Localized Provoked Vulvodynia Research Articles

Multimodal and Interdisciplinary Interventions for the Treatment of Localized Provoked Vulvodynia: A Scoping Review of the Literature from 2010 to 2023.

Localized provoked vulvodynia (LPV) is a chronic condition characterized by pain in the vulvar vestibule, which can be provoked by pressure or touch and which is not tied to a clear underlying cause. Research into the etiology of and most appropriate treatment strategy for LPV is still limited. Using Arksey and O'Malley's model for scoping reviews, we evaluated the research question: what is the current evidence regarding the efficacy/effectiveness of multimodal or interdisciplinary interventions for the treatment of LPV? We collated and analyzed articles from 2010 to 2023 to capture the current research landscape. Our review identified 27 studies, which either compared treatments between classes (eg pharmacologic versus psychologic modalities) or described interdisciplinary treatment programs. We identify several trends in the literature. First, outcome measures are inconsistent between studies, often unvalidated, and may not adequately mirror patient concerns. Second, the absence of appropriate comparator groups in many studies restricts providers' ability to appraise which treatments may be most efficacious. Third, selection bias and demographic homogeneity limit generalizability. Finally, we highlight the need for head-to-head trials of vestibulectomy with other treatments considered first line for vulvodynia management. There is insufficient evidence to suggest the superiority of one treatment modality for LPV relative to others or to recommend a particular interdisciplinary management strategy. Future research should use a head-to-head design where sham control is impossible, incorporate patient-centered outcome measures, and investigate impacts of treatment among diverse samples of LPV patients.

Physical Modalities for the Treatment of Localized Provoked Vulvodynia: A Scoping Review of the Literature from 2010 to 2023.

Localized provoked vulvodynia (LPV) is a prevalent sexual health condition with significant negative impacts on quality of life. There is a lack of consensus regarding effective management. We used Arksey and O'Malley's five-step method to identify, collate, and evaluate literature published between 2010 and 2023. The scoping review investigated the efficacy or effectiveness of interventions in the management of LPV. The aim of this paper is to map the literature on the efficacy or effectiveness of physical interventions. The review produced 19 primary studies of physical interventions for LPV. These include acupuncture, laser therapy, physiotherapy, transcutaneous electrical nerve stimulation, low-intensity shockwave therapy, transcranial direct current stimulation, and vestibulectomy. Published studies that investigated a range of physical treatments for LPV showed some positive effects, except for transcranial direct-current stimulation. The remaining modalities demonstrated improved sexual pain and treatment satisfaction, when measured. Findings were mixed for non-sexual pain. There was insufficient evidence to draw conclusions regarding other outcomes. Researchers are encouraged to conduct larger, high-quality studies that sample more diverse patient populations and use patient-oriented outcomes to assess effectiveness of physical modalities.

Pharmacological Treatments for Localized Provoked Vulvodynia: A Scoping Review

Introduction Localized provoked vulvodynia (LPV) is a chronic pain condition without an identifiable cause that is localized to a portion of the vulva and provoked by pressure or touch. LPV is a commonly occurring but poorly understood condition lacking consensus on management. Method This scoping review used Arksey and O’Malley’s approach to identify and evaluate literature published between 2010 and 2023 that addressed the question: What is the current evidence on the efficacy or effectiveness of pharmacological treatments in the management of LPV? Results This review evaluated 18 papers reporting on the efficacy or effectiveness of oral, topical, and injectable medications. Seven of the studies were randomized controlled trials. Oral gabapentin and oral desipramine showed some improvement in sexual function compared to placebo. Small sample sizes and methodological issues limited confidence in interpreting findings. Pain was reduced in descriptive studies of tricyclic antidepressants, milnacipran, injectable anesthetics, and botulinum toxin. Where pain did not improve with treatment, some oral medications improved participants’ mood and sexual function. Some topical agents may be effective in reducing peripherally mediated neuropathic pain. Botulinum toxin was the most well-studied injectable but yielded mixed outcomes related to pain, quality of life, and sexual function. Conclusion There is a lack of convincing evidence to draw conclusions about the efficacy or effectiveness of pharmacological therapies for LPV. The breadth of therapies for treating LPV warrants the development of evidence-based, consensus guidelines for measuring treatment outcomes and improving comparisons across studies. Recommendations for research include addressing methodological shortcomings and diversifying the participant pool to increase the generalizability of findings.

