Pimecrolimus cream 1% in the treatment of lichen sclerosus

BACKGROUND: Lichen sclerosus (LS) is a chronic inflammatory skin condition, which most commonly causes dysuria, pruritus and soreness of the vulval and perianal areas. Potent topical corticosteroids are used for the treatment of LS, but it is well known that they inhibit collagen synthesis and cause skin atrophy as a side effect. METHODS: The present pilot study evaluated the efficacy and safety of pimecrolimus cream 1% applied twice daily for up to 6 months in 29 women with severe LS. RESULTS: Of the 26 subjects who completed the follow-up period, 42% (11/26) were in complete remission with relief from itchiness, pain and inflammation. A 3.5-fold increase in type I collagen synthesis and a 7.5-fold increase in type III collagen synthesis of the affected areas was detected after 2 months of pimecrolimus treatment. There were no systemic adverse reactions, although mild local skin reactions were reported by 50% of the patients. Blood concentrations of pimecrolimus were checked in 10/26 patients (39%) and were undetectable in all cases. CONCLUSIONS: Patient-applied 1% pimecrolimus cream is safe and effective for the treatment of LS.     

Pimecrolimus for the treatment of vulvar lichen sclerosus: a report of 4 cases

BACKGROUND: Lichen sclerosus is a chronic cutaneous disorder with a predilection for the vulva. The etiology is unknown. Superpotent topical corticosteroids are the most effective treatment. Dermal atrophy, however, is a well-known complication associated with changes of lichen sclerosus superpotent topical corticosteroids. In addition, some women do not respond adequately to topical steroids. Therefore, a treatment regimen that does not rely on corticosteroids may be beneficial. As lichen sclerosus is a T-lymphocyte-mediated disorder, it has been suggested that a topical macrolide immunosuppressant, such as pimecrolimus, may be a safe and effective alternative treatment for lichen sclerosus. Since pimecrolimus does not affect collagen synthesis, it does not cause thinning of the dermis. CASES: Four patients with biopsy-proven lichen sclerosus were treated with 1% pimecrolimus cream twice daily. At the end of 3 months of treatment, 3 of the 4 patients reported complete resolution of their symptoms of vulvar itching and burning. Two patients had repeat vulvar biopsies at the end of treatment that showed reversal of the histologic changes of lichen sclerosus. CONCLUSION: In this small series, pimecrolimus appeared to be a safe and effective treatment of vulvar lichen sclerosus. A randomized, controlled trial comparing pimecrolimus and clobetasol propionate should be performed to determine which is the safer and more effective medication for the long-term treatment of lichen sclerosus.     

Pimecrolimus for the treatment of vulvar lichen sclerosus in a premenarchal girl

BACKGROUND: Lichen sclerosus is a chronic cutaneous disorder with a predilection for the vulva. Lichen sclerosus affects more than one in 900 girls. Superpotent corticosteroids like clobetasol propionate are the most effective treatment for vulvar lichen sclerosus. However, recurrence after stopping steroids is very high. As repeated courses of corticosteroids are frequently needed, there are concerns about potential side effects. Therefore, a treatment regimen that does not rely on corticosteroids may be beneficial. As lichen sclerosus is a T-lymphocyte mediated disorder, it has been suggested that pimecrolimus, a topical T-lymphocyte inhibitor, may be safe and effective for the treatment of lichen sclerosus in children. CASE REPORT: A 10-year-old girl with lichen sclerosus was initially treated with clobetasol. Remission was achieved, but 3 months later she had a recurrence. Subsequent treatment with clobetasol led to a breakdown of her peri-anal skin with a superimposed infection. She was then treated with pimecrolimus and remission was achieved. She has had no recurrence of active lichen sclerosus and has less burning with pimecrolimus than with clobetasol. CONCLUSION: Pimecrolimus may be an effective treatment of vulvar lichen sclerosus. Pimecrolimus has been shown to be very safe in the pediatric population for the treatment of mild to moderate eczema, without causing dermal atrophy, tachyphylaxis, striae, rebound flares, or hypothalamic-pituitary axis suppression. As the recurrence rate of active lichen sclerosus in prepubertal girls treated with topical corticosteroids is high, and the majority of prepubertal girls with lichen sclerosus continue to have disease after menarche, a treatment regimen that does not rely on corticosteroids may be beneficial.     

