Vulvovaginal Candidiasis (VVC)
VVC usually is caused by Candida albicans but can occasionally be caused by other Candida species or yeasts. Typical symptoms of VVC include pruritus, vaginal soreness, dyspareunia, external dysuria, and abnormal vaginal discharge. None of these symptoms is specific for VVC. An estimated 75% of women will have at least one episode of VVC, and 40%–45% will have two or more episodes. On the basis of clinical presentation, microbiology, host factors, and response to therapy, VVC can be classified as either uncomplicated or complicated (Box 4). Approximately 10%–20% of women will have complicated VVC, requiring special diagnostic and therapeutic considerations.
- Sporadic or infrequent VVC
- Mild-to-moderate VVC
- Likely to be Candida albicans
- Nonimmunocompromised women
- Recurrent VVC
- Severe VVC
- Non-albicans candidiasis
Women with diabetes, immunocompromising conditions (e.g., HIV infection), underlying immunodeficiency, or immunosuppressive therapy (e.g., corticosteroids)
Abbreviation: HIV, human immunodeficiency virus.
Uncomplicated Vulvovaginal Candidiasis
A diagnosis of Candida vaginitis is clinically indicated by the presence of external dysuria and vulvar pruritus, pain, swelling, and redness. Signs include vulvar edema, fissures, excoriations, and thick curdy vaginal discharge. Most healthy women with uncomplicated VVC have no identifiable precipitating factors. The diagnosis can be made in a woman who has signs and symptoms of vaginitis when either a wet preparation (saline, 10% KOH) of vaginal discharge demonstrates budding yeasts, hyphae, or pseudohyphae, or a culture or other test yields a positive result for a yeast species. Candida vaginitis is associated with normal vaginal pH (<4.5). Use of 10% KOH in wet preparations improves the visualization of yeast and mycelia by disrupting cellular material that might obscure the yeast or pseudohyphae. Examination of a wet mount with KOH preparation should be performed for all women with symptoms or signs of VVC, and women with a positive result should be treated. For those with negative wet mounts but existing signs or symptoms, vaginal cultures for Candida should be considered. If Candida cultures cannot be performed for these women, empiric treatment can be considered. Identifying Candida by culture in the absence of symptoms or signs is not an indication for treatment because approximately 10%–20% of women harbor Candida species and other yeasts in the vagina. The majority of PCR tests for yeast are not FDA cleared, and providers who use these tests should be familiar with the performance characteristics of the specific test used. Yeast culture, which can identify a broad group of pathogenic yeasts, remains the reference standard for diagnosis.
Short-course topical formulations (i.e., single dose and regimens of 1–3 days) effectively treat uncomplicated VVC. Treatment with azoles results in relief of symptoms and negative cultures in 80%–90% of patients who complete therapy.
Over-the-Counter Intravaginal Agents
Clotrimazole 1% cream 5 g intravaginally daily for 7–14 days
Clotrimazole 2% cream 5 g intravaginally daily for 3 days
Miconazole 2% cream 5 g intravaginally daily for 7 days
Miconazole 4% cream 5 g intravaginally daily for 3 days
Miconazole 100 mg vaginal suppository one suppository daily for 7 days
Miconazole 200 mg vaginal suppository one suppository for 3 days
Miconazole 1,200 mg vaginal suppository one suppository for 1 day
Tioconazole 6.5% ointment 5 g intravaginally in a single application
Prescription Intravaginal Agents
Butoconazole 2% cream (single-dose bioadhesive product) 5 g intravaginally in a single application
Terconazole 0.4% cream 5 g intravaginally daily for 7 days
Terconazole 0.8% cream 5 g intravaginally daily for 3 days
Terconazole 80 mg vaginal suppository one suppository daily for 3 days
Fluconazole 150 mg orally in a single dose
The creams and suppositories in these regimens are oil based and might weaken latex condoms and diaphragms. Patients should refer to condom product labeling for further information. Even women who have previously received a diagnosis of VVC by a clinician are not necessarily more likely to be able to diagnose themselves; therefore, any woman whose symptoms persist after using an over-the-counter preparation or who has a recurrence of symptoms <2 months after treatment for VVC should be evaluated clinically and tested. Unnecessary or unapproved use of over-the-counter preparations is common and can lead to a delay in treatment of other vulvovaginitis etiologies, which can result in adverse outcomes. No substantial evidence exists to support using probiotics or homeopathic medications for treating VVC.
Follow-up typically is not required. However, women with persistent or recurrent symptoms after treatment should be instructed to return for follow-up visits.
Management of Sex Partners
Uncomplicated VVC is not usually acquired through sexual intercourse, and data do not support treatment of sex partners. A minority of male sex partners have balanitis, characterized by erythematous areas on the glans of the penis in conjunction with pruritus or irritation. These men benefit from treatment with topical antifungal agents to relieve symptoms.
