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

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

and time missed from work. increased white blood cells.2 complaints of a thick white discharge often lead to repeated use of unnecessary antifungal therapy and raise fears of recurrent infection. digital introduction. and perhaps 8–10% will suffer from four or more episodes every year. Hormonal influences will change a discharge. a woman’s perception of her discharge correlates quite poorly with vulvovaginal candidiasis.7 Parabasal cells.4. external dysuria. a common event for almost every woman. 6white blood cells. irritation.7 Negative Clinical diagnosis Vulvovaginal candidiasis . were estimated to be $1. Because many women and health care providers are taught that a thick white discharge is most frequently caused by vulvovaginal candidiasis. Repeated sampling through patient vaginal self-culture for yeast may further aid in diagnosis. burning. examination may reveal vulvar redness. and despite evidence that the symptom of discharge is nonspecific. VULVOVAGINAL CANDIDIASIS With the proliferation of over-the-counter antifungal drugs. pelvic ultrasonography or sonohysterography should be considered. in a study at a Dutch dermatology clinic.4. blastospores Negative Bacterial vaginosis $4. bacillary flora Hyphae. the current definition of recurrent disease. or excoriations. depending on the health care provider. is present in normal healthy women. discharge usually becomes heavier. decreased mixed flora Parabasal cells.7 Unremarkable. an abnormal discharge may sometimes be the result of occult urinary incontinence.14 Thus. vaginal signs are usually limited to erythema or occasionally thrush. 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. Diagnosing a discharge as physiologic can only be done by excluding potential causes. the annual market has been estimated at $275 million.4. may have high false-positive rates. polymerase chain reaction. when a discharge is physiologic. which will be discussed later.12 Office microscopy (Table 1). the prerequisite is colonization with Candida species.7 $4. swelling. or sexual transmission. which typically causes itching. and these medications number in the top 10 of all over-the-counter medications sold in the United States. 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.11 Although most people believe that a thick white discharge is the hallmark symptom of yeast infections.12 Although findings may be minimal.10 The associated annual costs of vulvovaginal candidiasis in the United States in 1995.8 billion.7 Clue cells. Even more uncommonly. soreness. OBSTETRICS & GYNECOLOGY Copyright ª American College of Obstetricians and Gynecologists . Furthermore. 4 Nyirjesy Management of Persistent Vaginitis 50% of women will experience sporadic recurrences. a heavy discharge coming from the upper genital tract may be the result of an endometrial polyp or fallopian tube malignancy. Vaginal colonization occurs through multiple routes. Candida colonization. or dyspareunia. some patients require multiple visits with normal evaluations to be fully reassured. including medical and treatment expenses. fissures. coccobacillary flora Positive Trichomoniasis Varies Trichomonads Variable Atrophic vaginitis Desquamative inflammatory vaginitis $4. usually with Candida albicans.15 To develop a symptomatic infection. certainly in women with recurrent infection and possibly in those in whom candidiasis is suspected but not proven. the first line in diagnosis. almost doubling the rate of diagnosis. yeast cultures with speciation should be obtained to confirm the diagnosis. Testing for Causes of Vaginitis Vaginal pH Saline or 10% Potassium Hydroxide Microscopy Normal . only has a sensitivity of approximately 50%13 and. with women noting a clear mucus midcycle to a thick white discharge at other times. including local transport from the perineum and perianal areas. 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 suspected. travel costs.Table 1.11 Approximately 75% of women will develop symptomatic vulvovaginal candidiasis at least once in their lives. In our experience. up to 30% at any single time and 70% if followed longitudinally for 1 year.

