Vulvar lichen sclerosus: Management

INTRODUCTION — Lichen sclerosus (LS) is a chronic dermatologic condition characterized by marked inflammation, epithelial thinning, and distinctive changes in the dermis. Vulvar LS can cause hypopigmentation, atrophy, and fissuring on anogenital skin and can be associated with intense pruritus or pain (picture 1A-D). Untreated vulvar LS may result in adhesions, scarring, and a loss of vulvar architecture.

The management of vulvar LS will be reviewed here (algorithm 1). The clinical manifestations and diagnosis of vulvar LS are reviewed separately. Extragenital LS and LS involving the penis are also reviewed separately.

●(See "Vulvar lichen sclerosus: Clinical manifestations and diagnosis".)

●(See "Extragenital lichen sclerosus: Clinical features and diagnosis".)

●(See "Extragenital lichen sclerosus: Management".)

●(See "Balanitis in adults".)

WHOM TO TREAT — Vulvar LS can result in physical dysfunction, disfigurement, and impaired quality of life. Therefore, we treat all patients with vulvar LS, including those who are asymptomatic, with the aim of preventing the progression of the disease. (See "Vulvar lichen sclerosus: Clinical manifestations and diagnosis", section on 'Clinical manifestations and natural history'.)

TREATMENT GOALS AND TIMING — Early treatment of vulvar LS is preferred whenever feasible [1]. The primary goals of therapy are:

●Resolution of symptoms (pruritus and pain)

●Resolution of signs of active disease, such as fissuring, ecchymoses, and hyperkeratosis/scale

Reduced risk for vulvar squamous cell carcinoma (SCC) and progressive scarring may be additional benefits of treatment [2,3]. In a prospective cohort study of adults with vulvar LS (n = 507), long-term adherence to topical corticosteroid treatment was associated with lower rates of adhesions, scarring, and vulvar intraepithelial neoplasia or SCC [2]. (See 'Superpotent topical corticosteroids' below.)

The responses of skin atrophy and hypopigmentation to treatment vary [4,5]. Existing atrophic anatomical changes (eg, resorption of the labia minora) and scarring generally persist despite medical treatment. Disabling adhesions or scarring may improve with surgical treatment and physical therapy. (See 'Treatment of adhesions and scarring' below.)

Clinical photography is helpful for monitoring the disease.

INITIAL THERAPY — The initial management of LS involves patient education and pharmacologic therapy (algorithm 1).

Patient and caregiver education — As with other chronic, progressive diseases, patient education is a key component in the management of vulvar LS. In addition to a discussion in the clinic, we provide the patient with written information sheets about vulvar LS.

Our approach involves a discussion of the following:

●Status and potential course of vulvar lichen sclerosus:

•The patient's individual disease status, with tactful coverage of existing vulvar architectural changes

•The chronic nature of vulvar LS, the expectation for frequent recurrences and remissions of signs and symptoms, and the potential for uncontrolled disease to result in disfiguring or disabling scarring (eg, introital stenosis) (see "Vulvar lichen sclerosus: Clinical manifestations and diagnosis", section on 'Clinical manifestations and natural history')

•The expectation that pharmacologic treatment usually improves symptoms and signs of active vulvar LS (eg, resolution of fissures and ecchymoses with variable improvement in skin texture, depigmentation, and atrophy) (see 'Pharmacologic therapy for adults' below)

•The expectation that existing scarring or vulvar architectural changes will persist and that surgery and physical therapy are options for complications related to these changes (eg, surgical adhesion release or introital widening) (see 'Treatment of adhesions and scarring' below)

●Proper application of topical treatments – We provide 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 the involved areas so that they know exactly where to apply the topical treatment. (See 'Superpotent topical corticosteroids' below.)

