Definition and Etiology

Vaginitis is a term that is applied to vulvovaginal symptoms of varying causes. Symptoms of vaginitis are common and account for about 10 million office visits a year. However, the symptoms are nonspecific and multifactorial. Infection is the most common cause; some of the other causes are listed in Box 1. Careful history taking combined with physical examination and simple microscopic analysis can help ascertain a diagnosis and tailor a treatment. This can help avoid misdiagnosis and treatment failure as well as symptom recurrence.

Epidemiology

The exact incidence of vaginitis is unknown, but it is estimated that most women experience at least one episode in their lifetime. The associated distress and discomfort often lead women to self-diagnose vaginitis and use over-the-counter preparations improperly. The three most common causes of vaginitis include bacterial vaginosis, candidal vulvovaginitis, and trichomonas vaginitis.

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Symptoms and Signs

Clinical Signs and Symptoms

Symptoms of vaginitis include vaginal discharge, irritation, pruritus, odor, and, occasionally, dyspareunia, vaginal bleeding, and dysuria. Symptoms tend to be nonspecific and overlap among the different etiologic factors. Some historical clues can help suggest a diagnosis.

Bacterial vaginosis manifests with a scant, homogenous, sometimes malodorous discharge with limited symptoms of inflammation, such as pruritus and soreness. Women often admit to a recent change in sex partner. Bacterial vaginosis is also associated with vaginal douching.

Candida classically manifests with a scant, curdy, white discharge associated with marked pruritus and soreness. Medications that can be associated with vulvovaginal candidiasis include systemic antibiotics, oral contraceptive pills (especially those containing higher estrogen levels), oral steroids, and other immunosuppressive agents. Diabetes can cause sporadic as well as recurrent vulvovaginal candidiasis.

Trichomonas vaginitis manifests with frothy green discharge and inflammatory signs. The patient might give a history of a recent change in sex partner.

Atrophic vaginitis occurs in postmenopausal women and manifests with vaginal dryness, dyspareunia, and dysuria.

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Physical Examination

Physical examination should mainly be used to evaluate for the presence of cervical inflammation (suggesting an alternative etiology) and to exclude the clinical presence of pelvic inflammatory disease.

On physical examination, the vaginal discharge is thick, white, and adherent in candidiasis; thin and fishy-smelling in bacterial vaginosis, and greenish-yellow and purulent in trichomoniasis. Candidiasis and trichomoniasis (but not bacterial vaginosis) are also associated with vulvar and vaginal erythema. Atrophic vaginitis is associated with scant, thin vaginal discharge and atrophic changes, such as thinning and loss of rugae in the vaginal mucosa.

Cervical inflammation suggests cervicitis contributing to vaginal discharge. Cervical motion tenderness suggests pelvic inflammatory disease.

Vaginal pH should be obtained at the time of the physical examination and is probably the most important diagnostic clue.

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Diagnosis

Due to the nonspecific nature of the symptoms and physical examination findings, the diagnosis of vaginitis is mainly made by using a combination of vaginal pH, amine test, microscopy findings, and, sometimes, vaginal cultures. Table 1 provides a summary of the differential diagnosis of vaginal discharge.

Vaginal pH

Vaginal pH is obtained by placing a drop of the vaginal discharge on a pH strip. It must be remembered that the pH can be altered by vaginal lubricants as well as other factors such as blood or urine. Vulvovaginal candidiasis is associated with a normal vaginal pH between 4.0 and 4.5. A vaginal pH greater than 4.5 suggests infections such as bacterial vaginosis and trichomonal vaginitis.

Amine Test

The amine or whiff test is done by placing a drop of the vaginal discharge on a slide and adding a drop of 10% KOH. A fishy amine odor indicates bacterial vaginosis. The odor is caused by volatilization of amines, a by-product of anaerobic metabolism. The amine test is occasionally positive with trichomoniasis.

Microscopy

Microscopy should be performed using saline and 10% KOH mounts. Figure 1 provides an illustration of various saline microscopic findings.

