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

Gardnerella.for Disease Control and Prevention7 stress the importance of in-office testing for vaginal pH. Obstet Gynecol 2014.9 For other tests for vaginal infections (ie. and in the case of PCR testing for yeast and bacterial vaginosis. Advances in diagnosing vaginitis: development of a new algorithm. they are also occasional causes of purulent vaginitis. and group B streptococci are frequently found. A pH-based framework for diagnosing the most common causes of vaginitis. and those in whom evaluation is consistent with recurrent bacterial vaginosis. culture of the vagina demonstrates a variety of organisms. fissures. During a woman’s reproductive years. vulvar biopsies. Finally. Figure 2. Under the influence of estrogen. 0. the gold standard test remains either culture or the more easily available polymerase chain reaction (PCR) with the U. estrogen plays a key role in maintaining the normal vaginal environment. Although these latter two organisms may be commensals.7. VOL. treating. the vaginal epithelium thickens. office testing has poor performance characteristics. and. Gardnerella vaginalis. We perform this latter test in all of our patients at risk for a sexually transmitted infection. As shown in Table 1. NO. including skin and fecal flora and lactobacilli. or ulcers should routinely lead to PCR tests for herpes simplex virus and possibly type-specific immune globulin G antibody testing. vaginal biopsies. Food and Drug Administration–cleared APTIMA T vaginalis assay. If Trichomonas vaginalis infection is suspected but not proven. yeast cultures with speciation of the organism play an integral part in diagnosing. NORMAL VAGINAL PHYSIOLOGY AND DISCHARGE With physiologic discharge occurring as the final diagnosis in 9% of the patients referred to our tertiary care program. and ruling out vulvovaginal candidiasis. vaginal pH testing in particular can be used to drive the entire diagnostic process. particularly if the etiology is unclear. and ancillary tests are frequently indicated. PCR testing for yeast and bacterial vaginosis). Nyirjesy. should be considered for focal abnormalities. those with many white blood cells on microscopy. they are more costly than current modalities. and trichomoniasis. amines. Frequently underused. enterococci.7:458–62. because normal vaginal flora such as Escherichia coli. Curr Infect Dis Rep 2005. Management of Persistent Vaginitis. MONTH 2014 Nyirjesy Management of Persistent Vaginitis Copyright ª American College of Obstetricians and Gynecologists 3 .4 understanding the normal vaginal environment is important. The findings of vesicles.S. Vaginal Fig. 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. However. 0. In addition. Of those. Figure 1 describes the pH-based algorithm that we use in practice. Routine bacterial cultures are otherwise unhelpful and can be misleading. point-of-care enzymatic. these easily available tests can frequently diagnose common forms of vaginitis. and both saline and 10% potassium hydroxide microscopy.8 Saline microscopy can aid in diagnosing bacterial vaginosis and trichomoniasis. Before puberty. Sobel JD. antigen and DNA tests for candida. by assessing for increased white blood cells and abnormal cytology such as parabasal cells. Reprinted with kind permission from Springer Science+Business Media: Nyirjesy P. Lactobacilli become the dominant flora. the vagina is thinned and has a high pH. there is currently little evidence that they are superior to current gold standards. 1. which lowers the pH of the vagina to less than 4. less commonly. saline microscopy tests for atrophic vaginitis and desquamative inflammatory vaginitis.

