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Pathogenesis, clinical manifestations, and diagnosis of morphea (localized scleroderma) in adults

Pathogenesis, clinical manifestations, and diagnosis of morphea (localized scleroderma) in adults
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: Nov 15, 2021.

INTRODUCTION — Morphea, also known as localized scleroderma, is an idiopathic, inflammatory disorder that causes sclerotic changes in the skin. Morphea is distinct from systemic sclerosis (scleroderma), an autoimmune connective tissue disorder characterized by acral or diffuse cutaneous sclerosis and frequent systemic manifestations. Use of the term morphea diminishes the likelihood of confusion between these two disorders, which can lead to unnecessary patient anxiety. (See "Clinical manifestations and diagnosis of systemic sclerosis (scleroderma) in adults".)

Patients with morphea present with single or multiple inflammatory or sclerotic plaques. Disease activity typically persists for three to six years; some patients develop more persistent or recurring involvement. Cosmetic disfigurement or functional impairments due to atrophy or contractures often remain after the resolution of active disease. (See "Morphea (localized scleroderma) in adults: Management", section on 'Prognosis'.)

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

EPIDEMIOLOGY — Morphea is a relatively uncommon disorder that affects adults and children [1-4]. The annual incidence of morphea was approximately 3 per 100,000 people in a population in the United States between 1960 and 1993 [5].

Although morphea can occur at any age, many patients (50 to 65 percent) develop the disease as adults [4-6]. In a nested case-control study of 110 patients with adult-onset morphea and 77 patients with juvenile-onset disease conducted at an academic medical center, the mean ages of disease onset were 45 years and 10 years, respectively [6]. Females are more susceptible to morphea than males; in a retrospective study of 82 patients with morphea, the female-to-male ratio was 2.6:1 [5].

PATHOGENESIS — The pathogenesis of morphea is poorly understood. Theories on the pathogenesis of morphea are often extrapolated from studies of systemic sclerosis [7]. A variety of factors, including autoimmunity, genetics, and vascular dysfunction may play a role in morphea. Multiple environmental factors (eg, radiation, infections, skin trauma [eg, friction, surgery], or environmental exposures) also have been proposed as contributors to disease expression [8]. However, avoidance of medically necessary surgery or radiation therapy is not indicated for patients with morphea (see "Juvenile localized scleroderma", section on 'Etiology and pathogenesis'):

Immune dysfunction – It is generally accepted that immune dysfunction is involved in the development of morphea [4,9-11]. A role for autoimmunity in the development of this disorder is supported by the following:

A clinically evident inflammatory stage often precedes the development of sclerosis [12].

Histopathologic studies of early lesions demonstrate an influx of large numbers of mononuclear lymphocytes (primarily activated T lymphocytes), plasma cells, and eosinophils [7].

Cytokines associated with Th2 immune responses, such as interleukin (IL) 4, are detected at increased levels in patients with morphea [13]. IL-4 produced by CD4+ Th2 lymphocytes can upregulate the production of transforming growth factor (TGF)-beta by T lymphocytes and other cells [7]. TGF-beta is capable of stimulating fibroblast production of collagen and other extracellular matrix proteins.

Increased autoantibody levels are present in some patients with morphea, particularly those with the generalized or linear variants [4,9,10].

Transcriptional profile studies support associations between increased expression of genes associated with inflammatory responses and disease activity in children with morphea [14,15]. (See "Juvenile localized scleroderma", section on 'Etiology and pathogenesis'.)

Vascular dysfunction – The detection of reduced numbers of dermal capillaries, abnormalities in basal lamina of blood vessels, and endothelial cell damage in specimens from lesional skin support a role for vascular dysfunction in the development of morphea [16].

One theory of the pathogenesis of morphea proposes that injury to the vascular endothelium during the inflammatory stage stimulates the release of cytokines that upregulate the expression of vascular adhesion molecules, including vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin [7,16]. These adhesion molecules facilitate the recruitment of T-lymphocytes that are capable of producing profibrotic cytokines (IL-4, IL-6, and TGF-beta), and may contribute to the development to sclerosis [7,16]. Of note, increased levels of vascular adhesion molecules have been detected in serum from patients with morphea [17].

