Neurochemical characterization of the vestibular nerves in women with vulvar vestibulitis syndrome

Women with vulvar vestibulitis syndrome (VVS) have a distinct burning pain provoked by almost any stimuli in the area around the vaginal introitus. In a previous study we observed an increased number of intraepithelial free nerve endings in women with VVS. The aim of the present study was to neurochemically characterize the superficial nerves in the vulvar vestibular mucosa of women with VVS. Immunohistochemical methods were used to detect neuropeptides normally found in various types of nerve fibers. Calcitonin gene-related peptide, which is known to exist in nociceptive afferent nerves, was the only neuropeptide detected in the superficial nerves of the vestibular mucosa. These findings confirm our previous theory that the free nerve endings within the epithelium are nociceptors. Copyright Copyright 1999 S. Karger AG, Basel     

Human papillomaviruses and vulvar vestibulitis

OBJECTIVE: To assess the relationship between human papillomavirus (HPV) infection and vulvar vestibulitis syndrome. METHODS: From November 1995 to December 1997, 135 women with vulvar vestibulitis were compared with 322 controls who had no evidence of vulvar vestibulitis. Human papillomavirus DNA was amplified by polymerase chain reaction and detected with liquid-capture molecular assay. RESULTS: Human papillomavirus DNA was found in 29.6% of cases and in 23.9% of controls (relative risk [RR] 1.4; 95% confidence interval [CI].8, 2.2). The prevalence of HPV tended to decrease with increasing duration of pain among cases. Thus, prevalences were 37. 5%, 29.6%, and 22.0% for pain durations of 3-6 months, 7-12 months, and 13-24 months, respectively (P =.14). Prevalence of HPV also tended to increase with pain intensity among cases, but that association was not statistically significant (P =.57). Prevalence percentages for women with low, moderate, or severe pain were 27.5%, 28.8%, and 34.4%, respectively. Prevalence of HPV was slightly higher in cases with the most severe pain (34.4%) than in controls (23.9%) (RR 1.8; 95% CI.8, 4.0). In cases with the most pain in the shortest time (3-6 months), prevalence of HPV was double that of controls (50% versus 23.9%) (RR 3.5; 95% CI 1.0, 12.7; P =.054). CONCLUSION: There was little support for the idea that HPV might be related to vulvar vestibulitis.     

Human papillomavirus DNA in tissue biopsy specimens of vulvar vestibulitis patients treated with interferon.

Thirteen women with the diagnosis of vulvar vestibulitis based on clinical symptoms, presence of vestibular tenderness on physical examination, and acetowhite changes of the vulvar vestibule were treated with intradermal injection of alpha-interferon. Biopsies of the acetowhite areas were analyzed for human papillomavirus (HPV) DNA using polymerase chain reaction amplification and dot blot hybridization. Eleven of 13 subjects harbored one of the HPV DNA types; six of these were type 16 and/or 18 and the others were unidentified. Five subjects (all HPV DNA-positive) reported resolution of symptoms with interferon therapy. Our results indicate the presence of HPV DNA in a subset of patients with vulvar vestibulitis, but its presence is not predictive of response to interferon therapy.     

Hyperoxaluria in women with vulvar vestibulitis syndrome

OBJECTIVE: To determine whether evaluation and treatment of hyperoxaluria in vulvar vestibulitis syndrome (VVS) is justified. STUDY DESIGN: Forty women (mean age, 24.5 years; range, 18-35) diagnosed with VVS at a sex therapy clinic participated. Diagnosis of VVS relied upon Friedrich's criteria: (1) severe vulvar vestibular pain upon touch or attempted vaginal entry, (2) tenderness to pressure localized within the vulvar vestibule, and (3) physical findings confined to vulvar erythema of various degrees. Oxalate was measured in 24-hour urine samples. Women with hyperoxaluria (urine oxalate >50 mg/24 h) were placed on a low-oxalate diet and oral calcium citrate as single therapy and reevaluated 3 months later. RESULTS: Hyperoxaluria was diagnosed in 7 women (17.5%), of whom 1 demonstrated an objective improvement and could have pain-free vaginal intercourse following treatment, yielding a 2.5% benefit from the evaluation and treatment of hyperoxaluria. CONCLUSION: There is no justification for evaluation and treatment of hyperoxaluria in women with VVS due to its low yield and economic burden.     

