Extragenital lichen sclerosus: Management

INTRODUCTION — Lichen sclerosus (also known as lichen sclerosus et atrophicus) is a chronic, inflammatory skin disorder characterized by atrophic plaques on the skin or mucous membranes.

Extragenital lichen sclerosus refers to lichen sclerosus in sites other than the anogenital area. Extragenital involvement typically presents as porcelain-white, hypopigmented or hyperpigmented, atrophic plaques (picture 1A-E) and may accompany genital lichen sclerosus, occur alone, or overlie lesions of morphea. (See "Vulvar lichen sclerosus: Clinical manifestations and diagnosis" and "Pathogenesis, clinical manifestations, and diagnosis of morphea (localized scleroderma) in adults".)

The management of extragenital lichen sclerosus will be reviewed here (algorithm 1). The clinical manifestations and diagnosis of extragenital lichen sclerosus and the diagnosis and management of genital lichen sclerosus are discussed separately.

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

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

●(See "Balanitis in adults".)

OVERVIEW — There are few data on the efficacy of treatments specifically for extragenital lichen sclerosus. Vulvar lichen sclerosus has been studied more extensively than extragenital disease.

Topical medications, phototherapy, and systemic agents have been used for treatment. Recommendations for the use of specific agents are primarily based upon case reports, small uncontrolled studies, and data from studies in genital disease.

IMPACT OF CLINICAL FEATURES ON TREATMENT SELECTION — Disease activity, disease severity and distribution, and the presence or absence of concomitant morphea influence treatment selection (algorithm 1).

Assessment of disease activity — The activity of skin lesions is a critical factor in determining the approach to therapy:

●Active disease – Active lesions of extragenital lichen sclerosus exhibit erythema, either of the entire lesion or at the periphery of the sclerotic center. The erythema may be subtle in patients with highly pigmented skin. In our experience, active lesions are most responsive to treatment. (See 'Active skin disease' below.)

●Inactive disease – Inactive lesions of extragenital lichen sclerosus show atrophy, telangiectasia, and pigmentary alteration. Lesion erythema is absent in inactive disease. Inactive lesions are unlikely to improve with treatment. (See 'Inactive skin disease' below.)

Disease severity and distribution — Extragenital lichen sclerosus is a benign condition; if there is limited cutaneous involvement, topical corticosteroid therapy is the preferred treatment. Reasons for escalating treatment include persistent disease activity or symptoms despite topical corticosteroid therapy and extensive or progressively worsening disease. (See 'Limited, active skin disease' below and 'Extensive or spreading, active skin disease' below.)

Phototherapy is the mainstay of treatment for extensive disease and limited disease that responds poorly to topical therapy. Systemic therapy is rarely utilized due to the paucity of efficacy data and the potential for serious adverse effects. Systemic therapy is primarily reserved for severe disease that fails to respond to phototherapy (algorithm 1). (See 'Refractory, extensive, active disease' below.)

Oral disease does not often require treatment. However, improvement with treatment has been reported. (See 'Oral disease' below and "Extragenital lichen sclerosus: Clinical features and diagnosis", section on 'Oral lesions'.)

Concomitant morphea — Patients with both morphea and extragenital lichen sclerosus are managed similarly to patients with morphea. (See "Extragenital lichen sclerosus: Clinical features and diagnosis", section on 'Concomitant morphea' and "Morphea (localized scleroderma) in adults: Management".)

ASSESSMENT OF RESPONSE — The following clinical findings define a satisfactory treatment response:

●Resolution of clinical signs of inflammation

●Cessation of the formation of new lesions

●Cessation of the extension of existing lesions

Most patients with a history of well-established lesions will have permanent pigmentary alteration and atrophy.

PATIENT COUNSELING — Extragenital lichen sclerosus is benign, and some patients defer treatment. Common reasons for desiring therapy include symptomatic, cosmetically distressing, extensive, or progressively worsening disease.

Providing patients with realistic expectations for treatment outcomes is important. We typically communicate that although symptoms and the appearance and texture of lesions can improve with treatment, lesions usually do not disappear. (See 'Assessment of response' above.)

ACTIVE SKIN DISEASE — Patients with active skin disease may benefit from anti-inflammatory treatments. (See 'Assessment of disease activity' above.)

The preferred approach differs for limited disease, extensive or spreading disease, and refractory disease. (See 'Limited, active skin disease' below and 'Extensive or spreading, active skin disease' below and 'Refractory, extensive, active disease' below.)

