Acta Obstetricia et Gynecologica. 2010; 89: 1504–1510 ACTA OVERVIEW Medical and physical predictors of localized provoked vulvodynia NINA BOHM-STARKE Karolinska Institutet, Department of Clinical Sciences, Division of Obstetrics and Gynecology, Danderyd Hospital, Stockholm, Sweden Abstract Vulvodynia in young women is a significant clinical challenge. This overview focuses on localized provoked vulvodynia (LPV) with regard to medical and physical predictors of the condition. Several causative factors have been proposed and one major conceptual issue is the role of inflammation. Trauma to the vestibular mucosa causes an initial inflammatory response which may result in peripheral and central pain sensitization. In women with LPV, evidence of mucosal nerve fiber proliferation and enhanced systemic pain perception has been found. A dysfunction of the pelvic floor muscles is common and many patients also suffer from other bodily pain. In general, the level of scientific quality in published studies on vulvodynia is low. Further research on epidemiology, etiology and conduction of clinical trials with high evidence grade is desired. Key words: Human sexuality, vulvodynia, provoked vestibulodynia, predictors, etiology Introduction therefore focus on the localized and provoked form of For personal use only. vulvodynia with regard to medical and physical pre- Vulvodynia means ‘pain in the vulva’ and includes dictors of the condition. many clinical features. Some patients have continu- ous pain in the major part of the vulvar area, whereas others suffer from more localized pain, usually pro- Method voked by vaginal intercourse or tampon use. The symptoms often interfere with the patients’ sexual The references included in this overview are publica- function and psychological well-being (1). Superficial tions found in Medline (PubMed) from any date. dyspareunia confined to the vaginal opening is the Primary search terms were vulvodynia (285), vesti- most common form of vulvodynia in young women. bulodynia (326), superficial dyspareunia (80) and This condition was formerly called vulvar vestibulitis vulvar vestibulitis syndrome (153), including both Acta Obstet Gynecol Scand Downloaded from informahealthcare.com by 90.229.197.73 on 12/26/10 syndrome due to the inflammatory appearance of the reviews and original articles. The search results vestibular mucosa. It is, however, now classified as a showed a significant overlap for these terms. Addi- pain syndrome and a new nomenclature for vulvar tional search terms were predictors, etiology, inflam- pain has been proposed by the International Society mation and pain mechanisms. No meta-analyses or for the Study of Vulvovaginal Disease (ISSVD) (2). systematic reviews were found. When no recognized underlying cause of the pain is identified, the vulvodynia is either classified as gen- eralized or localized and further categorized into Localized provoked vulvodynia provoked, unprovoked or mixed subgroups. The gen- eralized form of vulvodynia is less common and only a Women with localized provoked vulvodynia (LPV) few studies have been conducted. This overview will seek medical care due to an inability to have vaginal Correspondence: Nina Bohm-Starke, Karolinska Institutet, Department of Clinical Sciences, Division of Obstetrics and Gynecology, Danderyd Hospital, 182 88 Stockholm, Sweden. E-mail: [email protected] (Received 2 May 2010; accepted 25 September 2010) ISSN 0001-6349 print/ISSN 1600-0412 online Ó 2010 Informa Healthcare DOI: 10.3109/00016349.2010.528368 Predictors of vulvodynia 1505 intercourse. Some women have a primary form of abandoned and the condition is now regarded as a LPV, experiencing pain ever since first tampon use or pain syndrome. intercourse. For others, various period of pain free In vulvar biopsies obtained from women with LPV, vaginal penetration preceded the onset of symptoms an infiltration of mainly T-lymphocytes is located in (secondary LPV). The pain is often described as the subepithelial part of the lamina propria and is burning and sometimes knife-sharp at contact, typi- often described as a nonspecific chronic inflammation cally located between 4 and 8 o’clock on the introitus, by pathologists (9,10). However, in later studies with just exterior to the hymenal ring. In severe cases, the better selection of control specimens, similar infiltra- major part of the vestibular mucosa, including the tion of inflammatory cells is also seen in healthy openings of the paraurethral glands, might be women and cannot serve as a histological indicator affected. Erythema around the openings of the of LPV (11,12). Bartolin’s glands and in the posterior fourchette is Studies on the pro-inflammatory mediators inter- often found. The mucosa is presented with an allo- leukin I-b (IL-1b) and tumor necrosis factor alpha dynia (sensation of pain from a light touch) and (TNF-a) in vulvar tissue of patients with LPV have hypersensitivity to mechanical stimuli such as touch, been published with conflicting results. Foster and pressure and