as many 5%. more recently. its eradication results in a relief of symptoms in up to 90% of cases. exogenous estrogen use increases the risk of both candidal colonization and infection. and 1-day to 7-day regimens. Diabetics may be more prone to developing infections caused by Candida glabrata18. it was felt that these women had a decreased immune response.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.23 Although up to 20% of male partners of women with recurrent infections may harbor candida strains on their penises. particularly orogenital sex. glycosuria may be one mechanism contributing to both colonization and symptomatic infection. 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. with C glabrata and Candida parapsilosis being the most common. approximately 30% of women will be infected by other species of yeast. they all have similar efficacy for C albicans infections with an expected cure rate of 80– 90% in uncomplicated patients. but. proteases. With C albicans infections. there are no clear risk factors.28 For uncomplicated disease. Of these.16 After colonization. other women. and mycotoxins. other host factors. and subsequent germination promotes subsequent vaginitis. this is a transient asymptomatic event. 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. leading to an inflammatory response to yeast colonization. In the past. C albicans remains by far the most common cause of infection. Furthermore. it has been suggested that symptomatic candidiasis is the result of an increased sensitivity to yeast.24 As reviewed by Fidel. including genetic factors. An effective approach to resolve the question is to treat her and see if successful treatment. may inhibit phagocytic activity and suppress the local immune system.11 The transition from asymptomatic colonization to symptomatic infection may be the result of intrinsic host. 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 many women asymptomatically colonized with yeast. NO. Although each has its own advantages and disadvantages. MONTH 2014 In most women with vulvovaginal candidiasis. phospholipases.23 As reviewed by Sobel.25 most affected women seem to exhibit altered local immunoregulatory mechanisms. and with C parapsilosis. which result in increased susceptibility to infection. usually with the same strain of yeast. women with uncomplicated infections are otherwise healthy women with mild-to-moderate symptoms resulting from sporadic episodes of infections caused by C albicans. perhaps with sporadic recurrence.26 In tertiary care vaginitis programs. immunosuppression.21 In our experience. actual transmission is thought to be uncommon.7 In at least half of women with recurrent vulvovaginal candidiasis. diabetes. 0. and treatment of the male partner to prevent vulvovaginal candidiasis is not recommended.23 Whatever the cause. an intrauterine device. environmental. is associated with a relief of symptoms. should be considered complicated and are more likely to fail standard antifungal therapy. VOL. which in turn causes symptoms. may be at play. including those with recurrent vulvovaginal candidiasis and those with nonalbicans Candida infections. ranging from oral to topical. antibiotic and estrogen use.27 Most treatment guidelines distinguish between uncomplicated and complicated vulvovaginal candidiasis. systemic immunosuppression is rare in women with vulvovaginal candidiasis. when a woman with persistent vaginitis has a positive yeast culture.25 Finally. 0. Sexual activity.27 However.26 adherence of yeast cells to vaginal epithelium causes colonization. candida may be a commensal organism.for most. or a diaphragm with spermicide have all been associated with increased infection. and behavioral factors are familiar to most health care providers. there are many available treatments. Women with recurrent infections have increased vaginal Candida species colonization rates.22 and using contraception with oral contraceptives. but some women develop a symptomatic infection that goes away easily with standard antifungal therapy. with C glabrata. prescription to over-the-counter. In an even smaller group. Virulence factors produced by Candida species. For infections resulting from C albicans. these regimens are clearly inadequate in women with complicated disease with failure rates of 35% within just 1 month of treatment.7 However. although topical and systemic corticosteroid use may be more common. 40% have a similar result. including secreted aspartate proteinases. symptomatic episodes seem to occur mainly in women with preexisting colonization. the approach that is commonly used is maintenance Nyirjesy Management of Persistent Vaginitis Copyright ª American College of Obstetricians and Gynecologists 5 .7 In general. behavioral. determined by a negative follow-up culture.6.20 In menopausal women.19 With antibiotic use. perhaps 54% of women have no improvement of symptoms after successful eradication. or organism-related factors.