●Risk for malignancy – We discuss the slightly increased risk of malignancy in adults with vulvar LS (especially when the disease is untreated), the importance of monthly self-examination for signs of malignancy, the procedure for performing a self-examination, and the need for clinical follow-up at least once yearly. (See "Vulvar lichen sclerosus: Clinical manifestations and diagnosis", section on 'Association with malignancy' and 'Follow-up' below.)

●Psychologic support and sexual counseling – Vulvar LS can negatively impact quality of life. Patients experiencing psychosocial adverse effects may benefit from referrals to patient support groups or assistance from mental health professionals. In addition, we discuss sexual function and any concerns for the patient and/or their partner(s). We reassure patients that their disease is not contagious and refer patients to a sexual counselor to address concerns, when needed.

Pharmacologic therapy for adults — There are few randomized trials to support decisions on the medical management of vulvar LS [6]. Topical corticosteroids are the mainstay of therapy (algorithm 1). Intralesional corticosteroid therapy may be beneficial for thick, hypertrophic plaques that topical corticosteroids may not penetrate adequately. (See 'Superpotent topical corticosteroids' below and 'Intralesional corticosteroids' below.)

Superpotent topical corticosteroids — Treatment with a superpotent topical corticosteroid (group 1 (table 1)), such as clobetasol propionate, is the standard of care for vulvar LS (algorithm 1):

●Administration – Treatment regimens used for superpotent topical corticosteroid therapy vary, and the ideal treatment regimen is unknown.

•Formulations and frequency – We typically begin treatment with clobetasol propionate 0.05% ointment, halobetasol propionate 0.05% ointment, or another superpotent topical corticosteroid. We prefer ointment formulations because ointments enhance medication absorption, and in our experience, some patients find cream formulations (which generally contain more excipients than ointments) more irritating. (See "Topical corticosteroids: Use and adverse effects", section on 'Ointments'.)

The patient applies the corticosteroid for 12 weeks as the initial course of treatment. Both once-nightly treatment regimens and tapering treatment regimens can successfully treat LS [7-10].

Our typical approach is once-nightly application for 12 weeks, with the goal of inducing remission. We reserve tapering regimens for the treatment of milder disease (eg, limited skin involvement and no evidence of scarring). Our tapering regimen resembles the regimen described in the 2018 British Association of Dermatologists guidelines: application at night for four weeks, then every other night for four weeks, then twice weekly for four weeks [11].

•Application instructions – The ointment is applied and spread over the affected area. We advise patients to 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) (figure 1). A 30 g tube of ointment is typically enough to last for the initial treatment period.

Before the patient leaves the office, they should be shown (via a large mirror or using clinical photographs) exactly where on the vulva to apply the ointment.

•Response assessment – We aim to re-evaluate the patient after an initial 12 weeks of therapy. A good response is indicated by relief of pruritus and pain and resolution of hyperkeratosis, fissuring, and ecchymoses [11]. In our experience, patients notice improvement in symptoms of itching and burning within the first one to two weeks.

-Inadequate response – If the response is inadequate (ie, partial response or absent response) after 12 weeks of daily therapy, the clinician should evaluate the patient for factors that may contribute to an inadequate response. (See 'Failure of initial therapy' below.)

Patients without identifiable reasons for an inadequate response can continue topical corticosteroid treatment for an additional 12 weeks. We tend to switch to a different superpotent topical corticosteroid when signs of improvement are completely absent, though it has not been proven that switching to a different superpotent topical corticosteroid increases the likelihood of response to treatment.

If the response remains inadequate after 24 weeks of topical corticosteroid therapy, we proceed to other therapies. (See 'Failure of initial therapy' below.)

•Maintenance regimen – Because symptoms often recur in patients who terminate therapy, we routinely prescribe a maintenance regimen after achievement of a satisfactory response [1,4,12-16]. Furthermore, adherence to long-term maintenance therapy to maintain normality of skin color and texture has been associated with a reduced incidence of differentiated vulvar intraepithelial neoplasia and vulvar cancer [2]. (See "Vulvar lichen sclerosus: Clinical manifestations and diagnosis", section on 'Association with malignancy'.)

