. Sobel JD. the vaginal epithelium thickens. Before puberty. PCR testing for yeast and bacterial vaginosis).9 For other tests for vaginal infections (ie. However. fissures. which lowers the pH of the vagina to less than 4. If Trichomonas vaginalis infection is suspected but not proven. and in the case of PCR testing for yeast and bacterial vaginosis. vulvar biopsies. there is currently little evidence that they are superior to current gold standards. The findings of vesicles. because normal vaginal flora such as Escherichia coli. As shown in Table 1. Lactobacilli become the dominant flora. In addition. Advances in diagnosing vaginitis: development of a new algorithm. treating. they are also occasional causes of purulent vaginitis. yeast cultures with speciation of the organism play an integral part in diagnosing. MONTH 2014 Nyirjesy Management of Persistent Vaginitis Copyright ª American College of Obstetricians and Gynecologists 3 . NORMAL VAGINAL PHYSIOLOGY AND DISCHARGE With physiologic discharge occurring as the final diagnosis in 9% of the patients referred to our tertiary care program. they are more costly than current modalities.4 understanding the normal vaginal environment is important. vaginal pH testing in particular can be used to drive the entire diagnostic process.7. and. Vaginal Fig. Finally. vaginal biopsies. VOL. the vagina is thinned and has a high pH. Although these latter two organisms may be commensals. Curr Infect Dis Rep 2005. and trichomoniasis. office testing has poor performance characteristics. and both saline and 10% potassium hydroxide microscopy. point-of-care enzymatic. antigen and DNA tests for candida.S. saline microscopy tests for atrophic vaginitis and desquamative inflammatory vaginitis. and group B streptococci are frequently found. Figure 2.8 Saline microscopy can aid in diagnosing bacterial vaginosis and trichomoniasis. NO. estrogen plays a key role in maintaining the normal vaginal environment. Reprinted with kind permission from Springer Science+Business Media: Nyirjesy P. and ruling out vulvovaginal candidiasis. culture of the vagina demonstrates a variety of organisms. the gold standard test remains either culture or the more easily available polymerase chain reaction (PCR) with the U. We perform this latter test in all of our patients at risk for a sexually transmitted infection. Obstet Gynecol 2014. amines. these easily available tests can frequently diagnose common forms of vaginitis. 1. Gardnerella vaginalis. those with many white blood cells on microscopy. less commonly. or ulcers should routinely lead to PCR tests for herpes simplex virus and possibly type-specific immune globulin G antibody testing. Of those. Frequently underused.7:458–62. and those in whom evaluation is consistent with recurrent bacterial vaginosis. enterococci.for Disease Control and Prevention7 stress the importance of in-office testing for vaginal pH. Figure 1 describes the pH-based algorithm that we use in practice. Management of Persistent Vaginitis. should be considered for focal abnormalities. particularly if the etiology is unclear. 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. A pH-based framework for diagnosing the most common causes of vaginitis. 0. 0.