Genetics – Although susceptibility genes for the development of morphea have not been identified, reports of familial case clusters [4,18,19] and the detection of increased rates of autoimmune disorders in family members of patients with morphea [4,9,20] suggest a genetic contribution.

CLINICAL MANIFESTATIONS — Morphea is divided into several subtypes [21], all of which transition through an early inflammatory stage followed by sclerosis and subsequent atrophy (figure 1). The depth of involvement may be superficial (primarily dermal) or deep (involving the deep dermis plus the subcutis, fascia, and/or bone).

Lesion evolution — Sclerotic lesions in the skin manifest as firm, bound-down plaques or nodules. However, in morphea, the initial sign of disease is often an inflammatory, erythematous patch or edematous plaque. Some patients may note unexplained pain or itching at the site of disease prior to the development of a clinically evident lesion. Sclerosis usually begins in the center of inflammatory lesions, initially leaving an erythematous or violaceous border (picture 1A-B). Hypopigmentation, hyperpigmentation, alopecia secondary to loss of hair follicles, and a shiny cutaneous surface are common additional features of sclerotic lesions (picture 6B).

After a period of months to years, sclerotic plaques soften and transition into hypopigmented or hyperpigmented atrophic plaques (picture 5B). Atrophy in lesions that primarily involve the dermis may present as areas of fine, cigarette-paper like skin or shallow (cliff drop-like) depressions. Patients with deep morphea, which extends into the subcutis and beyond, may be left with deep indentations after the resolution of active disease.

Subtypes — There is a lack of consensus on the appropriate classification system for morphea [16,21]. We prefer the clinically based division of morphea into circumscribed, generalized, linear, pansclerotic, and mixed subtypes (table 1). A number of other previously described morphea subtypes are better classified as descriptors because they are in any of the subtypes listed above and, therefore, do not describe a distinct group of patients. These include deep morphea (defined as lesions with pathology involving the subcutis or underlying soft tissue and beyond), keloidal morphea, and bullous morphea.

Circumscribed lesions are the most common manifestation of morphea in adults and, like the generalized variant, are more frequently observed in adults than in children. Linear morphea most often appears in childhood and is the most common subtype of morphea in children [1,3-6,22-25]. In one series, 95 of 291 patients with linear morphea (33 percent) had adult-onset disease [25].

Studies conflict on the relative frequency of morphea subtypes; differences in classification criteria likely contribute to the discrepant results. A retrospective study of 113 adults with morphea found the following frequencies of clinical variants [23]:

Circumscribed ‒ 65 percent

Generalized ‒ 8 percent

Linear ‒ 6 percent

En coup de sabre (a form of linear disease) ‒ 3.5 percent

Circumscribed (plaque) morphea — Circumscribed morphea, also known as plaque morphea, presents as single or multiple, well-defined, oval to round plaques that fail to meet criteria for generalized morphea (picture 1A, 1C-D). In some patients, linear or generalized morphea initially presents with features consistent with circumscribed disease, indicating the need to follow patients with circumscribed lesions over time. (See "Juvenile localized scleroderma", section on 'Circumscribed (plaque) morphea'.)

Generalized morphea — Generalized morphea is defined by the presence of ≥4 morpheaform plaques involving at least two different anatomic sites (picture 2A-B) [16,26]. In contrast to systemic sclerosis, generalized morphea does not present with sclerosis primarily involving acral skin or sclerodactyly; also absent is Raynaud's phenomenon. Lesions of generalized morphea frequently begin on the trunk before spreading acrally, and the fingers and toes are spared. (See "Clinical manifestations and diagnosis of systemic sclerosis (scleroderma) in adults".)

Generalized morphea has two patterns of cutaneous distribution that are useful to identify because they are associated with different extracutaneous manifestations [26]. One, called symmetric, is characterized by lesions distributed symmetrically over the arms, breasts, abdomen, and lower extremities. Although female predominant, most men with generalized morphea have this subset. These lesions are more frequently deep and associated with limited range of motion in underlying joints and pain. The other, called isomorphic, occurs almost exclusively in postmenopausal women and is characterized by lesions distributed in areas of chronic friction (ie, waistband, bra straps, inguinal creases, axilla, etc). These lesions exhibit dermal involvement and overlying lichen sclerosus more commonly. In patients with the isomorphic pattern, limited range of motion is rarely encountered, but genital involvement is more common [26].

