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Vulvar lichen sclerosus

Vulvar lichen sclerosus
Authors:
Susan M Cooper, MB ChB, MRCGP, FRCP, MD
Stephanie J Arnold, FACD, MBBS (Hons), BSc (Hons)
Section Editors:
Robert L Barbieri, MD
Jeffrey Callen, MD, FACP, FAAD
Deputy Editor:
Abena O Ofori, MD
Literature review current through: Jul 2022. | This topic last updated: May 23, 2022.

INTRODUCTION — Lichen sclerosus (LS) is a benign, chronic, progressive dermatologic condition characterized by marked inflammation, epithelial thinning, and distinctive dermal changes accompanied by symptoms of pruritus and pain (picture 1A-C) [1]. The previous designation was lichen sclerosus et atrophicus; the "et atrophicus" was dropped because areas of thickening and hyperplasia often occur.

LS usually occurs in the anogenital region (85 to 98 percent of cases) but can develop on any skin surface [2,3]. Extragenital lesions are present in up to 15 percent of patients, although this may be an underestimate.

The clinical manifestations, diagnosis, and management of vulvar LS will be reviewed here. Extragenital LS and LS involving the male genitalia are discussed separately. (See "Extragenital lichen sclerosus" and "Balanitis in adults".)

EPIDEMIOLOGY — Vulvar LS can occur at any age but tends to have two peaks of onset: prepubertal girls and perimenopausal or postmenopausal women [4,5]. It is one of the most common conditions treated in vulvar clinics. The true prevalence is not known; estimates range from 1 in 30 older adult women to 1 in 59 women in a general gynecology practice to 1 in 300 to 1000 patients referred to dermatologists [6-10]. The incidence of vulvar LS in adult women appears to be rising; a study looking at Dutch pathology registry data found the incidence rate of vulvar LS to have increased from 7.4 per 100,000 woman-years in 1991 to 14.6 per 100,000 woman-years in 2011 [5].

ETIOLOGY — The etiology of lichen sclerosus (LS) is unknown. A number of mechanisms have been proposed based upon epidemiologic data:

Genetic factors – Familial aggregations of LS among fathers and daughters, mothers and daughters, sisters, and twins (identical and fraternal) have been reported [4,11,12]. A study that compared two unrelated families with vulvar LS using whole-exome sequencing found germline variants in four genes, including two related to neutrophil and macrophage function [13]. Trauma, injury, and sexual abuse may trigger symptoms in genetically predisposed individuals, which suggests presence of the Koebner phenomenon (ie, development of isomorphic pathologic lesions in the traumatized uninvolved skin of patients who have a cutaneous disease) [14].

Local factors – A study using skin grafts showed that a graft placed on the vulva developed LS, and skin with LS from the vulva became normal when grafted to the thigh [15]. This suggests that local vulvar factors facilitate disease expression.

Immunologic abnormality – Disorders of the immune system are more common among patients with LS, suggesting autoimmune mechanisms and immune dysregulation may be involved in the etiology of the disease [16-24]. For example:

LS has been associated with autoimmune diseases such as alopecia areata, vitiligo, thyroid disorders, pernicious anemia, and diabetes mellitus. In addition, a few cases of concomitant LS and celiac disease have been published [25,26]. In one study of 350 women with histologically confirmed LS (of which 98 percent had vulvar disease), 22 percent had an autoimmune disorder and 42 percent had one or more autoantibodies (anti-thyroid, anti-gastric parietal cell, antinuclear, anti-smooth muscle, or antimitochondrial antibodies) with titers greater than 1:20 [27]. A separate study of 190 women with vulvar LS and 922 female controls also found an increased likelihood for autoimmune disorders among patients with vulvar LS (28 versus 9 percent) [24]. However, an increase in the prevalence of a similar panel of autoantibodies was not detected.

There is an increased level of antibody formation against extracellular matrix protein 1 (a key component of the dermis) in up to 75 percent of women with LS [28]; however the relevance to disease pathogenesis requires further investigation.

Hormonal factors – The highest incidence of LS in women is observed during low-estrogen physiologic states, such as the premenarchal child and the postmenopausal woman [27], suggesting a hormonal influence on the pathogenesis of the disease. Although there may be a negative association between progesterone-only forms of contraception and LS, systematic reviews have not found evidence to support the efficacy of topical application of progesterone, nor of hormone replacement therapy [29,30]. (See 'Other therapies' below.)

Androgen levels do not appear to be related to LS. An early, poorly designed study noted that patients with vulvar LS have decreased serum levels of dihydrotestosterone, free testosterone, and androstenedione compared with age-matched controls without the disease [31]. However, many subsequent studies have been unable to confirm these findings, and testosterone is not an effective treatment for the disease. (See 'Other therapies' below.)

Infection – Infectious agents (eg, Borrelia burgdorferi, variably acid-fast bacteria, human papillomavirus [HPV]) have been postulated to induce LS [32-36], but no clear relationship has been demonstrated [37].

Cell kinetics – An elastase-type enzyme produced by vulvar fibroblasts may lead to the destruction of connective tissue in patients with LS [38]. Despite this destruction, there appears to be active regeneration with significant collagen synthesis [39]. In a study of keratin differentiation markers using specific monoclonal antibodies, keratins 6 and 16 were associated with increased cell turnover in LS, consistent with a hyperproliferative state [40]. This was confirmed in another study using flow cytometry analysis [41]. The clinical significance of these findings has not been established.

Vulvar skin affected by LS has a wide range of proliferative capacity [42]. Proliferation markers as well as the tumor-suppressor p53, are upregulated in genital LS, perhaps reflecting increased levels of oxidative stress [42,43].

CLINICAL MANIFESTATIONS AND NATURAL HISTORY — Pruritus and soreness or irritation are the most common symptoms of vulvar LS.

