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Clinical Expert Series

Management of Persistent Vaginitis
Paul Nyirjesy,


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


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.
Corresponding author: Paul Nyirjesy, MD, 245 North 15th Street, New
College Building, 16th Floor, Philadelphia, PA 19102; e-mail: pnyirjes@
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
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.


Copyright ª American College of Obstetricians and Gynecologists


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

they are also occasional causes of purulent vaginitis. and in the case of PCR testing for yeast and bacterial vaginosis. Gardnerella vaginalis. there is currently little evidence that they are superior to current gold standards. less commonly. which lowers the pH of the vagina to less than 4. Vaginal Fig. Gardnerella. Food and Drug Administration–cleared APTIMA T vaginalis assay. the vaginal epithelium thickens. the vagina is thinned and has a high pH. and. Advances in diagnosing vaginitis: development of a new algorithm. Obstet Gynecol 2014.9 For other tests for vaginal infections (ie. enterococci. office testing has poor performance characteristics. vaginal biopsies. 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. If Trichomonas vaginalis infection is suspected but not proven. and trichomoniasis. A pH-based framework for diagnosing the most common causes of vaginitis. During a woman’s reproductive years. Although these latter two organisms may be commensals. estrogen plays a key role in maintaining the normal vaginal environment. including skin and fecal flora and lactobacilli. the gold standard test remains either culture or the more easily available polymerase chain reaction (PCR) with the U. Under the influence of estrogen. those with many white blood cells on microscopy. and ruling out vulvovaginal candidiasis. Nyirjesy. vulvar biopsies. should be considered for focal abnormalities. NO.4 understanding the normal vaginal environment is important. PCR testing for yeast and bacterial vaginosis). by assessing for increased white blood cells and abnormal cytology such as parabasal cells. As shown in Table 1. Of those. treating. antigen and DNA tests for candida. 0. point-of-care enzymatic. Sobel JD. they are more costly than current modalities. Lactobacilli become the dominant flora. In addition. or ulcers should routinely lead to PCR tests for herpes simplex virus and possibly type-specific immune globulin G antibody testing.for Disease Control and Prevention7 stress the importance of in-office testing for vaginal pH. 0. Before puberty. yeast cultures with speciation of the organism play an integral part in diagnosing. Finally. and ancillary tests are frequently indicated. MONTH 2014 Nyirjesy Management of Persistent Vaginitis Copyright ª American College of Obstetricians and Gynecologists 3 . Management of Persistent Vaginitis. amines. Frequently underused. vaginal pH testing in particular can be used to drive the entire diagnostic process. We perform this latter test in all of our patients at risk for a sexually transmitted infection. and both saline and 10% potassium hydroxide microscopy.7:458–62. fissures. However. VOL. Figure 2. 1.8 Saline microscopy can aid in diagnosing bacterial vaginosis and trichomoniasis. and group B streptococci are frequently found. because normal vaginal flora such as Escherichia coli. The findings of vesicles. particularly if the etiology is unclear. and those in whom evaluation is consistent with recurrent bacterial vaginosis.S. culture of the vagina demonstrates a variety of organisms. saline microscopy tests for atrophic vaginitis and desquamative inflammatory vaginitis. Curr Infect Dis Rep 2005. Figure 1 describes the pH-based algorithm that we use in practice. these easily available tests can frequently diagnose common forms of vaginitis. Reprinted with kind permission from Springer Science+Business Media: Nyirjesy P.7. NORMAL VAGINAL PHYSIOLOGY AND DISCHARGE With physiologic discharge occurring as the final diagnosis in 9% of the patients referred to our tertiary care program. Routine bacterial cultures are otherwise unhelpful and can be misleading.

