(266) Miconazole Vaginal Cream-Induced Acquired Neuroproliferative Vestibulodynia

Abstract

Abstract Introduction The endodermal vestibule lies between the ectodermal vulva and the mesodermal vagina. Unlike the vulvar skin, the vestibular epithelium is thin, non-keratinized, and its submucosal immune cells are more susceptible to activation. Topical pharmaceutical agents that are applied to the genitals for various medical indications are likely to contact the vestibular epithelium. For example, miconazole vaginal cream (MVC) is approved for treatment of vaginal yeast infections and the irritation associated with the yeast infection. Active and inactive ingredients in MVC include miconazole nitrate, benzoic acid, cetyl alcohol, isopropyl myristate, polysorbate 60, potassium hydroxide, propylene glycol, purified water and stearyl alcohol. We have observed cases where individuals, previously without vestibular pain, have applied MVC to their genitals and immediately experienced excruciating burning that resulted in persistent unrelenting severe pain throughout the vestibule, which is a symptom of acquired neuroproliferative vestibulodynia (ANPV). Objective Our objective is to report cases of patients who used MVC and were diagnosed with ANPV in order to provide awareness of this condition. Methods We performed a retrospective chart review of persons with vulvas presenting to a single sexual medicine clinic between 6/2019-6/2023 who were clinically suspected to have ANPV after experiencing an allergic reaction following use of MVC. Patients were included who failed conservative treatments for provoked vestibular pain, underwent vestibulectomy and were histopathlogically diagnosed with ANPV (>8 CD117 stained immunopositive cells per high-power field (HPF), consistent with mast cells, and excess PGP117 stained immunopositive cells, consistent with nerves). Demographic data, prior diagnoses and treatments, and results from validated questionnaires were collected. Results Our patient cohort included 7 individuals who met the criteria for MVC-induced ANPV. Mean age at time of MVC-induced vestibular pain was 23 (range 18-29) years. Mean age of presentation to our sexual medicine facility was 28 (range 22-33) years. Mean years of delay in diagnosis of MVC-induced ANPV was 5 (range 1-12) years. 71% and 29% were previously diagnosed and unsuccessfully managed as hormone-mediated vestibulodynia and interstitial cystitis, respectively. The mean pain score and overall score for the Female Sexual Function Index (FSFI) was 1.2/6 (range 0-3.2/6) and 11.7/36 (range 4.2-18.1/36), respectively. All total FSFI scores were <26 and indicative of sexual dysfunction. The mean Female Sexual Distress Scale-Revised score was 32.2/52 (21-39/52), consistent with significant distress. Conclusions Our cohort of patients with MVC-induced ANPV experienced several years of misdiagnoses, unsuccessful treatments, and significant pain and distress. It is hypothesized that MVC induces ANPV in genetically susceptible individuals possibly due to activation of the innate submucosal immune cells from an allergic reaction to active or inactive ingredients in the MVC. This allergic reaction results in accumulation of mast cells in the subepithelial stroma that release cytokines and growth factors leading to proliferation of nerves with subsequent symptoms of allodynia and hyperalgesia. Avoidance of topical medications and use of systemic antifungal strategies in individuals with yeast infections may be advisable. Disclosure No.