系统性硬化病诊断及治疗指南

1概述 系统性硬化病(systemic sclerosis,SSc)是一种以皮肤变硬和增厚为主要特征的结缔组织病,女性多见,多数发病年龄在30～50岁.根据患者皮肤受累的情况将SSc分为5种亚型:①局限性皮肤型SSc(limited cutaneous SSc):皮肤增厚限于肘(膝)的远端,但可累及面部、颈部.②CREST综合征(CREST syndrome):局限性皮肤型SSc的一个亚型,表现为钙质沉着(calcinosis,C),雷诺现象(Raynaud's phenomenon,R),食管功能障碍(esophageal dysmotility,E),指端硬化(sclerodactylv,S)和毛细血管扩张(telangiectasia,T).③弥漫性皮肤型SSc (diffuse cutaneous SSc):除面部、肢体远端外,皮肤增厚还累及肢体近端和躯干.④无皮肤硬化的SSc(SSc sine scleroderma):无皮肤增厚的表现,但有雷诺现象、SSc特征性的内脏表现和血清学异常.⑤重叠综合征(overlap syndrome):弥漫或局限性皮肤型SSc与其他诊断明确的结缔组织病同时出现,包括系统性红斑狼疮、多发性肌炎/皮肌炎或类风湿关节炎.     

系统性硬化病诊断及治疗指南

1概述 系统性硬化病(systemic sclerosis,SSc)是一种以皮肤变硬和增厚为主要特征的结缔组织病,女性多见,多数发病年龄在30～50岁.根据患者皮肤受累的情况将SSc分为5种亚型:①局限性皮肤型SSc(limited cutaneous SSc):皮肤增厚限于肘(膝)的远端,但可累及面部、颈部.②CREST综合征(CREST syndrome):局限性皮肤型SSc的一个亚型,表现为钙质沉着(calcinosis,C),雷诺现象(Raynaud's phenomenon,R),食管功能障碍(esophageal dysmotility,E),指端硬化(sclerodactylv,S)和毛细血管扩张(telangiectasia,T).③弥漫性皮肤型SSc (diffuse cutaneous SSc):除面部、肢体远端外,皮肤增厚还累及肢体近端和躯干.④无皮肤硬化的SSc(SSc sine scleroderma):无皮肤增厚的表现,但有雷诺现象、SSc特征性的内脏表现和血清学异常.⑤重叠综合征(overlap syndrome):弥漫或局限性皮肤型SSc与其他诊断明确的结缔组织病同时出现,包括系统性红斑狼疮、多发性肌炎/皮肌炎或类风湿关节炎.     

系统性硬化病合并肾危象16例临床分析

目的 通过分析和总结系统性硬化病(SSc)合并肾危象患者的临床资料,以提高临床医生对其的认识.方法 回顾分析2004年5月至2013年5月北京协和医院住院的16例SSc合并肾危象患者的临床、实验室检查结果、治疗和预后.结果 16例SSc合并肾危象患者中男性5例,女性11例;SSc合并肾危象起病年龄为(49.9±12.3)岁,从SSc起病进展为SSc合并肾危象的时间平均为3.2年;弥漫性皮肤型SSc 10例,局限性皮肤型SSc 6例.16例患者抗着丝点抗体均阴性.16例患者在病初均有高血压和肾功能不全,8例病初需要透析,7例有血栓性微血管病.3例行肾活检,病理均见肾脏小血管管壁增厚和管腔狭窄.16例患者3例失访;13例随访患者中,11例接受了规律的血管紧张素转换酶抑制剂治疗,5例死亡,8例存活者中2例需要长期透析,1例在接受血管紧张素转换酶抑制剂联合内皮素受体拮抗剂治疗后脱离透析,5例无需透析.结论 SSc合并肾危象常在SSc病程早期出现,多见于弥漫性皮肤型SSc患者,抗着丝点抗体阳性患者少见.早期足量使用血管紧张素转换酶抑制剂为治疗SSc合并肾危象的基础.内皮素受体拮抗剂在SSc合并肾危象中的治疗作用还需进一步研究.     

