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Morphea (localized scleroderma) in adults: Management

Morphea (localized scleroderma) in adults: Management
Author:
Heidi Jacobe, MD
Section Editor:
Jeffrey Callen, MD, FACP, FAAD
Deputy Editor:
Abena O Ofori, MD
Literature review current through: Sep 2022. | This topic last updated: Jul 28, 2020.

INTRODUCTION — Morphea, also known as localized scleroderma, is an idiopathic inflammatory disorder that causes sclerotic changes in the skin. Affected patients present with single or multiple inflammatory and sclerotic plaques, findings considered manifestations of active disease. These plaques eventually resolve, leaving permanent dermal or soft tissue atrophy and pigmentary changes (skin damage). Disease activity typically persists for three to six years, although some patients develop more persistent periods of activity or recurring episodes of activity. (See "Pathogenesis, clinical manifestations, and diagnosis of morphea (localized scleroderma) in adults".)

There are multiple treatment options for active morphea; however, evidence in support of many of these therapies is limited. The majority of patients are managed with observation, topical medications, phototherapy, or systemic immunosuppressive therapy. The level of disease activity, depth of involvement, body surface area involved, and the presence of functional impairment or cosmetic disfigurement determine the most appropriate approach to treatment (algorithm 1).

Systemic therapy is often warranted for patients with extensive, active morphea that is rapidly progressing or causing significant cosmetic disfigurement, joint contractures, or other functional impairment. Occupational and physical therapy are important interventions for patients who have or are at risk for disability.

The management of morphea in adults will be reviewed here. Pediatric morphea and the pathogenesis, clinical manifestations, and diagnosis of morphea in adults are discussed elsewhere. (See "Juvenile localized scleroderma" and "Pathogenesis, clinical manifestations, and diagnosis of morphea (localized scleroderma) in adults".)

GOALS OF TREATMENT — The definition of successful treatment of morphea is not the return to completely normal skin, although this may occur in very early, inflammatory lesions. Therapeutic success for active lesions is defined first by improvement or resolution of erythema and later by softening of sclerotic lesions or hair regrowth on affected skin. Successful treatment of spreading disease inhibits lesion expansion and new lesion formation. Additional treatment goals for active and inactive disease include improvement of associated functional impairment and disfigurement. (See 'Active disease' below and 'Inactive disease' below and 'Functional impairment' below and 'Disfigurement' below.)

SELECTION OF THERAPEUTIC APPROACH — The evolving and often self-limited course of morphea and the varied clinical presentations warrant individualized approaches to treatment. The level of disease activity (active versus inactive), depth of tissue involvement (dermal versus deep morphea), body surface area involved (few lesions versus widely distributed lesions), and the presence or potential for functional impairment or cosmetic disfigurement determine the most appropriate approach to treatment.

Disease activity — Treatment to alter the course of morphea is considered most effective for patients with active disease. Active lesions can occur both in recent-onset morphea and long-standing morphea [1].

In contrast, inactive disease is unlikely to respond to the immunomodulatory and ultraviolet light therapies utilized for this purpose. Interventions for inactive morphea are primarily focused on improvement of functional impairment and disfigurement. (See 'Inactive disease' below.)

Disease activity can be identified through the physical examination. Findings consistent with active disease include inflammatory, erythematous patches or edematous plaques that progressively develop sclerotic features. Other indicators of active disease include peripheral induration accompanied by erythema, lesion expansion, and the formation of new lesions. (See "Pathogenesis, clinical manifestations, and diagnosis of morphea (localized scleroderma) in adults", section on 'Lesion evolution'.)

Serial clinical photographs are helpful for identifying progressing disease [2]. The Localized Scleroderma Assessment Tool (LoSCAT), a scoring method that assesses skin thickness, inflammation, lesion extension, and damage, has also been used for this purpose but has limitations and is primarily employed in clinical studies [3]. (See 'Assessment of response' below and "Juvenile localized scleroderma", section on 'Evaluation of progression or response to therapy'.)

Inactive disease characteristically presents as sclerotic plaques with a hyperpigmented border that eventually become hypopigmented or hyperpigmented, atrophic plaques. Telangiectasia may also be present. Atrophy of morphea plaques may demonstrate finely wrinkled skin or shallow "cliff drop-like" depressions. Atrophy of deep morphea may present as deep indentations with loss of soft tissue or muscle and, sometimes, bony changes. (See "Pathogenesis, clinical manifestations, and diagnosis of morphea (localized scleroderma) in adults", section on 'Lesion evolution'.)

Depth of involvement — Patients with active deep morphea, morphea that involves subcutaneous tissue, fascia, or muscle, require a more aggressive approach to treatment than patients with involvement limited to the dermis, as deep morphea often leads to functional impairment. Systemic immunosuppressive therapy is often needed for these patients. (See 'Deep morphea' below and 'Functional impairment' below.)

Clinical findings supportive of deep tissue involvement include poorly circumscribed, indurated, and tethered plaques and linear depressions (groove sign). Functional impairment and pain may also suggest deep involvement. Imaging studies can be used to confirm deep involvement. (See "Pathogenesis, clinical manifestations, and diagnosis of morphea (localized scleroderma) in adults", section on 'Deep morphea' and "Pathogenesis, clinical manifestations, and diagnosis of morphea (localized scleroderma) in adults", section on 'Imaging studies'.)

Extent of skin involvement — Topical or intralesional therapy may be sufficient for the management of disease involving a relatively small proportion of the body surface area. In contrast, these interventions are often impractical and insufficiently effective for more extensive morphea, such as generalized morphea. Phototherapy or systemic therapy is typically necessary for extensive disease. (See 'Extensive dermal plaques' below and 'Deep morphea' below.)