Drug Allergy, Intolerance, and Adverse Reactions
Topical agents usually cause no systemic side effects, although local burning or irritation might occur. Oral azoles occasionally cause nausea, abdominal pain, and headache. Therapy with the oral azoles has rarely been associated with abnormal elevations of liver enzymes. Clinically important interactions can occur when oral azoles are administered with other drugs (1141).
Complicated Vulvovaginal Candidiasis
Vaginal culture or PCR should be obtained from women with complicated VVC to confirm clinical diagnosis and identify non–albicans Candida. Candida glabrata does not form pseudohyphae or hyphae and is not easily recognized on microscopy. C. albicans azole resistance is becoming more common in vaginal isolates (1144,1145), and non–albicans Candida is intrinsically resistant to azoles; therefore, culture and susceptibility testing should be considered for patients who remain symptomatic.
Recurrent Vulvovaginal Candidiasis
Recurrent VVC, usually defined as three or more episodes of symptomatic VVC in <1 year, affects <5% of women but carries a substantial economic burden (1146). Recurrent VVC can be either idiopathic or secondary (related to frequent antibiotic use, diabetes, or other underlying host factors). The pathogenesis of recurrent VVC is poorly understood, and the majority of women with recurrent VVC have no apparent predisposing or underlying conditions. C. glabrata and other non–albicans Candida species are observed in 10%–20% of women with recurrent VVC. Conventional antimycotic therapies are not as effective against these non–albicans yeasts as against C. albicans.
Most episodes of recurrent VVC caused by C. albicans respond well to short-duration oral or topical azole therapy. However, to maintain clinical and mycologic control, a longer duration of initial therapy (e.g., 7–14 days of topical therapy or a 100-mg, 150-mg, or 200-mg oral dose of fluconazole every third day for a total of 3 doses [days 1, 4, and 7]) is recommended, to attempt mycologic remission, before initiating a maintenance antifungal regimen.
Oral fluconazole (i.e., a 100-mg, 150-mg, or 200-mg dose) weekly for 6 months is the indicated maintenance regimen. If this regimen is not feasible, topical treatments used intermittently can also be considered. Suppressive maintenance therapies are effective at controlling recurrent VVC but are rarely curative long-term (1147). Because C. albicans azole resistance is becoming more common, susceptibility tests, if available, should be obtained among symptomatic patients who remain culture positive despite maintenance therapy. These women should be managed in consultation with a specialist.
Severe Vulvovaginal Candidiasis
Severe VVC (i.e., extensive vulvar erythema, edema, excoriation, and fissure formation) is associated with lower clinical response rates among patients treated with short courses of topical or oral therapy. Either 7–14 days of topical azole or 150 mg of fluconazole in two sequential oral doses (second dose 72 hours after initial dose) is recommended.
Non–albicans Vulvovaginal Candidiasis
Because approximately 50% of women with a positive culture for non–albicans Candida might be minimally symptomatic or have no symptoms, and because successful treatment is often difficult, clinicians should make every effort to exclude other causes of vaginal symptoms for women with non–albicans yeast (1148). The optimal treatment of non–albicans VVC remains unknown; however, a longer duration of therapy (7–14 days) with a nonfluconazole azole regimen (oral or topical) is recommended. If recurrence occurs, 600 mg of boric acid in a gelatin capsule administered vaginally once daily for 3 weeks is indicated. This regimen has clinical and mycologic eradication rates of approximately 70% (1149). If symptoms recur, referral to a specialist is advised.
Management of Sex Partners
No data exist to support treating sex partners of patients with complicated VVC. Therefore, no recommendation can be made.
Women with underlying immunodeficiency, those with poorly controlled diabetes or other immunocompromising conditions (e.g., HIV), and those receiving immunosuppression therapy (e.g., corticosteroid treatment) might not respond as well to short-term therapies. Efforts to correct modifiable conditions should be made, and more prolonged (i.e., 7–14 days) conventional treatment is necessary.
VVC occurs frequently during pregnancy. Only topical azole therapies, applied for 7 days, are recommended for use among pregnant women. Epidemiologic studies indicate a single 150-mg dose of fluconazole might be associated with spontaneous abortion (1150) and congenital anomalies; therefore, it should not be used (1151).
Vaginal Candida colonization rates among women with HIV infection are higher than among women without HIV with similar demographic and risk behavior characteristics, and the colonization rates correlate with increasing severity of immunosuppression (1152). Symptomatic VVC is also more frequent among women with HIV infection and similarly correlates with severity of immunodeficiency (1153). In addition, among women with HIV, systemic azole exposure is associated with isolation of non–albicans Candida species from the vagina.
Treatment for uncomplicated and complicated VVC among women with HIV infection should not differ from that for women who do not have HIV. Although long-term prophylactic therapy with fluconazole 200 mg weekly has been effective in reducing C. albicans colonization and symptomatic VVC (1154), this regimen is not recommended for women with HIV infection in the absence of complicated VVC (98). Although VVC is associated with increased HIV seroconversion among HIV-negative women and increased HIV cervicovaginal levels among women with HIV infection, the effect of treatment for VVC on HIV acquisition and transmission remains unknown.