Clobetasol propionate in the treatment of premenarchal vulvar lichen sclerosus

OBJECTIVE: To assess the effectiveness of treating premenarchal vulvar lichen sclerosus with clobetasol propionate. METHODS: A retrospective chart review was performed of girls presenting to the University of Michigan Pediatric and Adolescent Gynecology Clinic from January, 1995, to July, 2000, with premenarchal lichen sclerosus. Subjects in the study were treated with topical clobetasol propionate ointment 0.05% for 2-4 weeks, and then tapered to a less potent steroid. Information was extracted concerning age at onset, symptoms, vulvar examination, previous treatments, effectiveness of clobetasol, follow-up, and complications. The parents were contacted for a follow-up telephone survey. RESULTS: Fifteen girls averaging 5.7 years at the start of symptoms met criteria. The diagnosis of lichen sclerosus was made visually in 11 and by biopsy in four. Follow-up ranged from 2 months to 6 years. Fourteen girls had good improvement within 4-7 weeks. One girl developed a yeast superinfection and one developed transient erythema. At least 1 year of follow-up by clinic visit or telephone interview was available in 11 girls. Of these 11, two girls had no further vulvar symptoms after the initial treatment, five had one or two total flares, three reported three to eight flares per year, and one girl continues to be unresponsive to therapy. CONCLUSION: Clobetasol propionate was an effective treatment of premenarchal vulvar lichen sclerosus in this small group; however, recurrences were common and required additional steroid treatment. Furthermore, complications of treatment were infrequent, minor, and easily treatable.     

Topical testosterone versus clobetasol for vulvar lichen sclerosus.

OBJECTIVE: To compare the effects of topical testosterone and clobetasol treatments on symptoms remission and recurrence rates in patients with vulvar lichen sclerosus (LS). METHODS: A retrospective review of the records showed that, of 140 patients with biopsy-proven vulvar LS, 80 were treated with applications of testosterone propionate 2% in petrolatum and 60 with clobetasol 17-propionate 0.05%. RESULTS: The response rates after 6 months were 77.5% for patients treated with testosterone and 91.7% for those treated with clobetasol (P=0.02). The recurrence rates were 20% and 6.7% in the 2 groups, respectively (P=0.02). Premenopausal patients had higher remission rates and lower recurrence rates than postmenopausal patients (P>0.05). Considering whole patients, low remission rates and high recurrence rates were observed in patients who had had a hysterectomy (P>0.05). CONCLUSION: Treatment of LS with a corticosteroid provided excellent remission rates. In this study, clobetasol 17-propionate 0.05% was superior to testosterone for both remission induction and maintenance therapy.     

Calcineurin antagonists in vulvar lichen sclerosus

Lichen sclerosus et atrophicus is a chronic inflammatory disorder that mainly affects girls of premenarchial age and women in their fifties. Besides the anogenital region, lichen sclerosus (LS) may also affect extragenital or mucosal areas. Symptoms include soreness and pruritus, but other less common symptoms are not rare. An increased activity of fibroblasts causes increased sclerosis of the affected skin. Latest studies have identified LS as a chronic inflammatory dermatosis. Auto-antibodies against the extracellular membrane protein-1 are present in up to 80% of the patients. Moreover, in the widely accepted therapy with potent corticosteroids promising results have been presented using calcineurin antagonists in the treatment of LS. An interdisciplinary management and a continued care of patients with LS will improve the clinical manifestations and quality of life.     

Genetic aspects of vulvar lichen sclerosus

Thirteen instances of familial lichen sclerosus have been recorded in the literature. This report documents the disease in two additional families and adds genetic data on their HLA characteristics. The relationship of these factors to a possible autoimmune mechanism for the disease is discussed.     

Risk factors for vulvar lichen sclerosus

To assess risk factors for vulvar lichen sclerosus data were collected in a case-control study of 75 cases and 225 age-matched control subjects. Questions concerned personal characteristics and habits, gynecologic and obstetric data, general indicators of sexual habits, and selected dietary habits. The risk of vulvar lichen sclerosus was greater in parous women than nulliparous women, but there was little tendency for the risk to increase with number of births; the finding was not significant when only married women were considered. There was no material difference between cases and control subjects in relation to major indicators of sexual habits (age at first intercourse and number of sexual partners). A smaller proportion of cases was married, but no difference was observed in the distribution of cases and controls with reference to education, smoking habits, body mass index, and previous history of diabetes. There was no association between retinoids and risk of vulvar lichen sclerosus, but intake of carotenoids was inversely and strongly associated with vulvar lichen sclerosus. This apparent protection did not materially change after adjustment for socioeconomic status and other potential confounding factors.     

