Abstract Introduction Vestibular fibroblasts from patients with neuroproliferative vestibulodynia (NPV) versus age-matched controls produced higher proinflammatory cytokine levels of various interleukins when provoked with candida albicans in vitro. In genetically susceptible patients, this enhanced cytokine synthesis is hypothesized, in part, to lead to neuroproliferation in vestibular tissue resulting in allodynia/hyperalgesia. Patients with acquired NPV, who initially experienced pain-free penetration in their early adult reproductive life, may experience persistent severe vestibular burning following an allergic reaction to a topical agent applied to the non-keratinized vestibular epithelium. In contrast, patients with lifelong NPV present with the classic history of inability to insert a tampon at menarche (mean age 12.4 years). Patients with lifelong NPV may have unknowingly been exposed to an allergen early in their childhood, potentially even triggered from ointments used in infancy to protect from diaper rash, resulting in local vestibular mast cell accumulation in genetically susceptible patients. Agents commonly used to prevent are zinc oxide 40%, (Desitin) with inactive ingredients petrolatum, cod liver oil, lanolin, talc, glycerin, sorbitan sesquioleate, beeswax, tocopheryl acetate and fragrance and A+D ointment that includes petroleum jelly, lanolin, lavender oil, light liquid paraffin, vitamin A and vitamin D. It is possible an allergic reaction could result from any of these ingredients when applied to the non-keratinized vestibular epithelium. Objective We wished to better understand the possible triggering event in patients with lifelong NPV. Methods A chart review was performed of patients who presented between January 2019 and June 2023 who were clinically suspected to have lifelong NPV based on a history of inability to use tampons and inability to have pain-free penetration and histopathlogically confirmed to have NPV. Information was obtained from a parent or caregiver who regularly changed patient’s diapers as to what agents were utilized to manage diaper rash. Results Our patient cohort included 14 individuals with vulvas, mean age 25 (range 18-37) years. One patient prone to diaper rash was treated with A+D baby diaper rash ointment and Flanders buttocks ointment (zinc oxide, white petrolatum, white beeswax, Peruvian balsam). One patient had a “bad” yeast infection as a baby and received “topical antibiotics”. Five patients claimed Desitin and Vaseline were used while six patients claimed Desitin alone, two of whom cryied every time they Desitin was applied. One patient from Puerto Rico, received “a sock filled with cornstarch that dabbed the vaginal area and crevices after wiping the area clean”. Conclusions The endodermal vestibular epithelium is not protected by a keratin layer, including in babies at a very young age. In genetically susceptible babies, an allergic reaction to an active/inactive agent used to prevent or treat diaper rash could have potentially triggered mast cell accumulation in the baby’s vestibule leading to increased synthesis of cytokines and growth factors resulting in neuroproliferation consistent with lifelong NPV, evidenced by the inability to place a tampon at menarche. More research into this concern is needed. Disclosure No.