无皮肤硬化伴广泛皮下软组织钙化的系统性硬化一例

系统性硬化(SSc)是纤维组织异常增生为主的疾病,皮肤改变是SSc的标记性症状.现将我科收治的1例无皮肤硬化,伴有多系统损害、广泛皮下软组织钙化的SSc报告如下.     

系统性硬化病治疗进展

系统性硬化病(systemic sclerosis,SSc)是一种全身性自身免疾病,以皮肤纤维化及内脏受累(肺、消化系统、肾、心脏等)为特征.SSc的发病机制复杂,目前尚未阐明.因此SSc一直缺乏有效的治疗方法.现就SSc的免疫调节治疗、血管病治疗、抗纤维化治疗综述如下.     

系统性硬化病相关肺动脉高压

系统性硬化病（SSc）是一种以皮肤和某些内脏小血管壁增生、管腔阻塞、造成皮肤广泛纤维化和脏器功能不全为主要特点的结缔组织病。SSc相关肺动脉高压（SSc—PAH）多发且死亡率较高。     

氧化应激异前列腺素与系统性硬化症

系统性硬化症(systemic sclerosis,SSc)是一种累及皮肤和内脏,最终导致组织纤维化的多系统损害的疾病.虽然SSc的发病机制还未完全阐明,但皮肤和内脏器官细胞外基质的过度积聚,血管内皮细胞功能紊乱及免疫异常已经作为其特征性改变而被认识.近年很多研究发现氧化应激在SSc的发生发展中起重要作用,而目前认为体内最适用的氧化应激标志是异前列腺素(isoprostanes,iso-PGs).其具有多种潜在的生物学活性.与SSc组织损伤密切相关.本文就近年来氧化应激及iso-PGs在SSc中的研究进展作一综述.     

系统性硬化病动物模型的研究进展

系统性硬化病(SSc)是一种以局限性或弥漫性皮肤增厚和纤维化为特征的全身性自身免疫性疾病,其发病机制目前尚不完全清楚,临床亦缺乏行之有效的治疗方式.构建理想的动物模型是探索SSc发病机制和检测新治疗策略重要的临床前平台.根据构建方法不同,可将SSc动物模型分为诱导模型和基因模型两大类.其中,诱导模型包括博来霉素诱导小鼠...     

系统性硬化病免疫学机制的研究进展

系统性硬化病(systemic sclerosis,SSc)是一种以皮肤和内脏器官纤维化为主要特征的自身免疫性疾病,除皮肤外受累器官还包括消化道、肺脏、心脏及肾脏等.典型的SSc首发症状往往是雷诺现象,为微血管损伤的表现,随后才逐渐出现皮肤增厚及内脏器官纤维化.月前其发病机制集中在血管病变、免疫炎症及纤维化3个方面.本文就以上3个方面的研究进展进行综述,希望通过了解其发病机制,加深对疾病的认识,寻求更有效的治疗方法.     

系统性硬化病免疫学机制的研究进展

系统性硬化病(systemic sclerosis,SSc)是一种以皮肤和内脏器官纤维化为主要特征的自身免疫性疾病,除皮肤外受累器官还包括消化道、肺脏、心脏及肾脏等.典型的SSc首发症状往往是雷诺现象,为微血管损伤的表现,随后才逐渐出现皮肤增厚及内脏器官纤维化.月前其发病机制集中在血管病变、免疫炎症及纤维化3个方面.本文就以上3个方面的研究进展进行综述,希望通过了解其发病机制,加深对疾病的认识,寻求更有效的治疗方法.     

Clinical significance of serum hyaluronan levels in systemic sclerosis: association with disease severity

OBJECTIVE: To determine any clinical association of serum levels of hyaluronan in patients with systemic sclerosis (SSc). METHODS: Hyaluronan levels in serum samples from patients with SSc (n = 66) and hyaluronan expression in skin were assessed. RESULTS: Serum hyaluronan levels in SSc patients were higher than those in healthy controls. SSc patients with elevated hyaluronan levels had more frequent involvement of several clinical manifestations and immunological abnormalities compared to those with normal levels. Thus, hyaluronan levels correlated with disease severity. Hyaluronan expression in the sclerotic skin from SSc patients was more intense, relative to expression in normal skin. CONCLUSION: These results suggest that elevated serum hyaluronan levels are associated with disease severity and immunological abnormalities in patients with SSc.     