Given the often asymptomatic and self-limited nature of morphea, forgoing therapy is a reasonable alternative for patients with morphea that involves a relatively small area of skin, particularly when deep involvement is absent, risk for functional impairment appears minimal, and lesions are not located in cosmetically sensitive areas. Close clinical follow-up for progressing disease is still necessary for these patients. (See 'Decision to treat' below.)

Risk for functional impairment and disfigurement — Morphea causing functional impairment (eg, contractures, reduced range of motion) or significant disfigurement or that exhibits features that suggest impending risk for these events (eg, facial involvement, tethered or deeply sclerotic lesions that overly joints) may require treatment with systemic immunosuppressive drugs. Involvement of a multidisciplinary team is also often indicated to maximize function and minimize risk for further disability. Moreover, patients with lesions in locations that are at risk for disabling contractures should be referred to physical and occupational therapy before movement deficits appear. (See 'Functional impairment' below.)

ACTIVE DISEASE — Persistent disease activity may result in lesion expansion, involvement of new sites, increasing functional impairment, or worsening disfigurement. Thus, treatment of active morphea is often initiated in an attempt to minimize the development of these features; however, not all patients require treatment. (See 'Goals of treatment' above and 'Decision to treat' below.)

Decision to treat — Because disease activity in morphea often spontaneously ceases within several years, the decision to treat is based upon consideration of a variety of factors, such as the potential for functional impairment and disfigurement, the need for relief from associated symptoms (eg, pain, pruritus), and patient preference. In general, we initiate treatment in all patients who have functional impairment or appear to be at risk for functional impairment or significant disfigurement, as these features may worsen with continued disease progression and can persist following the resolution of disease activity. This typically includes patients with generalized morphea, deep morphea, or linear morphea. (See 'Risk for functional impairment and disfigurement' above.)

Deferring treatment is considered of lesser consequence for patients with milder presentations of morphea, such as limited skin involvement that spares deep tissues. This often includes patients with circumscribed morphea, the most common subtype of morphea. Although our experience is that many of these patients elect to try at least topical or intralesional therapy, deferring treatment is a reasonable alternative. Patients who do not initiate treatment still require close clinical follow-up to facilitate early detection of disease progression that may benefit from treatment. (See "Pathogenesis, clinical manifestations, and diagnosis of morphea (localized scleroderma) in adults", section on 'Subtypes'.)

Treatment groups — In our experience, an algorithmic approach to active morphea that is based upon disease extent, disease depth, and risk for complications is more helpful than outlining approaches based upon the clinical subtype. (See 'Selection of therapeutic approach' above and "Pathogenesis, clinical manifestations, and diagnosis of morphea (localized scleroderma) in adults", section on 'Subtypes'.)

We utilize the following categories to outline suggested approaches to treatment:

Single or few dermal plaques – Single or few morphea plaques involving a limited area of skin that spare deeper tissues, such as subcutaneous tissue, fascia, and muscle. This category typically includes patients with circumscribed morphea. (See "Pathogenesis, clinical manifestations, and diagnosis of morphea (localized scleroderma) in adults", section on 'Circumscribed (plaque) morphea'.)

Extensive dermal morphea – Morphea involving more than a limited area of skin (multiple lesions involving more than one body site or large plaques) that spares deeper tissues, such as subcutaneous tissue, fascia, and muscle. This category typically includes patients with generalized morphea but may include other subtypes. (See "Pathogenesis, clinical manifestations, and diagnosis of morphea (localized scleroderma) in adults", section on 'Generalized morphea'.)

Limited deep morphea – Morphea involving a limited area that includes involvement of deep tissues, including subcutaneous tissue, fascia, or muscle. (See "Pathogenesis, clinical manifestations, and diagnosis of morphea (localized scleroderma) in adults", section on 'Deep morphea'.)

Extensive deep morphea – Morphea involving large areas or multiple body sites that includes involvement of deep tissues, including subcutaneous tissue, fascia, or muscle. (See "Pathogenesis, clinical manifestations, and diagnosis of morphea (localized scleroderma) in adults", section on 'Deep morphea'.)

Morphea causing or at risk for causing functional impairment or significant disfigurement – Morphea associated with contractures or reduced range of motion, morphea located in sites in which progressing disease is likely to lead to these events, and morphea involving cosmetically sensitive areas. (See 'Risk for functional impairment and disfigurement' above.)

Assessment of response — Determining the response of active morphea to treatment can be challenging. The physical examination is the primary method of assessing the response.

There is a lack of consensus on the definition of an optimal response to treatment. We consider the resolution of clinical signs of disease activity (resolution of erythema and edema plus cessation of both new lesion formation and lesion expansion) achievement of an optimal response. Improvement of sclerosis is not mandatory. In our experience, improvement of sclerosis and progression to the atrophic stage of morphea occurs gradually over time following successful resolution of signs of disease activity [1].

Adjunctive response assessment measures include scoring tools (eg, the Localized Scleroderma Cutaneous Assessment Tool [LoSCAT]) and radiologic imaging. The LoSCAT, a scoring system based upon the physical findings, is primarily used in clinical studies and is composed of an activity index, a damage index, and the physician's global assessment of disease activity and damage [3]. Calculation of the indexes involves division of the body surface area into 18 anatomic sites and application of a score between 0 and 3 for various features related to disease activity and skin damage. In a prospective study of 120 adults and children with morphea, the LoSCAT appeared effective for identifying clinically significant improvements in disease activity [4]. (See "Juvenile localized scleroderma", section on 'Evaluation of progression or response to therapy'.)

The role of radiologic imaging in assessment of treatment response is unclear. Data from an uncontrolled study of 22 adults with morphea involving deep tissues suggest that magnetic resonance imaging (MRI) may be useful [5]. The study found reductions in mean MRI scores for subcutaneous septal thickening, fascial thickening, and fascial enhancement after treatment among patients who met clinical criteria for a response to methotrexate and prednisolone therapy. Other radiologic techniques have also been utilized. (See "Juvenile localized scleroderma", section on 'Evaluation of progression or response to therapy'.)

