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Clinical Expert Series

Management of Persistent Vaginitis
Paul Nyirjesy,

MD

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

V

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

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

VOL. 0, NO. 0, MONTH 2014

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

OBSTETRICS & GYNECOLOGY

Copyright ª American College of Obstetricians and Gynecologists

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

Advances in diagnosing vaginitis: development of a new algorithm. because normal vaginal flora such as Escherichia coli. Gardnerella. office testing has poor performance characteristics. these easily available tests can frequently diagnose common forms of vaginitis.8 Saline microscopy can aid in diagnosing bacterial vaginosis and trichomoniasis. Figure 2. they are also occasional causes of purulent vaginitis. estrogen plays a key role in maintaining the normal vaginal environment. saline microscopy tests for atrophic vaginitis and desquamative inflammatory vaginitis. Figure 1 describes the pH-based algorithm that we use in practice. they are more costly than current modalities. there is currently little evidence that they are superior to current gold standards. and ruling out vulvovaginal candidiasis. and those in whom evaluation is consistent with recurrent bacterial vaginosis. and trichomoniasis. and in the case of PCR testing for yeast and bacterial vaginosis. 0.4 understanding the normal vaginal environment is important. the vagina is thinned and has a high pH. Management of Persistent Vaginitis. fissures. 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. PCR testing for yeast and bacterial vaginosis). amines. enterococci. Reprinted with kind permission from Springer Science+Business Media: Nyirjesy P. In addition. point-of-care enzymatic. However. Lactobacilli become the dominant flora. Frequently underused. As shown in Table 1. The findings of vesicles.7. including skin and fecal flora and lactobacilli. Obstet Gynecol 2014.for Disease Control and Prevention7 stress the importance of in-office testing for vaginal pH. During a woman’s reproductive years. If Trichomonas vaginalis infection is suspected but not proven. and both saline and 10% potassium hydroxide microscopy. treating. the vaginal epithelium thickens.7:458–62.S. 1. A pH-based framework for diagnosing the most common causes of vaginitis. Vaginal Fig. Although these latter two organisms may be commensals. Of those. and ancillary tests are frequently indicated. and. those with many white blood cells on microscopy. Curr Infect Dis Rep 2005. the gold standard test remains either culture or the more easily available polymerase chain reaction (PCR) with the U. yeast cultures with speciation of the organism play an integral part in diagnosing. Under the influence of estrogen. We perform this latter test in all of our patients at risk for a sexually transmitted infection. 0. Routine bacterial cultures are otherwise unhelpful and can be misleading. vaginal biopsies. particularly if the etiology is unclear. Finally. by assessing for increased white blood cells and abnormal cytology such as parabasal cells. Sobel JD. Gardnerella vaginalis. NO. Food and Drug Administration–cleared APTIMA T vaginalis assay. Nyirjesy. which lowers the pH of the vagina to less than 4. Before puberty. MONTH 2014 Nyirjesy Management of Persistent Vaginitis Copyright ª American College of Obstetricians and Gynecologists 3 . vulvar biopsies. VOL. should be considered for focal abnormalities. or ulcers should routinely lead to PCR tests for herpes simplex virus and possibly type-specific immune globulin G antibody testing. vaginal pH testing in particular can be used to drive the entire diagnostic process. NORMAL VAGINAL PHYSIOLOGY AND DISCHARGE With physiologic discharge occurring as the final diagnosis in 9% of the patients referred to our tertiary care program. less commonly. and group B streptococci are frequently found. antigen and DNA tests for candida. culture of the vagina demonstrates a variety of organisms.9 For other tests for vaginal infections (ie.

