Increased expression of tenascin in the dermis in scleroderma

The expression of tenascin, a recently discovered extracellular matrix protein, was studied by immunohistochemical techniques in scleroderma skin and compared with its distribution in normal skin. In progressive systemic sclerosis, a marked increase in tenascin content was observed in the superficial reticular dermis. In localized scleroderma, the deposition of tenascin was increased both in the superficial and deep dermis of involved skin, whereas in clinically uninvolved skin the distribution of tenascin was the same as in normal control skin, i.e. the papillary dermis and peri-appendiceal zone. The distribution of tenascin did not strictly parallel that of fibronectin. These findings and the current knowledge of tenascin biology suggest that the overproduction of tenascin in scleroderma dermis could be secondary to stimulation of fibroblasts by immune cell-derived cytokines, or could be due to abnormal fibroblasts, or a subpopulation of fibroblasts, producing high levels of this extracellular matrix protein.     

Nodular Scleroderma in a Worker Using a Silica-containing Abrasive

A patient with progressive systemic sclerosis and high levels of serum IgE developed multiple papules at/on an area of non-sclerotic skin. Histologic examination of the papule revealed the typical features of scleroderma. For several years, the patient had been working on polishing watches with an abrasive agent composed mainly of aluminum, chromium dioxide, and silica. An association of the abrasive agent, especially of the silica component, with the scleroderma was circumstantially suspected. To the best of our knowledge, this is the first report of nodular scleroderma which occurred in the course of PSS being associated with chemical agents.     

Keloid morphea and nodular scleroderma: two distinct clinical variants of scleroderma?

BACKGROUND: For nearly a century, the terms "keloid morphea" and "nodular scleroderma" have been used interchangeably without defined clinical or histologic criteria. OBJECTIVE: To define the conditions "keloid morphea" and "nodular scleroderma" by correlating the clinical and histologic features. METHODS: We retrospectively identified six patients with keloidal lesions and nodules from 70 consecutive patients with scleroderma seen in the dermatology clinic. The clinical presentation and histopathological findings were reviewed. RESULTS: Six of 70 patients with scleroderma (45 systemic and 25 morphea) exhibited keloidal or nodular lesions. All these patients had systemic sclerosis. Clinically one patient (case 1) had nodules; five (cases 2-6) had keloids. The nodular lesions had histologic findings consistent with keloid, while the keloidal plaques were variably keloids or morphea histopathologically. There was no correlation between the clinical morphology and the histologic findings, except for cases 5 and 6. These patients were African-American, with a family history of keloids and typical keloids clinically and histologically that developed from sites with normal skin. CONCLUSION: Keloid morphea and nodular scleroderma are clinical terms that describe keloidal and nodular lesions in patients most commonly with scleroderma. The clinicopathologic association is variable. Based on a review of the English literature and our series of six patients, we identified two clinical variants; (1) keloidal or nodular lesions arising from sclerodermatous skin with histologic findings of keloid or scleroderma, (2) typical keloids clinically and histologically, arising in normal skin in patients with a family history of keloids. Awareness of these entities is important for proper diagnosis of the cutaneous lesions and for recognizing that the cutaneous findings may be a sign of systemic sclerosis     

Scleroderma and thyroid diseases

The authors report a prospective study of the thyroid function of 18 consecutive patients with systemic scleroderma and 7 patients with morphea. A history was taken and patients were examined for thyroid disease. The patients were tested for free thyroxin, TSH, cholesterolemia, circulating TeBG, anti-microsomial and anti-thyroglobulin antibodies and had a TRH test. The incidence of thyroid diseases was correlated with an age and sex-matched control population consisting of 2,534 subjects of the Loire department. None of the patients with morphea had a history of thyroid pathology and the thyroid screenings were within normal limits. A familial history of thyroid disease was found in 7 out of 18 patients with systemic scleroderma, and 8 out of 18 patients had a thyreopathy (one Hashimoto's disease, one Graves' disease, one toxic adenoma, one hypothyroidism, two euthyroid goiters, two nodular thyroids). The TRH test only revealed a toxic adenoma. A thyroid disease preceded systemic scleroderma in 5 out of 18 cases with delays ranging from 1 to 38 years. In 3 cases, the thyroid disease occurred within two years after the onset of systemic scleroderma. The prevalence of thyroid disease was significantly higher than in a comparable population sample of subjects from the same geographic region (p less than 0.01). The authors review the literature and discuss the physiopathologic relationships between the two clinical entities. The authors suggest to perform a thyroid screening (ultrasensitive TSH assay) on all patients with systemic sclerosis and especially on those whose clinical follow-up is atypical and on those with a familial and/or personal history of thyroid disease.     