Limited, active skin disease — Potent topical corticosteroids are the preferred initial therapy for patients with limited, active disease (eg, inflammatory but relatively stable skin disease involving less than 10 percent of the body surface area) (algorithm 1). This is due to the observed efficacy of topical corticosteroid therapy for genital lichen sclerosus, reports of clinical improvement in patients with extragenital lichen sclerosus, and the ease of administration and relative safety of topical corticosteroid therapy. (See 'Assessment of disease activity' above.)

Patients who respond poorly to topical corticosteroids are typically treated with phototherapy (algorithm 1). (See 'Phototherapy' below.)

Topical corticosteroids

●Administration – We typically prescribe once-daily application of a superpotent topical corticosteroid, such as clobetasol propionate (table 1) [1]. If there is no improvement after two months (four to six weeks for intertriginous sites) or if adverse effects are noted, we discontinue treatment and consider alternative therapies. (See 'Assessment of response' above.)

Once resolution of disease activity is achieved, we reduce the frequency of application to two days per week for maintenance therapy. If the response is maintained over the subsequent three months, tapering of the frequency of application can continue as tolerated.

●Efficacy – Although the efficacy of topical corticosteroids in extragenital lichen sclerosus has not been formally studied, improvement in genital disease during topical corticosteroid therapy has been reported in randomized trials and uncontrolled and retrospective studies [2-6]. Multiple reports of clinical experience documenting successful treatment of extragenital lichen sclerosus with superpotent topical corticosteroids also support use for this disease [1,7-13]. Still, clinical experience suggests that topical corticosteroids are less consistently effective for extragenital lesions than for genital lesions [1]. (See "Vulvar lichen sclerosus: Management", section on 'Superpotent topical corticosteroids'.)

●Adverse effects – Potential adverse effects of topical corticosteroid therapy include local cutaneous atrophy and systemic absorption resulting in suppression of the hypothalamic-pituitary axis. Intertriginous skin and facial skin areas have the greatest risk for corticosteroid-induced atrophy. Hypothalamic-pituitary axis suppression is most likely to occur with the use of high-potency agents or during the treatment of large areas. (See "Topical corticosteroids: Use and adverse effects", section on 'Adverse effects'.)

Extensive or spreading, active skin disease — In the setting of widespread, active disease (eg, inflammatory skin disease involving more than 10 percent of the body surface area), applying topical corticosteroids to all lesions is often impractical. Phototherapy is typically used for the initial treatment of active disease in these patients (algorithm 1). We also tend to use phototherapy for more limited disease when patients are actively developing multiple new lesions in an attempt to suppress disease progression. Topical corticosteroids can be used as an adjunctive treatment for the more bothersome lesions during phototherapy. (See 'Assessment of disease activity' above and 'Topical corticosteroids' above.)

Patients who experience insufficient responses to phototherapy or who are unable to receive phototherapy are candidates for systemic therapy. (See 'Refractory, extensive, active disease' below.)

Phototherapy — Phototherapy offers the ability to treat large areas of skin, thereby facilitating the treatment of patients with widespread lesions. The mechanism through which phototherapy improves extragenital lichen sclerosus is unknown but may involve factors such as the stimulation of matrix metalloproteinases and the depletion of proinflammatory cytokines [14]. (See "UVA1 phototherapy" and "UVB phototherapy (broadband and narrowband)" and "Psoralen plus ultraviolet A (PUVA) photochemotherapy".)

●Administration – Several forms of phototherapy have been used for extragenital lichen sclerosus. We favor ultraviolet A1 (UVA1) phototherapy. If UVA1 phototherapy is unavailable, we suggest using narrowband ultraviolet B (NBUVB) phototherapy. Psoralen plus ultraviolet A (PUVA) photochemotherapy is a less favorable option due to the additional precautions and side effects of this therapy. (See "Psoralen plus ultraviolet A (PUVA) photochemotherapy", section on 'Safety measures' and "Psoralen plus ultraviolet A (PUVA) photochemotherapy", section on 'Drug interactions' and "Psoralen plus ultraviolet A (PUVA) photochemotherapy", section on 'Adverse effects'.)

UVA1 phototherapy is usually given three to five times per week, and NBUVB phototherapy is usually given three times per week. Our typical dose range for UVA1 is 60 to 100 J/cm², and we administer NBUVB according to the standard regimen. (See "UVA1 phototherapy", section on 'Dosimetry' and "UVB phototherapy (broadband and narrowband)", section on 'Dosimetry and treatment protocols'.)