-General approach – In the maintenance phase, the patient tapers treatment with the superpotent topical corticosteroid ointment to two to three nights per week as tolerated. We re-evaluate 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 clobetasol propionate 0.05% or mometasone furoate 0.1% ointment, a potent corticosteroid, have both been found to be safe and effective for long-term maintenance of LS [17]. Most of our patients continue long-term, twice-weekly application. However, some patients who experience a prolonged period of complete remission from signs or symptoms of LS (ie, remission lasting at least 6 to 12 months) are able to successfully taper to once-weekly or less frequent application.

-Maintenance regimen not feasible – If the patient is unable or unwilling to perform maintenance therapy, we advise re-examination every three to six months. Asymptomatic recurrence resulting in scarring and loss of architecture can occur over a relatively short period of time. Furthermore, poor adherence to maintenance therapy may increase the risk of development of vulvar neoplasia [2].

Some patients will achieve long-term remission without maintenance therapy, but it is impossible to predict which patients will fall into this category. In our experience, this outcome is less common.

●Efficacy – Multiple studies and national guidelines support use of clobetasol propionate for vulvar LS [1,6,7,11-14,18]:

•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 patients 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 [12]. 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 with other interventions for LS also support its efficacy [7-9]. (See 'Topical calcineurin inhibitors' below and 'Less potent topical corticosteroids' below.)

●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 patients with vulvar LS has not generally demonstrated these changes since the modified mucous membranes of the labia and clitoris are relatively resistant to the side effects of topical corticosteroids [15,18,19].

In contrast, 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 for this adverse effect [19]. Patients should be advised to use, on average, no more than one 30 g tube of superpotent topical steroid in the first three months and then for 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 (algorithm 1). In these cases, injection of triamcinolone acetonide or triamcinolone hexacetonide directly into the area of involvement once per month for three months may be tried [20]. 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. (See "Intralesional corticosteroid injection".)

For small lesions (no more than 2 x 2 cm), we add 2 mL saline to 1 mL of triamcinolone acetonide (at a dose of 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.

Pharmacologic therapy for children — Our initial management of children with vulvar LS is similar to the management of the disease in adults (ie, use of a superpotent topical corticosteroid once nightly for three months). Most children respond well to topical corticosteroid therapy. (See 'Superpotent topical corticosteroids' above.)

One of the largest, prospective, pediatric studies of outcomes from topical corticosteroid therapy for vulvar LS supports the use of superpotent topical corticosteroids in children [21]. Among 62 prepubertal patients 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 [22]. Our regimen for maintenance therapy in children is similar to our regimen in adults. (See 'Superpotent topical corticosteroids' above.)

A retrospective study divided a cohort of 46 prepubertal females with vulvar LS into two groups: those that reported long-term adherence to treatment (using topical steroids all or most of the time [33 patients]) versus those who were nonadherent to long-term treatment (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 nonadherent group, 69 percent progressed, and 23 percent developed scarring.

Symptom management — Symptoms of pruritus or pain typically improve with local corticosteroid therapy. Other measures that may be useful include:

●Removal of potential exacerbating factors – We encourage patients to avoid scratching and to implement components of good vulvar hygiene (table 2) to minimize exposure to factors that may exacerbate symptoms.

●Topical emollients – Daily use of a greasy, fragrance-free topical emollient may help to maintain symptom relief after topical corticosteroid treatment [23].

●Vaginal lubricants – Patients with dyspareunia benefit from use of a vaginal lubricant. Neutral pH, oil-based lubricants are generally well tolerated. Oil-based lubricants should not be used with rubber (latex) condoms. (See "External (formerly male) condoms", section on 'Material'.)