Saline Mount

Cells that can be seen in the saline mount include vaginal epithelial cells, rods and cocci, polymorphonuclear cells (PMNs), clue cells, motile trichomonads, and candidal hyphae. Normal vaginal epithelial cells are squamous. Parabasal cells appear in postmenopausal women and are associated with atrophic vaginitis.

Rods are the predominant microorganisms in normal vaginal discharge and with candidiasis. Loss of rods and increased coccobacilli occur with bacterial vaginosis and atrophic vaginitis.

Abundant PMNs are seen with the purulent discharge associated with trichomoniasis. Motile trichomonads, which are slightly larger than PMNs, are only seen in 60% to 70% of culture-confirmed cases of trichomoniasis.

Clue cells are the single most reliable predictor of bacterial vaginosis. These are epithelial cells studded with adherent coccobacilli and represent between 5% and 50% of the epithelial cells seen in bacterial vaginosis.

Potassium Hydroxide Mount

The KOH mount is particularly useful for diagnosing candidal vaginitis. Branching hyphae of Candida albicans can be seen.

Vaginal Cultures

Due to the low sensitivity of microscopic tests, vaginal cultures can be obtained in microscopy-negative cases. Vaginal candidiasis often manifests with a compatible history and normal pH and negative microscopy. In these cases, hypersensitivity, contact dermatitis, and allergic or chemical vaginitis can be excluded by obtaining a vaginal culture. Similarly, culture techniques have a high sensitivity in trichomonas vaginitis (95%) and should be considered in patients with an elevated vaginal pH, increased numbers of PMNs, and absence of motile trichomonads and clue cells or when microscopy is unavailable or yields unreliable results.

Cervical Cultures

Cervical cultures for DNA amplification and diagnosis of Chlamydia trachomatis and Neisseria gonorrhoeae infection should be obtained in women with a history of high-risk sexual behavior, symptomatic sexual partners, and cervical motion tenderness on physical examination (suggesting pelvic inflammatory disease).

The Amsel criteria are used to diagnose bacterial vaginosis. The diagnosis requires three of the following four characteristics:

• Homogenous, thin discharge
• pH >4.5
• Positive whiff test
• Clue cells on microscopy

The prevalence of bacterial vaginosis and trichomoniasis is high in HIV-seropositive women and in seronegative controls matched for high-risk behavior. Hence, identification of these infections should prompt screening for HIV and other sexually transmitted diseases.

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Treatment

Bacterial Vaginosis

Standard regimens can achieve cure rates between 70% and 90% for confirmed cases of bacterial vaginosis (Table 2). Oral and topical routes have equal efficacy, and nitroimidazole and clindamycin regimens are also equally efficacious. Vaginal routes have the main advantage of reduced gastrointestinal symptoms, but they have the disadvantage of being inconvenient and being associated with a high risk of vaginal candidiasis.

Asymptomatic bacterial vaginosis should only be treated in pregnant women and before elective gynecologic surgery. Bacterial vaginosis in pregnant women is associated with an increased risk of preterm prelabor rupture of membranes and preterm delivery as well as endometritis and wound infections after cesarean delivery. Bacterial vaginosis has also been implicated in post-hysterectomy vaginal-cuff cellulitis. Despite the association between bacterial vaginosis and preterm birth, most studies in general obstetric populations have not found that treatment of asymptomatic infection reduced the incidence of preterm labor or delivery. Based on these data, screening and treating all pregnant women who have asymptomatic bacterial vaginosis to prevent preterm birth and its consequences are not recommended by the United States Preventive Services Task Force (USPSTF). Screening and treatment of bacterial vaginosis could be considered in women with a previous preterm birth so as to lower the rate of preterm prelabor rupture of membranes and low birth weight, because these conditions are associated with maternal and neonatal morbidity.