Whether exposure of uninvolved skin during phototherapy prevents the development of new lesions has not been proven. However, we believe this might be a benefit of phototherapy, and we expose both involved and uninvolved skin for patients with progressive development of new lesions.

Early signs of improvement from phototherapy (transitioning of erythema to postinflammatory hyperpigmentation, reduction in the development of new lesions, and slowing of lesion enlargement) are usually evident within approximately 15 treatments. If signs of improvement remain absent after 15 to 20 appropriately administered treatments, phototherapy can be stopped, and consideration can be given to systemic treatment. (See 'Refractory, extensive, active disease' below.)

Our usual treatment course for patients with disease that improves with phototherapy is 40 to 50 treatments. We typically stop treatment at this point. The resolution of erythema and the cessation of lesion expansion and new lesion formation characterize treatment success. We continue to follow patients closely after the end of treatment. Responders often exhibit continued improvement in skin texture over the subsequent six months after treatment. (See 'Assessment of response' above.)

●Efficacy – The largest study involved the treatment of 10 patients with 40 sessions of UVA1 light at a dose of 20 J/cm² four times per week [15]. All patients exhibited lesion softening and improvement in pigmentation. In addition, a few case reports have documented marked improvements in disease severity following treatment with NBUVB light [7,14]. PUVA photochemotherapy involves the administration of an oral or topical photosensitizer (psoralen) before light treatment. Case reports document responses to oral PUVA used alone or combined with topical tacrolimus [16,17].

●Adverse effects – Adverse effects of phototherapy include burning or blistering of the skin and potential increased risks for premature skin aging and cutaneous malignancy. The risk for malignancy appears to be highest with long-term PUVA treatment. (See "UVA1 phototherapy", section on 'Adverse effects' and "UVB phototherapy (broadband and narrowband)", section on 'Short- and long-term adverse effects' and "Psoralen plus ultraviolet A (PUVA) photochemotherapy", section on 'Adverse effects'.)

Refractory, extensive, active disease — Systemic immunosuppressive therapy is rarely used to manage extragenital lichen sclerosus. It is a treatment option for active, extensive disease in patients who have failed to respond to topical corticosteroids and phototherapy or who cannot receive phototherapy (algorithm 1). (See 'Assessment of disease activity' above.)

Oral methotrexate is the mainstay of systemic immunotherapy. Patients with severe, rapidly progressing disease may benefit from the addition of systemic glucocorticoid therapy. (See 'Severe, rapidly progressing disease' below and 'Stable or slowly progressing disease' below.)

We do not use systemic glucocorticoids as monotherapy. Long-term systemic glucocorticoid therapy is associated with risk for multiple serious adverse effects, and activity of lichen sclerosus may recur after glucocorticoid withdrawal. (See 'Methotrexate and systemic glucocorticoids' below and "Major adverse effects of systemic glucocorticoids".)

Severe, rapidly progressing disease — We treat refractory, extensive extragenital lichen sclerosus that is progressing rapidly or associated with severe symptoms with both methotrexate and a systemic glucocorticoid (algorithm 1).

Methotrexate and systemic glucocorticoids

●Administration – Methotrexate and systemic glucocorticoids (eg, prednisone) are started simultaneously. Systemic glucocorticoids are continued during the first few months of treatment to induce improvement while awaiting the slower onset of action of methotrexate.

•Initial regimen – We typically begin prednisone at a dose of 1 mg/kg per day or 40 to 60 mg per day. Regimens for initiating methotrexate vary. We usually begin with a dose of 10 to 15 mg per week given orally; some clinicians begin with a lower dose followed by dose increases every one to two weeks in the absence of evidence of significant toxicity. Folic acid supplementation (at a dose of 1 mg per day) is typically given during methotrexate therapy to reduce the risk of some side effects of methotrexate. Close laboratory monitoring is also indicated. (See "Use of methotrexate in the treatment of rheumatoid arthritis", section on 'Folic acid supplementation' and "Use of methotrexate in the treatment of rheumatoid arthritis", section on 'Precautions and prevention of adverse effects'.)

