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Objective: The aim of the study was to describe the clinical and histopathologic features required for a clinicopathologic diagnosis of vulvar lichen planus (LP), which is divided into 3 types: erosive, classic, and hypertrophic., Materials and Methods: The International Society of the Study of Vulvovaginal Diseases tasked the Difficult Pathologic Diagnoses committee with development of a consensus document for the clinicopathologic diagnosis of vulvar LP, lichen sclerosus, and differentiated vulvar intraepithelial neoplasia. The LP subgroup reviewed the literature and formulated diagnostic criteria, then approved by the International Society of the Study of Vulvovaginal Diseases membership., Results: The clinicopathologic diagnosis of erosive LP incorporates 5 criteria: (a) a well-demarcated, glazed red macule or patch at labia minora, vestibule, and/or vagina, (b) disease affects hairless skin, mucocutaneous junction, and/or nonkeratinized squamous epithelium, (c) evidence of basal layer damage, categorized as degenerative or regenerative, (d) a closely applied band-like lymphocytic infiltrate, and (e) absent subepithelial sclerosis. The clinicopathologic diagnoses of classic and hypertrophic LP each require a characteristic clinical appearance accompanied by hyperkeratosis, hypergranulosis, acanthosis, basal layer degeneration, a closely applied lymphocytic infiltrate, and absent dermal sclerosis, with hypertrophic LP showing marked epithelial abnormality compared with classic LP., Conclusions: Clinicopathological correlation yields the most reliable diagnosis of vulvar LP. Disease appearance overlaps with other physiologic, dermatologic, infectious, and neoplastic entities; a low threshold for biopsy at all morphologically distinct areas is recommended. Use of the histopathologic criteria described in this document may reduce the nondiagnostic biopsy rate for clinically diagnosed LP.

Vulvar squamous cell carcinoma associated with lichen sclerosus (VLS-VSCC) are rare tumors but with higher recurrence and worse prognosis than other types of VSCC. Lack of experimental models has limited the search for better understanding of the biology and development of treatment modalities. In this study, we isolated and characterized primary cells from VSCC (n = 7) and normal vulvar tissue adjacent to tumor (n = 7). Detailed characterization of the novel spontaneously immortalized cell line, VCC1 revealed a characteristic epithelial morphology in vitro and a well-differentiated keratinizing SCC histology in vivo, closely resembling the tumor of origin. VCC1 expressed higher levels of epithelial-mesenchymal transition markers and higher clonogenic properties as compared to other established non VLS-VSCC cell lines. In vitro 3D organotypic assays and in vivo xenografts revealed a prominent role of cancer-associated fibroblasts in VCC1 invasion and tumor formation. In conclusion, VCC1 mirrored several major VLS-VSCC features and provided a robust experimental tool for further elucidation of VLS-related oncogenesis and drug testing., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Lichen sclerosus (LS) is a chronic, inflammatory, mucocutaneous disorder of genital and extragenital skin (1). Simultaneous involvement of the oral mucosa is extremely rare, but it may be the only affected area (2). A 55-year-old woman was referred to the Department of Oral Medicine, School of Dental Medicine University of Zagreb due to whitish lesions on the right ventrolateral part of the tongue and buccal mucosa with desquamative gingivitis (Figure 1, a-c). The lesions were asymptomatic but indurated on palpation. Histology was conclusive for oral lichen sclerosus (OLS). The lesions on gingiva were successfully treated with betamethasone ointment, three times a day for two weeks. One year earlier, she had been referred to the Department of Dermatology and Venereology with progressive pruritus and dyspareunia, white patches, obliteration of the labia minora, and stenosis of the introitus (Figure 2). Histology was conclusive for vulvar LS (Figure 3, a and b). She was successfully treated for 5 months with clobetasol propionate 0.05% ointment. The patient was taking levothyroxine to treat hypothyroidism associated with Hashimoto's thyroiditis and was otherwise healthy. Oral LS is clinically characterized by the appearance of white macules, papules, or plaques mostly appearing on labial mucosa but also on buccal, palate mucosa and on the lower lip (2,3). On the genitals, it typically manifests as atrophic white plaques, which may be accompanied by purpura or fissuring (1). While vulvar LS is often associated with pruritus, dyspareunia, and dysuria, OLS is often asymptomatic, although pain, soreness, pruritus, and tightness when opening the mouth can be present (1,2). Oral manifestations of LS, as well as association of anogenital and oral LS, are rarely reported in the literature (4-6). Tomo et al. searched the Medline database for papers reporting oral LS cases with histological diagnosis confirmation from 1957 to 2016 and found only 34 cases of oral LS with histopathologic confirmation of the diagnosis (4). Kakko et al. reported 39 histologically proven cases of OLS (2). Attilli et al. (5) reviewed the clinical and histologic features of 72 cases of LS with oral/genital involvement. They reported that LS was diagnosed with exclusive genital lesions in 45, exclusive lip involvement in 20, and orogenital involvement in only 7 cases (5). Some believe that many cases of clinically diagnosed lichen planus may actually be LS and that isolated oral mucosal LS may not be as rare as is generally thought (2). While vulvar LS can occur at any age with increasing incidence with age, the median age of patients with OLS was 34 years and most of the patients were female (1,2,5). Due to the small number of patients in the literature, treatment recommendations for OLS are not available. In case of symptomatic oral lesions, topical or intralesional corticosteroids are considered to be the first-line treatment (2). First-line treatment for anogenital LS is a potent to very potent topical corticosteroid ointment, and second-line therapies include topical calcineurin inhibitors 1% pimecrolimus and 0.1% and 0.03% tacrolimus (1). For treatment-resistant genital LS, oral retinoids, methotrexate, and possibly local steroid injections for single lesions are mainly applicable for women (1). There is limited evidence for systemic treatments for both conditions. If it is not treated, genital LS is associated with a greater degree of scarring and an elevated risk of progression to squamous cell cancer; however, malignant transformation of OLS has not been reported (1-6). Due to the very rare presentation in the oral cavity, it is important to notice these lesions during a dental exam.

