139 women with RVVC and at least one C. albicans positive culture from either vagina or external vulva at the first visit were enrolled in the study.
Clinical symptoms were documented and colposcopy, pH measurement and microscopy from vaginal smears performed.
Swabs from both vagina and external vulva (interlabial sulci) were collected for yeast cultures.
122 women were treated with fluconazole 100mg once daily for 20 days in combination with ciclopiroxolamin cream applied on the external vulva for 4 weeks. Follow-up visits at 1, 3, 6, 9 and 12 months.
The strength of the association between C. albicans positive vulvar culture results and clinical symptoms were measured using Cornfield 95% confidence intervals (CI - p value < 0.05) and odds ratios (OR).
The Value of Vulvar Cultures as a Diagnostic Method in Women with Recurrent Vulvovaginal Candidiasis
FC BEIKERT1, MT LE1 , A. CLAD1
1 Department of Obstetrics and Gynecology, University of Freiburg, Germany
Table 1. Vulvar cultures, clinical symptoms and colposcopic findings at day 0
Clinical symptoms and
signs
Vulva-pos Vulva-neg OR
(95%CI)
p
n=105 (%) n=34 (%)
Pruritus 93 (89) 20 (59) 5.4 (2.0 – 14.9) .00
Vulvar edema 28 (27) 3 (9) 3.8 (1.0 – 16.8) .03
Vulvar fissures 63 (60) 13 (38) 2.4 (1.0 – 5.8) .03
Microscopy with
pseudohyphae 28 (27) 3 (9) 3.8 (1.0 – 16.8) .03
Background
florian.beikert@gmx.de andreas.clad@uniklinik-freiburg.de
To date the pathogenesis of RVVC remains an unresolved issue. The stratum corneum of the vulva might represent an important site of C. albicans persistence in patients with RVVC.
Skin biopsies (figure 1) definitely prove C. albicans invasion of the stratum corneum, but they are painful and not suited for routine diagnosis.
Collection of swabs from the external vulva increases the detection rate of C. albicans in women with RVVC and is associated with pruritus, vulvar edema and fissures. Our data suggest that the moist keratinizing epithelium of the interlabial sulci, rather than the non-keratinizing epithelium of the vagina, respresents the site of C. albicans persistence and source of endogenous reinfection in patients with RVVC.
Based on this hypothesis and in analogy with the treatment of nail mycosis [9] we used a combination of the fungistatic fluconazole and fungicidal ciclopiroxolamin cream. A comparison of our treatment results and published fluconazole maintenance therapy regimens [10,11] is shown in table 3.
Although diagnosis and treatment of vulvovaginal candidiasis (VVC) is straightforward in most cases, 5-8% of women in child-bearing age will experience recurrent VVC (RVVC) over years. In most cases, recurrences are caused by identical Candida strains [1,2,3,4,5]. These findings suggest a site of Candida albicans persistence in female genitalia.
Adherence and invasion of the deep layers of the non- keratinizing epithelium [6,7] induce an inflammatory response - with leucocytes penetrating the vaginal walls - leading to the elimination of Candida albicans from the vagina. In uncomplicated cases single shot treatment with fluconazole is highly effective [8].
As a complication, C. albicans can infect the keratinizing epithelium of the external vulva (figure 1). The moist folds of the interlabial sulci might represent an important source of endogenous reinfections of the vagina in recurrent VVC.
1. To determine the value of C. albicans cultures from the external vulva (interlabial sulci) in women with RVVC.
2. To evaluate the effectiveness of combined systemic and topical treatment in women with RVVC.
At the first visit (day 0), 97 (70%) out of 139 women with RVVC had positive C. albicans cultures from both external vulva and vagina, 34 (24%) from the vagina only and 8 (6%) from the external vulva (interlabial sulci) only.
[1] Soll DR et al. (1989) Switching of Candida albicans during successive episodes of recurrent vaginitis, J. Clin. Microbiol
[2] Gary ES et al. (1991) Use of rDNA restriction fragment length polymorphisms to differentiate strains of C. albicans in women with VVC.Diagn Mirobiol Inf Dis
[3] Vazquez JA et al. (1994) Karyotyping of C. albicans isolates obtained longitudinally in women with RVVC. J Infec Dis [4] Fidel PL Jr, Sobel JD (1996) Immunopathogenesis of RVVC. Clin Microbiol Rev
[5] El-Din SS et al. (2001) An investigation into pathogenesis of VVC. Sex Transm Infec [6] Yun-Liang Yang (2003) Virulent factors of C. albicans. J Microbiol Immunol Infec
[7] Zink S et al. (1996) Migration of the fungal pathogen C. albicans across endothelial monolayers. Infect Immun
[8] Sobel JD et al. (1998) Vuvlovaginal candiasis: epidemiologic, diagnostic, and therapeutic considerations. Am J Obstet Gynecol [9] Ivan R.Bristow, Robert Baran (2006) Topical and oral combination therapy for toenail onychomycosis. J Am Podiatric Med Asso [10] Gilbert Donders et al. (2008) Individualized decreasing-dose maintenance fluconazole regimen for RVVC. Am J Obs & Gyn [11] Sobel JD et al. (2004) Maintenance fluconazole therapy for RVVC. The new Eng J of Med
Figure 1: Skin biopsy with pseudohyphae in the stratum corneum of the external vulva without visible inflammatory response. (Angela Köninger,MD, Dept. of Obstetrics and Gynecology, University of Essen)
Background Study design
Objectives
Discussion
Results
Table 2. Recurrence rates after treatment with 20-day fluconazole orally + ciclopiroxolamin cream topically
Follow-up Vulva-positive at day 0
Vulva-negative at day 0
Sum
n=98 (%) n=24 (%) n=122 (%)
After 1 month 3 (3) 1 (4) 4 (3)
After 3 months 16 (16) 4 (17) 20 (16)
After 6 months 26 (27) 7 (29) 33 (27)
After 9 months 32 (33) 8 (33) 40 (33)
After 12 months 33 (34) 8 (33) 41 (34)
Table 3. Recurrence rates after treatment of RVVC Follow-up Our data
n=122
Donders*[10] n=117 12 months fluconazole
Sobel** [11] n=387 6 months fluconazole After 3 months 16%
After 6 months 27% 15% 9%
After 9 months 33% 27%
After 12 months 34% 30% 57%
•600mg induction+200mg weekly for 2 months, 200mg biweekly for 3 months, 200mg monthly for 6 months
** 3 sequential 150mg at 72 hours intervals, 150mg weekly for 6 months
