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

Author:Heidi Jacobe, MDSection Editor:Jeffrey Callen, MD, FACP, FAADDeputy Editor:Abena O Ofori, MD
Literature review current through: Nov 2017. | This topic last updated: May 25, 2017.

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 "Overview
of the clinical manifestations 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 "Treatment of morphea (localized scleroderma) in adults", 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 "Localized scleroderma in childhood".)

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 to 1 [5].

Ethnicity also may influence the risk for morphea. The results of retrospective studies suggest that the
disorder may be more common in Caucasians and may occur at a lower than expected frequency in
African-Americans [3,4]. Additional studies are necessary to confirm these findings.

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 "Localized
scleroderma in childhood", section on 'Etiology'.)

●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].
●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 [14].
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 [7,14]. 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 [7,14]. Of note, increased levels of vascular adhesion
molecules have been detected in serum from patients with morphea [15].
●Genetics – Although susceptibility genes for the development of morphea have not been identified,
reports of familial case clusters [4,16,17] and the detection of increased rates of autoimmune disorders
in family members of patients with morphea [4,9,18] suggest a genetic contribution.
CLINICAL MANIFESTATIONS — Morphea is divided into several subtypes [19], 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 7B).

After a period of months to years, sclerotic plaques soften and transition into hypopigmented or
hyperpigmented atrophic plaques (picture 6B). 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.

Variants — There is a lack of consensus on the appropriate classification system for morphea [14,19]. We
prefer the clinically-based division of morphea into circumscribed, generalized, linear, and mixed forms
(table 1).

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 is the most
common subtype of morphea in children [1,3-6,20-22]. Less common variants of morphea include
guttate, bullous, and keloidal disease. (See "Localized scleroderma in childhood", section on 'Clinical
manifestations'.)

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 [21]:

●Circumscribed ‒ 65 percent
●Generalized ‒ 8 percent
●Linear ‒ 6 percent
●En coup de sabre (a form of linear disease) ‒ 3.5 percent
●Deep (morphea profunda) ‒ 3.5 percent
●Guttate or bullous ‒ less than 1 percent each
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. (See "Localized scleroderma in childhood", section on
'Circumscribed (plaque) morphea'.)

Deep morphea — Deep morphea, or morphea profunda, is a form of circumscribed morphea that
primarily involves the deep dermis and subcutaneous tissue and may extend to underlying fascia and
muscle. Plaques are poorly circumscribed and often occur in a symmetrical distribution (picture 2).
Clinical examination reveals lesions that have an indurated texture and feel tightly tethered to underlying
fascia and muscle. Linear areas of depression (the "groove sign") may be present at sites with underlying
tendons and ligaments. Other forms of morphea, particularly linear and generalized morphea, may also
demonstrate involvement of deep tissues.

Generalized morphea — Generalized morphea is defined by the presence of ≥4 morpheaform plaques

involving at least two different anatomic sites (picture 3A-B) [14]. In contrast to systemic sclerosis,
generalized morphea does not present with sclerosis primarily involving acral skin or sclerodactyly.
Lesions of generalized morphea frequently begin on the trunk before spreading acrally, and the fingers
and toes are spared. (See "Overview of the clinical manifestations of systemic sclerosis (scleroderma) in
adults".)

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 4) [23,24]. (See "Localized scleroderma in childhood", section on 'Generalized morphea'.)

Linear morphea — Linear morphea (aka linear scleroderma) manifests as morpheaform plaques
arranged in a linear distribution. Lesions most frequently occur on the extremities or face, but may also
appear on the trunk, where the differential diagnosis includes circumscribed morphea (picture 5A-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 [25]. (See
"Localized scleroderma in childhood", 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 6A-B). Bone marrow inflammation has also been reported in patients with
linear morphea [26,27].

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 7A-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 "Localized
scleroderma in childhood", section on 'Linear scleroderma of the face'.)

It is controversial whether progressive facial hemiatrophy (Parry-Romberg syndrome), which is

characterized by unilateral atrophy of the skin, soft tissues, muscles, and/or bones of the face, is a
variant of linear morphea or an independent disorder (picture 8). In this condition, facial atrophy may be
accompanied by classic linear morphea lesions on the face or elsewhere. (See "Localized scleroderma in
childhood", section on 'Linear scleroderma of the face'.)

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

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 [21]. Raynaud phenomenon also has been reported in a minority
of children and adults with morphea [4,21].

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 tests [28].
Occasionally, 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 children with en coup de sabre have neurologic or ocular complications,
including seizures, headaches, uveitis, episcleritis, and adnexal abnormalities involving the eyelids,
eyelashes, or lacrimal glands; the proportion of adults with these findings is uncertain [18,29-31]. En
coup de sabre or other lesions involving the face also may produce dental malocclusion, altered
dentition, and atrophy of tongue and salivary glands. The approach to patients with suspected joint,
neurologic, ocular, or oral involvement is discussed separately. (See "Treatment of morphea (localized
scleroderma) in adults", section on 'Other interventions'.)

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).
Infrequently, patients with systemic sclerosis develop morpheaform plaques [32]. 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 "Diagnosis and differential 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.
All biopsy specimens should include subcutaneous fat. 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 performed.

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 and 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.

The histopathologic findings may correlate with patient symptoms. 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 [33]. The study also found a nonstatistically significant trend towards an association
between severe inflammation and symptoms of pain and functional limitation.

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
[4,6,21,34,35]. 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, anti-topoisomerase IIα, antiphospholipid, and rheumatoid factor [4,10,34,36-41].
Although associations between certain autoantibodies and the severity of linear morphea have been
reported [6,35], 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), magnetic resonance imaging (MRI) should be used to assess lesion depth
and involvement of subcutaneous structures [27,42]. Ultrasonography is an alternative to MRI [43]. 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 [42].

MRI and ultrasound have also been used to monitor disease activity [27,44]. With both modalities,
discussion with the radiologist is essential to correlate the radiologic findings with clinical disease.

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) [42].

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 "Overview of the clinical manifestations of systemic
sclerosis (scleroderma) in adults" and "Diagnosis and differential diagnosis of systemic sclerosis
(scleroderma) in adults", section on 'Differential diagnosis'.)
●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)
[45-47]. (See "Management of locoregional recurrence of breast cancer after mastectomy", section on
'Presenting signs and symptoms'.)
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) [48]. 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 [49]. Clinical findings consistent with morphea and eosinophilic
fasciitis may also coexist [50-52].

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 and preferentially affects females. (See 'Epidemiology' above.)
●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.)
●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.)
●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.)
●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 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.)
●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 "Treatment of
morphea (localized scleroderma) in adults", section on 'Other interventions'.)