and these medications number in the top 10 of all over-the-counter medications sold in the United States. 4 Nyirjesy Management of Persistent Vaginitis 50% of women will experience sporadic recurrences. Even more uncommonly. and perhaps 8–10% will suffer from four or more episodes every year. the current definition of recurrent disease. swelling. in a study at a Dutch dermatology clinic. including medical and treatment expenses. external dysuria. a heavy discharge coming from the upper genital tract may be the result of an endometrial polyp or fallopian tube malignancy.12 Office microscopy (Table 1). Hormonal influences will change a discharge.2 complaints of a thick white discharge often lead to repeated use of unnecessary antifungal therapy and raise fears of recurrent infection. may have high false-positive rates.4. In our experience. polymerase chain reaction. OBSTETRICS & GYNECOLOGY Copyright ª American College of Obstetricians and Gynecologists . Diagnosing a discharge as physiologic can only be done by excluding potential causes. depending on the health care provider. the prerequisite is colonization with Candida species.7 Parabasal cells. almost doubling the rate of diagnosis. is present in normal healthy women. 6white blood cells. were estimated to be $1. the annual market has been estimated at $275 million. Testing for Causes of Vaginitis Vaginal pH Saline or 10% Potassium Hydroxide Microscopy Normal . 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. usually with Candida albicans. a woman’s perception of her discharge correlates quite poorly with vulvovaginal candidiasis. Furthermore.7 $4. vaginal signs are usually limited to erythema or occasionally thrush. Candida colonization. or sexual transmission. when suspected. increased white blood cells.4. pelvic ultrasonography or sonohysterography should be considered. some patients require multiple visits with normal evaluations to be fully reassured.7 Clue cells. or excoriations. digital introduction.Table 1.7 Negative Clinical diagnosis Vulvovaginal candidiasis . up to 30% at any single time and 70% if followed longitudinally for 1 year. blastospores Negative Bacterial vaginosis $4. travel costs. which typically causes itching. discharge usually becomes heavier. fissures.15 To develop a symptomatic infection. Repeated sampling through patient vaginal self-culture for yeast may further aid in diagnosis. and despite evidence that the symptom of discharge is nonspecific. bacillary flora Hyphae.8 billion. and time missed from work. 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. irritation. with women noting a clear mucus midcycle to a thick white discharge at other times. the first line in diagnosis. which will be discussed later. certainly in women with recurrent infection and possibly in those in whom candidiasis is suspected but not proven.14 Thus. only has a sensitivity of approximately 50%13 and. or dyspareunia.12 Although findings may be minimal. including local transport from the perineum and perianal areas.10 The associated annual costs of vulvovaginal candidiasis in the United States in 1995.7 Unremarkable. VULVOVAGINAL CANDIDIASIS With the proliferation of over-the-counter antifungal drugs.11 Although most people believe that a thick white discharge is the hallmark symptom of yeast infections. soreness. Because many women and health care providers are taught that a thick white discharge is most frequently caused by vulvovaginal candidiasis. when a discharge is physiologic. burning.11 Approximately 75% of women will develop symptomatic vulvovaginal candidiasis at least once in their lives. a common event for almost every woman. an abnormal discharge may sometimes be the result of occult urinary incontinence. examination may reveal vulvar redness. Vaginal colonization occurs through multiple routes. decreased mixed flora Parabasal cells. coccobacillary flora Positive Trichomoniasis Varies Trichomonads Variable Atrophic vaginitis Desquamative inflammatory vaginitis $4. yeast cultures with speciation should be obtained to confirm the diagnosis. 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.