polymerase chain reaction. coccobacillary flora Positive Trichomoniasis Varies Trichomonads Variable Atrophic vaginitis Desquamative inflammatory vaginitis $4. which typically causes itching. decreased mixed flora Parabasal cells. travel costs.4. 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. when a discharge is physiologic. and time missed from work.7 $4. Hormonal influences will change a discharge. vaginal signs are usually limited to erythema or occasionally thrush. or excoriations. which will be discussed later. fissures. a heavy discharge coming from the upper genital tract may be the result of an endometrial polyp or fallopian tube malignancy. is present in normal healthy women. 6white blood cells. Because many women and health care providers are taught that a thick white discharge is most frequently caused by vulvovaginal candidiasis. the prerequisite is colonization with Candida species. swelling. burning. 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. Testing for Causes of Vaginitis Vaginal pH Saline or 10% Potassium Hydroxide Microscopy Normal .7 Clue cells. an abnormal discharge may sometimes be the result of occult urinary incontinence. almost doubling the rate of diagnosis. with women noting a clear mucus midcycle to a thick white discharge at other times. In our experience. may have high false-positive rates. Vaginal colonization occurs through multiple routes. increased white blood cells. pelvic ultrasonography or sonohysterography should be considered. 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. only has a sensitivity of approximately 50%13 and.15 To develop a symptomatic infection.7 Unremarkable. a woman’s perception of her discharge correlates quite poorly with vulvovaginal candidiasis.12 Although findings may be minimal. Candida colonization. up to 30% at any single time and 70% if followed longitudinally for 1 year. were estimated to be $1. and perhaps 8–10% will suffer from four or more episodes every year. some patients require multiple visits with normal evaluations to be fully reassured. irritation.4. examination may reveal vulvar redness. and despite evidence that the symptom of discharge is nonspecific. or dyspareunia. when suspected. bacillary flora Hyphae. digital introduction. depending on the health care provider.7 Negative Clinical diagnosis Vulvovaginal candidiasis . Diagnosing a discharge as physiologic can only be done by excluding potential causes. Even more uncommonly. the first line in diagnosis. a common event for almost every woman. external dysuria. including local transport from the perineum and perianal areas.7 Parabasal cells.14 Thus. the current definition of recurrent disease. soreness.2 complaints of a thick white discharge often lead to repeated use of unnecessary antifungal therapy and raise fears of recurrent infection. in a study at a Dutch dermatology clinic.11 Although most people believe that a thick white discharge is the hallmark symptom of yeast infections. yeast cultures with speciation should be obtained to confirm the diagnosis.4.11 Approximately 75% of women will develop symptomatic vulvovaginal candidiasis at least once in their lives. and these medications number in the top 10 of all over-the-counter medications sold in the United States. including medical and treatment expenses.12 Office microscopy (Table 1). 4 Nyirjesy Management of Persistent Vaginitis 50% of women will experience sporadic recurrences. 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. Furthermore. Repeated sampling through patient vaginal self-culture for yeast may further aid in diagnosis. OBSTETRICS & GYNECOLOGY Copyright ª American College of Obstetricians and Gynecologists . blastospores Negative Bacterial vaginosis $4.10 The associated annual costs of vulvovaginal candidiasis in the United States in 1995. usually with Candida albicans.Table 1. the annual market has been estimated at $275 million. discharge usually becomes heavier. or sexual transmission.8 billion.

perhaps 54% of women have no improvement of symptoms after successful eradication. immunosuppression. which in turn causes symptoms. it was felt that these women had a decreased immune response. 