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

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

North American Menopause Society. used daily for 14 days. The initial regimen used was 100 mg ketoconazole daily for 6 months. and 42. has been shown to be effective32 but has become prohibitively expensive. those specific formulations are no longer commercially available. and only one had a mild elevation in aminotransferase levels.30 women were initially given three doses of 150 mg fluconazole.. They were then randomized to weekly 150 mg fluconazole or placebo for 6 months (treatment phase). and 22%. but it is no longer recommended because of the risk of liver toxicity. Current guidelines7 suggest using topical regimens intermittently. Although resistance to fluconazole seems to be fortunately rare. then once/wk36 mo Boric acid 600-mg capsules vaginally per d32 wk Metronidazole 0.625 mg/g) cream 0. to induce a negative culture. and then followed for an additional 6 months (observation phase). Although unstudied. For women who recur after maintenance therapy (approximately 50%). The second line of therapy.34 For other non-albicans Candida infections. in the placebo group (P.32 Apart from occasionally causing local irritation and an abnormal discharge. evidence is limited to case reports or small case series. 3 g/d34 wk Sobel30 Sobel32 Sobel43 CDC7 NAMS51 Sobel58 CDC. it is inexpensive and well-tolerated. then twice a week for 6 months. 3 days apart. NAMS. Although clinical and in vitro resistance to C albicans is rare.001). then 1 g 1–3 times/wk Conjugated estrogen (0.antifungal therapy. alternate doses of fluconazole (100 or 200 mg) are also recommended.6 The advent of fluconazole in the early 1990s led to the replacement of ketoconazole by fluconazole as maintenance. given 5 g daily for 14 days. 28. gastrointestinal discomfort. Centers for Disease Control and Prevention. or cost. a recent report by Marchaim31 of clinically fluconazole-resistant C albicans vulvovaginal candidiasis.7 because they may be more easily accepted by prescription plans.9% compared with 36. 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. allergy. 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. 5 g/d34 wk Hydrocortisone 10% vaginal cream. maintenance fluconazole therapy is a well-tolerated and effective approach to treating recurrent C albicans infections (Table 2).33 Finally. then twice/wk34 mo Tinidazole 2 g/d daily for 5 d Estradiol 0. Limited experience with topical amphotericin B as a 50-mg suppository offers another option for C glabrata infections. Regimens of miconazole 2% cream or clotrimazole 1% cream. In a study of maintenance fluconazole for recurrent vulvovaginal candidiasis. possibly induced by long-term use of fluconazole.5 g twice/wk Estradiol (0.6. There are some situations such as pregnancy. with C parapsilosis.5% vaginal cream. Only one patient discontinued treatment because of an adverse event (headache) attributable to fluconazole. Although alternate topical maintenance regimens with clotrimazole have been described and shown to be effective. This approach gives almost all women a prolonged period of symptom relief.01% vaginal cream 2–4 g/d daily for 1–2 wk. have been used successfully in our practice (unpublished observation).32 Vaginal boric acid at 600 mg. 6 Nyirjesy Management of Persistent Vaginitis OBSTETRICS & GYNECOLOGY Copyright ª American College of Obstetricians and Gynecologists . then twice/wk Estradiol (2 mg) ring every 3 mo Clindamycin 2% vaginal cream. which prevent the use of fluconazole. in which patients are treated with a prolonged (usually 6-month) regimen. 73. and 12 months in the fluconazole group were 91. headaches.75% vaginal gel 5 g/d310 d. 9.7. is recommended as initial therapy and cures up to 70% of C glabrata infections (Table 2). many health care providers restart maintenance if the pathogen remains C albicans.010 mg) tablet/d32 wk. administered daily in a gelatin capsule for 14 days. flucytosine compounded into a 15. 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. but the approaches used for C glabrata or Table 2. the same cannot be said for non-albicans Candida species. the proportions of women who remained disease-free at 6. Thus. Of the 343 patients who were studied for efficacy. respectively.