●Treatment of concomitant genitourinary syndrome of menopause (vulvovaginal atrophy) – Symptoms and signs of genitourinary syndrome of menopause can overlap with findings in vulvar LS. In our experience, treatment of genitourinary syndrome of menopause can be helpful for reducing symptoms and distinguishing symptoms and signs of active vulvar LS from those of genitourinary syndrome of menopause. (See "Genitourinary syndrome of menopause (vulvovaginal atrophy): Clinical manifestations and diagnosis" and "Genitourinary syndrome of menopause (vulvovaginal atrophy): Treatment".)

FAILURE OF INITIAL THERAPY — 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 before resorting to a trial of an alternative drug (algorithm 1).

Patient assessment — Our evaluation of contributors to treatment failure includes:

●Confirmation of proper use of medication – It is often helpful to allow the patient to show you their technique (ie, how much and where the ointment is applied). 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? Knowing where to apply the ointment can be challenging unless patients are shown repeatedly with a mirror. (See 'Superpotent topical corticosteroids' above.)

Use of an excessive amount of medication may contribute to skin irritation [24]. Our practice is to encourage patients to bring their topical corticosteroid tube to follow-up visits so that we can better assess the amount of medication used.

●Assessment of need for intralesional corticosteroid therapy – Topical corticosteroid therapy alone may not be sufficient for the treatment of thick, hyperkeratotic plaques. Patients with such lesions may benefit from targeted intralesional corticosteroid therapy. (See 'Intralesional corticosteroids' above.)

●Confirmation of diagnosis and consideration of malignancy – When patients fail to respond to treatment and have not had a prior biopsy, we consider performing a biopsy to confirm the diagnosis. Ideally, the biopsy specimen should be sent to an experienced dermatopathologist for review. (See "Vulvar lichen sclerosus: Clinical manifestations and diagnosis", section on 'Diagnosis' and "Vulvar lichen sclerosus: Clinical manifestations and diagnosis", section on 'Differential diagnosis'.)

Malignancy should also be considered when an involved area fails to respond to therapy. Erosions, ulcers, and hyperkeratotic plaques that fail to improve with treatment can be signs of squamous cell carcinoma (SCC). We advise patients with these findings to treat LS intensively for one to two weeks. If lesions fail to resolve within this period, prompt clinical reassessment and consideration of a biopsy is warranted. (See "Vulvar lichen sclerosus: Clinical manifestations and diagnosis", section on 'Association with malignancy'.)

●Assessment for other contributors to symptoms – Concomitant conditions may mimic symptoms of active vaginal LS. Examples include:

•Superinfection – Occasional patients have an initial, 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) [25]. Active infections should be treated with appropriate therapy. (See "Candida vulvovaginitis: Clinical manifestations and diagnosis".)

•Vulvovaginal atrophy – Menopausal individuals may have vulvar discomfort and distortion related to vulvovaginal atrophy. (See "Genitourinary syndrome of menopause (vulvovaginal atrophy): Clinical manifestations and diagnosis".)

•Vulvodynia – Superimposed vulvodynia should be considered if pain and dyspareunia persist despite resolution of pruritus and signs of active disease. Vulvodynia may represent 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".)

•Corticosteroid allergy – Rarely, an allergy to a topical corticosteroid 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".)

Topical calcineurin inhibitors — When topical or intralesional corticosteroid therapy is ineffective or poorly tolerated in adults or children, our preferred second-line treatment is topical tacrolimus, a topical calcineurin inhibitor (algorithm 1).

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 some topical corticosteroids, can cause stinging or burning after application, and questions remain about the long-term safety of topical calcineurin inhibitor therapy for vulvar LS.

●Administration – We instruct patients to apply topical tacrolimus 0.1% ointment sparingly to the affected area twice daily for three months and re-evaluate after this period. Initial signs of improvement may be evident within the first month of treatment [9].

We use the 0.1% concentration of topical tacrolimus for both adults and children. However, US Food and Drug Administration (FDA) approval of tacrolimus in children is limited to use of the 0.03% concentration for atopic dermatitis in children. (See "Tacrolimus (topical): Pediatric drug information".)

