Necrotizing Vaginitis in a 45-Year-Old Woman With Metastatic Breast Cancer.

Vaginitis emphysematosa (VE) is a rare, benign, and self-limited condition often diagnosed by the presence of intramuscular vaginal air observed on computed tomography (CT) scan. Although it is a nonpathologic, self-limited condition requiring no intervention, it is important to rule out a more serious infectious pathology. This report highlights a clinical dilemma and the potential consequences of over-reliance on CT in distinguishing benign VE from pathologic necrotizing vaginitis. A high clinical suspicion for infection should be maintained, especially when relevant clinical and laboratory markers suggest a more serious pathology. We describe the case of a 45-year-old woman who presented to the hospital with abdominal pain and vaginal bleeding. CT scan demonstrated intramuscular vaginal air, which was reported as VE. Classic imaging findings of VE falsely reassured clinicians. She died shortly thereafter of necrotizing vaginitis.

Prospective Evaluation of Molecular Assays for Diagnosis of Vaginitis.

Molecular tests to diagnose conditions involving the disruption of normal microbiota are difficult to optimize. Using Nugent-scored Gram stain (NS) as the reference standard, we evaluated the performance of 3 molecular assays for the diagnosis of bacterial vaginosis (BV) and examined the impact of an incremental increase in bacterial targets. The BD Affirm assay includes a DNA probe for Gardnerella vaginalis, the Hologic transcription-mediated amplification (TMA) analyte-specific reagent (ASR) assay adds a second Lactobacillus sp. target, and the recently cleared in vitro diagnostic use (IVD) Aptima BV assay includes a third target (Atopobium vaginae). The diagnosis of vulvovaginal candidiasis (VVC) by the Affirm and Candida vaginitis Hologic TMA ASR assays was assessed using microscopy for yeast as the reference standard. From May to December 2018, 111 women with vaginitis symptoms prompting the clinician to order an Affirm test were enrolled with informed consent for the collection of additional specimens. Clinicians accurately predicted BV as the most likely diagnosis for 71% of the 45 patients with BV. Coinfection occurred in 13.5% of patients. For BV, the specificity of the Aptima IVD assay (86.3%) was higher than the Affirm assay (60.6%, P = 0.0002), but sensitivities were not significantly different. For VVC, the sensitivity of the ASR assay (100%) was higher than Affirm (75.9%; P = 0.023) and the specificity of the Affirm assay (98.8%) was higher than the ASR assay (86.6%; P = 0.004).

The role of the miR1976/CD105/integrin αvß6 axis in vaginitis induced by Escherichia coli infection in mice.

Vaginitis is very common among women, especially women of childbearing age, and is associated with significantly increased risk of preterm birth and pelvic inflammatory diseases. An imbalance in the vaginal flora, the primary cause of vaginitis, promotes the initiation and progression of vaginal infections. However, the responsible mechanisms are still poorly understood. Using a murine vaginitis model of Escherichia coli infection, we demonstrated that decreased expression of microRNA1976 and increased expression of CD105 and integrin αvß6 were closely associated with the progression of vaginal infection. Importantly, we demonstrated for the first time that the microRNA1976/CD105/integrin αvß6 axis regulates E. coli-mediated vaginal infection in mice, as evidenced by the finding that E. coli-induced vaginal infection was reversed by microRNA1976 overexpression and exacerbated by CD105 overexpression. The regulation of CD105 and integrin αvß6 by microRNA1976 was further confirmed in a murine model of vaginitis with adenoviral vector treatment. Taken together, our data suggested that microRNA1976 negatively regulates E. coli-induced vaginal infection in mice at least in part by suppressing CD105 and integrin αvß6 expression. These findings may provide new insight into the mechanisms of E. coli-induced vaginitis, identify a novel diagnostic biomarker and a potential therapeutic target for flora imbalance-associated vaginitis.

Mechanisms of sexually transmitted infection-induced inflammation in women: implications for HIV risk.