If patients fail an initial course of treatment. Bacteroides species. having a regular sex partner throughout the study. pelvic inflammatory disease. 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.37 Culture for G vaginalis is not recommended because of a lack of specificity. 0. Diagnosis relies on finding three of four Amsel’s criteria (abnormal gray discharge. including urinary tract infections. a single recurrence or more may occur in up to 58% of women within 12 months. Megasphaera type 1. thus setting the stage for recurrence after treatment.6 Although at least 50% of infected women have no symptoms. Usually. P. Biofilms are a type of slime produced by bacteria. and postpartum endometritis in pregnant women. As noted earlier. having less than a high school education. A vaginal Gram stain. Amsel’s criteria have a sensitivity of 92%.7 After treatment. mode of administration. Mobiluncus species.7 Although commercial laboratories now offer VOL. Megasphaera species. gonococcal.6. is considered the gold standard. and douching. and that hormonal contraception had a protective effect. Leptotrichia species and many others.7 They offer equivalent efficacy and can be distinguished from each other on the basis of cost. In women with disease. and greater than 20% clue cells on saline microscopy).28 BACTERIAL VAGINOSIS Affecting approximately 30% of women. or having a female sex partner. Prevotella species. bacterial vaginosis is considered the most common form of vaginitis.41 recent studies have found that 90% of women with and 10% without bacterial vaginosis have a complex polymicrobial biofilm. Initially thought to be caused by G vaginalis.001).2 Associated sociodemographic factors include a younger age. 0. With standard antibiotic regimens.6. including Atopobium vaginae. which coats certain surfaces and within which bacteria hide from and are protected from the effects of antibiotics.36 This disturbed vaginal flora is a risk factor for many infectious morbidities.. bacterial vaginosis-associated bacteria-2. known as the Nugent score. These data suggest that it is not the mere presence of G vaginalis that causes bacterial vaginosis. 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%. cervicitis. Metronidazole (oral or topical). Nyirjesy Management of Persistent Vaginitis Copyright ª American College of Obstetricians and Gynecologists 7 . which can be demonstrated on electron microscopy of vaginal biopsies. later research suggested that it was instead caused by complex changes in vaginal flora and G vaginalis was ignored until recently.C parapsilosis are likely to be effective. the most common complaints are of an abnormal vaginal discharge and a fishy odor. but rather biofilm-associated G vaginalis. the vulvovaginal examination will be normal apart from a discharge described as watery and gray. the best known example is the biofilm that occurs on infected foreign bodies such as central venous catheters.6 Compared with the Nugent score and much easier to perform in an office setting. there may be less of a need to treat non-albicans Candida infections. and genital herpes infections in nonpregnant women as well as spontaneous abortion. are found in vaginal samples of infected women. the biofilm consists primarily of G vaginalis and sometimes with A vaginae. chlamydial. more recent studies using standard culture and DNA-based technologies have shown that a broad range of bacteria. trichomonal. Fusobacterium species. positive amine test.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.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. Eggerthella species. preterm birth. and adverse events. After the early report by Gardner and Dukes40 describing G vaginalis as a possible cause of bacterial vaginosis. and clindamycin (oral or topical) are all recommended as initial treatments.38 In a cohort of 130 Australian women treated with a 7-day course of oral metronidazole. and an increased susceptibility to human immunodeficiency virus. As reviewed by Verstraelen and Swidsinski. Bradshaw and colleagues found that the risk factors for recurrence were a history of bacterial vaginosis. MONTH 2014 PCR-based modalities to diagnose bacterial vaginosis using various criteria. the bacterial load may be decreased but the biofilm may not be eliminated. increased risk of infection after gynecologic surgery. NO. In a molecular analysis of uncultivated organisms. because the yeast may be an innocent bystander in at least 50% of cases. particularly those resulting from C glabrata. being non-Hispanic black or Mexican American. high vaginal pH. living at or near the federal poverty level. where the presence or absence of different bacterial morphotypes is scored. Peptostreptococcus species. tinidazole (oral). bacterial vaginosisassociated bacteria. they can often be cured with a second course of the same therapy. bacterial vaginosis-associated bacteria-3.

