Clinical Appearance Classification

Plaque Morphea

Morphea en Plaque

This commonest form of LS is defined by the presence of lesions >1cm in diameter, occurring in 1 or 2 anatomical sites (Peterson et al. 1995 & 1997). The trunk is the most commonly involved site (41-74% patients), but plaques can occur anywhere, including the face and neck (12-13% of patients) (Christi-anson et al. 1956; Peterson et al. 1997). Onset is usually slow and insidious. Circumscribed oval patches may be erythematous and oedematous in the earliest stages, becoming indurated, yellowish-white or ivory coloured (Figure 2a). A surrounding violaceous halo, the "lilac ring", suggests active inflammation, but was documented in only 43% of patients in one study (Peterson et al. 1997). The patches subsequently become waxy, shiny and sclerotic. Over months to years they soften, become atrophic and hypo- or hyperpigmented. Atrophy may involve the epidermis, dermis and/or subcutaneous tissue, producing wrinkling or depression of the skin surface. Lesions may be pruritic and/or paraesthetic. Loss of appendigeal structures results in reduced hair growth and decreased sweating.

Guttate Morphea

These lesions resemble morphea en plaque, but are smaller (<1 cm in diameter), and occur on the upper trunk as multiple, faintly erythematous oval lesions, which become yellowish, mildly indurated and which resolve leaving pigmentary changes. Winkelmann (1985) and Tuffanelli (1998) consider this to be a type of lichen sclerosis associated with morphea. The histologic features of lichen sclerosus and its frequent occurrence with other morphea subtypes (both in the same patients and the same biopsy specimen) suggest that these conditions share a common pathogenesis (Uitto et al. 1980). Interestingly, patients with lichen sclerosus specifically demonstrate antibodies to extracellular matrix protein 1 (Oyama et al. 2003; Oyama et al. 2004). Lesions of lichen sclerosis, but not of morphea, demonstrate discontinuities of the basement

Hemifacial Pediatric Violaceous

Fig. 2. a) Morphea en plaque with induration and pigmentary changes. b) Generalized morphea of the chest, with erythema, edema and induration. Note sparing of the areolae. c) Linear lesion on the thigh. d) Eosinophilic fasciitis showing erythema, swelling and induration

(Peau d'orange)

Fig. 2. a) Morphea en plaque with induration and pigmentary changes. b) Generalized morphea of the chest, with erythema, edema and induration. Note sparing of the areolae. c) Linear lesion on the thigh. d) Eosinophilic fasciitis showing erythema, swelling and induration

(Peau d'orange)

membrane zone (Kowalewski et al. 2004) possibly in relation to the presence of these auto-antibodies. Whether patients with morphea or clinical overlap with lichen sclerosus develop auto-antibodies with this specificity is unknown.

Atrophoderma of Pasini and Pierini

Atrophoderma is uncommon and thought to represent a superficial abortive form of morphea with a benign course (Jablonska 1975b; Kencka et al. 1995).

It usually occurs in childhood, with lesions distributed symmetrically on the trunk (Canizares et al. 1958), but it may occur in a zosteriform distribution (Wakelin and James 1995). Superficial morphea is a term coined by McNiff and colleagues in 1999 to describe patients with pigmentary changes, minimal cutaneous induration and superficial reticular dermal change (McNiff et al. 1999) and that likely describes a condition that overlaps with atrophoderma (Jablonska and Blaszczyk 2004). Atrophoderma of Moulin is a term used to describe clinically and histologically identical, but linear lesions, which follow the lines of Blaschko (Wollenberg et al. 1995). They consist of depressed areas of skin, typically with a sharply demarcated "cliff-drop" border, and grey or blue-brown pigmentation. The histology resembles the late atrophic stages of morphea. In a study of 139 patients followed for a mean of 10 years, areas of induration appeared within the lesions in 17% and plaques of morphea elsewhere on the body were found in 22% of cases (Kencka et al. 1995).