INTRODUCTION: Globally, sexually transmitted infections (STI) affect >300 million people annually, and are a major cause of sexual and reproductive health complications in women. In this commentary, we describe how STIs interact with the immune and non-immune cells, both within and below the cervicovaginal mucosal barrier, to cause inflammation, which in turn has been associated with increased HIV acquisition risk. DISCUSSION: STIs have a major impact on the female genital mucosa, which is an important biological and physical barrier that forms the first line of defence against invading microorganisms such as HIV. Pattern recognition of STI pathogens, by receptors expressed either on the cell surface or inside the cell, typically triggers inflammation at the mucosal barrier. The types of mucosal responses vary by STI, and can be asymptomatic or culminate in the formation of discharge, ulcers and/or warts. While the aim of this response is to clear the invading microbes, in many cases these responses are either evaded or cause pathology that impairs barrier integrity and increases HIV access to target cells in the sub-mucosa. In addition, innate responses to STIs can result in an increased number of immune cells, including those that are the primary targets of HIV, and may contribute to the association between STIs and increased susceptibility to HIV acquisition. Many of these cells are mediators of adaptive immunity, including tissue-resident cells that may also display innate-like functions. Bacterial vaginosis (BV) is another common cause of inflammation, and evidence for multiple interactions between BV, STIs and HIV suggest that susceptibility to these conditions should be considered in concert. CONCLUSIONS: STIs and other microbes can induce inflammation in the genital tract, perturbing the normal robust function of the mucosal barrier against HIV. While the impact of STIs on the mucosal immune system and HIV acquisition is often under-appreciated, understanding their interactions of the infections with the immune responses play an important role in improving treatment and reducing the risk of HIV acquisition. The frequent sub-clinical inflammation associated with STIs underscores the need for better STI diagnostics to reverse the immunological consequences of infection.

Successful mast-cell-targeted treatment of chronic dyspareunia, vaginitis, and dysfunctional uterine bleeding.

Dyspareunia, vaginitis and dysfunctional uterine bleeding (DUB) are common problems which, despite their polygenicity, commonly appear idiopathic and treatment-refractory. Mast cell (MC) activation syndrome (MCAS) is a newly-recognised, prevalent, chronic multisystem polymorbidity of general themes of inflammation ± allergic-type phenomena ± aberrant growth/development in assorted tissues. MCs produce significant quantities of heparin, too. As such, MCAS may underlie some cases of chronic dyspareunia, vaginitis or DUB. We report five such patients; all who responded well to MC-targeted treatment. We review aspects of MC biology and pathobiology of potential relevance to otherwise idiopathic persistent inflammatory or coagulopathic genital tract problems. Diagnostic testing for MCAS may be warranted in some patients with chronic dyspareunia, vaginitis or DUB (especially patients whose histories well fit the general profile of MCAS), and prospective therapeutic trials of MC-directed topical and/or systemic therapies may be warranted in such populations. Impact statement What is already known on this subject? Chronic, idiopathic, treatment-refractory female genital tract inflammation or bleeding are common problems for which mast cell (MC) disease, previously generally thought to consist of just rare cases of mastocytosis, and is seldom considered in the differential diagnosis. What do the results of this study add? The substantial prevalence of the newly recognised 'mast cell activation syndrome' (MCAS), featuring chronic inappropriate MC activation with little-to-no MC neoplasia, and its clinical presentation with chronic multisystem inflammation ± allergic-type phenomena ± aberrant growth/development in assorted tissues, raises the possibility that MCAS might underlie the aforementioned genital tract problems, especially in patients whose larger clinical presentations fit the MCAS profile. We report five example patients (among many more we have similarly treated) who enjoyed excellent responses to safe, inexpensive MC-targeted treatments, often given just intravaginally. What are the implications of these findings for clinical practice and/or further research? Our report identifies a potentially significant new MC-focused direction, of relevance to millions of affected women worldwide, for clinical treatment as well as for basic and clinical research, which historically has yielded major advancements disappointingly disproportionate to the scope of the affected population.

