Effectiveness of Combination of Tibolone and Lactobacilli Plus Lactoferrin in Postmenopausal Women with Vulvar Vestibular Pain: A Preliminary Report.

BACKGROUND: Postmenopausal dyspareunia and vulvar pain are common complaints, affecting about 60% of women within a few years after hormone levels begin to decline (such as estrogen and androgen). Atrophic changes mainly located in the vulvar vestibule and vulnerability to vulvovaginal infections in postmenopause could be predisposing factors to the development of vulvar burning/pain and introital dyspareunia (vestibulodynia secondary to atrophy). Tibolone is the most effective and safe alternative for treating menopausal symptoms. The role of Lactobacilli and lactoferrin shows its effectiveness in the treatment of vaginal microbiota dysbiosis. The aim of the present study was to assess the efficacy of the combination of tibolone and an oral-specific Lactobacilli mixture in combination with bovine lactoferrin as synergistic therapy for the treatment of vestibulodynia related to atrophy. METHODS: In this study, we included 35 postmenopausal women with at least 1 year of amenorrhea, affected by vulvar burning/pain and introital dyspareunia. All participants received treatment with open-label, oral Tibolone 2.5 mg and Lactobacilli mixture (5 × 109 CFU per capsule) in combination with bovine lactoferrin (Respecta®). Each product was taken once daily for 90 days. RESULTS: After 90 d of therapy with TIB+ Respecta®, in 30 women that completed the treatment, there was a statistically significant decrease from the baseline in the mean of the Visual Analog Scale for vulvar burning/pain and a reduction in scores in the pain evaluation test. CONCLUSIONS: This study provides evidence that the combination of TIB+ Respecta® was effective in reducing symptoms related to vestibular pain and hypersensitivity in a postmenopausal setting.

Histopathologic patterns of female genital tuberculosis with clinical correlation: a 10-year (2013-2022) retrospective cross-sectional study.

OBJECTIVE: Underdiagnosis of female genital tuberculosis (FGTB) often leads to infertility. In this study, we aimed to determine the site and histopathologic patterns of FGTB and its correlation with clinical presentation and acid-fast bacilli (AFB) status. METHODS: A retrospective cross-sectional study was conducted on 122 patients with a histopathological diagnosis of FGTB at the Department of Pathology, College of Health Sciences (CHS), Tikur Anbessa Specialized Hospital (TASH), Addis Ababa University (AAU), from January 1, 2013, to August 30, 2022. RESULTS: Female genital tuberculosis was found in 0.94% of the gynecology specimens examined. The most common presentations were menstrual disturbance, abdominopelvic pain, and infertility. Among patients with FGTB, 4.6% exhibited misleading clinical and radiologic findings, leading to suspicion of malignancy and subsequent aggressive surgical management. The endometrium was the most frequently affected organ, followed by the fallopian tube, ovary, cervix, and vulva. In the majority of tuberculous endometritis cases (53.3%), histopathology revealed early-stage granulomas. Acid-fast bacilli were found in a significant proportion (42.6%) of FGTB tissues with TB histopathology. The ovary had the highest rate of AFB detection, followed by the fallopian tube, endometrium, and cervix. CONCLUSION: Female genital tuberculosis should be considered in reproductive-age women presenting with menstrual irregularities, abdominopelvic pain, infertility, or an abdominopelvic mass. The endometrium is commonly affected, displaying early granulomas with low AFB positivity.

Characterization of Bovine papillomavirus 28 (BPV28) and a novel genotype BPV29 associated with vulval papillomas in cattle.

