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.

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.

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.

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.

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.

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.

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.

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.

[Saforelle - a new approach to treat vaginitis].

Infections of the vulva and vagina are one of the most common gynecological diseases. They can be determined by a variety of physical, chemical and biological factors. The main risk factors contributing to vaginitis are aerobic and anaerobic bacterias, fungal and viral infections, and irritants. Subjective complaints are pruritus, vulvar and/or perivulvar erytema and different in volume and characterization discharge. Excepting etiological treatment in most cases it is necessary to use additional agents, for example Saforelle.

Can Lactobacillus fermentum LF10 and Lactobacillus acidophilus LA02 in a slow-release vaginal product be useful for prevention of recurrent vulvovaginal candidiasis?: A clinical study.

OBJECTIVE: To assess the effectiveness of the association of 2 specific strains, Lactobacillus fermentum LF10 (DSM 19187) and Lactobacillus acidophilus LA02 (DSM 21717), specifically formulated in slow-release effervescent tablets, in patients with recurrent vulvovaginal candidiasis. STUDY DESIGN: The study was a clinical trial of 58 women diagnosed with recurrent VVC (≥4 culture-confirmed episodes in a 12-mo period). All patients were given 200 mg of fluconazole orally as an induction dose for 3 alternate days during the first treatment week. Afterward, the patients were given a new product formulated in slow-release vaginal tablets containing at least 0.4 billion live cells of each of lactobacillus L. fermentum LF10 and L. acidophilus LA02 (first phase of the prophylactic period), on alternate days for 10 consecutive nights. Patients who were still free of symptoms were given 1 vaginal tablet every week for the next 10 weeks (second phase of the prophylactic period). Patients asymptomatic after the total duration of the observation phase (7 mo) were considered as responders. RESULTS: During the second 10-week prophylactic phase, 49 of 57 (86.0%) patients remained free of clinical recurrence, whereas symptomatic VVC occurred in 8 patients (14.0%). During the 7-month follow-up, 42 patients of 49 (85.7%) were symptom free at the end of the protocol, whereas clinical recurrences occurred in 7 women (14.3%). Overall, 42 of 58 women enrolled in the study (72.4%) experienced no clinical recurrence throughout the 7-month observation phase (responders). CONCLUSIONS: This study strengthens the evidence supporting the use of specific lactobacilli with well-demonstrated activities associated with the creation and maintenance of a vaginal biofilm that hinders the persistence of an infection caused by Candida.

Vulvar pseudoepitheliomatous hyperplasia associated with herpes simplex virus type II mimicking cancer in an immunocompromised patient.

We report an exaggerated dermatological inflammatory condition in an immunocompromised patient. The patient was a 51-year-old woman who had HIV infection and a history of cervical cancer. Three years after highly active antiretroviral therapy with an improved immune status, and 2 years after remission of cervical cancer, she developed verrucous perineal masses. Provisional diagnosis was recurrent cervical cancer or primary vulvar cancer. Pathological features revealed pseudoepitheliomatous hyperplasia associated with herpes viral infection. After minimal response to systemic oral antiviral drugs and topical imiquimod, she had clinical resolution with the addition of systemic oral corticosteroid.

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.

Comparison of clinical and microbiological features of vulvovaginitis in prepubertal and pubertal girls.

BACKGROUND/PURPOSE: Vulvovaginitisis the most common gynecological problem of childhood. The aim of the study was to determine and compare clinical and microbiological features of vulvovaginitis in prepubertal and adolescent girls. METHODS: In this retrospective study, the records of patients who were diagnosed with vulvovaginitis between January 2005 and December 2010 in the pediatric outpatient clinic at Fatih University Hospital were retrieved. Information regarding age, symptoms, history of antibiotic use within 1 month prior to presentation, findings on urinalysis, serum antistreptolysin-O levels, and results of urine/vaginal cultures was collected. RESULTS: The records of 112 patients were evaluated, 72 of which were prepubertal (64.2%) and 40 were pubertal (35.7%) at the time of diagnosis. Thirty-eight prepubertal patients (52.7%) had a positive result on vaginal culture, the most commonly encountered microorganism being group A beta-hemolytic streptococcus (15.2%). Culture positivity rate in the pubertal group was 47.5% (19 patients), with Candida albicans being the most frequently isolated microorganism (27.5%). CONCLUSION: The etiopathogenesis and culture results differ between prepubertal and adolescent girls with vulvovaginitis, which should be taken into consideration in the treatment approach of this disorder.

Recurrent vulvovaginal candidosis: focus on the vulva.

Recurrent vulvovaginal candidosis is a frequent disease with a serious impact on women's quality of life. Mostly, recurrences are caused by identical Candida strains suggesting C. albicans persistence in the female anogenital area. Objectives of the presented work were to identify the site of C. albicans persistence, to determine clinical symptoms and signs related to C. albicans positive vulvar cultures and to introduce a new therapeutic approach in women with RVVC. Women with an acute, culture-confirmed episode of RVVC at time of visit were included in this prospective case series. Swabs were obtained from both vagina and inter-labial sulcus. Women received a combined 20-day regimen of 100 mg oral fluconazole and ciclopiroxolamin cream topically. Follow-up visits were at 3, 6, 9 and 12 months. Of 139 women, 105 (76%) had at least one C. albicans positive culture from the external vulva. Vulvar positive cultures correlated with pruritus (OR 5.4; P < 0.001), vulvar edema (OR 3.8; P = 0.03) and fissures (OR 2.4; P = 0.03). Recurrence rates were 27%, 33% and 34% (at 6, 9, 12 months, respectively). The external vulva appears to represent a site of C. albicans persistence and source of endogenous re-infection in patients with RVVC. The combined treatment compared favorably with published fluconazole maintenance regimens.

