系统性硬皮病治疗的研究进展

系统性硬皮病（SSc）是一种导致皮肤和内脏器官纤维化的自身免疫性疾病,以组织纤维化,闭塞性微血管病变,免疫异常为特点.对其治疗目前尚无特效的药物,除了围绕其发病机制展开外（抗纤维化药物、免疫抑制剂、血管活性药物）,近年来对其并发症的有效治疗使该病的生存率大为提高.本文旨在概括以往治疗经验,着重介绍近年治疗研究进展.     

固有免疫应答在系统性硬皮病发病机制中的研究进展

系统性硬皮病（systemic sclerosis, SSc）是以皮肤及各内脏器官慢性纤维化为特征的自身免疫病。SSc发病中,固有免疫应答在激活免疫系统和纤维化过程中均发挥重要作用。固有免疫系统一方面通过抗原提呈作用,建立与适应性免疫应答的桥梁;另一方面通过分泌和调节关键的细胞因子促进炎症反应和组织纤维化过程。本文针对固有免疫系统中关键的单核/巨噬细胞、肥大细胞、中性粒细胞和树突状细胞等细胞成分,以及近年来重点关注的Toll样受体及其配体和IL-4、IL-6、TGF-β等细胞因子进行综述,旨在阐明固有免疫应答在SSc发病中的作用,以助于本病的临床评估及靶向分子治疗。     

B淋巴细胞参与系统性硬化症发病机制的研究进展

系统性硬化症(SSc),是一种病因不明的、以皮肤增厚和纤维化、微血管改变和细胞免疫、体液免疫异常为特征,可累及心、肺、肾和消化道等内脏器官的自身免疫性疾病,最终导致组织和器官萎缩硬化,预后不良.T细胞活化已被证明可促进SSc中的纤维化和微血管病变.近期研究表明,B细胞也可能参与SSc发病,如SSc患者的B细胞CD19表...     

系统性硬皮病的血管病变发病机制研究进展

系统性硬皮病(SSc)是一种不明病因的自身免疫性疾病，以进行性的皮肤和内脏纤维化、微血管系统改变和多种细胞、体液免疫异常为特征。SSc的临床表现差异较大，从局限的皮肤硬化、轻微的内脏损害到严重的皮肤及多内脏纤维化，形成一个范围较广的病谱．血管病变是SSc多数临床表现的病理学改变基础本文就SSc血管结构及功能的改变、血管活性相关的细胞因子、血管内皮细胞的凋亡、抗内皮细胞抗体等方面的研究进展进行了综述。     

系统性硬化病病理生理机制研究进展

系统性硬化病(SSc)是一种以皮肤增厚和纤维化为特征,同时伴有内脏器官受累的自身免疫性疾病。SSc的发病机制目前仍然不明,通常认为与遗传及环境因素有关。而血管损伤、免疫功能失调、多器官纤维化及三者间的相互作用,则是导致SSc发生和发展的主要因素。该文主要从上述3个方面总结归纳了其病理生理学研究的主要进展,对内皮细胞活化及效应因子的释放、免疫细胞激活及相关免疫因子的表达、基质细胞的激活及促纤维化因子的分泌,以及三者之间的关联作一综述。     

阿维A与糖皮质激素治疗系统性硬皮病近期疗效初探

系统性硬皮病（SSc）为不明原因的结缔组织病，以细胞外基质成分（主要是Ⅰ、Ⅲ型胶原纤维）过量沉积于皮肤或内脏器官为特征。常规治疗一般选用糖皮质激素、D-青霉胺、秋水仙碱和其他免疫抑制剂等。近年来笔者口使用阿维A治疗SSc取得明显疗效，并与糖皮质激素等药物治疗SSc的近期疗效进行对比，现报告如下。     

系统性硬皮病的治疗现状

系统性硬皮病(SSc)是一种导致皮肤和内脏纤维化的自身免疫疾病,病因不明,可能与遗传、环境因素导致的免疫系统激活、微血管功能障碍、成纤维细胞增殖、胶原增生有关.临床治疗方法虽有多种,包括血管活性药物、阻止纤维化药物、免疫抑制剂和对症治疗等,但没有一种绝对有效的药物,对心、肺、肾和胃肠等内脏器官损害的有效治疗可延长病人的生命.本文简要综述并分析当前国内外缓解该病的治疗方法(如血管活性剂,结缔组织抑制剂,免疫抑制剂的应用)并介绍新的治疗手段,如自体干细胞移植等.     