Papillomavirus (PV) infections are associated with the development of cutaneous and mucosal tumors in humans and various animal species. In humans, infection of high-risk human PVs (HPVs) causes anogenital cancers, while in animals, anogenital-associated PVs are not well understood. Among animal PVs, Bos taurus PVs (BPVs) have the most diverse genotypes, up to 28 of them. The present study will report two unique BPVs identified in vulval papilloma lesions from two Holstein Friesian cattle by conventional PCR and sequencing. In the first case, BPV28 harboring two L1 open reading frames (ORFs) due to a five-nucleotide deletion was identified. In the second case, histologically diagnosed as papilloma, an unclassified BPV genotype was detected. However, in both cases, the immunohistochemistry against PV antigen was negative. The full genome of the unclassified BPV was amplified by inverse PCR and analyzed by genome-walking sequencing. The L1 nucleotide sequence was most identical to BPV genotype 6 (BPV6), showing 78 % identity, indicating that this novel BPV should be classified as species Xipapillomavirus 1, genotype BPV29. The mRNA expression of three early genes (E1, E2, E10), but not L1, was confirmed in both BPV28- and BPV29-detected papilloma lesions. The present study suggests the involvement of novel types of BPV in vulval papilloma. The alteration of BPV28 pathogenicity due to the frameshift mutation of L1 needs to be elucidated in the future.

Features of the Vaginal and Vestibular Microbioma in Patients With Vestibulodynia: A Case-Control Study.

OBJECTIVE: Our objective was to determine the role of vaginal and/or vestibular microbiota disturbance as an associated factor of symptom characteristic of provoked vestibulodynia (PVD). STUDY DESIGN: In an observational case-control study, the bacterial microbiomes in the vagina and vestibule from 20 women with PVD and 18 healthy controls were compared using a 16S rRNA gene-based molecular analysis. Clinical data were recorded through a 0- to 10-point visual analog scale related to dyspareunia and vulvovaginal pain/burning. RESULTS: Comparative assessment of the bacterial taxa (cutoff ≥15%) revealed 105 genera in the vaginal samples of PVD patients and 113 genera in the vestibular samples. Similarly, 120 genera were detected in the vaginal samples and 151 in the vestibular samples of the control group. Bacterial complexity was higher in the vestibular samples than in vaginal samples in both groups, without statistically significant differences. The following 3 dominant taxonomic units were found: Lactobacillus, Gardnerella, and Atopobium in PVD patients and Lactobacillus, Gardnerella, and Bifidobacterium in the control group. Lactobacillus gasseri was dominant only in women with PVD, showing a significant correlation with burning/pain intensity and dyspareunia severity (0.255 and 0.357, respectively, p < .001). CONCLUSIONS: Our data suggest that bacterial communities in vaginal discharge are an important contributor to the vestibular microbiota. Lactobacillus gasseri may be an element of vulnerability toward the development of vaginal dysbiosis. We can postulate its association as a potential etiologic organism in some individuals, either by itself or in some combination with other trigger factors.

Vulvar tuberculosis.

Genital tuberculosis (TB) in women is a chronic disease with low-grade symptoms. Genital tract tuberculosis is usually secondary to extragenital TB. The fallopian tubes are most commonly affected, and along with endometrial involvement, it causes infertility in such patients. Involvement of the cervix and the vulva is very rare. We present one such rare case of vulvar tuberculosis presented with a large ulcer diagnosed on histopathology and treated with antitubercular chemotherapy.

Kerion of the pubis and vulva with bacterial superinfection: a rare occurrence.

Kerion is a severe hypersensitivity reaction to fungal infection that is rarely seen in the groin. Frequent shaving of pubic hair and religious conservatism surrounding genital hygiene are common among Bedouin women in the Negev Desert, and may predispose to kerion. This case highlights the clinical course of a 20-year-old Bedouin woman who presented with severe kerion celsi of the pubis and vulva with secondary bacterial infection. The patient was successfully treated with intravenous antibiotics, oral antifungal medication and wet topical dressings. The case outlines the risk factors and treatment for severe kerion celsi of the groin, as well as possible preventive measures that may reduce its incidence.

Comparative study of vulva and abdominal skin microbiota of healthy females with high and average BMI.

