Polymorphism in a gene coding for the inflammasome component NALP3 and recurrent vulvovaginal candidiasis in women with vulvar vestibulitis syndrome.
Division of Immunology and Infectious Diseases, Department of Obstetrics and Gynecology, Weill Medical College of Cornell University, New York, NY 10065, USA.
OBJECTIVE: Patients with vulvar vestibulitis syndrome (VVS) and control subjects were tested for a polymorphism in the gene coding for the NALP3 component of inflammasomes, cytoplasmic structures regulating interleukin (IL)-1beta production. STUDY DESIGN: DNA from 143 women with VVS and 182 control women were tested for a length polymorphism in intron 4 of the gene (CIAS1) that codes for NALP3. Vestibular tissue was examined for NALP3 expression. Whole blood cultures were tested for Candida albicans-induced IL-1beta production. RESULTS: The allele 12 frequency was higher in control subjects than in the patients with VVS (P = .02). Among patients with VVS and a self-reported history of recurrent vulvovaginal candidiasis (RVVC), the allele 7 frequency was 43.9% as compared with 30.8% in patients with no history of RVVC and 26.9% in control women (P = .035 vs other patients and .001 vs control subjects). NALP3 was identified in vestibular tissue. C albicans-induced IL-1beta production was reduced in samples from women with the 7,7 genotype (P = .030). CONCLUSION: Polymorphism in the CIAS1 gene may play a central role in the triggering of VVS in a subset of patients.
Surgery combined with muscle therapy for dyspareunia from vulvar vestibulitis: an observational study.
Goetsch MF-J Reprod Med.2007 Jul;52(7):597-603.
OBJECTIVE: To explore the dual importance of treating vestibule
allodynia and pelvic floor myalgia in correcting dyspareunia associated
with severe vulvar vestibulitis. STUDY DESIGN: In this observational
study, 111 women were treated by modified superficial vestibulectomy
and were evaluated for referral to physical therapists for pelvic floor
myalgia. They were followed with interval repeat examinations. Later
cohort assessment was by patient questionnaire surveys. Data from
pelvic floor muscle examinations and physical therapy referrals were
added by retrospective chart review. Primary outcomes were swab touch
sensitivity and dyspareunia. RESULTS: Eighty-five percent of subjects
ultimately had nontender vestibule examinations postoperatively. Fewer,
numbering 64%, reported resolution of dyspareunia, 24% had less
dyspareunia, 9% were no better, and 3% reported they were worse. Fifty
percent of those with continued dyspareunia had no remaining
vestibulitis, but had tight or tender pelvic muscles. Failure of
surgery and physical therapy to correct dyspareunia related
significantly to length of symptoms before therapy (p = 0.02).
Follow-up averaged 3.7 years, with a range of 0.25-14. CONCLUSION:
Superficial surgery can correct vulvar vestibulitis, but without
treatment for pelvic floor myalgia, women may continue to have
dyspareunia. Physical therapy is an important adjunct to achieve
comfort.
Vulvar vestibulitis syndrome and estrogen dose of oral contraceptive pills.
Greenstein A, Ben-Aroya Z, Fass O, Militscher I, Roslik Y, Chen J, Abramov L
J Sex Med. 2007 Nov;4(6):1679-83.
Introduction. Vulvar vestibulitis syndrome (VVS) is a diverse,
multifactorial phenomenon. Its precise etiology is unknown. Aim. To
define the association between oral contraceptive (OC) estrogen dosage
and VVS. Methods. Women diagnosed as having VVS participated in the
study. Main Outcome Measures. Data on type and usage of oral
contraceptive pills (OC) were obtained by a questionnaire, and they
were compared for the data on OC usage in the general population.
Results. Available commercial data on Israeli women taking OC showed
that 51% of them use low-dose estrogen (</=20 microg) OC and 49% use
higher-dose estrogen (30-35 microg) OC. Of the 132 women in the study,
86 (65%) used OC: 68 (79%) used low-dose estrogen OC (P < 0.002
compared to the general population), while only 18 (21%) used high-dose
estrogen OC (P < 0.002 compared to the general population).
Conclusion. Significantly more patients who are treated in our clinic
for VVS use low-dose estrogen than those who use high-dose estrogen OC.
Vulvodynia. Development of a psychosexual profile.