Deciphering the complex interplay between microbiota, HPV, inflammation and cancer through cervicovaginal metabolic profiling.

BACKGROUND: Dysbiotic vaginal microbiota have been implicated as contributors to persistent HPV-mediated cervical carcinogenesis and genital inflammation with mechanisms unknown. Given that cancer is a metabolic disease, metabolic profiling of the cervicovaginal microenvironment has the potential to reveal the functional interplay between the host and microbes in HPV persistence and progression to cancer. METHODS: Our study design included HPV-negative/positive controls, women with low-grade and high-grade cervical dysplasia, or cervical cancer (n = 78). Metabolic fingerprints were profiled using liquid chromatography-mass spectrometry. Vaginal microbiota and genital inflammation were analysed using 16S rRNA gene sequencing and immunoassays, respectively. We used an integrative bioinformatic pipeline to reveal host and microbe contributions to the metabolome and to comprehensively assess the link between HPV, microbiota, inflammation and cervical disease. FINDINGS: Metabolic analysis yielded 475 metabolites with known identities. Unique metabolic fingerprints discriminated patient groups from healthy controls. Three-hydroxybutyrate, eicosenoate, and oleate/vaccenate discriminated (with excellent capacity) between cancer patients versus the healthy participants. Sphingolipids, plasmalogens, and linoleate positively correlated with genital inflammation. Non-Lactobacillus dominant communities, particularly in high-grade dysplasia, perturbed amino acid and nucleotide metabolisms. Adenosine and cytosine correlated positively with Lactobacillus abundance and negatively with genital inflammation. Glycochenodeoxycholate and carnitine metabolisms connected non-Lactobacillus dominance to genital inflammation. INTERPRETATION: Cervicovaginal metabolic profiles were driven by cancer followed by genital inflammation, HPV infection, and vaginal microbiota. This study provides evidence for metabolite-driven complex host-microbe interactions as hallmarks of cervical cancer with future translational potential. FUND: Flinn Foundation (#1974), Banner Foundation Obstetrics/Gynecology, and NIH NCI (P30-CA023074).

2018 European (IUSTI/WHO) International Union against sexually transmitted infections (IUSTI) World Health Organisation (WHO) guideline on the management of vaginal discharge.

Four common pathological conditions are associated with vaginal discharge: bacterial vaginosis, aerobic vaginitis, candidosis, and the sexually transmitted infection, trichomoniasis. Chlamydial or gonococcal cervical infection may result in vaginal discharge. Vaginal discharge may be caused by a range of other physiological and pathological conditions including atrophic vaginitis, desquamative inflammatory vaginitis, cervicitis, and mucoid ectopy. Psychosexual problems may present with recurrent episodes of vaginal discharge and vulval burning. These need to be considered if tests for specific infections are negative. Many of the symptoms and signs are non-specific and a number of women may have other conditions such as vulval dermatoses or allergic and irritant reactions.

Genital diseases in the mature woman.

Vulvovaginal conditions are common in mature women. This reflects age-related changes in immunity and skin barrier function of vulvovaginal tissues. Vaginal atrophy is commonly complicated by dryness and inflammation, which makes postmenopausal atrophic vaginitis a virtually ubiquitous condition. The differential of vaginitis includes inflammatory, infectious, and malignant diseases, plus drug hypersensitivity. Atrophic vaginitis is treated with estrogen replacement therapy. Vulvovaginal malignant melanoma occurs predominantly in postmenopausal women and carries a poor prognosis. Similarly, the incidence of vulvovaginal malignancies, such as squamous cell carcinoma and extramammary Paget disease, rises exponentially after 65 years of age. Early diagnosis of these malignancies is of utmost importance. Lichen sclerosus et atrophicus and vulvovaginal candidosis are among the most common postmenopausal vulvovaginal conditions. Lichen sclerosus et atrophicus is associated with significant morbidity, and its management can be challenging. The incidence of vulvovaginal candidosis increases in patients on estrogen replacement therapy.