not all patients with trichomoniasis are straightforward. Other tests. respectively. 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. discharge. patients who are allergic to nitroimidazoles represent a therapeutic challenge. the cleaning of shared sex toys between uses is encouraged. the most common issues pertaining to trichomoniasis in women with persistent vaginitis are missed diagnosis (31%) and metronidazoleresistant infection (33%). Fortunately.42 and recolonization with lactobacillus supplements.6.001). 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. The mainstay of therapy has been metronidazole and.43 In this study of 127 evaluable women. However. The finding of polymicrobial G vaginalis–dominant biofilm in men has added further fuel to the debate. metronidazole-resistant trichomoniasis is primarily a clinical diagnosis. Although up to 50% of infected women may be asymptomatic. With a resistant infection. or persistence of a vaginal biofilm. more recently. 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. health care providers may also encounter women with allergic reactions to nitroimidazoles. Although hypersensitivity reactions have been rare.1%. culture or PCR is recommended. but this theory was later discounted. a variety of potential treatment interventions make sense.S. the only controlled study consisted of metronidazole gel twice weekly for 4 months after an initial 10-day course of therapy (Table 2). treatment of partner studies. Treatment failure can be related to noncompliance. Because in vitro resistance correlates poorly with clinical outcome. To date. saline microscopy alone is simply not a good enough test to reliably diagnose trichomoniasis.41 Thus. In women who have sex with women. it remains difficult to truly cure women with recurrent bacterial vaginosis. infection recurred in 26% of metronidazole gel and 59% of placebo patients (P5. if a patient returns with ongoing trichomoniasis after treatment.Gardner and Dukes40 had also hypothesized that bacterial vaginosis was sexually transmitted. Based on these various theories.47 Thus. health care providers should check to make sure that the treatment was taken and that reinfection did not occur. the best approach seems to be maintenance therapy.7 For now.7 In an attempt to prevent reinfection.42 data in favor of sexual transmission include evidence that bacterial vaginosis can be transmitted between female sexual partners. 78. as summarized by Muzny and Schwebke. bacterial vaginosis and its recurrence could be the result of one or several mechanisms: reinfection through sexual activity. With resistance. With a sensitivity of 60–70%.7 However. Food and Drug Administration–cleared OSOM Trichomonas Rapid Antigen Test may provide a rapid (less than 10 minutes) result in the office.7 and 10. Centers for Disease Control and Prevention guidelines recommend obtaining cultures OBSTETRICS & GYNECOLOGY Copyright ª American College of Obstetricians and Gynecologists . 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. a patient with this uncommon clinical scenario should be managed in conjunction with an allergist. vulvovaginal soreness and itching. Physical findings include vulvovaginal erythema. the latter estimated at anywhere between 1.44 Cumulative cure at 12. failure to reestablish normal lactobacillus-dominant flora. if T vaginalis infection is suspected but not proven. despite serious limitations. such as the U. reinfection. However. Although these results represent the most promising ones to date. To date. As noted in a review of 45 cases seen in a specialty vaginitis clinic. Thus.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). Most uncomplicated cases will be cured with treatment with either oral metronidazole or tinidazole along with treatment of the sexual partner. and 65%. 16. although data supporting this recommendation are lacking.45 symptomatic women will complain of an abnormal discharge (clear to yellow–green and frothy). and metronidazole resistance. have shown no benefit and are not recommended.7 However.48 Thus. and 28 weeks from the initial visit was 87. the in vitro mechanisms are the result of both aerobic and anaerobic pathways. TRICHOMONIASIS Considered the third most common cause of infectious vaginitis. with a failure rate of 50% by 36 weeks of follow-up. we routinely recommend consistent condom use for 3–6 months. and occasionally punctate hemorrhages of the vaginal mucosa and cervix. other cases were incident cases occurring in women being treated for other conditions. tinidazole. but routine screening or treatment of the female partner is not. and pain on urination.6.46 Occasionally. dyspareunia.