系统性硬皮病的治疗现状

系统性硬皮病（SSc）是一种导致皮肤和内脏纤维化的自身免疫疾病，病因不明，可能与遗传、环境因素导致的免疫系统激活、微血管功能障碍、成纤维细胞增殖、胶原增生有关。临床治疗方法虽有多种，包括血管活性药物、阻止纤维化药物、免疫抑制剂和对症治疗等，但没有一种绝对有效的药物，对心、肺、肾和胃肠等内脏器官损害的有效治疗可延长病人的生命。本文简要综述并分析当前国内外缓解该病的治疗方法（如血管活性剂，结缔组织抑制剂，免疫抑制剂的应用）并介绍新的治疗手段，如自体干细胞移植等。     

系统性硬化病及相关疾病患者血清中白介素-8及其自身抗体测定

系统性硬化病(SSc)是以皮肤和受累器官的胶原纤维过多的积聚为特征。目前,SSc的发病机理尚不清楚,但有许多细胞因子在组织纤维化的过程中起作用。在成纤维细胞     

系统性硬化症相关间质性肺病的诊治现状和进展

【摘要】 系统性硬化症（SSc）是一种罕见的伴有内脏器官纤维化的慢性结缔组织病,其并发的间质性肺病（ILD）是SSc患者死亡的首要原因。SSc相关ILD发病隐匿,不及时治疗进展迅速,患者生存质量和生存率明显下降。本文综述SSc-ILD早期诊断方法和治疗时机,并对传统的免疫抑制剂和新近出现的靶向药物、造血干细胞移植、肺移植等治疗方法做出综述。     

Systemic and localized scleroderma

Sclerosing conditions of the skin are manifested by a full spectrum of presentations that includes skin-limited forms as well as those which can involve internal organs and result in death. At this point, we are just beginning to understand the mechanisms of tissue fibrosis, and it is likely that the fibrotic processes are a heterogeneous group of disorders in which perturbation of multiple molecular pathways, including vascular and immunologically mediated pathways, can lead to fibrosis. We now have some moderately effective therapies for vascular aspects of systemic sclerosis (eg, bosentan for pulmonary arterial hypertension, calcium-channel blockers for Raynaud's, or angiotensin-converting enzyme inhibitors for renal crisis). We also are beginning to find treatments interrupting the immunologic pathways that manifest as systemic sclerosis (eg, methotrexate for the skin or cyclophosphamide for the lungs). The basic process of fibrosis, however, awaits proven, effective therapy.     

Localized and systemic scleroderma

Scleroderma is a broad term encompassing both localized and systemic sclerosis. Localized scleroderma is a cutaneous limited fibrosis that manifests as plaque morphea, generalized morphea, linear scleroderma, and deep morphea. Systemic scleroderma (sclerosis) can manifest as either limited or diffuse disease. Limited systemic sclerosis is typically preceded by Raynaud's phenomenon, involves cutaneous sclerosis distal to the elbows, with gastrointestinal and pulmonary fibrosis, and anticentromere antibody positivity. Diffuse systemic scleroderma is characterized by simultaneous Raynaud's phenomenon, cutaneous skin involvement proximal to the elbow with gastrointestinal, pulmonary, renal and cardiac fibrosis, and positive serology for antitopoisomerase and anti-RNAP III antibodies. This article discusses the classification, epidemiology, pathogenesis, clinical manifestations, treatment, and prognosis of the scleroderma.     