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

The initial regimen used was 100 mg ketoconazole daily for 6 months. or cost. and 42. then 1 g 1–3 times/wk Conjugated estrogen (0. to induce a negative culture.32 Vaginal boric acid at 600 mg. headaches. is recommended as initial therapy and cures up to 70% of C glabrata infections (Table 2). allergy. in which patients are treated with a prolonged (usually 6-month) regimen.9% compared with 36. Regimens of miconazole 2% cream or clotrimazole 1% cream. 6 Nyirjesy Management of Persistent Vaginitis OBSTETRICS & GYNECOLOGY Copyright ª American College of Obstetricians and Gynecologists . For women who recur after maintenance therapy (approximately 50%). Of the 343 patients who were studied for efficacy. NAMS.. has been shown to be effective32 but has become prohibitively expensive. 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. used daily for 14 days. 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. and 12 months in the fluconazole group were 91. it is inexpensive and well-tolerated.6 The advent of fluconazole in the early 1990s led to the replacement of ketoconazole by fluconazole as maintenance.01% vaginal cream 2–4 g/d daily for 1–2 wk.32 Apart from occasionally causing local irritation and an abnormal discharge. a recent report by Marchaim31 of clinically fluconazole-resistant C albicans vulvovaginal candidiasis. given 5 g daily for 14 days. Although clinical and in vitro resistance to C albicans is rare. with C parapsilosis. and 22%. and only one had a mild elevation in aminotransferase levels. flucytosine compounded into a 15. possibly induced by long-term use of fluconazole.30 women were initially given three doses of 150 mg fluconazole. many health care providers restart maintenance if the pathogen remains C albicans. 73.75% vaginal gel 5 g/d310 d. 28. 9. The second line of therapy.7.5% vaginal cream. then twice/wk Estradiol (2 mg) ring every 3 mo Clindamycin 2% vaginal cream. 3 days apart.7 because they may be more easily accepted by prescription plans. 5 g/d34 wk Hydrocortisone 10% vaginal cream.34 For other non-albicans Candida infections. Centers for Disease Control and Prevention. 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. This approach gives almost all women a prolonged period of symptom relief. 3 g/d34 wk Sobel30 Sobel32 Sobel43 CDC7 NAMS51 Sobel58 CDC.010 mg) tablet/d32 wk. alternate doses of fluconazole (100 or 200 mg) are also recommended. North American Menopause Society. in the placebo group (P. evidence is limited to case reports or small case series.33 Finally.antifungal therapy. but the approaches used for C glabrata or Table 2. maintenance fluconazole therapy is a well-tolerated and effective approach to treating recurrent C albicans infections (Table 2). respectively. the proportions of women who remained disease-free at 6.625 mg/g) cream 0. There are some situations such as pregnancy.001). then twice a week for 6 months. Only one patient discontinued treatment because of an adverse event (headache) attributable to fluconazole. then twice/wk34 mo Tinidazole 2 g/d daily for 5 d Estradiol 0. In a study of maintenance fluconazole for recurrent vulvovaginal candidiasis. Although resistance to fluconazole seems to be fortunately rare. but it is no longer recommended because of the risk of liver toxicity. then once/wk36 mo Boric acid 600-mg capsules vaginally per d32 wk Metronidazole 0.6. have been used successfully in our practice (unpublished observation). gastrointestinal discomfort. which prevent the use of fluconazole. They were then randomized to weekly 150 mg fluconazole or placebo for 6 months (treatment phase).5 g twice/wk Estradiol (0. and then followed for an additional 6 months (observation phase). Although alternate topical maintenance regimens with clotrimazole have been described and shown to be effective. those specific formulations are no longer commercially available. Current guidelines7 suggest using topical regimens intermittently. the same cannot be said for non-albicans Candida species. administered daily in a gelatin capsule for 14 days. Thus. Although unstudied. Limited experience with topical amphotericin B as a 50-mg suppository offers another option for C glabrata infections.