In the pansclerotic type of generalized morphea, deep morphea lesions occur in a generalized, circumferential distribution and involve the majority of the body surface area, excluding fingers and toes (picture 3) [27,28]. (See "Juvenile localized scleroderma", section on 'Generalized morphea'.)

Linear morphea — Linear morphea (also known as linear scleroderma) manifests as morpheaform plaques arranged in a linear distribution. Lesions occur on the extremities or face but also appear on the trunk, where the differential diagnosis includes circumscribed morphea (picture 4A-B). Patients may have single or multiple sites of involvement. The results of one retrospective study of 65 children with linear morphea suggested that linear morphea can follow the lines of Blaschko [29]. (See "Juvenile localized scleroderma", section on 'Linear scleroderma'.)

Involvement of deep tissues (subcutaneous tissue, muscle, or bone) in linear morphea can lead to significant deformities, including muscle weakness, joint contractures, and in growing children, limb length discrepancies (picture 5A-B). Bone marrow inflammation has also been reported in patients with linear morphea [30,31].

En coup de sabre — En coup de sabre is a type of linear morphea that affects the head and neck. Lesions manifest as hyperpigmented atrophic plaques that resemble the cut of a sword (picture 6A-D). The forehead is the most common site of involvement; lesions may extend onto the scalp, where they cause permanent alopecia. Other classic sites of involvement include the temple and chin. (See "Juvenile localized scleroderma", section on 'Linear scleroderma of the head/face'.)

Progressive facial hemiatrophy — Progressive facial hemiatrophy (Parry-Romberg syndrome) is a variant of linear morphea characterized by unilateral atrophy of the skin, soft tissues, muscles, and/or bones of the face (picture 7). Facial atrophy may be accompanied by classic, linear morphea lesions on the face or elsewhere. (See "Juvenile localized scleroderma", section on 'Linear scleroderma of the head/face'.)

Mixed morphea — Mixed morphea is a term used to describe the simultaneous presence of more than one subtype.

Morphea descriptors

Deep morphea — Deep morphea, or morphea profunda, is a form of morphea that primarily involves the deep dermis and subcutaneous tissue and may extend to underlying fascia and muscle. Plaques are poorly circumscribed (picture 8) with an indurated texture and feel tightly tethered to underlying fascia and muscle. Areas of depression (the "groove sign") may be present at sites with underlying tendons and ligaments, reflecting tethering to these underlying structures. The presence of deep morphea is more frequently associated with functional limitations and pain than morphea with more superficial involvement. Deep morphea can occur across all subtypes and should be considered a descriptor rather than a subtype onto itself.

Other descriptors — Nodular and keloidal morphea as well as bullous morphea have been described in the literature. It is becoming increasingly accepted that keloidal morphea is the occurrence of keloids within a lesion of morphea, similar to the occurrence of keloids in acne lesions. Similarly, bullous morphea has largely been described in dependent areas in patients with deeply sclerotic lesions. It is our opinion that this represents secondary changes resulting from edema in the affected extremity [32].

Extracutaneous manifestations — Disorders of the musculoskeletal system (arthralgias, joint swelling, myalgias, limb contractures, and limited range of motion) can occur in patients with morphea (picture 9) [4]. Adults with generalized or deep morphea may be more likely than other affected adults to experience musculoskeletal symptoms [23]. Raynaud phenomenon also has been reported in a minority of children and adults with morphea [4,23].

Pulmonary and esophageal abnormalities occur in a minority of patients with morphea; however, in the vast majority of cases, this has been asymptomatic and only detectable with investigational studies [33]. More commonly, symptoms of dysphagia or dyspnea may develop secondary to the restrictive effects of extensive cutaneous sclerosis. Evaluation for pulmonary or esophageal abnormalities is not indicated in the absence of symptoms.

Approximately 4 percent of individuals with linear lesions affecting the head, including en coup de sabre and/or hemifacial atrophy, have neurologic or ocular complications, including seizures, headaches, uveitis, episcleritis, and adnexal abnormalities involving the eyelids, eyelashes, or lacrimal glands [20,34-36]. Linear morphea of the head, particularly of the face, may be associated with dental malocclusion, altered dentition, and atrophy of the tongue and salivary glands. A destructive gingivitis has also been reported in patients with facial morphea lesions, usually of the linear subtype. This is characterized by inflammation of the gingiva followed by regression of gingiva and bone, likely representing the same pathologic process as in the overlying skin [37]. The approach to patients with suspected joint, neurologic, ocular, or oral involvement is discussed separately. (See "Morphea (localized scleroderma) in adults: Management", section on 'Extracutaneous involvement'.)