Other women are asymptomatic; in these patients, LS is detected by careful inspection of the vulva for the characteristic thin, white, wrinkled skin and changes in vulvar architecture (see 'Signs' below). For example, there may be loss of portions or all of the labia minora, and the clitoris may become buried under the fused prepuce. Although uncommon, active disease may be asymptomatic.

Symptoms — The major symptoms of vulvar LS are:

Vulvar pruritus – Vulvar pruritus, which is the hallmark of the disease, is often so intense that it interferes with sleep. Although most women present with pruritus, some women present with pain and a small group are asymptomatic. Pruritus is not specific to LS as pruritus is a feature of most vulvar disorders (table 1).

Anal discomfort – Patients with vulvar LS may also have involvement of perianal skin (picture 1B-C). Pruritus ani, painful defecation, anal fissures, and rectal bleeding are common symptoms. In children, constipation may be a presenting symptom [44].

Dyspareunia – Dyspareunia and other forms of sexual dysfunction are common in women with LS and may significantly impact a patient's quality of life [45]. Sexual dysfunction may occur due to inflammatory disease, or as a late symptom if associated with introital stenosis, fissures, or posterior deflection of fused labial tissues at the time of intromission. Fusion over the clitoris can also cause diminished sexual sensation or even anorgasmia, although this is not common. Marked dyspareunia may occur in perimenopausal or postmenopausal women with estrogen deficiency in addition to vulvar LS.

A questionnaire-based study that examined patients' views of their sexual problems following the diagnosis of vulvar LS found that the majority of 45 sexually active respondents described detrimental effects on sexual function, including dyspareunia, apareunia, and difficulty achieving orgasm [46]. These symptoms appeared to be due to continuing inflammation and anatomic changes and scarring from long-standing, active disease. Other studies have quantified the effect of LS on sexual function using the Female Sexual Function Index and have found a significant impact across a range of domains, including desire, arousal, lubrication, orgasm, satisfaction, and pain [47,48].

Dysuria – Dysuria and difficulty voiding can occur, especially when there is fusion of the labia minora over the urethra with advanced disease.

Signs — Classic vulvar LS is expressed as white, atrophic papules that may coalesce into plaques; follicular plugging may be observed in early lesions. LS can also be hemorrhagic, purpuric, hyperkeratotic, bullous, eroded, or ulcerated [49]. The lesions most frequently affect the labia minora and/or labia majora (picture 1A, 1D), although the whitening may extend over the perineum and around the anus in a keyhole fashion (picture 1B-C). Extension onto the genitocrural folds or buttocks also may occur [50]. Fissuring is frequently seen at the posterior fourchette, perianally, in the interlabial folds, or around the clitoris. The introitus may have a yellow, waxy appearance. Fordyce spots (small raised papules along the inner aspect of the labia minora, which represent normal sebaceous glands) disappear.

Scratching may result in excoriations and secondary mild lichenification (thickening of the epidermis with exaggeration of normal skin lines), often associated with edema of the labia minora and the prepuce (picture 2). Relatively minor rubbing or intercourse may lead to hemorrhage and/or petechiae with purpura and ecchymoses due to the fragility of the involved skin (picture 3A-B).

The vulvar architecture remains intact early in the course of the disease (picture 4). As the disease progresses, the distinction between the labia majora and minora is lost and the clitoris becomes buried under the fused prepuce (picture 5A-C). Shrinkage of the introitus and perineum causes dyspareunia and more fissuring upon intercourse or insertion of a speculum. At the end-stages of LS, the vulva is pallid and featureless due to midline fusion, which leaves only a posterior pinhole orifice.

Although vaginal involvement traditionally has not been considered a feature of LS, a few cases of combined vulvar and vaginal LS have been reported [51,52]. Additional studies are necessary to clarify the prevalence of vaginal LS. Cervical LS does not occur.

Extragenital LS may be present in patients with vulvar LS. Extragenital lesions consist of white papules or atrophic plaques (picture 6A-B) [3]. In patients with dark skin, lesions may demonstrate hyperpigmentation or hypopigmentation rather than a white color [53]. Potential sites for extragenital LS include the thighs, breasts, wrists, shoulders, neck, back, and, rarely, the oral cavity [54]. Unlike vulvar LS, extragenital LS is usually asymptomatic. (See "Extragenital lichen sclerosus".)

DIAGNOSIS — The diagnosis of vulvar LS is based upon the presence of characteristic clinical manifestations, ideally with histologic confirmation [49].

Evidence-based guidelines [55] from the European Academy of Dermatology and Venereology state that not all cases of adult-onset vulvar LS require a confirmatory biopsy. However, a biopsy may be helpful to confirm the diagnosis, or to reevaluate the diagnosis if initial treatment fails or if malignancy is suspected. Our practice is to biopsy most adult-onset vulvar LS at the time of initial diagnosis because of the broad differential diagnosis of vulvar whitening, the possibility of underlying atypia or malignancy, and because typical histologic findings are less evident after treatment with topical corticosteroids.

In children, the diagnosis of vulvar LS is often made based upon the clinical examination only. Biopsy may be reserved for children with atypical clinical features or treatment-refractory disease [56,57].

Biopsy — A 4 mm vulvar punch biopsy typically provides sufficient tissue to confirm the diagnosis and to evaluate for atypical histologic features. (See 'Associated malignancy' below.)

Histopathology — On histologic examination, the epidermis is typically thinned (accounting for the older nomenclature "lichen sclerosus et atrophicus"), although areas of hyperkeratosis may be observed (picture 7) and early lesions may demonstrate mild, irregular epidermal acanthosis [58]. The upper dermis exhibits homogenization of collagen with a band of lymphocytes below this region. The characteristic histologic findings may be absent if the biopsy misses an area of active pathology.

Clinical judgment should guide the diagnosis and treatment of LS when biopsy results are not specific. For example, when clinical signs that strongly suggest vulvar LS (eg, local pruritus plus depigmentation or loss of vulvar architecture) are present in conjunction with inconclusive biopsy results, we proceed with treatment. Clinicopathologic correlation with a dermatopathologist can be helpful.