Changes in the Vaginal Microbiota of Women With Secondary Localized Provoked Vulvodynia.

The etiology of localized provoked vulvodynia (LPV) remains unknown, but observations suggest the involvement of the vaginal microbiota. We examined the vaginal microbiota of women with LPV and healthy controls, upon after a low-oxalate diet (LOD). A total of 9 women diagnosed with secondary LPV and 21 healthy controls were recruited from the Galilee Medical Center in Israel and subjected to prospective evaluations of their vaginal microbiota. Total DNA was extracted from vaginal discharge samples provided before and after following LOD for 3 weeks and was then subjected to 16S sequencing. Data obtained were then used to evaluate α and β diversity, identify differentially abundant bacterial taxa in LPV, and determine their impact on the metabolism. These evaluations revealed decreased diversity in the vaginal microbiota of women with LPV and identified the Ochrobactrum genus and Pseudomonadaceae family as indicators for LPV. In addition, we identified 23 differentially expressed bacterial metabolic pathways between the LPV and control samples and revealed that LOD could induce changes in the β diversity of LPV vaginal microbiomes, which was further supported by some degree of pain reduction in patients. Localized provoked vulvodynia and LOD were associated with shifts in the vaginal microbiota. However, the impact of these changes on the development of LPV requires additional studies with a larger cohort.

“Off-label” use of common medicines could target the vulvodynia mechanism

ABSTRACT Introduction Vulvodynia is a devastating disease that significantly impairs the quality of life of our patients. Although there is at least limited evidence for the use of various therapeutics, none target the underlying causes of disease, perhaps save surgical excision of the affected tissue. One of our goals is to elucidate the poorly understood causes of vulvodynia to improve treatment and possibly avoid surgical intervention. This approach can be used to identify new targets for less invasive medical therapies. Inflammation has been implicated in the vulvodynia mechanism, and targeting different aspects of this mechanism or augmenting the resolution of inflammation are reasonable strategies for treatment. Objective We have identified several agents that have the capacity to alleviate vulvar allodynia, but these will need to undergo lengthy drug development steps. Therefore, we also wish to identify FDA-approved agents that could act on the vulvodynia mechanism. Methods We conducted a lipidomic screen of nearly 200 lipids involved in inflammation and its resolution in vulvar biopsies collected from a group of 10 localized provoked vulvodynia (LPV) cases and 10 controls without vulvar pain. Paired biopsies were taken from painful sites within the vulvar vestibule and non-painful sites within the external vulva. Anatomically identical sites were also biopsied in asymptomatic controls, allowing us to compare lipid profiles at painful and non-painful sites within cases and between cases and controls. This screen was followed up with enzymatic assays, gene expression profiling, and enzyme-linked immunosorbent assays to further explore these pathways and identify new candidate therapies. Results We found that lipid profiles in painful areas showed reduced expression of pro-resolving lipids, such as 14,15-epoxyeicosatrienoic acid, while proinflammatory mediators, such as prostaglandin E2 were elevated, pointing to an alteration in arachidonic acid metabolism. Arachidonic acid is a polyunsaturated fatty acid that serves as a substrate for the production of proinflammatory and pro-resolving lipids. In LPV, it appears that arachidonic acid metabolism is skewed towards heightened production of inflammatory mediators associated with pain. We found that the activity and expression of enzymes involved in proinflammatory mediator expression is comparatively higher in painful areas, while enzymes involved in producing pro-resolving lipids are less active. We identified three enzymes families involved in this bioactive lipid mechanism: lipoxygenase, cyclooxygenase (COX), and cytochrome P450 (CYP450). Both COX and CYP450 can be targeted with FDA-approved agents. Conclusions The vulvodynia mechanism is complex, but it offers several targets for therapeutic intervention. We have identified targets for both drug development and “off-label” use of existing therapies. The use of medicines “off-label” may result in faster alleviation of symptoms, even if only as a stop-gap to stave off surgery until new drugs are introduced. Disclosure No