including local transport from the perineum and perianal areas.7 Negative Clinical diagnosis Vulvovaginal candidiasis . which will be discussed later.7 Clue cells. may have high false-positive rates. burning.10 The associated annual costs of vulvovaginal candidiasis in the United States in 1995.2 complaints of a thick white discharge often lead to repeated use of unnecessary antifungal therapy and raise fears of recurrent infection. vaginal signs are usually limited to erythema or occasionally thrush. bacillary flora Hyphae. fissures. 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. or excoriations. 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. including medical and treatment expenses. Vaginal colonization occurs through multiple routes. OBSTETRICS & GYNECOLOGY Copyright ª American College of Obstetricians and Gynecologists . when a discharge is physiologic. decreased mixed flora Parabasal cells.7 Unremarkable. Candida colonization. and time missed from work. a heavy discharge coming from the upper genital tract may be the result of an endometrial polyp or fallopian tube malignancy. when suspected. up to 30% at any single time and 70% if followed longitudinally for 1 year. only has a sensitivity of approximately 50%13 and. the current definition of recurrent disease. and despite evidence that the symptom of discharge is nonspecific.4. in a study at a Dutch dermatology clinic. Testing for Causes of Vaginitis Vaginal pH Saline or 10% Potassium Hydroxide Microscopy Normal . irritation. travel costs.11 Although most people believe that a thick white discharge is the hallmark symptom of yeast infections. the first line in diagnosis. pelvic ultrasonography or sonohysterography should be considered. Even more uncommonly. which typically causes itching.Table 1. discharge usually becomes heavier. usually with Candida albicans.11 Approximately 75% of women will develop symptomatic vulvovaginal candidiasis at least once in their lives.8 billion. or dyspareunia. or sexual transmission.12 Office microscopy (Table 1). with women noting a clear mucus midcycle to a thick white discharge at other times. 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. Furthermore. some patients require multiple visits with normal evaluations to be fully reassured.7 Parabasal cells. and perhaps 8–10% will suffer from four or more episodes every year.4. the prerequisite is colonization with Candida species. blastospores Negative Bacterial vaginosis $4. In our experience. Because many women and health care providers are taught that a thick white discharge is most frequently caused by vulvovaginal candidiasis.7 $4. is present in normal healthy women. yeast cultures with speciation should be obtained to confirm the diagnosis. soreness. VULVOVAGINAL CANDIDIASIS With the proliferation of over-the-counter antifungal drugs. were estimated to be $1. digital introduction.14 Thus. certainly in women with recurrent infection and possibly in those in whom candidiasis is suspected but not proven. an abnormal discharge may sometimes be the result of occult urinary incontinence. examination may reveal vulvar redness. Hormonal influences will change a discharge. a woman’s perception of her discharge correlates quite poorly with vulvovaginal candidiasis.4. depending on the health care provider. coccobacillary flora Positive Trichomoniasis Varies Trichomonads Variable Atrophic vaginitis Desquamative inflammatory vaginitis $4. swelling. external dysuria. almost doubling the rate of diagnosis. Repeated sampling through patient vaginal self-culture for yeast may further aid in diagnosis. 6white blood cells.15 To develop a symptomatic infection. increased white blood cells. the annual market has been estimated at $275 million. polymerase chain reaction. 4 Nyirjesy Management of Persistent Vaginitis 50% of women will experience sporadic recurrences. a common event for almost every woman. and these medications number in the top 10 of all over-the-counter medications sold in the United States.12 Although findings may be minimal. Diagnosing a discharge as physiologic can only be done by excluding potential causes.