A case of nodular scleroderma

Nodular scleroderma is a rare complication of systemic sclerosis; the pathogenetic implications are still unknown, although many factors are supposed to play a role in lesion development. We report the case of a young woman suffering from systemic sclerosis, who developed nodular lesions during therapeutic management with D-penicillamine and plasmapheresis. In order to better understand the essence of this disease, we examined all the possible pathogenetic mechanisms that could be implicated in nodular lesion development.     

Dermatopontin expression is decreased in hypertrophic scar and systemic sclerosis skin fibroblasts and is regulated by transforming growth factor-beta1, interleukin-4, and matrix collagen

Dermatopontin is a recently discovered extracellular matrix protein with proteoglycan and cell-binding properties and is assumed to play important roles in cell-matrix interactions and matrix assembly. In this study we examined the expression of dermatopontin mRNA and protein in skin fibroblast cultures from patients with hypertrophic scar and patients with systemic sclerosis. Dermatopontin mRNA and protein levels were reduced in fibroblast cultures from hypertrophic scar lesional skin compared with fibroblasts from normal skin of the same hypertrophic scar patient. Fibroblast cultures from systemic sclerosis patient involved skin also showed significantly reduced expression of dermatopontin compared with normal skin fibroblasts from healthy individuals. We also investigated the effects of cytokines and matrix collagen on dermatopontin expression in normal cultured fibroblasts. Transforming growth factor-beta1 increased dermatopontin mRNA and protein levels, while interleukin-4 reduced dermatopontin expression. Substrate coated with type I collagen reduced dermatopontin mRNA levels, the reduction being more prominent in three-dimensional collagen matrices. Our results suggest that the decreased expression of dermatopontin is associated with the pathogenesis of fibrosis in hypertrophic scar and systemic sclerosis, and that the effect of the cytokines and matrix collagen on dermatopontin may have important implications for skin fibrosis.     

Scleroderma: Nomenclature,etiology, pathogenesis,prognosis, and treatments: Facts and controversies

Scleroderma refers to a heterogeneous group of autoimmune fibrosing disorders. The nomenclature of scleroderma has changed dramatically in recent years, with morphea (localized scleroderma), limited cutaneous systemic sclerosis, diffuse cutaneous systemic sclerosis, and systemic sclerosis sine scleroderma encompassing the currently accepted disease subtypes. Major advances have been made in the molecular studies of morphea and systemic sclerosis; however, their etiologies and pathogenesis remain incompletely understood. Although morphea and systemic sclerosis demonstrate activation of similar inflammatory and fibrotic pathways, important differences in signaling pathways and gene signatures indicate they are likely biologically distinct processes. Morphea can cause significant morbidity but does not affect mortality, whereas systemic sclerosis has the highest disease-specific mortality of all autoimmune connective tissue diseases. Treatment recommendations for morphea and systemic sclerosis are based on limited data and largely expert opinions. Current collaborative efforts in morphea and systemic sclerosis research will hopefully lead to better understanding of the etiology and pathogenesis of these rare and varied diseases and improved treatment options.     

Scleroderma

ABSTRACT: Scleroderma presents a formidable therapeutic challenge for both the physician and the patient. Over the years many medications and interventions have been reported to be beneficial in scleroderma. With equal regularity, however, when put to the test of the randomized controlled trial, many of these same medications have subsequently been shown to be ineffective. This is true for both the localized and systemic forms of the disease. Two of the most recent additions to this inauspicious list for systemic sclerosis include D-penicillamine and methotrexate. At the very least these outcomes should point to our deficiencies in understanding the pathogenesis of this unusual disorder. It should raise the possibility that collagen and inflammatory or immune cells are not good therapeutic targets and new targets should be sought. Despite the scope of these problems and the lack of definitive therapy, there is a great deal an individual physician can do to help a patient living with scleroderma. This article presents management approaches to patients with either localized or systemic scleroderma.     

Nodular scleroderma in systemic sclerosis under D-penicillamine therapy.

A case of systemic sclerosis (SS) which developed keloidal lesions (nodular scleroderma) on the chest during D-penicillamine (DPC) therapy is reported. The 36-year-old woman showed rapidly progressing skin sclerosis with lung and esophageal involvement, and DPC was started at the age of 38. Skin sclerosis as a whole had improved to some extent, when keloidal nodules developed on the upper chest at the age of 44. Since there were no other findings suggestive of adverse reactions caused by DPC, we speculate that activation of the fibroblasts in these lesions occurred despite the suppressive effect of DPC.     