THE ROLE OF B LYMPHOCYTES AND PRESENCE OF GERMINAL CENTERS IN PATIENTS WITH LOCALIZED PROVOKED VULVODYNIA

Objective: The aim of the study is to assess local immune activation through B lymphocytes density and the presence of germinal centers in the vestibular mucosa of patients with localized provoked vulvodynia (LPV). Materials and Methods: Vestibulectomy specimens of 29 patients with LPV and colporrhaphy posterior specimens of 20 control women were included in the study. Immunohistochemical staining with CD20 antibodies for B lymphocytes were performed and subsequently, microscopical evaluation for B lymphocytes density and the presence of germinal centers was conducted. Results: B lymphocyte densities were higher in the vestibular mucosa of patients with LPV compared to control women (87 vs 21, p<0.01). The presence of germinal centers was only observed in the specimens of patients with LPV (0.31 vs 0, p<0.011). Conclusion: The presence of germinal centers with increased B lymphocyte density underlines a local immune activation in the vestibule of patients with LPV. An abnormal germinal center response can trigger the pathway to the development of autoimmunity through the emergence of an autoreactive B cell clone and autoantibodies. LPV can potentially emerge as an autoimmune disease of the vestibule. More studies are needed to understand the pathophysiology of LPV and its association with autoimmunity.

Localized Provoked Vulvodynia-An Ignored Vulvar Pain Syndrome.

Localized provoked vulvodynia (LPV) causes dyspareunia among reproductive aged women. We review the pathogenesis of LPV and suggest that LPV is an inflammatory pain syndrome of the vestibular mucosa triggered by microbial antigens in a susceptible host. Tissue inflammation and hyperinnervation are characteristic findings which explain symptoms and clinical signs. Education of health care providers of LPV is important since this condition is common, often unrecognized, and patients often become frustrated users of health care. Research is needed on the antigen triggers of the syndrome. Randomized clinical trials are needed to evaluate treatment modalities.

Specialized Pro-resolving Mediators Reduce Pro-nociceptive Inflammatory Mediator Production in Models of Localized Provoked Vulvodynia

Localized provoked vulvodynia (LPV) is the most common cause of chronic dyspareunia in premenopausal women, characterized by pain with light touch to the vulvar vestibule surrounding the vaginal opening. The devastating impact of LPV includes sexual dysfunction, infertility, depression, and even suicide. Yet, its etiology is unclear. No effective medical therapy exists; surgical removal of the painful vestibule is the last resort. In LPV, the vestibule expresses a unique inflammatory profile with elevated levels of pro-nociceptive proinflammatory mediators prostaglandin E2 (PGE2) and interleukin-6 (IL-6), which are linked to lower mechanical sensitivity thresholds. Specialized pro-resolving mediators (SPMs), lipids produced endogenously within the body, hold promise as an LPV treatment by resolving inflammation without impairing host defense. Ten of 13 commercially available SPMs reduced IL-6 and PGE2 production by vulvar fibroblasts, administered either before or after inflammatory stimulation. Using a murine vulvar pain model, coupling proinflammatory mediator quantification with mechanical sensitivity threshold determination, topical treatment with the SPM, maresin 1, decreased sensitivity and suppressed PGE2 levels. Docosahexaenoic acid, a precursor of maresin 1, was also effective in reducing PGE2 in vulvar fibroblasts and rapidly restored mouse sensitivity thresholds. Overall, SPMs and their precursors may be a safe and efficacious for LPV.Perspective: Vulvodynia, like many pain conditions, is difficult to treat because disease origins are incompletely understood. Here, we applied our knowledge of more recently discovered vulvodynia disease mechanisms to screen novel therapeutics. We identified several specialized pro-resolving mediators as likely potent and safe for treating LPV with potential for broader application.

Expression of Estrogen-Related Receptors in Localized Provoked Vulvodynia.

