Recent Advances in Presentation, Diagnosis and Treatment for Mixed Vaginitis.

Mixed vaginitis is the simultaneous presence of at least two types of vaginitis, contributing to an abnormal vaginal milieu and leading to vaginal symptoms and signs. However, associations between symptoms and the type of mixed vaginitis have not been clearly elucidated, and research on mixed vaginitis is still in the preliminary stage. Therefore, the pathogenic mechanism of mixed vaginitis remains understudied. Mixed vaginitis generally involves the formation of mixed biofilms. The study of polymicrobial interactions and mixed biofilms will provide a new idea for the understanding of mixed vaginitis. Moreover, this review summarizes some effective management and laboratory diagnosis of mixed vaginitis to avoid inappropriate therapy, recurrence, and reinfection. It is of high clinical importance to obtain relevant clinical data to improve clinical knowledge about mixed vaginitis.

A Clinicopathological Diagnostic and Therapeutic Approach to Cytolytic Vaginosis: An Extremely Rare Entity that may Mimic Vulvovaginal Candidiasis.

OBJECTIVES: Cytolytic vaginosis is a very rare entity that may be clinically misdiagnosed as vulvovaginal candidiasis. The aim of this study was to determine the incidence of cytolytic vaginosis in patients displaying symptoms similar to vulvovaginal candidiasis and to develop a clinicopathological diagnostic and therapeutic approach. MATERIALS AND METHODS: In total, 3000 cervical smear samples were evaluated at our center between 2015 and 2018. Patients whose PAP smears demonstrated significant epithelial cytolysis, naked nuclei, excessive increase in lactobacilli population, absent or minimal neutrophils and no microorganisms were subjected to a symptom assessment questionnaire and had their vaginal pHs measured. They were classified into two groups according to their complaints, symptoms and vaginal pHs: Cytolytic vaginosis and Asymptomatic intravaginal lactobacillus overgrowth. A standardized NaHCO3 Sitz bath therapy was applied to the cytolytic vaginosis group. RESULTS: Fifty-three of the patients (1.7%) were diagnosed as cytolytic vaginosis. After Sitz bath therapy, there was a statistically significant decrease in the cytolysis and lactobacillus scores of the patients. Vaginal discharge of 43 (81%) patients ceased completely while that of the remaining 10 (19%) patients decreased after the therapy. The improvement was statistically significant (P < 0.001). There was a complete resolution in 28 (96%) patients with severe; and in 21 (94%) patients with intermediate vaginal discomfort, after the therapy. Dyspareunia was resolved in 35 (97%) patients (P < 0.001). CONCLUSION: Cytolytic vaginosis is a rare entity that can be diagnosed with the help of cytopathology and has a therapy based on the modulation microbiota by decreasing the vaginal pH.

Laboratorial aspects of cytolytic vaginosis and vulvovaginal candidiasis as a key for accurate diagnosis: a pilot study / Aspectos laboratoriais da vaginose citolítica e candidíase vulvovaginal como uma chave para o diagnóstico preciso: Um estudo piloto

Abstract Objective To identify clinical, microscopic, and biochemical characteristics that differentiate cytolytic vaginosis (CV) from vulvovaginal candidiasis (VVC). Methods The present cross-sectional study analyzed the vaginal contents of 24 non-pregnant women aged 18 to 42 years who were attended at the Genital Infections Clinic at Centro de Atenção Integral à Saúde da Mulher da Universidade Estadual de Campinas (CAISM-UNICAMP). They were diagnosed either with (CV = 8, VVC = 8) or without vulvovaginitis or vaginal dysbiosis (controls). The socio-demographic, clinical, and gynecological data were obtained from a detailed patient interview. Samples of the vaginal contents were collected for analysis of vaginal pH, gram stain, and specific fungal culture. The Kruskal-Wallis and Fisher exact tests were used to compare the differences between the groups. Odds ratios were used to compare the categorical variables. The significance level was considered at p < 0.05. Results Both women with CV and VVC had a lumpy vaginal discharge (p = 0,002) and vaginal hyperemia (p = 0.001), compared with controls. The inflammatory process was more intense in the VVC group (p = 0.001). In the CV group, there was statistical significance for the lactobacillus amount (p = 0.006), vaginal epithelium lysis (p = 0.001), and vaginal pH (p = 0.0002). Conclusion Cytolytic vaginosis and VVC diagnoses rarely differ on clinical characteristics but have different laboratorial findings. The present study highlights the importance of conducting an accurate investigation through laboratory tests rather than clinical criteria to avoid misdiagnosis.

