Interstitial Cystitis Research Articles

Pelvic Floor Physiotherapy in the Treatment of a Patient with Interstitial Cystitis: A Case Report

Pelvic Floor Physiotherapy in the Treatment of a Patient with Interstitial Cystitis: A Case Report

Promising Experimental Treatment in Animal Models and Human Studies of Interstitial Cystitis/Bladder Pain Syndrome.

Interstitial cystitis/bladder pain Syndrome (IC/BPS) remains a mysterious and intricate urological disorder, presenting significant challenges to healthcare providers. Traditional guidelines for IC/BPS follow a hierarchical model based on symptom severity, advocating for conservative interventions as the initial step, followed by oral pharmacotherapy, intravesical treatments, and, in refractory cases, invasive surgical procedures. This approach embraces a multi-tiered strategy. However, the evolving understanding that IC/BPS represents a paroxysmal chronic pain syndrome, often involving extravesical manifestations and different subtypes, calls for a departure from this uniform approach. This review provides insights into recent advancements in experimental strategies in animal models and human studies. The identified therapeutic approaches fall into four categories: (i) anti-inflammation and anti-angiogenesis using monoclonal antibodies or immune modulation, (ii) regenerative medicine, including stem cell therapy, platelet-rich plasma, and low-intensity extracorporeal shock wave therapy, (iii) drug delivery systems leveraging nanotechnology, and (iv) drug delivery systems assisted by energy devices. Future investigations will require a broader range of animal models, studies on human bladder tissues, and well-designed clinical trials to establish the efficacy and safety of these therapeutic interventions.

Cellular and Molecular Aspect of Bladder Pain Syndrome: An Entry Point to Exploration of Its Pathogenesis

<i>Background:</i> Bladder pain syndrome/interstitial cystitis (BPS/IC) can cause pelvic pain, frequent urination, and a strong urge to urinate. These symptoms can significantly reduce quality of life, causing psychological distress, sexual dysfunction, poor sleep quality, decreased work productivity, and increased morbidity. Despite the prevalence of this condition, determining the most effective treatment guidelines for BPS/IC remains a challenge due to the complexity of its pathogenesis. <i>Objective:</i> Understanding cellular and molecular aspects is essential to explore different cell types in changes in function and sensitivity of the urothelial layer and chronic inflammation. <i>Main Ideas:</i> Cellular aspects in the pathogenesis of BPS/IC include Umbrella Cells, Basal and Intermediate Cells, Paraneuron Cells, Myofibroblasts and Telocytes, Detrusor Smooth Muscle Cells, Nerve Cells, Astrocytes, Microglia, CD68+ Macrophages, CD74+ Lymphocytes, Eosinophils, and Mast Cells. Disruption of these cells leads to altered urothelial barrier function, sensitivity, and chronic inflammation. Molecular aspects include chronic inflammation with increases in p38-mitogen activated protein kinase (p38 MAPK), Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α), Nerve Growth Factor (NGF), Brain-Derived Neurothropic Peptide (BDNF), and other molecules. <i>Conclusion:</i> Changes in the urothelial barrier and bladder wall sensitivity are also significant. Complex interactions between the immune and nervous systems contribute to chronic inflammation through positive feedback. Therefore, this article aims to understand the cellular and molecular aspects that play a role in the pathogenesis of BPS/IC and help provide appropriate treatment.

Unplanned 30-Day Readmissions After Hospitalization for Irritable Bowel Syndrome.

