Overview
Unlike oropharyngeal candidiasis, Candida vulvovaginitis is generally not considered an opportunistic infection. The majority of cases of Candida vulvovaginitis occur in perfectly healthy women and respond well to (A):conventional antifungal treatments for Candida vulvovaginitis.
Epidemiology
Vaginal colonization
Candida spp. are part of the lower genital tract flora in 20 to 50% of healthy asymptomatic women [855]. Carriage rates are higher in:
- Women treated with broad spectrum antibiotics [346, 1693].
- Pregnant women [256, 346].
- Diabetic women [2300].
- Women with the diagnosis of AIDS (CD4+ counts < 200 cells/mL) [629]. Lower CD4+ T-cell counts are associated with higher rates of colonization [346].
Candida albicans is both the most frequent colonizer and responsible for most cases of vulvovaginal candidiasis [629, 1699]. Nevertheless, over the last decades there have been reports demonstrating an increment in the frequency of cases caused by non-albicans species [2124]. Candida glabrata has consistently been the leading species, and we provide a special discussion of (A): Candida glabrata vulvovaginitis below.
Risk factors for Candidal Vulvovaginitis
Almost any premenopausal woman can develop Candida vulvovaginitis. In fact, 70 to 75% of healthy adult women have at least one episode of Candida vulvovaginitis during their reproductive life and half of all college women will, by the age of 25, have had one episode of Candida vulvovaginitis diagnosed by a physician [1087, 2122].
The only well proven risk factors for Candida vulvovaginitis are pregnancy, diabetes mellitus, and the use of broad spectrum antibiotics [1585, 1693, 2300]. For details see the following table:
| Well proven risk factors | References |
|---|---|
| Estrogen-related | |
| Pregnancy | [1585] |
| OC with high estrogen content | [1672] |
| Diabetes Mellitus | [2300] |
| Use of broad spectrum antibiotics | [1693] |
| Poorly supported risk factors | |
| Use of sponge, intrauterine devices, diaphragms, condoms | Conflicting results from the following studies: [750, 1064, 1699, 2138] |
| Orogenital sex | |
| Douching | |
| Intercourse |
Clinical Manifestations
The principal symptoms of Candida vulvovaginitis are vulvar and/or vaginal pruritus and a thick vaginal discharge. Clinicians should be aware that these complaints are very nonspecific. For example, vaginal pruritus predicted Candida vulvovaginitis only 38% of the time in one study [231]. On the other hand, almost all women with proven candidal vulvovaginitis complain of pruritus. Other possible symptoms are vulvar pain and dyspareunia (pain during sexual intercourse). On physical examination, whitish, curdlike thick secretions cover the vulva and vaginal walls with diffuse erythema. Edema and vulvar erythema are generally more prominent between the labia minora. The extent of involvement varies and the vaginal discharge may vary from thick to thin, and from white to simply watery [1537]. |
 Candidal vulvovaginitis |
Specific Diagnostic Strategies
The specificity of symptoms and signs of Candida vulvovaginitis is so low that it is not possible to make a diagnosis based solely on patient’s history and genital examination. Therefore, to have a positive diagnosis of Candida vulvovaginitis these steps are recommended:
- Confirmation of a normal vaginal pH (4-4.5)
- Prepare a wet mount of the vaginal discharge for identification of yeast cells and mycelia and to rule out other diagnoses (the “clue cells” of bacterial vaginosis and motile trichomonads of trichomoniasis).
- Examine a 10% KOH prep of the vaginal discharge. This has a higher sensitivity for identification of yeast. A gram-stained preparation (see photo) may also be used. Yeast are gram-positive. Interestingly, (A):Candida glabrata CVV have been associated with negative potassium hydroxide microscopy [818].
- If microscopic studies are negative and the index of suspicion for Candida vulvovaginitis continues to be high, send a sample for fungal culture. Microscopy is negative for yeast in as many as half of the patients with culture-proven Candida vulvovaginitis that will respond to antifungal therapy [2124].
Therapies
There are many effective antifungal agents, including both topical and oral choices. Many of them are available for sale over-the-counter. In summary, we can say that:
- All topical regimens are roughly equal in terms of efficacy (resolution of symptoms and making the fungal culture negative). Typical response rates are 80-90%.
- Oral regimens are popular because of their convenience [2243].
- Oral azole therapy has the potential of causing systemic side effects, particularly ketoconazole [1332].