After therapy, approximately 30% of patients with initial responses have a recurrence of symptoms within 3 months. The reasons include reinfection or, more likely, relapse due to failure to eradicate the organism or failure to re-establish the normal protective vaginal flora dominated by lactobacilli. Resistance has been seen with clindamycin, but metronidazole resistance has not yet been reported. Management of symptomatic relapsed patients should involve prolonged therapy for 10 to 14 days. Vaginal lactobacillus replacement is still considered a research endeavor, and commercially available lactobacillus preparations are not recommended. Maintenance regimen of vaginal metronidazole gel, 0.75%, has shown efficacy in excess of 70% but has a high rate of relapse on cessation of the suppressive therapy.

Despite evidence of sexual transmission, no study has demonstrated prevention of recurrence with treatment of male sexual partners.

Candida Vulvovaginitis

Candida albicans is the major yeast implicated in most cases of vaginitis (80%-90%). Other candidal species, including Candida torulopsis and Candida glabrata, can also be associated with vaginitis. Azoles, which are fungistatic and act by inhibiting cell wall metabolism, are the mainstay of treatment for vaginal candidiasis. They are available over the counter and by prescription. They are available in topical and oral forms. Table 3 provides a list of available formulations.

Cure rates of 80% to 90% can be achieved with all the azole agents listed in Table 3. Topical nystatin is less effective, with cure rates of 50% to 80%. The choice between oral and topical therapies should be based on patient preference as well as factors such as compliance, cost, ability to insert vaginal preparations, history of response or adverse reactions to prior treatments, and duration of therapy. The main disadvantage of the topical route is localized burning due to irritant or allergic reactions. Oral therapy with a single dose of fluconazole is as effective as a 3-day course of topical terconazole and a 7-day course of clotrimazole. Systemic side effects are mild, infrequent, and self-limited. They include gastrointestinal intolerance, headache, and rash. Persistent symptoms should be re-evaluated and vaginal yeast cultures should be obtained.

C. glabrata is less likely to respond to azole medications. Boric acid 600 mg topically daily for 14 days is an effective treatment option.

During pregnancy, topical therapy is preferred to limit drug exposure in the fetus. Fluconazole has been categorized as class C during pregnancy.

Recurrent Vulvovaginal Candidiasis

Recurrent vulvovaginal candidiasis (RVVC) is defined as four or more episodes of candidal infection per year. Less than 5% of healthy women are affected by this condition. Pathogenetic factors contributing to RVVC include infection with C. glabrata and other non-albicans Candida species, persistence of C. albicans due to inadequate treatment, diabetes mellitus and impaired glucose tolerance, recent antibiotic use, estrogen use, immunosuppressive therapy, and behavioral factors. Behavioral factors associated with RVVC include vaginal douching as well as contraceptive practices associated with a higher risk of candidiasis, such as diaphragm use, spermicide use, and intrauterine devices. However, in approximately one half of women with RVVC, there are no identifiable risk factors and the pathogenesis remains unknown. Sexual intercourse has not been associated with an increased incidence of Candida colonization. Hypotheses regarding Lactobacillus deficiency in women with RVVC have not been substantiated.

Before treatment for RVVC, a vaginal culture to confirm the diagnosis and determine the species is strongly advisable. Maintenance antifungal suppressive therapy for 6 months with either ketoconazole 100 mg orally daily, itraconazole 50 to 100 mg orally daily, clotrimazole 500-mg vaginal suppositories weekly, or fluconazole 150 mg orally weekly for 6 months is recommended. Approximately 50% of women have no symptoms after 6 months of treatment. Those who have recurrent symptoms after 6 months of therapy might need longer courses of maintenance therapy. Recurrent infections with C. glabrata can be treated with topical boric acid 600 mg daily for 2 weeks. Topical flucytosine can be used for resistant C. glabrata and C. tropicalis species. However, it is expensive, and prolonged use is associated with resistance. The use of combination therapy has not been studied. Studies have also failed to demonstrate a benefit to treating a woman’s partner. Other approaches, such as hormonal manipulation with depot medroxyprogesterone, eating yogurt, and desensitization to candida antigen, lack sufficient data to support recommending their use.