Keloid/Nodular Morphea

This rare subtype is characterized by the presence of keloid-like nodules in patients with previous or co-existent morphea elsewhere. Lesions are commonest on the upper trunk and may coalesce or occur in a linear pattern (Krell et al. 1995; Hsu et al. 1999). Histology shows homogenization and thickening of collagen bundles with an increase in mucin (Micalizzi et al. 1994). Such keloidal and nodular reactions have also been described in the setting of progressive systemic sclerosis (Cannick et al. 2003; Labandeira et al. 2003; Rencic et al. 2003) and likely arise in patients with scleroderma (either localized or progressive) predisposed to keloid formation.

Generalized morphea

Morphea is referred to as "generalized" when plaque type lesions occur in 3 or more anatomical sites (Peterson et al. 1995). Commonest sites are the trunk, upper thighs and lumbosacral region. Plaques are often distributed symmetrically and may become confluent (Figure 2b). Plaques at varying stages of evolution usually coexist.

Bullous morphea

This rare subtype is characterized by the presence of tense subepidermal bullae, which appear to develop as a result of subepidermal oedema, and which may occur in the presence of any of the subtypes of morphea (Su and Greene 1986; Kobayasi et al. 1990; Daoud et al. 1994). In a study of 13 cases, bullae were most frequent on the legs, and lymphatic dilatation, attributed to obstruction from sclerosis, was observed in 77% of the patients (Daoud et al. 1994).

Linear Morphea

Linear forms include linear morphea, en coup de sabre lesions and progressive hemifacial atrophy. Sclerotic lesions are distributed in a linear, bandlike pattern (Figure 2c). Clinical evidence of inflammation, the "lilac ring" is seen less often in this type (19%)(Peterson et al. 1997). Their distribution may be dermatomal, however, it has been argued that they follow Blaschko's lines and may thus occur partly as a result of postzygotic mosaicism (Hauser et al. 1996; Itin and Schiller 1999). Frontoparietal lesions in particular, appear "Blaschkoid" rather than dermatomal (Soma and Fujimoto 1998; Itin and Schiller 1999). Trauma is more often sited as a possible precipitating factor in this type of morphea (Falanga et al. 1986; Yamanaka and Gibbs 1999). Facial and limb asymmetry caused by impaired growth of the bones and soft tissues in the affected area, as well as multiple joint contractures, can cause severe cosmetic, orthopedic, and psychologic problems.

Linear Morphea

Unilateral lesions predominate, although bilateral lesions are described in 5.5% (Christianson et al. 1956) - 46%(Falanga et al. 1986) of patients. They most often occur on the lower limbs. Multiple sites are involved in up to 60% of cases, and plaque forms often coexist on the trunk (Falanga et al. 1986). Generalised arthralgias and edema of the involved extremity can precede the onset of disease (Christianson et al. 1956). Induration can involve the dermis, subcutis, underlying muscle and bone. Multiple joint contractures, are common, occurring in 56% of cases in one study (Falanga et al. 1986). Myopathic changes, atrophy and weakness of involved and adjacent muscles may occur (Uziel et al. 1994). Discrepancies of limb length are a frequent complication in children with limb involvement (Liu et al. 1994).

En Coup de Sabre

This type affects the face and scalp. Lesions generally follow one of two lines. The first descends vertically from the frontal scalp to the side of the nose, adjacent to the midline. The second starts close to the vertex and progresses forwards to the lateral forehead, and then medially towards the inner can-thus (Soma and Fujimoto 1998; Blaszczyk and Jablonska 1999). Bilateral lesions occur rarely (Rai et al. 2000). Concomitant linear and plaque lesions at other sites are commoner (Falanga et al. 1986; Peterson et al. 1997). The sclerosis is thought to involve the skin and subcutis first, and later extend to underlying fascia and bone (Jablonska 1975a). Epilepsy is the most frequent neurological complication occurring in up to 10% (Jablonska 1975a). Ocular and auditory complications may also be present (Luer et al. 1990; David et al. 1991). Intracranial calcification and white matter abnormalities have been noted on CT and MR scans (Liu et al. 1994). One case study suggests sclerodermatous involvement of underlying brain tissue (Chung et al. 1995): dense sclerosis with increased collagen deposition, gliosis, scattered calcifications, and thickened sclerotic blood vessel walls were present in the involved dura and brain. The presence of oligoclonal banding on CSF examination, of lymp-hocytic inflammation on brain biopsy and of improvement in MRI white matter abnormalities following corticosteroid treatment all attest to the primary inflammatory nature of the underlying CNS lesions (Stone et al. 2001; Unter-berger et al. 2003).