Autologous stem cell transplantation in a patient with diffuse systemic sclerosis

Systemic Sclerosis (SSc) is a systemic disease of unknown etiology presenting with disseminated skin thickening and fibrotic impairment of various organs including lung and kidney. According to the rate and degree of skin involvement, SSc can be classified in a limited and a diffuse form, the latter showing a severe and progressive lung involvement, which is responsible for its high related morbidity and mortality along with resistance to standard therapeutic protocols. High dose chemotherapy, followed by autologous stem cell transplantation, is a standard therapeutic regimen for haematological diseases: re-infusion of mobilised peripheral blood progenitor cells overcomes the myeloablative effect of super-maximal eradicative doses of chemotherapeutic agents. Recently, this therapeutic approach has been applied in some cases of resistant SSc and, albeit the low number of cases, it has been proven effective in early diagnosed and rapidly progressive forms of the disease showing a clinical improvement and an instrumentally detectable decrease of fibrosis extent. We report the case of a young woman affected by diffuse SSc with a rapid progression of clinical signs and instrumentally detectable lesions who underwent a conditioning regimen with fludarabine, cyclophosphamide and anti-thymoglobulines followed by re-infusion of autologous peripheral blood stem cells. Two years after transplantation a clinical and instrumental evidence of treatment was observed, with good control of disease evolution. The only sign of disease resumption was a slow worsening of skin involvement.     

Dermal mast cell degranulation in systemic sclerosis

Paired biopsy samples from involved and uninvolved skin were obtained from 19 patients with generalized scleroderma (11 with early, progressive disease and 8 with late, improving disease). Skin biopsy samples were double stained for mast cell granules and for mast cell membrane. The number of mast cells was increased in patients with systemic sclerosis (SSc), in both involved and uninvolved skin and in both early and late disease. There was an increase in the number of degranulated mast cells in the involved skin of patients with both early and late disease and in the not-yet-involved skin of patients with early disease; however, there was no increase in the number of degranulated mast cells in areas of previously involved but now normal skin of patients with late disease. Increases in mast cell number and degranulation precede clinically apparent dermal fibrosis in SSc. These observations and the absence of mast cell degranulation in regressing skin suggest a participatory role of the mast cell in the clinical progression of skin changes in SSc.     

Combined plasmapheresis and high-dose intravenous immunoglobulin treatment in systemic sclerosis for 12?months: follow-up of immunopathological and clinical effects

Systemic sclerosis (SSc) is an autoimmune disease which involves the skin, as well as several internal organs. Most therapies available in this disease are symptomatic. Authors present a case of diffuse SSc with progressive disease not responding to currently available treatments. Therefore a 12-month protocol of repeated plasmapheresis and high-dose intravenous immunoglobulin treatment was administered with good clinical efficacy. Apart from monitoring the clinical symptoms throughout the treatment, authors also assessed a number of humoral and cellular immunolaboratory markers in order to obtain information on the immunomodulatory effects of this combined treatment in SSc.     

Correlation of soluble adhesion molecules in the peripheral blood of scleroderma patients with their in situ expression and with disease activity

Objective. To correlate serum levels of the soluble adhesion molecules intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, and P-selectin with (a) clinical disease activity and progression and (b) the in situ expression and distribution of these adhesion molecules in lesional skin, in patients with systemic sclerosis (SSc). Methods. Serum samples from 12 SSc patients and 36 healthy controls were examined by enzymelinked immunosorbent assay. Immunohistologic staining was carried out on cryostat sections of lesional skin. Results. Patients whose SSc was in the early inflammatory stage or who had prominent disease progression showed elevated serum levels of soluble adhesion molecules. Serum levels correlated positively with the expression of these molecules on endothelial cells and fibroblasts in lesional skin. Conclusion. Serum levels of soluble ICAM-1, VCAM-1, P-selectin, and, to a lesser degree, E-selectin correlate well with their in situ activity and with clinical disease activity. These parameters therefore provide a useful tool for the characterization of disease stage, progression, and prognosis in SSc.     