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. With C albicans infections.23 Whatever the cause. In an even smaller group. Diabetics may be more prone to developing infections caused by Candida glabrata18.for most. with many women asymptomatically colonized with yeast. more recently. but. In the past.7 In at least half of women with recurrent vulvovaginal candidiasis. or a diaphragm with spermicide have all been associated with increased infection. environmental. other women.22 and using contraception with oral contraceptives.24 As reviewed by Fidel. when a woman with persistent vaginitis has a positive yeast culture.23 As reviewed by Sobel.26 adherence of yeast cells to vaginal epithelium causes colonization. should be considered complicated and are more likely to fail standard antifungal therapy. including those with recurrent vulvovaginal candidiasis and those with nonalbicans Candida infections. including secreted aspartate proteinases.20 In menopausal women.21 In our experience. leading to an inflammatory response to yeast colonization.6. and treatment of the male partner to prevent vulvovaginal candidiasis is not recommended.19 With antibiotic use. other host factors. ranging from oral to topical. prescription to over-the-counter. VOL. An effective approach to resolve the question is to treat her and see if successful treatment. and mycotoxins. candida may be a commensal organism. determined by a negative follow-up culture. its eradication results in a relief of symptoms in up to 90% of cases. this is a transient asymptomatic event. MONTH 2014 In most women with vulvovaginal candidiasis. which result in increased susceptibility to infection. Of these. it has been suggested that symptomatic candidiasis is the result of an increased sensitivity to yeast. perhaps with sporadic recurrence.7 In general. Although each has its own advantages and disadvantages. exogenous estrogen use increases the risk of both candidal colonization and infection. the approach that is commonly used is maintenance Nyirjesy Management of Persistent Vaginitis Copyright ª American College of Obstetricians and Gynecologists 5 . 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. approximately 30% of women will be infected by other species of yeast. diabetes. particularly orogenital sex. 40% have a similar result. an intrauterine device. Sexual activity.16 After colonization. as many 5%. these regimens are clearly inadequate in women with complicated disease with failure rates of 35% within just 1 month of treatment.27 Most treatment guidelines distinguish between uncomplicated and complicated vulvovaginal candidiasis. there are many available treatments. with C glabrata. women with uncomplicated infections are otherwise healthy women with mild-to-moderate symptoms resulting from sporadic episodes of infections caused by C albicans.28 For uncomplicated disease. usually with the same strain of yeast. Women with recurrent infections have increased vaginal Candida species colonization rates. NO.26 In tertiary care vaginitis programs. Furthermore.11 The transition from asymptomatic colonization to symptomatic infection may be the result of intrinsic host. but some women develop a symptomatic infection that goes away easily with standard antifungal therapy.23 Although up to 20% of male partners of women with recurrent infections may harbor candida strains on their penises. proteases. Virulence factors produced by Candida species.27 However. there are no clear risk factors. antibiotic and estrogen use. For infections resulting from C albicans. may inhibit phagocytic activity and suppress the local immune system. although topical and systemic corticosteroid use may be more common. they all have similar efficacy for C albicans infections with an expected cure rate of 80– 90% in uncomplicated patients. and with C parapsilosis. C albicans remains by far the most common cause of infection. symptomatic episodes seem to occur mainly in women with preexisting colonization. 0.25 most affected women seem to exhibit altered local immunoregulatory mechanisms. or organism-related factors. 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. is associated with a relief of symptoms. behavioral. may be at play. and subsequent germination promotes subsequent vaginitis.25 Finally. actual transmission is thought to be uncommon. with C glabrata and Candida parapsilosis being the most common. 0. and behavioral factors are familiar to most health care providers. glycosuria may be one mechanism contributing to both colonization and symptomatic infection. phospholipases. including genetic factors. and 1-day to 7-day regimens.7 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. systemic immunosuppression is rare in women with vulvovaginal candidiasis.