experience with paromomycin. However. 1 g two or three times a day orally along with 500 mg a day vaginally for 14 days.51 Finally. A longer course of metronidazole. atrophic vaginitis. and a yellow watery discharge. The presence of white blood cells on saline microscopy can distinguish it from atrophy. Unlike vulvovaginal atrophy. looking for group A streptococci or S aureus. Importantly.56 the cause remains unknown.4 Initially thought of as a possible bacterial overgrowth of an atrophic vagina55 or even a variant of lichen planus. For most women. 0.54 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. Laboratory findings are summarized in Table 1. systemic estrogen (with or without progesterone) or ospemifene may be considered. in 469 women with chronic vaginitis.52 DESQUAMATIVE INFLAMMATORY VAGINITIS First described by Gray and Barnes in 1965. 500 mg orally twice daily for 7 days. The typical patient with desquamative inflammatory vaginitis is hypoestrogenic (on continuous lowdose birth control pills. examination reveals severe introital and vaginal erythema and a copious vaginal discharge. usually described as yellow or brown. web site: http:// www. suggests that it may be one option in problematic women. is believed to be the most common cause of vulvovaginal symptoms in menopausal women. ie. very few controlled studies have been done to assess their effect. The most extensive published experience was from Wayne State University. yellow or watery. the degree of atrophic changes as measured by findings and maturation index does not correlate with symptoms. mostly to no avail. In a series of 33 patients who failed courses of high-dose metronidazole. Findings include atrophy of the labia majora or minora. Because some patients with severe atrophic vaginitis may have white blood cells on microscopy. contact bleeding.53 For those women preferring systemic therapy. if necessary. the medical literature is peppered with other medications used in resistant trichomonas cases. or perimenopausal or postmenopausal) and notices the onset of an abnormal discharge. paromomycin had a 58% cure rate. 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. NO. 5 g vaginally nightly. vestibular and vaginal pallor. affected women may sometimes note a heavier discharge.51 As summarized by the North American Menopause Society. along with burning and severe dyspareunia. recognition and treatment of atrophy are part of any discussion of chronic vaginitis.49 Apart from nitroimidazoles. However. patients are instructed to apply a barrier such as petrolatum to the vestibule.for resistance testing and can offer management recommendations (telephone: 404-718-4141. and even blood-tinged. it may be the result of a local toxin-induced inflammatory reaction to S aureus infection57 or even group A streptococcal infection. burning. Intravaginal dihydroepiandrosterone or hyaluronic acid may be considered as possible alternatives to estrogen. Used as a 5% cream. where they studied 98 women Nyirjesy Management of Persistent Vaginitis Copyright ª American College of Obstetricians and Gynecologists 9 . a lack of response to topical estrogen may also serve to distinguish between the two conditions. symptomatic vulvovaginal atrophy. it was diagnosed not only in women older than 50 years (48%) but also in younger women (5%). VULVOVAGINAL ATROPHY As one might expect. low-dose vaginal estrogen. MONTH 2014 continued sexual activity as initial therapy for women with vulvovaginal atrophy. 92% were cured with highdose tinidazole. Furthermore. vaginal erythema or even petechiae. itching. but vestibular and vulvar ulceration is a side effect that limits its use.49 Recently. then. 0. postpartum and breastfeeding. dyspareunia.50 To minimize the risk of ulceration. various treatment regimens have been proposed. In a minority of women.7 Beyond that. 2 g metronidazole or tinidazole orally daily for 5 days is recommended as initial therapy (Table 2).52 Thus.gov/std). used commonly in our practice. a loss of rugal folds. The main complaints are those of dryness. When we suspect desquamative inflammatory vaginitis. Despite the sensation of dryness. 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. we routinely perform vaginal bacterial cultures. can provide adequate symptom relief (Table 2). most women with vulvovaginal atrophy may not relate their symptoms to menopausal changes.51.51 Expert consensus opinion51 recommends nonhormonal vaginal lubricants and moisturizers as well as VOL.cdc. an aminoglycoside agent active against protozoa including T vaginalis. the most extensive experience is with high-dose tinidazole. although published experience is very limited. and PCR for T vaginalis. and external dysuria. The nuances and controversies surrounding treatment of vulvovaginal atrophy have recently been reviewed. Because the cause remains unknown.