Other autoimmune disorders may occur at a relatively high frequency in patients with morphea [4,6]. In a study of 123 adults with this disorder, 37 (30 percent) had another autoimmune disease [4]. Concomitant autoimmune disease was most common in adults with generalized morphea.

DIAGNOSIS — In many patients, the diagnosis of morphea can be made based upon the clinical findings. However, histopathologic studies and radiologic imaging can be useful to confirm a diagnosis or evaluate the extent of disease. A diagnostic algorithm for patients with clinical features suggestive of morphea is provided (algorithm 1).

History and physical examination — The patient history should include an assessment of the course and progression of lesions and associated symptoms (pruritus, pain, tightness).

A full skin examination should be performed to determine the extent of skin involvement. Patients should also be examined for contractures, limb length discrepancy, reduced range of motion, and other functional impairments. A genital examination should be performed on patients with generalized morphea or extragenital lichen sclerosus et atrophicus overlap with morphea to detect signs of genital lichen sclerosus. (See 'Lichen sclerosus' below.)

Infrequently, patients with systemic sclerosis develop morpheaform plaques [38]. Therefore, patients with findings consistent with morphea should be asked about a history of Raynaud phenomenon (a common early feature of systemic sclerosis) and should be evaluated clinically for other signs and symptoms of systemic sclerosis, such as nail fold capillary changes, sclerodactyly, or acrosclerosis. (See 'Differential diagnosis' below and "Clinical manifestations and diagnosis of systemic sclerosis (scleroderma) in adults", section on 'Evaluation for suspected systemic sclerosis'.)

Histopathology — Tissue biopsies are generally reserved for cases in which the diagnosis is in question. Biopsy specimens should include subcutaneous fat, if possible. A punch biopsy that extends into the subcutaneous fat can be performed in superficial lesions of morphea. In cases of deep involvement, a punch biopsy is unlikely to reach sufficient depth, and an incisional biopsy should be considered or soft tissue magnetic resonance imaging (MRI).

The biopsy specimen can be taken from the inflammatory or indurated border if present, or from a central sclerotic area. The pathologist should be informed of the clinical features of the site from which the biopsy is taken. For lesions with minimal clinical change, a second biopsy from unaffected skin in a location similar to the lesion site (eg, contralateral skin) should be performed to assist with interpretation of the lesional pathologic findings.

The pathology of morphea varies based upon biopsy site, lesion stage, and lesion depth. Biopsies performed from inflammatory lesions demonstrate an interstitial, periadnexal, and/or perivascular, inflammatory cell infiltrate composed primarily of lymphocytes and plasma cells. Eosinophils, mast cells, and macrophages may be present. Inflammation may extend into the subcutaneous tissues. In addition, tissue edema, enlarged tortuous vessels, and thickened collagen bundles may be observed.

As sclerosis progresses, lesions demonstrate homogenization of the papillary dermis and thickened collagen bundles extending into the reticular dermis or beyond (picture 10). Fat surrounding eccrine glands diminishes, and advanced sclerotic lesions exhibit compression and loss of appendageal structures. Few blood vessels are present, and those that remain exhibit fibrotic walls and narrowed lumina. In specimens from deep morphea, the deep reticular dermis, subcutis, and fascia show sclerotic changes.

The atrophic phase of morphea is characterized by loss of inflammatory cell infiltrate, less sclerosis, and an absence of appendageal structures. Telangiectasia may be evident. In some cases, basal keratinocytes display pigment along with underlying melanophages [39].

The histopathologic findings may correlate with patient symptoms [32,39]. A study of 83 adults and children with morphea found an association between a bottom-heavy pattern of sclerosis and symptoms of pain and tightness [32]. The study also found a nonstatistically significant trend towards an association between severe inflammation and symptoms of pain and functional limitation. A study of 137 adults and children with morphea found similar results as well as an association between the presence of tissue eosinophils or basal pigmentation and poor treatment response [39].