•Subsequent management – Patients are clinically assessed for a satisfactory response to methotrexate and prednisone (resolution of erythema and cessation of lesion expansion and new lesion formation) after receipt of 10 to 15 mg of methotrexate per week for one month. If this endpoint has not been reached, we increase the dose of methotrexate to 17.5 to 25 mg per week, continue 1 mg/kg of prednisone per day, and reassess after an additional month. Because absorption of oral methotrexate may be reduced at higher doses [18], we often give methotrexate subcutaneously, rather than orally, when doses exceed 15 mg per week or when patients fail to respond adequately to oral therapy. (See 'Assessment of response' above and "Use of methotrexate in the treatment of rheumatoid arthritis", section on 'Pharmacology' and "Use of methotrexate in the treatment of rheumatoid arthritis", section on 'Parenteral therapy'.)

In our experience, most patients respond to 15 to 25 mg of methotrexate per week and achieve satisfactory improvement (resolution of erythema and cessation of lesion expansion and new lesion formation) within this period, and tapering of prednisone can begin. Patients will not have complete resolution of lesions or substantial softening in this interval. Most patients who had well-established lesions will have permanent pigmentary alteration and atrophy that is unresponsive to treatment.

-Patients with a satisfactory response – We typically taper and discontinue prednisone slowly over three to four months while continuing the same dose of methotrexate. It is unusual for a patient to require a longer course of systemic glucocorticoid therapy.

For methotrexate, the duration of maintenance therapy and schedule of tapering has not been formally examined. Our practice is to continue methotrexate at a maintenance dose of 15 to 25 mg per week for a duration of six to nine months of sustained inactivity of the skin lesions. At that point, we decrease the dose of methotrexate by 2.5 mg every two to four weeks until cessation of methotrexate. We perform regular follow-up visits to assess for disease reactivation.

In our experience, patients rarely have disease reactivation on this regimen and often can successfully stop methotrexate. We counsel these patients to monitor for signs of new disease activity and continue regular clinical follow-up. Minor flares are treated with potent topical corticosteroids, while major flares generally respond to resuming methotrexate. Patients who cannot stop methotrexate without significant disease reactivation continue methotrexate at the lowest effective dose.

Importantly, genital or perianal lichen sclerosus requires maintenance therapy with potent topical corticosteroids and close clinical follow-up regardless of the status of extragenital lesions. (See "Vulvar lichen sclerosus: Management", section on 'Superpotent topical corticosteroids'.)

-Patients with an unsatisfactory response – Our patients who have not achieved a satisfactory response to methotrexate and prednisone within two months continue treatment for an additional one to two months.

If the response remains unsatisfactory, this treatment is unlikely to be effective. Methotrexate can be stopped, and prednisone can be tapered and discontinued at a rate that minimizes risks for complications of hypothalamic-pituitary axis suppression. (See "Glucocorticoid withdrawal".)

●Efficacy – Efficacy data are limited. The efficacy of glucocorticoids plus methotrexate is supported by a retrospective study of seven patients with progressively worsening extragenital lichen sclerosus that failed to respond to a potent topical corticosteroid (all patients) and phototherapy (six patients) [19]. Patients were treated with 15 mg per week of oral methotrexate and 1000 mg of intravenous methylprednisolone sodium succinate on three consecutive days per month. Treatment was continued for six months in six patients and 10 months in one patient who had a delayed response to treatment. A significant decrease in a nonvalidated clinical disease severity score was detected at the end of treatment. In most patients, signs of improvement were first noted after three months of therapy.

●Adverse effects – A variety of potential adverse effects are associated with treatment with methotrexate and glucocorticoids, and close monitoring for toxicity is needed.

Gastrointestinal distress is a common, dose-related side effect of oral methotrexate therapy that may occur less frequently when methotrexate is given as parenteral therapy. We typically attempt subcutaneous treatment in patients who develop gastrointestinal side effects during oral therapy. Splitting the total dose of oral methotrexate into a morning and an evening dose or instructing the patient to take the second half of the dose on the following day may also be helpful. (See "Major side effects of low-dose methotrexate" and "Use of methotrexate in the treatment of rheumatoid arthritis", section on 'Parenteral therapy'.)

Use of methotrexate is contraindicated in pregnancy, and relative contraindications for methotrexate therapy include alcohol abuse and pre-existing liver disease. Dose adjustments of methotrexate are necessary for patients with renal insufficiency. Methotrexate therapy also warrants close monitoring for hematologic toxicity, hepatotoxicity, and other toxicities. (See "Major side effects of low-dose methotrexate".)

The adverse effects of systemic glucocorticoids are broad and are reviewed separately. (See "Major adverse effects of systemic glucocorticoids".)