Laboratory tests — Since disorders of the immune system are more common among patients with LS (see 'Etiology' above), a review of systems should be performed in patients with this disease. When clinical signs or symptoms suggestive of autoimmune disease are evident, we select additional diagnostic studies based upon the suspected autoimmune disease (eg, thyroid disease, diabetes, pernicious anemia).

Clinicians must also remain alert to the possibility of coexisting bacterial or fungal infections. Investigative studies (eg, microscopy or culture) to diagnose infection should be performed if signs suggestive of vulvar or vaginal infection are present. Candida infection is not uncommon in vulvar LS patients who are taking estrogen and progestin preparations (eg, contraception, replacement therapy), or who are diabetic [59]. (See "Vaginal discharge (vaginitis): Initial evaluation".)

DIFFERENTIAL DIAGNOSIS — A variety of other disorders may be confused with vulvar LS. Therefore, we recommend diagnostic biopsy in adult patients:

Lichen planus – LS and lichen planus share several common features and may occur together on the vulva (picture 8) [60]. Both disorders produce intense itching and loss of architecture, but lichen planus usually also involves the vagina (inflammation and synechiae), whereas the vagina usually is not affected by LS. A punch biopsy is required to make the diagnosis and review by a dermatopathologist is helpful, although the histologic findings may be similar to those seen in LS. (See "Vulvar lichen planus".)

Lichen simplex chronicus – Lichen simplex chronicus, or squamous cell hyperplasia, does not denote a specific entity, but describes a nonneoplastic morphologic alteration of vulvar skin related to chronic irritation (picture 9). The histology consists of irregular thickening of the Malpighian layer of rete ridges (acanthosis), hyperkeratosis, and parakeratosis with a mid-dermal inflammatory infiltrate. Lichen simplex chronicus is diagnosed when anatomic and clinical findings have excluded specific causes of hyperplastic epithelial changes, such as lichen sclerosus, psoriasis, lichen planus, eczema, seborrheic dermatosis, human papillomavirus (HPV) infection, and Candida infection. (See "Vulvar dermatitis".)

Endogenous and exogenous dermatitis – Dermatitis of the vulva generally presents as vulvar itch and irritation, and clinical findings can range from diffuse erythema, scale, and fissuring to thick lichenification. The labia majora are commonly affected. Although the etiology classically has been divided into endogenous types of dermatitis (eg, seborrheic dermatitis and atopic dermatitis) and exogenous dermatitis (eg, contact irritant and allergic dermatitis), frequently the cause is multifactorial. Signs of atopic or seborrheic dermatitis are usually observed elsewhere on the skin. Dermatitis may be indistinguishable from early LS, in which case biopsy is indicated. (See "Vulvar dermatitis".)

Vitiligo – Vitiligo produces whitening and can be confused with LS if other manifestations of LS are minimal (picture 10). The coexistence of vitiligo and vulvar LS has been reported [24,61]. (See "Vitiligo: Pathogenesis, clinical features, and diagnosis".)

Mucous membrane pemphigoid – Mucous membrane pemphigoid, an uncommon bullous disease, should be considered, particularly if there is marked labial adhesion (picture 11). Biopsy will distinguish between LS and this disorder. (See "Clinical features and diagnosis of bullous pemphigoid and mucous membrane pemphigoid", section on 'Clinical features of mucous membrane pemphigoid'.)

Anal fissures and hemorrhoids – LS with anal involvement is sometimes confused with anal fissures or hemorrhoids, leading to unnecessary surgery as management of anal LS is similar to that for vulvar LS (picture 12). (See "Anal fissure: Clinical manifestations, diagnosis, prevention".)

Candidiasis Like vulvar LS, vulvovaginal candidiasis is characterized by chronic vulvar itching or burning (picture 13) [59]. A wet mount is performed to look for hyphae. If the wet mount is negative, then culture is indicated. (See "Candida vulvovaginitis: Clinical manifestations and diagnosis".)

Psoriasis – Psoriasis can occur in genital locations and is pruritic, but usually appears red rather than white (picture 14). (See "Psoriasis: Epidemiology, clinical manifestations, and diagnosis".)

Estrogen deficiency – Estrogen deficiency secondary to menopause or premature ovarian failure can lead to a thinned epidermis and labial adhesion, as well as dyspareunia (picture 15). These changes should respond to topical estrogen within two weeks of treatment. Failure of a response should prompt a vulvar biopsy to exclude LS. (See "Genitourinary syndrome of menopause (vulvovaginal atrophy): Clinical manifestations and diagnosis".)

ASSOCIATED MALIGNANCY — Women with vulvar LS are at increased risk of developing squamous cell cancer (SCC) of the vulva (picture 16A-B) [3,5,7,62-64]. Indeed, it is not uncommon for women who present with vulvar SCC to also have LS that has been undiagnosed, untreated, and asymptomatic. It is unclear whether there is increased risk for vulvar SCC in children with this disease [56].

There have been case reports of melanoma, basal cell carcinoma, and Merkel cell carcinoma with LS, but a relationship between LS and these cancers has not been established [50]. Whether there is a relationship between LS and melanoma is also unclear. There are rare reports of vulvar melanoma developing in association with vulvar LS in women [65], girls under age 16 years [66], and penile melanoma in men with genital LS [67].

Differentiated vulvar intraepithelial neoplasia (VIN) is a precursor to SCC and is often associated with LS (picture 17) but not human papillomavirus (HPV) infection. Usual type VIN, which is also a premalignant lesion, is mediated by HPV but is less likely to be associated with LS. (See "Vulvar squamous intraepithelial lesions (vulvar intraepithelial neoplasia)".)

