Management of recurrent vulvovaginal candidosis: Narrative review of the literature and European expert panel opinion

Donders, Gilbert; Sziller, István Oszkár; Paavonen, Jorma; Hay, Phillip; Seta, Francesco De; Bohbot, Jean-Marc; Kotarski, Jan; Vives, Jordi Antoni; Szabó, Béla; Cepuliené, Ramona; Mendling, Werner

doi:10.3389/fcimb.2022.934353

Cited by 28 publications

(27 citation statements)

References 111 publications

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“…It is generally recognized that RVVC is an inflammatory activation state, 12 but there is still no histological observation and evidence of human vaginal lesions. In the present study, histological observation of vaginal biopsy in RVVC intuitively confirmed that a large number of neutrophils, lymphocytes, and plasma cells infiltrated into the mucosa, basement membrane, and submucosa, which was the same direction that bacteria and fungi co‐infiltrate vaginal mucosa, described by Swidsinski et al 4 The fixation or adhesion of Candida microorganisms to the vaginal surface may be through the invasion of the hyphal mucosa.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory invasion on human vaginal mucosa correlated with combined drug treatment and recurrence in recurrent vulvovaginal candidiasis

Tang

Zhan³

et al. 2023

J of Obstet and Gynaecol

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Aim Recurrent vulvovaginal candidiasis (RVVC) is a chronic, difficult to treat vaginal infection, caused by Candida species, which affects women of all ages and ethnic and social background. Most RVVC studies use animal models, and there is still a lack of observation on human tissue samples and effective therapy to reduce recurrence. Materials and Methods We observed CD163+ macrophages and NLRP3 expression by immunohistochemistry, also investigated bacteria and fungi co‐invasion by fluorescence in situ hybridization from 144 human vaginal biopsy tissues (48 RVVC, 48 VVC, 48 healthy volunteers), and we also explored the effect of combining metronidazole in the treatment of RVVC. Results A large number of neutrophils, lymphocytes and plasma cells infiltrated the mucosa, basement membrane and submucosa, accompanied by significantly overexpressed NLRP3 inflammasome. While CD163+ macrophages often infiltrated under the basement membrane in patients with RVVC, 29.2% of cases were found Gardnerella and fungi jointly invaded the vaginal mucosas. RVVC vaginal mucosal histopathology revealed mucosal inflammatory responses dominated by neutrophils, which may involve activation of NLRP3 and immune tolerance of M2 macrophages (CD163+). Fluconazole combined with metronidazole can achieve higher efficiency (95.8% vs. 70.8%) and reduce the recurrence rate more (8.3% vs. 37.5%) at 6‐month follow‐up. Conclusion Inflammatory invasion on human vaginal mucosa correlated with combined drug treatment and recurrence in RVVC. The combined medication will need to further evaluate in future.

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Section: Discussionmentioning

confidence: 99%

Inflammatory invasion on human vaginal mucosa correlated with combined drug treatment and recurrence in recurrent vulvovaginal candidiasis

Tang

Zhan³

et al. 2023

J of Obstet and Gynaecol

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“…27 Currently, there is not a specific questionnaire that accurately assesses the consequences of RVVC on the QoL and sex life of people with RVVC; however, one is reported to be in development. 2 Future trial design incorporating a measurable framework of benefits of participant support, with a focus on psychological health, is warranted. This aligns with recommendations that RVVC patients receive psychological referrals as part of their long-term management.…”

Section: Adherence To Trial Procedures and Data Collection Limitationsmentioning

confidence: 99%

Intravaginal Combination Therapy of Acetic and Lactic Acid in premenopausal women with recurrent vulvovaginal candidiasis: A randomized, double-blind placebo-controlled feasibility trial

Strydom,

Khan,

Walpola

et al. 2023

Womens Health (Lond Engl)

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Background: Recurrent vulvovaginal candidiasis management primarily entails azole therapy used as required or as an extended daily or weekly maintenance therapy for 6 months or more. Unfortunately, relapse within 3–6 months of ceasing maintenance therapy is experienced for more than half the patients, for whom indefinite treatment is required. Objectives: To explore the feasibility of trial design examining a prophylaxis treatment to prevent recurrent vulvovaginal candidiasis symptomatic episodes and reduce adverse effects. Study Design: A double-blinded randomized controlled feasibility trial was conducted in Australia. Women with recurrent vulvovaginal candidiasis were enrolled. Methods: An intravaginal prophylaxis application of lactic acid and acetic acid (Intravaginal Combination Therapy of Acetic and Lactic Acid) was compared with placebo. Primary outcomes comprised recruitment and retention, compliance to study medications and study assessments. Secondary outcomes included the reduction of symptomatic recurrence over the trial period and the acceptability, satisfaction, safety and tolerability of the intervention. The feasibility of quality-of-life measures was also explored. Results: Fifteen participants were enrolled and randomized (active = 9, placebo = 6). Consent rate was 23.4%. Eight participants were lost to follow-up (active = 5, placebo = 3). Forty-seven per cent of participants (n = 7) were 100% compliant with the intervention, six of which completed the trial with good assessment compliance. The blinding process was effective. The study demonstrated a reduction in relapse in both active and placebo groups with only four participants across both groups reporting symptomatic episodes while enrolled. The intervention demonstrated good tolerability. Quality-of-life data showed minimal variance with a high quality-of-life measure. Conclusion: This trial assesses the feasibility of conducting a large-scale study exploring the efficacy of the Intravaginal Combination Therapy of Acetic and Lactic Acid intravaginal intervention and hints on the importance of psychological support through appropriate disease-specific communication and clinical attention. Consideration of the reported recruitment challenges, the inclusion of suitable quality-of-life measures and digital data collection is warranted for adaptation to a fully powered trial.