Differential characterization of women with vulvar vestibulitis syndrome

OBJECTIVE: We differentiated women with vulvar vestibulitis syndrome into subgroups on the basis of the time of symptom onset, a history of recurrent vulvovaginal candidiasis, and the interleukin-1 receptor antagonist gene polymorphism. STUDY DESIGN: One hundred sixty-two consecutive patients with strictly defined vulvar vestibulitis syndrome were asked to fill out a questionnaire with the assistance of their gynecologist. A buccal sample was collected from each subject for the analysis of interleukin-1 receptor antagonist gene polymorphism; vaginal and vestibular microbial investigations were performed. RESULTS: Symptoms began with the first act of coitus in 20.4% of patients. A history of a recurrent Candida vulvovaginal infection was reported in 42.6% of patients; 25.9% of the patients were positive for the homozygous interleukin-1 receptor antagonist 2,2 genotype. Women with primary vulvar vestibulitis syndrome differed from women with secondary vulvar vestibulitis syndrome; women with primary vulvar vestibulitis syndrome were younger at the time of the onset of the symptoms (23.8 vs 31.2 years, P <.0001) and had never been pregnant (84.8% vs 61.2%, P <.0001). Women with a history of recurrent Candida vulvovaginitis differed from the other subjects by having a higher frequency of constant vestibular pain (40.6% vs 20.4%, P =.005), a vaginal discharge (79.7% vs 45.2%, P <.0001), and dysuria (62.3% vs 29.0%, P =.0001). Women who were homozygous for interleukin-1 receptor antagonist 2,2 genotype had an earlier onset of symptoms (26 years) than did women who were allele 1 homozygotes (31.3 years, P <.05). They also had a shorter duration of symptoms (4.1 vs 5.9 years, P <.05) and a higher frequency of allergy (47.6% vs 23.4%, P =.002). Human papillomavirus in the vaginal vestibule occurred at a greater frequency in women who were homozygous for interleukin-1 receptor antagonist 2,2 genotype. CONCLUSION: Subgroups of women with vulvar vestibulitis syndrome may be differentiated by symptomatic and genetic variables.     

Psychological aspects of vulvar vestibulitis syndrome

This review is based on a MEDLINE/PSYCHINFO search for all papers on psychological aspects of vulvar vestibulitis syndrome (VVS) published 1995-2002. VVS is a condition in which painful patches appear on the vulva which make intercourse painful. Causation, natural history and prevalence of VVS are unknown. Attempts to identify psychological characteristics typical of women with VVS have not yielded consistent results with some studies suggesting high levels of psychopathology and others not. It is suggested that inconsistencies in findings reflect not only decisions by women about whether and how to access health care but also the health care system acting to actively filter those reaching specialist services and selecting those with particular psychological characteristics. There is no compelling evidence that VVS per se is associated with any particular psychological or behavioural characteristics other than the sort of difficulties in sexual functioning which might be expected with chronic vulval pain. However there is evidence for high levels of psychological distress in some samples of women with VVS being seen in secondary care.     

Somatization and psychological distress among women with vulvar vestibulitis syndrome

Objective

To investigate the distribution of psychological characteristics and pain reporting among women with vulvar vestibulitis syndrome (VVS).

Methods

In this exploratory study, 109 women with VVS completed a battery of questionnaires to assess pain with intercourse and psychological characteristics (e.g. somatization, anxiety, distress). The distribution of these characteristics was compared, first with a conventional binary classification schema (primary and secondary) and subsequently with a 3-category schema (primary, latent primary, secondary).

Results

Severity of pain with intercourse did not differ among the subgroups using either classification schema. Women with primary VVS consistently showed higher levels of somatization, anxiety, and distress compared with those with secondary VVS. Using a 3-tiered classification system, we found no difference between latent primary diagnosis and the other 2 groups (primary and secondary).

Conclusion

This study highlights the critical need for research on subtype definition and the role of psychological factors in VVS.     