the approach that is commonly used is maintenance Nyirjesy Management of Persistent Vaginitis Copyright ª American College of Obstetricians and Gynecologists 5 . may inhibit phagocytic activity and suppress the local immune system. glycosuria may be one mechanism contributing to both colonization and symptomatic infection. which result in increased susceptibility to infection.25 most affected women seem to exhibit altered local immunoregulatory mechanisms. An effective approach to resolve the question is to treat her and see if successful treatment. an intrauterine device. women with uncomplicated infections are otherwise healthy women with mild-to-moderate symptoms resulting from sporadic episodes of infections caused by C albicans.27 However. 0.29 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. For infections resulting from C albicans. may be at play. with many women asymptomatically colonized with yeast.16 After colonization. when a woman with persistent vaginitis has a positive yeast culture. antibiotic and estrogen use.11 The transition from asymptomatic colonization to symptomatic infection may be the result of intrinsic host. Virulence factors produced by Candida species. they all have similar efficacy for C albicans infections with an expected cure rate of 80– 90% in uncomplicated patients. which in turn causes symptoms. and treatment of the male partner to prevent vulvovaginal candidiasis is not recommended. prescription to over-the-counter. there is a more complicated course with either failure to respond to treatment and the development of chronic infection17 or relatively rapid relapse after successful antifungal therapy and eventual recurrent disease. With C albicans infections. there are many available treatments. perhaps 54% of women have no improvement of symptoms after successful eradication.for most. more recently.28 For uncomplicated disease.22 and using contraception with oral contraceptives.23 As reviewed by Sobel. as many 5%. with C glabrata. behavioral.7 However. Sexual activity. other host factors. its eradication results in a relief of symptoms in up to 90% of cases. and with C parapsilosis.23 Whatever the cause. or organism-related factors. proteases. but. immunosuppression. there are no clear risk factors. systemic immunosuppression is rare in women with vulvovaginal candidiasis. particularly orogenital sex. Women with recurrent infections have increased vaginal Candida species colonization rates. Diabetics may be more prone to developing infections caused by Candida glabrata18. approximately 30% of women will be infected by other species of yeast. candida may be a commensal organism.26 adherence of yeast cells to vaginal epithelium causes colonization.7 In at least half of women with recurrent vulvovaginal candidiasis. and mycotoxins. and 1-day to 7-day regimens. Of these.7 In general.6. symptomatic episodes seem to occur mainly in women with preexisting colonization. C albicans remains by far the most common cause of infection. diabetes. although topical and systemic corticosteroid use may be more common. other women. 40% have a similar result. In the past.25 Finally. it has been suggested that symptomatic candidiasis is the result of an increased sensitivity to yeast. Furthermore. In an even smaller group. or a diaphragm with spermicide have all been associated with increased infection. actual transmission is thought to be uncommon. perhaps with sporadic recurrence. 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. phospholipases. including genetic factors.26 In tertiary care vaginitis programs. these regimens are clearly inadequate in women with complicated disease with failure rates of 35% within just 1 month of treatment. and subsequent germination promotes subsequent vaginitis. it was felt that these women had a decreased immune response. with C glabrata and Candida parapsilosis being the most common.24 As reviewed by Fidel.20 In menopausal women. should be considered complicated and are more likely to fail standard antifungal therapy.27 Most treatment guidelines distinguish between uncomplicated and complicated vulvovaginal candidiasis. 0. and behavioral factors are familiar to most health care providers. ranging from oral to topical. leading to an inflammatory response to yeast colonization. environmental. usually with the same strain of yeast. but some women develop a symptomatic infection that goes away easily with standard antifungal therapy. 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. is associated with a relief of symptoms. Although each has its own advantages and disadvantages. NO. this is a transient asymptomatic event.19 With antibiotic use. MONTH 2014 In most women with vulvovaginal candidiasis. VOL.23 Although up to 20% of male partners of women with recurrent infections may harbor candida strains on their penises. including secreted aspartate proteinases. determined by a negative follow-up culture.21 In our experience. including those with recurrent vulvovaginal candidiasis and those with nonalbicans Candida infections. exogenous estrogen use increases the risk of both candidal colonization and infection.

