Barbara D. Reed

VULVOVAGINAL CANDIDIASIS: EPIDEMIOLOGIC, DIAGNOSTIC, AND THERAPEUTIC CONSIDERATIONS

Although it is the second most common vaginal infection in North America, vulvovaginal candidiasis is a non-notifiable disease and has been excluded from the ranks of sexually transmitted diseases. Not surprisingly, vulvovaginal candidiasis has received scant attention by public health authorities, funding agencies, and researchers. Epidemiologic data on risk factors and pathogenic mechanisms remain inadequately studied. Most important, standards of care, including diagnosis and therapy, remain undefined. A conference was held in April 1996 to define and summarize what is known and supported by scientific data in the areas of epidemiology, diagnosis, and treatment of vulvovaginal candidiasis; but, more important, the conference aimed at defining what is not known, poorly studied, and controversial. Guidelines for the treatment and diagnosis of the different forms of vulvovaginal candidiasis are suggested.

The vulvodynia guideline

Objective. To provide a review of the literature and make known expert opinion regarding the treatment of vulvodynia. Materials and Methods. Experts reviewed the existing literature to provide new definitions for vulvar pain and to describe treatments for this condition. Results. Vulvodynia has been redefined by the International Society for the Study of Vulvovaginal Disease as vulvar discomfort in the absence of gross anatomic or neurologic findings. Classification is based further on whether the pain is generalized or localized and whether it is provoked, unprovoked, or both. Treatments described include general vulvar care, topical medications, oral medications, injectables, biofeedback and physical therapy, dietary changes with supplementations, acupuncture, hypnotherapy, and surgery. No one treatment is clearly the best for an individual patient. Conclusions. Vulvodynia has many possible treatments, but very few controlled trials have been performed to verify efficacy of these treatments. Provided are guidelines based largely on expert opinion to assist the patient and practitioner in dealing with this condition.

Quantitative sensory testing in vulvodynia patients and increased peripheral pressure pain sensitivity.

OBJECTIVE: To assess both regional (vulvar) and overall (generalized) pain sensitivity in women with vulvodynia to determine whether both are increased, suggestive of altered central pain processing. METHODS: Seventeen patients (aged 18–60 years) with vulvodynia and 23 age-matched control subjects were included in this cross-sectional study. Pressure pain thresholds in the vulvar area were evaluated in 23 defined locations using a newly developed vulvodolorimeter. Peripheral pressure pain sensitivity was assessed by applying 1) continuously ascending pressures to 3 bilateral locations (thumb, deltoid, and shin), and 2) discrete pressure stimuli to the thumb using both an ascending and random sequence of varying pressures. RESULTS: Pain thresholds at all vulvar locations were lower in the women with vulvodynia than in pain-free control subjects. Similarly, peripheral pain thresholds were lower at the thumb in women with vulvodynia when obtained by discrete ascending or random staircase paradigms, as well as at the thumb, deltoid, and shin when tested by dolorimeter (P < .05). Findings were similar in both those with generalized vulvar dysesthesia and those with localized vestibulodynia. The quantitative results obtained with the vulvodolorimeter and with the more subjective cotton-tipped swab testing routinely used in diagnosis were strongly correlated. CONCLUSION: Women with vulvodynia displayed significantly increased pressure pain sensitivity in both the vulvar region and in peripheral body regions, suggesting a “central” component to the mechanisms mediating this disorder. Both the novel vulvodolorimeter and the thumb pressure stimulator may assist in future experimental tests of this and related hypotheses. LEVEL OF EVIDENCE: II-2

Fluconazole Susceptibility of Vaginal Isolates Obtained from Women with Complicated Candida Vaginitis: Clinical Implications