Childhood nocturnal enuresis in vulvar vestibulitis syndrome

OBJECTIVE: To define correlations between vulvar vestibulitis syndrome (VVS) and childhood nocturnal enuresis and the effect of biofeedback therapy. STUDY DESIGN: Of 104 women diagnosed with VVS, 54 (30 with primary vulvar vestibulitis syndrome [PVVS] and 24 with secondary vulvar vestibulitis syndrome [SVVS], mean age 24.5 years) chose Glazer biofeedback therapy. Information on lower urinary tract symptoms was recorded at the initial and final visits. RESULTS: Eight of the 30 women with PVVS (26.6%) had a history of childhood enuresis as compared to none of the women with SVVS (p < 0.01). The 8 women developed lower urinary tract symptoms following biofeedback treatment. None of the women with SVVS had urinary symptoms before or following biofeedback therapy. The high, unstable baseline muscle tone revealed by the Glazer technique to be present in all VVS patients underwent substantial reduction and stabilization at the end of biofeedback therapy. CONCLUSION: Childhood nocturnal enuresis is apparently common among women with PVVS. New urinary symptoms may develop following biofeedback therapy for PVVS.     

Estrogen receptor expression in vulvar vestibulitis syndrome

OBJECTIVE: A pilot study was performed to investigate the relationship between vulvar vestibulitis syndrome and estrogen receptor expression. STUDY DESIGN: Women with a diagnosis of vulvar vestibulitis syndrome had tissue samples taken for vulvar estrogen receptor-alpha expression and this was compared with a control group. RESULTS: The study group showed a significant decrease in estrogen receptor expression, and 50% of the samples did not exhibit any receptor expression. CONCLUSION: There appears to be a subgroup of women with vulvar vestibulitis syndrome who exhibit abnormal estrogen receptor-alpha expression. This may be helpful in explaining why some women are resistant to medical treatment and may allow treatment to be prescribed more effectively.     

Pelvic floor muscle functioning in women with vulvar vestibulitis syndrome

Vaginal sEMG biofeedback and pelvic floor physical therapists' manual techniques are being increasingly included in the treatment of vulvar vestibulitis syndrome (VVS). Successful treatment outcomes have generated hypotheses concerning the role of pelvic floor pathology in the etiology of VVS. However, no data on pelvic floor functioning in women with VVS compared to controls are available. Twenty-nine women with VVS were matched to 29 women with no pain with intercourse. Two independent, structured pelvic floor examinations were carried out by physical therapists blind to the diagnostic status of the participants. Results indicated that therapists reached almost perfect agreement in their diagnosis of pelvic floor pathology. A series of significant correlations demonstrated the reliability of assessment results across muscle palpation sites. Women with VVS demonstrated significantly more vaginal hypertonicity, lack of vaginal muscle strength, and restriction of the vaginal opening, compared to women with no pain with intercourse. Anal palpation could not confirm generalized hypertonicity of the pelvic floor. We suggest that pelvic floor pathology in women with VVS is reactive in nature and elicited with palpations that result in VVS-type pain. Treatment interventions need to recognize the critical importance of addressing the conditioned, protective muscle guarding response in women with VVS.     

Pelvic floor muscle functioning in women with vulvar vestibulitis syndrome

Vaginal sEMG biofeedback and pelvic floor physical therapists' manual techniques are being increasingly included in the treatment of vulvar vestibulitis syndrome (VVS). Successful treatment outcomes have generated hypotheses concerning the role of pelvic floor pathology in the etiology of VVS. However, no data on pelvic floor functioning in women with VVS compared to controls are available. Twenty-nine women with VVS were matched to 29 women with no pain with intercourse. Two independent, structured pelvic floor examinations were carried out by physical therapists blind to the diagnostic status of the participants. Results indicated that therapists reached almost perfect agreement in their diagnosis of pelvic floor pathology. A series of significant correlations demonstrated the reliability of assessment results across muscle palpation sites. Women with VVS demonstrated significantly more vaginal hypertonicity, lack of vaginal muscle strength, and restriction of the vaginal opening, compared to women with no pain with intercourse. Anal palpation could not confirm generalized hypertonicity of the pelvic floor. We suggest that pelvic floor pathology in women with VVS is reactive in nature and elicited with palpations that result in VVS-type pain. Treatment interventions need to recognize the critical importance of addressing the conditioned, protective muscle guarding response in women with VVS.     