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%. Megasphaera species. increased risk of infection after gynecologic surgery. known as the Nugent score. and an increased susceptibility to human immunodeficiency virus.. With standard antibiotic regimens. Eggerthella species. Nyirjesy Management of Persistent Vaginitis Copyright ª American College of Obstetricians and Gynecologists 7 . Mobiluncus species.6.6 Although at least 50% of infected women have no symptoms. Diagnosis relies on finding three of four Amsel’s criteria (abnormal gray discharge. the vulvovaginal examination will be normal apart from a discharge described as watery and gray. 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. having a regular sex partner throughout the study.41 recent studies have found that 90% of women with and 10% without bacterial vaginosis have a complex polymicrobial biofilm. high vaginal pH. particularly those resulting from C glabrata. A vaginal Gram stain. and adverse events. 0. These data suggest that it is not the mere presence of G vaginalis that causes bacterial vaginosis. which can be demonstrated on electron microscopy of vaginal biopsies.C parapsilosis are likely to be effective. having less than a high school education. preterm birth. 0. chlamydial. living at or near the federal poverty level.6 Compared with the Nugent score and much easier to perform in an office setting.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. they can often be cured with a second course of the same therapy. positive amine test. because the yeast may be an innocent bystander in at least 50% of cases.7 Although commercial laboratories now offer VOL. Prevotella species. Metronidazole (oral or topical). As reviewed by Verstraelen and Swidsinski. Leptotrichia species and many others. but rather biofilm-associated G vaginalis. Biofilms are a type of slime produced by bacteria.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. a single recurrence or more may occur in up to 58% of women within 12 months. NO. bacterial vaginosisassociated bacteria. and that hormonal contraception had a protective effect. In a molecular analysis of uncultivated organisms. pelvic inflammatory disease. In women with disease. and postpartum endometritis in pregnant women. bacterial vaginosis-associated bacteria-3. later research suggested that it was instead caused by complex changes in vaginal flora and G vaginalis was ignored until recently. and genital herpes infections in nonpregnant women as well as spontaneous abortion. are found in vaginal samples of infected women.38 In a cohort of 130 Australian women treated with a 7-day course of oral metronidazole. is considered the gold standard.6.37 Culture for G vaginalis is not recommended because of a lack of specificity. including urinary tract infections. being non-Hispanic black or Mexican American.001). bacterial vaginosis-associated bacteria-2.36 This disturbed vaginal flora is a risk factor for many infectious morbidities. where the presence or absence of different bacterial morphotypes is scored. the bacterial load may be decreased but the biofilm may not be eliminated. Fusobacterium species. the biofilm consists primarily of G vaginalis and sometimes with A vaginae. As noted earlier. the most common complaints are of an abnormal vaginal discharge and a fishy odor. Bacteroides species. Peptostreptococcus species. After the early report by Gardner and Dukes40 describing G vaginalis as a possible cause of bacterial vaginosis.2 Associated sociodemographic factors include a younger age. including Atopobium vaginae. MONTH 2014 PCR-based modalities to diagnose bacterial vaginosis using various criteria. or having a female sex partner.7 After treatment. If patients fail an initial course of treatment. bacterial vaginosis is considered the most common form of vaginitis.7 They offer equivalent efficacy and can be distinguished from each other on the basis of cost. mode of administration.28 BACTERIAL VAGINOSIS Affecting approximately 30% of women. Megasphaera type 1. Amsel’s criteria have a sensitivity of 92%. cervicitis. Usually. Initially thought to be caused by G vaginalis. and clindamycin (oral or topical) are all recommended as initial treatments. more recent studies using standard culture and DNA-based technologies have shown that a broad range of bacteria. there may be less of a need to treat non-albicans Candida infections. thus setting the stage for recurrence after treatment. the best known example is the biofilm that occurs on infected foreign bodies such as central venous catheters. gonococcal. Bradshaw and colleagues found that the risk factors for recurrence were a history of bacterial vaginosis. P. and douching. and greater than 20% clue cells on saline microscopy). tinidazole (oral). trichomonal. which coats certain surfaces and within which bacteria hide from and are protected from the effects of antibiotics.