ABSTRACT Despite considerable evidence of azole resistance in oral candidiasis due to Candida species, little is known about the azole susceptibilities of the genital tract isolates responsible for vaginitis. The fluconazole susceptibilities of vaginal isolates obtained during a multicenter study of 556 women with complicated Candida vaginitis were determined by evaluating two fluconazole treatment regimens. Of 393 baseline isolates of Candida albicans, 377 (96%) were highly susceptible to fluconazole (MICs, <8 μg/ml) and 14 (3.6%) were resistant (MICs, ≥64 μg/ml). Following fluconazole therapy, one case of in vitro resistance developed during 6 weeks of monitoring. In accordance with the NCCLS definition, in vitro fluconazole resistance correlated poorly with the clinical response, although a trend of a higher mycological failure rate was found (41 versus 19.6% on day 14). By using an alternative breakpoint of 1 μg/ml, based upon the concentrations of fluconazole achievable in vaginal tissue, no significant differences in the clinical and mycological responses were observed when isolates (n = 250) for which MICs were ≤1 μg/ml were compared with isolates (n = 30) for which MICs were >1 μg/ml, although a trend toward an improved clinical outcome was noted on day 14 (odds ratio, >2.7; 95% confidence interval, 0.91, 8.30). Although clinical failure was uncommon, symptomatic recurrence or mycological relapse almost invariably occurred with highly sensitive strains (MICs, <1.0 μg/ml). In vitro fluconazole resistance developed in 2 of 18 initially susceptible C. glabrata isolates following fluconazole exposure. Susceptibility testing for women with complicated Candida vaginitis appears to be unjustified.

Risk factors for Candida vulvovaginitis.

Although Candida vulvovaginitis occurs commonly, the reasons for its occurrence and recurrence are often unclear. Several potential risk factors have been described, including the recent use of antibiotics and oral contraceptives, the presence of diabetes mellitus, dietary practices, gastrointestinal colonization by the organism, clothing and sanitary protection practices, sexual communicability of the organism, and specific immunological defects. However, the data supporting each of these factors are conflicting, and to date none are predictive of infection. In this review, the data evaluating these potential risk factors are described. From this information, implications for clinical practice are discussed.

Reliability and validity of self-reported symptoms for predicting vulvodynia.

OBJECTIVE: To evaluate the reliability and validity of self-reported symptoms to predict vulvodynia, compared with examination-based confirmation. METHODS: Between August 5, 2004, and December 13, 2004, 1,046 members of the University of Michigan Women’s Health Registry were surveyed regarding the presence of symptoms suggestive of vulvodynia. Diagnoses of vulvodynia and of control status based on survey responses were made, and a subset of these respondents was evaluated in the office. RESULTS: One thousand forty-six of 1,447 (72.3%) eligible women, aged 19 to 92 years, completed the survey. Seventy-nine (7.6%) of the survey respondents who reported ongoing vulvar pain lasting more than 3 months were predicted to have vulvodynia, while women reporting no current pain with intercourse and no history of prolonged vulvar pain were predicted to be controls (N=543). Agreement between the history taken at the office and that reported on the survey was very good (reliability: Cohen’s &kgr;=0.86, 95% confidence interval 0.73–0.99). Of the 28 women predicted to have vulvodynia who were examined in the office, 27 (96.4%) were confirmed to have vulvodynia, and 28 of the 34 (82.4%) asymptomatic women examined did not have increased vulvar sensitivity (Cohen’s &kgr;=0.78, 95% confidence interval 0.64–0.92). CONCLUSION: Excellent reliability and validity of survey responses for predicting vulvodynia were demonstrated. LEVEL OF EVIDENCE: II-2

Treatment of vulvodynia with tricyclic antidepressants: efficacy and associated factors.

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.

Pain at the Vulvar Vestibule: A Web-Based Survey

Objective. To assess the prevalence, characteristics, and ethnic distribution of pain in the vulvar vestibule among a national sample of women completing a web-based survey. Methods. Female participants of the SurveySpot Internet research panel (Survey Sampling International) were invited via e-mail to respond to a web-based questionnaire on womens health issues. The frequency and characteristics of reported pain of the vulvar vestibule were assessed among 994 respondents, using univariate and multivariate analyses. Results. Between May 24, 2002, and June 6, 2002, 730 non-African American women and 364 African American women responded to the invitation to participate, and 94.5% completed the survey. A history of pain at the vulvar vestibule was reported by 288 women (27.9%), with 80 (7.8% of the initial 1032) reporting pain within the past 6 months, 31 (3.0%) reporting pain that lasted 3 or more months, and 18 (1.7%) reporting vestibular pain lasting 3 or more months that occurred within the past 6 months. The prevalence of pain was similar in African American and non-African American women. Conclusions. The prevalence of pain at the vulvar vestibule is more common than previously estimated. The perception that vulvar pain is rare among African American women was not supported in this survey.