then 1 g 1–3 times/wk Conjugated estrogen (0. but the approaches used for C glabrata or Table 2. 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. and 42. is recommended as initial therapy and cures up to 70% of C glabrata infections (Table 2).6. those specific formulations are no longer commercially available.001).01% vaginal cream 2–4 g/d daily for 1–2 wk. Only one patient discontinued treatment because of an adverse event (headache) attributable to fluconazole. then twice/wk Estradiol (2 mg) ring every 3 mo Clindamycin 2% vaginal cream.7. 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 d33.5 g twice/wk Estradiol (0. to induce a negative culture. They were then randomized to weekly 150 mg fluconazole or placebo for 6 months (treatment phase). maintenance fluconazole therapy is a well-tolerated and effective approach to treating recurrent C albicans infections (Table 2). used daily for 14 days. This approach gives almost all women a prolonged period of symptom relief. have been used successfully in our practice (unpublished observation).5% vaginal cream. given 5 g daily for 14 days. Thus. evidence is limited to case reports or small case series. Regimens of miconazole 2% cream or clotrimazole 1% cream. 3 days apart.7 because they may be more easily accepted by prescription plans. Current guidelines7 suggest using topical regimens intermittently. administered daily in a gelatin capsule for 14 days. and only one had a mild elevation in aminotransferase levels. Limited experience with topical amphotericin B as a 50-mg suppository offers another option for C glabrata infections. gastrointestinal discomfort.9% compared with 36. North American Menopause Society. and then followed for an additional 6 months (observation phase). 6 Nyirjesy Management of Persistent Vaginitis OBSTETRICS & GYNECOLOGY Copyright ª American College of Obstetricians and Gynecologists . Centers for Disease Control and Prevention. a recent report by Marchaim31 of clinically fluconazole-resistant C albicans vulvovaginal candidiasis.32 Apart from occasionally causing local irritation and an abnormal discharge. In a study of maintenance fluconazole for recurrent vulvovaginal candidiasis. the proportions of women who remained disease-free at 6. Although resistance to fluconazole seems to be fortunately rare.30 women were initially given three doses of 150 mg fluconazole. The second line of therapy. but it is no longer recommended because of the risk of liver toxicity.6 The advent of fluconazole in the early 1990s led to the replacement of ketoconazole by fluconazole as maintenance. respectively. For women who recur after maintenance therapy (approximately 50%).32 Vaginal boric acid at 600 mg.625 mg/g) cream 0. it is inexpensive and well-tolerated. then once/wk36 mo Boric acid 600-mg capsules vaginally per d32 wk Metronidazole 0. 73. has been shown to be effective32 but has become prohibitively expensive. 3 g/d34 wk Sobel30 Sobel32 Sobel43 CDC7 NAMS51 Sobel58 CDC. 28.34 For other non-albicans Candida infections. many health care providers restart maintenance if the pathogen remains C albicans. or cost. There are some situations such as pregnancy. 5 g/d34 wk Hydrocortisone 10% vaginal cream. possibly induced by long-term use of fluconazole.antifungal therapy. The initial regimen used was 100 mg ketoconazole daily for 6 months. Although alternate topical maintenance regimens with clotrimazole have been described and shown to be effective. 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. 9. Although clinical and in vitro resistance to C albicans is rare. Although unstudied. then twice/wk34 mo Tinidazole 2 g/d daily for 5 d Estradiol 0. flucytosine compounded into a 15. in which patients are treated with a prolonged (usually 6-month) regimen. and 22%.010 mg) tablet/d32 wk. which prevent the use of fluconazole. then twice a week for 6 months. and 12 months in the fluconazole group were 91.33 Finally.75% vaginal gel 5 g/d310 d. allergy. NAMS.. alternate doses of fluconazole (100 or 200 mg) are also recommended. Of the 343 patients who were studied for efficacy. the same cannot be said for non-albicans Candida species. headaches. in the placebo group (P. with C parapsilosis.

gonococcal. and adverse events. which coats certain surfaces and within which bacteria hide from and are protected from the effects of antibiotics. and postpartum endometritis in pregnant women. tinidazole (oral). Eggerthella species. the best known example is the biofilm that occurs on infected foreign bodies such as central venous catheters. NO.6. Prevotella species.2 Associated sociodemographic factors include a younger age. bacterial vaginosis is considered the most common form of vaginitis. including Atopobium vaginae. chlamydial. bacterial vaginosis-associated bacteria-2. After the early report by Gardner and Dukes40 describing G vaginalis as a possible cause of bacterial vaginosis. they also found that women with both A vaginae and G vaginalis present initially had a much higher rate of recurrence at 1 year than those in whom G vaginalis alone was present (83% compared with 38%. but rather biofilm-associated G vaginalis. Initially thought to be caused by G vaginalis. In women with disease. where the presence or absence of different bacterial morphotypes is scored. increased risk of infection after gynecologic surgery. 