Genital candidosis in heterosexual couples.

BACKGROUND: Evidence suggests that Candida can be sexually transmitted; however, the contribution of sexual transmission to the pathogenesis of genital candidosis needs further elucidation. OBJECTIVE: The aim was to evaluate genital candidosis and its transmissibility in heterosexual couples. METHODS: Heterosexual couples were recruited among attendees of an Sexually Transmitted Diseases clinic. Specimens for yeast culture were collected from the glans penis and inner preputial layer using direct impression on CHROMagar Candida medium; vaginal exudates were collected using a cotton swab with subsequent inoculation on CHROMagar Candida medium. Mitochondrial DNA restriction analysis was performed to compare Candida isolates from both partners. RESULTS: A total of 64 couples were enrolled in the study. Frequency of sexual intercourse was significantly higher in couples where both partners yielded positive cultures and with at least one having genital candidosis (Odds ratios: 6.844; 95% CI 1.408-33.266). The same Candida species was found in both partners in 25% (16/64) of all couples but only 17.2% (11/64) were genetically similar. In total 12 of the 34 women suffering from vulvovaginal candidosis (VVC) had recurrent VVC (RVVC); two sexual partners of RVVC women (16.7%) had candida positive cultures, compared with 15 (68.2%) sexual partners of non RVVC women (Odds ratios: 0.093; 95% CI 0.016-0.544). CONCLUSIONS: Only in a few heterosexual couples a genetic similarity of Candida species recovered from both partners was found. RVVC women were more likely to have an asymptomatic candida negative sexual partner. This study suggests that male genitalia do not represent a relevant reservoir for RVVC; thus, the relevance of sexual transmission should not be emphasized.

An investigator blinded cross-over study to characterize the cutaneous effects and suitability of modern sanitary pads for menstrual protection for women residing in the USA.

BACKGROUND: The cutaneous and sensory effects of the practical usage of sanitary pads have been studied globally. However, clinical studies in the United States were conducted only quite a long time ago, and the results of these studies were not published. METHODS: Fifty-four women residing in the United States were asked to use commercially available sanitary pads with a nonwoven unique surface sheet and pads with a perforated film. This was a cross-over study design conducted over the course of two menstrual periods. A board certified dermatologist evaluated the levels of erythema and fissuring, burning, stinging and itching sensations based on clinical observations and interviews. Measurement of pH and swabs for bacteria counting of vulvar skin were also performed. Data from the first clinical evaluation conducted prior to the first menstrual cycle were used as the baseline. At the end of the study, the subjects were asked to complete self-assessment questionnaires about product suitability. RESULTS: Forty-two women (age: 18-50, mean: 37.5) completed the study. No signs of irritation or meaningful differences from the baseline were found in the clinical observations or in the interviews by the dermatologist for either product. No significant difference from baseline was found in the vulvar skin surface pH or in the number of total bacteria for either product. The results of the suitability indicated that the majority of subjects were highly satisfied with both types, but they especially preferred the sanitary pad with a nonwoven unique surface top sheet. CONCLUSION: These results revalidate the results of a previous clinical study in the United States and are consistent with recent reports of worldwide clinical trials of high performance sanitary pads.

Management of recurrent vulvo-vaginal candidosis as a chronic illness.

For sporadic acute Candida vaginitis, any oral or local antifungal therapy can be used. For women with recurrent vulvo-vaginal candidosis (RVC), on the other hand, such simple approaches are insufficient, regardless of the product chosen. Instead, RVC should be managed as any other chronic disease and requires long-term, prophylactic, suppressive antifungal treatment. A regimen using individualized, decreasing doses of oral fluconazole (the ReCiDiF regimen) was proven to be highly efficient and offered great comfort to the patients. During this regimen, it is crucial that patients are carefully examined by anamnestic, clinical, microscopic and culture-proven absence of Candida. If a relapse occurs, the medication is adjusted and efforts are taken to find a possible triggering factor for the reactivation of the infection. Care has to be taken not to accumulate 'don't do's', unless the efficiency of a measure has been proven, by trying to eliminate one risk factor at a time for 2 months. Known possible triggers to be kept in mind are (1) antibiotic use, (2) use of specific contraceptives, especially combined contraceptive pills, (3) disturbed glucose metabolism, (4) the use of personal hygienic products, and (5) tight clothing or plastic panty liners. In therapy-resistant cases, non-albicans infection must be ruled out, and alternative therapies should be tried. Boric acid is proven to be efficient in most of these resistant cases, but other non-azoles like amphotericin B, flucytosine, gentian violet, and even caspofungin may have to be tried. As a final remark it has to be said that many patients feel poorly understood and inefficiently managed by many care-givers, increasing their feelings of guilt and sexual inferiority. Therefore, attention has to be given to take the disease seriously, follow strict treatment regimens, and advise precisely and based on individual evidence concerning any possible risk factors for recurrence. In case of therapy-resistant vulvo-vaginitis, reconsider your diagnosis and/or consider referral to specialized therapists.