Psychosexual aspects of vulvar vestibulitis.

OBJECTIVE: To explore the psychological, interpersonal and sexual correlates of vulvar vestibulitis via qualitative and quantitative analysis. STUDY DESIGN: Sixty-nine women diagnosed with vestibulitis were recruited from a vulvar/vaginal disease clinic to complete a comprehensive quantitative and qualitative questionnaire designed to assess general health concerns, mental health, sexual functioning and interpersonal relationships. RESULTS: The majority of participants reported drastic changes in sexuality associated with the onset of vestibulitis. Upon developing vestibulitis, 88% reported decreased interest in sexual activity, 87% indicated that they were less willing to participate in sexual activity, and 94% maintained that they were less able to participate in sexual activity. High levels of frustration and symptoms of depression also were frequently reported. CONCLUSION: Vulvar vestibulitis is associated with significant changes in sexuality, intimate relationships and psychological well-being. When treating women with vestibulitis, medical professionals should consider the psychological and sexual aspects of the disease in addition to physical concerns.     

Improvement in vulvar vestibulitis with montelukast

OBJECTIVE: To determine if montelukast treatment improves symptoms in patients with vulvar vestibulitis. STUDY DESIGN: We administered montelukast to a series of patients with vestibulitis seen at the Pennsylvania State University Vulvodynia Clinic over a period of 2.5 years. We reviewed outcomes using a scoring scheme to quantify signs and symptoms, before and after treatment, in 29 montelukast-treated subjects and 18 subjects in a comparison group treated with standard therapies. RESULTS: Subjects treated with montelukast showed an average of 52% in improvement in symptoms as compared to a 15% improvement in the controls (p < 0.0001). CONCLUSION: Montelukast is a viable treatment option for women with vulvar vestibulitis. This finding implies that leukotrienes have a role in the pathophysiology of vulvar vestibulitis.     

The major histopathologic characteristics in the vulvar vestibulitis syndrome

OBJECTIVE: In order to better understand the etiology of the vulvar vestibulitis syndrome, we examined the histopathologic parameters in vestibular mucosa, and compared the findings in specimens obtained from women with vulvar vestibulitis with those obtained from the control group. STUDY DESIGN: Specimens of vestibulitis were obtained from 24 patients, undergoing circumferential vestibulectomy under general anesthesia due to the symptoms and signs consistent with vulvar vestibulitis. Control specimens were obtained from 16 women, without symptoms or signs of vulvar vestibulitis, undergoing reconstructive introital surgery due to roomy vagina, rectocele or painful episiotomy. All vestibular tissue specimens were examined for intensity of inflammation, extension of inflammatory cells into the epithelium, vascular proliferation, the presence of mast cells and proliferation of peripheral nerve bundles. RESULTS: No significant difference was found regarding the degree of inflammation, the extension of inflammatory cells into the epithelium, the vascular proliferation and the presence of mast cells while comparing the study and the control groups. The only histopathologic feature, differentiating the patients with vulvar vestibulitis from the control group, was the proliferation of peripheral nerve bundles found in 19 out of 24 (79.1%) specimens expressing vestibulitis and in none of 16 control specimens (p < 0.0001). CONCLUSION: Our results, therefore, support the existence of peripheral nerve hyperplasia in vestibular tissue obtained from patients with vulvar vestibulitis, and exclude the role of active inflammation or mast cells as probable etiologies for the vulvar vestibulitis syndrome.     

Pruritic vulvar squamous papillomatosis: evidence for human papillomavirus etiology

The origin of squamous papillae of the vulvar vestibule is controversial. Although some are considered as asymptomatic normal variants of pelvic anatomy, a review of 12 cases of vulvar squamous papillae in patients visiting the Infectious Diseases Clinic at UCLA reveals a distinctly symptomatic variety. A syndrome complex of premonitory vulvar vestibular pruritis, pain or burning, dyspareunia, and progressive development of squamous papillae was noted. Microscopic examination of tissue specimens of the areas of squamous papillae reveals the presence of koilocytic change suggestive of viral infection with human papillomavirus. Furthermore, immunoperoxidase stain revealed human papillomavirus capsid antigen in two cases, which has heretofore not been reported in the literature to the authors' knowledge. Evidence of partner infection on physical examination of sexual partners of these women revealed changes consistent with human papillomavirus in four of six partners who were available for examination. Treatment with podophyllin, cryotherapy, laser, or a combination seems to give predictable resolution of the condition and associated symptoms.     