Background Irritable bowel syndrome (IBS) continues to posesignificant healthcare challengesdue to its broad differential diagnosis and the often extensive yet inconclusive workup. We investigated the rates and characteristics of unplanned 30-day readmissions in adult patients hospitalized with IBS. In addition, weidentified factors that predict readmission within 30 days of initial discharge. Methods We analyzed the 2020 Nationwide Readmission Database. Using the International Classification of Diseases, Tenth Revision, Clinical Modification code, we identified hospitalizations in adult patients with IBS. We excluded hospitalizations for minors and planned or elective readmissions. To compare baseline characteristics between readmissions and index hospitalizations, χ2 tests were employed. We used multivariate Cox regression analyses to identify independent predictors of readmissions. Results A total of 5,729 adult hospitalizations with IBS as the primary diagnosis were discharged alive, and 638(11.1%) readmissions occurred within 30 days. The most common diagnoses associated with readmission were noninfective gastroenteritis and colitis, sepsis, enterocolitis due to Clostridium difficile, and irritable bowel syndrome with or without diarrhea. Patients in readmissions had a mean age of 56.3 years, similar to index hospitalizations (54.5 years, p=0.093). Readmissions had a higher burden of comorbidity (Charlson comorbidity index (CMI) scores ≥3: 26.7%, 170 cases vs. 16.6%, 953 cases;p<0.001) and were mostly Medicare beneficiaries (49.5%, 316% vs. 44.9%, 2,578) compared with index hospitalizations. Readmissions had a longer mean length of stay (LOS) (5.2 vs. 3.6 days, p<0.0001), higher inpatient mortality (0.8%, 5% vs. 0.2%, 11; p=0.032), and higher mean hospital costs ($47,852 vs. $34,592; p<0.0001) compared with index admissions. Secondary diagnoses of ulcerative colitis (adjusted hazard ratio (AHR), 2.82; p<0.0001), interstitial cystitis (AHR, 5.37; p=0.007), peripheral vascular disease (AHR, 1.59; p=0.027), and discharge to short-term hospitals (AHR, 1.03; p<0.0001) were significantly associated with ahigher likelihood of readmission within 30 days. Conclusion IBS readmissions have poorer outcomes than index hospitalizations. Patients with an existing history of ulcerative colitis, interstitial cystitis, and peripheral vascular disease and those discharged to short-term hospitals following index hospitalization are more likely to be readmitted within 30 days.

Genital Pain and the Spectrum of Bladder-Related Symptoms: Findings from the Prevention of Lower Urinary Tract Symptoms Research Consortium RISE FOR HEALTH Study, USA.

Women with vulvovaginal or genital pain more commonly experience interstitial cystitis/bladder pain syndrome (IC/BPS) and urinary tract infections. However, the relationship between genital pain and bladder health is lacking. Women in the Prevention of Lower Urinary Tract Symptoms Consortium's RISE FOR HEALTH population-based study answered questions about bladder health globally, and across nine bladder health domains of holding, efficacy, social-occupation, physical activity, intimacy, travel, emotion, perception, and freedom. Bladder function was assessed across six indices including urinary frequency, sensation, continence, comfort, emptying, and dysbiosis (e.g., urinary tract infections). Participants were grouped by no pain beyond transitory events (i.e., minor headaches, toothaches, or sprains), nongenital-related pain only, and any genital pain using a validated pain diagram. Mean adjusted scores and indices were compared using general linear modelling. Of 1,973 eligible women, 250 (12.7%) reported genital pain, 609 (30.9%) reported nongenital pain only, and 1,114 (56.5%) reported no pain. Women with any genital pain had lower (worse) adjusted mean scores across all bladder health scales (BHS; BHS global adjusted mean 47.5; 95% CI 40.8-54.1), compared with those with nongenital pain only (53.7; 95% CI 47.6-59.8), and no pain (59.3; 95% CI 53.3-65.4). Similarly, adjusted mean total Bladder Functional Index scores were lower for those with genital pain (63.1; 95% CI 58.4-67.9) compared with nongenital pain (72.1; 95% CI 67.7-76.5) and no pain (77.4; 95% CI 73.0-81.8). Heightened awareness of the relationship between genital pain and bladder health should prompt clinicians caring for women with genital pain to assess bladder health and function.

Divergent histopathological and molecular patterns in chemically induced interstitial cystitis/bladder pain syndrome rat models

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a complex chronic pain disorder with an elusive etiology and nonspecific symptoms. Although numerous animal models with phenotypes similar to human disease have been established, no available regimen can consistently alleviate clinical symptoms. This dilemma led us to question whether current animal models adequately represent IC/BPS. We compared four commonly used IC/BPS rat models to determine their diverse histopathological and molecular patterns. Female rats were given single treatments with hydrochloric acid (HCL), acetic acid (AA), protamine sulfate plus lipopolysaccharide (PS + LPS), or cyclophosphamide (CYP) to induce IC/BPS. Bladder sections were stained for histopathologic evaluation, and mRNA expression profiles were examined using next-generation sequencing and gene set analyses. Mast cell counts were significantly higher in the HCL and AA groups than in the PS + LPS, CYP, and control groups, but only the AA group showed significant collagen accumulation. The models differed substantially in terms of their gene ontology and Kyoto encyclopedia of genes and genomes pathways. Our observations suggest that none of these rat models fully reflects the complexity of IC/BPS. We recommend that future studies apply and compare multiple models simultaneously to fully replicate the complicated features of IC/BPS.