0. 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. the bacterial load may be decreased but the biofilm may not be eliminated. which can be demonstrated on electron microscopy of vaginal biopsies. later research suggested that it was instead caused by complex changes in vaginal flora and G vaginalis was ignored until recently. Diagnosis relies on finding three of four Amsel’s criteria (abnormal gray discharge. Fusobacterium species.37 Culture for G vaginalis is not recommended because of a lack of specificity. Bacteroides species.41 recent studies have found that 90% of women with and 10% without bacterial vaginosis have a complex polymicrobial biofilm. or having a female sex partner. MONTH 2014 PCR-based modalities to diagnose bacterial vaginosis using various criteria. known as the Nugent score. Amsel’s criteria have a sensitivity of 92%. Metronidazole (oral or topical).6 Although at least 50% of infected women have no symptoms. thus setting the stage for recurrence after treatment.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. These data suggest that it is not the mere presence of G vaginalis that causes bacterial vaginosis. trichomonal. As reviewed by Verstraelen and Swidsinski..7 They offer equivalent efficacy and can be distinguished from each other on the basis of cost. Megasphaera type 1.6. bacterial vaginosisassociated bacteria. If patients fail an initial course of treatment. A vaginal Gram stain. and douching. In a molecular analysis of uncultivated organisms. living at or near the federal poverty level. and genital herpes infections in nonpregnant women as well as spontaneous abortion. P. is considered the gold standard.001). particularly those resulting from C glabrata. and greater than 20% clue cells on saline microscopy). more recent studies using standard culture and DNA-based technologies have shown that a broad range of bacteria. Leptotrichia species and many others. Biofilms are a type of slime produced by bacteria. positive amine test. mode of administration. With standard antibiotic regimens.28 BACTERIAL VAGINOSIS Affecting approximately 30% of women. being non-Hispanic black or Mexican American. and that hormonal contraception had a protective effect. having a regular sex partner throughout the study. preterm birth. there may be less of a need to treat non-albicans Candida infections. are found in vaginal samples of infected women. a single recurrence or more may occur in up to 58% of women within 12 months. high vaginal pH. they can often be cured with a second course of the same therapy.C parapsilosis are likely to be effective. the most common complaints are of an abnormal vaginal discharge and a fishy odor. the biofilm consists primarily of G vaginalis and sometimes with A vaginae. Peptostreptococcus species. Usually.6 Compared with the Nugent score and much easier to perform in an office setting. the vulvovaginal examination will be normal apart from a discharge described as watery and gray. cervicitis. having less than a high school education. and an increased susceptibility to human immunodeficiency virus. bacterial vaginosis-associated bacteria-3. Megasphaera species. pelvic inflammatory disease. because the yeast may be an innocent bystander in at least 50% of cases. Mobiluncus species. Nyirjesy Management of Persistent Vaginitis Copyright ª American College of Obstetricians and Gynecologists 7 .7 After treatment. including urinary tract infections. 0.35 Bacterial vaginosis is marked by a disturbance in the vaginal microflora with a lack of the normal hydrogen peroxide-producing lactobacilli and an overgrowth of primarily anaerobic organisms. As noted earlier.7 Although commercial laboratories now offer VOL.38 In a cohort of 130 Australian women treated with a 7-day course of oral metronidazole. Bradshaw and colleagues found that the risk factors for recurrence were a history of bacterial vaginosis.36 This disturbed vaginal flora is a risk factor for many infectious morbidities. and clindamycin (oral or topical) are all recommended as initial treatments.

the best approach seems to be maintenance therapy. the most common issues pertaining to trichomoniasis in women with persistent vaginitis are missed diagnosis (31%) and metronidazoleresistant infection (33%). 16. and 28 weeks from the initial visit was 87. respectively. The finding of polymicrobial G vaginalis–dominant biofilm in men has added further fuel to the debate. the in vitro mechanisms are the result of both aerobic and anaerobic pathways. Although hypersensitivity reactions have been rare. the only controlled study consisted of metronidazole gel twice weekly for 4 months after an initial 10-day course of therapy (Table 2).7 For now. Fortunately. As noted in a review of 45 cases seen in a specialty vaginitis clinic. The mainstay of therapy has been metronidazole and. have shown no benefit and are not recommended. discharge.44 Cumulative cure at 12. or persistence of a vaginal biofilm. although data supporting this recommendation are lacking.6.001). if T vaginalis infection is suspected but not proven. However. and 65%. 