(107) Uncovering the Role of Mast Cell Dysfunction in the Pathophysiology of Vulvodynia, Post-orgasmic Illness Syndrome, and Interstitial Cystitis (2023)

Abstract Introduction Certain sexual disorders are under-reported, under-researched, and rarely discussed. Many patients have suffered from ailments such as vulvodynia, a subset of vulvodynia called vestibulodynia, post-orgasmic illness syndrome (POIS), and interstitial cystitis (IC) without clear and optimal treatment strategies. To bring more awareness to these conditions, researchers and other medical professionals are working to elucidate their pathophysiologies in order to provide patients with therapeutic solutions. Mast cell dysfunction is one proposed mechanism of disease for these conditions. Mast cells are CD34+/CD117+/CD13 pluripotent progenitors of hematopoietic stem cells. They serve as innate immune cells that play a significant role in allergic responses, inflammation, and tissue homeostasis. They undergo maturation via growth factors and interleukins in the periphery and are heavily implicated in processes such as anaphylaxis, arthritis, coronary artery disease, autoimmune disorders, and cancer. As the body of research grows surrounding the function of mast cells and mast cell activation, researchers are finding that they may be implicated in multiple disease processes, even in genitourinary disorders. We know little about the etiology of disorders that affect sexual function like vulvodynia, POIS, and IC, but when considering their inflammatory and/or allergic-type symptoms, such as itching, burning, and congestion, we hypothesize that their pathophysiology may be correlated to mast cell function impairment. Objective The purpose of this study is to determine if mast cell dysfunction correlates with the pathophysiology of vulvodynia, POIS, and IC based on a literature review. Methods The authors reviewed existing literature published from January 2010 - June 2022 that explored the histopathological, pathophysiological, and etiological nature of vulvodynia, POIS, and IC. The selection criteria for this narrative review included: original articles (randomized and non-randomized clinical trials, including prospective observational studies, retrospective cohort studies, and case-control studies), review articles, and Cochrane analyses concerning the relationship between sexual disorders and allergens and/or immunology. Eighteen articles met the inclusion criteria. Results From the studies evaluated, it is reasonable to infer that vulvodynia, POIS, and IC have an immunological component to their pathophysiology. The inflammatory nature of all the diseases above indicates a definite immunological involvement, but as more research emerges, several medical providers and authors alike are noting that immunology and, certainly, mast cells may play a more significant role than initially hypothesized. While mast cells are likely not the sole cause of disease, it would be in the patient’s and provider’s best interest to consider their involvement in multifactorial pathophysiology for sexual disorders. Conclusions The pathophysiology of sexual disorders like vulvodynia, POIS, and IC is not currently well understood. However, review of existing literature supports that mast cell activation and, to a lesser extent, Toll-like receptors (TLRs) and lymphocytes may play a cardinal role in the pathophysiology of the sexual disorders described. Further research needs to be conducted on the possible pathophysiology of sexual disorders broadly so healthcare practitioners can provide effective, evidence-based treatment that will provide patients optimal relief. Disclosure No