Characterization and Therapeutic Potential of Curcumin-Loaded Cerium Oxide Nanoparticles for Interstitial Cystitis Management.

Oxidative stress resulting from reactive oxygen species (ROS) is often considered to be the leading cause of interstitial cystitis (IC), which is a chronic inflammatory disease. Antioxidants have been proven to have promising therapeutic effects on IC. In this study, we present an antioxidant intervention for IC by introducing curcumin-loaded cerium oxide nanoparticles (Cur-CONPs). Recognizing oxidative stress as the primary contributor to IC, our research builds on previous work utilizing cerium oxide nanoparticles (CONPs) for their outstanding antioxidant and anti-inflammatory properties. However, given the need to effectively relieve acute inflammation, we engineered Cur-CONPs to harness the short-term radical-scavenging antioxidant prowess of curcumin. Through in vitro studies, we demonstrate that the Cur-CONPs exhibit not only robust antioxidant capabilities but also superior anti-inflammatory properties over CONPs alone. Furthermore, in vivo studies validate the therapeutic effects of Cur-CONPs on IC. Mice with IC subjected to the Cur-CONP treatment exhibited improved micturition behaviors, relief from pelvic pain sensitivity, and reduced expression of inflammatory proteins (IL-6, IL-1β, TNF-α, Cox2). These findings suggest that the synergistic antioxidant properties of the Cur-CONPs that combine the sustained antioxidant properties of CONPs and acute anti-inflammatory capabilities of curcumin hold promise as a novel treatment strategy for IC.

The efficacy and safety of monoclonal antibody therapies for interstitial cystitis/bladder pain syndrome: A meta-analysis of randomized controlled trials.

This study aimed to assess the efficacy and safety of monoclonal antibody therapies (MATs) for interstitial cystitis/bladder pain syndrome (IC/BPS). A systematic search was conducted across databases including PubMed, Embase, clinicalTrial.gov, and the Cochrane Library Central Register of Controlled Trials. Randomized controlled trials (RCTs) comparing MATs versus placebo were included. Primary outcomes comprised the Global Response Assessment (GRA) scale and the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI). Additional analyses encompassed mean daily frequency of voids, the O'Leary-Sant Interstitial Cystitis Problem Index, pain scores, and complications. Statistical analyses were performed using Review Manager 5.3. Five high-quality RCTs, comprising 263 patients with IC/BPS, were ultimately selected. MATs were generally effective in treating IC/BPS. Patients receiving MATs exhibited a higher satisfaction rate (odds ratio [OR]: 2.7, confidence interval [CI]: 1.31-5.58, p = 0.007) and lower ICSI scores (mean difference [MD]: -1.44, CI: -2.36 to -0.52, p = 0.002). Moreover, MAT recipients experienced reduced pain (MD: -0.53, CI: -0.79 to -0.26, p < 0.0001) and decreased frequency of urination (MD: -1.91, CI: -2.55 to -1.27, p < 0.00001). Importantly, there were no disparities regarding complication incidence in the MAT and control groups. The current findings indicate that MATs are effective and safe for treating IC/BPS. Nonetheless, future RCTs with larger sample sizes and long-term follow-up are warranted.

Outcomes of Cystodistension for Bladder Pain Syndrome: A Monocentric Analysis

Introduction: Bladder pain syndrome (BPS) is a chronic condition characterized by pelvic pain and urinary urgency/frequency. While the exact cause of BPS is unknown, various treatment options exist. This study aimed to evaluate bladder hydrodistension's short- and long-term efficacy in BPS patients. Methods: A retrospective analysis of four female BPS patients treated with bladder hydrodistension over 10 years was conducted. Symptoms, cystoscopy findings, and treatment outcomes were reviewed. Results: The average patient age was 40 years. All patients reported pain, with an average of 13 daytime and 3 nighttime urinary voids per day. Hydrodistension improved symptoms in 75% of patients, reducing daytime frequency and nocturia. Cystoscopy after hydrodistension revealed Hunner's ulcers in one patient and petechiae in three. One patient required a second hydrodistension. Transient worsening of symptoms and hematuria occurred in one patient each. Discussion: Bladder hydrodistension appears to be a safe and effective treatment for BPS, improving symptoms in most patients in our study. The findings are consistent with previous reports suggesting. Our study adds to the growing body of evidence supporting hydrodistension as a valuable tool in managing BPS. Conclusion: Bladder hydrodistension is a simple and minimally invasive technique that has proven its efficacy with a low complication rate. Our findings support the existing literature on the benefits of hydrodistension for BPS.