78. but routine screening or treatment of the female partner is not.7 In an attempt to prevent reinfection. other cases were incident cases occurring in women being treated for other conditions.7 However. more recently.41 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. a variety of potential treatment interventions make sense.S. infection recurred in 26% of metronidazole gel and 59% of placebo patients (P5. Most uncomplicated cases will be cured with treatment with either oral metronidazole or tinidazole along with treatment of the sexual partner.43 In this study of 127 evaluable women. but this theory was later discounted. To date. 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. bacterial vaginosis and its recurrence could be the result of one or several mechanisms: reinfection through sexual activity. 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.42 and recolonization with lactobacillus supplements. To date. health care providers should check to make sure that the treatment was taken and that reinfection did not occur. failure to reestablish normal lactobacillus-dominant flora. vulvovaginal soreness and itching. Because in vitro resistance correlates poorly with clinical outcome.6. Based on these various theories. Food and Drug Administration–cleared OSOM Trichomonas Rapid Antigen Test may provide a rapid (less than 10 minutes) result in the office.1%. as summarized by Muzny and Schwebke.48 Thus. Although up to 50% of infected women may be asymptomatic. culture or PCR is recommended. reinfection.42 data in favor of sexual transmission include evidence that bacterial vaginosis can be transmitted between female sexual partners. and metronidazole resistance.7 and 10. the latter estimated at anywhere between 1. tinidazole. Centers for Disease Control and Prevention guidelines recommend obtaining cultures OBSTETRICS & GYNECOLOGY Copyright ª American College of Obstetricians and Gynecologists .7 However. and occasionally punctate hemorrhages of the vaginal mucosa and cervix. With a sensitivity of 60–70%. dyspareunia. such as the U. the cleaning of shared sex toys between uses is encouraged. if a patient returns with ongoing trichomoniasis after treatment. we routinely recommend consistent condom use for 3–6 months. despite serious limitations. Physical findings include vulvovaginal erythema. saline microscopy alone is simply not a good enough test to reliably diagnose trichomoniasis. health care providers may also encounter women with allergic reactions to nitroimidazoles.Gardner and Dukes40 had also hypothesized that bacterial vaginosis was sexually transmitted. a patient with this uncommon clinical scenario should be managed in conjunction with an allergist. Although these results represent the most promising ones to date. With a resistant infection. with a failure rate of 50% by 36 weeks of follow-up. patients who are allergic to nitroimidazoles represent a therapeutic challenge. TRICHOMONIASIS Considered the third most common cause of infectious vaginitis. Thus. it remains difficult to truly cure women with recurrent bacterial vaginosis.46 Occasionally. Other tests. However.45 symptomatic women will complain of an abnormal discharge (clear to yellow–green and frothy).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). With resistance. not all patients with trichomoniasis are straightforward. In women who have sex with women. 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. metronidazole-resistant trichomoniasis is primarily a clinical diagnosis. treatment of partner studies.47 Thus. Treatment failure can be related to noncompliance. and pain on urination.

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

92:757–65. most health care providers should be able to help the vast majority of women with chronic vaginitis achieve significant control of their symptoms. and 16% were only partially controlled with ongoing treatment. Barlow R. American College of Obstetricians and Gynecologists. and. Berg AO.18:549–52. Lev-Sagie A. However. 6. and cervix  perform vaginal pH. when appropriate. vulvar or vaginal biopsies.111:1243–53. Candida vaginitis: self. 72. Mårdh P-A. Heidrich FE. JAMA 2004. Koutsky LA. a gratifying outcome for patient and health care provider alike. Pap test for bacterial vaginosis) Management Assuming that positive cultures or PCR for group B streptococci. Cur Infect Dis Rep 2005. Vaginitis. Centers for Disease Control and Prevention (CDC). Neisseria gonorrhoeae and Candida trachomatis PCR. 93. Foxman B. D’Arcy H. 1999. American College of Obstetricians and Gynecologists. 191–203. Sobel JD. Stamm WE. Obstet Gynecol 2008. 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. J Fam Pract 1984. Bergman JJ. Some of these pitfalls such as selfdiagnosis and telephone diagnosis are at times unavoidable. Reyes I. 26% of treated women were cured. vagina. Gillespie B.13:178–82. 