Background: We present an adolescent with multiple vulvar angiokeratomas within a background of lichen sclerosus., Case: A 13-year-old girl presented with vulvar pruritus and wart-like vulvar lesions. Four lesions were resected because of discomfort and uncertainty of the diagnosis. Pathology revealed angiokeratomas with chronic inflammation suggestive of lichen sclerosus. Postoperatively, pruritus continued in the largest excised lesion, which was associated with lichen sclerosus, and symptoms were treated successfully with topical steroids., Summary and Conclusion: Vulvar angiokeratomas are asymptomatic red papular lesions and are rare in the female adolescent population. In this case, the pathology revealed the rare co-occurrence of angiokeratomas and lichen sclerosus. Biopsies of vulvar vascular lesions in symptomatic adolescents are recommended. Vulvar angiokeratomas might manifest rare genetic disease in otherwise asymptomatic female patients and warrant further follow-up., (Copyright © 2019. Published by Elsevier Inc.)

Objective: There is no agreed upon standard way to measure vulvar lichen sclerosus disease severity. The Female Genital Self-Image Scale (FGSIS) is a validated survey tool assessing female genital self-image and is positively correlated with women's sexual function. A lower score represents a negative genital self-image. We evaluated the FGSIS in women with vulvar lichen sclerosus., Methods: Women with biopsy-proven lichen sclerosus and women presenting for routine gynecologic care without lichen sclerosus matched by age were surveyed with the 7-item FGSIS. National surveys of healthy women in the United States have shown the mean 7-item FGSIS score is 21. To detect one standard deviation (20% absolute difference) between groups with a power of 80% at p < .05, 15 women would are needed in each group., Results: Sixteen women with lichen sclerosus and 16 matched controls were surveyed between February and July 2018. The mean ± SD age of women with lichen sclerosus was 56.8 ± 13.5 years, 94% were white, 69% married, 81% college educated, 69% postmenopausal, and 18% on hormone replacement therapy. None of these differences were statistically different from control women. Women with vulvar lichen sclerosus had a significantly lower median 7-item FGSIS when compared with control subjects, 18 (interquartile range = 16-21) versus 25 (interquartile range = 23-27), respectively, Mann-Whitney U test, p < .001., Conclusions: Women with vulvar lichen sclerosus have a lower score on the 7-item Female Genital Self-Image Scale compared with healthy controls.

Mucinous metaplasia of the vulva (MMV) is a histopathologic finding that has been reported previously in only 3 patients and needs to be distinguished from vulvar extramammary Paget disease. We report 3 additional instances of MMV associated to Zoon vulvitis and vulvar lichen sclerosus et atrophicus. Histochemical and immunohistochemical studies were performed on biopsies from erythematous and erosive vulvar lesions of 3 women aged 64, 80 and 84 years, with features of Zoon vulvitis (2 cases) and lichen sclerosus et atrophicus (1 case). Mucin-containing epithelial cells were present on the uppermost layers of the squamous epithelium. On immunohistochemical study the metaplastic cells were positive for cytokeratin 7, epithelial membrane antigen and carcinoembryonic antigen, thus mimicking the phenotype of Paget disease. MMV is most likely related to chronic inflammation. Cytological and architectural features allow for distinction from Paget disease because the mucin-containing cells of mucinous metaplasia of the vulva lack atypia and are predominantly located on the most superficial layers of the surface epithelium.

The aims of the study were to review cases of clinically diagnosed lichen sclerosus (LS) and to compare the histological features found on biopsy to clinical features seen on examination., Methods: A retrospective chart review was undertaken of patients attending a specialist vulval service between 2013 and 2015 with a clinical diagnosis of LS. Patients in whom there was clinical diagnostic uncertainty or those with features of lichen planus or lichen planus/LS overlap were excluded. We determined the proportion of these patients who underwent vulval biopsy and reviewed their histology., Results: One hundred fifteen charts were reviewed. Sixty-nine (69/115, 60%) had a firm diagnosis of established LS, and of these, 39 (39/69, 56.5%) had a biopsy performed in the previous 5 years. Thirteen (13/39, 33.3%) of these biopsies fell short of a diagnosis of LS histologically with some suggestive but nondiagnostic and some showing nonspecific features., Conclusions: Reliance on biopsies solely to establish or exclude the diagnosis of LS is inadvisable. A good level of knowledge of the characteristic clinical features is imperative among gynecologists, dermatologists, and general practitioners.

The main purpose of the present study was to compare the dermoscopic changes on vulvar lichen sclerosus (VLS) induced by two different 12-week treatment protocols, namely mometasone furoate 0.1% ointment plus tretinoin 0.05% cream in short-contact therapy (group A) versus the same corticosteroid plus emollient (group B). All dermoscopic images captured before and after treatment were assessed. Each dermoscopic variable selected for the study purpose was arbitrarily graded according to a 4-point scale by dermatologists blinded to both the time at which the images were captured and treatment allocation. Seventeen patients in group A and 15 in group B were included. The vessel mean dermoscopic scores increased significantly after treatment, whereas the scores of (a) patchy, structure-less, whitish areas, (b) whitish background, (c) comedo-like openings, and (d) purpuric blotches decreased. At the control visit, the two protocols did not differ significantly for any of the dermoscopic parameters, both in terms of mean score change and in the number of patients showing changes. Although the complementary action of the two molecules may suggest a therapeutic benefit, the association of tretinoin in short contact therapy with a potent corticosteroid did not induce significant changes in the dermoscopic features of VLS compared with the same corticosteroid alone., (© 2018 Wiley Periodicals, Inc.)

Objective: Dysregulation of the Hedgehog (Hh) pathway has been described in a variety of cancers, including cervical cancer, a disease which shares a common aetiology with vulval squamous cell carcinoma (VSCC). Here, we investigate a large number of primary VSCC cases for evidence of Hedgehog pathway activation and examine the implications of pathway activity on clinical outcomes in a cohort of patients with primary VSCC., Methods: Archival histology blocks containing VSCC and histologically normal adjacent epithelium were retrieved from a cohort of 91 patients who underwent treatment for primary VSCC. Immunohistochemistry staining was undertaken to assess for the expression of key Hh pathway components (SHH, PTCH1, GLI1). A competing risks statistical model was used to evaluate the implications of the levels of key Hh pathway components on clinical outcomes., Results: We show that 92% of primary VSCC cases over-expressed one or more components of the Hh signalling pathway when compared to the adjacent normal epithelium. While expression of SHH and GLI1 did not correlate with any clinicopathological criteria, over- or under-expression of PTCH1 was associated with a reduced or increased risk of developing a local disease recurrence, respectively. In VSCC arising on a background of Lichen Sclerosus, the risk of local recurrence was potentiated in cases where PTCH1 was under-expressed., Conclusions: Our findings reveal, for the first time, that the Hh pathway is activated in VSCC and that PTCH1 expression can be used as a biomarker to stratify patients and inform clinicians of the risk of their local recurrence, particularly in cases of VSCC associated with LS., Competing Interests: The authors have declared that no competing interests exist.