Evaluation of contact sensitization in vulvar lichen simplex chronicus. A proposal for a battery of selected allergens

OBJECTIVE: To determine the role of contact sensitization in vulvar lichen simplex chronicus and to select appropriate batteries of allergens to test. STUDY DESIGN: Between 1993 and 2000, 61 women affected by vulvar lichen simplex chronicus were enrolled to evaluate the role of contact hypersensitivity. All the patients underwent patch tests with the Italian standard series and with a wide battery of allergens (preservatives, perfumes, emulsifiers, medicaments) and products they used routinely. RESULTS: Of the women, 47.5% had at least one positive patch test, and relevant positivities were observed in 26%. The relevant allergens were usually medicaments and preservatives. CONCLUSION: It would be acceptable to reduce the number of allergens tested, in particular omitting the perfume series. Patch tests are a helpful diagnostic tool in vulvar lichen simplex chronicus and improve prescribing practice.     

Overnight 5% lidocaine ointment for treatment of vulvar vestibulitis

OBJECTIVE: To assess the effectiveness of nightly application of 5% lidocaine ointment for treatment of vulvar vestibulitis. METHODS: Over 17 months, we assessed women presenting to our pain clinic for evaluation of introital pain; 61 women met the criteria for vulvar vestibulitis and participated in a treatment trial. We measured daily pain and intercourse-related pain using a 100-mm visual analog scale. We compared ability to have intercourse and pain ratings before and after treatment, and investigated whether prior treatment or gynecologic comorbidities predicted response to treatment. RESULTS: After a mean of 7 weeks of nightly treatment, 76% of women reported ability to have intercourse, compared with 36% before treatment (P =.002). Intercourse-related pain score was 39.11 (95% confidence interval [CI] 30.39, 47.83) points lower after treatment (P <.001), with a decrease of 10.37 (95% CI 3.53, 17.21) points in daily pain score (P =.004). We found no association between response to prior episodic use of lidocaine and response to nightly therapy with lidocaine ointment. Few patient characteristics predicted response to treatment; however, women with interstitial cystitis and other vulvar conditions were least likely to benefit. CONCLUSION: Long-term, nightly application of 5% lidocaine ointment shows promise as a treatment for management of vulvar vestibulitis; a randomized, double-blind, clinical trial is warranted.     

Citalopram in the treatment of women with chronic pelvic pain: an open-label trial

OBJECTIVE: To determine the efficacy of citalopram in the treatment of chronic pelvic pain by measuring changes in pain severity, depressive symptoms and functional disability. STUDY DESIGN: Fourteen women between 18 and 50 years of age with chronic pelvic pain were enrolled in a 12-week, open-label, flexible-dose study. Following a single-blind washout, placebo nonresponders were treated with citalopram (20-60 mg/d). RESULTS: Twelve patients completed the study. Depression scores decreased significantly on the Hamilton Psychiatric Rating Scale for Depression (p = 0.006), pain severity showed a trend toward improvement on the McGill Pain Intensity Scale (p = 0.096), but there was no significant differences on the Pain Disability Index (p = 0.158). Eleven of 12 (91.7%) patients elected to continue taking citalopram after study completion. CONCLUSION: Citalopram is effective in reducing depressive symptoms, shows a statistical trend toward improvement in pain intensity in women with chronic pelvic pain and is well tolerated. It appears minimally effective in reducing disability. Larger, controlled studies are needed to evaluate the role of citalopram in treating chronic pelvic pain.     

Effectiveness of hypnosis for the treatment of vulvar vestibulitis syndrome: a preliminary investigation

IntroductionVulvar vestibulitis syndrome (VVS) is a common cause of vulvar pain. Therapeutic options target different pain systems believed to be involved in its development and maintenance. Most treatments target the pain component with the assumption that sexual function will increase once the pain has decreased, yet this is not necessarily the case.AimsResearch has supported the effectiveness of hypnosis for many chronic pain disorders, and a case report demonstrated pain reduction and an increase in intercourse pleasure in a woman with VVS. This preliminary study examined the effectiveness of hypnosis on pain and psychosexual function in VVS.MethodsEight women suffering from VVS completed a hypnosis screening assessment, an interview, pain and psychosexual questionnaires, a gynecologic examination, vestibular pain threshold measurement, a psychosexual assessment, and six hypnotherapy sessions. The physical examinations, interview, and questionnaires were repeated at 1 and 6 months posttreatment.Main Outcome MeasuresThese included pain ratings during the gynecologic examination, vestibular pain thresholds, scores on the McGill Pain Questionnaire and Pain Catastrophizing Scale, and responses to questions on intercourse-related and nonintercourse-related pain. Measures of psychosexual function included the Female Sexual Function Index, State-Trait Anxiety Scale, Beck Depression Inventory-II, and the Brief Symptom Inventory.ResultsResults indicated significant decreases in gynecologic examination pain and in several measures assessing intercourse pain, and nonsignificant increases in threshold. Some indices of noncoital vulvar pain decreased. Overall sexual function, particularly sexual satisfaction, increased at posttreatment. There were no differences on any psychological measure. Participants reported satisfaction with the treatment and rated their VVS pain reduction as average.ConclusionsHypnotherapy appears to be a promising treatment for reducing intercourse pain and some aspects of noncoital vulvar pain, and for restoring sexual function in women with VVS. These results suggest that a large controlled trial should be considered. Pukall C, Kandyba K, Amsel R, Khalifé S, and Binik Y. Effectiveness of hypnosis for the treatment of vulvar vestibulitis syndrome: A preliminary investigation.     

