Linear Scleroderma en coup de sabre With Associated Neurologic Abnormalities

CASE REPORTS

Case2.

A 6-year-old previously healthy boy was first noted to have decreased movement of the right side of his mouth at the age of 5. Several months later, it was noted that the palsy had progressed to include his right cheek. The patient was also experiencing mild headaches 2 to 3 times per week and intermittent abdominal pain with poor weight gain. The patient was evaluated by a neurologist and was found to have palsy of the mandibular branch of the right facial nerve. An MRI was normal, and the etiology of his neurologic changes was unexplained. No cause was found for the abdominal symptoms.

Several months after his neurologic symptoms began, his parents noted a small annular, erythematous area of alopecia on his right parietal scalp. The lesion expanded slowly over the next several months and extended anteriorly toward the forehead and posteriorly toward his occiput. Linear scleroderma was diagnosed; however, his parents were told that his skin changes were not related to his neurologic abnormalities. Treatment with monthly intramuscular triamcinolone acetonide injections was started after a trial of oral steroids was not tolerated.

At the time of presentation to our clinic, the patient's parents reported rapid expansion of the cutaneous lesion. On examination, there was a 12-cm indurated, linear plaque on the right parietal scalp that extended from just behind the ear to the frontal hairline (Fig 1). This lesion was mostly yellow in color, but the advancing edge was violaceous. On the right upper arm the patient also had four 2- to 3-cm, dull pink-brown, atrophic patches. An atrophic, smooth, elliptical patch orientated longitudinally was also noted on the right side of the patient's tongue (Fig 2). A detailed neurologic examination revealed decreased retraction and depression of the right angle of the mouth, which affected his smile. Elevation of the right angle of the mouth was slightly diminished compared with the left with nasolabial fold sparing. Taste was decreased on the right side of his tongue compared with his left. All other cranial nerves were intact. Follow-up MRIs have been normal.

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FIGURE 1

Indurated, yellowish, linear plaque on parietal scalp.

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FIGURE 2

An atrophic, smooth, elliptical patch present on the tongue.

The patient was treated with intravenous methylprednisolone and subcutaneous methotrexate. The protocol included receiving 3 consecutive days of intravenous methylprednisolone at 30 mg/kg per day followed by monthly infusions of methylprednisolone at 30 mg/kg for 3 months. Weekly subcutaneous methotrexate 7.5 mg was started in combination with the methylprednisolone. The patient's cutaneous and neurologic disease has stabilized on this regimen.

DISCUSSION

Scleroderma is a connective tissue disorder of unknown etiology that encompasses a wide range of disease from systemic involvement of internal organs to localized cutaneous involvement. When internal organ involvement is present, many experts prefer the term systemic sclerosis, although both terms continue to be used interchangeably. To add to the confusing nosology, the term “morphea” is synonymous with the localized form. Although both systemic and localized forms are characterized by sclerosis of the skin and subcutaneous tissue, localized scleroderma lacks internal organ involvement. Localized scleroderma or morphea may be subdivided into 5 main types: bullous morphea, plaque morphea, generalized morphea, deep morphea, and linear scleroderma.2 Unlike most forms of localized scleroderma, which lack extracutaneous manifestations, a subset of linear scleroderma referred to as en coup de sabre has been associated with several neurologic abnormalities.3–9

Many of the epidemiologic studies of scleroderma have come from dermatology and rheumatology centers, where referral bias influences estimates of the incidence, prevalence, and severity of this disease. Systemic scleroderma is rare in the pediatric population, and localized scleroderma has been estimated to be at least 10 times more common than systemic disease.10,11 A population-based retrospective study of Olmsted County in Rochester, Minnesota, over a 33-year period has provided some epidemiologic information regarding localized scleroderma. Of the subtypes of localized scleroderma, the predilection of linear scleroderma for childhood is well recognized.3,12 In the Minnesota study, 67% of the patients with linear scleroderma were diagnosed before the age of 18. All forms of localized scleroderma have a 3:1 female predominance except for linear scleroderma, in which males and females are affected equally.1

Linear scleroderma en coup de sabre is a rare subset of linear scleroderma defined by its characteristic location on the forehead and scalp. Clinically, it is manifested by ivory-colored, sclerotic plaques with violaceous borders distributed in a band-like fashion on the frontoparietal scalp and forehead. Alopecia of the affected scalp is common and often the presenting complaint. Lesions may extend to the nose, cheek, chin, and neck.13,14 Facial hemiatrophy may develop as a result of hypoplasia of the underlying bone and soft tissues. Progressive hemifacial atrophy (Parry-Romberg syndrome) is a related disorder characterized by progressive hemifacial atrophy without cutaneous sclerosis. Debate continues as to whether Parry-Romberg syndrome is a distinct disease entity or a variant of linear scleroderma, but many would agree that they are closely related forms of craniofacial scleroderma. The diagnosis is a clinical one that relies on the characteristic cutaneous and soft tissue findings because there are currently no diagnostic laboratory tests. ANA with homogeneous and speckled patterns may be positive in 37% to 50% of patients with linear scleroderma, and anti–single-stranded-DNA antibodies may be present.1,15,16 More specific autoantibodies such as Scl-70, anticentromere, Ro/La, and U1RNP may precede development of systemic disease, and patients with these markers should be followed closely for several years.15