Eight percent of women suffer from vulvodynia, a chronic pain condition with unknown etiology. Inflammation and dysregulation of estrogen signaling have been suggested to play a role in the pathogenesis of localized provoked vulvodynia (LPV). Therefore, the aim of the study was to analyze protein expression levels of estrogen-related receptors ERRα, ERRß, ERRγ, estrogen receptor (ERα), and progesterone receptor (PRα) and CD3-positive T cells in the vulvar vestibulum obtained from women suffering from LPV in comparison to healthy, unaffected controls. Vulvar vestibulum tissue specimens were obtained from LPV patients (n = 12) who had undergone modified posterior vestibulectomy and from 15 healthy controls. Protein expression of ERRα, ERRß, ERRγ, ERα, and PRα and CD3-positive T cells was analyzed by immunohistochemistry (IHC). Expression of ERRß was significantly more pronounced in samples from LPV compared to healthy controls (p = 0.006). No significant difference in the expression patterns of ERRα, ERRγ, ERα, PRα, or CD3 cells was detected. To our knowledge, this is the first study reporting ERR expression in normal vestibulum and in vestibulectomy samples from LPV patients. The higher level of ERRß expression detected by IHC may reflect dysregulation of estrogen signaling in LPV.

The histopathological results of vestibulectomy specimens in localized provoked vulvodynia in Turkey

IntroductionLocalized Provoked Vulvodynia (LPV) is a gynecological disease that is difficult to manage. Despite the wide spectrum of pathophysiological mechanisms and treatment modalities, there is limited success in the management of this disease. Surgical treatment is usually performed as the last resort. We aimed to investigate the histopathological results of 38 women with LPV who underwent surgical vestibulectomy.Methodsof the 55 women that were diagnosed with LPV and underwent vulvar vestibulectomy, 38 patients with complete histopathological results were included in this retrospective study.Resultsin 14 patients, the pathological reports revealed Low-Grade Squamous Intraepithelial Lesions (LGSIL) (36.8%) whereas for 21 cases (55.2%), the findings were concordant with vestibulitis. The remaining three patients (7.8%) were diagnosed with lichen simplex chronicus.Conclusionthe presence of LGSIL in the surgical specimens of LPV cases is noteworthy. In this group of patients, surgical excision may contribute to the prevention of progression into high-grade lesions. The relationship between Human Papilloma Virus (HPV) infections and LPV should be further investigated.

Combination of Treatments With or Without Surgery in Localized Provoked Vulvodynia: Outcomes After Three Years of Follow-Up.

Most vulvodynia patients receive combinations of several treatment modalities for their chronic painful condition. If conservative treatments fail, vestibulectomy is considered to be the ultimate treatment option for localized provoked vulvodynia (LPV). The aim of this descriptive study was to analyze relief of pain, quality of life (QoL), and complications associated with combining surgery with conservative treatments among LPV patients, both in short term and after 3 years of follow-up.The study population consisted of a retrospective patient cohort of surgically (n = 16) and only conservatively (n = 50) treated LPV patients. QoL data were assessed by a validated questionnaire (RAND-36). Data were collected by reviewing patient records and by aid of postal questionnaires. Efficacy of treatments in relief of pain was measured by numerical rating scale (NRS). Two months after surgery, the NRS scores assessed by a physician were lower in the surgery group than in patients treated only conservatively (p = 0.008). However, after a median of 36 months of follow-up, self-reported NRS scores and QoL showed no difference between the two patient cohorts. Complication rate after vestibulectomy was 18.8%. The findings suggest that combining surgery with conservative treatments may result in a more effective short-term reduction of pain. However, the effect seemed to be only temporary, as no long-term benefit was achieved.

Localized Provoked Vulvodynia: Association With Nerve Growth Factor and Transient Receptor Potential Vanilloid Type 1 Genes Polymorphisms.