Progressive Hemifacial Atrophy (Parry-Romberg Syndrome)

This is thought to be a primary atrophic disorder of the subcutaneous tissue, muscle and bone. The absence of skin induration distinguishes it from "en coup de sabre" lesions (Sakuraoka et al. 1992). Progressive hemifacial atrophy (PHA) often begins at the sites described above, and then extends to involve the cheek, tongue and mandible. Hypoplasia of the maxilla and mandible may cause marked facial asymmetry, particularly if lesions first develop in early childhood. There is overlap between the two conditions (Menni et al. 1997; Blaszczyk and Jablonska 1999). In one series 20/58 cases of linear scle-roderma of the face (en coup de sabre) showed transition to PHA (Jablonska 1975a). Similar radiographic and clinical neurologic abnormalities and ocular complications are encountered, but may be commoner in PHA (Fry et al. 1992; Liu et al. 1994). Morphea lesions elsewhere have been noted in patients with PHA and both groups with PHA (without skin induration) and those with "en coup de sabre" lesions have abnormalities in cerebral blood flow as detected by SPECT analysis (Blaszczyk et al. 2003).

Deep Morphea

In deep morphea the sclerotic process occurs in the subcutaneous tissue, in other words, in the fat, fascia or superficial muscle. The various subtypes are classified according to the level of maximal involvement on a deep tissue biopsy. Lesions are frequently bilateral and symmetrical and involve the upper and lower limbs (Peterson et al. 1997).

Subcutaneous Morphea

The primary site of involvement is the subcutaneous fat, although the fascia may also be involved, making it difficult to distinguish this form from "morphea profunda". In Person and Su's description of 16 cases, plaques were usually extensive, ill-defined and bound-down, and showed rapid centrifugal progression (Person and Su 1979). Disease activity ranged from 6 months to 7 years. Five patients had coexistent plaques of morphea or lichen sclerosus, and five had a peripheral eosinophilia.

Morphea Profunda

Su and Peterson (1981) originally suggested a number of diagnostic criteria: the presence of diffuse, taut, bound-down deep cutaneous sclerosis; of significant hyalinization and thickening of collagen bundles in both the subcutaneous fat and fascia; and a response to treatment with antimalarials or corticosteroid. Some authors do not distinguish between this subtype and subcutaneous morphea (Weedon 1997). Solitary lesions have been described both in children (Kobayashi et al. 1991) and adults (Whittaker et al. 1989). Recently 3 unusual cases of deep linear, primarily atrophic lesions, without preceding inflammation or sclerosis, involving the subcutis and deeper tissues were described. They may have a more benign outcome. Their relationship to morphea is underscored by the coexistence of hemifacial atrophy in one case (Blaszczyk et al. 2000).

Eosinophilic Fasciitis (Shulman Syndrome)

This condition is characterized by a diffuse sclerosis, predominantly involving the fibrous septa of the subcutis and deep fascia, a high ESR, hypergam-maglobulinaemia and peripheral eosinophilia (Mitchet et al. 1981; Shulman 1974). Inflammatory changes may extend into the underlying muscle (Weedon 1997). It usually occurs on the extremities, but spares the hands and feet (Figure 2d). It can result in severe joint contractures and associated morbidity. Associated haematologic abnormalities including aplastic anemia, thrombocytopenia and leukaemia have been noted (Doyle and Ginsburg 1989). Other subtypes of morphea may be present (Miller 1992).

Disabling Pansclerotic Morphea of Childhood

This extremely rare variant is at the most severe end of the clinical spectrum. Rapid progression of deep cutaneous fibrosis occurs, extending to involve muscle, fascia and bone (Diaz-Perez et al. 1980). It usually results in severe joint contractures and cutaneous ulceration. Unlike other forms of LS, this disease does not undergo spontaneous remission. Increased serum IgG, a positive ANA and peripheral eosinophilia are documented (Scharffetter-Kochanek et al. 1995; Todd et al. 1998).