BACKGROUND: Obesity is known to modulate human health in a number of ways including altering the microbiome of the gut. Very few studies have examined the how obesity may affect the microbiomes of sites distant to the gut. We hypothesized that vulva and abdominal skin may be especially susceptible to body mass index (BMI)-induced alterations in biophysical properties and the microbiome due increased maceration and skin folds at those sites. The aim of this study was to determine if high BMI (≥30) was associated with alterations in the biophysical properties and microbiomes of vulva and abdominal skin. RESULTS: The vulvar microbial communities of healthy reproductive-aged females were examined using 16S rRNA sequencing techniques. Our results show that vulvar pH of women with high body mass index (BMI) was statistically higher than that of women with average BMI. Phylogenetic analysis of the vulvar microbiota indicated that women with average BMI have a predominately Lactobacillus-dominated flora, whereas women with high BMI and higher pH were predominately colonized by Finegoldia and Corynebacterium. This BMI-associated shift in microbiota was not observed in samples collected from the exposed skin around the belly, indicating the effect is not global. CONCLUSION: These results indicate that physiological changes associated with changes in BMI may modulate the vulva microbiome.

Tuberculosis and HIV co-infection; the deadly duos in vulva.

Human Immunodeficiency Virus induced immune suppression leads the way for various infections with tuberculosis being the most common. Tuberculosis of the vulva is an extremely rare entity and is seen in only 1-2% of genital TB with increased risk in HIV co-infection. The co-infection places an immense burden on health care systems and poses particular diagnostic & therapeutic challenges with high mortality and morbidity. We present, here, a rare case of a 47 years postmenopausal female, who presented with itchy ulcerating lesions in the vulva with diagnostic dilemma turned to be vulval tuberculosis and during investigations, was found to be co-infected with HIV. The early diagnosis of TB and HIV in atypical looking lesions of vulva with high index of suspicion could lead to improved outcome.

Sexual behaviour and extra-genital colonisation in women treated for recurrent Candida vulvo-vaginitis.

OBJECTIVE: This study analyses a relation between sexual habits and the presence of Candida in extra-genital locations as well as a potential effect on therapy response. MATERIAL AND METHODS: Candida cultures were obtained from mouth, nose, anus, urine and perineum of 117 women enrolled in a RVVC treatment trial (ReCiDiF). Sexual behaviour and carriage rates of extra-genital Candida of women responding well to treatment were compared to that of non-responders. RESULTS: Most respondents were heterosexual. All but one practiced vaginal sex. Regular receptive oral sex was not related to multiple site colonisation with Candida (OR = 1.27; CI95% 0.36-4.48), nor to non-response to therapy (OR = 1.3; CI 95% 0.41-4.73). Also, masturbation was not related to response to therapy (OR 0.8; CI95% 0.31-1.84), nor was anal sex (OR = 0.54; CI95% 0.11-2.72). CONCLUSION: Neither oral nor casual anal sex, nor masturbation can be held responsible for the association of the multiple site/anal colonisation with Candida and inferior response to fluconazole maintenance therapy. Changing sexual behaviour during fluconazole maintenance treatment for RVVC in otherwise healthy women should not be advocated. Also, treatment of asymptomatic sexual partners of women with RVVC is not recommended.

Is Vulvovaginal Lichen Planus Associated With Squamous Cell Carcinoma?

OBJECTIVE: The aim of the study was to assess for the presence of vulvar lichen planus (LP) in association with human papillomavirus (HPV)-independent squamous cell carcinoma (SCC). MATERIALS AND METHODS: We performed a clinicohistopathologic review of consecutive vulvectomies and wide local excisions for HPV-independent vulvar or vaginal SCC from 2007 to 2017. Data collected included site of SCC, adjacent precursor lesions and dermatoses, dermatologic treatment, and outcome. RESULTS: There were 43 cases of primary HPV-independent vulvar SCC treated by excision, but no vaginal cancers. Eighteen women (42%) had a preoperative diagnosis of lichen sclerosus (LS); none had a diagnosis of LP. Topical corticosteroids were prescribed in 19 (44%) of 43, with 4 women placed on maintenance therapy. Tumors arose from the labia minora, labia majora, and periclitoris, but not from vestibule or perianus. On histopathological review, LS was present in 41 (95%) of 43 specimens, 1 had a nonspecific lichenoid reaction, and 1 had lichen simplex; both of the latter had subsequent biopsies showing LS. Lichen planus was not seen in association with SCC. Differentiated vulvar intraepithelial neoplasia (dVIN) was present in 38 (88%) of 43 specimens, whereas 1 had acanthosis with altered differentiation and 4 (9%) had no precursor lesion. Differentiated vulvar intraepithelial neoplasia had standard, basaloid, and hypertrophic morphology, superficially resembling erosive LP in 9 (24%) of 38 and hypertrophic LP in 6 (16%) of 38. CONCLUSIONS: Lichen planus was not seen in association with HPV-independent vulvar SCC, whereas LS was underrecognized and inadequately treated in this group. Pathologists should be aware that dVIN may superficially resemble erosive or hypertrophic LP.