Taxane-induced scleroderma

We report five women who presented with scleroderma due to taxanes, mimicking systemic sclerosis. All five patients had received taxane chemotherapy for the treatment of metastatic breast cancer. Marked oedema began first, followed by skin sclerosis occurring mainly at the distal ends of the extremities 6-12 months after the administration of taxane in all patients. Skin biopsies showed full-layer dermal fibrosis with thickened collagen bundles, and perivascular monocytic cell infiltration. These cases resemble systemic sclerosis in terms of their clinical course and histological findings. However, clinical findings including Raynaud's phenomenon and pulmonary fibrosis as well as immunological abnormalities associated with systemic sclerosis were not detected in any of the patients. Although the mechanisms have not been clarified, it should be noted that taxane is causally involved in the formation of scleroderma-like skin conditions.     

Phototherapy in systemic sclerosis: Review

Systemic scleroderma—also known as systemic sclerosis (SSc)—is a chronic systemic connective tissue disease characterized by collagen deposition in cutaneous and internal organs, leading to skin sclerosis and multiple organ fibrosis. The pathogenesis is complex and remains poorly understood. Treatment is based on organ involvement and requires a multidisciplinary approach. Skin sclerosis can cause disability, leading to decreasing quality of life. Various systemic antifibrotic therapies have been used; however, most have unsatisfactory results. Recently, phototherapy and in particular ultraviolet A (UVA) has been used to treat skin sclerosis in SSc patients with satisfactory results. The main mechanisms include lymphocyte apoptosis, cytokine alteration, inhibition of collagen synthesis and increased collagenase production, and neovascularization, leading to the breakdown of collagen fibrils resulting in skin softening or even healing digital ulcers. Most studies reported that psoralen plus UVA (PUVA) and UVA1 phototherapy improved clinical outcomes vis‐à‐vis skin sclerosis, joint mobility, ulcers, and histopathology. PUVA and UVA1 phototherapy therefore have potential as an alternative or adjunctive therapy for patients with SSc.     

生物制剂治疗系统性硬化病的研究进展

系统性硬化病是一种以皮肤及各系统胶原纤维硬化为主要特征的慢性自身免疫性疾病,以免疫调节、减少纤维化和改善血液循环为基础的传统疗法,但疗效欠佳.近年来愈来愈多的证据显示,T淋巴细胞、B淋巴细胞及多种细胞因子在系统性硬化病的发病中起重要作用.研究显示,依那西普、英夫利西单抗、利妥昔单抗等生物制剂治疗难治性系统性硬化病疗效显著.     

Symptomatic scleroderma caused by bleomycin

Side effects of bleomycin therapy are most frequent in the skin and as pulmonary fibrosis because of the nearly selective concentration in these organs. The cutaneous manifestations include a variety of clinical symptoms, most frequently erythema and infiltrations with marked hyperpigmentation. A 38-year-old patient is reported who received 615 mg bleomycin for therapy of a malignant testicular teratoma and in the following time developed numerous morphoea-like lesions, acrocyanosis, Raynaud's phenomenon, acrosclerosis, and cutaneous calcinosis. Histologically, the alterations were similar to those of scleroderma. In contrast to progressive systemic sclerosis the symptomatic character of the lesions is evident, for the skin changes resolved several months after the drug was discontinued.     

Treatment of systemic sclerosis with γ-interferon

Numerous drugs have been recommended for the treatment of systemic sclerosis, but without any significant effect on the fibrotic stage of this disorder. Because recombinant gamma-interferon (gamma-IFN) is a potent and selective inhibitor of fibroblast proliferation and collagen production by human dermal fibroblasts in vitro, we assessed the effects of gamma-IFN treatment on the skin and on pulmonary function in patients with systemic sclerosis. Fourteen patients entered the study, and nine completed the 12-month trial. Fifty micrograms/day of gamma-IFN was administered subcutaneously 3 days per week. At the end of the 12-month treatment period a significant improvement was observed in total skin score, and blood gas analysis showed a significant increase in Pa O2 during therapy with gamma-interferon. Other clinical parameters (dysphagia, Raynaud's phenomenon, cardiac involvement) were not altered significantly. No serious adverse effects were noted. These results suggest a beneficial effect of gamma-IFN on the cutaneous fibrotic abnormalities and on lung fibrosis in systemic sclerosis.     