Berg AO. J Fam Pract 1984. There remain unresolved issues with each of the conditions discussed that will require ongoing research in this often-neglected area of medicine. Diagnosis and management of vulvar skin disorders. Culhane JF. Ledger WJ. vestibule. 7. Causes of chronic vaginitis: analysis of a prospective database of affected women. management algorithm. Reyes I.58 After initial treatment. Marrazzo JM.18:549–52. Peyton C. Hawes SE. vagina. Weitz MV. Sex Transm Dis 2000. and cervix  perform vaginal pH. 9. 14. Gillespie B. Robinson J. bacterial culture. Koutsky LA. 86% of women were fully controlled with the remainder partially improved. Gardnerella vaginalis. Anecdotally. 26% of treated women were cured. 6. Obstet Gynecol 2006. Culhane JF.reported incidence and associated costs. However. However. when appropriate. 2010. Holmes KK. 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.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. 72. with longer follow-up at 1 year. Vulvovaginal candidiasis. Eckert LO. other ancillary laboratory tests*  realize that one patient may have multiple causes for her symptoms Depending on inappropriate criteria to diagnose or exclude vulvovaginal infections (eg. risk factors. 191–203. Difficulties in the diagnosis of Candida vaginitis.59:1–110.27:230–5. Anderson MR. Foxman B. 5. Yih MC. vulvar or vaginal biopsies. because of the potential role of hypoestrogenism in triggering desquamative inflammatory vaginitis. Centers for Disease Control and Prevention (CDC). Box 1. Mathew L. 7:458–62. p. 58% required some sort of maintenance therapy. Sharp LK.107: 1195–206. et al. Workowski KA. ACOG Practice Bulletin No. Nyirjesy P. Sparling PF. Jeremias J.111:1243–53. Alternative therapies in women with chronic vaginitis. Evaluation of vaginal complaints. Impact of vaginal antifungal products on utilization of health care services: evidence from physician visits. herpes simplex virus PCR and type-specific immune globulin G antibodies. Mathew L. 93. and. Obstet Gynecol 2008. Sexually transmitted disease treatment guidelines. Pap test for bacterial vaginosis) Management Assuming that positive cultures or PCR for group B streptococci. 10. Possible Pitfalls in the Treatment of Women With Chronic Vaginitis Evaluation Accepting patient self-diagnosis or telephone diagnosis Failure to:  get appropriate problem-focused history  inspect vulva. Sobel JD. Witkin SS. Berman S. 4. Piot P. summarized in Box 1. Lemon SM. most health care providers should be able to help the vast majority of women with chronic vaginitis achieve significant control of their symptoms. a gratifying outcome for patient and health care provider alike. and 16% were only partially controlled with ongoing treatment. D’Arcy H. Nyirjesy P. Clinical comparison of microscopic and culture techniques in the diagnosis of Candida vaginitis. JAMA 2004. Heidrich FE.326:993–4. Neisseria gonorrhoeae and Candida trachomatis PCR. J Am Board Fam Pract 2000. Vaginitis. Bergman JJ. Candida vaginitis: self. and saline and potassium hydroxide microscopy  obtain yeast culture with speciation. most experts will use exogenous estrogen after initial treatment to decrease the chance of recurrence. 3. ACOG Practice Bulletin No. Polaneczky MM. by acknowledging they exist and steering clear of them when possible. American College of Obstetricians and Gynecologists.9:66–9. Lev-Sagie A. Sobel JD. Lipsky MS. Stamm WE. 11. Cur Infect Dis Rep 2005. 8. Stevens CE. Barlow R. Normal genital flora. Waters T.291:1368–79. In: Holmes KK. Cohrssen A. Hillier SL. 3rd ed. MMWR Recomm Rep 2010. Nyirjesy P. Klink K. No conclusions could be made in terms of the relative efficacy of either drug.108:1185–91. 2. OBSTETRICS & GYNECOLOGY Copyright ª American College of Obstetricians and Gynecologists . Obstet Gynecol 2011.117:856–61. 1999. Eschenbach DA. enterococcus and Escherichia coli represent true infection Treating for vulvovaginal candidiasis or bacterial vaginosis presumptively Too short a course of treatment for patients with refractory or recurrent infections Not bringing the patient back after therapy to assess her response Forgetting that treatment with topical creams or ointments can cause symptoms similar to what the patient had in the past *Trichomonas vaginalis polymerase chain reaction (PCR) or culture. Advances in diagnosing vaginitis: development of a new algorithm. 12. 13. Mårdh P-A. Schneeweis R.13:178–82. Some of these pitfalls such as selfdiagnosis and telephone diagnosis are at times unavoidable. Obstet Gynecol 1998. BMJ 2003. Infect Dis Clin Pract 2000. Sexually transmitted diseases. New York (NY): McGraw-Hill. editors. Vulvovaginal candidiasis: clinical manifestations. amine test. American College of Obstetricians and Gynecologists. it is easy to fall into many traps.92:757–65. Obstet Gynecol 2006. REFERENCES 1. Tolbert V.