Cessation of treatment — An individualized approach is typically taken to determine the appropriate therapeutic course following the resolution of signs of disease activity. Treatments may be stopped abruptly or continued or tapered for a period of time.

Factors such as the treatment type, the duration of treatment already received, and disease severity influence our approach to treatment cessation. Suggested approaches for specific treatments are reviewed below. Close clinical follow-up is advised for all patients because of the potential for recurrence of disease activity.

Single or few dermal plaques — Patients with limited dermal morphea who desire treatment usually can be managed with topical therapy, intralesional therapy, or phototherapy. We favor phototherapy for patients with unstable, spreading lesions. Systemic immunosuppressive drugs are usually reserved for select patients with refractory disease and functionally limiting or disfiguring presentations. (See 'Spreading or topical therapy-resistant lesions' below and 'Refractory disease' below and 'Functional impairment' below and 'Disfigurement' below.)

Stable lesions — Topical corticosteroids, topical tacrolimus, topical vitamin D analogs, and intralesional injection of corticosteroids are often used as first-line therapies for patients with limited, stable dermal morphea who proceed with treatment due to the relative safety of these interventions [6]. Data to support these therapies are limited, and the relative efficacy of these therapies is unclear. We primarily utilize topical corticosteroids.

One of the challenges of topical therapy for morphea is achieving sufficient penetration of medication to the site of inflammation. In our experience, lesions that exhibit associated epidermal changes, such as lichen sclerosus-like features overlying indurated plaques, seem to respond best to topical therapy (picture 1). Intralesional corticosteroid therapy allows for delivery of corticosteroids directly into the dermis; however, use is limited to relatively small lesions because of the need to administer injections throughout lesions.

Patients presenting with lesions associated with worsening functional impairment or worsening disfigurement may benefit from a more aggressive approach to treatment. (See 'Functional impairment' below and 'Disfigurement' below.)

Topical and intralesional corticosteroids — Topical and intralesional corticosteroids have anti-inflammatory and antifibrotic effects that may be beneficial in morphea (see "Topical corticosteroids: Use and adverse effects", section on 'Mechanism of action'):

Administration – High-potency topical corticosteroids (groups 1 or 2 (table 1)) are typically applied to affected skin once or twice daily. Use of an occlusive dressing over the site of application may help to augment benefit.

Signs of response are expected within 12 weeks. In our experience, if there is no response within this period, benefit is unlikely and treatment should be discontinued. (See 'Assessment of response' above.)

Upon resolution of clinical signs of disease activity, we attempt to taper the frequency of corticosteroid application as well as the potency of the topical corticosteroid, as tolerated. If signs of disease activity recur during tapering, we return to daily application of the high-potency topical corticosteroid until disease activity ceases.

Intralesional corticosteroid injections involve periodic injection of a corticosteroid (eg, triamcinolone acetonide 5 to 10 mg/mL) directly into the dermis in affected areas. Injections of approximately 0.1 mL are placed approximately 1 cm apart within lesions. Our experience suggests that injections into the periphery of active lesions may be particularly helpful for reducing clinical signs of inflammation.

The status of disease should be closely monitored. In patients who demonstrate improvement following an injection session, we repeat injections every four to six weeks until resolution of signs of disease activity is achieved. Patients who exhibit continued disease progression (lesion extension or new lesion formation) despite this treatment are transitioned to other treatments. (See 'Spreading or topical therapy-resistant lesions' below.)

Efficacy – The wide use of topical and intralesional corticosteroids for morphea is based upon clinical experience that suggests an ability of these agents to abrogate the inflammatory process and soften sclerotic lesions. No formal studies have evaluated efficacy.

Adverse effects – Cutaneous atrophy is a common, local adverse effect of topical and intralesional corticosteroid therapy but is often a desired effect when treating sclerotic skin. Hypopigmentation may also occur. Suppression of the hypothalamic-pituitary-adrenal axis is another potential effect but is less likely to occur with the treatment of limited areas of skin. Adverse effects of topical and intralesional corticosteroid therapy are reviewed in detail separately. (See "Topical corticosteroids: Use and adverse effects", section on 'Adverse effects' and "Intralesional corticosteroid injection", section on 'Side effects, complications, and pitfalls'.)

Topical tacrolimus — Topical tacrolimus, a topical calcineurin inhibitor, is an alternative to topical corticosteroid therapy:

AdministrationTacrolimus 0.1% ointment is applied twice daily to affected skin. As with topical corticosteroids, signs of improvement are expected within 12 weeks.

The best approach to treatment cessation is unclear. Upon resolution of signs of disease activity, we progressively decrease the frequency of application and eventually discontinue treatment, provided there is no return of clinical signs of disease activity.

Efficacy – Data on topical tacrolimus therapy are limited. In an intraindividual trial that included 10 adults with active, circumscribed morphea, two lesions on each patient were randomly assigned to either tacrolimus ointment or petrolatum, both applied twice daily for 12 weeks [7]. Greater improvement in skin hardness and clinical feature scores occurred in lesions treated with tacrolimus. Uncontrolled studies and a case report also suggest benefit of topical tacrolimus [8-10].

Adverse effects – Topical calcineurin inhibitors may be associated with transient burning, erythema, or pruritus after application. Although the US Food and Drug Administration (FDA) issued warnings in 2005 regarding a possible link between topical calcineurin inhibitor use and cancer, a causal relationship has not been established. (See "Treatment of atopic dermatitis (eczema)", section on 'Safety'.)