How Intravesical Platelet-Rich Plasma Can Help Patients with Interstitial Cystitis/Bladder Pain Syndrome: A Comprehensive Scoping Review.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a condition characterized by chronic inflammation that affects the bladder. The study was aimed at evaluating the effectiveness of intravesical platelet-rich plasma (PRP) injections in patients with IC/BPS. We conducted a comprehensive search strategy to involve studies that investigate the efficacy of intravesical PRP injections or instillations over different time intervals. Various outcome measures were assessed, including pain scores, functional outcomes, urodynamic parameters, and surface expressions on the urothelium. Our search strategy revealed 1,125 studies. After screening, ten articles met the inclusion criteria. Intravesical PRP significantly reduced the visual analog scale (VAS) compared with baseline scores. Several clinical trials reported significant improvements in the global response rate (GRA), O'Leary-Sant Symptom (OSS) questionnaire, Interstitial Cystitis Symptom Index (ICSI), and Interstitial Cystitis Problem Index (ICPI). Urodynamic parameters such as maximum flow rate (Qmax) and post-voiding residual (PVR) showed significant improvements in some studies. The study concluded that intravesical PRP injections could be a promising effective treatment option for IC/BPS patients by their significant ability to reduce pain. However, improvement of urodynamic and functional outcomes is still not clear. Further large comparative trials are still warranted to assess the efficacy of PRP instillation.

Effect of Low Intensity Laser Therapy on Painful Bladder Syndrome

Effect of Low Intensity Laser Therapy on Painful Bladder Syndrome

Symptomatic Autonomic Dysfunction in Interstitial Cystitis/Bladder Pain Syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a highly prevalent condition with incompletely understood pathophysiology, especially in relation to the systemic symptoms experienced. The role of autonomic nervous system dysfunction in IC/BPS remains poorly understood. The purpose of this study was to assess the relationship between autonomic symptom severity and clinical characteristics of patients with IC/BPS. This is a retrospective cohort study of 122 IC/BPS patients who completed the Composite Autonomic Symptoms Score (COMPASS-31) questionnaire. Data were collected on anesthetic bladder capacity (BC), Hunner lesion (HL) status, results for validated IC/BPS symptom questionnaires (O'Leary Sant Interstitial Cystitis Symptom Index and Interstitial Cystitis Problem Index (ICSI/ICPI) and the Pelvic Pain and Urgency/Frequency (PUF) scale), and comorbid nonurologic associated syndromes. Using the first quartile of COMPASS-31 scores as the cutoff, we compared patients within the first quartile (low symptom load; n = 30), to the remainder of the patients (high symptom load; n = 92). Patients scoring ≥20.36 were significantly less likely to be HL positive (10.9% vs 26.7%; P = 0.043) and had a significantly higher BC (823.10 ± 396.07 vs 635.00 ± 335.06; P = 0.027), higher scores on the PUF questionnaire (23.80 ± 4.98 vs; 19.61 ± 5.22 P < 0.001), and a higher number of nonurologic associated syndromes (5.65 ± 2.90 vs 2.60 ± 1.89; P < 0.001). Patients with IC/BPS experience widespread symptoms associated with autonomic nervous system dysfunction. A higher symptom load strongly correlates with a nonbladder-centric phenotype. These findings provide further evidence that total body nervous system dysfunction is present in patients with nonbladder centric IC/BPS.

This pain drives me crazy: Psychiatric symptoms in women with interstitial cystitis/bladder pain syndrome

BACKGROUND Interstitial cystitis/bladder pain syndrome (IC/BPS) is an at least 6-mo noninfectious bladder inflammation of unknown origin characterized by chronic suprapubic, abdominal, and/or pelvic pain. Although the term cystitis suggests an inflammatory or infectious origin, no definite cause has been identified. It occurs in both sexes, but women are twice as much affected. AIM To systematically review evidence of psychiatric/psychological changes in persons with IC/BPS. METHODS Hypothesizing that particular psychological characteristics could underpin IC/BPS, we investigated in three databases the presence of psychiatric symptoms and/or disorders and/or psychological characteristics in patients with IC/BPS using the following strategy: ("interstitial cystitis" OR "bladder pain syndrome") AND ("mood disorder" OR depressive OR antidepressant OR depression OR depressed OR hyperthymic OR mania OR manic OR rapid cyclasterisk OR dysthymiasterisk OR dysphoriasterisk). RESULTS On September 27, 2023, the PubMed search produced 223 articles, CINAHL 62, and the combined PsycLIT/PsycARTICLES/PsycINFO/Psychology and Behavioral Sciences Collection search 36. Search on ClinicalTrials.gov produced 14 studies, of which none had available data. Eligible were peer-reviewed articles reporting psychiatric/psychological symptoms in patients with IC/BPS, i.e. 63 articles spanning from 2000 to October 2023. These studies identified depression and anxiety problems in the IC/BPS population, along with sleep problems and the tendency to catastrophizing. CONCLUSION Psychotherapies targeting catastrophizing and life stress emotional awareness and expression reduced perceived pain in women with IC/BPS. Such concepts should be considered when implementing treatments aimed at reducing IC/BPS-related pain.