Increased serum interleukin 23 in patients with systemic sclerosis

OBJECTIVE: The relationship between systemic sclerosis (SSc) and interleukin 23 (IL-23), a cytokine associated with the differentiation of T lymphocytes, is unknown. We investigated serum IL-23 levels and their clinical association in patients with SSc. METHODS: Serum IL-23 levels were examined by ELISA in 63 patients with SSc, 15 patients with systemic lupus erythematosus (SLE), and 31 healthy individuals. SSc patients comprised 25 with limited cutaneous SSc and 38 with diffuse cutaneous SSc. RESULTS: Serum IL-23 levels were significantly elevated in SSc patients compared to patients with SLE (p < 0.05) and controls (p < 0.005). Elevated serum IL-23 levels were associated with the disease duration (p < 0.05) and the prevalence of pulmonary fibrosis (p < 0.05), although they were not associated with other clinical features, including the extent of skin sclerosis or the severity of pulmonary fibrosis. CONCLUSION: The results suggest that IL-23 is associated with induction of SSc and that blockade of IL-23 can be a potential therapeutic strategy in early SSc.     

Clinical and laboratory features of scleroderma patients developing skeletal myopathy

Skeletal muscle involvement, or myopathy, has been a recognized feature of systemic sclerosis (SSc). We studied retrospectively 302 Japanese patients with SSc to elucidate the clinical and laboratory features in scleroderma patients developing skeletal myopathy during their clinical course. Forty-three patients (14%) developed skeletal myopathy during their course of the disease. The mean age of the patients who developed skeletal myopathy was significantly lower than that of those who did not. The ratio of male to female was significantly higher in the myopathic patients. The patients with diffuse cutaneous SSc were more likely to develop myopathy than those with limited cutaneous SSc. The prevalences of heart involvement, pulmonary fibrosis, diffuse pigmentation of the skin, and contracture of phalanges were significantly greater in those with skeletal myopathy than in those without. None of the patients with skeletal myopathy had anticentromere antibody. These findings suggested that the SSc patients with severe internal organ involvement, such as pulmonary fibrosis and heart disease, and some other complications were prone to develop skeletal myopathy during their clinical course of the disease.     

Current approaches to the management of early active diffuse scleroderma skin disease

Skin sclerosis is a clinical hallmark of systemic sclerosis (SSc) and provides a means to classify and evaluate patients. In the diffuse cutaneous subset, skin involvement is often extensive and warrants direct therapy. Currently, broad spectrum immunosuppressive strategies are used, but more targeted specific approaches are now emerging. This article reviews the evidence for efficacy of current treatment approaches and future developments for managing skin disease in early diffuse cutaneous SSc.     

Quantification of fetal microchimeric cells in clinically affected and unaffected skin of patients with systemic sclerosis

OBJECTIVE: Fetal microchimerism has been hypothesized as a potential pathogenic mechanism for systemic sclerosis (SSc). This hypothesis was based on the clinical similarities between SSc and graft-vs-host disease and the identification of microchimeric cells in affected SSc tissues. The aim of this study was to compare the quantity of microchimeric cells in clinically affected and non-affected skin of female patients with SSc. METHODS: Fluorescence in situ hybridization (FISH) and real-time PCR were employed in paired skin biopsies obtained from clinically affected and unaffected areas from five female SSc patients with diffuse cutaneous SSc (dcSSC) and 10 healthy women. All women in the study had delivered a male fetus. RESULTS: FISH analysis revealed the presence of male fetal cells in 1/5 SSc patients (20.0%) compared with 0/10 healthy women (P = 0.0037), whereas quantification by real-time PCR revealed that all SSc samples were positive for male DNA compared with none of the controls. In the five patients with dcSSc, there were similar numbers of microchimeric cells in both affected and unaffected skin (P = 0.4) CONCLUSION: The presence of higher numbers of microchimeric cells in clinically unaffected SSc skin, before any clinically detectable evidence of sclerotic changes, suggests that an influx of microchimeric cells may precede the development of tissue fibrosis. This provides additional support to the hypothesis that fetal microchimerism may play a role in the pathogenesis of SSc.