Vulvar lichen sclerosus is an important skin disease that is common in women in their 50 s and beyond; however, it can also affect females of any age, including children. If not treated, it has the potential to cause significant and permanent scarring and deformity of the vulvar structure. In addition, if untreated, it is associated with a 2-6% lifetime risk of malignant squamous neoplasia of the vulva. Lichen sclerosus has been considered a difficult to manage condition; however, both serious complications can potentially be prevented with early intervention with topical corticosteroid, suggesting that the course of the disease can be treatment modified.

Vulval lichen planus-lichen sclerosus overlap is an emerging observation. Few clinical reports exist with no reviews of literature. We present a focused update of this phenomenon and discuss a clinical case. We report a 63-year-old woman with a 20-year history of ulcerative vulvo-vaginitis, initially diagnosed as benign mucous membrane (cicatricial) pemphigoid. This led to prolonged treatment with oral corticosteroids with minimal improvement in symptoms. Subsequent complications of long-term use of systemic corticosteroid ensued. A clinico-pathological diagnosis of severe erosive lichen planus was made on clinical findings and on non-specific biopsy changes of ulceration and inflammation. Treatment with topical clobetasol propionate 0.05% ointment twice daily led to dramatic improvement of ulceration, easing of discomfort and marked improvement in quality of life. Clinical examination revealed Wickham's striae on the labia majora supporting the diagnosis. Six years after commencement of topical clobetasol, white plaques were noticed on the labia majora, perineum and peri-anal region consistent with lichen sclerosus, confirmed by repeat vulval skin biopsy and on vulvectomy. This case highlights the challenge of diagnosis of extensive vulvo-vaginal ulceration and the necessity to re-examine a previous diagnosis if there is poor response to treatment.

Objectives This study aimed to investigate the usefulness and tolerability of topical tacrolimus in paediatric vulvar lichen sclerosus (LS). We examined whether there was improvement of the most problematic symptoms, such as itching, pain, and vulvar constipation. Methods Ten girls, aged from 4 to 9 years old who were affected by vulvar LS, were enrolled in an open clinical study to confirm the efficacy of tacrolimus 0.03% ointment to treat LS. Tacrolimus was applied twice a day for 6 weeks and then stopped during the follow-up period. The study duration included 6 weeks of treatment and 6 weeks of follow-up. A literature search of the PubMed (MEDLINE) database was conducted of reports published since 1 January, 2004. Results Our study and previous studies indicated the potential effectiveness of tacrolimus in LS. Treatment with topical tacrolimus was well tolerated with significant improvement of itching, pain, and constipation. Conclusion Tacrolimus may be a safe and effective alternative treatment, without the risk of corticosteroid-related vulvar atrophy, for paediatric vulvar LS. LS could become a further indication of topical tacrolimus therapy if these promising results are confirmed in the future.

Vulvar lichen sclerosus (VLS) is an uncommon, chronic inflammatory skin disease lacking clinical data of large sample size in China. This study was intended to provide missing data on this condition through investigating the clinical characteristics of Chinese VLS patients. The medical records of 129 VLS patients from our vulvar outpatient clinic were analyzed with SPSS version 18.0 software. The age of onset followed a normal distribution, with the peak at 25-30 years. Of all cases, the incidence rate during the postmenopausal period was 14.0% with an average duration of 9.22 years. The most frequently involved site was the bilateral labia minora (71.3%). Itching was the principal symptom (94.6%); meanwhile, patients with severe itching more commonly experienced longer duration, flaring at night, hyperkeratotic lesions or rashes on the posterior commissure than those with mild to moderate itching (P < 0.05). Furthermore, 60% of the enrolled patients suffered from sexual dysfunction. The major sign was pallor (92.2%), followed by hyperkeratosis (55.0%) and atrophy (40.3%). The patients with atrophy had a significantly longer duration of the disease, and the older patients presented more frequently with edema in the area of lesions (both P < 0.05). Of our patients, 9.3% suffered concomitantly from autoimmune diseases, mostly thyroid with one case being complicated by vulvar squamous cell carcinoma (SCC). In our study, the severity of pruritus was partly related to clinical manifestations. Moreover, Chinese patients could have developed VLS mostly in the reproductive period, with less complications of autoimmune diseases or SCC., (© 2018 Japanese Dermatological Association.)

Importance: Molecular alterations in lichen sclerosus-associated vulvar squamous cell carcinoma (LS-VSCC) are largely unknown., Objective: To determine whether the retinoic acid receptor β (RARβ) tumor-suppressor gene is involved in the onset and/or progression of LS-VSCC., Design, Setting, and Participants: The case-control study, conducted at University-Hospital of Ferrara, Italy, included 20 LS-VSCC (mean [SD] age, 75 [3] years) and 20 cancer-associated vulvar LS (caVLS; mean [SD] age, 62 [11] years) formalin-fixed embedded tissue specimens, 20 cancer-free vulvar LS (cfVLS), and 20 normal skin fresh specimens from diagnostic biopsies and women surgically treated for nonmalignant skin lesions, respectively. RARβ gene expression and promoter methylation were investigated in LS-VSCC and caVLS adjacent to VSCC specimens, and in cfVLS and normal skin specimens, as controls, by RT-Q real-time polymerase chain reaction (PCR) analysis, and sequencing of PCR-amplified bisulfite-treated DNA. c-Jun expression, an RARβ pathway-related gene, was also investigated., Main Outcomes and Measures: RARβ expression, correlation with its promoter methylation and c-Jun expression, and association with onset or progression of LS-VSCC., Results: In LS-VSCC, RARβ messenger RNA was 3.4-, 3.6-, and 4.8-fold lower than in caVLS (P = .001), cfVLS (P = .005), and normal skin (P < .001), respectively. The RARβ mRNA levels were similar in caVLS, cfVLS, and normal skin. The RARβ promoter was hypermethylated in 18 (90%) of 20 LS-VSCC, 11 (55%) of 20 cfVLS, 10 (50%) of 20 caVLS, and 5 (25%) of 20 in the normal skin group. The degree of methylation of RARβ promoter was higher in LS-VSCC, ranging from 5 to 9 (full promoter methylation) CpGs methylated, than in caVLS (P = .02), cfVLS (P = .03), or normal skin (P < .001), which was up to 5 CpGs methylated. Importantly, 0 of 8 LS-VSCC with 5 to 6 CpGs methylated and 5 (63%) of 8 LS-VSCC with 7 to 8 CpGs methylated were from patients with lymph node metastasis at diagnosis, respectively, whereas there were 2 of 2 (100%) LS-VSCC samples with 9 CpG methylated from patients with lymph node metastasis at diagnosis and subsequent recurrence. In LS-VSCC c-Jun mRNA was 4.3-, 1.4-, and 2.6-fold higher than in caVLS (P < .001), cfVLS (P = .001), and normal skin (P < .001), respectively. The expression of c-Jun was similar in caVLS, cfVLS, and normal skin., Conclusions and Relevance: Hypermethylation-induced RARβ down-expression was associated with LS-VSCC and correlates with the upregulation of c-Jun. The degree of methylation of RARβ promoter increased with the malignancy of LS-VSCC. Therefore, RARβ gene dysregulation may play a role in progression of LS-VSCC, and RARβ promoter methylation status may be used as a prognostic marker in clinical treatment of patients with LS-VSCC.

