The Relationship Between Vulvovaginal Candidiasis and Provoked Vulvodynia: A Systematic Review

Abstract

Background Provoked vulvodynia (PVD) is a chronic vulvar pain condition affecting up to 8.3% of the female population. Despite many years of research, no clear cause for PVD has been identified. Several risk factors have been studied, including vulvovaginal candidiasis (VVC). However, to date, the role of Candida infections in PVD has remained unclear. VVC and PVD have an overlap of symptoms that may contribute to diagnostic inaccuracy and mistreatment. Aim To systematically review the literature on the relationship between VVC and PVD. Methods Cohort and case-control studies were included that compared women with PVD with healthy controls with respect to the presence of a history of Candida vulvovaginitis. PVD had to be diagnosed by Friedrich’s criteria or the International Society for the Study of Vulvovaginal Disease criteria. The inclusion process as well as the quality appraisal of the studies, using the Newcastle-Ottawa Quality Assessment Scale, were performed independently by 2 authors. Main Outcome Measure Outcomes of the population-based case-control studies were listed as odds ratio. Outcomes of the pathophysiological studies were based on local pro-inflammatory responses on Candida in vitro. Results We included a total of 14 studies, both population and clinic-based case-control, and pathophysiological research. 7 studies were of low methodological quality, and 7 studies were of medium methodological quality. The population-based case-control studies showed a significantly increased odds ratio for self-reported VVC in PVD cases compared with controls. The pathophysiological studies revealed a tendency for an increased local proinflammatory response on Candida in vitro in patients with PVD. Owing to the substantial heterogeneity of the studies, meta-analysis was not performed. Clinical Implications Health care providers may consider a diagnosis of PVD in women with self-reported VVC, and to act on this properly. Reiteration of antifungal prescriptions by physicians without a decent diagnosis, will lead to mistreatment. Women should be informed by their health care provider that intercourse during (or shortly after) the treatment of VVC might worsen the vulnerability of the vulvar skin. Strength and Limitations This is the first systematic review performed to describe the relation between VVC and PVD. An independently performed in- and exclusion process and quality appraisal, ensured optimal internal validity. However, there were important methodological limitations and the size of heterogeneity prevented establishing a meta-analysis. Conclusion This systematic review is unable to draw conclusions regarding a relationship between actual VVC and PVD because studies were based on self-reported VVC. Until new evidence becomes available, we advocate that PVD should be considered as an unexplained chronic pain condition. In women with recurrent or persistent VVC-like complaints, physicians should consider a diagnosis of PVD.

Localized Provoked Vulvodynia-An Ignored Vulvar Pain Syndrome

“…Women with LPV have a history of recurrent vulvovaginal candidiasis (RVVC) more often than control women. This finding has been consistently replicated in several case-control studies of LPV (Leusink et al, 2018). Further, women with LPV often have cutaneous hypersensitivity to Candida albicans as detected by patch skin testing.…”

“…In areas with the highest densities of inflammation, T and B cells form lymphoid aggregates that represent secondary lymphoid tissue (Tommola et al, 2015;Figures 2A, B). The presence of lymphoid aggregates and increased density of B cells, including activated plasma cells are the major differences between the vestibular tissue from women with LPV and samples from control women (Leusink et al, 2018). Overall, the total number of inflammatory cells is markedly increased in the tender areas of the vestibule (Tommola et al, 2015).…”

Antifungal (oral and vaginal) therapy for recurrent vulvovaginal candidiasis: a systematic review protocol

“…In addition, it is still important to recognise that the excessive use and overuse of such topical agents have had other adverse consequences such as oedema, irritability of the skin and maybe even chronic vulvar pain condition (vulvodynia) 12 13…”

Emerging Evidence of Macrophage Contribution to Hyperinnervation and Nociceptor Sensitization in Vulvodynia

“…However, vulvodynia is primarily a pain disorder and not secondary to factors such as vaginismus, disordered arousal or lack of vaginal lubrication (Heim, 2001). Frequently there is no history of trauma or infection, though many women report prior candiasis (Leusink et al, 2018). Women and girls of all ages can be affected but most are in younger age groups and a high proportion under 25 years (Harlow et al, 2014).…”