Resumo Objetivo Identificar características clínicas, microscópicas e bioquímicas que diferenciam a vaginose citolítica (VC) da candidíase vulvovaginal (CVV). Métodos O presente estudo de corte transversal analisou o conteúdo vaginal de 24 mulheres não grávidas, com idades entre 18 e 42 anos, atendidas no ambulatório de Infecções Genitais do Centro de Atenção Integral à Saúde da Mulher da Universidade Estadual de Campinas (CAISM-UNICAMP). Elas foram diagnosticadas com (CV = 8, CVV = 8) ou sem vulvovaginite ou disbiose vaginal (controles = 8). Os dados sociodemográficos, clínicos e ginecológicos foram obtidos em uma entrevista detalhada do paciente. Amostras do conteúdo vaginal foram coletadas para análise do pH vaginal, coloração de Gram e cultura específica de fungos. Os testes exatos de Kruskal-Wallis e Fisher foram utilizados para comparar as diferenças entre os grupos. A razão de chances foi utilizada para comparar as variáveis categóricas. O nível de significância considerado foi de p < 0,05. Resultados As mulheres com VC e CVV apresentaram corrimento vaginal irregular (p = 0,002) e hiperemia vaginal (p = 0,001), em comparação aos controles. O processo inflamatório foi mais intenso no grupo CVV (p = 0,001). No grupo VC, houve significância estatística para a quantidade de lactobacilos (p = 0,006), lise do epitélio vaginal (p = 0,001) e pH vaginal (p = 0,0002). Conclusão Os diagnósticos de VC e CVV raramente diferem nas características clínicas, mas apresentam achados laboratoriais diferentes. O presente estudo destaca a importância de conduzir uma investigação precisa por meio de testes laboratoriais, em vez de critérios apenas clínicos, a fim de evitar erros de diagnóstico.

Characterization of the vaginal microbiome during cytolytic vaginosis using high-throughput sequencing.

BACKGROUND: Cytolytic vaginosis (CV) is a common disease that results in pruritus, dyspareunia, and vulvar dysuria. However, the pathological mechanisms of the disease are still unclear. Compared to traditional methods, high-throughput sequencing can obtain more accurate qualitative and quantitative information on the microbiome. METHODS: We collected 75 samples from 32 healthy women (average age 44 ± 8) and 43 patients with CV (average age 38 ± 8). We used high-throughput sequencing of the 16S rRNA V3-V4 region to characterize and compare the vaginal microbiota of patients with CV and healthy women and to identify potential biomarkers for CV. RESULTS: The vaginal pH of patients with CV was ≤3.8, and the vaginal concentration of H2 O2 was ≥2 µmol/L. Colony densities of Lactobacillus spp. in patients with CV ranged from +++ (5-30) to ++++ (>30) and were significantly higher than those in healthy women. High-throughput sequencing showed that Lactobacillus was the most prominent genus both in patients with CV and in healthy women, with abundances of 83.8% and 97.2%, respectively (P < 0.001). Lactobacillus crispatus was more abundant in patients with CV, whereas Lactobacillus sp. L-YJ was more abundant in healthy women, with area under the curve (AUC) values of 0.9375 and 0.8379, respectively. CONCLUSION: The abundance of Lactobacillus spp. in CV patients was significantly different from that of healthy patients. Two suitable biomarkers, L. crispatus and Lactobacillus sp. L-YJ, were identified. These results will be useful for the identification of women at risk of serious illness before they develop obvious symptoms.