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analysis of a prospective database. diagnosis and treatment. Desquamative inflammatory vaginitis: a new subgroup of purulent vaginitis responsive to topical 2% 57.ATIONAL)NSTITUTESOF(EALTH. (OWARD(UGHES-EDICAL)NSTITUTE0UBLICACCESS!VAILABLEATHTTPWWWHHMIORG about/research/journals/main?action=search. Schlievert PM. Edlind TD. Vaginal toxic shock reaction triggering desquamative inflammatory vaginitis. Available at http://publicaccess. Retrieved October 7. Reichman O. Vaginitis in women. Sobel JD. 2014. J Low Genit Tract Dis 2013. Am J Obstet Gynecol 1994. Obstet Gynecol 1988.nih. 55.)( 1 s4HE(OWARD(UGHES-EDICAL)NSTITUTE((-) 2 s4HE7ELLCOME4RUST3 As a service to our authors. 54.pdf) provides the mechanism for identifying such articles. Nyirjesy P. Edwards L. Gray LA. Within medical research. 53. Prognosis and treatment of desquamative inflammatory vaginitis. clindamycin therapy.283:539–43. Sobel JD.71:832–6. J Low Genit Tract Dis 2012.17:88–91. The comparison of hyaluronic acid vaginal tablets with estradiol vaginal tablets in the treatment of atrophic vaginitis: a randomized controlled trial. Barnes ML.77 WILLIDENTIFYTOTHE. 58. the journal’s publisher (Lippincott Williams & 7ILKINS.gov/. 16:24–9.com/ong/accounts/agreementform. Arch Gynecol Obstet 2011.117:850–5. et al.- ARTICLES THATREQUIREDEPOSIT4HEJOURNALSAUTHORAGREEMENTFORMAVAILABLEAT http://edmgr. 56. Yoo W.92:125–36.. Gencer I. Temur M.IBRARYOF-EDICINE. 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$EPARTMENTOF(EALTHAND(UMAN3ERVICES.ATIONAL. Uhri M. Yas¸ar L. Am J Obstet Gynecol 1965. Friedrich EG Jr. Ekin M.171: 1215–20. 2014. Desquamative vaginitis: lichen planus in disguise. Obstetrics & Gynecology and Public Access A number of research-funding agencies now require or request authors to submit the postprint (the article after peer review and acceptance but not the final published article) to a repository that is accessible online by all without charge.ATIONAL)NSTITUTESOF(EALTHPUBLIC access. Misra D. 7ELLCOME4RUST/PENACCESSPOLICY!VAILABLEATHTTPWWWWELLCOMEACUK!BOUT US 0OLICY0OLICY AND POSITION STATEMENTS74$HTM2ETRIEVED/CTOBER. Pereira N. Retrieved October 7. Savan K. Obstet Gynecol 2011.ovid. three funding agencies in particular have announced such policies: s4HE.

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