Inguinal Hyperhidrosis: Case Report of an Uncommon Cause of Vaginitis.

BACKGROUND: Hyperhidrosis (excessive sweating) affects 1%-3% of the population. Primary focal hyperhidrosis most commonly affects the axilla, palms, and soles. There are few case reports of hyperhidrosis of the genital region, typically described as inguinal hyperhidrosis or Hexsel's hyperhidrosis. CASE: A 17-year-old girl presented with 3 years of copious, clear "vaginal" discharge causing significant emotional distress. After extensive gynecologic and urologic workup was negative, further review of her history was notable for excessive axillary sweating. Inguinal hyperhidrosis was suspected and she was treated with topical aluminum chloride hexahydrate with complete resolution of her symptoms. SUMMARY AND CONCLUSIONS: Inguinal hyperhidrosis, compared with other sites, is not widely described in the literature. Awareness of inguinal hyperhidrosis is important because it causes significant social embarrassment but is a treatable condition.

Microperforate Hymen and Pyocolpos: A Case Report and Review of the Literature.

BACKGROUND: Microperforate hymen is a rare congenital anomaly characterized by a small pinpoint opening in the hymen; girls with this anomaly are prone to develop ascending pelvic infections and recurrent urinary tract infections. CASE: We report the case of a 3-year-old girl who presented with fevers, abdominal pain, recurrent vaginitis, and dysuria. She was found to have a microperforate hymen and pyocolpos. She was treated with intravenous antibiotics and underwent hymenotomy and drainage of 150 cc of purulent fluid. SUMMARY AND CONCLUSION: This case highlights the need to perform thorough genital inspection and to consider hymenal anomalies in the differential diagnosis of girls who present with recurrent dysuria, vaginitis, fevers, and abdominal pain. Early intervention might prevent the development of pyocolpos and other sequelae associated with this anomaly.

Risk of bacterial vaginosis, Trichomonas vaginalis and Candida albicans infection among new users of combined hormonal contraception vs LNG-IUS.

OBJECTIVE: The study assessed the risk of bacterial vaginosis, Trichomonas vaginalis and Candida albicans infection among new users of either a combined oral contraceptive pill (COC) or the levonorgestrel-releasing intrauterine system (LNG-IUS). METHODS: This prospective observational study included 430 women, without active vaginitis at inclusion, who were divided into two groups according to their chosen method of contraception: COC group (n = 236) and LNG-IUS group (n = 194). Participants were examined for bacterial vaginosis, T. vaginalis and C. albicans infection initially and then at 6 weeks, 6 months and 12 months after the start of contraceptive use. Data were collected and statistically analysed. RESULTS: The rates of acquisition of bacterial vaginosis, T. vaginalis and C. albicans infection during follow-up were significantly increased and comparable between the groups (p < .001) and decreased in frequency over time (p < .05). The rates of acquisition of bacterial vaginosis among COC users (Nugent score) were 24.6, 18.6 and 15.2% and among LNG-IUS users 20.6, 13.5 and 9.3% at 6 weeks, 6 months and 12 months, respectively (p < .001). Body mass index >25 kg/m2, history of bacterial vaginosis, history of sexually transmitted infection, vaginal douching more than five times per week and coital frequency more than five times per week were strong risk factors for acquisition of bacterial vaginosis during the follow-up period (p < .001). CONCLUSIONS: The use of COCs and LNG-IUS is associated with an increased, comparable risk of acquisition of bacterial vaginosis, T. vaginalis and C. albicans infections, which is greatest during initial use of the method but which improves over time.

Vaginitis: Beyond the Basics.

Vaginal complaints are one of the most common reasons women seek the advice of a health care provider. Uncomplicated infections such as vulvovaginal candidiasis, bacterial vaginosis, or trichomoniasis are easy to diagnose and treat. However, about 8% of patients will have a more complicated course with failure to respond to treatment or rapid recurrence of symptoms. Understanding the need for a methodical, diagnostic approach to help these women with recurrent or refractory cases of vaginal symptoms will aid the clinician achieve successful patient outcomes.