Vaginosis citolítica en pacientes con diagnóstico clínico de vulvovaginitis candidiásica / Cytolytic vaginosis in patients with clinical diagnosis of vulvovaginal candidiasis

La microbiota vaginal en la edad fértil está dominada por Lactobacillus spp. Su sobrecrecimiento provoca el aumento en la producción de ácido láctico, disminución del pH vaginal y lisis de células del epitelio vaginal, causando vaginosis citolítica, la cual se confunde con vulvovaginitis candidiásica (VVC) por la aparición de signos y síntomas similares. Se determinó la prevalencia de vaginosis citolítica, así como sus características clínicas y epidemiológicas en pacientes que consultaron con clínica sugestiva de VVC durante el período agosto-septiembre del año 2015. Se encontraron 12 pacientes con clínica compatible de VVC. En 11 (91,7%) se realizó el diagnóstico de vaginosis citolítica y en 1 (8,3%) de vulvovaginitis candidiásica. El 63,7% de las pacientes (7) tenían diagnóstico previo de VVC recurrente. Los síntomas más frecuentes fueron prurito vaginal o vulvar y secreción vaginal blanquecina de aspecto grumoso como leche cortada. La clínica iniciaba entre los 4-6 días posteriores a la menstruación, y desaparecía días antes o justo con el inicio de una nueva fase menstrual. En conclusión, se encontró que en las pacientes examinadas la sintomatología de ambas patologías resultó indistinguible, por tanto el diagnóstico clínico no es suficiente y debe recurrirse al diagnóstico de laboratorio para distinguir entre vaginosis citolítica y vulvovaginitis candidiásica.

The vaginal microbiota in fertile age is dominated by Lactobacillus spp. Its overgrowth causes increased production of lactic acid, decreased vaginal pH and lysis of cells of the vaginal epithelium, causing cytolytic vaginosis, which can be confused with vulvovaginal candidiasis (VVC) due to the similar signs and symptoms. The prevalence of cytolytic vaginosis, as well as its clinical and epidemiological characteristics was determined in patients who consulted with suggestive signs and symptoms of VVC during the period August to September of the year 2015. Twelve patients with signs and symptoms compatible with VVC were considered. Of those, 11 (91.7%) were diagnosed as cytolytic vaginosis and 1 (8.3%) corresponded to vulvovaginal candidiasis. From the 12 patients included, 7 (63.7%) had previous diagnosis of recurrent VVC. The most frequent symptoms recorded were vaginal or vulvar pruritus and whitish, cheesy or curd-like vaginal discharge. Signs and symptoms started between 4 to 6 days after menstruation, and disappeared days before or just with the onset of a new menstrual cycle. In conclusion, it was found that in the patients examined, signs and symptoms of both pathologies were indistinguishable. Therefore, the clinical diagnosis is not enough and laboratory studies should be used to distinguish between cytolytic vaginosis and vulvovaginal candidiasis.

Vaginosis citolítica: presentación de un caso clínico / Cytolytic vaginosis: presentation of a clinical case

La vaginosis citolítica, descrita hace 30 años como citólisis de Döderlein, es frecuente en mujeres en la edad reproductiva y, por las características de flujo vaginal blanquecino y síntomas clínicos, es indistinguible de la vulvovaginitis micótica. Se presenta el caso de una paciente, con diagnóstico clínico presuntivo de vulvovaginitis por Candida spp. a repetición, tratada empíricamente con antifúngicos por año y medio sin ninguna mejoría. Luego de estudios microbiológicos, la coloración de Gram, demostró la presencia de 50 bacilos grampositivos por campo y abundantes núcleos celulares desnudos. El cultivo resultó puro para Lactobacillus spp., lo que permitió confirmar el diagnóstico de vaginosis citolítica. La paciente fue tratada con ampicilina-sulbactam y no ha vuelto a presentar recidivas. En conclusión, es fundamental determinar el pH vaginal de las pacientes en la consulta, así como practicar una coloración de Gram de la secreción vaginal para poner en evidencia los cambios celulares por el exceso de ácido en la vagina y así evitar tratamientos antifúngicos innecesarios que acrecentarán los trastornos de la microbiota vaginal.

Cytolytic vaginosis, described 30 years ago as Döderlein cytolysis, is common in women of reproductive age and, due to the characteristics of whitish vaginal discharge and clinical symptoms, is indistinguishable from mycotic vulvovaginitis. We describe the case of a patient with presumptive clinical diagnosis of recurrent vulvovaginitis by Candida spp. treated empirically with antifungal agents for one and a half years without improvement. After microbiological studies, Gram staining demonstrated the presence of 50 Gram-positive bacilli per field and abundant nude cell nuclei. The culture recovered pure Lactobacillus spp. which permitted the diagnosis of cytolytic vaginosis. The patient was treated with ampicillin-sulbactam and since, has not had recurrences. In conclusion, it is essential to examine the pH of the patient vaginal discharge, as well as to practice a Gram staining of the vaginal secretion to demonstrate the cellular changes produced by the excess of acid in the vagina and therefore avoid unnecessary antifungal treatments that will produce undue changes of the vaginal microbiota.