Topical vitamin D analogs — Topical vitamin D analogs, particularly calcipotriene, have been utilized for morphea. Vitamin D may exert inhibitory effects on fibroblast proliferation, collagen synthesis, and T lymphocyte activation [11]:

Administration – Topical vitamin D analogs are applied twice daily to affected skin. Signs of improvement are expected within 12 weeks. The best approach to treatment cessation is unclear. Once signs of clinical activity have resolved, we gradually taper the frequency of application and eventually discontinue treatment, provided there is no return of signs of disease activity.

Efficacy – Efficacy data for topical vitamin D analogs are limited. In a three-month, open-label study, 12 adolescents and adults with morphea that had failed to respond to topical corticosteroids were treated with twice-daily application of topical calcipotriene 0.005% ointment under occlusion [12]. Clinical improvement occurred in all patients. Improvement after treatment with a combination calcipotriol and betamethasone dipropionate ointment has also been reported [13].

Adverse effects – Topical vitamin D analogs are generally well tolerated. Skin irritation may occur. Hypercalcemia is an uncommon side effect. (See "Calcipotriol (calcipotriene): Drug information".)

Spreading or topical therapy-resistant lesions — Phototherapy is our preferred treatment for active, limited dermal morphea exhibiting lesion expansion, new lesion formation, or failure to improve with topical or intralesional therapy.

Phototherapy — Phototherapy, including ultraviolet A1 (UVA1), narrowband ultraviolet B (UVB), and broadband ultraviolet A (UVA), modalities are used for the treatment of morphea. Treatment may be limited to involved body areas or administered to almost the entire skin surface. Total body treatment is typically performed for patients who are continuing to develop new lesions in an attempt to inhibit the development of new lesions. (See "UVA1 phototherapy" and "UVB therapy (broadband and narrowband)".)

Principles of phototherapy for limited dermal morphea are similar to phototherapy for extensive disease. The administration, efficacy, and adverse effects of phototherapy for morphea are reviewed below. (See 'Phototherapy' below.)

Refractory disease — Systemic immunosuppressant drugs are not usually prescribed for limited dermal morphea because of the potential for serious adverse effects. However, immunosuppressive therapy is occasionally used for limited dermal morphea that continues to progress despite phototherapy or for patients who cannot receive phototherapy. Given the limited skin involvement and the potential for spontaneous cessation of disease progression, the risks of immunosuppressive therapy should be carefully considered prior to the initiation of therapy.

The regimens for systemic immunosuppressive therapy for refractory, limited dermal morphea are similar to regimens used for other presentations requiring systemic immunosuppressive therapy. Methotrexate is the mainstay of therapy. (See 'Systemic immunosuppressants' below.)

Extensive dermal plaques — Patients with more than limited skin involvement usually require phototherapy or systemic therapy because topical and intralesional treatment becomes less practical as the affected body surface area increases. Unlike topical and intralesional therapy, in which treatment is limited to existing lesions, phototherapy and systemic therapy may help to reduce the formation of new lesions.

Preferred initial therapy — Phototherapy is the preferred initial treatment for most patients with extensive dermal morphea, with topical therapies often used as an adjunctive treatment, and systemic immunosuppressive therapy typically reserved for patients who cannot receive phototherapy or who continue to progress despite phototherapy. The relatively favorable side effect profile compared with systemic immunosuppressant drugs is the major advantage of phototherapy.

However, the initial use of immunosuppressive therapy can be appropriate in some scenarios. Phototherapy requires frequent clinic visits or acquisition of specialized equipment for home phototherapy, requirements that are not feasible for all patients. In addition, patients with rapidly progressing disease, worsening functional impairment, or worsening disfigurement may benefit from a more aggressive approach to treatment, consisting of early use of immunosuppressive therapy. (See 'Functional impairment' below and 'Disfigurement' below and 'Systemic immunosuppressants' below.)

Phototherapy — Ultraviolet (UV) light therapy is used for the treatment of a variety of sclerotic diseases of the skin, including morphea. Immunomodulatory effects and stimulatory effects on collagen breakdown may contribute to benefit of phototherapy:

Selection of regimen – Phototherapy options for morphea include devices that emit UVA or UVB light. UVA1 (340 to 400 nm), narrowband UVB (311 to 313 nm), and broadband UVA (320 to 400 nm) are the primary forms of phototherapy used. Psoralen plus ultraviolet A (PUVA) phototherapy, which involves the administration of photosensitizing psoralens prior to exposure to UVA, has fallen out of favor because of the added complexity of psoralen administration and a less favorable side effect profile. (See "UVA1 phototherapy" and "UVB therapy (broadband and narrowband)" and "Psoralen plus ultraviolet A (PUVA) photochemotherapy".)

In general, when UVA1 phototherapy is available, we favor this modality of phototherapy for morphea, based upon the availability of more evidence suggestive of efficacy. UVA1 is a newer form of UVA phototherapy that eliminates the shorter, less deeply penetrating wavelengths in broadband UVA light. This results in a lower risk of sunburn compared with broadband UVA. A disadvantage of UVA1 phototherapy is relatively long treatment times compared with shorter times required to administer other forms of phototherapy. (See "UVA1 phototherapy".)

When UVA1 is unavailable, we opt for narrowband UVB or broadband UVA phototherapy. Due to the lesser depth of penetration of UVB, we usually reserve narrowband UVB for patients with lesions that are relatively superficial, exhibiting only mild induration. Patients with signs of deeper dermal involvement are preferably treated with broadband UVA.

Administration – The optimum dose (low versus medium versus high) and regimen for UVA1 phototherapy have yet to be determined. We treat most patients with a medium (40 to 60 J/cm2) to high (90 J/cm2) dose regimen, with treatments administered three to five times per week for a total of around 40 treatments.

