He Xinyi, Tang Qionglan, Zhan Fengshu, Mao Yiwen, Ye Fei, Weng Zeping, Jiang Xuefeng, Swidsinski Alexander
Department of Obstetrics and Gynecology, the First Affiliated Hospital of Jinan University, Guangzhou, China.
Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
J Obstet Gynaecol Res. 2023 May;49(5):1443-1451. doi: 10.1111/jog.15577. Epub 2023 Feb 11.
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.
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.
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.
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.
复发性外阴阴道念珠菌病（RVVC）是一种由念珠菌属引起的慢性、难治性阴道感染，影响各年龄、种族和社会背景的女性。大多数RVVC研究使用动物模型，目前仍缺乏对人体组织样本的观察以及降低复发率的有效治疗方法。
我们通过免疫组织化学观察CD163巨噬细胞和NLRP3的表达，还采用荧光原位杂交技术对144份人类阴道活检组织（48例RVVC、48例VVC、48例健康志愿者）进行细菌和真菌共感染情况调查，并探讨甲硝唑联合用药治疗RVVC的效果。
大量中性粒细胞、淋巴细胞和浆细胞浸润黏膜、基底膜和黏膜下层，同时伴有NLRP3炎性小体明显过表达。RVVC患者中，CD163巨噬细胞常浸润于基底膜下方，29.2%的病例发现加德纳菌和真菌共同侵袭阴道黏膜。RVVC阴道黏膜组织病理学显示以中性粒细胞为主导的黏膜炎症反应，这可能涉及NLRP3的激活和M2巨噬细胞（CD163）的免疫耐受。在6个月的随访中，氟康唑联合甲硝唑可取得更高的有效率（95.8%对70.8%），且复发率降低更多（8.3%对37.5%）。
人类阴道黏膜的炎性侵袭与RVVC的联合药物治疗及复发相关。联合用药未来还需进一步评估。