The aim of the study was to study the associations between localized provoked vulvodynia (LPV) and several single-nucleotide polymorphisms (SNPs) in the transient receptor potential vanilloid type 1 (TRPV1), nerve growth factor (NGF), and the heparanase (HPSE) genes. Prevalence of SNPs among 65 women with moderate or severe primary LPV (initial symptoms occur with first provoking physical contact) and 126 healthy, ethnically matched controls was analyzed in an observational case-control study. Each participant answered a questionnaire addressing familial LPV occurrence and comorbid pain conditions. Familial occurrences of LPV, temporomandibular joint (TMJ) symptoms, recurrent vaginitis, and irritable bowel syndrome were significantly higher among LPV women than healthy controls. Genotyping analyses revealed a novel, statistically significant high prevalence of polymorphism c.945G>C (rs222747) of TRPV1 and a SNP in the promoter region of NGF (rs11102930) in LPV women compared with controls. A logistic regression model for rs222747 and rs11102930 frequent alleles indicates significant LPV association within the entire study group and Ashkenazi Jewish women, respectively. Comparison of pain conditions with frequent alleles showed the rs222747 "CC" genotype of TRPV1 associated with women with TMJ, recurrent vaginitis, and LPV. Our results suggest novel genetic susceptibility to primary LPV associated with specific alleles in genes TRPV1 and NGF and propose the rs222747 "C" allele of TRPV1 as a common genetic predisposition for other pain syndromes.

Abnormal vaginal microbioma is associated with severity of localized provoked vulvodynia. Role of aerobic vaginitis and Candida in the pathogenesis of vulvodynia.

Localized provoked vulvodynia (LPV) causes introital dyspareunia in up to 14% of premenopausal women. Vaginal infections like candidosis may play a initiating role. The aim of this study was to test a possible association of vaginal microbiota alternations such as Candida vaginitis (CV), aerobic vaginitis (AV) and bacterial vaginosis (BV) with severity of vulvodynia and painful intercourse. In an observational study, Q-tip touch test (score 1 (no pain) to 10 (worst possible pain)) was performed on seven vestibular locations in 231 LPV patients presenting in the Vulvovaginal Disease Clinics in Tienen, Leuven and Antwerp, Belgium. Severity of pain upon attempting sexual intercourse was recorded in a similar scale. Both scales were compared to results from fresh wet mount phase contrast microscopy on vaginal fluid smears tested for abnormal vaginal flora (AVF), BV, AV and CV according the standardized microscopy method (Femicare). Fisher's exact test was used. Average age was 31.3 ± 11.6years, and 58.8% (n = 132) had secondary vestibulodynia. There was an inverse relation between the presence of Candida in the vaginal smears and pain score (p = 0.03). There was no relation of pain score, nor Q-tip score with BV. LPV patients with Q-tip score above 7 at 5 and/or 7 o'clock or at 1 and/or 11 o'clock had more often AV than women with lower pain scores (30 vs 14.5%, p = 0.01, and 39 vs 14.7%, p < 0.005, respectively). Detailed study of the vaginal microflora in patients demonstrates that the most severe patients suffer more from AV and less from Candida. These abnormalities need to be actively looked for and corrected before considering surgery or other therapies.

Toll-Like Receptor Signaling Contributes to Proinflammatory Mediator Production in Localized Provoked Vulvodynia.

Localized provoked vulvodynia (LPV) afflicts approximately 8% of women in the United States and represents a huge financial, physical, and psychological burden. Women with LPV experience intense pain localized to the vulvar vestibule (area immediately surrounding vaginal opening). We have identified mechanisms involved in the development of LPV whereby vulvar fibroblasts respond to proinflammatory stimuli to perpetuate an inflammatory response that causes pain. However, these mechanisms are not fully elucidated. Therefore, we explored the role of toll-like receptors (TLRs), a class of innate immune receptors that rapidly respond to microbial assaults. To determine whether TLRs are expressed by vulvar fibroblasts and whether these contribute to proinflammatory mediator production and pain in LPV, we examined TLR expression and innate immune responses in fibroblasts derived from painful vestibular regions compared with nonpainful external vulvar regions. Human vulvar fibroblasts express functional TLRs that trigger production of inflammatory mediators associated with chronic pain. We focused on the TLR-7-imiquimod proinflammatory interaction, because imiquimod, a ligand of TLR-7, may exacerbate pain in women during treatment of human papillomavirus-associated disease. Human vulvar fibroblasts express a broad spectrum of TLRs (a new finding). A significantly higher TLR-mediated proinflammatory response was observed in LPV case vestibular fibroblasts, and with respect to the imiquimod-TLR 7 interaction, development of chronic vestibular pain and inflammation may be a possible sequelae of treatment of vulvar human papillomavirus-associated disease. Suppressing enhanced TLR-associated innate immune responses to a spectrum of pathogen-associated molecular patterns may represent a new/effective therapeutic approach for vulvodynia.