The treatment of vulvar lichen sclerosus and female sexual dysfunction

IntroductionWomen with lichen sclerosus (LS) are more likely to have dyspareunia, decreased orgasm, and decreased coital frequency as compared to unaffected women. It is unknown whether standard medical therapy to treat LS results in improved sexual functioning.AimsTo describe sexual function in women with LS and to assess if LS‐associated sexual dysfunction decreases after appropriate medical therapy.MethodsWomen enrolled in a double‐blind trial 12‐week trial comparing clobetasol vs. pimecrolimus for the treatment of LS were administered the Female Sexual Distress Scale (FSDS) upon enrollment and at the end of the trial. The difference in the total score on the FSDS between the two groups before and after treatment was assessed with a paired t‐test.Main Outcome MeasuresThe change in mean FSDS score from baseline to 12 weeks.ResultsA total of 31 out of 36 enrolled women had adequate treatment of LS as determined by a dermatopathologist's evaluation of pre and post‐treatment biopsy specimens. The mean baseline FSDS score for the clobetasol group was 29 and, post‐treatment, it was 15 (P = 0.001). In the pimecrolimus group, the mean baseline FSDS score was 27 and, post–treatment, it was 21 (P = 0.001).ConclusionsDespite adequate treatment, women with LS continue to have significant sexual dysfunction as assessed by the FSDS. Burrows LJ, Creasey A, and Goldstein AT. The treatment of vulvar lichen sclerosus and female sexual dysfunction.     

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.     

Childhood vulvar lichen sclerosus. The course after puberty

OBJECTIVE: To identify girls with vulvar lichen sclerosus (LS) and to follow them through puberty, documenting the course of the disease. STUDY DESIGN: Twenty-one postpubertal girls were identified from a cohort of 75 girls with LS presenting prepubertally and attending a pediatric vulvar clinic. Details of current symptoms, findings on examination and treatment needs were recorded. A database of 263 women with LS was reviewed for onset of LS premenarche. RESULTS: Of the 21 postpubertal girls, 16 reported an improvement in symptoms, but 11 stated that they still experienced occasional pruritus, requiring intermittent topical steroid application. Although the disorder appeared less active in most cases, definite physical signs persisted in 16 patients (75%); in 5 patients no physical signs of the disease remained. Of 251 postmenopausal women with LS, < 5 could recall symptoms in childhood. Of 12 young adult premenopausal patients with vulvar LS, 4 could recall symptoms in childhood. One of these, a 32-year-old with well-documented LS in childhood resolving at puberty, presented with and died of vulvar squamous cell carcinoma (SCC). CONCLUSION: Patients should be aware that LS may improve symptomatically but usually does not entirely resolve at puberty and that the disease in women may be associated with development of vulvar SCC. Ideally, long-term follow-up should be the standard of care.     

Topical mometasone furoate for vulvar lichen sclerosus

OBJECTIVE: To assess the efficacy and safety of treating vulvar lichen sclerosus with mometasone furoate, a synthetic analogue of beclomethasone. STUDY DESIGN: Thirty-one consecutive patients with biopsy-proven vulvar lichen sclerosus (LS) seen at the Florence Vulvar Clinic were entered into the study. Each subject's symptoms and the gross appearance of the lesions were recorded using a severity score according to the authors' previous studies. The patients were treated with a regimen of 0.1% mometasone furoate cream applications to the affected areas once daily for 4 weeks and then twice weekly for 8 weeks. After 12 weeks of treatment, the subjects were asked to rate the changes in their symptoms and were reevaluated by the same examiner for the gross appearance of the lesions. In every patient the before/after treatment total severity scores were compared using Wilcoxon's signed-rank test for statistical significance. RESULTS: With mometasone furoate all the patients had a significant improvement (P < .001) in the gross aspects of the disease and a very dramatic decrease in symptoms (P < .001), with nearly all the subjects having complete symptomatic remission. Compliance was excellent, and no side effects were observed. CONCLUSION: The improved risk/benefit ratio of mometasone furoate may minimize the possible long-term side effects expected when using a very potent topical steroid. Therefore, momentasone furoate cream may be an alternative to clobetasol propionate for treatment of vulvar LS, with similar efficacy but higher levels of safety and tolerability.     