Although clinical and in vitro resistance to C albicans is rare. Centers for Disease Control and Prevention. alternate doses of fluconazole (100 or 200 mg) are also recommended. NAMS. those specific formulations are no longer commercially available. possibly induced by long-term use of fluconazole. Although alternate topical maintenance regimens with clotrimazole have been described and shown to be effective. then twice/wk Estradiol (2 mg) ring every 3 mo Clindamycin 2% vaginal cream.75% vaginal gel 5 g/d310 d. given 5 g daily for 14 days.9% compared with 36. to induce a negative culture. has been shown to be effective32 but has become prohibitively expensive. In a study of maintenance fluconazole for recurrent vulvovaginal candidiasis.625 mg/g) cream 0. it is inexpensive and well-tolerated. Thus. 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. then twice a week for 6 months. 9. 73.32 Apart from occasionally causing local irritation and an abnormal discharge. evidence is limited to case reports or small case series.5 g twice/wk Estradiol (0.32 Vaginal boric acid at 600 mg. but the approaches used for C glabrata or Table 2. and only one had a mild elevation in aminotransferase levels. 5 g/d34 wk Hydrocortisone 10% vaginal cream. headaches. 3 days apart. in which patients are treated with a prolonged (usually 6-month) regimen.5% vaginal cream. in the placebo group (P. Only one patient discontinued treatment because of an adverse event (headache) attributable to fluconazole. Although unstudied.7 because they may be more easily accepted by prescription plans. This approach gives almost all women a prolonged period of symptom relief. The initial regimen used was 100 mg ketoconazole daily for 6 months. 28. and then followed for an additional 6 months (observation phase). many health care providers restart maintenance if the pathogen remains C albicans. and 42.010 mg) tablet/d32 wk. administered daily in a gelatin capsule for 14 days. flucytosine compounded into a 15. which prevent the use of fluconazole. the same cannot be said for non-albicans Candida species. respectively. gastrointestinal discomfort.001).6.6 The advent of fluconazole in the early 1990s led to the replacement of ketoconazole by fluconazole as maintenance. then twice/wk34 mo Tinidazole 2 g/d daily for 5 d Estradiol 0. 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.33 Finally. the proportions of women who remained disease-free at 6. 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.. a recent report by Marchaim31 of clinically fluconazole-resistant C albicans vulvovaginal candidiasis. then once/wk36 mo Boric acid 600-mg capsules vaginally per d32 wk Metronidazole 0. For women who recur after maintenance therapy (approximately 50%). or cost. They were then randomized to weekly 150 mg fluconazole or placebo for 6 months (treatment phase). with C parapsilosis. 3 g/d34 wk Sobel30 Sobel32 Sobel43 CDC7 NAMS51 Sobel58 CDC. allergy. North American Menopause Society.antifungal therapy. and 12 months in the fluconazole group were 91. Of the 343 patients who were studied for efficacy. There are some situations such as pregnancy. but it is no longer recommended because of the risk of liver toxicity. maintenance fluconazole therapy is a well-tolerated and effective approach to treating recurrent C albicans infections (Table 2). is recommended as initial therapy and cures up to 70% of C glabrata infections (Table 2). have been used successfully in our practice (unpublished observation). used daily for 14 days. Regimens of miconazole 2% cream or clotrimazole 1% cream.01% vaginal cream 2–4 g/d daily for 1–2 wk. Current guidelines7 suggest using topical regimens intermittently.34 For other non-albicans Candida infections.7. then 1 g 1–3 times/wk Conjugated estrogen (0. 6 Nyirjesy Management of Persistent Vaginitis OBSTETRICS & GYNECOLOGY Copyright ª American College of Obstetricians and Gynecologists . Limited experience with topical amphotericin B as a 50-mg suppository offers another option for C glabrata infections. The second line of therapy.30 women were initially given three doses of 150 mg fluconazole. and 22%. Although resistance to fluconazole seems to be fortunately rare.

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

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). and 65%. Although hypersensitivity reactions have been rare. In women who have sex with women.7 In an attempt to prevent reinfection. To date. tinidazole. the only controlled study consisted of metronidazole gel twice weekly for 4 months after an initial 10-day course of therapy (Table 2). with a failure rate of 50% by 36 weeks of follow-up. 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. discharge. 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. such as the U. To date. if a patient returns with ongoing trichomoniasis after treatment.6. Centers for Disease Control and Prevention guidelines recommend obtaining cultures OBSTETRICS & GYNECOLOGY Copyright ª American College of Obstetricians and Gynecologists .42 and recolonization with lactobacillus supplements. reinfection.7 However. saline microscopy alone is simply not a good enough test to reliably diagnose trichomoniasis. but this theory was later discounted. Thus. With a resistant infection. 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. have shown no benefit and are not recommended.43 In this study of 127 evaluable women. However.7 and 10. other cases were incident cases occurring in women being treated for other conditions.1%.6.47 Thus.46 Occasionally.S. and occasionally punctate hemorrhages of the vaginal mucosa and cervix.7 For now. the latter estimated at anywhere between 1. 