Stable or slowly progressing disease — We treat patients with refractory, extensive extragenital lichen sclerosus associated with slow disease progression (eg, only a few new lesions or limited lesion expansion expected to occur over two months) with methotrexate without a systemic glucocorticoid (algorithm 1). This approach is also reasonable for patients who are poor candidates for systemic glucocorticoid therapy.

Methotrexate — The regimen for methotrexate given without a systemic glucocorticoid is similar to the regimen used for combination therapy. Patients require close monitoring for adverse effects of methotrexate. (See 'Methotrexate and systemic glucocorticoids' above.)

Improvement of extragenital lichen sclerosus with methotrexate alone has been reported in case reports and case series [20,21]. In a retrospective case series that included 28 female patients with genital lichen sclerosus and/or extragenital lichen sclerosus who had failed to respond to topical therapy, 15 (54 percent) improved during treatment with methotrexate (at a dose of 2.5 to 17.5 mg of methotrexate per week, median dose 10 mg per week) and topical agents [21]. Six additional patients showed initial improvement but discontinued methotrexate due to adverse effects or other indications. The median time to improvement was 3 months (range 1 to 17 months).

Other therapies — Other topical, procedural, and systemic treatments have been used to treat extragenital lichen sclerosus. Efficacy data for these interventions are limited.

●Topical calcineurin inhibitors – In general, we do not use topical tacrolimus or pimecrolimus to treat extragenital lichen sclerosus on the skin. Although topical tacrolimus is an accepted second-line treatment for genital lichen sclerosus, it appears less likely to be effective in extragenital lichen sclerosus. (See "Vulvar lichen sclerosus: Management", section on 'Topical calcineurin inhibitors'.)

In a prospective, uncontrolled study in which 16 patients with lichen sclerosus applied tacrolimus 0.1% ointment twice daily to affected areas, a partial or complete response was observed in 9 of 10 patients with anogenital lesions but only in one of six patients with extragenital lesions [22]. The solitary patient with improved extragenital lichen sclerosus achieved only a partial response.

Topical pimecrolimus, which has also been used successfully for vulvar disease [2], was ineffective for extragenital lichen sclerosus in a case report [23].

●Other topical or procedural therapies – Treatments reported to be effective in small numbers of patients include topical calcipotriol [24], pulsed dye laser [25,26], photodynamic therapy [26], and carbon dioxide laser vaporization [27].

●Systemic therapies – The efficacy of other systemic treatments used in genital lichen sclerosus (eg, oral retinoids, cyclosporine) for extragenital disease is unknown. In the author's experience, mycophenolate mofetil has seemed beneficial for patients who cannot tolerate or do not respond to methotrexate.

Improvement in extragenital lichen sclerosus complicated by bullae and ulceration during hydroxychloroquine treatment and improvement in pediatric extragenital lichen sclerosus during oral baricitinib treatment are described in case reports [28,29].

INACTIVE SKIN DISEASE — If lesions are inactive (eg, stable, atrophic plaques without associated erythema), supportive therapy with emollients and wound care for fissures and erosions is indicated (algorithm 1). Bland emollients (eg, petrolatum) and nonstick dressings are helpful. Clinical experience suggests that phototherapy and topical or systemic anti-inflammatory therapies are unlikely to benefit inactive disease. (See 'Assessment of disease activity' above.)

OTHER CLINICAL PRESENTATIONS

Oral disease — The treatment of oral lesions of lichen sclerosus is not often required and is usually only initiated in the setting of cosmetic concerns or symptoms. Treatments that have been associated with improvement in this disorder include superpotent or medium-potency topical corticosteroids [30,31], intralesional corticosteroid injections (at a dose of 10 mg/mL triamcinolone acetonide) [32], topical tacrolimus [33], topical pimecrolimus [34], topical corticosteroids followed by topical testosterone [35], surgical excision [36], oral colchicine [36], and oral griseofulvin [37].

We believe topical or intralesional corticosteroids and topical calcineurin inhibitors are appropriate first-line treatments. We typically involve an oral maxillofacial surgeon or dentist in caring for these patients.

Morphea with lichen sclerosus features — Patients with morphea who present with coexisting lesions consistent with extragenital lichen sclerosus should be managed similarly to other patients with morphea (algorithm 1). (See "Extragenital lichen sclerosus: Clinical features and diagnosis", section on 'Differential diagnosis' and "Morphea (localized scleroderma) in adults: Management" and "Juvenile localized scleroderma", section on 'Treatment'.)