The patient's minimal dose to elicit erythema (minimal erythema dose) determines appropriate dosing for broadband UVA and narrowband UVB. Treatments are usually administered three times per week. Our typical course is between 40 and 60 treatments. The dose is escalated in a manner similar to dose escalation protocols for the treatment of psoriasis. (See "UVB therapy (broadband and narrowband)", section on 'Dosimetry and treatment protocols'.)

Improvement, defined as discontinuation of disease progression and reduction in erythema, usually occurs within 10 to 20 treatments with UV light. We aim to assess patients after the first 10 to 15 treatments; patients who continue to have significant disease progression are typically transitioned to systemic treatment. (See 'Systemic immunosuppressants' below.)

Patients who achieve resolution of signs of activity are candidates for cessation of phototherapy. Once these patients have received at least 40 treatments, we discontinue phototherapy. We do not taper treatment. We re-evaluate these patients periodically and resume phototherapy for recurrences of signs of disease activity. (See 'Follow-up' below.)

Disease activity may recur following successful phototherapy, and continued follow-up is necessary after completion of treatment. In a series of 37 adults and children with morphea who responded to UVA1 phototherapy and were followed for at least six months after completing treatment, 17 (46 percent) developed recurrences of active disease [14]. The two- and three-year recurrence rates were 44.5 percent (95% CI 30.1-62.2 percent) and 48.4 percent (95% CI 33.2-66.1 percent), respectively. A longer duration of disease prior to treatment was associated with a slightly increased risk for recurrence of active disease (hazard ratio 1.15, 95% CI 1.06-1.27).

Efficacy – The mechanisms through which UV light improves sclerotic skin disease are not fully understood. Theories for the efficacy of UV light have included effects on collagen synthesis or breakdown (eg, UV-induced upregulation of fibroblast production matrix metalloproteinases that stimulate collagen breakdown) as well as UV-induced immunomodulation [15-21].

High-quality evidence to confirm efficacy of UVA1, broadband UVA, and narrowband UVB phototherapy for morphea are lacking. A systematic review of randomized trials that identified one nonblinded trial (n = 64) that compared low-dose UVA1 (20 J/cm2), medium-dose UVA1 (50 J/cm2), and narrowband UVB phototherapy in children and adults with active morphea found little to no difference among these modalities for overall improvement of disease activity or disease damage [22]. Statistically significant reductions in a clinical evaluation score based upon skin thickness and proportion of skin involved occurred in all groups. In addition, a case series of 12 patients with morphea treated with broadband UVA (20 J/cm2) three times per week for 20 sessions suggests benefit of broadband UVA [23]. All treated patients exhibited lesion softening. Early lesions responded best to therapy.

Adverse effects – Adverse effects of phototherapy include erythema, pruritus, hyperpigmentation, burns, and reactivation of herpes simplex virus infection. Accelerated skin aging and skin cancer are potential long-term effects of phototherapy. (See "Psoralen plus ultraviolet A (PUVA) photochemotherapy", section on 'Adverse effects' and "UVB therapy (broadband and narrowband)", section on 'Short- and long-term adverse effects' and "UVA1 phototherapy".)

Systemic immunosuppressants — Patients with extensive dermal morphea that fails to improve with phototherapy or that is rapidly progressing or causing worsening functional impairment or disfigurement are candidates for systemic immunosuppressive treatment (algorithm 1). Other patients may also be appropriate candidates for systemic treatment. (See 'Single or few dermal plaques' above and 'Deep morphea' below and 'Functional impairment' below and 'Disfigurement' below.)

Methotrexate given alone or in conjunction with systemic glucocorticoids is considered the most appropriate approach to systemic therapy for morphea [6]. Mycophenolate is an alternative therapy primarily reserved for patients who cannot tolerate methotrexate or fail to respond to methotrexate. (See 'Methotrexate and systemic glucocorticoids' below and 'Mycophenolate' below.)

Methotrexate and systemic glucocorticoids — Methotrexate is an immunosuppressant that may be effective for morphea either as monotherapy or in conjunction with systemic glucocorticoids. Systemic glucocorticoid therapy is added in an attempt to accelerate and optimize improvement of more severe clinical presentations:

Selection of regimen – We treat most patients with methotrexate alone, reserving the addition of systemic glucocorticoids for patients with very inflammatory, rapidly progressive morphea (eg, evolution to involve multiple body sites or rapid extension of lesions over multiple joints within less than six months). (See "Methotrexate: Drug information".)

Administration – Data are insufficient to determine the optimal route, dose, and duration of methotrexate and systemic glucocorticoid therapy, and practice varies widely. Methotrexate is usually given orally or subcutaneously at a dose of 15 to 25 mg per week. Systemic glucocorticoids, when given, are started simultaneously with methotrexate. We typically give intravenous methylprednisolone (30 mg/kg per day for three consecutive days per month) or oral prednisone (1 mg/kg per day).

Cessation of signs of disease activity (erythema, progression) is usually noted within two to five months with these regimens. When patients fail to respond, we typically add other treatments in an attempt to attain disease control. Typically, we add UVA1 phototherapy or mycophenolate and continue methotrexate. (See 'Assessment of response' above.)

In patients who respond well, methotrexate is continued for an extended period following resolution of signs of disease activity. Patients are often treated for a total of one to two years. We begin to taper methotrexate (reduce dose by 2.5 mg every two to four weeks) after 6 to 12 months of documented inactivity. Softening of sclerotic plaques is often delayed, becoming evident after 6 to 12 months of methotrexate treatment. If a disease flare occurs during tapering of methotrexate, we return to the last effective dose and maintain that dose for six months prior to reattempting tapering.

