The Falsetta lab is committed to translational women’s health research. Our goal is to identify previously unknown mechanisms of disease for disabling vulvar conditions, namely vulvodynia and lichens. By understanding the mechanisms of disease we can 1) identify new targets for therapy, 2) better adapt current modalities of treatment for rapid improvements in care, and 3) create new metrics to identify disease at an early stage and objectively track disease progression and response to treatment. Our research focuses on the basic science of disease, while directly interfacing with the clinical experts delivering care.
Localized provoked vulvodynia (LPV) is characterized by acute and lasting pain in response to light touch of the vulvar vestibule (area immediately surrounding the vaginal opening), which is associated with a reduction in quality of life. Although women afflicted with LPV experience profound pain that negatively impacts their sexual health, they show no overt signs of disease. The origins of vulvodynia are poorly understood, and no current therapy targets the root of the disease or is completely curative, perhaps save surgical removal of the affected tissue. The goal of our research is to identify less invasive, ideally topical, therapies. We have determined that a persistent low level of inflammation, generally undetectable clinically, is a key contributor to vulvodynia. Mostly recently, we have uncovered evidence pointing to a defect in the ability to resolve this inflammation, which may be the product of alterations in the presence or abundance of the molecules that help resolve inflammation named specialized pro-resolving mediators (SPMs) and the receptors that recognize these SPMs. Exogenous SPM treatment can overcome such defects, reducing inflammatory markers in both tissue culture and mouse models of disease, as well as measures of pain in mice, suggesting SPMs are excellent therapeutic candidates. SPMs are naturally produced by the body through metabolism of omega-3 and omega-6 fatty acids and are safe. Although our work in this area is ongoing, our findings suggest vulvodynia is the product of “two hits.” The first hit involves exaggerated inflammatory signaling, rendering the vestibule hypersensitive to inflammatory stimuli, such that a woman’s own natural flora may elicit a response. We are currently focusing on investigating the second hit, involving dysregulation of the resolution machinery.
Lichen planus (LP) and lichen sclerosus (LS) are common inflammatory dermatoses of the vulva characterized by intense pruritus (itching), burning, and changes in the architecture of the vulvar anatomy. Architectural changes can cause a loss of plasticity of the vagina, loss of mobility of the clitoral hood and/or fusion to the clitoral glans, and urinary symptoms (e.g. incontinence, dysuria). Additional manifestations include ulcers, erosions, and pre-cancerous or cancerous lesions. The standard of care for patients with LP and LS is topical application of ultrapotent steroids, more frequently to start and tapering off to weekly maintenance dosing, increasing frequency with flares or complications. Therefore, these are lifelong disorders, requiring long term treatment and regular follow up. Currently, there are no curative treatments available, and any architectural changes occurring prior to or during treatment are irreversible. The causes of lichen dermatoses are not well understood. Although these diseases are considered scarring dermatoses and the architectural changes are referred to as “scars,” limited and conflicting information about the role of scarring in is available. There is some evidence to implicate alterations in scarring/wound healing in lichenoid vulvar disease, and our research in this area aims to evaluate the role of scarring in lichenoid disease by identifying specific pathways and targets that may be aberrant.