To determine if vestibulovaginal sclerosis and lichen sclerosus (LS) are 2 distinct entities. Biopsies obtained from the vagina or vulvar vestibule that contained abnormal subepithelial collagen were reviewed. Cases were categorized either as LS or vestibulovaginal sclerosis based on presence or absence of basal layer degeneration and lymphocytic infiltrate. Clinical data collected included examination findings, biopsy site and indication, previous vulvovaginal surgery, medications at time of biopsy, vulvar LS, treatment, and response. There were 15 cases with a mean age of 62 yr (range: 32-86 yr); 12 (80%) specimens were from vestibule and 3 from vagina. Nine cases were categorized as LS because of lymphocytic infiltrate in combination with basal layer degeneration, of these 8 had LS elsewhere on vulvar skin. Six cases were classified as vestibulovaginal sclerosis and had an absent or sparse lymphocytic infiltrate and essentially normal epithelium; none of these had vulvar LS. While vestibulovaginal sclerosis and lichen sclerosus are distinguishable clinically and histopathologically, further studies are needed to determine if vestibulovaginal sclerosis is a subset of LS or a different condition.

Most human papillomavirus (HPV)-associated vulvar squamous cell carcinomas (VSCCs) originate from high-grade squamous intraepithelial lesions, also named usual type vulvar intraepithelial neoplasia. However, growing evidence suggests that morphologic studies have limitations in predicting HPV status in vulvar lesions. We aimed to evaluate adjacent intraepithelial lesions in a series of DNA HPV-positive VSCCs, focusing on unusual histologic patterns mimicking differentiated vulvar intraepithelial neoplasia (dVIN) or lichen sclerosus (LS). We identified 326 DNA HPV-positive VSCC with at least 1 cm of skin adjacent to the invasive tumor and analyzed HPV typing, HPV E6*I mRNA, and p16 immunohistochemistry in all cases. A careful histologic evaluation was conducted. A conclusive association with HPV was based on a positive p16 or HPV E6*I mRNA result or both in addition to the HPV DNA, whereas cases negative for both markers were classified as nonconclusively associated with HPV. One hundred twenty-one tumors (37.1%) had normal adjacent skin, 191 (58.6%) had only high-grade squamous intraepithelial lesions, also named usual type vulvar intraepithelial neoplasia, and unusual intraepithelial lesions were identified in 14 (4.3%) tumors. Seven cases showed dVIN-like features, 5 showed adjacent LS-like lesion, and in 2 cases dVIN-like and LS-like lesions were identified simultaneously. Six of them were conclusively associated with HPV (3 dVIN-like, 2 LS-like, 1 with combined dVIN/LS-like features). All 6 tumors were associated with HPV16 and were positive for both p16 and HPV mRNA, and p16 was also positive in the dVIN-like and LS-like lesions. In summary, a small subset of VSCCs conclusively associated with HPV may arise on intraepithelial lesions, mimicking precursors of HPV-independent VSCC.

Background: Two etiologic pathways for vulvar squamous cell carcinoma (SCC) are described: in a background of lichen sclerosus and/or differentiated vulvar intraepithelial neoplasia and related to high-risk human papillomavirus (HPV) infection with high grade squamous intraepithelial lesion (HSIL) as precursor. The aim was to compare the predilection site and survival of HPV-related to non HPV-related vulvar SCCs., Methods: Data of patients treated for primary vulvar SCC at the Radboudumc between March 1988 and January 2015 were analyzed. All histological specimens were tested for HPV with the SPF 10 /DEIA/LiPA 25 system assay and p16 INK4a staining was performed using CINtec® histology kit. Vulvar SCCs were considered HPV-related in case of either >25% p16 INK4a expression and HPV positivity or >25% p16 INK4a expression and HSIL next to the tumor without HPV positivity. Tumor localization, disease specific survival (DSS), disease free survival (DFS) and overall survival (OS) of patients with HPV-related and non HPV-related vulvar SCC were compared., Results: In total 318 patients were included: 55 (17%) had HPV-related (Group 1) and 263 (83%) had non HPV-related vulvar SCC (Group 2). Tumors in Group 1 were significantly more often located at the perineum compared to Group 2, 30% and 14%, respectively (p=0.001). The DSS, DFS and OS were significantly better in HPV-related than in non HPV-related vulvar SCC patients., Conclusion: HPV-related vulvar SCCs are more frequently located at the perineum and have a favorable prognosis compared to non HPV-related vulvar SCCs. Both localization and HPV-relation could explain this favorable prognosis. HPV-related vulvar SCC seems to be a separate entity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We present a patient with the bullous form of lichen sclerosus of the vulva. She had no lesions in other cutaneous and mucosal areas. We used topical tacrolimus and topical clobetasol propionate. The patient was lesion free at the first-year follow-up.

