Acta Dermatovenerol APA
Acta Dermatovenerologica
Alpina, Pannonica et Adriatica
2015;24:11-12
doi: 10.15570/actaapa.2015.4
Treatment of vulvovaginal candidiasis: a review of the literature
Andraž Dovnik1 H, Andrej Golle2, Dušan Novak2, Darja Arko1, Iztok Takač1, 3
Abstract
Vulvovaginal candidiasis (VVC) affects around three-quarters of all women during their reproductive age, although the exact incidence of VVC is difficult to determine because many patients are self-treated. The infections are divided into complicated and uncomplicated. Uncomplicated VVC is most effectively treated with local azoles. Oral treatment with a single dose of fluconazole is also effective for treating uncomplicated VVC. Treatment of complicated VVC is prolonged and most commonly consists of multiple doses of oral fluconazole or at least 1 week of local azoles. The role of probiotics in treating VVC is still disputed. This article presents a review of the literature on the various treatment options for VVC. Treatment for the most common pathogens that cause complicated VVC is also discussed.
Keywords: fungal infection, vulva, vagina, local azoles, systemic treatment, probiotics
Received: 17 January 2015 | Returned for modification: 30 January 2015 | Accepted: 2 February 2015
Introduction
Fungal infection of the vulva and the vagina is estimated to be the second most common cause of inflammation after bacterial vaginosis (1). About three-quarters of women during their reproductive age have at least one episode of vulvovaginal candidiasis (VVC) and approximately half have two or more episodes (2). The most common pathogen is Candida albicans, which is isolated in 85 to 90% of all cases (3). Asymptomatic colonization with Candida spp. is also common. It can be found in about one-third of women without any symptoms and was identified in 70% of women during a 1-year observation period (4). In a study of 612 women, Bauters et al. found 20% overall colonization with Candida spp. and a 6.3% rate of clinical infection (5). Colonization with Candida spp. was also determined in 10 to 20% of women undergoing conization for cervical intraepithelial neoplasia (6).
VVC is divided into uncomplicated and complicated cases. Uncomplicated cases are sporadic episodes of mild infections caused by C. albicans (7). Complicated cases are cases of VVC caused by other species of Candida, cases of severe infection, VVC during pregnancy, or VVC associated with other medical conditions such as immunosuppression or diabetes. Recurrent VVC (RVVC) is also a form of complicated infection and is defined as four or more episodes of VVC per year (4, 8, 9). About 5 to 8% of VVC cases are recurrent, and C. glabrata and other non-C. albicans forms are isolated in 10 to 20% of these cases (2, 9). However, it is difficult to evaluate the exact incidence of VVC due to the high rate of self-treatment with over-the-counter medications. Moreover, the diagnosis is frequently based entirely on signs and symptoms without any tests to confirm the diagnosis (4).
Treatment depends on whether the infection is complicated or uncomplicated (10). This article presents a review of the literature on treating VVC.
Etiology
C. albicans, which most commonly causes VVC, is part of normal vaginal microflora (9). The second most common pathogen
identified in women with VVC is C. glabrata, which is isolated in 7 to 16% of cases (4). Clinical inflammation occurs in cases of disturbed balance between the host and the colonizing microorganisms (4). Lactobacilli are an important element of vaginal microflora because their production of lactic acid keeps the vaginal pH low and prevents overgrowth of other pathogens (4, 11). Risk factors for VVC are pregnancy, diabetes, and behavioral risk factors such as the use of oral contraceptives with a high dose of estrogen, the use of condoms, spermicides, frequent oral sexual intercourse, and the use of tight synthetic underwear (12-14).
The use of antibiotics causes a change in vaginal microflora, which increases colonization with Candida spp. Colonization with C. albicans is increased from approximately 10% to 30%, and VVC is diagnosed in 28 to 33% of cases (15). Despite the role of lactobacilli, which help maintain the low vaginal pH and prevent other pathogenic species from growing disproportionately, it has not been proven that changes in the vaginal microflora in the absence of antibiotic use lead to VVC (16).
The risk factors for complicated VVC are the same as in uncomplicated VVC. Recurrent cases of VVC can be associated with coexistent dermatological diseases, such as lichen sclerosus, and with immunosuppression, such as in HIV infection (2).
Clinical presentation and diagnosis
The most common symptoms are burning pain and pruritus of the vulva with discomfort that can lead to dysuria and dyspareunia in more severe cases (17). Clinical signs of VVC are edema and erythema of the vulva and the vagina accompanied by an abnormal vaginal discharge that may be watery, cheese-like, or minimal (17). The vaginal discharge typically resembles cottage cheese (8).