Skin diseases of the vulva: Infectious diseases.

A multitude of infectious diseases of viral (genital herpes, herpes zoster, genital warts and molluscum contagiosum), bacterial (syphilis, chancroid, lymphogranuloma venereum, donovanosis, erysipelas, cellulitis and necrotising fasciitis, folliculitis, impetigo, bartholin gland abscess, trichomycosis and erythrasma), fungal (candidiasis and dermatophytosis) and parasitic (pediculosis pubis) origin may affect the vulvar area. Herein, we review the infections and their skin manifestations in the vulvar area.

Candida vulvovaginitis: A store with a buttery and a show window.

Although being an utterly frequent, non-mortal, yet distressing disease, and despite good knowledge of the pathogenesis and the availability of specific and safe treatment, vulvovaginal Candida (VVC) infection remains one of the most enigmatic problems for both physicians and patients. Good treatment requires a proper diagnosis. Too many caregivers (and patients treating themselves) react too simple-minded on the symptoms of VVC and treat VVC where they see it on the vulva. In this opinion paper, we plea for a thorough examination of women with VVC, especially in those women who suffer from recurrent disease since a long time, sometimes decades, which necessitates intensive examination of the vaginal flora, as this is invariably the reservoir for relapses and recurrent vulvitis. Examination of such complicated cases requires experienced clinical judgement, expertise bedside phase contrast microscopy of fresh vaginal fluid, classical cultures on Sabouroud medium and, if still unresolved, repetitive cultures taken by the patient herself at moments of symptoms, and/or nuclear acid amplification techniques to detect Candida genes in the vaginal fluid. Even if only vulvitis is evident, thorough expert examination of vaginal fluid is obligatory to diagnose VVC.

Vaginal Dysbiosis from an Evolutionary Perspective.

Evolutionary approaches are powerful tools for understanding human disorders. The composition of vaginal microbiome is important for reproductive success and has not yet been characterized in the contexts of social structure and vaginal pathology in non-human primates (NHPs). We investigated vaginal size, vulvovaginal pathology and the presence of the main human subtypes of Lactobacillus spp./ BV-related species in the vaginal microflora of baboons (Papio spp.). We performed morphometric measurements of external and internal genitalia (group I, n = 47), analyzed pathology records of animals from 1999-2015 (group II, n = 64 from a total of 12,776), and evaluated vaginal swabs using polymerase chain reaction (PCR) (group III, n = 14). A total of 68 lesions were identified in 64 baboons. Lactobacillus iners, Gardnerella vaginalis, Atopobium vaginae, Megasphaera I, and Megasphaera II were not detected. L. jensenii, L. crispatus, and L. gasseri were detected in 2/14 (14.2%), 1/14 (7.1%), and 1/14 (7.1%) samples, respectively. BVAB2 was detected in 5/14 (35.7%) samples. The differences in the vaginal milieu between NHP and humans might be the factor associated with human-specific pattern of placental development and should be taken in consideration in NHP models of human pharmacology and microbiology.

Prevalence and antifungal susceptibility of Candida albicans and its related species Candida dubliniensis and Candida africana isolated from vulvovaginal samples in a hospital of Argentina.