外阴硬化性苔藓外阴上皮局部免疫状态初探

目的:探索外阴硬化性苔藓、外阴鳞状细胞癌上皮局部免疫状态。方法:选取2015年8月～2017年10月正常外阴患者15例、外阴硬化性苔藓患者30例和外阴鳞状细胞癌患者5例,免疫组化法检测外阴鳞状上皮免疫因子IFN-γ、IL-4、IL-17、HD-5、IgG的表达情况,透射电镜观察超微结构特点。结果:正常外阴组织、外阴硬化性苔藓、外阴癌鳞状上皮均不同程度表达IFN-γ、IL-4、IL-17、HD-5及IgG。外阴硬化性苔藓鳞状上皮IFN-γ、IgG免疫组化染色较正常外阴更深。与正常外阴鳞状上皮相比,外阴硬化性苔藓、外阴癌鳞状上皮IFN-γ、IL-4、IL-17、HD-5及IgG表达无显著差异。与外阴硬化性苔藓相比,外阴癌鳞状上皮上皮源性IgG表达显著下降。电镜下可见外阴硬化性苔藓鳞状上皮载色素细胞的减少。外阴鳞状细胞癌鳞状上皮可见细胞间桥减少,桥粒增多;细胞浆中张力源纤维减少;核仁中可见核小体等。结论:外阴硬化性苔藓发病可能与Th1类细胞因子IFN-γ、上皮源性IgG表达升高相关,与IL-4、IL-17及HD-5无显著相关性。     

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.     

Prevalence of vulvar lichen sclerosus in a general gynecology practice

OBJECTIVE: To describe the rate of vulvar lichen sclerosus in 1 general gynecology practice. STUDY DESIGN: A database of 1,675 consecutive patients presenting in a 3-year period to a general gynecology practice was utilized to identify women with lichen sclerosus. Data included age, menopausal status, symptoms and physical examination findings. Pathology specimens were reexamined by a gynecologic pathologist to confirm the diagnosis of lichen sclerosus. RESULTS: Of the 1,675 patients, 28 (1.7%) had biopsy-proven vulvar lichen sclerosus. Nine patients been diagnosed previously, and 19 were new cases. The mean age at diagnosis was 52.6 years (SD +/- 15.9) versus 37.1 years (SD +/- 16.4) for those without lichen sclerosus (p < 0.001). Fifteen of the 28 patients (54%) were post-menopausal at the time of diagnosis. Of the 19 women with newly diagnosed lichen sclerosus, 8 (42%) were symptomatic. Of the 11 asymptomatic women, 7 (64%) had scarring of the clitoral prepuce or resorption of the labia minora. CONCLUSION: The rate of vulvar lichen sclerosus in 1 general gynecology private practice is approximately 1.7%. Clinicians must maintain a high index of suspicion to make the diagnosis, as at least one third of patients may be asymptomatic.     

Photodynamic therapy of vulvar lichen sclerosus with 5-aminolevulinic acid

Objective: To evaluate the therapeutic effect of photodynamic therapy on vulvar lichen sclerosus.Methods: Twelve women with lichen sclerosus were enrolled in a prospective, single-arm pilot study. Four to 5 hours before photodynamic therapy, 10 mL of a 20% solution of 5-aminolevulinic acid was applied topically to the vulva. Photodynamic therapy was administered with an irradiation of 80 J/cm² at an irradiance of 40–70 mW/cm². Light with a wavelength of 635 nm was delivered by an argon ion–pumped dye laser. The degree of pruritus was evaluated using a horizontal visual analog scale before and after 6–8 weeks, and patients were followed tri-monthly after photodynamic therapy.Results: Two women underwent two cycles of photodynamic therapy, one underwent three cycles, and the remaining nine women underwent one cycle each. Treatment was tolerated moderately well, with eight patients not requiring any analgesia; three treated with opioids intravenously during the procedure, due to burning sensations; and one undergoing separation of adhesions under general anesthesia. Minimal local toxicity included vulvar erythema but no necrosis, sloughing, or scarring. No generalized cutaneous photosensitivity was present. Six to 8 weeks after photodynamic therapy, pruritus significantly improved in ten of the 12 women. A prolonged effect of photodynamic therapy was reported, with a mean of 6.1 months.Conclusion: Photodynamic therapy after topical application of 5-aminolevulinic acid produced statistically significant relief of symptoms of vulvar lichen sclerosus for an average of 6.1 months with minimal side effects.     

Guidelines for the follow-up of women with vulvar lichen sclerosus in specialist clinics

It is recommended that women with vulvar lichen sclerosus be followed in specialist clinics where difficulty exists with symptom control or where there is clinical evidence of localized skin thickening. Follow-up is also recommended for women who have previously been treated for squamous cell carcinoma of the vulva (arising in lichen sclerosus or vulvar intraepithelial neoplasia) or where the pathologist expresses concern and is unable to make a definitive diagnosis of differentiated vulvar intraepithelial neoplasia.