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“…The available treatment is related to therapeutic constraints like low therapeutic efficacy that may lead to recurrence, poor bioavailability, flushing due to high content of vaginal discharge, poor patient compliance, low adhesion to the vaginal mucosa, frequent dosing, and long duration of therapy . To overcome the aforesaid challenges, a strategic formulation with improved therapeutic outcomes for eliminating and countering the recurrence of the disease is necessary . Therefore, developing a novel system is required for localized drug delivery with a prolonged release in a single dose and enhanced fiber adhesion, retention, and drug penetration to the vaginal mucosa .…”

Section: Introductionmentioning

confidence: 99%

“…10 To overcome the aforesaid challenges, a strategic formulation with improved therapeutic outcomes for eliminating and countering the recurrence of the disease is necessary. 11 Therefore, developing a novel system is required for localized drug delivery with a prolonged release in a single dose and enhanced fiber adhesion, retention, and drug penetration to the vaginal mucosa. 12 There is a dearth of evidence regarding luliconazole (LCZ) use in vaginal candidiasis treatment.…”

Section: ■ Introductionmentioning

confidence: 99%

Investigation of Luliconazole-Loaded Mucoadhesive Electrospun Nanofibers for Anticandidal Activity in the Management of Vaginal Candidiasis

Vidyadhari,

Singh,

Singh

et al. 2023

ACS Omega

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In this study, we fabricated and evaluated luliconazoleloaded electrospun nanofibers for anticandidal activity in the management of vaginal candidiasis. Polycaprolactone (PCL)/gelatin nanofibers were designed by the electrospinning technique, and the Box−Behnken design (BBD) was adopted for optimization to get tailored fibers. The luliconazole (LCZ) drug was mixed into different concentrations (2.5, 5, 7.5, and 10%) of tea tree oil (TT oil) and loaded into the PCL/gelatin nanofibrous mats. The effective anticandidal potential of nanofiber samples were analyzed by the disk-diffusion method. Scanning electron microscopy (SEM), Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), XRD analysis, and in silico study were performed. The entrapment efficiency, swelling degree, mechanical strength, contact angle, mucoadhesion, drug release, and permeation study were assessed. The average diameter of the PCL/gelatin-optimized nanofiber was 153 nm. SEM reflected that the fabricated nanofibers were uniform and bead-free. FTIR and DSC analyzed the interaction and physical entrapment of the drug in the polymeric fibers. The entrapment efficiency of the drug-loaded nanofiber was found to be 89.2 ± 0.8%. Maximum swelling percentages at 4 h were 40.8, 18.9, and 14.0% and contact angles were 46.5°, 62.95°, and 65.78°for the blank, TT oil-loaded, and drug-loaded nanofiber, respectively, which indicated the hydrophilic nature of the fibers. The drug-loaded nanofiber had a high tensile strength with satisfactory mucoadhesive property that led to its adhesion to the vaginal mucosa with no tear. The drug-loaded nanofiber had a cumulative drug release of 67.7 ± 3.4% in 48 h, and the 12.8 ± 0.53 mm of zone of inhibition (ZOI) in 48 h illustrated an effective anticandidal activity. The TT oil-loaded nanofiber also exhibited a small ZOI of 4.3 ± 0.30 mm, indicating a synergistic effect to the antifungal activity of the drug-loaded nanofiber. LCZ-loaded nanofibers can emerge as a novel approach for vaginal drug delivery in the treatment of candida infection. Thus, this pharmaceutical investigation can help in formulating preclinical and clinical models.

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Management of recurrent vulvovaginal candidosis: Narrative review of the literature and European expert panel opinion

Cited by 28 publications

References 111 publications

Inflammatory invasion on human vaginal mucosa correlated with combined drug treatment and recurrence in recurrent vulvovaginal candidiasis

Inflammatory invasion on human vaginal mucosa correlated with combined drug treatment and recurrence in recurrent vulvovaginal candidiasis

Intravaginal Combination Therapy of Acetic and Lactic Acid in premenopausal women with recurrent vulvovaginal candidiasis: A randomized, double-blind placebo-controlled feasibility trial

Investigation of Luliconazole-Loaded Mucoadhesive Electrospun Nanofibers for Anticandidal Activity in the Management of Vaginal Candidiasis

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