Localized Severe Scleroderma: A Retrospective Study of 26 Pediatric Patients

Abstract: Juvenile localized scleroderma includes different conditions characterized by skin hardening with increased collagen deposition. Although juvenile localized scleroderma is considered a relatively benign disease, lesions may extend through the dermis, subcutaneous tissue, muscles, and the underlying bone, leading to significant functional and cosmetic deformities. Furthermore, extracutaneous manifestations are described. We retrospectively analyzed a cohort of 26 patients with severe Juvenile localized scleroderma with particular attention to clinical features, therapy, and long‐term outcome. A subgroup of three patients has been further evaluated with infrared thermography. Our findings were consistent with the current literature for demographic, laboratory, and clinical characteristics at disease onset, but, with our patients, the prevalence of extracutaneous manifestations was higher, thus confirming the potential for severe juvenile localized scleroderma to affect organs other than the skin, without increased risk of development toward systemic sclerosis. Correlation between various treatments and clinical endpoint showed that systemic therapy lead to a better outcome: in particular, methotrexate appeared the most effective drug, capable in halting the progression of the disease and sometimes inducing its regression.     

Scleroderma

Sclerodermas may occur in two basic forms: localized sleroderma (LSc) and systemic scleroderma (SSc). Pseudoscleroderma as well as overlap syndromes have to be differentiated from these two variants. From the clinical point of view, localized scleroderma can be subdivided into type I = plaque-like LSc (= morphea), type II = linear LSc, and type III = deep LSc. According to the degree of the cutaneous involvement, systemic scleroderma can likewise be classified into type I = sclerodactylia, type II = acrosclerosis, and type III = scleroderma with primary involvement of the trunk (diffuse scleroderma). In LSc, we never find systemic involvement; SSc, in contrast, is almost always associated with Raynaud's phenomenon, changes of the esophagus, as well as an increased titer of antinuclear antibodies (Hep-2 cell test). Only 23% of our patients with LSc showed elevated ANA titers. We present and discuss data of 56 patients with LSc and 52 patients with SSc. Evidence in the literature as well as our own findings suggest that the pathogenesis of LSc is different from that of SSc. The influence of various mediators and cytokines on the collagen metabolism might be regarded as a theoretical approach in order to develop new therapeutic regimens. This is even more important since there is still no efficient mode of treatment for neither localized nor systemic scleroderma.     

结节性硬皮病

报告1例结节性硬皮病,患者在诊断为系统性硬皮病4年后,胸、背部出现瘢痕疙瘩样皮损,根据病史和组织病理学改变诊断为结节性硬皮病。该型硬皮病多继发于系统性硬皮病,治疗困难。     

硬皮病皮损中TGF-β1,Smad_3和Smad_7的检测及意义

目的探讨TGF-β1,Smad3和Smad7在硬皮病发病机制中的作用。方法采用免疫组化SABC法检测30例硬皮病患者皮损中TGF-β1,Smad3和Smad7的表达,并以10例正常人皮肤组织作为对照。结果TGF-β1,Smad3和Smad7在硬皮病皮损中的表达强度均高于正常对照组(P<0.05)。直线相关分析显示,TGF-β1和Smad3呈正相关。结论TGF-β1,Smad3和Smad7在硬皮病皮损中均表达上调,提示它们在硬皮病病理过程中起一定作用;TGF-β1和Smad3在硬皮病的发病机制中可能起着协同作用;Smad7作为细胞内Smad信号的抑制剂在硬皮病皮损中表达上调,可能为机体的一种负反馈调节作用。     

Successful Treatment of Scleroderma with PUVA Therapy

PUVA therapy was carried out on four patients with scleroderma; three of them had cutaneous manifestations of progressive systemic sclerosis and one other exhibited generalized morphea. PUVA therapy was given with daily doses of 0.25 J/cm² or 0.4 J/cm² for 3–8 weeks, resulting in total doses between 3.5 J/cm² and 9.6 J/cm². All four patients responded well to this treatment; improvements of hand closure, skin sclerosis index, and flexion of fingers or knee joints were obtained. Thus, PUVA appeared to be beneficial for treating scleroderma.     