vaginal penetration (3). In many Hasday found elevated tissue levels of IL-1b and women, a varying degree of vaginismus is also found. TNF-a, but these pro-inflammatory mediators were The prevalence and incidence for LPV is unclear. actually at higher levels in the surrounding vulvar As for vulvodynia, the prevalence shows a great variety tissue than in the area of inflammation, confirming from 3 to 18% in epidemiological studies (4,5). Ini- the clinical finding of a wider area of involvement tially, vulvodynia was thought to primarily affect Cau- beyond the area of erythema (13). In contradiction, casian women (6,7). In survey of ethnically diverse Eva et al. found no differences between patients and women, similar lifetime prevalence rates of chronic controls regarding these mediators (14). The two vulvar burning or pain on contact were reported (8). inducible enzymes nitric oxide synthase (iNOS) No single causative factor has yet been identified for and cyclooxygenase 2 (COX 2) are hardly detectable LPV and the etiology is considered multi-factorial. in the skin and mucosa under normal conditions. Most probably a vast number of “triggers” may ini- However, its expression increases in response to var- tiate the pain and if not properly taken care of, a more ious mediators released at site of inflammation or less chronic pain condition might develop. (15,16). COX 2 and iNOS were not upregulated in For personal use only. A combination of causes might include psychosexual biopsies obtained from the vestibular mucosa in factors as well as more obvious physical trauma to the women with LPV as compared to healthy controls. tissue such as recurrent infections. Much effort has This finding is inconsistent with an ongoing cell- been made to find pathophysiological changes char- mediated inflammation and may also explain why acteristic for LPV. corticosteroids are not helpful for LPV (17). The vestibular mucosa Infections and antigen The vestibular mucosa is of endodermal origin and by Allergy has been discussed as a causative factor for definition visceral tissue, but has a somatic innerva- LPV. The most likely antigen candidate would be Acta Obstet Gynecol Scand Downloaded from informahealthcare.com by 90.229.197.73 on 12/26/10 tion with perception for pain, temperature and tactile from microbes commonly affecting the vulva. Human stimuli. It has a non-pigmented epithelium covered by papillomavirus (HPV) was first considered, but in a thin keratinized layer. The mucosa serves as a thin multiple studies the detection of HPV using PCR mechanical and immunological barrier susceptible to was as common in controls as in women with LPV infections as well as mechanical trauma. (18,19). Herpes simplex virus (HSV) is also a com- mon vulvar infection, but to date, HSV does not appear to cause LPV (20). Bacterial vaginosis (BV) Inflammation with an overgrowth of anaerobic bacteria is also a common cause of vaginitis in young women. Accord- LPV or the former vulvar vestibulitis syndrome was ing to case–control studies, women with LPV are first regarded as a chronic local inflammatory condi- more likely to report a history of BV than asymptom- tion generating an interest among physicians for atic controls (21,22). potential inflammatory mechanisms. Based on a Candida is frequently present in the vulva. Up to number of small pilot studies, in addition to clinical 75–80% of women develop symptomatic candidiasis observations, the initial inflammatory theory has been during their lifetime (23). In many cases patients with 1506 N. Bohm-Starke LPV have a history of recurrent candidiasis and they ever-users of COCs compared to non-users. When often relate the onset of LPV to an acute episode of COCs were used before the age 16, the relative risk yeast infection (24). However, the evidence for a reached 9.3 and increased with the duration of COC correlation between LPV and genital infections is use up to 2–4 years. The relative risk was higher when scanty. A correlation to recurrent symptomatic yeast the pill used was highly pro-gestogenic and andro- infections has been reported in case–controls studies, genic but low in estrogenic potency (31). These but the data are often based on self-reported infec- findings were not, however, confirmed by a tions. There is a need for prospective observational population-based case–control study from 2008 (32). studies with clinically and culture-confirmed cases The hormonal effect of COCs on genital mucosa before any conclusions can be drawn. has mainly been studied in the endometrium. In a previous study, it was observed that women Recently, it was observed that the vestibular mucosa with a history of hives were 2.5 times more likely to of healthy women on COCs undergoes changes com- develop vulvodynia, suggesting that environmentally pared to non-users (33). The dermal papillae become induced allergic reactions could alter the immuno- shallower and sparser which might result in a more inflammatory response and predispose for the devel- fragile and sensitive mucosa (34).