flucytosine compounded into a 15. in the placebo group (P. Although resistance to fluconazole seems to be fortunately rare. then twice a week for 6 months. it is inexpensive and well-tolerated. 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. Although clinical and in vitro resistance to C albicans is rare. headaches. 9. They were then randomized to weekly 150 mg fluconazole or placebo for 6 months (treatment phase).5% vaginal cream. or cost. NAMS. maintenance fluconazole therapy is a well-tolerated and effective approach to treating recurrent C albicans infections (Table 2). and 12 months in the fluconazole group were 91.33 Finally. which prevent the use of fluconazole. possibly induced by long-term use of fluconazole.75% vaginal gel 5 g/d310 d. This approach gives almost all women a prolonged period of symptom relief. is recommended as initial therapy and cures up to 70% of C glabrata infections (Table 2).625 mg/g) cream 0. Thus. Although unstudied. 3 days apart. but the approaches used for C glabrata or Table 2. then twice/wk Estradiol (2 mg) ring every 3 mo Clindamycin 2% vaginal cream. a recent report by Marchaim31 of clinically fluconazole-resistant C albicans vulvovaginal candidiasis. the same cannot be said for non-albicans Candida species. 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. Only one patient discontinued treatment because of an adverse event (headache) attributable to fluconazole. then 1 g 1–3 times/wk Conjugated estrogen (0..7 because they may be more easily accepted by prescription plans. have been used successfully in our practice (unpublished observation).5 g twice/wk Estradiol (0. evidence is limited to case reports or small case series. to induce a negative culture. then once/wk36 mo Boric acid 600-mg capsules vaginally per d32 wk Metronidazole 0. many health care providers restart maintenance if the pathogen remains C albicans. Of the 343 patients who were studied for efficacy.9% compared with 36. Current guidelines7 suggest using topical regimens intermittently. The initial regimen used was 100 mg ketoconazole daily for 6 months. then twice/wk34 mo Tinidazole 2 g/d daily for 5 d Estradiol 0.32 Apart from occasionally causing local irritation and an abnormal discharge. the proportions of women who remained disease-free at 6. 73. in which patients are treated with a prolonged (usually 6-month) regimen. with C parapsilosis. those specific formulations are no longer commercially available.6. used daily for 14 days.7. Regimens of miconazole 2% cream or clotrimazole 1% cream.30 women were initially given three doses of 150 mg fluconazole.6 The advent of fluconazole in the early 1990s led to the replacement of ketoconazole by fluconazole as maintenance. 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. has been shown to be effective32 but has become prohibitively expensive. but it is no longer recommended because of the risk of liver toxicity. 28. and 42. administered daily in a gelatin capsule for 14 days. and only one had a mild elevation in aminotransferase levels. gastrointestinal discomfort.32 Vaginal boric acid at 600 mg. 3 g/d34 wk Sobel30 Sobel32 Sobel43 CDC7 NAMS51 Sobel58 CDC. and then followed for an additional 6 months (observation phase). In a study of maintenance fluconazole for recurrent vulvovaginal candidiasis. There are some situations such as pregnancy.010 mg) tablet/d32 wk. given 5 g daily for 14 days.34 For other non-albicans Candida infections. and 22%. Limited experience with topical amphotericin B as a 50-mg suppository offers another option for C glabrata infections.001). For women who recur after maintenance therapy (approximately 50%). 6 Nyirjesy Management of Persistent Vaginitis OBSTETRICS & GYNECOLOGY Copyright ª American College of Obstetricians and Gynecologists . 5 g/d34 wk Hydrocortisone 10% vaginal cream. The second line of therapy.antifungal therapy. respectively. alternate doses of fluconazole (100 or 200 mg) are also recommended. allergy.01% vaginal cream 2–4 g/d daily for 1–2 wk. Centers for Disease Control and Prevention. Although alternate topical maintenance regimens with clotrimazole have been described and shown to be effective. North American Menopause Society.