Elevated plasma histamine levels in systemic sclerosis (scleroderma)

Systemic sclerosis is characterized by excessive deposition of collagen and other matrix proteins in the skin and internal organs. One hypothesis supports fibroblast stimulation for production of excess amounts of collagen by factors present in the blood or released by cells composing inflammatory tissue infiltrates. Increased numbers of mast cells are present in the involved skin of patients with systemic sclerosis, and histamine has been thought to be a possible mediator of fibrosis in this and other fibrotic conditions. We therefore measured plasma histamine levels in 32 patients with systemic sclerosis and found elevated levels in 18 patients (56%). Elevated plasma histamine levels were more common in patients with diffuse disease (74%), in contrast to limited disease (31%). The degree of clinical activity and the duration of disease could not be correlated with histamine levels.     

Function blocking autoantibodies against matrix metalloproteinase-1 in patients with systemic sclerosis

Systemic sclerosis is characterized by fibrosis and systemic autoimmunity; however, roles of autoantibodies in the development of fibrosis remain unknown in systemic sclerosis. The net accumulation of extracellular matrix is dependent on the balance between the synthesis and degradation of extracellular matrix components, the latter process regulated by matrix metalloproteinases. Matrix metalloproteinase-1 (interstitial collagenase-1) can initiate degradation of collagen types I-III that are major extracellular matrix constituents in affected skin of systemic sclerosis. In this study, we tested the hypothesis that systemic autoimmunity in systemic sclerosis induced anti-matrix metalloproteinase-1 autoantibodies that inhibited matrix metallo-proteinase-1 activity, resulting in collagen accumulation. Enzyme-linked immunosorbent assay using human recombinant matrix metalloproteinase-1 revealed that IgG anti-matrix metalloproteinase-1 autoantibody levels were significantly elevated in sera from patients with systemic sclerosis, but not patients with active systemic lupus erythematosus or dermatomyositis, relative to normal controls. IgG anti-matrix metalloproteinase-1 autoantibody levels were significantly higher in patients with diffuse cutaneous systemic sclerosis than those found in patients with limited cutaneous systemic sclerosis. Furthermore, IgG anti-matrix metalloproteinase-1 antibody levels significantly correlated with the extent of fibrosis in the skin, lung, and renal blood vessels. The presence of IgG anti-matrix metalloproteinase-1 autoantibody in sera from systemic sclerosis patients was confirmed by immunoblotting analysis. Remarkably, IgG anti-matrix metalloproteinase-1 autoantibody in sera from systemic sclerosis patients inhibited matrix metalloproteinase-1 collagenase activity. Collectively, the results of this study suggest that anti-matrix metalloproteinase-1 autoantibody contributes to the development of fibrosis by inhibiting matrix metalloproteinase-1 collagenase activity and reducing the extracellular matrix turnover and suggest that the presence of anti-matrix metalloproteinase-1 autoantibody in systemic sclerosis is the link between systemic autoimmunity and fibrosis.     

Panniculitis–an unusual cutaneous manifestation of systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune systemic disease characterized by small vessel involvement that leads to tissue ischemia and fibroblast stimulation resulting in accumulation of collagen (fibrosis) in the skin and internal organs. Lipomembranous panniculitis is a peculiar type of fat necrosis and has been reported with clinical conditions, commonly with peripheral vascular diseases. We describe a case of a 43‐year‐old woman with SSc manifestations, who presented with black scaly skin plaques, associated with thickening of the subcutaneous fat tissue, on the lateral surface of her thighs, her calves, gluteal area and lower abdomen. Biopsy revealed lipomembranous panniculitis. Lipomembranous changes have been seen in connective tissue disorders such as lupus profundus, morphea, systemic sclerosis and panniculitis associated with dermatomyositis, but rarely in thighs, calves, gluteal area and lower abdomen. Almeida MSTM, Lima SCB, Carvalho LL, Almeida JVM, Santos LG, Rolim JRA, Rocha TE. Panniculitis–An unusual cutaneous manifestation of systemic sclerosis.