J Reprod Med. 2007 Jan;52(1):63-71
OBJECTIVE: To assess the psychosexual profile of vulvodynia
patients, focusing on the age at onset and age distribution, and to
analyze the impact of vulvodynia on the emotional, social and sexual
well-being of this patient population. STUDY DESIGN: A retrospective
review was performed of patient files consisting of questionnaires,
psychometric tests, sexual history, electromyographic assessments and
clinical notes. RESULTS: The highest prevalence of vulvodynia in this
clinical sample occurred before the age of 25 years; 75% of the 744
patients were under the age of 34. A comparison of primary and
secondary vulvodynia patients showed the average age at symptom onset
to be 19.1 years for primary cases and 25.0 years for secondary cases.
There were significant differences in duration of symptoms, age at
first sexual intercourse and number of sexual partners, even when
controlling for age (p < 0.001). Marriage provided an effective
buffer against depression and anxiety. CONCLUSION: Vulvodynia can have
an early onset and affect social relationships. Given the psychologic
distress associated with vulvodynia, early diagnosis and treatment of
the medical aspects are essential, as is focusing on the psychosexual
implications of this pain syndrome.
Prevalence of vulvar pain in an urban, minority population.
J Reprod Med. 2007 Jan;52(1):59-62
OBJECTIVE: To determine the prevalence of vulvar pain in a large,
urban, minority population. STUDY DESIGN: Women who presented to the
University of Texas Southwestern Medical Center neighborhood clinic
system for family planning services or gynecologic care were asked to
complete a confidential questionnaire on the signs and symptoms of
chronic vulvar pain. Responses were analyzed by ethnic group for the
presence of vulvar pain. RESULTS: Three hundred twenty questionnaires
were distributed, and 242 were completed,for a response rate of 75.6%.
The population that completed the questionnaire (74% Hispanic, 20%
African American, 5% Caucasian and 0.8% other) was similar in
racial/ethnic distribution to the total population served in our health
care system (66% Hispanic, 25% African American, 8% Caucasian and 1%
other). Twenty-six (11%) women indicated they experienced vulvar pain.
Sixteen women reported the start dates for the pain. Ten (63%) reported
vulvar pain for more than 1 month. Of the 26 women reporting pain, the
racial distribution was similar to that of our surveyed population (85%
Hispanic, 11% African American, 4% Caucasian and 0% other). CONCLUSION:
The prevalence of vulvar pain in this urban minority population was
11%. The prevalence of vulvar pain was similar among women of different
racial/ethnic groups.
Treatment of vulvodynia with tricyclic antidepressants: efficacy and associated factors.
Reed BD, Caron AM, Gorenflo DW, Haefner HK.
J Low Genit Tract Dis Oct 2006; 10(4):245-51
OBJECTIVE: To determine the efficacy of tricyclic antidepressants
(TCAs) as treatment for vulvodynia, and to identify demographic factors
and pain characteristics associated with improvement. MATERIALS AND
METHODS: Between January 2001 and April 2004, women diagnosed with
vulvodynia were offered TCA therapy. The patients rated their worst
recent pain on a 10-point scale at baseline and at follow-up;
improvement was classified as at least 50% reduction in reported pain
from baseline. RESULTS: Of 271 women diagnosed with vulvodynia, 209
(77.1%) were treated initially with a TCA (amitriptyline [n = 183],
desipramine [n = 23], and other tricyclic medications [n = 3]). One
hundred sixty-two (59.8%) of the women were followed up at a median
period of 3.2 months after their initial visit, including 122 women who
had started on a TCA. Of 83 women taking a TCA at the first follow-up,
49 (59.3%) improved by more than 50%, compared with 30 of 79 women not
taking TCA at follow-up (improvement rate = 38.0%; p =.007; odds ratio
= 2.35; 95% CI = 1.23-4.42). Multivariate analysis indicated that age,
severity of pain, diagnosis (localized vs generalized vulvar pain),
length of time with pain before treatment, age at menarche, use of oral
contraceptives, and the number of previous pregnancies were not
associated with the outcome; however, taking a TCA at the time of the
first follow-up was strongly associated with improvement (p <.001;
odds ratio = 4.23; 95% CI = 1.98-9.01). Repeated analysis including
only those women prescribed with amitriptyline rather than any
tricyclic revealed similar results. CONCLUSIONS: Women with vulvodynia
who were prescribed a TCA in general (or amitriptyline, specifically)
were more likely to have pain improvement compared with those women not
taking these medications at follow-up. Randomized, controlled studies
of TCAs versus other treatments are needed to clarify the overall
effectiveness of these drugs.
Surgical treatment for the vulvar vestibulitis syndrome.
Traas MA, Bekkers RL, Dony JM, Blom M, van Haren AW, Hendriks JC, Vierhout ME.