Determining those cases of LS with a high likelihood of evolving into SCC is an active area of investigation [68]. An historical cohort study using a Dutch pathology registry found a higher rate of vulvar cancer development in women with LS who had concurrent VIN or were aged ≥70 years old at the time of diagnosis [5]. A preliminary study that compared expression of the interferon regulatory factor 6 (IRF6) tumor suppressor gene in specimens of vulvar SCC with adjacent vulvar LS, cancer-free vulvar LS, and normal skin from a total of 60 women found that dysregulation of the IRF6 gene via methylation of the IRF6 promoter may play a role in the development of vulvar SCC in vulvar LS [69]. Further study is necessary to determine whether methylation of the IRF6 promoter is a useful marker of cancer risk.

Although the risk of vulvar SCC in women with vulvar LS is increased, this risk is estimated to be less than 5 percent [50]. Much of the available evidence of the relationship between vulvar LS and SCC is based on historical studies and retrospective case series. A retrospective cohort study in northern Italy compared the incidence of vulvar cancer in women with histologically proven LS versus all women in the reference population (approximately 185,000 women) over 16 years using cancer registry data and found an overall incidence of 2.76 cases of vulvar cancer per 1000 patient-years [70]. Furthermore, vulvar LS accounted for 98 percent of the attributable risk on the incidence of vulvar cancer in this cohort.

However, risk has never been defined in terms of treated versus nontreated or unrecognized disease, or to the length of time the disease has been present. Earlier detection, the introduction of potent topical glucocorticoids, the more liberal use of biopsy, and excision of abnormally thickened skin resistant to treatment may lead to a reduction in risk of SCC for women diagnosed with LS [6,71]. A prospective cohort study of 507 women with vulvar LS followed over six years compared women who reported adherence to treatment (use of maintenance corticosteroids as directed all or most of the time) versus those who reported less adherence to treatment (use of maintenance topical corticosteroids as directed some, little, or none of the time). There was a statistically significant inverse association between treatment adherence and the risk of vulvar neoplasia (0 cases among 357 women in the adherent group versus 4 differentiated VIN and 3 invasive SCCs among 150 women in the nonadherent group [4.7 percent]) [71]. Nevertheless, we believe the skin of all patients with vulvar LS should be examined at least yearly for the remainder of the patient's life and nonresolving lesions (eg, persistent localized hyperkeratosis) should be biopsied.

In contrast to vulvar LS, reports of SCC in sites of extragenital LS are rare [72]. However, men with penile LS may have an increased risk of penile SCC. (See "Extragenital lichen sclerosus", section on 'Prognosis and follow-up' and "Balanitis in adults".)

MANAGEMENT — Vulvar LS can result in physical dysfunction, disfigurement, and impaired quality of life. Therefore, we recommend treatment of all women with vulvar LS, including those who are asymptomatic, to try to prevent progression of the disease. The goals of therapy should be resolution of the symptoms (pruritus and pain) and signs of disease, including hyperkeratosis, fissuring, and ecchymoses [50]. Atrophy and depigmentation may sometimes improve with therapy; however, scarring, if present, will remain. Clinical photography may assist in monitoring of the disease and can be helpful when showing patients where to apply topical therapy.

Early treatment of vulvar LS is preferred whenever feasible [55], as this relieves patient discomfort and reverses many of the skin changes, such as pallor, ecchymoses, and hyperkeratosis [73-75]. However, there is little evidence to suggest that early treatment improves or prevents any changes to vulvar anatomy.

First-line therapy — The initial management of LS involves patient education and medical therapy.

Patient education — As with other chronic, progressive diseases, patient education is a key component in management of vulvar LS. Our approach involves the following:

Discussion of the patient's individual situation, with tactful coverage of architectural changes that may have occurred.

Discussion of the chronicity of vulvar LS and the expectation for frequent recurrences and remissions of signs and symptoms.

Reassurance that although LS has the potential to distort or destroy vulvar anatomy, the condition is manageable. Topical corticosteroid treatment is a highly effective therapy that can inhibit progression of the disease.

Discussion of the components of good vulvar hygiene (table 2) and the importance of cessation of scratching to minimize exposure to factors that may exacerbate symptoms.

Discussion of the increased risk of malignancy in adult women with LS, the importance of self-examination for signs of malignancy, and the need for clinical follow-up at least once yearly. Patients should examine the vulvar area with a mirror and fingertips on a monthly basis and should return for evaluation if they detect thickened areas of skin or sores that do not heal, particularly if resolution does not occur after a period of intensive topical therapy to the area. (See 'Associated malignancy' above.)

Discussion of sexual function and any concerns for the patient and/or their partner. Patients should be reassured that their disease is not contagious. A referral to a sexual counsellor to address any problems may be required.

Provision of written information sheets that educate the patient about vulvar LS. We also emphasize that pictures on the internet often represent untreated, end-stage disease that can be prevented with appropriate treatment. (See "Patient education: Vulvar lichen sclerosus (Beyond the Basics)".)

Provision of written instructions for the use of the prescribed therapy. We also use clinical photography (with patient consent) and/or a hand mirror to show the patient what areas are involved so that she knows exactly where to apply the topical treatment.

Provision of information regarding local and national patient support groups.

Medical therapy — There are few randomized trials upon which to base decisions on the medical management of vulvar LS [76]. Topical corticosteroids are the mainstay of therapy. Intralesional corticosteroid therapy is an additional option that is useful for the treatment of thick hypertrophic plaques that topical corticosteroids may not penetrate adequately.

Topical corticosteroids — Treatment with a superpotent topical corticosteroid (group 1 (table 3)), such as clobetasol propionate, has long been considered the standard of care for vulvar LS:

Efficacy – The use of clobetasol propionate for vulvar LS is supported by multiple studies and national guidelines [50,55,75-80]. A three-month, randomized trial that compared the efficacy of clobetasol propionate 0.05%, topical testosterone 2%, topical progesterone 2%, and a placebo cream in 79 women with biopsy-proven, long-standing vulvar LS found that statistically significant improvement in LS (as assessed via investigator global assessment scoring) occurred in patients treated with clobetasol propionate (applied twice daily for one month, then once daily for two months), but not in patients assigned to twice-daily applications of the placebo cream [75]. In addition, patient-reported symptom scores improved in 18 of 20 patients (90 percent) treated with clobetasol compared with only 6 of 19 patients (32 percent) treated with placebo. Other randomized trials comparing clobetasol propionate to other interventions for LS also support its efficacy [80-82].