- The most popular regimens are those that can be used successfully once per day [2243]. However, oral regimens do not produce relief until 48 hours after been taken, so in a very symptomatic patient a local agent may be recommended for at least the first day of treatment. In addition, single-dose oral regimens may not be as effective for patients with complicated, persistent, or severe disease. As suggested by Sobel et al. [2124], it is helpful to think of patients with Candida vulvovaginitis as belonging to one of two groups:
Risk stratification of Candida vulvovaginitis
Group Clinical feature Uncomplicated Complicated Host Normal Locally or systemically immunocompromised (e.g. diabetic) Severity Mild or Moderate Severe Regularity Infrequent Frequent/recurrent Candida species Candida albicans Non-albicans species Any patient who shows one or more of the features of complicated disease should be considered for more prolonged therapy, with the topical agents generally being preferred.
Antifungal regimens for Candida vulvovaginitis
A good recent reference for therapy is [88].
Conventional multi-day antifungal treatments for Candida vulvovaginitis
| Drug (see also Other Topical Agents) | Drug format | Dosage |
|---|---|---|
| Butoconazole | 2% cream | 5 grams qd hs x 1-7 days1 |
| Clotrimazole | 1% cream, 100 mg tablets | 5 grams qd hs or 100 mg qd hs x 1-7 days1 |
| Miconazole | 2% cream, 100 mg & 200 mg suppositories | 5 grams qd hs, 100 mg supp qd hs, 200 mg supp qd hs x 1-7 days1 |
| Nystatin | 100,000 units vaginal tablets | 1 tab/day x 7-14 days1 |
| Terconazole | 0.4% cream, 0.8% cream, 80 mg suppositories | 0.4% cream qd, 0.8% cream hs or 80 mg supp qd hs x 1-7 days1 |
1Length of therapy depends on risk classification
One day regimens for uncomplicated Candida vulvovaginitis
| Drug | Drug format | Dosage |
|---|---|---|
| Topical (see Other Topical Agents) | ||
| Clotrimazole | 500 mg tablets | 500mg qd x 1 day |
| Tioconazole | 6.5% ointment | 5 grams x 1 |
| Butoconazole | 2% cream (Sustained-released formulation) | 5 grams x 1 |
| Oral | ||
| Fluconazole | 150 mg tablet | 150 mg x 1 tablet |
| Itraconazole | 100 mg capsules | 200 mg BID x 1 day |
Other oral alternatives for Candida vulvovaginitis
| Drug | Drug format | Dosage |
|---|---|---|
| Ketoconazole | 200 mg tablets | 200 mg/day x 5-7 days, 400mg/day x 3 days |
| Itraconazole | 100 mg capsules | 400 mg first dose then 200 mg/day x 2 days |
Difficult Clinical Situations
Relapsing or Recurrent Candida vaginitis (RCVV)
The woman who presents with recurrent episodes of Candida vulvovaginitis (CVV) is a special challenge for her physician. Relapsing or recurrent Candida vulvovaginitis (RCVV) is a condition that affects less than 5% of healthy women. Thus, the first step in approaching this problem is to make sure that the patient actually has Candida vulvovaginitis. The initial examination and history should focus on (a) proving that Candida vulvovaginitis is present and (b) ensuring that the many possible alternative causes of vaginitis are absent.
Differential Diagnosis of Recurrent Candida Vulvovaginitis (RCVV)
- Inadequate therapy of true Candida vulvovaginitis due to use of ineffective therapy, insufficient length of therapy, or (in the case of oral regimens) drug-drug interactions that lower the level of the administered drug
- Other infections (trichomoniasis, bacterial vaginitis)
- Contact dermatitis
- Atrophic vaginitis
- Hypersensitivity
- Erosive lichen planus
- Allergic
- Behcet’s syndrome
- Chemical
- Pemphigus syndromes
If none of these diseases are present and if the physical examination and microbiological examinations support the diagnosis of Candida vulvovaginitis, the possibility of RCVV should be entertained. In general, this label is reserved for women having had four or more episodes per year of Candida vulvovaginitis [2122].
Specific Therapeutic Strategies
Treating RCVV is a long-term endeavour. The following steps are often helpful:
- Eliminate factors predisposing to Candida vulvovaginitis. Unfortunately, in the large majority of women suffering from RCVV, a responsible and reversible factor cannot be identified.
- Use an effective antifungal regimen until the patient is completely asymptomatic and vaginal culture has turned negative.
- Close observation upon cessation of therapy.