The microbiota in patients with interstitial cystitis/bladder pain syndrome: a systematic review.

To comprehensively review and critically assess the literature on microbiota differences between patients with interstitial cystitis (IC)/bladder pain syndrome (BPS) and normal controls and to provide clinical practice guidelines. In this systematic review, we evaluated previous research on microbiota disparities between IC/BPS and normal controls, as well as distinctions among IC/BPS subgroups. A comprehensive literature search was conducted across PubMed/MEDLINE, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials. Relevant studies were shortlisted based on predetermined inclusion and exclusion criteria, followed by quality assessment. The primary focus was identifying specific taxonomic variations among these cohorts. A total of 12 studies met the selection criteria. Discrepancies were adjudicated by a third reviewer. The Newcastle-Ottawa Scale was used to assess study quality. Predominantly, the studies focused on disparities in urine microbiota between IC/BPS patients and normal controls, with one study examining gut microbiota differences between the groups, and two studies exploring vaginal microbiota distinctions. Unfortunately, analyses of discrepancies in other microbiota were limited. Our findings revealed evidence of distinct bacterial abundance variations, particularly involving Lactobacillus, alongside variations in specific metabolites among IC/BPS patients compared to controls. Currently, there is evidence suggesting significant variations in the diversity and species composition of the urinary microbiota between individuals diagnosed with IC/BPS and control groups. In the foreseeable future, urologists should consider urine microbiota dysbiosis as a potential aetiology for IC, with potential clinical implications for diagnosis and treatment.

Unsupervised Machine Learning Reveals a Vulvodynia-Predominant Subtype in Bladder Pain Syndrome/Interstitial Cystitis.

Background Bladder pain syndrome/interstitial cystitis (BPS/IC) is a chronic condition characterized by pelvic pain and urinary symptoms. Despite its significant impact on patients' quality of life, the heterogeneity of BPS/IC symptoms and the presence of comorbidities such as vulvodynia may not be adequately captured by validated questionnaires. Identifying vulvodynia in BPS/IC patients is crucial for providing appropriate treatment options. This study aimed to identify subtypes of BPS/IC patients using unsupervised machine learning and to investigate the prevalence of vulvodynia in each subtype. Methods We conducted a prospective cross-sectional study of 123 BPS/IC patients and 64 age-matched controls. Hierarchical clustering was performed using data from validated questionnaires, including the Numerical Rating Scale-11, Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Pelvic Pain and Urgency/Frequency scores, Overactive Bladder Questionnaire Short Form (OABq SF), Overactive Bladder Symptom Score (OABSS), and Pelvic Floor Distress Inventory-20. The optimal number of clusters was determined using the elbow method, and the characteristics of each cluster were analyzed. All participants underwent a vulvodynia swab test to assess vulvodynia symptoms. Results Unsupervised machine learning revealed three distinct clusters of BPS/IC patients. Clusters 0 and 2 differed significantly, with Cluster 2 characterized by significantly higher vulvodynia scores compared to other clusters (P < 0.001). In contrast, Cluster 2 had lower bladder pain scores (ICSI and ICPI) and overactive bladder symptom scores (OABq SF and OABSS) compared to other clusters. Clusters 0 and 1 were characterized by a predominance of bladder pain and urinary frequency symptoms, with Cluster 0 exhibiting more severe symptoms. Conclusions Our study identified distinct subtypes of BPS/IC patients using unsupervised machine learning, with Cluster 2 representing a vulvodynia-predominant subtype. This finding, along with the potential of targeted therapies such as non-ablative erbium YAG laser for vulvodynia, underscores the importance of assessing extravesical symptoms, particularly vulvodynia, for the diagnosis and treatment of BPS/IC. A tailored approach, including laser therapy for vulvodynia-predominant patients, may be necessary for optimal management of BPS/IC. The vulvodynia swab test plays a crucial role in assessing vulvodynia symptoms, underlining the limitations of validated questionnaires in capturing the full spectrum of BPS/IC symptoms. A comprehensive evaluation of patients, including the vulvodynia swab test, is essential for accurate subtyping and management of BPS/IC. Further research with larger sample sizes and investigation of the relationship between identified subtypes and other clinical data is warranted to advance our understanding and management of BPS/IC.