There is some evidence that mometasone furoate, a less potent topical corticosteroid (group 3) with greater anti-inflammatory activity and a longer duration of action than corticosteroids of similar potency, may be an effective alternative to superpotent topical corticosteroid therapy (table 3) [81,83]. In a 12-week open-label trial, 54 women with clinical or histologically confirmed diagnoses of vulvar LS were randomly assigned to treatment with clobetasol propionate 0.05% ointment or mometasone furoate 0.1% ointment [81]. The medications were applied five days per week for four weeks, on alternate days for four weeks, and then twice weekly for four weeks. After 12 weeks, 89 percent of patients in both groups had responded to therapy. Additional studies will be useful for confirming whether mometasone furoate treatment is equivalent to superpotent topical corticosteroid therapy.

Administration – Treatment regimens used for superpotent topical corticosteroid therapy vary and the ideal treatment regimen is unknown. We typically begin treatment with clobetasol propionate 0.05% ointment or halobetasol propionate 0.05% ointment (another superpotent topical corticosteroid). The patient applies the corticosteroid for 6 to 12 weeks as the initial course of treatment. Both once-nightly treatment regimens and tapering treatment regimens can successfully treat LS [80-82,84]. An example of a tapering treatment regimen is application at night for four weeks, then every other night for four weeks, then twice weekly for four weeks [50]. We prefer to use ointment formulations of topical corticosteroids because in our experience, patients sometimes find cream formulations more irritating.

The ointment is applied and spread in a film over the affected area. We recommend patients use 0.5 fingertip units (FTUs) per application; 1 FTU is the amount of ointment expressed from a tube with a 5 mm nozzle, applied from the distal skin crease of the index finger to the tip (approximately 0.5 g). A 30 g tube of ointment is typically enough to last for the initial treatment period. Before the woman leaves the office, she should be shown (via a large mirror or using clinical photographs) exactly where to apply the ointment. In our experience, women begin to notice improvement in symptoms of itching and burning within the first one to two weeks of treatment.

We reevaluate the patient after the initial 6 to 12 weeks of therapy. A good response is indicated by relief of pruritus and pain and resolution of hyperkeratosis, fissuring, and ecchymoses [50].

Because symptoms often recur in women who terminate therapy, we routinely prescribe a maintenance regimen [55,73,75,77,78,85,86]. Furthermore, adherence to long-term maintenance therapy to maintain normality of skin color and texture is also associated with a reduced incidence of differentiated vulvar intraepithelial neoplasia (VIN) and vulvar cancer [71]. (See 'Associated malignancy' above.)

In the maintenance phase, the patient tapers treatment with the superpotent topical corticosteroid ointment to two to three nights per week as tolerated. We reevaluate the patient after 12 weeks to ensure disease is adequately controlled with the maintenance regimen. If symptoms recur during or after tapering, the frequency of treatment is increased until there is satisfactory clinical improvement. Twice-weekly mometasone furoate 0.1% ointment, a potent corticosteroid, has been found to be safe and effective for long-term maintenance of LS [87].

If the patient is unwilling to perform maintenance therapy, we examine her every three to six months because asymptomatic recurrence resulting in scarring and loss of architecture can occur over a relatively short period of time. Furthermore, evidence suggests that poor adherence to maintenance therapy may increase the risk of development of vulvar neoplasia [71]. Some patients will achieve long-term remission without maintenance therapy, but it is impossible to predict which patients will fall into this category.

Adverse effects – Potent topical corticosteroids can induce cutaneous atrophy, telangiectasia, and striae as early as two to three weeks following daily application. However, long-term follow-up of vulvar LS patients generally has not demonstrated these changes since the modified mucous membranes of the labia and clitoris are relatively resistant to the side effects of topical corticosteroids [79,85,88]. The groin fold creases, hair bearing skin of the labia majora, and perianal skin are more prone to corticosteroid-induced skin atrophy and need to be monitored [88]. Patients should be advised to use, on average, no more than one 30 g tube of superpotent topical steroid every six months once in the maintenance phase. (See "Topical corticosteroids: Use and adverse effects".)

Intralesional corticosteroids — Thickened hypertrophic plaques may respond poorly to topical corticosteroids. In these cases, we suggest injection of triamcinolone hexacetonide or triamcinolone acetonide directly into the area of involvement once per month for three months [89]. Pretreatment with a small amount of a topical anesthetic (eg, eutectic mixture of lidocaine and prilocaine) and use of a small gauge needle help to minimize patient discomfort.

For small lesions (no more than 2 x 2 cm), we add 2 mL saline to 1 mL of triamcinolone (10 mg/mL) to make a solution of 3.3 mg/mL. We then inject 0.5 to 1 mL intralesionally with a 25 to 30 gauge needle to treat a lesion of 1 to 2 cm. For lesions covering a larger area, we perform several injections using the same concentration. We do not inject more than 3 mL per treatment session.

Symptom management — Symptoms of pruritus or pain typically improve with local corticosteroid therapy. Daily use of topical emollients may help to maintain symptom relief after topical corticosteroid treatment [90]. Women with dyspareunia may benefit from use of a vaginal lubricant.

Treatment failure — Local corticosteroid therapy is highly effective for vulvar LS. Therefore, if a patient does not respond well to treatment, it is important to evaluate for contributing factors:

Ensure proper use of medication – Is the patient applying the corticosteroid to the right place, in the right amount (a thin layer to the affected area), and with the appropriate frequency? Women often are unclear as to where to put the ointment unless they are shown repeatedly with a mirror. Use of an excessive amount of medication may contribute to skin irritation [91]. (See 'Topical corticosteroids' above.).

