Severe Allergic, Inflammatory and Traumatic Reactions of the Vestibule Associated with Acquired Neuroproliferative Vestibulodynia
Authors: Goldstein S , Yee A , Goldstein I 
Published: July 2022

ABSTRACT

Introduction
The endodermal vestibule epithelial surface is very thin (∼ 50 um) and unlike the ectodermal vulva has no protective keratinized stratified squamous epithelium, therefore the vestibule is particularly susceptible to injury as a reaction to allergy, inflammation, or trauma. In some women these injuries result in excess mast cell and nerve accumulation in the vestibular epithelium and stroma, leading to neuroproliferative vestibulodynia (NPV). Acquired NPV is diagnosed by first obtaining a detailed history. Penetration must have initially been pain-free, followed by persistent entrance dyspareunia after exposure of the endodermal vestibule to: a topical agent causing a severe allergic reaction such as an antifungal vaginal cream; recurrent inflammatory conditions including vaginal candidiasis; or repeated blunt trauma, as with horseback riding. Acquired NPV is often observed in women with very sensitive genital skin. There are limited data regarding the various agents and conditions associated with acquired NPV.

Objective
The objective of this study was to examine the various agents and conditions that potentially caused NPV among our patients. Identification of iatrogenic or other topical triggers of NPV could inform both providers and the public of agents to potentially avoid applying these to the vestibule.

Methods
A retrospective chart review of women who underwent complete vestibulectomy for suspected NPV between June 2019 – November 2021 was performed. Inclusion criteria for this study: i) a history consistent with acquired NPV, ii) undergone vulvoscopy to rule out other forms of vestibulodynia, iii) a positive vestibular anesthesia test, iv) treatment by complete vestibulectomy with vaginal advancement flap, and v) a diagnosis of neuroproliferative vestibulodynia confirmed by immunohistochemical staining of excised vestibular tissue by CD117 and PGP9.5.

Results
A total of 47 charts were reviewed: 43% (n = 20, mean age 34 ± 15 years) had acquired NPV and met inclusion criteria; 57% (n = 27, mean age 28 ± 10 years) had congenital NPV. A history of entrance dyspareunia following a severe allergic reaction to a topical agent occurred in 12 women, the most common substance being topical miconazole (n=7, 58%). Other topical agents included a hotel shampoo (n=1), hair dye (n=1), lubricant (n=1), scented soap (n=1), and spermicide (n=1). Four (20%) reported recurrent inflammatory conditions including vaginal candidiasis treated with oral medication; four (20%) reported symptoms after blunt perineal trauma including a 30 fall from a waterfall (n=1), horseback riding (n=1), bicycle riding (n=1), and straddle injury (n=1). Eight patients (40%) reported having sensitive genital skin.

Conclusions
In our patient population, the most common agent triggering NPV was topical miconazole which contains inactive ingredients that may be associated with allergic reactions including: benzoic acid, beta hydroxy acid, peglicol 5 oleate, and pegoxol 7 stearate. Since the endodermal vestibule epithelium is thin without keratin, making it vulnerable to injury, topical agents to the vestibule, especially when it is inflamed, should be avoided and oral agents for inflammatory conditions be considered when appropriate. Women often purchase over the counter topical miconazole without knowledge of the potential side effects.

Disclosure
No