2. Polaneczky MM.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. Impact of vaginal antifungal products on utilization of health care services: evidence from physician visits. Evaluation of vaginal complaints. However. Culhane JF. 3. Holmes KK. Jeremias J. Mathew L.59:1–110. summarized in Box 1. Waters T. Alternative therapies in women with chronic vaginitis.291:1368–79. Clinical comparison of microscopic and culture techniques in the diagnosis of Candida vaginitis. Nyirjesy P. Sharp LK. In: Holmes KK. Obstet Gynecol 1998. 2010. vestibule. Klink K.reported incidence and associated costs. Eschenbach DA.9:66–9. Lipsky MS. Normal genital flora. Anecdotally. Causes of chronic vaginitis: analysis of a prospective database of affected women. BMJ 2003. Hillier SL. OBSTETRICS & GYNECOLOGY Copyright ª American College of Obstetricians and Gynecologists .58 After initial treatment. management algorithm. Piot P. Sobel JD. Robinson J. 13. 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. Infect Dis Clin Pract 2000.27:230–5. Sexually transmitted disease treatment guidelines. Gardnerella vaginalis. Peyton C. Marrazzo JM. 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. 7:458–62. New York (NY): McGraw-Hill. 12. Weitz MV. Eckert LO. p. 9. Vulvovaginal candidiasis: clinical manifestations. 5. Sexually transmitted diseases. most experts will use exogenous estrogen after initial treatment to decrease the chance of recurrence. herpes simplex virus PCR and type-specific immune globulin G antibodies.326:993–4. Stevens CE. 7. ACOG Practice Bulletin No. Sex Transm Dis 2000. Vulvovaginal candidiasis. Anderson MR. and saline and potassium hydroxide microscopy  obtain yeast culture with speciation. Diagnosis and management of vulvar skin disorders. Obstet Gynecol 2006. et al. Witkin SS. Culhane JF. risk factors. REFERENCES 1. Mathew L. J Am Board Fam Pract 2000. Workowski KA. bacterial culture. 4. with longer follow-up at 1 year. There remain unresolved issues with each of the conditions discussed that will require ongoing research in this often-neglected area of medicine. Yih MC. Sparling PF. Ledger WJ. 86% of women were fully controlled with the remainder partially improved. 3rd ed. Advances in diagnosing vaginitis: development of a new algorithm. Box 1. MMWR Recomm Rep 2010. 14. 8. ACOG Practice Bulletin No. Difficulties in the diagnosis of Candida vaginitis. by acknowledging they exist and steering clear of them when possible. 11. Hawes SE. Nyirjesy P. because of the potential role of hypoestrogenism in triggering desquamative inflammatory vaginitis. Berman S. 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. Obstet Gynecol 2011. Cohrssen A. 58% required some sort of maintenance therapy.107: 1195–206. 10. it is easy to fall into many traps. editors. Lemon SM. Obstet Gynecol 2006. Nyirjesy P. No conclusions could be made in terms of the relative efficacy of either drug.117:856–61.108:1185–91. Tolbert V. Schneeweis R. amine test.

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Misra D.77 WILLIDENTIFYTOTHE. Ekin M.pdf) provides the mechanism for identifying such articles. Schlievert PM. Temur M. Barnes ML. Vaginitis in–36.- ARTICLES THATREQUIREDEPOSIT4HEJOURNALSAUTHORAGREEMENTFORMAVAILABLEAT http://edmgr. Within medical research. Retrieved October 7. 2014. Uhri M.17:88–91. three funding agencies in particular have announced such policies: s4HE. Reichman O.71:832–6. 56. clindamycin therapy. Yas¸ar L. Desquamative inflammatory vaginitis: a new subgroup of purulent vaginitis responsive to topical 2% 57.171: 1215–20. The comparison of hyaluronic acid vaginal tablets with estradiol vaginal tablets in the treatment of atrophic vaginitis: a randomized controlled trial. Friedrich EG Jr. Yoo W. J Low Genit Tract Dis 2012.ATIONAL)NSTITUTESOF(EALTH.ATIONAL)NSTITUTESOF(EALTHPUBLIC access. Sobel JD. 16:24–9.ovid.IBRARYOF-EDICINE. Gray LA. 53. Gencer I.analysis of a prospective database.117:850–5. Vaginal toxic shock reaction triggering desquamative inflammatory vaginitis. Obstet Gynecol 2011. Available at http://publicaccess. Edlind TD.)( 1 s4HE(OWARD(UGHES-EDICAL)NSTITUTE((-) 2 s4HE7ELLCOME4RUST3 As a service to our Nyirjesy P. Arch Gynecol Obstet 2011. Sobel JD. 55. 54. Am J Obstet Gynecol 1965. 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$EPARTMENTOF(EALTHAND(UMAN3ERVICES. Desquamative vaginitis: lichen planus in disguise. Retrieved October 7. Edwards L. Savan K.283:539–43. J Low Genit Tract Dis 2013. Am J Obstet Gynecol 1994. et al.. diagnosis and treatment. Obstet Gynecol 1988. 7ELLCOME4RUST/PENACCESSPOLICY!VAILABLEATHTTPWWWWELLCOMEACUK!BOUT US 0OLICY0OLICY AND POSITION STATEMENTS74$HTM2ETRIEVED/CTOBER. (OWARD(UGHES-EDICAL)NSTITUTE0UBLICACCESS!VAILABLEATHTTPWWWHHMIORG about/research/journals/main?action=search. Prognosis and treatment of desquamative inflammatory vaginitis. 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. 2014. Pereira N. the journal’s publisher (Lippincott Williams & 7ILKINS. 58.nih.

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