Exclude superinfection – A small number of women initially have a partial response to medical treatment, but have ongoing burning, irritation, and pain. In these cases, we obtain cultures to exclude superinfection (eg, Staphylococcus, Streptococcus, or Candida infection) [59]. Active infections should be treated with appropriate antibiotic or antimycotic drugs.

Determine whether intralesional corticosteroid therapy is needed – Topical corticosteroid therapy alone may not be sufficient for the treatment of thick hyperkeratotic plaques. Patients with such lesions may benefit from intralesional corticosteroid therapy. (See 'Intralesional corticosteroids' above.)

Confirm diagnosis and consider malignancy – When patients fail to respond to treatment, we consider repeating the biopsy to confirm the diagnosis (see 'Differential diagnosis' above). Ideally, the biopsy specimen should be sent to a dermatopathologist for review.

In particular, malignancy should be considered when an area fails to respond to therapy. Erosions, ulcers, and hyperkeratotic plaques that fail to improve with treatment can be signs of squamous cell carcinoma. (See 'Associated malignancy' above.)

Consider other causes of symptoms – Menopausal women may have vulvar discomfort and distortion related to vulvovaginal atrophy. Estrogen is an effective treatment for postmenopausal vulvovaginal atrophy. (See "Genitourinary syndrome of menopause (vulvovaginal atrophy): Treatment".)

A diagnosis of superimposed vulvodynia should be considered if pain and dyspareunia persist despite resolution of pruritus and signs of active disease. It is likely that vulvodynia represents neuropathic pain, which is pain arising from abnormal neural activity secondary to disease, irritation, or injury of the nervous system that persists in the absence of ongoing disease or acute injury. (See "Vulvar pain of unknown cause (vulvodynia): Clinical manifestations and diagnosis".)

In rare cases, an allergy to topical corticosteroid product may present as a tendency for symptoms to worsen with therapy. The cause may be an allergic reaction to components of the drug vehicle, a preservative, or less frequently, the corticosteroid itself. Referral for patch testing is useful for confirming an allergy. (See "Topical corticosteroids: Use and adverse effects", section on 'Adverse effects' and "Patch testing".)

Second-line therapy — Given the high therapeutic efficacy of local corticosteroid therapy, potential causes of corticosteroid failure should be carefully considered in women with persistent symptoms before resorting to a trial of an alternative drug (see 'Treatment failure' above). When topical corticosteroid therapy is ineffective or poorly tolerated, our preferred second-line treatment is a topical calcineurin inhibitor.

Topical calcineurin inhibitors — An advantage of topical calcineurin inhibitor therapy is the absence of risk for the drug-induced cutaneous atrophy associated with topical corticosteroid use. However, these drugs tend to be more expensive than topical corticosteroids and questions remain about the long-term safety of topical calcineurin inhibitor therapy for vulvar LS:

Efficacy – Topical calcineurin inhibitors appear to have efficacy for vulvar LS, but may be less potent therapies than clobetasol propionate. In randomized trials, once-daily tacrolimus was less effective than once-daily clobetasol propionate, and twice-daily applications of pimecrolimus demonstrated similar clinical efficacy but lesser histologic efficacy in comparison to once-daily applications of clobetasol propionate. The representative trials are described below:

A three-month, randomized trial in which 58 female children and adults with vulvar LS were randomly assigned to treatment with tacrolimus 0.1% ointment (once daily) or clobetasol propionate 0.05% ointment (once daily) found that although both treatments improved vulvar LS, clobetasol propionate was more effective [82]. At study end, 19 of 28 tacrolimus-treated patients had residual clinical signs of LS compared with only 9 of 27 patients in the clobetasol propionate group. In addition, significantly more patients had no clinical signs or symptoms of LS in the clobetasol group (15 versus 4 patients).

In a 12-week, randomized trial of 38 women with vulvar LS that compared pimecrolimus 1% cream (twice daily) to clobetasol 0.05% cream (once daily), both agents significantly reduced patient symptoms and improved histopathologic inflammation [80]. The degree of improvement in histopathologic inflammation with clobetasol was superior, supporting the status of superpotent topical corticosteroids as the preferred choice for initial therapy.

Additional support for benefit from topical calcineurin inhibitors comes from uncontrolled studies and case reports. Patients with vulvar LS, including some with topical corticosteroid-refractory disease, have exhibited improvement with pimecrolimus cream [92-96] or tacrolimus ointment [93,97-101].

Administration – When treating with topical pimecrolimus or topical tacrolimus, we instruct patients to apply the medication sparingly to the affected area twice daily for three months and reevaluate after this period. Initial signs of improvement may be evident within the first month of treatment [82].

Adverse effects Tacrolimus can cause a burning sensation on application, and is often discontinued by patients for this reason. Although the US Food and Drug Administration has issued a "black box" warning for topical calcineurin inhibitors due to concern regarding an elevated risk for internal malignancy, a definitive relationship between these agents and internal malignancy has not been established. The impact of topical calcineurin inhibitor therapy on risk for vulvar SCC in patients with vulvar LS is unknown. Long-term safety data on topical calcineurin inhibitor use for vulvar LS are lacking. (See "Treatment of atopic dermatitis (eczema)", section on 'Safety' and 'Associated malignancy' above.)

Other therapies — Other therapies that have been utilized for vulvar LS include medications, phototherapy, and photodynamic therapy. Factors such as limited efficacy data, inconvenience of treatment, and associated adverse effects make these agents less favorable options for initial therapy:

Oral acitretin – Retinoids appear to reduce connective tissue degeneration in LS [102]. Treatment with oral acitretin (20 to 30 mg per day for 16 weeks) was effective in one placebo-controlled randomized trial [103]. Doses of 8 to 30 mg daily for four months have been used.

However, use of acitretin is limited by significant and potentially harmful side effects including cheilitis, xerosis, teratogenicity, elevated liver enzymes, hypertriglyceridemia, abdominal pain, and alopecia. If a trial of retinoids is being considered, consultation with a dermatologist is recommended before initiating therapy.