Objective: To generate a list of items through international expert consensus consisting of both symptoms and clinical signs for inclusion in an adult vulvar lichen sclerosus severity scale., Methods: This study was carried out as a three-stage Delphi consensus exercise. After an extensive literature review, any items used to determine disease severity in previous clinical trials were compiled into a survey. The Delphi participants were recruited from the International Society for the Study of Vulvovaginal Disease most of whom were gynecologists and in practice for more than 20 years. Participants were asked to rate the importance of these items. Consensus was defined as 75% agreeing that an item was very important or essential toward determining disease severity. Participants were also asked to indicate preferred method of measurement for these items., Results: Of approximately 400 members of the International Society for the Study of Vulvovaginal Disease, 66 participated in the study. Of the 14 symptoms presented, 7 reached consensus for inclusion. Of the 23 signs presented, 11 reached consensus for inclusion and 1 reached consensus for exclusion. Of the six architectural changes presented, all six reached consensus for inclusion. No consensus was reached regarding method of measurement for any of the symptoms and signs that reached consensus for inclusion., Conclusion: International consensus was reached for a variety of items for use in an adult vulvar lichen sclerosus severity scale that will be further developed and tested. Ideally, this scale will be used in clinical practice and in research to allow for high-quality trials.

Lichen sclerosus is a chronic skin disease, mainly localised at the introitus and perineum. When the condition remains untreated, gradual atrophy of skin structures leads to permanent scarring, making early diagnosis and treatment crucial. We reviewed all patients diagnosed with lichen sclerosus presenting to a tertiary referral centre for paediatric and adolescent gynaecology between January 2011 and December 2015 to assess disease presentation and response to treatment. We identified 15 cases, with a mean age at diagnosis of 8.8 years. Their main presenting symptoms were vulvar pruritus and vulvar soreness. Seven girls had already atrophic changes, and in four girls, this amounted to clitoral phimosis, labial resorption or labial adhesion formation. The median delay in diagnosis was 7 months. Thirteen patients received local treatment with potent corticosteroids, responding well to treatment. However, 4 girls relapsed within 2 to 36 months. Two adolescents required surgical treatment, one because of urinary retention and the second because of dyspareunia caused by clitoral entrapment., Conclusions: There was a delay in diagnosis in most patients and this resulted in irreversible genital skin changes, which would have been preventable, had treatment been instituted promptly. The response to treatment with local corticosteroids was usually effective, leading to both symptom alleviation and prevention of disease progression. Atrophic changes and skin complications however were not reversed. What is Known: • Lichen sclerosus affects women of all ages, including girls, particularly prior to adolescence. • Lichen sclerosus responds well to local corticosteroid treatment. What is New: • In the majority of patients with lichen sclerosus there was a long delay between onset of symptoms and diagnosis. • Nearly half of the children diagnosed with lichen sclerosus had irreversible atrophic genital skin changes at the time of first presentation. These changes may have been prevented by a timely diagnosis and intervention.

A variety of disorders may be confused with vulvar or genital lichen sclerosus, as they can share several common features. This article discusses diagnosis, workup, and management of vulvar lichen sclerosus with specific attention on distinguishing it from other dermatologic mimics., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Women with vulvar lichen sclerosus (LS) have an increased risk of developing differentiated vulvar intraepithelial neoplasia and vulvar squamous cell carcinoma (SCC). Our primary aim was to determine the prevalence of LS among women with vulvar SCC. All patients who underwent excision for invasive SCC of the vulva from January 1, 2009 to December 31, 2013 were identified by searching our institution's electronic laboratory information system (n=111). The vulvar excision specimens from these patients were reviewed for the presence of adjacent LS. The grade of the SCC and clinical data were also documented for each case. The proportion of vulvar SCCs with adjacent LS identified on the excision specimen was 0.29 (95% confidence interval, 0.21-0.38). The proportion of patients in our study population who have ever had a histopathologic diagnosis of LS was 0.36 (95% confidence interval, 0.28-0.45). The presence of LS was not associated with the grade of the adjacent SCC. Patients with synchronous LS on excision were older on average than patients without LS. Tobacco users in our population were more likely to have a history of lower genital tract dysplasia, more likely to be younger, and less likely to have LS identified on the vulvar SCC excision specimen. Given the strong association between LS, differentiated vulvar intraepithelial neoplasia, and vulvar SCC, we recommend careful evaluation of these patients from a clinical and pathologic standpoint.

A 67-year-old woman presented with a firm plaque in the perineal region, 16 months after diagnosis of a high-grade basaloid squamous cell carcinoma of the vagina and treatment by external beam radiation therapy and vaginal cuff brachytherapy. The differential diagnosis included radiation-induced morphea, radiation dermatitis, or, possibly, radiation-induced lichen sclerosus. Biopsy findings, including special staining, confirmed the diagnosis of radiation-induced lichen sclerosus. To our knowledge, this is the first report of radiation-induced lichen sclerosus of the vulvar region.

Background: Lichen sclerosus (LS) is an uncommon idiopathic chronic inflammatory debilitating disease with predilection for the genital region. Our recent encounter with an LS case exhibiting perineural inflammation microscopically prompted us to assess the features of all patients diagnosed with LS at our institution., Materials and Methods: All cases of LS diagnosed between 1990 and 2014 were retrospectively reviewed. Diagnosis was confirmed with demonstration of microscopic features typical of LS., Results: Sixty patients (42 women and 18 men) with 65 biopsy specimens of LS were identified, of which 41 were extragenital, 16 genital, and three had both. Histopathologically, significantly higher proportions of follicular plugging, atrophy, and vacuolar interface changes were observed in extragenital LS cases, while angiokeratoma-like, mycosis fungoides-like, and pseudoepitheliomatous changes were only seen in genital LS. Perineural inflammation was observed as a novel finding in 22 cases (33.8%) of LS., Conclusion: Features of patients with LS in this study are generally comparable to those published in the literature, with some differences. In contrast to the literature, extragenital LS was more frequently encountered. Histopathologically, perineural inflammation was not an uncommon feature of LS and thus may serve as a clue in the differentiation of LS from its mimickers., (© 2016 The International Society of Dermatology.)