Associated Symptoms

Arthralgias are relatively common (40% of patients) (Christianson et al. 1956; Uziel et al. 1994b). Synovitis has been documented mainly in deep forms (Peterson et al. 1997). Associated pulmonary and esophageal involvement can occur. Routine testing revealed that 7/41 (17%) patients had esophageal dysmotility and 9/53 (17%) had abnormal gas transfer on lung function testing. These abnormalities were asymptomatic over 4yrs follow up in all but 2 of the patients (Dehen et al. 1994). In a series of 16 cases of subcutaneous morphea, 4/10 and 3/10 patients investigated had asymptomatic abnormal lung function and esophageal dysmotility respectively (Person and Su 1979). This suggests that the frequency of internal involvement may be underestimated. Other associated findings include carpal tunnel syndrome (Winkelmann et al. 1982) and vertebral anomalies (in particular spina bifida) present in 47% of 68 patients examined radiographically (Christianson et al. 1956). Associated cutaneous diseases include lichen sclerosus (see above), vitiligo, alopecia areata, and lichen planus (Uitto et al. 1980; Winkelmann 1985). Morphea may also occur with other connective tissue diseases, including lupus erythematosus (Dubois et al. 1971; Umbert and Winkelmann 1978), dermatomyositis and rheumatoid arthritis (Jablonska 1975b). Morphea has also been associated with Hashimoto's thyroiditis (Lee et al. 2002), another auto-immune condition.

Laboratory Abnormalities

Eosinophilia occurs in all types of morphea, but is more pronounced in patients with generalized and deep forms. Levels of eosinophilia may parallel disease activity (Falanga et al. 1986). A mean of 5.4% (percentage of total leukocytes) at diagnosis and 2.8% at last follow up was observed in Peterson et al's series (Peterson et al. 1997). Polyclonal hypergammaglobulinemia and a positive rheumatoid factor were present in 50% and 26% respectively of 53 patients with linear or generalized morphea. Both were correlated with more extensive, active disease (Falanga et al. 1986). In recent studies on Hep2 cells, anti-nuclear antibody (ANA)-positivity occurred in 46-76% of cases, in decreasing order of frequency in generalized, linear and plaque forms (Falanga et al. 1986; Rosenberg et al. 1995; Uziel et al. 1994b). Antibodies to ssDNA are usually of the IgM subtype (Ruffatti et al. 1991), and are seen mainly in patients with longstanding, extensive linear or generalized disease (Falanga et al. 1985; Rosenberg et al. 1995). Antihistone antibodies may also be present but anti-Scl 70 (polymerase III) and anticentromere antibodies are rare. Anti-phospholipid antibodies of both the IgM and IgG subtypes are detected with increased frequency in patients with generalized and linear morphea, in the absence of increased thrombotic events (Sato et al. 2003). The similarity in auto-antibody specificities between drug-induced lupus and morphea has prompted the suggestion that morphea, like drug-induced lupus, is an environmentally driven disease. Recent studies have identified serum autoantibodies to fibrillin 1 (Arnett et al. 1999), the major component of microfibrils in the extracellular matrix, and to Hsp73 (Fujimoto et al. 1995). It is likely that these autoantibodies are by-products of the underlying pathologic process, rather than being primarily pathogenic. Unique disease-associated auto-antibody profiles may nevertheless give a clue to pathogenesis. In this regard, 76% of patients with localized disease and 85% of patients with generalized disease are found to have antibodies to anti DNA topoisomerase IIa in contrast to only 14% of patients with progressive systemic sclerosis (Hayakawa et al. 2004). This is a ubiquitous enzyme that modulates the topologic state of DNA and it was hypothesized that, as this protein is selectively cleaved during Fas-mediated apoptotic cell death, it may be presented to the immune system during the endothelial cell apoptosis detected in early morphea lesions. Most patients (41/46) with morphea and 13/13 patients with generalized morphea were recently shown to have antibodies to a cytosolic form of superoxide dismutase (Cu/Zn SOD or SOD1) (Nagai et al. 2004). In patients with generalized disease, the presence of IgM antibodies to Cu/Zn SOD correlated with severity of disease. These observations suggest that reactive oxygen species may participate in disease pathogenesis.

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  • PETRA EGGER
    Is morphea associated with rhumetoid arthritis?
    2 years ago

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