Topical pimecrolimus 1% cream can also be used, but in our experience, it seems less potent in vulvar LS and seems to induce vulvar irritation more frequently. Compared with ointments, cream formulations often contain more excipients, which may contribute to vulvar irritation.

If stinging (a common side effect of both topical tacrolimus and topical pimecrolimus) occurs, our approach is to mix the topical calcineurin inhibitor with a potent topical corticosteroid in a 50:50 ratio. This seems to improve tolerability. The ratio of the calcineurin inhibitor to the topical corticosteroid can then be progressively increased over the course of a few days, until the topical calcineurin inhibitor can be applied alone.

As with topical corticosteroids, we typically prescribe a maintenance regimen for patients who respond well to a topical calcineurin inhibitor. This generally consists of application of the topical calcineurin inhibitor two to three times weekly. If symptoms recur during or after tapering, the frequency of treatment is increased until there is satisfactory clinical improvement. (See 'Superpotent topical corticosteroids' above.)

●Efficacy – Topical calcineurin inhibitors appear to have efficacy for vulvar LS but are generally considered to 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 with 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 (applied once daily) or clobetasol propionate 0.05% ointment (applied once daily) found that although both treatments improved vulvar LS, clobetasol propionate was more effective [9]. At the end of the study, 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 patients with vulvar LS that compared pimecrolimus 1% cream (applied twice daily) with clobetasol 0.05% cream (applied once daily), both agents significantly reduced patient symptoms and improved histopathologic inflammation [7]. The degree of improvement in histopathologic inflammation with clobetasol was superior.

Additional support for the 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 [26-30] or tacrolimus ointment [27,31-35].

Successful treatment of children with topical calcineurin inhibitor therapy has been reported in case reports and uncontrolled studies [34,36-39], including as maintenance therapy after induction treatment [37,40]. In one uncontrolled study, 5 of 14 prepubertal females with anogenital LS had at least 75 percent improvement of signs and symptoms after eight weeks of twice-daily treatment with tacrolimus 0.03% ointment, and 9 of 14 achieved this endpoint after 16 weeks [37].

●Adverse effects – Tacrolimus can cause a burning sensation on application and is often discontinued by patients for this reason. Although the FDA 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 'Topical calcineurin inhibitors' and "Vulvar lichen sclerosus: Clinical manifestations and diagnosis", section on 'Association with malignancy'.)

REFRACTORY DISEASE — Oral acitretin, oral methotrexate, phototherapy, photodynamic therapy, and laser therapy have been used for vulvar LS. Factors such as limited efficacy data, inconvenience of treatment, or associated adverse effects make these agents less favorable options for initial therapy (algorithm 1). We typically treat with oral acitretin prior to considering other therapies.

Oral acitretin — Retinoids appear to reduce connective tissue degeneration in LS [41]. Treatment with oral acitretin (at a dose of 20 to 30 mg per day for 16 weeks) appeared effective for vulvar LS in adults in one placebo-controlled, randomized trial (n = 78) [42]. Of the 46 patients considered eligible for efficacy analysis (ie, patients who fulfilled the inclusion criteria and completed 12 weeks of treatment or stopped treatment prior to 12 weeks because of lack of efficacy), 14 of 22 patients in the acitretin group (64 percent) improved, compared with 6 of 24 patients in the placebo group (25 percent). Our typical dose range for acitretin is 20 to 50 mg per day.

However, use of acitretin is limited by its adverse effect profile, including cheilitis, xerosis, teratogenicity, elevated liver enzymes, hypertriglyceridemia, abdominal pain, and alopecia. Consultation with a dermatologist is advised before initiating therapy. Oral acitretin is contraindicated in pregnant individuals, and individuals who take acitretin should avoid pregnancy for three years after stopping therapy.