Serum autoantibodies — Many adults and children with morphea have elevated antinuclear antibody (ANA) levels. Reported rates of ANA positivity among patients with morphea range from 18 to 68 percent [4,6,23,40,41]. The increased prevalence of ANA positivity compared with the general population was evident in a nested case-control study of 187 adults and children with morphea conducted at an academic medical center; a positive ANA was detected in 34 percent of the morphea patients compared with only 11 percent of 651 matched controls [6]. Other autoantibodies that are detected less frequently than ANA in patients with morphea include anti-single-stranded DNA (ssDNA), anti-double-stranded DNA (dsDNA), antihistone, antitopoisomerase II alpha, antiphospholipid, and rheumatoid factor [4,10,40,42-47].

Although associations between certain autoantibodies and the severity of linear morphea have been reported [6,41], the prognostic significance of autoantibodies in morphea remains unclear. Thus, testing for autoantibodies is not indicated in the absence of clinical signs that suggest the presence of another autoimmune disorder.

Other serum abnormalities — Peripheral eosinophilia, hypergammaglobulinemia, and increased erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels may occur with active disease of any type. Based upon our observations, when eosinophilia is present in patients with deep morphea, the level of eosinophilia may correlate with disease activity. This finding may reflect the overlapping features of deep morphea and eosinophilic fasciitis. (See 'Eosinophilic fasciitis' below.)

Imaging studies — In patients who present with clinical findings that suggest morphea that extends beyond the dermis (eg, tightly bound-down quality on skin examination, muscle weakness, contractures, or limb length discrepancies), MRI should be used to assess lesion depth and involvement of soft tissue [31,48]. Ultrasonography is an alternative to MRI [49]. MRI findings that may be seen in morphea include fascial thickening, fascial enhancement, articular synovitis, tenosynovitis, perifascial enhancement, myositis, enthesitis, bone marrow involvement, and subcutaneous septal thickening [48].

MRI and ultrasound have also been used to monitor disease activity [31,50]. With both modalities, discussion with the radiologist is essential to correlate the radiologic findings with clinical disease and assure the correct imaging protocols are used for the scan.

Data are insufficient to determine whether MRI should be performed routinely in patients without clinical findings suggestive of deep involvement. A retrospective study of 43 patients with deep circumscribed, linear, or generalized (plaque or pansclerotic) morphea found MRI evidence of musculoskeletal involvement in 6 of 16 patients in whom such involvement was not clinically suspected (38 percent) [48].

DIFFERENTIAL DIAGNOSIS — A number of other disorders can present with clinical features that resemble morphea:

Systemic sclerosis – Systemic sclerosis (scleroderma) is an autoimmune disorder characterized by progressive sclerosis of the skin and frequent internal organ involvement. Systemic sclerosis generally begins with the Raynaud phenomenon, and patients commonly exhibit initial puffiness and eventual sclerosis in the fingertips (sclerodactyly), frequently accompanied by nailfold capillary change. These changes are absent in patients with morphea. (See "Clinical manifestations and diagnosis of systemic sclerosis (scleroderma) in adults".)

Lipodermatosclerosis – Lipodermatosclerosis is a fibrosing panniculitis that usually occurs on the lower legs in association with chronic venous insufficiency. Patients present with indurated, sometimes circumferential plaques that may give the lower leg the appearance of an inverted champagne bottle. (See "Clinical manifestations of lower extremity chronic venous disease", section on 'Lipodermatosclerosis'.)

Carcinoma en cuirasse and postirradiation morphea – Lesions involving the breast should be biopsied to exclude carcinoma en cuirasse, a rare condition that occurs most frequently in the setting of breast cancer. Tumor infiltrates skin and subcutaneous tissue, causing diffuse sclerotic changes on the chest. Morpheaform changes in the breast also rarely occur as a complication of radiation therapy (picture 11) [51-53]. (See "Clinical manifestations and evaluation of locoregional recurrences of breast cancer", section on 'Postmastectomy recurrence'.)

Additional disorders in the differential diagnosis are provided in a table (table 2).