Systemic glucocorticoid therapy is discontinued more quickly following resolution of signs of disease activity. We typically discontinue intravenous methylprednisolone after three to four months. For patients receiving oral prednisone, we begin to slowly taper the dose of oral prednisone once disease activity ceases, with a goal of discontinuing treatment within three to four months. In our experience, it is unusual for patients to require systemic glucocorticoids for longer than four months. If a disease flare occurs during tapering, we return to the effective dose used immediately prior to the flare and increase the dose of methotrexate up to a maximum of 25 mg per week. (See 'Assessment of response' above.)

Some patients treated with methotrexate relapse after the discontinuation of therapy, indicating that therapy likely has a suppressive, rather than curative, effect [24]. Patients who relapse may respond to additional treatment courses.

Efficacy Data on the efficacy of methotrexate and glucocorticoids in morphea are limited. Although a randomized trial found lower relapse rates among children with juvenile morphea who were treated with combination therapy with methotrexate and a three-month course of prednisone than among children treated with a three-month course of prednisone alone [25], no randomized trials have been performed to confirm similar results in adults with this disease. (See "Juvenile localized scleroderma", section on 'Pharmacologic measures'.)

An uncontrolled, prospective study of 15 adults with severe, generalized or linear morphea offers support for a beneficial effect of methotrexate and glucocorticoids in the adult population. Treatment with oral methotrexate (initial dose 15 mg/week) and pulsed intravenous methylprednisolone (1000 mg for three days once monthly) for at least six months was associated with resolution of inflammation and marked softening of sclerotic skin in all but one patient [26]. Improvement was evident within two months after the start of treatment in most patients.

Moreover, in a series of 61 patients with adult-onset linear morphea in which outcomes for the 23 percent of treatment regimens that included methotrexate (with or without systemic glucocorticoids) were compared with outcomes for regimens that did not include methotrexate, disease resolution was more likely (29 versus 4 percent) and progression and recurrence less likely (4 versus 34 percent and 13 versus 56 percent, respectively) with treatment regimens that included methotrexate [27]. The mean follow-up period was 38 months.

Data from an uncontrolled study also suggests benefit of methotrexate monotherapy. In a 24-week, uncontrolled study of nine adults with generalized morphea, treatment with oral methotrexate (15 to 25 mg per week) led to improvement in both the modified skin score and patient-reported feelings of tightness and itching [28]. However, three patients discontinued the study due to adverse effects, and two patients required dose reductions due to side effects.

Adverse effects The adverse effects of methotrexate and systemic glucocorticoids are reviewed elsewhere. (See "Major side effects of low-dose methotrexate" and "Major side effects of systemic glucocorticoids".)

Although improvement with systemic glucocorticoid therapy alone has been reported, efficacy data are limited, relapses after cessation may be common, and avoidance of extended courses of glucocorticoids is preferred due to the risk for serious drug-related adverse effects [25,29,30]. We do not use systemic glucocorticoids as monotherapy.

Mycophenolate — Mycophenolate (mycophenolate mofetil or mycophenolic acid) is our preferred systemic immunosuppressant for patients who have contraindications to or cannot tolerate methotrexate:

Administration – The optimal regimen of mycophenolate for morphea is unclear. We typically treat with mycophenolate mofetil 1 g twice daily, with a maximum dose of 1.5 g twice daily. In our experience, improvement occurs relatively slowly; a gradual decrease in disease activity often occurs over three to four months.

We typically continue the effective dose of mycophenolate for 6 to 12 months after resolution of disease activity prior to tapering the drug. Tapering is performed slowly, usually over several months. If disease activity recurs during tapering, we return to the lowest effective dose and continue treatment for an additional six months prior to another attempt at tapering.

Efficacy – Efficacy data for mycophenolate are limited. One of the largest studies, a retrospective study of 77 patients (primarily with generalized, pansclerotic, or linear morphea) treated with mycophenolate alone or in conjunction with other therapies, suggests benefit of this therapy [31]. After three to six months of treatment with mycophenolate, 44 of 73 patients (60 percent) had improvement (defined as absence of new or expanding lesions plus decreased erythema, decreased induration, or improvement of associated functional impairment), and 22 of 73 patients (30 percent) had stable disease. After 9 to 12 months, 33 of 54 patients (61 percent) had improved disease, and 14 of 54 patients (26 percent) had stable disease.

Benefit of mycophenolate mofetil was also suggested in a series of seven treated patients with deep, linear, generalized, or mixed morphea [32]. Four patients achieved disease remission, one maintained pre-existing remission, and one patient had progression of disease. One patient discontinued treatment due to elevated liver enzymes.

Adverse effects – Gastrointestinal distress and bone marrow suppression are among the most common adverse effects of mycophenolate. Infection and malignancy are additional potential adverse effects. (See "Mycophenolate: Overview of use and adverse effects in the treatment of rheumatic diseases", section on 'Adverse effects'.)

Deep morphea — Active deep morphea can result in functional impairment; therefore, treatment is generally indicated. Systemic immunosuppressive therapy is the primary mode of treatment. Intralesional corticosteroid injections are an alternative initial approach for select lesions, such as stable or slowly progressing small lesions that will not cause functional impairment and are not in cosmetically sensitive areas. Phototherapy is not effective for deep involvement because UV light has a poor ability to penetrate deep tissues.

Limited, slowly progressing deep morphea — Although systemic immunosuppressive therapy is considered the mainstay of treatment for active deep morphea, the potential for serious treatment-related adverse effects prompts consideration of less aggressive approaches to treatment for limited, slowly progressing disease that is not causing functional impairment and is not in cosmetically sensitive areas. Intralesional corticosteroid therapy is a reasonable alternative initial treatment for these patients. Patients who do not respond sufficiently to intralesional corticosteroid injections are treated with systemic therapy.