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. which can be demonstrated on electron microscopy of vaginal biopsies. In women with disease. known as the Nugent score. If patients fail an initial course of treatment. increased risk of infection after gynecologic surgery. Initially thought to be caused by G vaginalis. 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%.2 Associated sociodemographic factors include a younger age. MONTH 2014 PCR-based modalities to diagnose bacterial vaginosis using various criteria. the best known example is the biofilm that occurs on infected foreign bodies such as central venous catheters. living at or near the federal poverty level. the biofilm consists primarily of G vaginalis and sometimes with A vaginae. cervicitis.6. pelvic inflammatory disease. the most common complaints are of an abnormal vaginal discharge and a fishy odor. As reviewed by Verstraelen and Swidsinski. preterm birth. Eggerthella species. because the yeast may be an innocent bystander in at least 50% of cases.7 After treatment.35 Bacterial vaginosis is marked by a disturbance in the vaginal microflora with a lack of the normal hydrogen peroxide-producing lactobacilli and an overgrowth of primarily anaerobic organisms.6. In a molecular analysis of uncultivated organisms. Megasphaera type 1.7 They offer equivalent efficacy and can be distinguished from each other on the basis of cost. and postpartum endometritis in pregnant women. and genital herpes infections in nonpregnant women as well as spontaneous abortion.C parapsilosis are likely to be effective. there may be less of a need to treat non-albicans Candida infections. which coats certain surfaces and within which bacteria hide from and are protected from the effects of antibiotics.36 This disturbed vaginal flora is a risk factor for many infectious morbidities.001). and clindamycin (oral or topical) are all recommended as initial treatments.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. is considered the gold standard. bacterial vaginosis is considered the most common form of vaginitis. the vulvovaginal examination will be normal apart from a discharge described as watery and gray. Mobiluncus species. Bradshaw and colleagues found that the risk factors for recurrence were a history of bacterial vaginosis. thus setting the stage for recurrence after treatment. a single recurrence or more may occur in up to 58% of women within 12 months. 0. and greater than 20% clue cells on saline microscopy). the bacterial load may be decreased but the biofilm may not be eliminated. With standard antibiotic regimens. later research suggested that it was instead caused by complex changes in vaginal flora and G vaginalis was ignored until recently. Peptostreptococcus species. Diagnosis relies on finding three of four Amsel’s criteria (abnormal gray discharge.7 Although commercial laboratories now offer VOL. and adverse events. chlamydial. After the early report by Gardner and Dukes40 describing G vaginalis as a possible cause of bacterial vaginosis. including urinary tract infections.41 recent studies have found that 90% of women with and 10% without bacterial vaginosis have a complex polymicrobial biofilm. but rather biofilm-associated G vaginalis.28 BACTERIAL VAGINOSIS Affecting approximately 30% of women. bacterial vaginosis-associated bacteria-2. 0. and douching. Megasphaera species. Biofilms are a type of slime produced by bacteria. Metronidazole (oral or topical). 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. Nyirjesy Management of Persistent Vaginitis Copyright ª American College of Obstetricians and Gynecologists 7 . high vaginal pH. having less than a high school education. These data suggest that it is not the mere presence of G vaginalis that causes bacterial vaginosis. bacterial vaginosisassociated bacteria. mode of administration. tinidazole (oral). Prevotella species. having a regular sex partner throughout the study. particularly those resulting from C glabrata. P. being non-Hispanic black or Mexican American. and an increased susceptibility to human immunodeficiency virus. Leptotrichia species and many others. gonococcal. including Atopobium vaginae.37 Culture for G vaginalis is not recommended because of a lack of specificity. Bacteroides species. Usually. positive amine test. and that hormonal contraception had a protective effect. where the presence or absence of different bacterial morphotypes is scored. bacterial vaginosis-associated bacteria-3. A vaginal Gram stain. As noted earlier.6 Compared with the Nugent score and much easier to perform in an office setting. Fusobacterium species. trichomonal. more recent studies using standard culture and DNA-based technologies have shown that a broad range of bacteria.6 Although at least 50% of infected women have no symptoms. or having a female sex partner. they can often be cured with a second course of the same therapy. Amsel’s criteria have a sensitivity of 92%. NO.