78. vulvovaginal soreness and itching. TRICHOMONIASIS Considered the third most common cause of infectious vaginitis. Treatment failure can be related to noncompliance. 16.42 data in favor of sexual transmission include evidence that bacterial vaginosis can be transmitted between female sexual partners. The mainstay of therapy has been metronidazole and. we routinely recommend consistent condom use for 3–6 months. more recently. and metronidazole resistance. health care providers should check to make sure that the treatment was taken and that reinfection did not occur. culture or PCR is recommended. The finding of polymicrobial G vaginalis–dominant biofilm in men has added further fuel to the debate. Although up to 50% of infected women may be asymptomatic. However. the most common issues pertaining to trichomoniasis in women with persistent vaginitis are missed diagnosis (31%) and metronidazoleresistant infection (33%). the best approach seems to be maintenance therapy. as summarized by Muzny and Schwebke. patients who are allergic to nitroimidazoles represent a therapeutic challenge. or persistence of a vaginal biofilm.45 symptomatic women will complain of an abnormal discharge (clear to yellow–green and frothy). With resistance. metronidazole-resistant trichomoniasis is primarily a clinical diagnosis.001). Based on these various theories. but routine screening or treatment of the female partner is not. a patient with this uncommon clinical scenario should be managed in conjunction with an allergist.Gardner and Dukes40 had also hypothesized that bacterial vaginosis was sexually transmitted. it remains difficult to truly cure women with recurrent bacterial vaginosis. not all patients with trichomoniasis are straightforward. health care providers may also encounter women with allergic reactions to nitroimidazoles. 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. despite serious limitations. although data supporting this recommendation are lacking. treatment of partner studies.7 However.41 Thus. failure to reestablish normal lactobacillus-dominant flora.48 Thus. With a sensitivity of 60–70%. Other tests.44 Cumulative cure at 12. dyspareunia. bacterial vaginosis and its recurrence could be the result of one or several mechanisms: reinfection through sexual activity. respectively. Although these results represent the most promising ones to date. and pain on urination. the cleaning of shared sex toys between uses is encouraged. As noted in a review of 45 cases seen in a specialty vaginitis clinic. and 28 weeks from the initial visit was 87. infection recurred in 26% of metronidazole gel and 59% of placebo patients (P5. Because in vitro resistance correlates poorly with clinical outcome. Most uncomplicated cases will be cured with treatment with either oral metronidazole or tinidazole along with treatment of the sexual partner. if T vaginalis infection is suspected but not proven. Physical findings include vulvovaginal erythema. Food and Drug Administration–cleared OSOM Trichomonas Rapid Antigen Test may provide a rapid (less than 10 minutes) result in the office. the in vitro mechanisms are the result of both aerobic and anaerobic pathways. a variety of potential treatment interventions make sense.

Laboratory findings are summarized in Table 1. is believed to be the most common cause of vulvovaginal symptoms in menopausal women. Importantly. VULVOVAGINAL ATROPHY As one might expect. A longer course of metronidazole. 5 g vaginally nightly.gov/std). suggests that it may be one option in problematic women. However. 2 g metronidazole or tinidazole orally daily for 5 days is recommended as initial therapy (Table 2). postpartum and breastfeeding. itching.7 Beyond that. 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. Because the cause remains unknown. recognition and treatment of atrophy are part of any discussion of chronic vaginitis. a loss of rugal folds.51 As summarized by the North American Menopause Society. ie. paromomycin had a 58% cure rate. examination reveals severe introital and vaginal erythema and a copious vaginal discharge. and PCR for T vaginalis.for resistance testing and can offer management recommendations (telephone: 404-718-4141. it may be the result of a local toxin-induced inflammatory reaction to S aureus infection57 or even group A streptococcal infection.51. 92% were cured with highdose tinidazole. Findings include atrophy of the labia majora or minora. symptomatic vulvovaginal atrophy. and a yellow watery discharge.52 Thus. the most extensive experience is with high-dose tinidazole. experience with paromomycin. low-dose vaginal estrogen. In a series of 33 patients who failed courses of high-dose metronidazole. mostly to no avail. burning. can provide adequate symptom relief (Table 2). in 469 women with chronic vaginitis.51 Finally. various treatment regimens have been proposed. 