Clinical evaluation of econazole nitrate in 1% vaginal cream for treatment of vaginal candidosis.

30 patients with mycologically confirmed vaginal candidosis on culture were treated with econazole vaginal cream (Gyno-Pevaryl) applied intravaginally once a day for 2 wk. 8 days after the end of treatment, mycological and clinical cures were demonstrated in 26 patients. Symptoms generally subsided rapidly, and the drug was well tolerated. This study confirms the efficacy of econazole in the treatment of vaginal candidosis.     

Sexual functioning after treatment of in situ vulvar cancer: preliminary report

Forty-two patients treated for in situ vulvar cancer at two institutions participated in structured assessment interviews and completed questionnaires to examine postoperative sexual, marital, and psychological adjustment. Patient responses were compared with a matched sample of gynecologically healthy women. The results indicated a specific pattern of sexual disruption for the women treated for preinvasive disease. Sexual behavior patterns appeared to be maintained, as was the desire phase of the sexual response cycle. However, there was specific disruption of the phases of excitement and resolution and, to a lesser extent, orgasm. In addition to a two- to threefold increase in the frequency of sexual dysfunction, 30% of the sample was sexually inactive at follow-up. Although replication of these findings is necessary, this investigation suggests that sexual functioning correlates with the magnitude of treatment.     

Pure versus complicated vulvar vestibulitis: a randomized trial of fluconazole treatment

OBJECTIVE: To examine the effectiveness of a 6-month treatment consisting of a weekly oral dose of 150 mg fluconazole for women with vestibulitis, and to explore the causes of treatment failure. METHODS: Forty women with vestibulitis were randomized to either of two treatment groups. One group received a 6-month low oxalate diet with calcium citrate complement, as a placebo, and the second group the same diet and calcium citrate with the addition of a weekly oral tablet of 150 mg fluconazole. The women were examined 3 months after completing treatment, for response to therapy. RESULTS: The addition of intensive 6-month fluconazole treatment did not lead to an outcome better than that attained by maintaining a low oxalate diet with calcium citrate supplementation. The satisfactory response rate was 15 and 30%, respectively. The presence of 'complicated vestibulitis', candidiasis concomitant with vestibulitis, decreases the satisfactory response rate regardless of the type of treatment administered (odds ratio 19.9, 95% CI 1.6, 250). CONCLUSION: Prolonged oral fluconazole is an ineffective treatment of vestibulitis, whether pure or complicated by concomitant vulvovaginal candidiasis. The coexistence of candidiasis and vestibulitis - complicated vestibulitis - might represent a subset of vestibulitis that is resistant to the currently available medical therapy.     

Impact of a soy drink on climacteric symptoms: an open-label,crossover, randomized clinical trial

Objectives: The objective of this study is to evaluate the effects of a soy drink with a high concentration of isoflavones (ViveSoy®) on climacteric symptoms.

Methods: An open-label, controlled, crossover clinical trial was conducted in 147 peri- and postmenopausal women. Eligible women were recruited from 13 Spanish health centers and randomly assigned to one of the two sequence groups (control or ViveSoy®, 500?mL per day, 15?g of protein and 50?mg of isoflavones). Each intervention phase lasted for 12 weeks with a 6-week washout period. Changes on the Menopause Rating Scale and quality of life questionnaires, as well as lipid profile, cardiovascular risk and carbohydrate and bone metabolism were assessed. Statistical analysis was performed using a mixed-effects model.

Results: A sample of 147 female volunteers was recruited of which 90 were evaluable. In both sequence groups, adherence to the intervention was high. Regular consumption of ViveSoy® reduced climacteric symptoms by 20.4% (p?=?0.001) and symptoms in the urogenital domain by 21.3% (p?p?<0.05).

Conclusion: Regular consumption of ViveSoy® improves both the somatic and urogenital domain symptoms of menopause, as well as health-related quality of life in peri- and postmenopausal women.     