UVA1 phototherapy UVA1 phototherapy may be an additional treatment option for vulvar LS. In a randomized trial that compared the efficacy of home-administered, medium-dose UVA1 phototherapy (50 J/cm2) given four times a week with once-daily application of clobetasol 0.05% ointment in 30 women with vulvar LS, both therapies were associated with clinical improvement after three months of treatment [104]. The mean reduction in the total clinician's score (an unvalidated clinical assessment tool) was 51.4 percent (95% CI, 39.7-63.0 percent) in the clobetasol group and 35.6 percent (95% CI, 18.2-53.1 percent) in the UVA1 group.

Although the difference in efficacy between the two groups was not statistically significant, clobetasol treatment was superior to UVA1 phototherapy with respect to improvement in itch and quality of life. Clobetasol treatment also was more practical; administration of a 50 J/cm2 dose of UVA1 required 27 minutes.

The long-term safety of UVA1 phototherapy for vulvar LS is unknown. High potency topical corticosteroid therapy remains the gold standard for treatment. (See "UVA1 phototherapy".)

Photodynamic therapy – Successful treatment of vulvar LS with photodynamic therapy (PDT) has been reported in case reports and small pilot studies [105-110]. In an open study of 10 patients treated with two sessions of PDT, all patients reported some improvement in symptoms of vulvar LS (itching, burning, pain) [110]. However, improvements in objective measures of disease activity were minor. Additional studies are necessary to evaluate the role of PDT in this disorder.

Topical progesterone and topical testosterone – Historically, topical progesterone and topical testosterone creams were considered treatments for vulvar LS. However, small randomized trials have generally shown that progesterone and testosterone creams are less effective than clobetasol [75,111,112]. Testosterone was associated with more side effects and less histologic improvement than clobetasol [112] and testosterone maintenance therapy worsened symptoms after initial clobetasol therapy [113]. Placebo-controlled trials of testosterone cream have reported conflicting results regarding efficacy [76,114,115]. We do not prescribe these hormones.

Other treatments that have been reported to be effective in small numbers of patients include silk underpants [116], topical tretinoin [86], and oral cyclosporine [117,118]; oral methotrexate has been used in extragenital disease [119]. Human fibroblast lysate cream has been shown to not be effective and is not recommended [120]. Procedural therapies, such as cryotherapy [121], carbon dioxide laser [122,123], erbium-doped yttrium aluminum garnet (Er:YAG) laser [124], and focused ultrasound, also have been used [125].

A new surgical approach involving adipose-derived mesenchymal stem cells and platelet-rich plasma has shown promise in one case series [126]. In addition, a cohort study of 28 women found that intralesional platelet-rich plasma alone improved symptoms and reduced the size of lesions in a majority of patients [127]. However, more data need to be published before this treatment can be recommended.

Although topical and intralesional corticosteroids are first-line therapies for vulvar LS, oral glucocorticoids are not indicated for routine treatment of vulvar LS given the risk of systemic side effects and the high efficacy of local corticosteroid treatment. (See "Major side effects of systemic glucocorticoids".)

Children — The initial management of vulvar LS children is similar to the management of the disease in adults. A superpotent topical corticosteroid is the preferred first-line therapy. Most children respond well to this therapy.

One of the largest prospective pediatric studies of outcomes from topical corticosteroid therapy for vulvar LS supports the use of superpotent topical corticosteroids in this population [128]. Among 62 prepubertal girls with vulvar LS treated with clobetasol propionate 0.05% ointment daily for three months, 73 percent were completely clear of symptoms and 90 percent experienced improvement in clinical signs of vulvar LS after three months.

Similar to adults, maintenance therapy for children following induction treatment with topical corticosteroids is usually required to prevent progression or scarring [129]. A retrospective study divided a cohort of 46 prepubertal girls with vulvar LS into two groups: those that reported adherence to maintenance treatment (using topical steroids all or most of the time, 33 patients) versus those who were non-adherent (using topical corticosteroids only some or less of the time, 13 patients). In the adherent group, 93 percent had sustained remission with no progression or scarring, whereas in the non-adherent group, 69 percent progressed and 23 percent developed scarring.

Successful treatment of children with topical calcineurin inhibitor therapy has been reported [100,130-133], including as maintenance therapy after induction treatment [134]. However, as with adults, topical calcineurin inhibitors are not first-line therapy [56]. (See 'Topical calcineurin inhibitors' above.)

Treatment of adhesions and scarring — Severe adhesions and scarring are complications of vulvar LS that can lead to functional limitations and disfigurement. Surgical intervention is used to manage these complications. Ideally, surgery is deferred until the disease is well controlled with medication to avoid surgery-induced tissue irritation and symptom exacerbation. Surgery is not indicated for the management of uncomplicated vulvar LS.

Introital stenosis, posterior fissuring, and scarring at the fourchette can be treated by vulvoperineoplasty (figure 1) [135,136]. Since vaginal tissue rarely is affected by LS, part of the posterior vaginal wall is used in the repair to prevent recurrent adhesions and fissuring at the introitus. Release or excision of adhesions without vaginal advancement is seldom successful.

Adhesions burying the clitoris can result in formation of painful pseudocysts. Clitoral adhesions are released with delicate knife strokes and use of a lacrimal duct probe to free the hood from the glans [137].

There are few studies examining the effectiveness and long-term outcomes for women who require surgery for adhesions and scarring. One single-center, retrospective case series of 38 women treated with surgery found that although surgery improved function (such as resolution of dyspareunia or urinary problems) in the short term, the majority of patients eventually relapsed [138]. Just over half (55 percent) of the patients required more than one surgical intervention, usually due to relapse of the functional impairment. However, a patient survey conducted as part of this study found a high rate of patient satisfaction with both the surgery and their functional outcomes.