PROGNOSIS AND FOLLOW-UP — The natural history of extragenital lichen sclerosus has been poorly characterized. In our experience, the disease process often continues over years, with unpredictable periods of exacerbation and stability.

Periodic follow-up is indicated given that some patients who present with isolated plaques progress to extensive disease. Although there is a strong link between genital lichen sclerosus and the development of genital squamous cell carcinoma, reports of the development of squamous cell carcinoma in sites of extragenital lichen sclerosus are rare [38,39]. (See "Vulvar lichen sclerosus: Clinical manifestations and diagnosis", section on 'Association with malignancy'.)

The possibility of increased risk for breast cancer in female patients with lichen sclerosus has been raised based on the findings of a small, retrospective study [40]. However, more data are necessary to confirm this finding and determine whether changes to breast cancer screening protocols would benefit patients with lichen sclerosus.

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)")

SUMMARY AND RECOMMENDATIONS

●Overview – Extragenital lichen sclerosus is a chronic, inflammatory skin disorder characterized by atrophic plaques on the skin (picture 1A-E). Common reasons for therapy include symptomatic, cosmetically distressing, extensive, or progressively worsening disease. (See 'Introduction' above and 'Patient counseling' above.)

The major interventions for extragenital lichen sclerosus are topical corticosteroids, phototherapy, methotrexate, systemic glucocorticoids, and supportive interventions. The clinical presentation (disease activity, severity, distribution, and associated findings) influences treatment selection (algorithm 1). (See 'Introduction' above and 'Patient counseling' above and 'Impact of clinical features on treatment selection' above.)

●Active versus inactive disease – Disease activity is a critical factor for determining the approach to treatment. Signs of active disease include lesion erythema, new lesions, and expanding lesions. These findings are absent in inactive disease. (See 'Assessment of disease activity' above.)

●Management of inactive disease – Inactive disease is unlikely to respond to pharmacologic therapy or phototherapy interventions. For patients with inactive disease, we suggest supportive interventions (emollients, wound care for fissures and erosions) rather than anti-inflammatory drugs or phototherapy (Grade 2C). (See 'Inactive skin disease' above.)

●Management of active disease:

•Assessing the response of active disease to treatment – The following clinical findings define a satisfactory treatment response (see 'Assessment of response' above):

-Resolution of clinical signs of inflammation

-Cessation of the formation of new lesions

-Cessation of the extension of existing lesions

•Treatment of limited, active disease – For the initial treatment of patients with limited extragenital lichen sclerosus (eg, involving less than 10 percent of the body surface area), we suggest a superpotent topical corticosteroid rather than phototherapy or systemic therapy (algorithm 1) (Grade 2C). Patients with limited disease that fails to respond to topical corticosteroids are candidates for phototherapy. (See 'Limited, active skin disease' above.)

•Treatment of extensive or spreading active disease – For the initial treatment of patients with extensive or spreading extragenital lichen sclerosus, we suggest phototherapy rather than systemic therapy (algorithm 1) (Grade 2C). If ultraviolet A1 (UVA1) phototherapy is unavailable, patients may be treated with narrowband ultraviolet B (NBUVB) phototherapy. (See 'Extensive or spreading, active skin disease' above.)

•Treatment of extensive, active disease refractory to phototherapy – For patients with extensive extragenital lichen sclerosus that does not respond sufficiently to phototherapy, we use systemic therapy (algorithm 1). (See 'Refractory, extensive, active disease' above.)

-Severe, rapidly progressing, refractory disease – For patients with severe, rapidly progressing, extensive disease, we suggest combination therapy with methotrexate and systemic glucocorticoids rather than methotrexate alone (Grade 2C). (See 'Severe, rapidly progressing disease' above.)

-Stable or slowly progressing disease – For patients with stable or slowly progressing, extensive disease (eg, limited lesion expansion or spread within two months), we suggest treatment with methotrexate rather than combination methotrexate and glucocorticoid therapy (Grade 2C). The use of methotrexate alone avoids the risks of systemic glucocorticoid therapy. (See 'Stable or slowly progressing disease' above.)

●Recognition of associated genital disease or morphea – Extragenital lichen sclerosus can occur in association with genital lichen sclerosus or morphea. Clinical assessment for these conditions is warranted. (See "Extragenital lichen sclerosus: Clinical features and diagnosis", section on 'Concomitant genital involvement' and "Extragenital lichen sclerosus: Clinical features and diagnosis", section on 'Concomitant morphea'.)