health care providers may also encounter women with allergic reactions to nitroimidazoles. and pain on urination. 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. not all patients with trichomoniasis are straightforward. However. a variety of potential treatment interventions make sense.42 and recolonization with lactobacillus supplements.S. with a failure rate of 50% by 36 weeks of follow-up. Fortunately. Treatment failure can be related to noncompliance.7 However. saline microscopy alone is simply not a good enough test to reliably diagnose trichomoniasis. other cases were incident cases occurring in women being treated for other conditions. if T vaginalis infection is suspected but not proven. In women who have sex with women. To date. and 28 weeks from the initial visit was 87.43 In this study of 127 evaluable women. and 65%. it remains difficult to truly cure women with recurrent bacterial vaginosis. and occasionally punctate hemorrhages of the vaginal mucosa and cervix. although data supporting this recommendation are lacking. and metronidazole resistance. Although these results represent the most promising ones to date. but this theory was later discounted.7 However. 16.47 Thus. health care providers should check to make sure that the treatment was taken and that reinfection did not occur.41 Thus. failure to reestablish normal lactobacillus-dominant flora.1%. Based on these various theories. such as the U. With a sensitivity of 60–70%. as summarized by Muzny and Schwebke. With a resistant infection. the in vitro mechanisms are the result of both aerobic and anaerobic pathways.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).45 symptomatic women will complain of an abnormal discharge (clear to yellow–green and frothy). Although hypersensitivity reactions have been rare. dyspareunia. respectively. With resistance. despite serious limitations. oral or parenteral desensitization to metronidazole followed by treatment has been shown to be highly effective in a study of 15 patients treated and cured with such an approach. 78.46 Occasionally. TRICHOMONIASIS Considered the third most common cause of infectious vaginitis. Other tests. As noted in a review of 45 cases seen in a specialty vaginitis clinic. Thus. a patient with this uncommon clinical scenario should be managed in conjunction with an allergist.7 For now. discharge. the only controlled study consisted of metronidazole gel twice weekly for 4 months after an initial 10-day course of therapy (Table 2). or persistence of a vaginal biofilm.48 Thus. 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 cleaning of shared sex toys between uses is encouraged. but routine screening or treatment of the female partner is not. the most common issues pertaining to trichomoniasis in women with persistent vaginitis are missed diagnosis (31%) and metronidazoleresistant infection (33%).44 Cumulative cure at 12. metronidazole-resistant trichomoniasis is primarily a clinical diagnosis. Physical findings include vulvovaginal erythema. 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. The mainstay of therapy has been metronidazole and.7 In an attempt to prevent reinfection. Because in vitro resistance correlates poorly with clinical outcome.6. culture or PCR is recommended. infection recurred in 26% of metronidazole gel and 59% of placebo patients (P5. Although up to 50% of infected women may be asymptomatic.6. the best approach seems to be maintenance therapy. The finding of polymicrobial G vaginalis–dominant biofilm in men has added further fuel to the debate. Food and Drug Administration–cleared OSOM Trichomonas Rapid Antigen Test may provide a rapid (less than 10 minutes) result in the office. we routinely recommend consistent condom use for 3–6 months. have shown no benefit and are not recommended. To date. bacterial vaginosis and its recurrence could be the result of one or several mechanisms: reinfection through sexual activity. However. tinidazole.001). patients who are allergic to nitroimidazoles represent a therapeutic challenge. the latter estimated at anywhere between 1. more recently. Centers for Disease Control and Prevention guidelines recommend obtaining cultures OBSTETRICS & GYNECOLOGY Copyright ª American College of Obstetricians and Gynecologists . Most uncomplicated cases will be cured with treatment with either oral metronidazole or tinidazole along with treatment of the sexual partner. reinfection. vulvovaginal soreness and itching.42 data in favor of sexual transmission include evidence that bacterial vaginosis can be transmitted between female sexual partners.Gardner and Dukes40 had also hypothesized that bacterial vaginosis was sexually transmitted. if a patient returns with ongoing trichomoniasis after treatment.7 and 10. treatment of partner studies.

