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

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.

Automated summary

This study investigated 144 human vaginal biopsy tissues and found that RVVC patients showed a large influx of neutrophils, lymphocytes, and plasma cells in the mucosa, basement membrane, and submucosa. Importantly, 29.2% of RVVC cases were found to have co-invasion of Gardnerella and fungi. Combining fluconazole with metronidazole resulted in higher treatment efficacy and lower recurrence rate.