Form Of Localized Scleroderma Research Articles

Methotrexate, With or Without Corticosteroids, Might Benefit Sclerosing Skin Disease

Several reports of individual cases or small case series have documented potential benefits of methotrexate for cutaneous sclerotic diseases, including linear and widespread morphea. In this retrospective analysis, researchers examined the efficacy of methotrexate in 49 patients with localized forms of scleroderma, 5 patients with eosinophilic fasciitis, 2 patients …

Localized scleroderma

Localized scleroderma, also known as morphoea, has a variety of clinical manifestations that can include systemic involvement. Early recognition, diagnosis and treatment may improve the long-term outcome. A large multicentre study coordinated by the Pediatric Rheumatology European Society has yielded important information on the epidemiology and clinical manifestations of juvenile localized scleroderma, especially as it pertains to systemic manifestations. Previous results using methotrexate and corticosteroids have been confirmed. Studies on phototherapy have also demonstrated efficacy. A new immunomodulator, imiquimod, has shown promise in an initial case series. Studies over the past year highlight the wide range of extracutaneous manifestations and different forms of localized scleroderma and suggest that treatment may be beneficial.

Pulsed High-Dose Corticosteroids Combined With Low-Dose Methotrexate in Severe Localized Scleroderma

To evaluate the efficacy of pulsed high-dose corticosteroids combined with orally administered low-dose methotrexate therapy in patients with severe localized scleroderma (LS). A prospective, nonrandomized, open pilot study. Dermatology department at a university hospital in Bochum, Germany. Patients Fifteen patients with histologically confirmed severe LS. Interventions Oral methotrexate (15 mg/wk) combined with pulsed intravenous methylprednisolone (1000 mg for 3 days monthly) for at least 6 months. Treatment outcome was evaluated by means of a clinical score, 20-MHz ultrasonography, and histopathologic analysis. Safety assessment included the monitoring of adverse effects and clinical laboratory parameters. One patient discontinued therapy. In most of the remaining 14 patients, significant elimination of all signs of active disease (inflammation) and remarkable softening of formerly affected sclerotic skin that resulted in a decrease of the mean +/- SD clinical score from 10.9 +/- 5.3 at the beginning to 5.5 +/- 2.5 at the end of therapy was observed (P < .001). Clinical improvement was confirmed by histologic and ultrasonographic assessments. No serious adverse effects were noted. These data suggest that pulsed high-dose corticosteroids combined with orally administered low-dose methotrexate therapy is beneficial and safe in the treatment of patients with LS. This treatment regimen should especially be considered for severe forms of LS in which conventional treatments have failed.

Phototherapy for scleroderma: biologic rationale, results, and promise.

Scleroderma is a chronic disease of connective tissue characterized by deposition of large amounts of collagen. Localized scleroderma affects only the skin, whereas systemic disease, systemic sclerosis, may affect the lungs, gastrointestinal tract, kidneys, and heart in addition to the skin. Although the various forms of localized scleroderma are not life threatening, they result in considerable morbidity owing to joint contracture, loss of flexibility, and disfigurement. Although many different treatments have been attempted, until now none has proven to be effective. Accumulating evidence indicates that UVA irradiation offers a genuine opportunity to ameliorate localized scleroderma and the cutaneous manifestations of systemic sclerosis.

Hemifacial atrophy (Parry-Romberg syndrome, #141300) with papillitis, retinal alterations, and restriction of motility

J AAPOS 2002;6:126-9.

Scleroderma-like cutaneous syndromes.