Oral methotrexate — Oral methotrexate appeared beneficial for various forms of LS in an uncontrolled, retrospective study of 28 patients with vulvar LS (21 patients), anal LS (5 patients), and/or extragenital LS (24 patients) that had failed to respond to topical treatment. In the study, 21 patients (75 percent) improved during treatment with methotrexate (median dose = 10 mg per week [range = 2.5 to 17.5 mg per week]) [43]. The median time to improvement was 3 months (range = 1 to 17 months). The response rate for vulvar LS was not reported separately.

Methotrexate is associated with risk for gastrointestinal distress and hematologic, liver, lung, and other toxicities. Close laboratory monitoring is indicated during treatment. (See "Major side effects of low-dose methotrexate".)

Light-based therapies — Limited data suggest benefit of ultraviolet A1 (UVA1) phototherapy, photodynamic therapy, and laser therapy for vulvar LS:

●UVA1 phototherapy – 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 patients with vulvar LS, both therapies were associated with clinical improvement after three months of treatment [44]. 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. (See "UVA1 phototherapy".)

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 was also 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.

●Photodynamic therapy – Successful treatment of vulvar LS with photodynamic therapy has been reported in case reports and small pilot studies [45-50]. In an open, prospective study of 10 patients with vulvar LS treated with two sessions of photodynamic therapy, all patients reported some improvement in symptoms of vulvar LS (itching, burning, pain) [50]. However, improvements in objective measures of disease activity were minor. Additional studies are necessary to evaluate the role of photodynamic therapy in vulvar LS. (See "Photodynamic therapy".)

●Laser therapies – Additional study is necessary to clarify the efficacy of laser therapies for vulvar LS. Although fractional carbon dioxide (CO₂) laser, fractional erbium-doped yttrium aluminum garnet (Er:YAG) laser, and ablative (nonfractionated) CO₂ laser have appeared beneficial for patients with severe, recalcitrate LS in some case series [51-53], high-quality trials confirming efficacy of laser therapy are lacking [54].

One trial in which 40 adults with vulvar LS were randomly assigned to five treatments with either a fractionated CO₂ laser or a sham laser administered over 24 weeks did not find a statistically significant difference in efficacy based upon pretreatment and post-treatment histopathologic assessment [55]. Another trial in which 52 adults with vulvar LS were randomly assigned to either three fractionated CO₂ laser treatments (administered four to six weeks apart and with higher power settings than the sham laser comparison trial) or clobetasol (applied once nightly for one month, three times weekly for two months, then as needed) found greater improvement in the Skindex-29 score (an instrument to measure effects of skin disease on quality of life) at six months in the laser treatment group [56].

OTHER THERAPIES

Less potent topical corticosteroids — There is some evidence that mometasone furoate 0.1% ointment, a high-potency (group 3) topical corticosteroid 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 1) [8,57].

In a 12-week, open-label trial, 54 adults 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 [8]. 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 (ie, achieved a designated level of improvement in subjective and objective assessment scores).

Additional studies will be useful for confirming whether mometasone furoate treatment is equivalent to superpotent topical corticosteroid therapy.

Topical progesterone and topical testosterone — We do not use topical progesterone or topical testosterone for the treatment of vulvar LS. 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 [12,58-60]. In a small, randomized trial, testosterone was associated with more side effects and less histologic improvement than clobetasol [59], and testosterone maintenance therapy worsened symptoms after initial clobetasol therapy [61]. Placebo-controlled trials of testosterone cream have yielded conflicting results regarding efficacy [6,62,63].

Other therapies — Other treatments that have been reported to be beneficial in small numbers of patients include silk underpants [64], topical tretinoin [16], oral cyclosporine [65,66], and adalimumab [67]. Procedural therapies, such as cryotherapy [68] and focused ultrasound, also have been used [69].