RELATED DISORDERS

Lichen sclerosus — Clinical findings indicative of extragenital or genital lichen sclerosus, conditions that usually manifest as atrophic white patches with finely wrinkled surfaces, may occur in patients with morphea, particularly those with circumscribed or generalized morphea. An increased risk for lichen sclerosus in this population is supported by a prospective study of 76 patients with morphea and 101 controls that found genital lichen sclerosus in 38 percent of the patients with morphea, compared with only 3 percent of controls (odds ratio 19.8, 95% CI 5.7-106.9) [54]. Extragenital lichen sclerosus most commonly occurs on the trunk and proximal extremities (picture 12A-C). The labia minora, labia majora, glans penis, penile prepuce, and penile foreskin are frequent sites for genital disease (picture 13A-B). (See "Extragenital lichen sclerosus" and "Vulvar lichen sclerosus" and "Balanitis in adults".)

The relationship between lichen sclerosus and morphea remains controversial. It is unclear whether the appearance of lesions consistent with lichen sclerosus represents the simultaneous occurrence of two separate disorders or the development of clinical findings that resemble lichen sclerosus in lesions of morphea.

Atrophoderma of Pasini and Pierini — Atrophoderma of Pasini and Pierini is an idiopathic disorder that presents with single or multiple well-demarcated depressed patches. The areas of depression exhibit a cliff drop-like appearance. Lesions are usually round or oval, ranging in size from a few centimeters to large, expansive lesions. The trunk is most commonly involved, and lesions tend to have a symmetrical distribution.

The relationship between atrophoderma of Pasini and Pierini and morphea is unclear. Atrophoderma of Pasini and Pierini may represent the atrophic stage of plaque-type morphea or may be a separate disorder.

Eosinophilic fasciitis — Eosinophilic fasciitis, or Shulman syndrome, is a disorder that is characterized by the rapid onset of symmetric, painful, large, edematous plaques that evolve into fibrotic lesions. Some cases appear to be precipitated by trauma. (See "Eosinophilic fasciitis".)

The extremities are the most common sites of involvement. Similar to deep morphea, linear depressions (the "groove sign") may be present in involved areas. Laboratory abnormalities include peripheral eosinophilia, hypergammaglobulinemia, and an elevated erythrocyte sedimentation rate (ESR).

A history of sudden onset plus histopathologic findings demonstrating a characteristic marked thickening of the fascia accompanied by a mixed inflammatory infiltrate with lymphocytes, histiocytes, plasma cells, and eosinophils may help to distinguish this disorder from deep morphea. However, in some cases, the disorders cannot be distinguished [55]. Clinical findings consistent with morphea and eosinophilic fasciitis may also coexist [56-58].

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

Overview – 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 and preferentially affects females. (See 'Epidemiology' above.)

Pathogenesis – The pathogenesis of morphea is not well understood. The disorder is likely to have an autoimmune basis; genetic and environmental factors may also play a role in the development of this disease. (See 'Pathogenesis' above.)

Clinical manifestations – Morphea has a variety of clinical presentations. Lesions of morphea typically begin as inflammatory patches or plaques that evolve into firm, sclerotic plaques. Involvement may be limited to the dermis, or may extend to underlying subcutaneous fat, muscle, or bone. Atrophic changes often remain after lesion resolution. (See 'Clinical manifestations' above.)

Diagnosis – The identification of characteristic clinical findings often is sufficient for the diagnosis of morphea. Biopsy can be useful when the diagnosis is in question or to obtain information on the depth of disease. Biopsies should always extend at least into the subcutaneous fat. For sclerotic lesions, particularly those with modest clinical change, a second biopsy from unaffected skin in a similar location will assist with interpretation of the pathologic findings. (See 'Diagnosis' above.)

Role of autoantibody testing – Antinuclear antibody (ANA) levels are elevated in some patients with morphea. However, the significance of this finding is unknown, and routine testing for autoantibodies is not indicated in adults with morphea. (See 'Serum autoantibodies' above.)

Radiologic assessment of suspected deep morphea – Radiologic imaging should be performed on patients in whom clinical examination suggests the presence of morphea that extends deeper than the dermis (algorithm 1). Magnetic resonance imaging (MRI) or ultrasound can be used to assess the extent of involvement and may be useful for following disease activity during treatment. (See 'Imaging studies' above.)

Recognition of functional limitations – 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. (See "Morphea (localized scleroderma) in adults: Management", section on 'Functional impairment'.)

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Topic 13776 Version 21.0

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