and external dysuria. patients are instructed to apply a barrier such as petrolatum to the vestibule. A longer course of metronidazole. is believed to be the most common cause of vulvovaginal symptoms in menopausal women.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. we routinely perform vaginal bacterial cultures. vestibular and vaginal pallor. usually described as yellow or brown.51 Expert consensus opinion51 recommends nonhormonal vaginal lubricants and moisturizers as well as VOL. very few controlled studies have been done to assess their effect. In a series of 33 patients who failed courses of high-dose metronidazole.cdc. a loss of rugal folds.52 DESQUAMATIVE INFLAMMATORY VAGINITIS First described by Gray and Barnes in 1965. the most extensive experience is with high-dose tinidazole. Because some patients with severe atrophic vaginitis may have white blood cells on microscopy. along with burning and severe dyspareunia. However. recognition and treatment of atrophy are part of any discussion of chronic vaginitis.51.7 Beyond that. yellow or watery. 92% were cured with highdose tinidazole. then. The most extensive published experience was from Wayne State University. the degree of atrophic changes as measured by findings and maturation index does not correlate with symptoms. 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. However. vaginal erythema or even petechiae. an aminoglycoside agent active against protozoa including T vaginalis. affected women may sometimes note a heavier discharge. Unlike vulvovaginal it may be the result of a local toxin-induced inflammatory reaction to S aureus infection57 or even group A streptococcal infection. The presence of white blood cells on saline microscopy can distinguish it from atrophy. Because the cause remains unknown.50 To minimize the risk of ulceration. Intravaginal dihydroepiandrosterone or hyaluronic acid may be considered as possible alternatives to estrogen. For most women. In a minority of women. The main complaints are those of dryness. postpartum and breastfeeding. 0. it was diagnosed not only in women older than 50 years (48%) but also in younger women (5%). 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. most women with vulvovaginal atrophy may not relate their symptoms to menopausal changes. various treatment regimens have been proposed. 0.49 Recently. The nuances and controversies surrounding treatment of vulvovaginal atrophy have recently been reviewed. ie. web site: http:// www.49 Apart from nitroimidazoles. but vestibular and vulvar ulceration is a side effect that limits its use.for resistance testing and can offer management recommendations (telephone: 404-718-4141. Laboratory findings are summarized in Table 1. mostly to no avail. paromomycin had a 58% cure rate.51 Finally. When we suspect desquamative inflammatory vaginitis. 5 g vaginally nightly. Despite the sensation of dryness. and even blood-tinged. symptomatic vulvovaginal atrophy. 1 g two or three times a day orally along with 500 mg a day vaginally for 14 days. where they studied 98 women Nyirjesy Management of Persistent Vaginitis Copyright ª American College of Obstetricians and Gynecologists 9 . contact bleeding. a lack of response to topical estrogen may also serve to distinguish between the two conditions. or perimenopausal or postmenopausal) and notices the onset of an abnormal discharge. dyspareunia. VULVOVAGINAL ATROPHY As one might expect. in 469 women with chronic vaginitis. experience with paromomycin. if necessary. although published experience is very limited.4 Initially thought of as a possible bacterial overgrowth of an atrophic vagina55 or even a variant of lichen planus. Furthermore. MONTH 2014 continued sexual activity as initial therapy for women with vulvovaginal atrophy. NO. Findings include atrophy of the labia majora or minora. The typical patient with desquamative inflammatory vaginitis is hypoestrogenic (on continuous lowdose birth control pills. 2 g metronidazole or tinidazole orally daily for 5 days is recommended as initial therapy (Table 2). can provide adequate symptom relief (Table 2). suggests that it may be one option in problematic women.51 As summarized by the North American Menopause Society. Used as a 5% cream. Importantly.52 Thus. and PCR for T vaginalis. systemic estrogen (with or without progesterone) or ospemifene may be considered. looking for group A streptococci or S aureus. and a yellow watery discharge. used commonly in our practice. atrophic vaginitis. examination reveals severe introital and vaginal erythema and a copious vaginal discharge.56 the cause remains unknown. 500 mg orally twice daily for 7 days. the medical literature is peppered with other medications used in resistant trichomonas cases. low-dose vaginal estrogen. itching. burning.53 For those women preferring systemic therapy.