(028) IDENTIFYING A CORRELATION BETWEEN EHLERS DANLOS SYNDROME (HYPERMOBILITY TYPE) AND GENITOPELVIC PAIN IN WOMEN

Abstract Introduction Hypermobility Ehlers Danlos Syndrome (hEDS) is the most common subtype of The Ehlers Danlos Syndromes (EDS), a group of heritable connective tissue disorders. Signs and symptoms associated with hEDS include joint hypermobility, joint pain, back/neck pain, easy bruising, soft/velvety skin, stretchy skin, sensitive skin, allergies/hives, gastrointestinal symptoms, dizziness, dysautonomia, hernias, prolapse, and atrophic scaring. Patients with hEDS often display myofascial pain related to muscle overactivity, which may compensate for joint laxity. hEDS is strongly associated with mast cell activation syndrome (MCAS) and postural orthostatic tachycardia syndrome (POTS). Severity of the symptoms associated with hEDS falls on a spectrum. Patients who do not meet full diagnostic criteria for hEDS may still be diagnosed with hypermobile spectrum disorder (HSD). The 5-Point Hypermobility Questionnaire (5HQ) was designed to screen for HSD (1). A score of 2 or more has an 80-85% sensitivity and 80-90% specificity to detect HSD. As the molecular basis of hEDS is still unknown, the diagnosis of hEDS is made based on a positive diagnosis of HSD and additional criteria outlined in the 2017 International Classification of the EDS. Genitopelvic pain disorders (GPP) such as provoked vestibulodynia (PVD) and bladder pain syndrome (BPS) are highly associated with overactive pelvic floor muscle dysfunction (PFD) and mast cell proliferation/activation. As such, it seems likely that hEDS/HSD may play a role in GPP. Objective The objective of this study was to utilize the 5HQ to determine if there is a correlation between GPP and hEDS/HSD. Methods Adult female patients presenting to two clinics specializing in GPP between February 15th, 2023, to October 31st, 2023, prospectively completed the 5HQ. Patients presenting for complaints of a vulvar dermatoses were excluded from the analysis. If a patient screened positive on the 5HQ, a chart review was performed to obtain GPP diagnoses, including vestibulodynia (PVD), overactive pelvic floor muscle dysfunction (PFD), pudendal neuralgia (PN), bladder pain syndrome (BPS), vulvar candidiasis, and desquamative inflammatory vaginitis (DIV). Results Of the 234 patients who met inclusion criteria, 74 screened positive on the 5HQ (31.6%). Of the 74 patients, 73 had vestibulodynia (98.6%), 67 (90.5%) were diagnosed with PFD, 21 (28.4%) had PN, 16 had (probable) BPS (21.6.%), 13 (17.6%) had candidiasis, and 9 (12.2%) had DIV. Of the women with vestibulodynia 26 (35.1%) had allodynia confined to the posterior vestibule suggesting a PFD etiology and 47 (63.5%) had pain throughout their entire vestibule suggesting either an inflammatory or neuroproliferative etiology. Conclusions Nearly one-third of women with GPP screen positive for hESD/HSD. It is possible that myofascial sequelae of hEDS/HSD and MCAS may play a role in women with both GPP and hEDS/HSD. These results highlight the importance of screening women for joint hypermobility who present with GPP. Positive screening should warrant an examination and testing to rule in/out the diagnosis of hEDS and to guide appropriate referral to a specialist in this disorder. Further studies are planned to perform confirmatory diagnosis for hEDS and further explore associated medical conditions, such as MCAS, which may also contribute to forms of GPP. Reference: 1. Hakim AJ, Grahame R. 2003 Int J Clin Pract 57:163-166. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Dare bioscience, Incyte, Nuvig, AbbVie.