Objective: The aim of the study was to estimate the neoplastic potential of vulvar lichen sclerosus (VLS)., Materials and Methods: This was a retrospective study of 976 women with VLS. We recorded age at diagnosis of VLS, length of follow-up, and type of neoplasia, categorized as the following: (1) vulvar intraepithelial neoplasia (VIN), further subdivided in differentiated VIN (dVIN) and high-grade squamous intraepithelial lesion; (2) superficially invasive squamous cell carcinoma; and (3) frankly invasive squamous cell carcinoma. Neoplasia incidence risk, neoplasia incidence rate, and cumulative probability of progression to neoplasia according to the Kaplan-Meier method were estimated. Log-rank test was used to compare the progression-free survival curves by age at diagnosis of VLS., Results: The mean age at diagnosis of VLS was 60 (median = 60; range = 8-91) years. The mean length of follow-up was 52 (median = 21; range = 1-331) months. The following 34 patients developed a neoplasia: 8 VIN (4 dVIN, 4 high-grade squamous intraepithelial lesions), 6 keratinizing superficially invasive squamous cell carcinoma (5 with adjacent dVIN), and 20 keratinizing invasive squamous cell carcinoma (1 with adjacent dVIN). The neoplasia incidence risk was 3.5%. The neoplasia incidence rate was 8.1 per 1,000 person-years. The cumulative probability of progression to neoplasia increased from 1.2% at 24 months to 36.8% at 300 months. The median progression-free survival was significantly shorter in older women (≥70 years) when compared with that in younger women (p = .003)., Conclusions: Vulvar lichen sclerosus has a nonnegligible risk of neoplastic transformation and requires a careful and lifelong follow-up in all patients, particularly in elderly women. Early clinical and histological detection of preinvasive lesions is essential to reduce the risk of vulvar cancer.

Vulval lichen sclerosus is an uncommon skin condition that can usually be managed with topical corticosteroids to maintain remission. However, there is a subset of patients in whom it remains recalcitrant despite treatment with super-potent topical corticosteroids. We report a case series of four patients undergoing fractional carbon dioxide laser resurfacing and one with ablative carbon dioxide laser for severe, hyperkeratotic vulval lichen sclerosus not responding to super-potent topical corticosteroids. In these patients, carbon dioxide laser was successful in achieving remission. Their vulval lichen sclerosus was subsequently able to be maintained with topical corticosteroid treatment., (© 2015 The Australasian College of Dermatologists.)

Objective: Dermoscopic features of vulvar lichen sclerosus (VLS) were investigated in order to determine both vascular and non-vascular features of this disease., Materials and Methods: Dermoscopic images of 35 patients affected with histopathologically confirmed VLS were evaluated for the presence of predefined morphological criteria., Results: On dermoscopy, VLS lesions exhibited very sparse vessels, mainly linear, without a specific arrangement. Dotted vessels were observed mostly in the early stage of the disease. Patchy, structureless areas, whitish to white-yellowish to pink-whitish in colour over a diffuse whitish background, were a distinctive and constant dermoscopic feature. Grey-blue dots, usually with a characteristic peppered arrangement, corresponding to dermal melanophages, were also frequently seen. Comedo-like openings and scales were observed, as well as peculiar structures like ice slivers, not identified by histological examination., Conclusion: Our findings show that VLS exhibits characteristic dermoscopic patterns that can aid in its clinical diagnosis., (© 2015 S. Karger AG, Basel.)

OBJECTIVE. The aim of this study was to evaluate the efficacy of fat grafting in the treatment of severe vulvar lichen sclerosus (LS). Our primary outcome was to assess the improvement of mucocutaneous trophism, the resolution/reduction of symptoms, and the histological features of the vulvar skin after treatment. The secondary outcome was to evaluate the improvement in life quality, and in resumption and quality of sexual life. METHODS. Between 2011 and 2014, 36 patients were offered fat grafting to treat LS. Inclusion criteria were age between 25 and 80 years, histopathologic diagnosis of LS, good health, failure of previous first line treatments. RESULTS. 34 out of 36 patients (94%) showed a better vulvar trophismof the skin and mucosae; 27 (75%) had an improvement in caliber and elasticity of the vaginal introitus; clitoris burying degree was reduced in 18 patients (50%), 30 (83%) reported an increased volume of labia major a and minor a, 34 (94%) had a complete disappearance of scratching lesions, and 28 (78%) showed a remission of white lesions. Eventually 34 patients (95%) stopped using topical corticosteroids routinely. The improvement in life quality was significant for both DLQI (p b 0001) and FSFI (p b 0001). CONCLUSIONS. Fat grafting may have a role as a support and completion treatment in selected cases of women with vulvar LS who do not respond to first line therapy or in severe cases where the anatomical impairment does not allow a regular sexual function and a good quality of life.

Lichen sclerosus (LS) is an inflammatory skin disease that usually involves the anogenital area. All patients with symptoms or signs suspicious of lichen sclerosus should be seen at least once initially by a physician with a special interest in the disease in order to avoid delay in diagnosis, as early treatment may cure the disease in some and reduce or prevent scarring. The diagnosis is made clinically in most cases. Biopsies should only be performed under certain circumstances. The gold standard for treatment remains potent to very potent topical steroids; however, mild and moderate disease in boys and men may be cured by circumcision. Certain triggers should be avoided. http://www.euroderm.org/images/stories/guidelines/2014/S3-Guideline-on-Lichen-sclerosus.pdf http://www.awmf.org/fachgesellschaften/mitgliedsgesellschaften/visitenkarte/fg/deutsche-gesellschaft-fuer-gynaekologie-und-geburtshilfe-dggg.html., (© 2015 European Academy of Dermatology and Venereology.)

Importance: Adult vulvar lichen sclerosis (VLS) may be complicated by loss of vulvar structure and vulvar carcinoma. There is a lack of evidence as to the ideal method to maintain long-term remission and prevent complications., Objectives: To determine whether long-term preventive topical corticosteroid (TCS) treatment of VLS, with a target outcome of induction and maintenance of normal skin texture and color, reduces the risk of vulvar carcinoma, relieves symptoms, improves function, and preserves vulvar architecture, and to evaluate the adverse effects of treatment., Design, Setting, and Participants: A prospective longitudinal cohort study was conducted in 507 women with biopsy-proved VLS from January 2, 2008, through September 26, 2014, in the private practice of a dermatologist and a gynecologist in Sydney, Australia., Interventions: Preventive treatment using TCSs of various potencies, adjusted to meet a target outcome of normal skin color and texture, with regular long-term follow-up by a dermatologist or gynecologist., Main Outcomes and Measures: Symptoms or signs of VLS, scarring, development of malignant neoplasms, and adverse effects., Results: The mean age at presentation was 55.4 years (range, 18-86 years); duration of symptoms at presentation, 5.0 years (range, 0.1-40.0 years); and duration of follow-up, 4.7 years (range, 2.0-6.8 years). Remission was induced with a potent TCS, followed by regular preventive TCS treatment of a potency titrated to achieve the target outcome. Patients were followed up at least annually. A total of 150 patients (29.6%) did not carry out the advised treatment and were considered partially compliant. A total of 357 patients (70.4%) adhered to treatment instructions and were considered compliant. Biopsy-proved squamous cell carcinoma or vulvar intraepithelial neoplasia occurred during follow-up in 0 of the compliant patients vs. 7 (4.7%) of the partially compliant patients (P < .001). Suppression of symptoms occurred in 333 (93.3%) compliant patients vs. 87 (58.0%) partially compliant patients (P < .001). Adhesions and scarring occurred during follow-up in 12 (3.4%) compliant patients and 60 (40.0%) partially compliant patients (P < .001). Reversible TCS-induced cutaneous atrophy occurred in 4 (1.1%) compliant patients and 3 (2.0%) partially compliant patients., Conclusions and Relevance: This prospective, single-center, longitudinal cohort study of adult patients with VLS suggests that individualized preventive TCS regimens that achieve objective normality of skin color and texture and are used by compliant patients who attend regular long-term follow-up visits may modify the course of the disease. There was a significant difference in symptom control, scarring, and occurrence of vulvar carcinoma between compliant and partially compliant patients. The adverse effects of TCSs were minimal.