Obstet Gynecol Feb 2006; 107(2 Pt 1):256-62
OBJECTIVE: To study the outcome and complications of surgical
treatment for vulvar vestibulitis syndrome and to identify patient
characteristics that may have influenced the outcome. METHODS: Relevant
patient characteristics were extracted retrospectively from the medical
records of 155 women aged 40 years or younger who had received surgical
treatment for vulvar vestibulitis syndrome. To assess outcome and
complications, 126 of these 155 women (81%) participated in a telephone
interview, conducted 1 to 4 years after surgery. RESULTS: After surgery
93% of the patients could have sexual intercourse compared with 78%
before surgery; this increase was statistically significant
(Mantel-Haenszel odds ratio 3.43, 95% confidence interval [CI]
1.48-7.96). In 62% of the women (95% CI 53-70%), sexual intercourse was
painless after surgery. Eighty-nine percent (95% CI 84-95%) would
recommend surgical treatment to other women experiencing vulvar
vestibulitis syndrome. There were no major complications. Decreased
lubrication during sexual arousal was the most frequently reported
adverse effect (24%, 95% CI 16-32%), followed by the development of a
Bartholin´s cyst (6%, 95% CI 2-10%). More of the women aged 30
years or younger reported that they could have sexual intercourse after
surgery, and more of them would recommend surgical treatment to other
patients than women aged 31 years or older. CONCLUSION: Surgical
treatment for vulvar vestibulitis syndrome achieved high success rates
with an acceptable rate of complications. Age of 30 years or younger
was associated with a better outcome
Neural correlates of painful genital touch in women with vulvar vestibulitis syndrome.
Pukall CF, Strigo IA, Binik YM, Amsel R, Khalifé S, Bushnell MC.
Pain May 2005; 115(1-2):118-27
Vulvar vestibulitis syndrome (VVS) is a common cause of dyspareunia
in pre-menopausal women. Recent evidence points to the importance of
the sensory component in VVS, particularly the heightened processing of
tactile and pain sensation in the vulvar vestibule. The goal of the
present study was to examine the neural basis of heightened sensitivity
to touch (i.e. allodynia) in women with VVS. Using functional magnetic
resonance imaging, we compared regions of neural activity in 14 women
with VVS and 14 age- and contraceptive-matched control women in
response to the application of mild and moderate pressure to the
posterior portion of the vulvar vestibule. Intensity and unpleasantness
ratings were recorded after each scan; these ratings were significantly
higher for women with VVS than controls. All women with VVS described
moderate pressure as painful and unpleasant, and 6 of the 14 women with
VVS described mild pressure as painful and unpleasant. In contrast,
none of the stimuli was painful for control women. Correspondingly,
women with VVS showed more significant activations during pressure
levels that they found to be either painful or non-painful than did
controls during comparable pressure levels. During pressure described
as painful by women with VVS, they had significantly higher activation
levels in the insular and frontal cortical regions than did control
women. These results suggest that women with VVS exhibit an
augmentation of genital sensory processing, which is similar to that
observed for a variety of syndromes causing hypersensitivity, including
fibromyalgia, idiopathic back pain, irritable bowel syndrome, and
neuropathic pain.
Capsaicin and the treatment of vulvar vestibulitis syndrome: a valuable alternative?
Murina F, Radici G, Bianco V.
MedGenMed 2004; 6(4):48
OBJECTIVE: To assess the efficacy of topical capsaicin in the
treatment of vulvar vestibulitis syndrome. STUDY DESIGN: Thirty-three
consecutive women referred for vulvar vestibulitis syndrome were
treated with topical capsaicin 0.05 %. The capsaicin cream was applied
twice a day for 30 days, then once a Day for 30 days, and finally 2
times a week for 4 months. RESULTS: In 19 patients (59%), improvement
of symptoms was recorded, but no complete remission was observed.
Symptoms recurred in all patients after the use of capsaicin cream was
discontinued. A return to a twice-weekly topical application of the
cream resulted in the improvement of symptoms. Severe burning was
reported as the only side effect by all the patients. CONCLUSION:
Response to treatment was only partial, possibly due to the
concentration of the compound being too low, or to the need for more
frequent than daily applications. The therapeutic role of capsaicin
should hence be confined to a last-choice medical approach.
Hyperinnervation and mast cell activation may be used as histopathologic diagnostic criteria for vulvar vestibulitis.
Lowenstein L, Vardi Y, Deutsch M, Friedman M, Gruenwald I, Granot M, Sprecher E, Yarnitsky D.