The diagnosis is most frequently made clinically (8). Microscopic examination of the discharge is also helpful. Mycelia can be seen under microscopy in 50 to 80% of cases. The whiff test, in which 10% potassium hydroxide is added to the vaginal discharge, is used to distinguish between VVC and bacterial vaginosis. In bacterial vaginosis, an amine-like odor is released following this reaction. The test is negative in cases of VVC (8). The vaginal
•University Clinical Department of Gynecology and Perinatology, Maribor University Clinical Centre, Maribor, Slovenia. 'Department of Medical Microbiology, Medical Microbiology Center, National Laboratory of Health, Environment, and Food, Maribor, Slovenia. 3Department of Gynecology and Perinatology, University of Maribor Faculty of Medicine, Maribor, Slovenia. h Corresponding author: andrazdovnik@gmail.com
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pH in women with VVC is usually less than 4.5, and in cases of infection with Trichomonas vaginalis the pH is more than 4.5 (4). A fungal culture is recommended to confirm the diagnosis. When no fungal elements are identified under microscopy and no typical clinical signs are present, a woman is not likely to have VVC. Empirical treatment should not be started in this case except in cases of positive culture (8).
Treatment of vulvovaginal candidiasis
Treatment of VVC depends on whether the patient has uncomplicated or complicated VVC (10).
Treatment of uncomplicated vulvovaginal candidiasis
Short-term local therapy or single-dose oral treatment is effective for treating 90% of uncomplicated cases. It is not clear whether oral or local agents are more appropriate for treating uncomplicated VVC, and no single agent seems to be clearly superior to others (4, 10). The most easily available are local azoles. Short-term therapy of up to 3 days with local azoles is recommended and the symptoms usually disappear after 2 to 3 days. This treatment is effective in 80 to 90% of cases (8). Various local agents with similar effects are available, including clotrimazole, butoconazole, and miconazole (1). Agents that are used in short-term regimens contain higher doses of antifungal medicine, allowing higher concentrations for longer-lasting inhibitory effect (8). Topical azoles are more efficient than local nystatin in treating uncomplicated VVC (18). Recently, Mendling et al. performed a comparative study on 160 patients with VVC in which they compared treatment with clotrimazole vaginal suppositories alone and a combination of 2% clotrimazole cream for external use and clotrimazole vaginal suppositories. They concluded that the combination of both was better than the suppositories alone (19).
An alternative to local therapy of uncomplicated VVC is oral treatment with single-dose 150 mg fluconazole. The efficiency of single-dose fluconazole for treating acute VVC was evaluated in a prospective trial by Sekhavat et al. (20). They compared 1 week of clotrimazole vaginal suppositories and a single dose of 150 mg oral fluconazole. Clinical and mycological results in both groups were comparable and oral fluconazole proved to be effective in treating acute VVC (20). The Infectious Diseases Society of America made no preference and recommends both local azoles and oral fluconazole (10). However, the patients should be warned that the symptoms may last up to 3 days following the oral dose (8).
Treatment of complicated vulvovaginal candidiasis and recurrent vulvovaginal candidiasis
Complicated cases of VVC require prolonged treatment. Oral fluconazole can be given three times with a gap of 72 hours or local azoles applied daily for at least 1 week (4). Sobel et al. compared single-dose and two-dose regimens of fluconazole in women with complicated VVC. The two-dose regimen was shown to achieve higher mycological and clinical response rates (21).
Another American study assessed the effectiveness of flucona-zole maintenance therapy for treating recurrent VVC (22). A total of 387 patients were randomized into two groups. After initial treatment with three 150 mg doses of fluconazole every 72 hours, the first group of participants received weekly doses of 150 mg flu-
conazole for 6 months and the second group received a weekly placebo for 6 months. After 6 months of maintenance treatment, 90.8% of the women remained disease-free, compared to 35.9% in the placebo group. The time to recurrence was statistically significantly shorter in the placebo group compared to the fluconazole group (4.0 months vs. 10.2 months; p < 0.001). No proof of superinfection with C. glabrata and other non-C. albicans isolates was obtained and there was no evidence of C. albicans species developing resistance to fluconazole (22).
A comparison of vaginal nystatin and oral fluconazole for treating RVVC was performed in a recent study on 293 patients by a Chinese research group (23). Standard oral fluconazole regimens for treating RVVC were compared with 2 weeks of vaginal nystatin every month. The results showed that both oral fluconazole and vaginal nystatin are effective in treating RVVC and that in cases of fluconazole-resistant C. albicans or C. glabrata RVVC nystatin can also be efficient (23).