The Efficacy of CO2 Vaginal Laser in the Treatment of Recurrent, Post-Coital and Interstitial Cystitis: A Multicentric Prospective Study

Background: This multicentric prospective study was carried out at Fondazione Policlinico Universitario Campus Bio Medico and Ospedale di Stato of St. Marino Republic. Between 1 January 2019, and 31 December 2022, all pre- and post-menopausal women diagnosed with recurrent, post-coital, and interstitial cystitis at both centers were included in the study. The main aim of the study was to assess the effectiveness of vaginal CO2 laser treatment, alone or combined with intravesical hyaluronic acid instillations, in managing cystitis symptoms, such as dysuria, pollakiuria, and urgency, across the entire patient cohort. The secondary objective was to investigate the reduction in number of annual cystitis episodes post-treatment. Methods: Each woman underwent three to four sessions of micro-ablative CO2 vaginal laser treatment. A follow-up examination was conducted 12 months after the final laser session (up to December 2023), during which a post-treatment VAS assessment evaluated dysuria, daily pollakiuria, and urgency. The enrolled patients recorded the number of cystitis episodes experienced during the 12-month pre- and post-treatment period. Results: Results indicated the laser’s efficacy in reducing the total number of cystitis episodes per year and an improvement in symptoms up to one year post-treatment. Greater efficacy of the CO2 laser treatment, particularly when combined with intravesical hyaluronic acid instillation, was observed in both pre- and post- menopausal women. Conclusions: Fractional CO2 laser therapy represents a safe and efficacious, non-hormonal approach for pre- and post-menopausal women diagnosed with recurrent, post-coital, and interstitial cystitis.

(130) PREVALENCE OF CONDITIONS INVOLVING ABERRANT MAST CELL ACTIVITY IN PATIENTS WITH NEUROPROLIFERATIVE VESTIBULODYNIA

Abstract Introduction Neuroproliferative vestibulodynia (NPV) is a provoked vestibular pain shown to be associated with excess immunohistochemical staining for CD117 and PGP9.5, consistent with mast cells and nerves, respectively. NPV is distinguished from control tissue by having &amp;gt;8 mast cells/high power field. Objective In patients with a histopathologically confirmed diagnosis of NPV, we wished to assess the prevalence of concomitant conditions involving other aberrant mast cell activity. Methods Medical records from people with vulvas who underwent vestibulectomy between June 1, 2019 and October 31, 2023 at a single facility were retrospectively reviewed. All had histopathologically confirmed NPV, having observed &amp;gt; 8 positive CD117 stained cells/high power field in the sub-epithelial stroma. As part of their history, each patient provided a list of medical conditions which included disorders where aberrant mast cell activity has been reported. The following eight conditions were included in medical history forms: asthma, chronic sinusitis, endometriosis, food allergy/intolerance, interstitial cystitis, irritable bowel syndrome, migraine, and postural orthostatic tachycardia syndrome. Results A total of 88 NPV patients were included in this chart review. A total of 34 (39%) reported no other aberrant mast cell activity, however 54 (61%) had at least one concomitant condition. The most common conditions were migraine (n=21; 24%), interstitial cystitis (n=17; 19%) and endometriosis (n=15; 17%), followed by food allergy/intolerance (n=12; 14%), irritable bowel syndrome (n=9; 10%), asthma (n=9; 10%), chronic sinusitis (n=5; 6%) and postural orthostatic tachycardia syndrome (n=2; 2%). Among these 88 patients, a total of 33 (38%), 13 (15%), 3 (6%), 1 (1%) and 2 (2%) had one, two, three, four and five other conditions involving aberrant mast cell activity, respectively. There was no correlation between the number of concomitant conditions with aberrant mast cell activity reported and the density of CD117-immunopositive staining in the overall NPV cohort, whether diagnosed with lifelong or acquired NPV. Conclusions Patients with histopathologically confirmed NPV have a high prevalence of concomitant conditions associated with aberrant mast cell activity, possibly due to a genetic predisposition. While more studies are needed, NPV is likely part of a broader systemic collection of conditions associated with aberrant mast cell activity. This finding is relevant in terms of future diagnostic and treatment options for patients with NPV. Disclosure No.