A Role for Bradykinin Signaling in Chronic Vulvar Pain.

There is an unmet need for the development of more effective vulvodynia therapies. As we explore the mechanisms by which human vulvar fibroblasts respond to proinflammatory/propain stimuli, we move closer to understanding the origins of chronic vulvar pain and identifying new therapeutic targets, knowledge that could significantly improve patient care.

Site-specific mesenchymal control of inflammatory pain to yeast challenge in vulvodynia-afflicted and pain-free women.

Fibroblast strains were derived from 2 regions of the lower genital tract of localized provoked vulvodynia (LPV) cases and pain-free controls. Sixteen strains were derived from 4 cases and 4 controls, age and race matched, after presampling mechanical pain threshold assessments. Strains were challenged with 6 separate stimuli: live yeast species (Candida albicans, Candida glabrata, Candida tropicalis, and Saccharomyces cerevisiae), yeast extract (zymosan), or inactive vehicle. Production of prostaglandin E2 (PGE2) and interleukin 6 (IL-6) were proinflammatory response measures. Highest IL-6 and PGE2 occurred with vestibular strains after C albicans, C glabrata, and zymosan challenges, resulting in the ability to significantly predict IL-6 and PGE2 production by genital tract location. After C albicans and C glabrata challenge of all 16 fibroblast strains, adjusting for dual sampling of subjects, PGE2 and IL-6 production significantly predicted the presampling pain threshold from the genital tract site of sampling. At the same location of pain assessment and fibroblast sampling, in situ immunohistochemical (IHC)(+) fibroblasts for IL-6 and Cox-2 were quantified microscopically. The correlation between IL-6 production and IL-6 IHC(+) was statistically significant; however, biological significance is unknown because of the small number of IHC(+) IL-6 fibroblasts identified. A low fibroblast IL-6 IHC(+) count may result from most IL-6 produced by fibroblasts existing in a secreted extracellular state. Enhanced, site-specific, innate immune responsiveness to yeast pathogens by fibroblasts may be an early step in LPV pathogenesis. Fibroblast strain testing may offer an attractive and objective marker of LPV pathology in women with vulvodynia of inflammatory origin.

Identification of novel mechanisms involved in generating localized vulvodynia pain

Our goal was to gain a better understanding of the inflammatory pathways affected during localized vulvodynia, a poorly understood, common, and debilitating condition characterized by chronic pain of the vulvar vestibule. In a control matched study, primary human fibroblast strains were generated from biopsies collected from localized provoked vulvodynia (LPV) cases and from age- and race-matched controls. We then examined intracellular mechanisms by which these fibroblasts recognize pathogenic Candida albicans; >70% of vulvodynia patients report the occurrence of prior chronic Candida infections, which is accompanied by localized inflammation and elevated production of proinflammatory/pain-associated interleukin (IL)-6 and prostaglandin E2 (PGE2). We focused on examining the signaling pathways involved in recognition of yeast components that are present and abundant during chronic infection. Dectin-1, a surface receptor that binds C albicans cell wall glucan, was significantly elevated in vestibular vs external vulvar cells (from areas without pain) in both cases and controls, while its abundance was highest in LPV cases. Blocking Dectin-1 signaling significantly reduced pain-associated IL-6 and PGE2 production during the response to C albicans. Furthermore, LPV patient vestibular cells produced inflammatory mediators in response to low numbers of Calbicans cells, while external vulvar fibroblasts were nonresponsive. Inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (proinflammatory transcription factor) nearly abrogated IL-6 and PGE2 production induced by C albicans, in keeping with observations that Dectin-1 signals through the nuclear factor kappa-light-chain-enhancer of activated B cells pathway. These findings implicate that a fibroblast-mediated proinflammatory response to C albicans contributes to the induction of pain in LPV cases. Targeting this response may be an ideal strategy for the development of new vulvodynia therapies.