7 For now. Treatment failure can be related to noncompliance.41 Thus.46 Occasionally. With a sensitivity of 60–70%.48 Thus. and pain on urination. although data supporting this recommendation are lacking. bacterial vaginosis and its recurrence could be the result of one or several mechanisms: reinfection through sexual activity. As noted in a review of 45 cases seen in a specialty vaginitis clinic. 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.001). it remains difficult to truly cure women with recurrent bacterial vaginosis. 16. TRICHOMONIASIS Considered the third most common cause of infectious vaginitis. Based on these various theories. However. other cases were incident cases occurring in women being treated for other conditions. vulvovaginal soreness and itching. Because in vitro resistance correlates poorly with clinical outcome. Most uncomplicated cases will be cured with treatment with either oral metronidazole or tinidazole along with treatment of the sexual partner.S.7 However. Although up to 50% of infected women may be asymptomatic.44 Cumulative cure at 12. treatment of partner studies. or persistence of a vaginal biofilm. respectively. more recently. the data implicating the male partner from the Bradshaw study and the finding of similar flora in the male partners of women with bacterial vaginosis. To date. Other tests. such as the U. failure to reestablish normal lactobacillus-dominant flora. With resistance. if T vaginalis infection is suspected but not proven.7 and 10.2 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). The mainstay of therapy has been metronidazole and. dyspareunia. saline microscopy alone is simply not a good enough test to reliably diagnose trichomoniasis. culture or PCR is recommended.7 In an attempt to prevent reinfection. tinidazole. and occasionally punctate hemorrhages of the vaginal mucosa and cervix.1%. and 28 weeks from the initial visit was 87. the most common issues pertaining to trichomoniasis in women with persistent vaginitis are missed diagnosis (31%) and metronidazoleresistant infection (33%).47 Thus. 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. Centers for Disease Control and Prevention guidelines recommend obtaining cultures OBSTETRICS & GYNECOLOGY Copyright ª American College of Obstetricians and Gynecologists . a patient with this uncommon clinical scenario should be managed in conjunction with an allergist.6. In women who have sex with women.7 However. but routine screening or treatment of the female partner is not. Food and Drug Administration–cleared OSOM Trichomonas Rapid Antigen Test may provide a rapid (less than 10 minutes) result in the office. reinfection. and 65%. The finding of polymicrobial G vaginalis–dominant biofilm in men has added further fuel to the debate. 78. the latter estimated at anywhere between 1. have shown no benefit and are not recommended. patients who are allergic to nitroimidazoles represent a therapeutic challenge. health care providers may also encounter women with allergic reactions to nitroimidazoles. infection recurred in 26% of metronidazole gel and 59% of placebo patients (P5.Gardner and Dukes40 had also hypothesized that bacterial vaginosis was sexually transmitted. if a patient returns with ongoing trichomoniasis after treatment. a variety of potential treatment interventions make sense. Thus. as summarized by Muzny and Schwebke. health care providers should check to make sure that the treatment was taken and that reinfection did not occur.42 data in favor of sexual transmission include evidence that bacterial vaginosis can be transmitted between female sexual partners. not all patients with trichomoniasis are straightforward. with a failure rate of 50% by 36 weeks of follow-up. With a resistant infection. However. but this theory was later discounted.6. Fortunately. we routinely recommend consistent condom use for 3–6 months. metronidazole-resistant trichomoniasis is primarily a clinical diagnosis. 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. the cleaning of shared sex toys between uses is encouraged.45 symptomatic women will complain of an abnormal discharge (clear to yellow–green and frothy). To date. the only controlled study consisted of metronidazole gel twice weekly for 4 months after an initial 10-day course of therapy (Table 2). Although hypersensitivity reactions have been rare. discharge.43 In this study of 127 evaluable women. Although these results represent the most promising ones to date. Physical findings include vulvovaginal erythema. the in vitro mechanisms are the result of both aerobic and anaerobic pathways. despite serious limitations. and metronidazole resistance. the best approach seems to be maintenance therapy.42 and recolonization with lactobacillus supplements.