Human papillomavirus and the pathogenesis of vulvar carcinoma.

The pathogenesis of vulvar and cervical cancer are thought to be similar and to be related to a sexually transmitted agent, which, in recent years, has been demonstrated to be human papillomavirus. These two neoplasms differ dramatically in age distribution and relationship to precursor lesions, making a common etiology unlikely. The apparent discrepancies can be explained by a hypothesis that implicates human papillomavirus as an etiologic factor for the majority of cervical carcinomas but for only a small proportion of vulvar carcinomas. Most vulvar carcinomas occur in older women and are not related to human papillomavirus, whereas a subset of vulvar carcinomas occur in young women and are related to this virus. Characterization of two distinct types of vulvar carcinoma may clarify associated risk factors and may have important implications in the clinical management of this disease.     

Psychological profiles among women with vulvar vestibulitis syndrome: a chart review

The purpose of this study was to assess the prevalence and type of psychological distress in women with vulvar vestibulitis syndrome (VVS), A retrospective chart review was conducted of all women receiving a diagnosis of VVS referred to a tertiary care facility during a two-year period. Brief psychological questionnaires, including the Personality Assessment Screener, Fear of Negative Evaluation Scale, Golombok-Rust Inventory of Sexual Satisfaction, and the Phobia Rating Scale were administered.

Fifty-consecutive cases were reviewed along with 12-15 month follow-up data for 41 cases. Phobic anxiety to vaginal touch or entry was significantly higher in women with VVS than normative data. Fear of Negative Evaluation was a strong associated feature, and for 30% approached clinically significant levels. Twenty-six percent showed a moderate, while another 26% showed a mild clinically distressed profile. Negative affect and social withdrawal were among the most frequently endorsed variables. Improvement in allodynia and intercourse were both related to these psychological variables, and a multiple regression analysis supported the use of psychological instruments in addition to standard medical assessment.

A subgroup of women with VVS display clinically significant broad based psychological distress that warrants additional assessment. The use of psychological questionnaires in addition to medical assessment of women with VVS may provide valuable information predictive of treatment needs and response.     

Vestibulodynia-A subset of vulvar vestibulitis or a novel syndrome?

OBJECTIVE: Our purpose was to recognize special features of women with both vestibulitis and constant vulvar pain (vestibulodynia) and to determine whether vestibulodynia is a separate disease entity or a subset of vestibulitis. STUDY DESIGN: Ninety-one women with severe vulvar vestibulitis underwent perineoplasty by a single surgeon during 1992 to 1995. Twenty-five (27%) of them who had vestibulodynia were compared with 66 (73%) who had dyspareunia alone. With univariate and then multivariate analysis, the two groups were compared with regard to demographic, social, and medical variables, the presence of human papillomavirus deoxyribonucleic acid, physical findings in the vestibule, and surgical outcome. RESULTS: The vestibulodynia and vestibulitis groups differed in age (30.5 ± 10.6 years vs 24.7 ± 6.2 years respectively), as well as in marital status (married, 44% vs 18%, respectively), nonuse of contraception (20% vs 1%, respectively), presence of human papillomavirus deoxyribonucleic acid in the vestibule (80% vs 48%, respectively), and failure of surgical treatment (incomplete response rate, 64% vs 2%, respectively). With multivariate analysis, patients with human papillomavirus deoxyribonucleic acid present in the vestibule have an odds ratio of 5.44 (95% confidence interval, 1.45 to 20.33) of belonging to the group with vestibulodynia, whereas dysuria and age have odds ratios of 3.70 (95% confidence interval 1.09 to 12.55) and 1.14 (95% confidence interval 1.04 to 1.24), respectively. CONCLUSIONS: Vestibulodynia is a unique syndrome in that it affects women who are older than those who have vestibulitis alone and it is associated with human papillomavirus deoxyribonucleic acid, dysuria, and a higher surgical failure rate than that for vestibulitis.(Am J Obstet Gynecol 1997;177:43)