Treatment with platelet-rich plasma has been proposed, but further study is necessary to confirm efficacy [70]. A novel surgical approach involving adipose-derived mesenchymal stem cells and platelet-rich plasma appeared beneficial in one case series [71]. In addition, a cohort study of 28 adults found that intralesional platelet-rich plasma alone improved symptoms and reduced the size of lesions in a majority of patients [72].

Although topical and intralesional corticosteroids are first-line therapies for vulvar LS, oral corticosteroids 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 adverse effects of systemic glucocorticoids".)

Human fibroblast lysate cream does not appear to be effective [73].

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.

●Surgery – Select cases of introital stenosis, posterior fissuring, scarring at the fourchette, labial adhesions, and clitoral phimosis can be treated surgically (figure 2) [74-76]. Since vaginal tissue is rarely affected by LS, part of the posterior vaginal wall may be used in the repair to prevent recurrent adhesions and fissuring at the introitus. Release or excision of adhesions without vaginal advancement is seldom successful.

●Duration of benefit – There are few studies examining the effectiveness and long-term outcomes for patients who require surgery for adhesions and scarring. One single-center, retrospective case series of 38 patients 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 [77]. Just over one-half of the patients (55 percent) 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 – Postoperative care regimens vary among clinicians; however, maintaining the restored anatomy is a particular concern. We typically restart daily treatment with a potent topical corticosteroid three to four days after surgery. (See 'Superpotent topical corticosteroids' above.)

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 is not usually 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. We encourage patients to be vigilant about the reformation of adhesions to support early recognition and treatment.

PROGNOSIS — Vulvar LS is considered a chronic disease. The probability of improvement or remission (not cure) may 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) [4]. However, no patient over age 70 years had a complete clinical and histologic remission. Relapses after cessation of topical corticosteroid therapy were common among those patients who achieved remission. Fifty percent relapsed within 16 months, and 84 percent relapsed within four years.

Previously, it was thought that childhood LS typically resolved spontaneously at puberty. However, many children may experience persistent symptoms after puberty. In a study that identified 18 adolescents and young adults with prepubertal onset of vulvar LS, of the 12 who were not lost to follow-up, nine still had signs or symptoms that persisted after puberty [78].

Adult-onset vulvar LS is associated with an increased risk for vulvar intraepithelial neoplasia (particularly differentiated vulvar intraepithelial neoplasia) and vulvar squamous cell carcinoma (SCC). The relationship between vulvar LS and SCC is reviewed separately. (See "Vulvar squamous intraepithelial lesions (vulvar intraepithelial neoplasia)", section on 'Risk factors and prevention' and "Vulvar lichen sclerosus: Clinical manifestations and diagnosis", section on 'Association with malignancy'.)

FOLLOW-UP — Because of the often chronic course of vulvar LS and the potential for malignancy, long-term follow-up is warranted.

Patients with well-controlled disease and a stable treatment plan should be examined at least once yearly after the initial treatment period to identify recurrences of active disease. Because of the association of adult-onset vulvar LS with vulvar intraepithelial neoplasia and vulvar squamous cell carcinoma (SCC), we re-examine patients with adult-onset vulvar LS every 6 to 12 months, even in the setting of long-term remission. We also encourage patients to perform periodic self-examinations and to return for re-evaluation promptly if they notice a recurrence of LS signs or symptoms.

Examples of clinical findings that should raise suspicion for malignancy and consideration of a biopsy include hyperkeratotic plaques, erosions, or ulcers that fail to resolve with treatment. We encourage patients to look at and palpate the vulvar area once monthly to search for lumps or sores that do not heal. Patients should return for evaluation if they detect such findings, particularly if resolution does not occur after two weeks of topical therapy. (See "Vulvar lichen sclerosus: Clinical manifestations and diagnosis", section on 'Association with malignancy' and 'Patient and caregiver education' above.)

INDICATIONS FOR REFERRAL — Referral to a vulvar specialist or other clinician with expertise in the management of vulvar LS is beneficial for patients with disease that responds poorly to topical corticosteroids or patients with a history of vulvar intraepithelial neoplasia or vulvar squamous cell carcinoma (SCC).

