(132) MICONAZOLE VAGINAL CREAM AND ACQUIRED NEUROPROLIFERATIVE VESTIBULODYNIA
Authors: Schardein J , Wexler T , Goldstein S W , Yee A , Goldstein I 
Published: June 2024

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 (&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 &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.