A spectrum of invasive adenocarcinomas presumably arising from the anogenital mammary-like glands of the vulva has been reported. Even rarer are the cases of pure ductal carcinoma in situ that originated from these unique glandular structures. Herein, we report an 81-yr-old woman presented with an invasive well-differentiated squamous cell carcinoma of the vulva. Unexpectedly, the underlying dermis demonstrated a cystically dilated structure that displayed a layer of malignant squamous cells in the periphery, and a second centrally located population of neoplastic cells exhibiting glandular differentiation. In addition, a spindle and pleomorphic malignant cell population consistent with a sarcomatoid carcinoma was identified around the cystic structure. Scattered benign anogenital mammary-like glands were present in the adjacent dermis. The histologic and immunohistochemical findings were consistent with those of vulvar squamous cell carcinoma that has undergone sarcomatoid transformation after spreading in a pagetoid fashion into an underlying focus of ductal carcinoma in situ of anogenital mammary-like gland origin.

Background: There is sufficient published data on induction treatment with potent topical corticosteroid (TCS) in childhood vulvar lichen sclerosus (VLS) but limited data on long-term management. VLS has been shown to extend beyond menarche and repercussions of suboptimal long-term control may be devastating and permanent. This single-center retrospective study reviewed outcomes of long-term treatment using individualized regimens with target outcome of complete objective normality., Methods: Forty-six girls with prepubertal-onset VLS were studied for demographic data, previous treatment, induction and maintenance treatment, clinical response and compliance. Photographic records were available for all patients. The cohort was divided into two groups: adherent (using treatment all or most of the time) and non-adherent (using treatment some or less of the time)., Results: Twenty-six patients (56%) had received prior treatment however only three had achieved disease control using daily potent TCS. Twelve patients (26%) had scarring on presentation. All achieved initial objective disease suppression with induction treatment using potent TCS. Thirty-one of 33 adherent patients (93.93%) sustained complete disease remission with no progression or scarring. In contrast, 1 of the 13 nonadherent patients (8%) achieved complete disease remission (p < 0.001), 9 of the 13 (69.23%) experienced disease progression (p < 0.001) and 3 of the 13 (23%) developed scarring during follow-up. Those with established scarring on presentation did not recover with treatment., Conclusion: Our data support previous studies regarding initial treatment with potent TCS but additionally suggest maintenance treatment with individualized regimens that achieve objective normality in addition to symptom control provide optimal outcomes., (© 2015 Wiley Periodicals, Inc.)

Objective: Limited evidence is available on the effectiveness of treatments alternative to corticosteroids for vulvar lichen sclerosus (VLS). The present study aimed to assess the efficacy and tolerability of avocado and soybean extracts (ASE) as active principles of both a topical product and a nutritional supplement in the treatment of active mild-to-moderate VLS., Materials and Methods: Twenty-three patients were enrolled. Treatment consisted of a topical product containing ASE and other lenitive and anti-oxidant principles administered twice daily for 24 weeks, in association with a dietary supplement containing ASE, vitamin E and para-aminobenzoic acid for the first 12 weeks. The primary efficacy endpoint was the rate of patients achieving an improvement from baseline in global subjective score (GSS) and global objective score (GOS) of ≥ 75%. Secondary efficacy endpoint was the rate of patients achieving GSS50 and GOS50. Tertiary efficacy endpoint was the mean reduction in subjective and objective scores throughout the treatment., Results: By the end of the 24-week treatment, 12 (70.5% of symptomatic patients) and 13 patients (72.2%) achieved an improvement of at least 75% in subjective and objective global scores, respectively; 100% and 88.9% reached GSS50 and GOS50, respectively. Mean symptom and sign scores decreased significantly after treatment. The treatment was well tolerated., Conclusions: Our results provide evidence that the topical and dietary supplements used in the study, which contain active principles exerting anti-inflammatory, anti-fibrotic, emollient and lenitive actions, are effective alternatives in the treatment of symptoms and signs of mild-to-moderate VLS., (© 2014 European Academy of Dermatology and Venereology.)

Objectives: The vulva is the primary site affected in lichen sclerosus, a chronic dermatosis in women that is histologically characterized by a zone of collagen remodeling in the superior dermis. The normal physiological properties of the vulva depend on the assembly of collagen types I (COLI), III (COLIII) and V (COLV), which form heterotypic fibers, and extracellular matrix protein interactions. COLV regulates the heterotypic fiber diameter, and the preservation of its properties is important for maintaining normal tissue architecture and function. In the current work, we analyzed the expression of COLV and its relationship with COLI, COLIII, elastic fibers and extracellular matrix protein 1 in vulvar biopsies from patients with lichen sclerosus., Methods: Skin biopsies from 21 patients with lichen sclerosus, classified according to Hewitt histological criteria, were studied and compared to clinically normal vulvar tissue (N=21). Morphology, immunohistochemistry, immunofluorescence, 3D reconstruction and morphometric analysis of COLI, COLIII, COLV deposition, elastic fibers and extracellular matrix 1 expression in a zone of collagen remodeling in the superior dermis were performed., Results: A significant decrease of elastic fibers and extracellular matrix 1 protein was present in the hyalinization zone of lichen sclerosus compared to healthy controls. The non-homogeneous distribution of collagen fibers visualized under immunofluorescence in the hyalinization zone of lichen sclerosus and control skin was confirmed by histomorphometry. Lichen sclerosus dermis shows a significant increase of COLI, COLIII and COLV expression compared to the healthy controls. Significant inverse associations were found between elastic fibers and COLV and between COLV and extracellular matrix 1 expression. A direct association was found between elastic fiber content and extracellular matrix 1 expression. Tridimensional reconstruction of the heterotypic fibers of the lichen sclerosus zone of collagen remodeling confirmed the presence of densely clustered COLV., Conclusions: Increased deposition of abnormal COLV and its correlation with extracellular matrix 1 and elastic fibers suggest that COLV may be a trigger in the pathogenesis of lichen sclerosus.