Patients with clinical or histologic findings suggestive or confirmatory of vulvar intraepithelial neoplasia and vulvar cancer should be assessed and referred, as appropriate, for diagnosis and treatment. Referral to a gynecologic oncologist may be appropriate in some scenarios. (See "Vulvar squamous intraepithelial lesions (vulvar intraepithelial neoplasia)" and "Vulvar cancer: Epidemiology, diagnosis, histopathology, and treatment".)

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 5^th to 6^th 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 10^th to 12^th 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 – Vulvar lichen sclerosus (LS) is a chronic condition that can lead to hypopigmentation, atrophy, and fissuring on anogenital skin. Associated, intense pruritus and discomfort are common. Progressive disease can result in adhesions, scarring, and loss of vulvar architecture. (See 'Introduction' above.)

●Whom to treat – Treatment of vulvar LS is generally warranted in all patients because of the potential for physical dysfunction, disfigurement, and impaired quality of life. (See 'Whom to treat' above.)

●Treatment goals – Early treatment is preferred whenever feasible. The primary goals of treatment are the resolution of symptoms (pruritus, pain) and signs of disease (hyperkeratosis, fissuring, ecchymoses). The responses of skin atrophy and hypopigmentation to treatment vary. Atrophic anatomical changes and scarring persist. (See 'Treatment goals and timing' above.)

●Patient education – Patient education plays an important role in the management of LS. Important concepts to discuss with the patient include their disease status, potential disease course, proper use of treatments, risk for malignancy (in adults), and psychologic and sexual concerns. (See 'Patient and caregiver education' above.)

●Initial pharmacologic therapy – For the initial treatment of adult-onset and childhood-onset vulvar LS, we suggest a superpotent topical corticosteroid rather than other therapies (algorithm 1) (Grade 2C). Although studies comparing therapies for vulvar LS are limited, it is standard practice to use a superpotent topical corticosteroid as initial therapy. (See 'Initial therapy' above.)

●Maintenance therapy – For patients with disease that responds adequately to topical corticosteroids, we suggest maintenance therapy rather than cessation of therapy (Grade 2C). Our typical approach involves tapering the frequency of application to twice weekly and continuing long-term maintenance treatment. (See 'Superpotent topical corticosteroids' above.)

●Failure of initial therapy – Vulvar LS usually responds well to topical corticosteroids. If the disease fails to respond, potential reasons for treatment failure or persistent symptoms should be assessed (eg, improper medication use; poor penetration of topical corticosteroids into thick lesions; incorrect diagnosis; or presence of malignancy, infection, or other vulvar conditions).

For patients in whom such reasons for treatment failure are not identified, we suggest treatment with a topical calcineurin inhibitor rather than other therapies (algorithm 1) (Grade 2C). Other interventions may be beneficial for patients with refractory disease, such as oral acitretin, oral methotrexate, and light-based therapies. (See 'Refractory disease' above.)

●Management of adhesions and scarring – Complications such as adhesions and scarring will not improve with pharmacologic therapy. Surgical intervention may be helpful for the treatment of disabling or disfiguring lesions. Ideally, surgery is deferred until the disease is well controlled. Recurrence after surgery is common. (See 'Treatment of adhesions and scarring' above.)

●Follow-up – Long-term clinical follow-up after achievement of remission is indicated for patients with vulvar LS. We typically assess patients with well-controlled disease at least once yearly and advise patients to return for prompt reassessment if they develop lesions suspicious for malignancy (eg, hyperkeratotic plaques, erosions, or ulcers that fail to improve with treatment within two weeks). (See 'Prognosis' above and 'Follow-up' above.)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Elizabeth G Stewart, MD, and Susan M Cooper, MB ChB, MRCGP, FRCP, MD, who contributed to earlier versions of this topic review.