Candida africana taxonomical status is controversial. It was proposed as a separate species within the Candida albicans species complex; however, phylogenetic analyses suggested that it is an unusual variety of C. albicans. The prevalence of C. albicans-related species (Candida dubliniensis and C. africana) as vulvovaginal pathogens is not known in Argentina. Moreover, data on antifungal susceptibility of isolates causing vulvovaginal candidiasis is scarce. The aims of this study were to establish the prevalence of C. dubliniensis and C. africana in vaginal samples and to evaluate the antifungal susceptibilities of vaginal C. albicans species complex strains. We used a molecular-based method coupled with a new pooled DNA extraction methodology to differentiate C. dubliniensis and C. africana in a collection of 287 strains originally identified as C. albicans isolated from an Argentinian hospital during 2013. Antifungal susceptibilities to fluconazole, clotrimazole, itraconazole, voriconazole, nystatin, amphotericin B and terbinafine were evaluated by using the CLSI M27-A3 and M27-S4 documents. Of the 287 isolates, 4 C. dubliniensis and one C. africana strains (1.39% and 0.35% prevalence, respectively) were identified. This is the first description of C. africana in Argentina and its identification was confirmed by sequencing the ITS2 region and the hwp1 gene. C. dubliniensis and C. africana strains showed very low MIC values for all the tested antifungals. Fluconazole-reduced-susceptibility and azole cross-resistance were observed in 3.55% and 1.41% of the C. albicans isolates, respectively. These results demonstrate that antifungal resistance is still a rare phenomenon in this kind of isolates.

In vitro evaluation of nutrients that selectively confer a competitive advantage to lactobacilli.

An assay was developed that tested the ability of Lactobacillus acidophilus to outcompete a challenge of Escherichia coli in a mixed culture containing different test nutrients. Using this assay, addition of fructo-oligosaccharide to the media allowed L. acidophilus to outcompete a challenge of E. coli, whereas in a mixed culture without the prebiotic the trend was reversed. Growth curves generated for E. coli in a single culture showed that fructo-oligosaccharide did not affect growth, indicating that the carbohydrate was not toxic to E. coli. This indicates that fructo-oligosaccharides may increase the ability of beneficial microbes to outcompete a pathogenic challenge. These results were confirmed using a skin simulant model that incorporates growth of the organisms at an air-surface interface to mimic the vulvar environment. It is possible to use a co-culture assay as an in vitro screening tool to define nutrients that confer a competitive advantage to beneficial flora specific to the female urogenital tract.

Vaginal nystatin versus oral fluconazole for the treatment for recurrent vulvovaginal candidiasis.

Recurrent vulvovaginal candidiasis (RVVC) is a common condition that can physically and psychologically impact patients. We compared the efficacy and safety of vaginal nystatin suppositories for 14 days each month versus standard oral fluconazole regimens for the treatment for RVVC. Patients (n = 293) were enrolled in the study from April 2010 to September 2013. After the initial therapy, the mycological cure rates were 78.3% (119/152) and 73.8% (104/141) in the nystatin group and fluconazole group, respectively (95% CI, 0.749-2.197, p > 0.05). The mycological cure rates at the end of maintenance therapy were 80.7% (96/119) and 72.7% (72/99) in the two groups, respectively (95% CI, 0.954-3.293, p > 0.05).The mycological cure rates at the end without treatment for 6 months were 81.25% (78/96) and 82.19% (60/73) in the two groups, respectively (95% CI, 0.427-2.066, p > 0.05). The mycological cure rates of RVVC caused by C. albicans were 84.0% (89/106) and 81.8% (99/121) in the two groups, respectively. The mycological cure rates of RVVC caused by C. glabrata were 64.3% (27/42) and 12.5% (2/16) in the two groups, respectively. The initial and 6-month maintenance therapy were successful in five of the nine patients in the nystatin group with RVVC caused by fluconazole-resistant Candida, whereas in the fluconazole group, initial therapy failed in all patients with RVVC caused by fluconazole-resistant Candida (n = 7). We conclude that both fluconazole and nystatin therapies are effective in treating RVVC. Nystatin may also be effective for the treatment for RVVC caused by C. glabrata or fluconazole-resistant Candida.