Intralesional corticosteroid injections — Patients given intralesional corticosteroid injections as primary treatment for deep morphea should be selected carefully. Treatment should be limited to patients with a small area of involvement in whom the depth of morphea does not extend beyond the subcutaneous tissue. Patients with extensive deep morphea, fascia or muscle involvement, rapidly progressing deep morphea, or existing or perceived imminent functional impairment are better candidates for systemic immunosuppressive therapy (see 'Extensive, rapidly progressing, disabling, or disfiguring deep morphea' below):

Administration – We typically use triamcinolone acetonide at a concentration of 10 to 20 mg/mL for deep morphea, with the higher concentration (20 mg/mL) typically used for lesions exhibiting a greater degree of sclerosis. Injections are placed approximately 1 cm apart and administered throughout the lesion.

The status of disease should be closely monitored. In patients who demonstrate progressive clinical improvement, we repeat injections every four to six weeks until the resolution of signs of disease activity. Patients who continue to progress (eg, development of lesion extension or new lesion formation) during treatment are transitioned to other treatments.

Efficacy – Clinical experience suggests that intralesional corticosteroid injections can abrogate the inflammatory process and soften sclerotic areas in deep morphea. However, data to confirm efficacy of this approach are lacking.

Adverse effects – Potential adverse effects include cutaneous atrophy, hypopigmentation, and suppression of the hypothalamic-pituitary-adrenal axis. Adverse effects of intralesional corticosteroid injection are reviewed in detail separately. (See "Intralesional corticosteroid injection", section on 'Side effects, complications, and pitfalls'.)

Extensive, rapidly progressing, disabling, or disfiguring deep morphea — Patients with extensive, rapidly progressing, disabling, or disfiguring active deep morphea are generally given systemic immunosuppressive therapy. (See 'Functional impairment' below and 'Disfigurement' below.)

Systemic immunosuppressants — The approach to systemic therapy for deep morphea mirrors the approach for other presentations warranting systemic treatment. Methotrexate administered with or without systemic glucocorticoids is the mainstay of treatment. (See 'Systemic immunosuppressants' above.)

Other therapies — A variety of other therapies have been utilized for morphea. Concern for uncertain efficacy or adverse effects limits use of these therapies:

Topical – Limited data suggest benefit of topical imiquimod, a topical immunomodulator, for dermal morphea [33-35]. Proposed mechanisms of action include induction of interferon (IFN)-gamma, a cytokine that can inhibit transforming growth factor (TGF)-beta and the production of extracellular matrix proteins and downregulation of the profibrotic cytokine interleukin (IL) 4 [33,34]. In our experience, imiquimod is often irritating and poorly tolerated. We do not use this therapy.

Systemic – A wide variety of systemic therapies other than methotrexate, systemic glucocorticoids, and mycophenolate have been used for active morphea. However, data and experience with these interventions are insufficient to confirm efficacy or support routine use. Examples include penicillin, penicillamine, colchicine, hydroxychloroquine, cyclosporine, bosentan, infliximab, tofacitinib, and abatacept [11,36-46].

Although improvement with oral calcitriol (a form of oral vitamin D) has been reported in case reports and a small, uncontrolled study [47-50], there was no benefit of calcitriol (0.75 mcg per day for six months plus 1.25 mcg per day for three months) when compared with placebo in a randomized trial that included 20 patients with morphea [51]. We do not use oral vitamin D for the treatment of morphea.

Procedural – Procedures that have been reported to be effective in a few patients include photodynamic therapy [52] and pulsed dye laser or ablative fractional laser therapy for sclerotic lesions [53,54]. Benefit of perioral injection of intralesional hyaluronidase for microstomia in pansclerotic morphea has also been reported [55]. There are reports of benefit of extracorporeal photochemotherapy [56-58].

INACTIVE DISEASE — The immunomodulatory topical, intralesional, light-based, and systemic therapies utilized for active morphea are unlikely to be effective in patients who have reached the atrophic, inactive stage of disease. The management of inactive disease focuses on improving residual functional impairment, improving disfigurement, and monitoring for recurrence of disease activity. Managing these patients may involve physical and occupational therapy and consultations with specialties such as orthotics, orthopedics, podiatry, plastic surgery, and rheumatology, as needed (algorithm 1). (See 'Functional impairment' below and 'Disfigurement' below.)

FUNCTIONAL IMPAIRMENT — Functional impairment secondary to active or previously active morphea can have significant effects on patient quality of life. Patients should be clinically examined for contractures, limb length discrepancy, reduced range of motion, and other functional impairments at each follow-up visit. Risk for development of new impairment based upon lesion location and disease progression should also be assessed at follow-up visits.

Patients with progressing functional impairment require prompt initiation of systemic immunosuppressive therapy to reduce disease activity. In addition, these patients should receive consultations, as appropriate, with physical therapy, occupational therapy, physical medicine and rehabilitation, rheumatology, plastic surgery, orthopedics, or oral and maxillofacial surgery. The goal of treatment is to maximize function and minimize further damage. (See 'Systemic immunosuppressants' above.)

Surgical intervention is sometimes necessary for persistent, disabling contractures. However, there may be risk for stimulating exacerbation of morphea; the occurrence of new-onset or worsening morphea in sites of surgical incisions or radiation therapy has been reported [59].

Thus, surgical procedures should be undertaken with caution and should be limited to patients with inactive (atrophic stage) disease when possible. Occasionally, surgical intervention for functional impairment is necessary in the setting of active disease due to a substantial negative impact on quality of life. In these cases, we optimize medical treatment to limit activity prior to and after surgery. We also follow patients carefully for signs of worsening disease activity following surgery.

Monitoring for recurrence of inflammation and associated volume loss is difficult after surgical correction. Objective quantification of asymmetry with three-dimensional (3-D) photography or radiologic imaging shortly after recovery from the procedure is advised to provide a baseline volume assessment. These studies can be repeated if there is concern for additional volume loss after surgery.