Several distinct entities associated with dermal fibrosis can mimic scleroderma/systemic sclerosis. The list of scleroderma-like conditions or scleroderma variants includes eosinophilic fasciitis, localized forms of scleroderma, scleredema and scleromyxedema, keloids, and environmental exposure-associated conditions including eosinophilia-myalgia syndrome and pseudosclerodermas induced by various drugs. Although these conditions are relatively uncommon, their accurate recognition is essential to avoid misdiagnosis and inappropriate therapy. The pathogenesis of these scleroderma variants appears to share similarities with each other and with that of scleroderma. Better understanding of scleroderma-like disorders is emerging through epidemiologic investigations, and in vivo and in vitro experimental research. Activation of eosinophils and disordered regulation of fibroblast collagen synthesis, apoptosis, and proliferation are recurrent findings in these disorders. The etiologic role of infection with Borrelia species or other microorganisms remains controversial. Cytokines such as transforming growth factor-beta, interleukin-4, interleukin-13, and connective tissue growth factor contribute to fibrosis in these disorders by inducing an accentuated and persistent fibrogenic response to tissue injury. The role of genetic factors in susceptibility and clinical expression of scleroderma-like conditions remains to be systematically addressed. Because of the relative rarity of these conditions, few well-controlled clinical treatment trials have been performed. In addition, there is no consensus on optimal management. Much anecdotal information and small clinical series indicate that phototherapy may have a role in the treatment of scleroderma-like conditions.

Autoantibodies to the extracellular matrix microfibrillar protein, fibrillin 1, in patients with localized scleroderma.

Serum autoantibodies to fibrillin 1, the major component of microfibrils in the extracellular matrix, recently have been reported to occur in the tight skin mouse and in patients with systemic sclerosis, but not in patients with other connective tissue diseases. This study was undertaken to determine whether antifibrillin 1 antibodies could be detected in patients with localized forms of scleroderma. Sera from 50 patients with localized scleroderma (27 with linear scleroderma and 23 with morphea) and 51 normal controls were tested for IgG and IgM antifibrillin 1 autoantibodies, using a radioimmunoassay (RIA) and a human recombinant fibrillin 1 protein (rFbn-1). Both in patients with linear scleroderma and in those with morphea, mean levels of IgM and IgG binding to rFbn-1 were significantly higher than in controls. Eight patients with linear scleroderma (30%) and 6 patients with morphea (26%) had IgG autoantibodies to fibrillin 1 (rFbn-1) by RIA, compared with 3 controls (6%) (P = 0.006 and P = 0.022, respectively). No correlations between antifibrillin 1 antibodies and active skin disease or antinuclear antibody positivity were found. Autoantibodies to fibrillin 1 occur in patients with both forms of localized scleroderma (linear scleroderma and morphea). The clinical and pathogenetic significance of this autoimmune response remains to be determined.

Eosinophilia-myalgia syndrome, eosinophilic fasciitis, and related fibrosing disorders.

Clinically distinct fibrosing processes affecting the skin, selected internal organs, or both in a characteristic pattern are a common cause of morbidity. In addition to systemic sclerosis, the prototype idiopathic fibrosing disorder, these conditions include the eosinophilia-myalgia syndrome, epidemic toxic oil syndrome, eosinophilic fasciitis, localized forms of scleroderma, keloid, and the newly described entity of fibrosing colonopathy. The pathogenesis of these disorders, although still incompletely understood, appears to share similarities with that of systemic sclerosis. Insights into these diseases have recently emerged from epidemiologic and toxicoepidemiologic investigations, in situ hybridization and polymerase chain reaction amplification of target genomes, and in vivo and in vitro experimental research. Minor contaminants in food supplements, activation and degranulation of eosinophils, altered expression of CD34 antigen on dendritic cells, disordered regulation of fibroblast apoptosis and proliferation, infection with Borrelia organisms, and cytokines such as transforming growth factor-beta, interleukin-4, and connective tissue growth factor are implicated in inducing an accentuated and persistent fibrogenic host response to injury, resulting in tissue fibrosis. In addition, humoral and cellular autoimmunity may also be implicated.

Localized forms of scleroderma, including morphea, linear scleroderma, and eosinophilic fasciitis

Under the term localized scleroderma a spectrum of conditions is classified, ranging from localized plaques of morphea of cosmetic importance only, to deep lesions of linear scleroderma and eosinophilic fasciitis, which can result in considerable morbidity. The etiology is unknown; environmental, infectious, and autoimmune causes have been proposed. In the past year, a revised classification of morphea has been presented. Additional information relating to pathogenesis, laboratory studies, and associated manifestations is reviewed.