Pain Jan 2004; 107(1-2):47-53
Vulvar vestibulitis syndrome (VVS) is a common cause of dyspareunia
in pre-menopausal women. Previous quantitative sensory test (QST)
studies have demonstrated reduced vestibular pain thresholds in these
patients. Here we try to find whether QST findings correlate to disease
severity. Thirty-five vestibulitis patients, 17 with moderate and 18
with severe disorder, were compared to 22 age matched control women.
Tactile and pain thresholds for mechanical pressure and thermal pain
were measured at the posterior fourcette. Magnitude estimation of
supra-threshold painful stimuli were obtained for mechanical and
thermal stimuli, the latter were of tonic and phasic types. Pain
thresholds were lower and supra-threshold magnitude estimations were
higher in VVS patients, in agreement with disease severity. Cut-off
points were defined for results of each test, discriminating between
moderate VVS, severe VVS and healthy controls, and allowing calculation
of sensitivity and specificity of the various tests. Our findings show
that the best discriminative test was mechanical pain threshold
obtained by a simple custom made ´spring pressure device´.
This test had the highest kappa value (0.82), predicting correctly 88%
of all VVS cases and 100% of the severe VVS cases. Supra-threshold pain
magnitude estimation for tonic heat stimulation also had a high kappa
value (0.73) predicting correctly 82% overall with a 100% correct
diagnosis of the control group. QST techniques, both threshold and
supra-threshold measurements, seem to be capable of discriminating
level of severity of this clinical pain syndrome.
Overnight 5% lidocaine ointment for treatment of vulvar vestibulitis.
Tympanidis P, Terenghi G, Dowd P.
Br J Dermatol May 2003; 148(5):1021-7
BACKGROUND: Vulval vestibulitis is a condition characterized by the
sudden onset of a painful burning sensation, hyperalgesia, mechanical
allodynia, and occasionally pruritus, localized to the region of the
vulval vestibulus. It is considered the commonest subset of vulvodynia.
Pain precipitated in the absence of nociceptor stimuli might be
triggered by previous peripheral nerve injury, or by the release of
neuronal mediators, which set off inappropriate impulses in
nonmyelinated pain fibres sensitizing the dorsal horn neurones. The
pathophysiology of vulval vestibulitis is still unclear. OBJECTIVES:
The objective of this study was to evaluate the nerve fibre density and
pattern, in specimens of vulval vestibulus, in normal subjects and in
patients with vestibulitis, and provide objective diagnostic criteria
for this condition. Methods Twelve patients with a history of the
vestibulitis type of vulvodynia, and eight normal subjects underwent
biopsy of the posterior wall of the vulval vestibule. Quantitative
immunohistochemistry was performed, using antisera to the general
neuronal marker protein gene product (PGP) 9.5, and to the neuropeptide
calcitonin gene-related peptide (CGRP), on 15- microm sections.
RESULTS: There was a statistically significant increase of density and
number of PGP 9.5 immunoreactive in the papillary dermis of patients
with vulvodynia of the vestibulitis type, compared with those of
controls. However, the distribution pattern of the innervation showed
no significant change. There were no significant differences in CGRP
staining between patients and controls. CONCLUSIONS: It is concluded
that the increase of PGP 9.5 immunoreactive nerve fibres, in patients
with vulvodynia, may be either secondary to nerve sprouting, or may
represent neural hyperplasia. Increased innervation may be applied as
an objective diagnostic finding in vulval vestibulitis syndrome.
Vestibular tactile and pain thresholds in women with vulvar vestibulitis syndrome.
Pukall CF, Binik YM, Khalifé S, Amsel R, Abbott FV.
Pain Mar 2002; 96(1-2):163-75
Vulvar vestibulitis syndrome (VVS) is a common cause of dyspareunia
in pre-menopausal women. Little is known about sensory function in the
vulvar vestibule, despite Kinsey´s assertion that it is important
for sexual sensation. We examined punctate tactile and pain thresholds
to modified von Frey filaments in the genital region of women with VVS
and age- and contraceptive-matched pain-free controls. Women with VVS
had lower tactile and pain thresholds around the vulvar vestibule and
on the labium minus than controls, and these results were reliable over
time. Women with VVS also had lower tactile, punctate pain, and
pressure-pain tolerance over the deltoid muscle on the upper arm,
suggesting that generalized systemic hypersensitivity may contribute to
VVS in some women. In testing tactile thresholds, 20% of trials were
blank, and there was no group difference in the false positive rate,
indicating that response bias cannot account for the lower thresholds.