500 mg orally twice daily for 7 days. or perimenopausal or postmenopausal) and notices the onset of an abnormal discharge. NO. and even blood-tinged. vestibular and vaginal pallor. Intravaginal dihydroepiandrosterone or hyaluronic acid may be considered as possible alternatives to estrogen. although published experience is very limited.50 To minimize the risk of ulceration.52 DESQUAMATIVE INFLAMMATORY VAGINITIS First described by Gray and Barnes in 1965.49 Apart from nitroimidazoles. 0. The nuances and controversies surrounding treatment of vulvovaginal atrophy have recently been reviewed.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. vaginal erythema or even petechiae. When we suspect desquamative inflammatory vaginitis. affected women may sometimes note a heavier discharge. 1 g two or three times a day orally along with 500 mg a day vaginally for 14 days. Because some patients with severe atrophic vaginitis may have white blood cells on microscopy. dyspareunia. where they studied 98 women Nyirjesy Management of Persistent Vaginitis Copyright ª American College of Obstetricians and Gynecologists 9 .51 Expert consensus opinion51 recommends nonhormonal vaginal lubricants and moisturizers as well as VOL. contact bleeding.56 the cause remains unknown. In a minority of women. patients are instructed to apply a barrier such as petrolatum to the vestibule. very few controlled studies have been done to assess their effect. systemic estrogen (with or without progesterone) or ospemifene may be considered.cdc. Unlike vulvovaginal atrophy. usually described as yellow or brown. Despite the sensation of dryness. Furthermore. we routinely perform vaginal bacterial cultures. MONTH 2014 continued sexual activity as initial therapy for women with vulvovaginal atrophy. most women with vulvovaginal atrophy may not relate their symptoms to menopausal changes.53 For those women preferring systemic therapy. However. if necessary. it was diagnosed not only in women older than 50 years (48%) but also in younger women (5%). 0. the medical literature is peppered with other medications used in resistant trichomonas cases. atrophic vaginitis. web site: http:// www. looking for group A streptococci or S aureus. 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. the degree of atrophic changes as measured by findings and maturation index does not correlate with symptoms. but vestibular and vulvar ulceration is a side effect that limits its use. Used as a 5% cream. used commonly in our practice. a lack of response to topical estrogen may also serve to distinguish between the two conditions. then.49 Recently. The typical patient with desquamative inflammatory vaginitis is hypoestrogenic (on continuous lowdose birth control pills. along with burning and severe dyspareunia. The presence of white blood cells on saline microscopy can distinguish it from atrophy. The main complaints are those of dryness. an aminoglycoside agent active against protozoa including T vaginalis. and external dysuria. The most extensive published experience was from Wayne State University. For most women.4 Initially thought of as a possible bacterial overgrowth of an atrophic vagina55 or even a variant of lichen planus. yellow or watery.

Witkin SS.107: 1195–206. Obstet Gynecol 2008. Sharp LK. Obstet Gynecol 2006. Obstet Gynecol 1998. amine test. Foxman B. No conclusions could be made in terms of the relative efficacy of either drug. 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. MMWR Recomm Rep 2010. OBSTETRICS & GYNECOLOGY Copyright ª American College of Obstetricians and Gynecologists . vagina. Hawes SE. vulvar or vaginal biopsies. American College of Obstetricians and Gynecologists. Diagnosis and management of vulvar skin disorders. Vulvovaginal candidiasis. p. New York (NY): McGraw-Hill. Mårdh P-A. Ledger WJ. Lipsky MS. Culhane JF. Klink K. Berman S. In: Holmes KK.326:993–4. Heidrich FE. 9. Culhane JF. However. with longer follow-up at 1 year. Neisseria gonorrhoeae and Candida trachomatis PCR. Nyirjesy P. 26% of treated women were cured. Weitz MV. Reyes I. Piot P. 7:458–62. J Fam Pract 1984. Schneeweis R.9:66–9. Gardnerella vaginalis. Holmes KK. J Am Board Fam Pract 2000. management algorithm. REFERENCES 1. Obstet Gynecol 2006. Sparling PF. Alternative therapies in women with chronic vaginitis. Impact of vaginal antifungal products on utilization of health care services: evidence from physician visits. Candida vaginitis: self. 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.reported incidence and associated costs. Marrazzo JM. by acknowledging they exist and steering clear of them when possible. Hillier SL. vestibule. 