Postoperative care regimens vary among clinicians, however, maintaining the restored anatomy is a particular concern. We typically restart treatment with a potent topical corticosteroid three to four days after surgery. The patient is also asked to manually massage the area daily with a greasy emollient to separate any adhesions. Massage can be performed with fingers. Alternatively, a vaginal dilator (the largest size tolerated) can be used. Dilators should be gently inserted with a copious amount of lubricant and gradually rotated using gentle pressure for three to four minutes. Topical lidocaine may be beneficial for pain relief if dilation is very painful; however, it usually is not necessary.

Three weeks after surgery, the patient begins to gradually reduce the frequency of topical corticosteroid application and massage (or dilation), with the goal of reaching a maintenance regimen of twice weekly administration after an additional six weeks. Women should be warned to be vigilant about the reformation of adhesions.

PROGNOSIS — The probability of improvement or remission (not cure) appears to be associated with age. In one prospective study of 83 patients treated with clobetasol propionate for vulvar LS, complete clinical and histologic remission occurred in 45 patients (54 percent) [73]. However, no patient over age 70 years had a complete clinical and histologic remission. Relapses were common among those patients who achieved remission; 50 percent relapsed within 16 months and 84 percent relapsed within four years.

In the past, it was thought that childhood LS typically resolved spontaneously at puberty. However, it is now evident that many children may experience persistent symptoms after puberty. In a study that identified 18 adolescents and young adults with prepubertal onset of vulvar lichen sclerosus, of the 12 who were not lost to follow-up, 9 still had signs or symptoms that persisted after puberty [139].

Adult-onset vulvar LS is associated with increased risk for vulvar SCC. The relationship between vulvar LS and SCC is reviewed separately. (See 'Associated malignancy' above.)

FOLLOW-UP — Because of the often chronic course of vulvar LS, long-term follow-up is recommended. Patients with well-controlled disease and a stable treatment plan should be examined at least once yearly after the initial treatment period. Closer follow-up with a specialist is indicated for patients with atypical features, previous vulvar cancer or vulvar intraepithelial neoplasia, or persistent symptoms [50].

INDICATIONS FOR REFERRAL — Referral to a specialist is indicated in the following settings:

Women whose symptoms are not controlled with potent topical corticosteroids applied three or more times weekly or after using >30 g over six months.

Women with localized skin thickening/hyperkeratosis unresponsive to topical steroids.

Women previously treated for usual or differentiated type vulvar intraepithelial neoplasia (VIN) and/or SCC. (See "Vulvar squamous intraepithelial lesions (vulvar intraepithelial neoplasia)".)

Women with vulvar biopsy showing carcinoma or precancerous changes. Biopsy should be performed in women with clinical evidence of localized skin thickening/hyperkeratosis.

Women with biopsies where the pathologist expresses concern, but cannot make a definite diagnosis of differentiated VIN [6].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Lichen sclerosus".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Lichen sclerosus (The Basics)")

Beyond the Basics topics (see "Patient education: Vulvar lichen sclerosus (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Overview – Lichen sclerosus refers to a benign, chronic, progressive dermatologic condition characterized by marked inflammation, epithelial thinning, and distinctive dermal changes accompanied by pruritus and pain. Lichen sclerosus usually occurs in the anogenital region, but can develop on any skin surface and in women, men, and children (picture 1A-B). (See 'Introduction' above and "Extragenital lichen sclerosus".)

Clinical manifestations:

Mucocutaneous findings – The classic appearance is thin, white, wrinkled skin localized to the labia minora and/or labia majora (picture 1A, 1D), although the whitening may extend over the perineum and around the anus in a keyhole fashion (picture 1B). Areas of epithelial hyperplasia from chronic rubbing are often seen. Fissuring is frequently present perianally, in the intralabial folds, or around the clitoris. At the end-stages, the vulva is pallid and featureless due to midline fusion. (See 'Signs' above.)

Symptoms – Vulvar pruritus is a common symptom of vulvar lichen sclerosus and can be so intense that it interferes with sleep. Other symptoms include pruritus ani, painful defecation, rectal bleeding, dyspareunia, and dysuria. However, some patients are asymptomatic. (See 'Symptoms' above.)

Diagnosis – The diagnosis of vulvar lichen sclerosus is based upon the presence of characteristic clinical manifestations plus histologic confirmation. (See 'Diagnosis' above.)

Association with malignancy – There is a small increased risk of squamous cell cancer of the vulva in patients with lichen sclerosus. Adequate treatment of the disease seems to be associated with a reduced risk of development of neoplasia. The skin of patients with vulvar lichen sclerosus should be examined at least yearly, with biopsy of suspicious lesions, and women themselves should look at their skin and touch with fingertips monthly to search for thickened lumps or sores that do not heal. (See 'Associated malignancy' above.)

Management:

Patient education – Educating women with vulvar disorders about vulvar hygiene is important with any chronic vulvar condition, including lichen sclerosus (table 2). (See 'Patient education' above.)

Role of medical therapy – Medical therapy for vulvar lichen sclerosus will lead to symptomatic relief in most women; however, the effectiveness of medical therapy for preventing long-term sequelae, such as scarring and squamous cell cancer, is unclear (see 'Management' above):

-We recommend initial treatment of vulvar lichen sclerosus with a superpotent topical corticosteroid ointment (Grade 1B). We typically administer clobetasol propionate 0.05% ointment or halobetasol propionate 0.05% ointment daily at night for 6 to 12 weeks, followed by maintenance therapy two to three times per week if symptoms improve. Thickened hypertrophic plaques may respond best to intralesional corticosteroid therapy. (See 'Medical therapy' above.)

-In patients with persistent symptoms, we suggest a careful evaluation for causes of treatment failure. (See 'Treatment failure' above.)

Role of surgery – Surgical intervention is indicated for treating the postinflammatory sequelae of lichen sclerosus, and for diagnosis and treatment of an associated malignancy. (See 'Treatment of adhesions and scarring' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Elizabeth G Stewart, MD, who contributed to an earlier version of this topic review.

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