Nyirjesy P. 8. JAMA 2004. Anecdotally. Sobel JD. J Fam Pract 1984. Polaneczky MM.92:757–65. et al. amine test. Obstet Gynecol 2008.27:230–5. Nyirjesy P. Causes of chronic vaginitis: analysis of a prospective database of affected women. Mårdh P-A. summarized in Box 1. bacterial culture. vagina. Lev-Sagie A. Sparling PF. No conclusions could be made in terms of the relative efficacy of either drug. Normal genital flora. 10. Robinson J. However. ACOG Practice Bulletin No. Eckert LO.9:66–9. and 16% were only partially controlled with ongoing treatment. Piot P. 6. herpes simplex virus PCR and type-specific immune globulin G antibodies. 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. Cohrssen A. 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. 9. Weitz MV. 3. Witkin SS. Pap test for bacterial vaginosis) Management Assuming that positive cultures or PCR for group B streptococci. Hillier SL. American College of Obstetricians and Gynecologists. Berman S. ACOG Practice Bulletin No. Klink K. and cervix  perform vaginal pH. a gratifying outcome for patient and health care provider alike. Waters T. 13. Stamm WE. Sobel JD. Difficulties in the diagnosis of Candida vaginitis.108:1185–91. Obstet Gynecol 2011. Infect Dis Clin Pract 2000. Koutsky LA. 3rd ed. risk factors.291:1368–79. Lemon SM. BMJ 2003. REFERENCES 1. 2. Heidrich FE. Mathew L. Vulvovaginal candidiasis. In: Holmes KK.107: 1195–206. Culhane JF. 86% of women were fully controlled with the remainder partially improved. most experts will use exogenous estrogen after initial treatment to decrease the chance of recurrence.18:549–52. 72. Impact of vaginal antifungal products on utilization of health care services: evidence from physician visits. Sexually transmitted disease treatment guidelines. because of the potential role of hypoestrogenism in triggering desquamative inflammatory vaginitis. 7. 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Vulvovaginal candidiasis: clinical manifestations.reported incidence and associated costs. J Am Board Fam Pract 2000. Holmes KK. 11. Culhane JF. Box 1. Ledger WJ. Gillespie B. Eschenbach DA. Anderson MR. Gardnerella vaginalis. MMWR Recomm Rep 2010. and. Barlow R. Candida vaginitis: self. Nyirjesy P. Sharp LK. Foxman B.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. it is easy to fall into many traps. vestibule. American College of Obstetricians and Gynecologists.13:178–82. Yih MC. 2010. Obstet Gynecol 2006. Lipsky MS. D’Arcy H. Obstet Gynecol 1998. 5. There remain unresolved issues with each of the conditions discussed that will require ongoing research in this often-neglected area of medicine. Clinical comparison of microscopic and culture techniques in the diagnosis of Candida vaginitis.58 After initial treatment. Sexually transmitted diseases. 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analysis of a prospective database. 16:24–9.ATIONAL. 55. 58. the journal’s publisher (Lippincott Williams & 7ILKINS. Obstet Gynecol Yoo W. Retrieved October 7. Barnes ML. 56. Am J Obstet Gynecol 1994. Available at http://publicaccess. Am J Obstet Gynecol 1965. 53.nih. Nyirjesy P. Retrieved October 7. Vaginal toxic shock reaction triggering desquamative inflammatory vaginitis. (OWARD(UGHES-EDICAL)NSTITUTE0UBLICACCESS!VAILABLEATHTTPWWWHHMIORG about/research/journals/main?action=search.77 WILLIDENTIFYTOTHE. Desquamative inflammatory vaginitis: a new subgroup of purulent vaginitis responsive to topical 2% 57.IBRARYOF-EDICINE. Pereira N.)( 1 s4HE(OWARD(UGHES-EDICAL)NSTITUTE((-) 2 s4HE7ELLCOME4RUST3 As a service to our authors. Sobel JD.117:850–5. Temur M. Ekin M. Sobel JD.17:88–91.71:832–6. Prognosis and treatment of desquamative inflammatory vaginitis. Obstet Gynecol 2011. J Low Genit Tract Dis 2013.171: 1215–20. Within medical research. Misra D. Arch Gynecol Obstet 2011.92:125–36. 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$EPARTMENTOF(EALTHAND(UMAN3ERVICES. Savan K. diagnosis and treatment. Friedrich EG Jr. Gencer Yas¸ar L. Obstetrics & Gynecology and Public Access A number of research-funding agencies now require or request authors to submit the postprint (the article after peer review and acceptance but not the final published article) to a repository that is accessible online by all without charge. et al. 2014. 54. 2014.- ARTICLES THATREQUIREDEPOSIT4HEJOURNALSAUTHORAGREEMENTFORMAVAILABLEAT http://edmgr. Edlind TD. clindamycin therapy.ovid. Reichman O.. J Low Genit Tract Dis 2012. Schlievert PM. The comparison of hyaluronic acid vaginal tablets with estradiol vaginal tablets in the treatment of atrophic vaginitis: a randomized controlled trial. Desquamative vaginitis: lichen planus in disguise. Edwards L.pdf) provides the mechanism for identifying such articles. Gray LA. Vaginitis in women. Uhri M. 7ELLCOME4RUST/PENACCESSPOLICY!VAILABLEATHTTPWWWWELLCOMEACUK!BOUT US 0OLICY0OLICY AND POSITION STATEMENTS74$HTM2ETRIEVED/CTOBER.ATIONAL)NSTITUTESOF(EALTHPUBLIC access. three funding agencies in particular have announced such policies: s4HE.283:539–43.

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