(132) MICONAZOLE VAGINAL CREAM AND ACQUIRED NEUROPROLIFERATIVE VESTIBULODYNIA

Abstract Introduction The vestibular epithelium is non-keratinized and is thus susceptible to injury from an allergic reaction. Topical pharmaceutical agents applied to the genitals for various medical indications, such as miconazole vaginal cream to treat vaginal yeast infections, may absorb through the non-keratinized vestibular epithelium. Active and inactive ingredients in miconazole vaginal cream include miconazole nitrate, benzoic acid, cetyl alcohol, isopropyl myristate, polysorbate 60, potassium hydroxide, propylene glycol, purified water and stearyl alcohol. Patients without vestibular pain previously have reported applying miconazole vaginal cream to their genitals and immediately experienced excruciating burning that resulted in persistent unrelenting severe pain throughout the vestibule, symptoms consistent with acquired neuroproliferative vestibulodynia (NPV). Objective To review reports of clinic patients who used miconazole vaginal cream prior to a diagnosis of acquired NPV to provide awareness of the management of this condition. Methods We performed a chart review of individuals with vulvas presenting to a single sexual medicine clinic between June 2019 and June 2023 to identify those who met the following inclusion criteria. They were clinically suspected to have acquired NPV after an allergic reaction following use of miconazole vaginal cream. They failed conservative treatments for provoked vestibular pain and underwent vestibulectomy. Their excised vestibular specimens revealed an excess of CD117 immunopositive stained cells (&amp;gt;8 per high-power field), consistent with mast cells, and PGP9.5 immunopositive stained area, consistent with nerves, histopathologically confirming the diagnosis of NPV. In addition, demographic data, prior diagnoses and treatments, results from validated questionnaires, pertinent physical exam findings and treatment outcomes were collected. Results A total of 7 individuals met inclusion criteria. Mean age at the time of exposure to miconazole vaginal cream was 23 (range 18-29) years. Mean age at presentation to our sexual medicine facility was 28 (range 22-33) years, thus a delay in diagnosis of miconazole vaginal cream-induced acquired NPV of 5 (range 1-12) years. 71% were previously diagnosed and unsuccessfully managed as hormonally-mediated vestibulodynia and 29% as interstitial cystitis. The mean pain domain score and overall score for the Female Sexual Function Index was 1.2/6 (range 0-3.2/6) and 11.7/36 (range 4.2-18.1/36), respectively. A total score of &amp;lt;26 is indicative of sexual dysfunction. The mean Female Sexual Distress Scale-Revised score was 32.2/52 (range 21-39/52), consistent with significant distress. Conclusions Our cohort of patients with miconazole vaginal cream-induced acquired NPV experienced several years of misdiagnoses, unsuccessful treatments, significant pain, and distress. It is hypothesized that miconazole vaginal cream induces NPV in genetically susceptible individuals in part because the vestibular epithelium is non-keratinized and therefore more easily absorbs the ingredients in the miconazole vaginal cream, which may result in an allergic response in the subepithelial region of the vestibule. This allergic reaction results in accumulation of mast cells in the subepithelial stroma that release nerve growth factor leading to neuroproliferation with subsequent allodynia and hyperalgesia. In individuals who develop yeast infections, use of systemic strategies and rather than topical medication is encouraged to avoid potential allergic reactions and resultant acquired NPV. Disclosure No.

Cdk1/p53/p21 feedback loop mechanisms in the pathogenesis of interstitial cystitis/bladder pain syndrome

PurposeThis study aimed to elucidate the role of the Cdk1/p53/p21 feedback loop in the pathogenesis of interstitial cystitis (IC)/bladder pain syndrome (BPS). Materials and methodsAn IC/BPS cell model was established. Cell viability was determined using the CCK-8 assay. Flow cytometry was adopted to assess cell apoptosis rates. ELISA was employed to measure secretion levels of inflammatory factors (IL-6, IL-8, and TNF-α). Gene expressions were assessed using PCR, while protein expressions were analyzed through Western blotting analysis. Epithelial permeability was demonstrated using the phenol red leakage experiment and FITC-dextran permeability assay. The interaction between proteins was determined using co-immunoprecipitation, and protein localization was investigated using immunofluorescence. ResultsThe CCK-8 assay revealed a significantly reduced viability of IC/BPS cells compared to normal epithelial cells (p < 0.05). Elevated levels of IL-6, IL-8, and TNF-α were detected in IC/BPS cells. Changes in the expressions of E-cadherin and ZO-1 were evident, leading to increased epithelial permeability in IC/BPS cells. Furthermore, within IC/BPS cells, Cdk1 phosphorylated p53 in the nucleus. The Cdk1/p53/p21 feedback loop was established to influence urothelial permeability. Both p21 and Cdk1 inhibitors notably reduced the epithelial permeability in IC/BPS cells. ConclusionThe Cdk1/p53/p21 feedback loop was instrumental in IC/BPS, acting as a regulator of urothelial permeability. This discovery offered a novel therapeutic approach for IC/BPS management.