Relationship Between Vulvodynia and Chronic Comorbid Pain Conditions

OBJECTIVE: To estimate the relationship among the presence of vulvodynia, fibromyalgia, interstitial cystitis, and irritable bowel syndrome. METHODS: Validated questionnaire-based screening tests for the four pain conditions were completed by women with and without vulvodynia who were participating in the Michigan Woman to Woman Health Study, a longitudinal population-based survey in southeastern Michigan. Weighted population-based estimates of the prevalence and characteristics of participants with these chronic comorbid pain conditions were calculated using regression analyses. RESULTS: Of 1,940 women who completed the survey containing all four screening tests, 1,890 (97.4%) answered all screening questions and were included. The prevalences of the screening-based diagnoses ranged from 7.5% (95% confidence interval [CI] 6.2–9.0) for interstitial cystitis, 8.7% (95% CI 7.3–10.4) for vulvodynia, 9.4% (95% CI 8.1–11.0) for irritable bowel syndrome, to 11.8% (95% CI 10.1–13.7) for fibromyalgia with 27.1% screening positive for multiple conditions. The presence of vulvodynia was associated with the presence of each of the other comorbid pain conditions (P<.001, odds ratio 2.3–3.3). Demographic risk factors for each condition varied. Increasing age was not associated with greater numbers of comorbid conditions, and only low socioeconomic status was associated with having multiple comorbid conditions concurrently. CONCLUSION: Chronic pain conditions are common, and a subgroup of women with vulvodynia is more likely than those without vulvodynia to have one or more of the three other chronic pain conditions evaluated. LEVEL OF EVIDENCE: II

The Bali STD/AIDS Study: evaluation of an intervention for sex workers.

Background Prostitution has been an important factor in the spread of HIV infection in Asia. Interventions need to be developed to reduce the risk of transmission of sexually transmitted infections in this area. Goals To educate female sex workers about sexually transmitted infections and assess the impact of the educational intervention. Study Design Brothel areas in Denpasar, Bali, Indonesia, were divided into areas of high and low program (interventional) effort. The intervention included educational sessions for sex workers, treatment of sex workers for sexually transmitted disease (STD), condom distribution, and printed information for clients of the sex workers. A high-effort area was one in which a more intensive educational intervention occurred. A clinic was available for STD treatment in both areas. Behavioral surveys and STD testing were used to evaluate the programs. Six hundred female sex workers participated in behavioral surveys and STD examinations every 6 months for four rounds of data collection. Each round, about half of the women were new to the study. A total of 1586 women participated in at least one evaluation round. Changes were evaluated in AIDS knowledge, STD knowledge, and condom use, as well as in the prevalence of Neisseria gonorrhoeae, Chlamydia trachomatis, syphilis, and Trichomonas vaginalis. Testing for HIV was conducted anonymously. Results Improvements were noted in the knowledge of sex workers about AIDS and STDs and in the reduction of some bacterial STDs. Women who remained in the study area for more than one round had increased knowledge of HIV infection/STDs and condom use and had reduced levels of syphilis, gonorrhea, and trichomonas infection (P < 0.01). The additional education received by women in the high-effort program area was associated with a reduction in the prevalence of syphilis. Prevalence of HIV remained low throughout the study. The high level of turnover of female sex workers contributed to the maintenance of significant levels of STDs in this population. Conclusions Developers of HIV/STD prevention programs for sex workers need to consider the mobility of the sex worker population. Interventions combining behavioral and medical approaches can contribute to prevention of these diseases.