Progressive Systemic Sclerosis Sine Scleroderma which Developed after Exposure to Epoxy Resin Polymerization

Progressive systemic sclerosis (PSS) sine scleroderma is well known as a special form of scleroderma. Because of its rarity, its pathogenesis has not yet been elucidated. We experienced a 33-year-old man who developed PSS sine scleroderma while working with epoxy resin polymerization. He had short white frenulum linguae, diffuse hyperpigmentation and facial telangiectasia, positive antinuclear antibody, and pulmonary dysfunction, but not acrosclerosis or sclerodactylia. Modest dermal collagen proliferation in the forearm skin confirmed PSS sine scleroderma. Epoxy resin polymerizer appears to be a potent causative agent for PSS sine scleroderma as well as for generalized morphea-like PSS.     

Topical tocoretinate improved hypertrophic scar, skin sclerosis in systemic sclerosis and morphea

Four patients with systemic scleroderma (SSc), 4 patients with morphea, and 4 patients with hypertrophic scar were treated with topical tocoretinate for 6 months to 3 years and studied clinically and histopathologically. Clinically, all of the lesions responded to this therapy. The stiffness of the skin lesions, glossy appearance of the lesions, and telangiectasia improved. Histopathologically, the proliferated collagen fibers decreased in thickness, and the inter-fiber spaces increased. Immunoreactive tenascin-C expressed in the proliferated deep dermal fibers of the SSc and hypertrophic scar lesions was markedly decreased compared with the level before the topical tocoretinate therapy. Topical tocoretinate has been used for the treatment of ulcers; it is also a potent treatment for sclerotic skin diseases.     

Presence of eosinophilia in progressive systemic sclerosis and localized scleroderma

Summary Recent studies on eosinophilic fasciitis have lead to this investigation of eosinophilia in progressive systemic sclerosis and localized scleroderma.Eosinophilia (eosinophilic count >300/cmm) was found in ten of 63 progressive systemic sclerosis patients (15.8%) and in two of nine localized scleroderma cases (22.2%). In patients with progressive systemic sclerosis eosinophilia was found occasionally in six cases; it was transitory, but frequent in three cases; it was constant and very high in one case. In patients with localized scleroderma eosinophilia was found occasionally in one case and frequent, but not constant, in the other one.The possible influence of drugs could be excluded in five cases: three progressive systemic sclerosis cases and two affected with localized scleroderma.Therefore, it is possible to confirm that eosinophilia is not a distinctive sign of eosinophilic fasciitis in patients suffering from scleroderma-like syndromes.While eosinophilia is related to inflammation in eosinophilic fasciitis, eosinophilia and disease activity could not be correlated in our patients with PSS.Recently, it has been suggested that eosinophilia might be an unfavorable prognostic criterion in progressive systemic sclerosis. Our data does not allow confirmation of this assumption.     

Diagnostic pearl: bright field globe magnifier diascopy for large pigmented skin lesions: a practical approach to epiluminescence microscopy

Papular and nodular mucinosis is a distinct form of cutaneous mucinosis associated with systemic lupus erythematosis. We report a case in which papular and nodular mucinosis predated early findings of progressive systemic sclerosis.     

Scleroderma in children: a retrospective study of 70 cases

BACKGROUND: Scleroderma is uncommon in childhood. The aim of our study was to analyze the frequency of different clinical forms, their prognostic significance, biological features, and co-morbidities and to assess the pertinence of therapeutic options. PATIENTS AND METHODS: The files of 70 children with primary scleroderma seen from 1980 to 1997 were retrospectively reviewed. RESULTS: Localized scleroderma was observed in 56 children and diffuse lesions in 14. Localized scleroderma (44 girls, 12 boys) began early at a mean age of 7 years 2 months. The lesions presented as isolated bands (39 p. 100), associated with morphea (36 p. 100), or multiple morphea (5 p. 100). Mean duration of the clinical course was longer in cases with more and deeper lesions. Eosinophilia was observed at onset in 38 p. 100 of the cases and antinuclear antibodies were found in 28 p. 100. Local corticosteroid therapy (level I or II) appeared to be useful in the superficial and active lesions (morphea) but did not halt progression to deep scleroderma. General corticosteroid therapy (1 mg/kg/24 h) did not prevent the development of sequelae in cases with bands (16/16). Diffuse scleroderma corresponded to systemic scleroderma (6 cases), dual morbidity (dermatomyositis, mixed connective tissue disease) (6 cases), or scleroderma after eosinophil fasciitis (2 cases). Age at onset was around 9 years with female predominance. A particular gloves and socks form was observed and cardiac involvement was common, but there was no case of renal involvement. The therapeutic problems were similar to those in adults. DISCUSSION: Our findings emphasize that scleroderma occurs readily in childhood, unlike what has been reported 10 years ago. Prognosis depends on functional impairment resulting from major sequelae particularly important in localized forms and the life-threatening situations occurring in systemic forms.