Activation of vestibule-associated lymphoid tissue in localized provoked vulvodynia

Localized provoked vulvodynia (LPV) may have inflammatory etiology. We wanted to find out whether the cell-mediated immune system becomes activated in the vestibular mucosa in LPV. This was a controlled cross-sectional study. Vestibular mucosal specimens were obtained from 27 patients with severe LPV and 15 controls. Detailed clinical history of the patients was obtained. For immunohistochemistry, antibodies against CD3 (T cells), CD20 (B cells), IgA (mucosal plasma cells), CD163 (dendritic cells [DCs]), CD68 (macrophages), and CD117 (mast cells) were employed. Mann-Whitney U test and χ(2) test were used for statistical analyses. More B lymphocytes and mature mucosal IgA-plasma cellswere found in patients than in controls (P < .001 and P < .001, respectively). In LPV samples, B and T cells were arranged into germinal centers representing local immune activation. Germinal centers were not seen in controls. Antigen-presenting DCs and macrophages were found both in patients and controls with similar densities. DCs were found to extend their dendrites into the luminal space through an intact epithelium. Similar amounts of mast cells were found evenly scattered throughout the stroma of vestibular mucosa of both patients and controls. We demonstrate here local organized vestibule-associated lymphoid tissue analogous to mucosa-associated lymphoid tissue. Vestibule-associated lymphoid tissue may emerge as a response to local infection or inflammation in LPV.

Evaluation of Sexual Function in Brazilian Women with Recurrent Vulvovaginal Candidiasis and Localized Provoked Vulvodynia

Recurrent vulvovaginitis is an important trigger for inflammatory processes that in many cases may result in vulvovaginal pain. Vulvodynia, a vulvar disorder, can also cause a lot of pain in the female genitals. The sexual function in women with vulvodynia or recurrent vulvovaginitis will possibly be negatively affected and therefore should be evaluated. To assess sexual function in women with recurrent vulvovaginal candidiasis (RVVC) and localized provoked vulvodynia (LPV) in comparison with women without lower genital tract dysfunction. A 1-year cross-sectional study evaluated sexual function in 58 women (11 with RVVC, 18 with LPV, and 29 controls) seen at a university outpatient clinic. Sexual function was assessed by taking into account the results obtained from the application of the Female Sexual Function Index (FSFI) questionnaire. Kruskal-Wallis, Mann-Whitney, chi-square, and Fisher's tests were used for statistical analysis. FSFI, a validated questionnaire in Portuguese. There were no significant differences in the three groups with respect to age, marital status, schooling, race, body mass index, contraceptive method, and parity. The FSFI questionnaire total score found was 25.51 (±5.12), 21.17 (±5.15), and 29.56 (±3.87) for the RVVC, LPV, and control groups, respectively. The scores were significantly statistically lower in the study groups compared with the control group (P<0.05). Women with RVVC and LPV also had lower total scores compared with 26.55 values, considered a cutoff score for sexual dysfunction in literature. The LPV group showed a significant difference and scored worse in the domains of arousal, lubrication, orgasm, satisfaction, and pain but not in the domain of sexual desire. The same occurred with the RVVC group but only for the domains of orgasm and satisfaction. Women with RVVC and LPV had significantly more symptoms of sexual dysfunction than women without lower genital tract diseases.

Medical and physical predictors of localized provoked vulvodynia

Vulvodynia in young women is a significant clinical challenge. This overview focuses on localized provoked vulvodynia (LPV) with regard to medical and physical predictors of the condition. Several causative factors have been proposed and one major conceptual issue is the role of inflammation. Trauma to the vestibular mucosa causes an initial inflammatory response which may result in peripheral and central pain sensitization. In women with LPV, evidence of mucosal nerve fiber proliferation and enhanced systemic pain perception has been found. A dysfunction of the pelvic floor muscles is common and many patients also suffer from other bodily pain. In general, the level of scientific quality in published studies on vulvodynia is low. Further research on epidemiology, etiology and conduction of clinical trials with high evidence grade is desired.