Objective: The goal of this study was to test the hypothesis that responses to the McGill Pain Questionnaire are predictive of adjunctive neuropathic pain medication use by women with lichen sclerosus (LS)., Materials and Methods: This is a retrospective chart review of 430 women with vulvar LS treated at a tertiary referral vulvar care clinic. Demographics, responses to the McGill Pain Questionnaire, and use of neuropathic pain medications were collected. Bivariate and multivariable logistic regression analyses were performed to identify factors significantly associated with use of neuropathic pain medications., Results: Of the 430 subjects, 119 (27.7%) used neuropathic pain medications for vulvar pain. Factors significantly associated with use of these medications include lower body mass index (odds ratio [OR] = 0.96, p = .02), non-White race (OR = 2.97, p = .05), and total McGill Pain Questionnaire score (OR = 1.05, p < .001)., Conclusions: Vulvar pain is a common presenting symptom in women with LS. Responses to the McGill Pain Questionnaire may be helpful in the long-term management of women with LS as a screen to identify those patients who might benefit from adjunctive neuropathic pain medication use.

Background: The histopathologic diagnosis of lichen sclerosus (LS) is usually facilitated by a subepidermal zone of sclerosis. In the absence of sclerosis, LS mostly presents itself as a psoriasiform lichenoid dermatitis that may be difficult to distinguish from other diseases., Objective: We sought to assess histopathologic findings that allow recognition of LS in the absence of sclerosis., Methods: We studied 28 criteria in 100 biopsy specimens of LS from genital or perianal skin, including 55 cases with marked sclerosis, 16 cases with mild sclerosis confined to foci of the papillary dermis and 29 cases without sclerosis. Fifteen cases each of the early plaque stage of mycosis fungoides, lichen planus and lichen simplex chronicus were studied for comparison., Results: Some histopathologic hallmarks of LS were seen chiefly in sclerotic lesions and, therefore, did not contribute to the diagnosis of difficult cases, such as dissolution of elastic fibers. Others were seen rarely in non-sclerotic lesions but might be helpful in individual cases, including follicular hyperkeratosis and thickening of the basement membrane. Findings that were more common and may be utilized as clues to the histopathologic diagnosis of non-sclerotic LS include tiny foci of homogenized tissue in dermal papillae, marked fibrosis with thickening of the papillary dermis, marked thickening of individual collagen fibers, lymphocytes aligned in rows between those fibers, necrotic keratinocytes, often with preserved pyknotic nuclei, in all reaches of the epidermis, including the cornified layer, clustering of necrotic keratinocytes above elongated dermal papillae and vertical columns of parakeratosis with distinct dyskeratotic parakeratotic cells., Conclusion: In the absence of sclerosis, histopathologic diagnosis of LS depends on findings that are less distinctive. Nonetheless, a constellation of those findings allows a specific diagnosis to be made., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Pruritus of the vulva is a common symptom among patients attending to outpatient clinics. In the present study, we aimed to assess pathologies causing vulval pruritus in the reliability of biopsy in a tertiary referral centre. A total of 137 patients undergoing vulval colposcopy because of vulval pruritus were reviewed from the hospital records retrospectively. The mean age of the patients was 47.61 ± 11.88 years and 36.5% of the patients were postmenopausal. In 101 (73.7%) of the patients, macroscopic lesions were present. In 88 (64.2%) of the patients, tolidine-positive stained areas were determined under colposcopy. In total, 68 (49.6%) of the lesions were plain, whereas 51 (37.2%) of them were depigmented. Lichen simplex chronicus, lichen sclerosis and chronic inflammation were the major pathologies associated with vulval pruritus (25.5%, n = 35; 20.4%, n = 28; 14.6%, n = 20). In conclusion, several pathologies out of vulvovaginal candidiasis may lead to vulval pruritus and clinicians should be aware of the importance of biopsy in determining the underlying pathology.

Vulvar lichen sclerosus (VLS) is a chronic inflammatory disease with a huge impact on a person's quality of life. On the basis of the immunologic changes in VLS, treatment with a high potency topical corticosteroid is recommended. The currently available guidelines identified the ultra-potent corticosteroid clobetasol propionate 0.05% (CP) as the first-line recommended treatment but growing evidence supports the use of the potent corticosteroid mometasone furoate 0.1% (MMF). We reviewed the available studies assessing MMF in the treatment of VLS. Both non comparative and comparative studies were included in this review. Findings from clinical trials indicate that MMF is an effective and safe option in the treatment of VLS both in the active phase and in long-term maintenance treatment. Consistent with the findings from the comparative studies, MMF shows similar efficacy and safety to CP., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Guidelines identify a 3-month topical application of an ultra-potent corticosteroid ointment as the mainstay of medical treatment for vulvar lichen sclerosus (VLS). However, there are no trials providing evidence that any specific corticosteroid is superior to another., Objective: To assess the effectiveness and safety of a 12-week application of mometasone furoate (MMF) 0.1% ointment, with a tapering regimen, in achieving control of VLS signs and symptoms and to detect potential risk factors for VLS non-response., Methods: 147 patients affected with VLS were enrolled in a 12-week active treatment phase (ATP) with topical 0.1% MMF. The primary efficacy endpoint was the rate of patients achieving clinical response, as defined by protocol parameters. The secondary efficacy endpoint was to assess the changes of mean VLS-related symptoms after the 12-week ATP compared with baseline., Results: By the end of the ATP, 113 patients (80.7%) experienced a treatment response, whereas 27 women (19.3%) were judged as non-responders. Mean symptom scores decreased significantly in the study patients, regardless of their clinical response at the end of the ATP. Among all the epidemiological and clinical data considered, only the absence of previous medical therapies was found to be related to a significantly higher risk of non-response to treatment., Conclusions: Application of 0.1% MMF ointment for 12 weeks on a tapering regimen was found to be an effective and safe therapy option in the ATP of VLS and could represent an alternative first-line treatment to an ultra-potent molecule., (© 2013 European Academy of Dermatology and Venereology.)