Botulinum toxin type A for the treatment of provoked vestibulodynia: an open-label, pilot study

OBJECTIVE: To evaluate the effects of botulinum toxin type Afor the treatment of provoked vestibulodynia. STUDY DESIGN: Open-label, dose-escalation, pilot study. Primary outcome measure was a standard numeric pain rating scale of 0-10. Secondary measures were improvements in quality of life and change in medication use. RESULTS: The 7 patients who received 35 units of botulinum toxin type A had a baseline mean pain score (0-10) of 8.1 (SD = 0.70). Thirty days after treatment, these patients had a mean pain score of 2.9 (SD= 1.17). The duration of effect was 8 weeks, and there were no side effects. The 12 patients who received 50 units of botulinum toxin type A had a baseline mean pain score of 7.4 (SD = 0.10). Thirty days after treatment, these patients had a mean pain score of 1.8 (SD= 0.72). The duration of effect was 14 weeks, and there were no side effects. Significant improvement was also seen in medication use and quality of life for these patients. CONCLUSION: This study provides further clinical evidence of the nociceptive effects of botulinum toxin type A in pelvic inflammatory pain-related disorders. Doubleblind, placebo-controlled trials to evaluate the efficacy of botulinum toxin in treating patients with provoked vestibulodynia are warranted.     

Butoconazole nitrate 2% for vulvovaginal candidiasis. New, single-dose vaginal cream formulation vs. seven-day treatment with miconazole nitrate. Gynazole 1 Study Group

OBJECTIVE: To compare the safety and efficacy of a single vaginal dose of a butoconazole nitrate 2% bioadhesive, sustained-release cream* (butoconazole 1-BSR) with a seven-day schedule of miconazole nitrate vaginal cream 2% (miconazole 7). STUDY DESIGN: The clinical trial was conducted according to a randomized, parallel, investigator-blind, multicenter study design. The patients self-administered the respective creams to the posterior vaginal fornix. Two hundred twenty-three patients started the trial and were analyzed for safety. A total of 205 patients qualified for efficacy analysis, 101 receiving butoconazole 1-BSR and 104 using miconazole 7. Patients receiving butoconazole 1-BSR inserted one applicator full of medication once. Those assigned to receive miconazole 7 inserted one applicator full daily for seven days. Patients were evaluated 7-10 and 30 days after completion of therapy. RESULTS: Butoconazole 1-BSR rapidly relieved the signs and symptoms of vulvovaginal candidiasis. The proportion of patients with severe symptoms declined from the pretreatment 20% to 6% on the 1st day, to 3% on the 4th day, and to 2-1% on the 5th-7th day after single-dose application. Eight to ten days after treatment completion, clinical symptoms regressed in 92%, and fungal cultures were negative in 87% of patients. At the 30-day posttreatment visit, 88% of patients remained clinically cured, and 74% had negative fungal cultures. In the miconazole 7 group, the proportion of patients with severe symptoms declined from 23% to 19% after the first dose; thereafter, symptom relief proceeded more rapidly. Eight to ten days after treatment completion, clinical symptoms regressed in 92% and fungal cultures were negative in 87% of patients. At the 30-day follow-up examination, 86% patients were clinically cured, and 77% were culture negative. After single-dose butoconazole 1-BSR, severe symptoms receded faster than after the first dose of miconazole 7, and the difference was statistically significant (P = .01). In all other efficacy parameters, the differences between the two groups were not statistically significant. Neither treatment regimen caused significant adverse events. CONCLUSIONS: This clinical trial demonstrated that butoconazole 1-BSR is an effective and safe alternative to longer-term therapy with miconazole nitrate (seven days) for vulvovaginal candidiasis.     

Evidence-based medicine for treatment: an in vitro fertilization trial

Evidence-based evaluation of treatment is a pivotal component of an effective and satisfying clinical practice. When the best evidence has been identified, it can be efficiently assessed on three levels: Are the methods valid? Is the effect sufficiently large to be meaningful to patients? Are the patients, intervention(s), and outcomes studied applicable to our own patients? These criteria were applied to a multicenter trial that evaluated whether intracytoplasmic sperm injection (ICSI) was superior to in vitro fertilization (IVF) among infertile couples with no known male factor who were on a waiting list for IVF. The study was a well-designed randomized controlled trial that effectively concealed the randomization list and took reasonable steps to exclude bias. The results seemed important because the number needed to treat (13) was relatively low and significant, but the primary outcome (implantation rate) was not clinically meaningful. The trial results would have been relevant to most infertile couples with no known male factor if it had been powered to evaluate a difference in a more relevant clinical outcome, such as live birth. Thus, it has not been shown definitively that ICSI is inferior to IVF among couples with no known male factor, and clinical demand for ICSI may continue to rise.