Trichomoniasis

The 5-nitroimidazole group of drugs, which includes metronidazole and tinidazole, are effective treatment choices for trichomoniasis. Oral therapy is preferred because infections of urethra and periurethral glands, which are not eradicated by vaginal therapy, are sources for endogenous recurrence. The recommended treatment choice of the Centers for Disease Control and Prevention (CDC) guidelines is a single 2-g oral dose of metronidazole. The alternative regimen is metronidazole 500 mg twice a day for 7 days. Treatment of all sexual partners is necessary to avoid recurrence. Cure rates approach 90% with either regimen. The side effects of metronidazole therapy are nausea, headache, metallic taste in the mouth, and disulfiram-like effect with alcohol. The advantages of single-dose therapy include better compliance, a lower total dose, a shorter period of alcohol avoidance, and possibly decreased candida superinfection.

Metronidazole resistance in T. vaginalis isolates is uncommon. Most T. vaginalis strains are usually susceptible to metronidazole with a minimum inhibitory concentration (MIC) of 1 μg/mL. Low-level resistance, defined as a MIC of 50 to 100 μg/mL, occurs in 1% to 3% of isolates. These strains manifest with early relapse or failure to respond to single-dose 2-g therapy. Conventional therapy with metronidazole 500 mg twice a day for 7 days can achieve adequate treatment of low-level resistant strains. Higher levels of metronidazole resistance require oral metronidazole 2 g per day for 3 to 5 days according to the CDC guidelines. However, failure of this high-dose regimen has also been reported. Tinidazole, which is now available in the United States, is an alternative for metronidazole-resistant strains of T. vaginalis. Tinidazole has been approved at a dose of 2-g single dose orally as first-line therapy for trichomoniasis. The optimal dose and duration of therapy for metronidazole-resistant T. vaginalis infections are as yet to be determined. For metronidazole-resistant strains, a more prolonged course may be necessary. Tinidazole is better tolerated than metronidazole in terms of both gastrointestinal and central nervous system side effects, especially at higher doses. Tinidazole should also be prescribed to the partner of the woman harboring the resistant T. vaginalis.

Trichomoniasis treatment during pregnancy is controversial. Metronidazole readily crosses the placenta; however, it is unclear if it is teratogenic. Most physicians prefer to avoid it in the first trimester of pregnancy. Clotrimazole can temporarily relieve the symptoms of trichomoniasis. Treatment may be delayed until after the first trimester of pregnancy. Breast-feeding should be delayed or withheld for 24 hours after taking metronidazole.

Other Causes of Vaginitis

The treatment for other types of vaginitis depends on the cause. Atrophic vaginitis can be treated with local or systemic estrogens. Desquamative inflammatory vaginitis is a chronic purulent vaginitis with negative cultures, which responds to topical 2% clindamycin. Bacterial vaginitis complicating atrophic vaginitis or a foreign body superinfection can be treated with antibiotics and foreign body removal, when appropriate. Noninfectious causes of vaginitis include irritants and allergens. Management includes removing the offending agent, applying topical corticosteroids (used cautiously to avoid local burning), taking sodium bicarbonate sitz baths, and applying vegetable oil topically.

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Summary

• A careful history, physical examination, and simple microscopy can help ascertain a diagnosis and tailor treatment while avoiding misdiagnosis, treatment failure, and symptom recurrence.
• The three most common causes of vaginitis are bacterial vaginitis, candidal vulvovaginitis, and trichomonal vaginitis.
• Physical examination should mainly be used to evaluate for cervical inflammation (suggesting an alternative cause) and to exclude pelvic inflammatory disease.
• The diagnosis of vaginitis is mainly made by using a combination of vaginal pH, amine test, microscopy findings, and, sometimes, vaginal cultures.
• Other causes of vaginitis include atrophic vaginitis, desquamative inflammatory vaginitis, a foreign body infection, and irritants and allergens.

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Suggested Reading

• Amsel R, Totten PA, Spiegel CA, et al: Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations. Am J Med 1983;74(1):14-22.

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