- If culture proven (A):Candida glabrata CVV is diagnosed special (A):therapeutic recommendations may be of value.
If CVV recurs within 3 months, use of a maintenance-suppressive regimen (see table below) is appropriate. These regimens are used for 2-4 months, and then discontinued. If symptoms again recur, the maintenance regimen is reinstituted for a longer period. Some women will ultimately break their cycle of RCVV with this approach, while a few will require very long-term suppression.
Maintenance-suppressive regimen for relapsing or recurrent Candida vulvovaginitis
Drug Dosage Ketoconazole 100 mg/day Clotrimazole (see Other Topical Agents) 500 mg suppositories/ week Fluconazole 100 mg/ week
Candida Vulvovaginitis in Women with HIV-AIDS
There has been a large debate about the relationship between the Candida vulvovaginitis and Human Immunodeficiency Virus (HIV). In general, a series of studies have made the point that Candida vulvovaginitis behaves like oropharyngeal candidiasis (OPC) in women with HIV.
It has also been claimed that Candida vulvovaginitis is an indicator of HIV infection, a marker of progression toward Acquired Immunodeficiency Syndrome (AIDS), and the most frequent clinical manifestation of HIV infection [379, 1093, 1916]. However, when rates of yeast vaginal colonization and vaginitis are compared between HIV-positive and HIV-negative there are no major differences between these groups [629]. Indeed, the Centers for Disease Control and Prevention (CDC) has not included Candida vulvovaginitis among the AIDS-defining conditions. Instead, the CDC has stated that “when Candida vulvovaginitis is persistent, frequent or poorly responsive to therapy“, the patient should be included in the clinical category B of its revised classification system for HIV infection [405].
However, the evidence available in this regard has a series of important methodological defects, including small numbers, lack of fungal cultures or other more reliable diagnostic techniques, retrospective analysis with excessive use of self-reported history, etc. In general, the approach to therapy in women with HIV or AIDS is similar to that in otherwise healthy women.
Candida Vulvovaginitis and Sexually Transmitted Diseases (STD)
Candida vulvovaginitis is not considered a sexually transmitted disease, because:
- Candida vulvovaginitis does affect celibate women.
- Candida spp., as previously discussed, are considered part of the normal vaginal flora [855].
However, this does not mean that Candida cannot be sexually transmitted. Indeed, evidence in favor of sexual transmission exists and includes:
- Penile colonization is four times more frequent in male sexual partners of women affected with Candida vulvovaginitis [1942].
- Infected partners commonly carry identical strains [1664].
- Orogenital transmission has been documented [1436].
Candida glabrata Vulvovaginitis
Candida glabrata is emerging as a significant cause of vulvovaginitis. The majority of cases are identified when failure of standard regimens prompt the use of vaginal cultures [125, 2421]. Few accurate data about the precise frequency of this phenomenon is available. However, two specialized clinics have reported rates of 10 to 20% of non-albicans CVV, and Candida glabrata has consistently been the dominant species [2122, 2138]. Sobel et al. have proposed the following possible reasons for the increment of non-albicans species [2124]:
- Use of short courses of either oral or topical regimens.
- The widespread use of over-the-counter antimycotics. This modality favors inappropriately short, incomplete courses of therapy. Consequently, elimination of the more sensitive species (Candida albicans) and selection of more azole-resistant species occur. As the non-albicans species, and most notably C. glabrata (see our discussion of N/A(L):typical susceptibility patterns), are less responsive to azoles, short course of low-dose therapy would naturally select the less susceptible species.
- Incremental use of antimycotic regimens for long periods to prevent recurrences.
Some special considerations arise when treating a case of Candida glabrata vulvovaginitis. First, the response to a complete course of a standard azole should be assessed. Clinical cures are documented in up to 67% of cases using this approach. If this fails or a recurrence appears immediately upon cessation of therapy, topical boric acid or topical flucytosine is recommended. Very little experience exists in this regard, but vaginal insertion of 600 mg gelatin capsules of boric acid have proven to be effective in about 80% of cases [2123]. A recent nonrandomized study found boric acid to have an efficacy similar to that of oral itraconazole [921].
Candida vulvovaginitis and Azole-Resistant Candida species
While relapses are frequent in at least some women, these generally are not due to antifungal resistance [2121]. A step-wise approach is recommended when confronting a case of (A):relapsing or recurrent Candida vaginitis. The step-wise approach described just above for Candida glabrata CVV may be of value.