Differential expression of lactic acid isomers, extracellular matrix metalloproteinase inducer, and matrix metalloproteinase-8 in vaginal fluid from women with vaginal disorders.

OBJECTIVE: Do metabolites in vaginal samples vary between women with different vaginal disorders. DESIGN: Cross-sectional study. SETTING: Campinas, Brazil. SAMPLE: Seventy-seven women (39.9%) with no vaginal disorder, 52 women (26.9%) with vulvovaginal candidiasis (VVC), 43 women (22.3%) with bacterial vaginosis (BV), and 21 women (10.9%) with cytolytic vaginosis (CTV). METHOD: Concentrations of D- and L-lactic acid, extracellular matrix metalloproteinase inducer (EMMPRIN), and matrix metalloproteinase-8 (MMP-8), and the influence of Candida albicans on EMMPRIN production by cultured vaginal epithelial cells, were determined by enzyme-linked immunosorbent assay (ELISA). Associations were determined by the Mann-Whitney U-test and by Spearman's rank correlation test. MAIN OUTCOME MEASURES: Metabolite levels and their correlation with diagnoses. RESULTS: Vaginal concentrations of D- and L-lactic acid were reduced from control levels in BV (P < 0.0001); L-lactic acid levels were elevated in CTV (P = 0.0116). EMMPRIN and MMP-8 concentrations were elevated in VVC (P < 0.0001). EMMPRIN and L-lactic acid concentrations (P ≤ 0.008), but not EMMPRIN and D-lactic acid, were correlated in all groups. EMMPRIN also increased in proportion with the ratio of L- to D-lactic acid in controls and in women with BV (P ≤ 0.009). Concentrations of EMMPRIN and MMP-8 were correlated in controls and women with VVC (P ≤ 0.0002). Candida albicans induced EMMPRIN release from vaginal epithelial cells. CONCLUSIONS: Vaginal secretions from women with BV are deficient in D- and L-lactic acid, women with VVC have elevated EMMPRIN and MMP-8 levels, and women with CTV have elevated L-lactic acid levels. These deviations may contribute to the clinical signs, symptoms, and sequelae that are characteristic of these disorders.

Vaginosis citolítica: un diagnóstico diferencial poco frecuente de vulvovaginitis micótica a repetición / Cytolytic vaginosis: a rare differential diagnosis of fungal recurrent vulvovaginitis

Los síntomas compatibles con vaginitis y vaginosis, son la causa más frecuente de consulta al ginecólogo. La descarga vaginal abundante y el prurito, constituyen la primera sospecha de estas patologías. Sin embargo, debemos tener presente que el aumento significativo de lactobacilos, conocido como lactobacilosis, puede expresarse también con los mismos síntomas y signos de una vulvovaginitis micótica. Si esta condición se mantiene en el tiempo, puede provocar un grado de acidez anormal en la vagina, y puede llevar a una lisis de las células epiteliales que se conoce como vaginosis citolítica. Este diagnóstico, aunque es poco frecuente, debemos sospecharlo especialmente, en aquellas mujeres que relatan tener múltiples consultas por candidiasis vaginal, con escasa o nula respuesta frente a la terapia antimicótica.

The symptoms consistent with vaginitis and vaginosis are the most common cause of the visit to the gynecologist. Heavy vaginal discharge and pruritus are the first suspicion of this pathology. However, the significant increase in lactobacilli, known as lactobacilosis can be expressed also with the same symptoms and signs of a fungal vulvovaginitis. If this condition is maintained overtime, can cause abnormal acidity in the vagina, and may lead to epithelial cell lysis, which is known as cytolytic vaginosis. This diagnosis, although rare, should be suspected especially in women who reported having multiple consultations for vaginal candidiasis, with little or no response to antifungal therapy.