The location of C. albicans persistence in patients with RVVC was evaluated by Beikert et al. (24). Swabs of 139 patients with an episode of microbiologically confirmed RVVC were taken from the interlabial sulcus on the vulva and from the vagina. This was followed by a combined 20-day treatment with topical Ciclopirox Olamin cream and 100 mg oral fluconazole. About three-quarters of the patients had at least one positive vulvar culture identifying C. albicans on one of the four follow-up visits. They concluded that the origin of reinfection in patients with RVVC seems to be the external vulva (24).
Witt et al. compared standard homeopathy and monthly itraconazole for treating RVVC in a prospective study of 150 patients (25). Patients treated with classic homeopathy experienced earlier recurrences. Almost 90% of patients treated with itraconazole had no Candida detected in the culture at the first follow-up visit compared to 47% in the standard homeopathy group (25). Maintenance therapy with 100 mg ketoconazole also proved effective, but it is not favored for treating RVVC due to its hepatotoxicity (26, 27).
Therapy with azoles is less effective in treating non-C. albicans VVC. All preparations used for treating non-C. albicans VVC have to be made in the pharmacy (4). Phillips studied the effectiveness of vaginal amphotericin B in women with non-C. albicans VVC that did not respond to the usual antimycotics. A 2-week regimen with 50 mg amphotericin B intravaginally was effective in 70% of cases (28). In a retrospective review, Sobel et al. evaluated the efficiency of topical treatment of C. glabrata VVC with flucytosine and boric acid (29). Topical boric acid was used in a dose of 600 mg and was administered intravaginally for 14 to 21 days. In the two groups of patients with C. glabrata VVC, boric acid was effective in 64 to 71% of patients. When the patients did not respond to boric acid, flucytosine was used and was effective in 90% (29).
The role of probiotics in treating recurrent vulvovaginal candidi-asis
Probiotics are living microorganisms that, in appropriate amounts, are beneficial for the health of the host (30). Studies evaluating the effectiveness of probiotics in preventing RVVC have shown conflicting results. In a review by Falagas et al., some studies supported the effectiveness of oral or local lactobacilli, particularly Lactobacillus rhamnosus GR-1, Lactobacillus fermentum RC-14, and Lactobacillus acidophilus, whereas other studies did not prove the effectiveness of lactobacilli. The authors emphasized
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Treatment of vulvovaginal candidiasis
the methodological difficulties of the studies reviewed. The majority of studies evaluated a small sample of participants with no placebo group. In addition, different strains of probiotics that have various effects on Candida were tested in the various trials included in the review with variable duration and dosage (30). A recent Croatian study evaluated the effectiveness of probiotics in restitution of normal vaginal microflora after vaginal infection (31). The study comprised patients diagnosed with vaginal infection containing VVC. They were randomized into two groups. The first group received a placebo containing capsules for 6 weeks and the second group received capsules containing the probiotics Lactobacillus reuteri RC-14 and Lactobacillus rhamnosus GR-1 for 6 weeks. The first follow-up visit was performed 6 weeks after the end of the treatment. Compared to 61.5% in the probiotics group, 26.9% of the participants in the placebo group had normal vaginal microflora at the first follow-up visit (31).
Witt et al. also studied the effect of added probiotics to itracon-azole in treating RVVC. Local lactobacilli were added for 6 days to monthly 200 mg itraconazole maintenance therapy following treatment of an acute episode of VVC. The lactobacilli did not offer any advantage in treating RVVC (25). Martinez et al. evaluated
the additional value of 4-week therapy with probiotics that were added to a single dose of 150 mg fluconazole in treating culture-positive VVC. After 4 weeks of treatment, 38.5% of participants in the probiotics group were culture-free compared to 10.3% of patients that received only fluconazole (32). A recent report by De Seta et al. evaluated the effectiveness of local Lactobacillus plan-tarum P17630. One group of patients received the standard treatment with local clotrimazole for 3 days and the other group had additional probiotic capsules applied intravaginally for 6 days and then once weekly for 4 weeks. They concluded that local Lactobacillus plantarum P17630 offers potential benefit for resolution of vaginal discomfort (33).
Conclusion
Vulvovaginal candidiasis is not a reportable disease and, due to the high degree of self-treatment and available over-the-counter agents, it is not possible to evaluate the exact incidence of this infection. Preventing VVC is as important as treating this condition. Treatment should be individual and depends on whether the patient has complicated or uncomplicated VVC.
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