Patients with localized scleroderma, by definition, have sclerosis limited to their skin and soft tissue. However, linear scleroderma, mainly the en coup de sabre subtype, often has extracutaneous associations. When linear scleroderma occurs on the extremities, local abnormalities such as limb-length discrepancy or joint contractures may occur secondary to sclerosis of the skin. In contrast, the en coup de sabre subtype of linear scleroderma is notorious for multisystem morbidity. Marzano et al3 reported the presence of ocular, oral, and neurologic abnormalities in almost half of the 17 patients identified with craniofacial involvement (including en coup de sabre, Parry-Romberg, and mixed types). Specific associations with craniofacial scleroderma reported in the literature are listed in Table 1. Development of cutaneous disease typically precedes the onset of extracutaneous manifestations. The time line for the development of systemic findings is typically on the order of months, but reports of delayed onset of neurologic disease several years later exist.4,17 Systemic signs and symptoms may not parallel cutaneous disease activity.17

Neurologic complications are the most common systemic association with linear scleroderma en coup de sabre. Complex partial seizures have been reported most frequently.5 Abnormalities on MRI and CT studies may be seen in patients with linear scleroderma en coup de sabre even in the absence of neurologic disease.6,7 Radiologic abnormalities are predominately ipsilateral to the skin disease but may be contralateral.4,8 Neuroradiologic abnormalities including cerebral atrophy, white-matter lesions, intraparenchymal calcification, meningeocortical alterations, and skull atrophy have all been described in the literature.4,6,7,9,18 Resolution and recurrence of radiologic lesions may correlate clinically with neurologic disease activity.4,9 Just as imaging may be abnormal in patients without neurologic symptoms, normal imaging can be seen despite the presence of neurologic disease as demonstrated by 2 of our patients as well as the case of a patient with facial and oculomotor nerve palsy and grand mal seizures described by Gambichler et al.19 The lack of specific and/or sensitive radiologic findings for the associated neurologic disease contributes to the difficulty in counseling these patients regarding prognosis. Certainly the presence of radiologic abnormalities warrants close clinical follow-up.

As in our third patient, brain biopsies have been performed when concerns for neoplasm arise.4,8 The reported histologic findings are variable; most cases report a perivascular infiltrate or vasculitis. Sclerosis, fibrosis, and gliosis involving brain parenchyma, meninges, and vasculature have also been reported.8,20 As in our patient and in keeping with the neuroimaging results often described in these patients, scattered calcifications can be seen, often in association with blood vessels.20

The pathogenesis of localized scleroderma is not completely understood. Most of the proposed pathogenic mechanisms relate to systemic scleroderma. Similar to systemic sclerosis, endothelial cell damage leading to increased fibroblast activity and ischemia through luminal narrowing with subsequent modification of collagen production has been proposed as the pathogenic mechanism.15,21,22 The inciting event for such microvascular damage remains unknown. Borrelia burgdorferi infection, although implicated in Europe and Japan, has not proven to be a major factor in the United States.12 Genetic factors also are thought to play a role, with higher incidence of connective tissue disease in family members. An association with preceding trauma has been found, particularly in the pediatric population.23

Linear scleroderma is usually a self-limited disease. Regression or softening of skin lesions often occurs, but complete resolution is unusual and reactivation can occur.21 Spontaneous resolution of extracutaneous changes may occur, but unfortunately pediatric patients are at an increased risk of long-term morbidity because they may have decreased growth of underlying bones and may develop limb and facial asymmetry.12,16,17 If cosmetic disfigurement develops, psychological disability may be pronounced.12 Additional orthopedic sequelae such as flexion contractures may occur when the skin overlying joints is involved.16 Reports of progression to systemic scleroderma in the pediatric population are exceedingly rare.3,12,21

Adequate treatment for linear scleroderma remains elusive. The self-limited nature of the disease coupled with mixed results obtained from small, uncontrolled trials with most therapeutic regimens makes decisions regarding treatment difficult. Topical, intralesional, and systemic corticosteroids reduce the inflammation of skin lesions. In an open-label study, use of topical calcipotriene in 12 patients with localized scleroderma (including linear scleroderma) led to improvement in the cutaneous lesions for all of them.24 Systemic agents used when more aggressive therapy is warranted include vitamin E, vitamin D₃ (oral calcitriol), aminobenzoate potassium, penicillin, retinoids, diphenylhydantoin, interferon-γ, immunosuppressive agents, and UV-A therapy.8,12,21,25 Immunosuppressive agents that have been used with reported efficacy include hydroxychloroquine, D-penicillamine, methotrexate, cyclosporine, and cyclophosphamide.8,12,21,25,26 For patients with disfiguring facial atrophy, reconstructive surgery may be beneficial.

In our patients, neurologic manifestations occurred before or concurrent with the diagnosis of linear scleroderma en coup de sabre. Their neurologic symptoms were previously unexplained when they presented to dermatology for evaluation of their skin lesions. These cases illustrate the need for placing craniofacial linear scleroderma on the differential of any patient with neurologic abnormalities such as partial seizures. A thorough examination of the skin should be performed in these patients, with particular attention to the face and scalp. Long and careful follow-up of these patients is prudent based on evidence that neurologic abnormalities may develop at any time during the course of the disease.