Women with VVS reported significantly more catastrophizing thoughts
related to intercourse pain, but there was no difference between groups
in catastrophizing for unrelated pains. Pain intensity ratings for
stimuli above the pain threshold increased in a parallel fashion with
log stimulus intensity in both groups, but the ratings of distress were
substantially greater in the VVS group than in controls at equivalent
levels of pain intensity. The data imply that VVS may reflect a
specific pathological process in the vestibular region, superimposed on
systemic hypersensitivity to tactile and pain stimuli.
Treatment of vulvar vestibulitis with submucous infiltrations of methylprednisolone and lidocaine. An alternative approach.
Murina F, Tassan P, Roberti P, Bianco V.
J Reprod Med Aug 2001; 46(8):713-6
OBJECTIVE: To assess the efficacy of submucous infiltrations of
methylprednisolone and lidocaine into the vulvar vestibule for the
treatment of vulvar vestibulitis. STUDY DESIGN: Twenty-two patients
were referred for vulvar vestibulitis. Methylprednisolone and lidocaine
were injected into the vulvar vestibule once a week for three weeks at
decreasing doses (1, 0.5, 0.3 mL). Follow-up was performed monthly for
three months, then at six and nine months. Fourteen women have had 12
months and 5 women, 24 months of follow-up. RESULTS: Fifteen women
(68%) responded favorably to the treatment, seven (32%) with absence of
symptoms and eight (36%) with a marked improvement. Seven patients
(32%) failed to respond in spite of a fourth dose (0.3 mL) given after
30 days. No relapse was observed at nine months´ follow-up, while
a further 0.5 mL infiltration followed by quick remission of symptoms
was needed after one year in five patients. Five patients completed the
24 months´ follow-up, with no need for further treatment.
CONCLUSION: Submucous infiltration allows methylprednisolone to be
deposited in the submucosa, the site of the inflammatory reaction,
while the depot formulation allows gradual and prolonged release of the
drug. Seven patients (32%) failed to respond, suggesting either that
they had a kind of vulvar vestibulitis syndrome where inflammation is
less remarkable or failure of the infiltrated drug to become adequately
diffused.
A randomized comparison of group cognitive--behavioral therapy, surface electromyographic biofeedback, and vestibulectomy in the treatment of dyspareunia resulting from vulvar vestibulitis.
Weström LV, Willén R.
Obstet Gynecol Apr 1998; 91(4):572-6
OBJECTIVE: To evaluate nerve fiber density in vestibular specimens
from women operated upon for vulvar vestibulitis. METHODS: Forty-seven
women with vulvar vestibulitis syndrome underwent modified posterior
vestibulectomies. Vestibular specimens were analyzed after being
stained for S-100 neural tissue protein. Women were followed up for 2
years. RESULTS: In specimens from 44 of 47 patients, the densities and
numbers of nerve fibers per square unit in the preparations were
greater than those in specimens from six control women. In the
patients, a statistically significant linear correlation was found
between inflammation and nerve bundle density in the preparations
(Spearman rank correlation coefficient rs=.41; P=.005). There were no
signs of infectious etiology in any preparation. No or slight
postoperative dyspareunia was reported by 38 of 42 women after 6
months, 36 of 39 after 12 months, and 26 of 28 after 24 months.
CONCLUSION: Vestibular neural hyperplasia may provide a morphologic
explanation of the pain in vulvar vestibulitis syndrome.
Treatment of vulvar vestibulitis syndrome with electromyographic biofeedback of pelvic floor musculature.
Glazer HI, Rodke G, Swencionis C, Hertz R, Young AW.
J Reprod Med Apr 1995; 40(4):283-90
Thirty-three women diagnosed as suffering from vulvar vestibulitis
syndrome, marked by a significant history of long-term moderate to
severe chronic introital dyspareunia and tenderness of the vulvar
vestibule, were selected for treatment. Patients were given a
computerized electromyographic evaluation of the pelvic floor muscles
and were then provided with portable electromyographic biofeedback
instrumentation and instructions on the conduct of daily, at-home,
biofeedback-assisted pelvic floor muscle rehabilitation exercises. They
received intermittent evaluations of pelvic floor muscles to ensure
compliance and monitor their progress and symptom changes. The results
show that after an average of 16 weeks of practice, pelvic floor muscle
contractions increased 95.4%, resting tension levels decreased 68%, and
the instability of the muscle at rest decreased by 62%. Subjective
reports of pain decreased an average of 83%. Twenty-eight patients had
abstained from intercourse for an average of 13 months. Twenty-two of
these 28 patients resumed intercourse by the end of the treatment
period. Six month follow-up indicated maintenance of therapeutic
benefits.