14. Sobel JD. BMJ 2003. 86% of women were fully controlled with the remainder partially improved. Vaginitis. Anderson MR. Stamm WE. 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. Cohrssen A. Gillespie B. Advances in diagnosing vaginitis: development of a new algorithm. Cur Infect Dis Rep 2005. editors. risk factors.18:549–52. 6. Stevens CE. when appropriate. JAMA 2004. Jeremias J. Infect Dis Clin Pract 2000. American College of Obstetricians and Gynecologists. 11. Difficulties in the diagnosis of Candida vaginitis. 58% required some sort of maintenance therapy. Eschenbach DA. 93. 2. Some of these pitfalls such as selfdiagnosis and telephone diagnosis are at times unavoidable. However. et al. summarized in Box 1. Eckert LO. and. and cervix  perform vaginal pH.13:178–82. Berg AO.58 After initial treatment. Pap test for bacterial vaginosis) Management Assuming that positive cultures or PCR for group B streptococci.291:1368–79. bacterial culture. Nyirjesy P.92:757–65. Peyton C. 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. 10. most experts will use exogenous estrogen after initial treatment to decrease the chance of recurrence. Yih MC. Waters T. Evaluation of vaginal complaints.59:1–110. Causes of chronic vaginitis: analysis of a prospective database of affected women. 3. 12. Sex Transm Dis 2000. Vulvovaginal candidiasis: clinical manifestations.111:1243–53. 7. Lev-Sagie A. because of the potential role of hypoestrogenism in triggering desquamative inflammatory vaginitis.27:230–5. Sobel JD. 72. 5. Mathew L. Nyirjesy P. 13. 1999. Sexually transmitted disease treatment guidelines. Anecdotally.108:1185–91. Robinson J. There remain unresolved issues with each of the conditions discussed that will require ongoing research in this often-neglected area of medicine. a gratifying outcome for patient and health care provider alike.117:856–61. 2010.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. most health care providers should be able to help the vast majority of women with chronic vaginitis achieve significant control of their symptoms. it is easy to fall into many traps. Mathew L. Polaneczky MM. 8. 4. Workowski KA. 3rd ed. and saline and potassium hydroxide microscopy  obtain yeast culture with speciation. Bergman JJ. Tolbert V. Lemon SM. ACOG Practice Bulletin No. D’Arcy H. Obstet Gynecol 2011. herpes simplex virus PCR and type-specific immune globulin G antibodies. ACOG Practice Bulletin No. Clinical comparison of microscopic and culture techniques in the diagnosis of Candida vaginitis. 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ATIONAL)NSTITUTESOF(EALTHPUBLIC access. Barnes ML. J Low Genit Tract Dis 2012. Ekin M. (OWARD(UGHES-EDICAL)NSTITUTE0UBLICACCESS!VAILABLEATHTTPWWWHHMIORG about/research/journals/main?action=search. Sobel JD. Available at http://publicaccess.17:88–91. 53. Obstet Gynecol 2011. 55. Sobel JD. Pereira N. 2014. Gencer I.117:850–5. Schlievert PM.gov/. Temur M. Vaginal toxic shock reaction triggering desquamative inflammatory vaginitis. et al. Desquamative inflammatory vaginitis: a new subgroup of purulent vaginitis responsive to topical 2% 57. Within medical research. 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.92:125–36. Arch Gynecol Obstet 2011.ATIONAL)NSTITUTESOF(EALTH. three funding agencies in particular have announced such policies: s4HE. Yas¸ar L. Obstet Gynecol 1988. 7ELLCOME4RUST/PENACCESSPOLICY!VAILABLEATHTTPWWWWELLCOMEACUK!BOUT US 0OLICY0OLICY AND POSITION STATEMENTS74$HTM2ETRIEVED/CTOBER. Vaginitis in women. Am J Obstet Gynecol 1994. Yoo W. Edlind TD. Reichman O.ovid. Friedrich EG Jr.283:539–43.- ARTICLES THATREQUIREDEPOSIT4HEJOURNALSAUTHORAGREEMENTFORMAVAILABLEAT http://edmgr. Retrieved October 7. 16:24–9.)( 1 s4HE(OWARD(UGHES-EDICAL)NSTITUTE((-) 2 s4HE7ELLCOME4RUST3 As a service to our authors. Retrieved October 7. the journal’s publisher (Lippincott Williams & 7ILKINS. The comparison of hyaluronic acid vaginal tablets with estradiol vaginal tablets in the treatment of atrophic vaginitis: a randomized controlled trial.com/ong/accounts/agreementform. diagnosis and treatment.77 WILLIDENTIFYTOTHE. J Low Genit Tract Dis 2013.analysis of a prospective database. Desquamative vaginitis: lichen planus in disguise. Uhri M. 58. Edwards L. 54. Am J Obstet Gynecol 1965. Nyirjesy P. Gray LA.171: 1215–20.IBRARYOF-EDICINE. 56. LWW will transmit the postprint of an article based on research funded in whole or in part by one or more of these THREEAGENCIESTO0UB-ED#ENTRAL References 53$EPARTMENTOF(EALTHAND(UMAN3ERVICES. Prognosis and treatment of desquamative inflammatory vaginitis. 2014. Misra D.. clindamycin therapy.ATIONAL. Savan K.71:832–6.pdf) provides the mechanism for identifying such articles.nih.

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