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

herpes simplex virus PCR and type-specific immune globulin G antibodies.111:1243–53. 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. 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. Nyirjesy P. 26% of treated women were cured. Causes of chronic vaginitis: analysis of a prospective database of affected women. Stevens CE.9:66–9. MMWR Recomm Rep 2010. JAMA 2004. Obstet Gynecol 2008. most experts will use exogenous estrogen after initial treatment to decrease the chance of recurrence. a gratifying outcome for patient and health care provider alike. Nyirjesy P. Sobel JD. New York (NY): McGraw-Hill. J Am Board Fam Pract 2000. Jeremias J. management algorithm. 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. REFERENCES 1.107: 1195–206. Heidrich FE. Witkin SS. Nyirjesy P. Koutsky LA. summarized in Box 1. Cur Infect Dis Rep 2005. 10. 72.291:1368–79. et al. Schneeweis R. Gardnerella vaginalis. because of the potential role of hypoestrogenism in triggering desquamative inflammatory vaginitis. 7. Peyton C. and 16% were only partially controlled with ongoing treatment. amine test. However. Diagnosis and management of vulvar skin disorders. Culhane JF. Hillier SL. Piot P. 5. Lemon SM. 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)( 1 s4HE(OWARD(UGHES-EDICAL)NSTITUTE((-) 2 s4HE7ELLCOME4RUST3 As a service to our authors. Sobel JD.analysis of a prospective database. Arch Gynecol Obstet 2011. 7ELLCOME4RUST/PENACCESSPOLICY!VAILABLEATHTTPWWWWELLCOMEACUK!BOUT US 0OLICY0OLICY AND POSITION STATEMENTS74$HTM2ETRIEVED/CTOBER.17:88–91. diagnosis and treatment. Uhri M. (OWARD(UGHES-EDICAL)NSTITUTE0UBLICACCESS!VAILABLEATHTTPWWWHHMIORG about/research/journals/main?action=search. 53. clindamycin therapy. Schlievert PM. Desquamative vaginitis: lichen planus in disguise. Vaginal toxic shock reaction triggering desquamative inflammatory vaginitis. 54. Am J Obstet Gynecol 1965. LWW will transmit the postprint of an article based on research funded in whole or in part by one or more of these THREEAGENCIESTO0UB-ED#ENTRAL References 53$EPARTMENTOF(EALTHAND(UMAN3ERVICES. 55. Prognosis and treatment of desquamative inflammatory vaginitis.. 2014. Available at http://publicaccess. Gray LA. Savan K. Reichman O. Edwards L. Retrieved October 7. et al.ATIONAL)NSTITUTESOF(EALTH. 16:24–9. Nyirjesy P. J Low Genit Tract Dis 2013.171: 1215–20. Pereira N.com/ong/accounts/agreementform.gov/. Ekin M. Within medical research. Gencer I.nih. Retrieved October 7. Am J Obstet Gynecol 1994. Edlind TD.pdf) provides the mechanism for identifying such articles. Friedrich EG Jr.IBRARYOF-EDICINE. Temur M. 2014. three funding agencies in particular have announced such policies: s4HE. Desquamative inflammatory vaginitis: a new subgroup of purulent vaginitis responsive to topical 2% 57.ATIONAL)NSTITUTESOF(EALTHPUBLIC access.71:832–6. Yas¸ar L. Sobel JD. 58.ATIONAL. Obstet Gynecol 2011.92:125–36. Vaginitis in women. Yoo W. Misra D. J Low Genit Tract Dis 2012.77 WILLIDENTIFYTOTHE.283:539–43.- ARTICLES THATREQUIREDEPOSIT4HEJOURNALSAUTHORAGREEMENTFORMAVAILABLEAT http://edmgr. Barnes ML. the journal’s publisher (Lippincott Williams & 7ILKINS.ovid. 56. The comparison of hyaluronic acid vaginal tablets with estradiol vaginal tablets in the treatment of atrophic vaginitis: a randomized controlled trial. 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. Obstet Gynecol 1988.117:850–5.

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