Inhalant allergy compounding the chronic vaginitis syndrome: characterization of sensitization patterns, comorbidities and responses to sublingual immunotherapy.

OBJECTIVE: To characterize sensitization patterns, diagnoses and comorbidities, and to assess the response of lower genital tract symptoms to sublingual immunotherapy for airborne allergens in a select population of patients with chronic vaginitis. METHODS: Fifty-two patients referred for allergy evaluation over a 44 month period were studied. Charts were retrospectively reviewed to establish: (1) gynecological diagnoses, (2) allergic-immunological diagnoses, and (3) IgE-mediated sensitivity to airborne allergens on presentation. Patients were contacted at 9-50 months of treatment to assess response to sublingual immunotherapy based on a questionnaire addressing frequency and severity of symptoms and use of medication to control symptoms. RESULTS: Recurrent vulvovaginal candidiasis was identified in 34 (65 %); vulvar vestibulitis syndrome in 12 (23 %); and contact dermatitis in 10 (19 %) patients. Comorbidities included: non-reflux gastrointestinal complaints in 11 (21 %), gastroesophageal reflux in 5 (9 %), migraines in 9 (17 %), chronic non-migrainous headaches in 8 (17 %), and chronic sinusitis in 6 patients (11 %). Asthma was diagnosed in 8 patients (15 %). Oral allergy syndrome was present in 6 (11 %). Most frequent sensitivities were to: ragweed in 33 (63 %), molds in 26 (50 %), dust mites in 23 (44 %), and grass in 12 (23 %) patients. Mono-sensitization was demonstrated for ragweed in 7 (13 %), and for molds, dust mites and grass for 3 (5 %) patients each. Candida sensitization was identified in 15 patients with chronic vaginitis (28 %). Eleven patients with recurrent vulvovaginal diagnosis (32 %) showed Candida sensitization. Response to immunotherapy was generally favorable with pruritus/irritation being more responsive than visceral pain. CONCLUSIONS: In a Midwestern referral population, chronic vaginitis compounded by inhalant allergy showed: (1) high incidence rate of recurrent vulvo-vaginal candidiasis, (2) Candida IgE-mediated sensitization in less than one-third of patients with recurrent vulvovaginal candidiasis, (3) comorbid conditions not dissimilar to those of other allergic patients, and (4) allergen sensitization pattern typical for the Midwest.

Diversion neovaginitis after sigmoid vaginoplasty: endoscopic and clinical characteristics.

OBJECTIVE: To assess the endoscopic characteristics of the sigmoid-derived neovagina, which have been scarcely described. DESIGN: Prospective observational study. SETTING: University tertiary medical center. PATIENT(S): Patients that underwent sigmoid vaginoplasty. INTERVENTION(S): Patients were invited yearly to undergo neovaginoscopy and sigmoidoscopy, preceded by taking a medical history and physical examination, as routine follow-up. MAIN OUTCOME MEASURE(S): Endoscopic signs of neovaginal inflammation. RESULT(S): Thirty-four patients with a sigmoid neovagina underwent a total of 43 combined neovaginoscopies and sigmoidoscopies. After a mean postoperative time of 23 months, the most notable endoscopic features of the sigmoid-derived neovagina comprised a diminished vascular pattern, edema, granularity, friability, decreased resilience, and erythema. In the control rectosigmoidoscopy images, no concurrent abnormalities were observed. When applying the MAYO score to the neovaginal images, 12 (35%) patients scored MAYO 0, 19 (56%) MAYO I, 3 (9%) MAYO II, and none MAYO III. The presence of neovaginal discharge and malodor correlated with inflammatory endoscopic alterations. CONCLUSION(S): The endoscopic appearance of a sigmoid segment after use in neovaginoplasty differs significantly from that of the remaining rectosigmoid. Inflammatory changes of the sigmoid-derived neovagina were observed in most patients. Clinically, the inflammatory changes appear similar to those encountered in diversion colitis.