DISFIGUREMENT — Morphea may lead to disfiguring pigmentary changes and tissue atrophy. Prompt initiation of systemic immunosuppressive therapy is appropriate for patients with active, progressing disease causing disfigurement in cosmetically sensitive areas. (See 'Systemic immunosuppressants' above.)

Other interventions may help to improve pigmentary changes and atrophy that has already occurred. Patients with hypopigmentation or hyperpigmentation can benefit from topical cosmetic camouflage agents.

Injectable soft tissue fillers may improve atrophic changes in inactive lesions [60]. Consultation with a plastic surgeon or procedural dermatologist with experience in treating patients with morphea is essential. In our practice, we favor autologous fat due to the long-lasting nature of this filler compared with more commonly used fillers and the ability to use large volumes of autologous fat to fill in sizable defects. (See "Injectable soft tissue fillers: Permanent agents", section on 'Autologous fat' and "Injectable soft tissue fillers: Temporary agents".)

Surgical procedures, including skin flaps or grafts, are occasionally used to improve the appearance of sites of atrophy. However, performance of large flaps or grafts should generally be limited to patients for whom autologous fat transfer will not yield reasonable benefit and in whom morphea is inactive. Concerns include risk for postsurgical tissue loss and reactivation of morphea.

ASSOCIATED CONDITIONS

Extracutaneous involvement — Patients with morphea can develop extracutaneous complications that require additional evaluation (algorithm 2) (see "Pathogenesis, clinical manifestations, and diagnosis of morphea (localized scleroderma) in adults", section on 'Extracutaneous manifestations'):

Joint pain – Rheumatologic evaluation is indicated in patients with symptoms suggestive of arthritis or synovitis.

Head or face involvement – Patients with lesions involving the head or face should be referred to ophthalmology to evaluate for the presence of ocular complications. Some authors have also recommended repeating ophthalmologic examinations every three to four months during the first three years of disease [61].

Neurologic symptoms – Patients with head or face involvement who have neurologic symptoms (eg, seizures, headaches, focal neurologic deficits, or neuropsychiatric abnormalities) should be referred to neurology for evaluation [62]. The most common findings on magnetic resonance imaging (MRI) in patients with neurologic involvement include hyperintensities in the subcortical white matter or other sites, focal tissue atrophy, and calcifications [62]. Routine radiologic imaging is not indicated in asymptomatic patients.

Dental involvement or jaw dysfunction – Referral to dentistry or oral and maxillofacial surgery is beneficial for patients with evidence of dental involvement or jaw dysfunction.

Genital involvement — Genital involvement of morphea, manifesting as lesions with the appearance of lichen sclerosus et atrophicus, may precede or follow the development of lesions consistent with morphea, particularly in patients with generalized morphea. Thus, periodic examination of the genitalia in patients with generalized morphea is prudent. Genital lesions are treated similarly to genital lichen sclerosus independent of morphea. (See "Pathogenesis, clinical manifestations, and diagnosis of morphea (localized scleroderma) in adults", section on 'Lichen sclerosus' and "Vulvar lichen sclerosus", section on 'Management'.)

PROGNOSIS — Morphea may have a remitting and relapsing course, with periods of activity and reactivation over several years [63]. Patients with pediatric-onset morphea may have repeated episodes of activity well into adulthood [64].

Reliable demographic, clinical, or laboratory risk factors for recurrence have not been identified. It is unknown whether treatment with systemic immunosuppressants reduces long-term risk for recurrence.

FOLLOW-UP — Patients with morphea may benefit from long-term clinical follow-up to support achievement of disease control and early recognition of recurrence of disease activity. We follow most patients with clinical examinations every two to four months during the first one to two years after diagnosis.

Provided disease control is achieved, we extend the period between examinations to every six months during the second year after diagnosis and perform annual clinical follow-up thereafter. Patients should be made aware of the possibility of recurrence and encouraged to return for evaluation if they note new lesion development or other signs of disease progression.

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: Morphea (localized scleroderma)".)

SUMMARY AND RECOMMENDATIONS

Morphea, also known as localized scleroderma, is a relatively uncommon idiopathic inflammatory disorder that leads to the development of sclerotic plaques in the skin. The disorder occurs in both adults and children. (See "Pathogenesis, clinical manifestations, and diagnosis of morphea (localized scleroderma) in adults", section on 'Epidemiology'.)

Because of the self-limited nature of morphea, some patients with limited dermal morphea (single or few dermal plaques) may elect to defer therapy. For adult patients with active but stable, limited dermal morphea who desire treatment, we suggest a high-potency topical corticosteroid or intralesional corticosteroid injections as the initial treatment (Grade 2C). Alternatives include topical tacrolimus and topical vitamin D analogs. (See 'Single or few dermal plaques' above.)

For patients with active extensive dermal morphea or spreading dermal morphea, we suggest phototherapy as initial treatment (Grade 2B). We suggest treatment with ultraviolet A1 (UVA1) over other forms of phototherapy (Grade 2C). If UVA1 is not available, other options for phototherapy include broadband ultraviolet A (UVA) and narrowband ultraviolet B (UVB). Phototherapy is unlikely to be effective for deep morphea involving the subcutaneous tissue, muscle, or bone. (See 'Extensive dermal plaques' above.)

Active morphea that is rapidly progressing and extensive and active morphea that is associated with worsening disability or disfigurement are generally treated with systemic therapy. For patients with these features, we suggest treatment with methotrexate (Grade 2C). We add systemic glucocorticoid therapy for highly inflammatory and rapidly progressive presentations. (See 'Systemic immunosuppressants' above.)

Morphea may cause joint contractures and other functional impairments secondary to tissue sclerosis. All patients should be clinically assessed for the development of these findings. Physical and/or occupational therapy is essential for patients who are at risk for or who show evidence of functional impairments. (See 'Functional impairment' above and 'Disfigurement' above.)

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References