Treatment of Severe Forms of Localized Scleroderma With Oral Corticosteroids: Follow-up Study on 17 Patients

Despite the lack of visceral involvement, localized scleroderma (LS) may be responsible for severe deformities and functional disabilities.¹No drug has been proven to be effective in the treatment of LS.^1-4In the present study, 17 patients with the most severe forms of LS were treated with oral corticosteroids in an open trial during a 10-year follow-up period in an attempt to assess the influence of oral corticosteroids on the course of LS. The inclusion criteria were the following: (1) the disease was severe and disabling and included facial scleroderma (en coup de sabre) in seven patients, linear scleroderma in five patients, and rapidly occurring generalized morpheas in five patients; (2) the diagnosis of scleroderma was established clinically and confirmed by skin biopsy specimen in 13 patients; (3) the absence of signs of progressive systemic scleroderma5 (in particular, no patient had visceral involvement); (4) treatment consisted of oral

Prevalence and Characteristics of Anti—Single-Stranded DNA Antibodies in Localized Scleroderma

Prevalence, levels, and immunoglobulin classes of anti-single-stranded DNA antibodies were determined by an enzyme-linked immunosorbent assay in 52 patients with localized scleroderma (33 with morphea, four with generalized morphea, and 15 with linear scleroderma), in 60 healthy controls, and, for comparison, in 31 patients with systemic lupus erythematosus. Localized scleroderma revealed a significant prevalence of anti-single-stranded DNA antibodies, mainly characterized by high levels and IgM and IgA isotypes. Comparison of antibody characteristics in different clinical forms of localized scleroderma showed some significant differences (levels and immunoglobulin isotypes). Comparison with systemic lupus erythematosus showed that frequency, high levels, and IgG isotype of anti-single-stranded DNA antibodies significantly prevailed in systemic lupus erythematosus, while the IgM isotype significantly prevailed in localized scleroderma. However, generalized morphea and linear scleroderma did not significantly differ from systemic lupus erythematosus as regards antibody frequency and prevalence of high antibody levels.

Toxic oil syndrome: A syndrome with features overlapping those of various forms of scleroderma

Thirty-two toxic oil syndrome (TOS) patients were selected because they presented with sclerodermalike changes and were observed during the first 36 months of evolution of the disease. Initially, these patients presented with a noncardiogenic pulmonary edema, eosinophilia, arthralgia/arthritis, peripheral edema, and myositis. Histologic investigations showed a widespread chronic interstitial infiltrate with lymphocytic vasculitis. They subsequently developed peripheral neuropathy, joint contractures, scleroderma-like changes, Raynaud phenomenon, pulmonary hypertension, sicca syndrome, and liver disease. Biopsy studies during this stage showed fibrosis and obliterating arteriopathy. Late features of TOS are musculoskeletal pain, cramps, livedo reticularis. carpal tunnel syndrome, and digital tuft changes. TOS is a new chemically induced scleroderma-like syndrome with features overlapping those of eosinophilic fasciitis, systemic sclerosis, and forms of localized scleroderma.

LICHEN SCLEROSUS ET ATROPHICUS

It is our belief that sclerosus et atrophicus, which has often been designated lichen planus sclerosus et (Hallopeau 1 ), lichen planus morphoeicus (Crocker 2 ) or white spot disease (Johnston and Sherwell 3 ) in the German literature, is a distinct entity and can be distinguished both clinically and pathologically from atrophic forms of planus on the one hand and from localized forms of scleroderma, including morphoea guttata, on the other hand. We urge the abandonment of the term white spot disease, which has been loosely employed in different countries and by different authors to designate both sclerosus 4 and morphoea guttata. 4a The present study is based on a review of 46 cases of sclerosus et atrophicus. In 19 the diagnosis was confirmed by removal of a specimen of skin for biopsy. Distinction was made between sclerosus et atrophicus and various forms of localized scleroderma,